44th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT), 28–31 May 2024, Munich, Germany

 

 

1. Osmol gaps in patients with alcoholic ketoacidosis

Abstract

Objective

Many hospitals are unable to determine toxic alcohol concentrations in a clinically relevant timeframe. As a result, clinicians are forced to use surrogate markers such as the osmol gap. Toxic alcohol ingestion is often implicated when the osmol gap is elevated. Based on our experience, many patients with alcoholic ketoacidosis (AKA) also have a very elevated osmol gap. We aimed to characterize the range of osmol gaps in patients with AKA.

Methods

This was a retrospective study from a single poison center from 2000 to 2023. Records were reviewed to identify cases coded as “methanol”, “ethylene glycol”, or “ethanol with a metabolic acidosis”. An additional search identified records with the word “osm” in the narrative. The case definition of AKA required: (1) documented alcohol use disorder; (2) presence of urine or serum ketones or elevated blood beta-hydroxybutyrate concentration; (3) an anion gap ≥14 mmol/L. Potential AKA cases that failed to fulfil all three criteria were adjudicated by a 2/3 majority of three board certified toxicologists who assessed cases independently. Exclusion criteria included (1) detectable toxic alcohol concentration, (2) hemodialysis and/or multiple doses of fomepizole, (3) no osmol gap documented, (4) other confounding diagnoses for metabolic acidosis including seizures, diabetic ketoacidosis or cardiac arrest. Demographics, pH, anion gap, and osmol gap were extracted.

Results

Of 1053 patients screened, 55 met diagnostic criteria for AKA (30 by definition and 25 after adjudication). Sixty-two percent were male, their mean age was 50 years. The median osmol gap was 25 [interquartile range 18–35]. The largest anion gap was 57 mmol/L and the lowest pH was 6.8. Forty-four (80%) of the patients with AKA had an osmol gap >10; 37 (67%) had an osmol gap >20; 23 (42%) had an osmol gap >30; and 11 (20%) had an osmol gap >40.

Conclusion

In this retrospective study, patients with AKA had a median osmol gap of 25, which is greater than previously reported [1]. Furthermore, a majority of these patients had an osmol gap classically associated with toxic alcohol poisoning. As such, AKA should not be excluded from the differential diagnosis of patients with an anion gap metabolic acidosis because the osmol gap is very elevated. AKA is easily treated with inexpensive therapies, and proper identification may prevent costly and invasive treatment directed at toxic alcohol poisoning.

2. Internet availability of synthetic cannabinoid receptor agonists for use with electronic vaping devices

Abstract

Objective

There are increasing reports of synthetic cannabinoid receptor agonists (SCRAs) being used in electronic vaping devices (EVDs). The aim of this study was to determine availability of SCRAs in vaping products for use by EVDs.

Methods

Using EMCDDA methodology [1], we undertook an Internet snapshot (October 2022 to January 2023) to assess availability of synthetic cannabinoid vaping products (SCVPs). We used the following search terms on google.com: “buy c-liquid vape”, “buy herbal incense vape liquid”, “buy cannabis vape liquid”, “buy hashish vape liquid”, “buy K2 vape liquid”. Information extracted from identified sites included: i) country of origin of website; ii) other novel psychoactive substances (NPS) and/or drugs sold; iii) information available for potential purchasers; iv) SCVP products sold; and v) SCVP product pricing (where necessary converted to GBP using the European Central Bank website).

Results

Of 612 results reviewed, 62 unique websites selling SCVPs were identified. The majority were based in the USA (41 sites; 66%) or UK (9; 15%). A minority (3; 5%) exclusively sold SCVPs; other products sold included: other non-SCVP SCRA preparations (57; 92%), cannabis/tetrahydrocannabinol (THC) products (42; 68%), cannabidiol (CBD) products (32; 51%), nicotine products/vaping paraphernalia (19; 31%), other NPS (27; 44%) and other illegal recreational drugs excluding NPS (34;55%). Websites offered a variety of purchase incentives: discreet packaging (38; 61%), discounts for bulk purchase (34; 55%), tracked delivery (30; 48%) and same-day shipping (28; 45%). Websites stated some/all products were not for human consumption (41; 66%), were for research purposes only (15; 24%), or were legal (28; 45%). Overall, 128 unique SCVP brands were identified, with a median of 16 (IQR: 7–25; range: 1–58) individual SCVP brands per-website. The three most common SCVP brands were Bizarro (73% of websites), Diablo (60%) and Blazing Blueberry (58%). Almost all products were sold as liquids for refilling EVDs (1220; 99.6%); the most common sizes were 5 mL (60%), 10 mL (11%) or 7 mL (4.5%). The median total volume of SCRA liquid per sale was 50 mL (IQR:10–200 mL; range:1–20,000 mL). The median price of liquid products was £3.39/mL (IQR:£2.01/mL–£5.29/mL). Most websites offered discounts with increasing purchase volume: £6.58/mL for ≤5 mL, £4.13/mL for 21–50 mL, £1.60/mL for >200 mL.

Conclusion

Vaping products containing synthetic cannabinoids are easily found from numerous Internet suppliers; they are cheap, with discounts for larger sales. Limited information is provided on the illegality or potential for harm. Further work is required to make accessing these products online less easy.

3. Model to predict the risk of developing atrioventricular block (AVB) in acute oleander poisoning: a prospective cohort study from Sri Lanka

Abstract

Objective

To develop a model to predict the risk of developing AVB in patients with acute yellow oleander (Cascabela thevetia, previously Thevetia peruviana) poisoning.

Methods

A prospective cohort study was carried out at Teaching Hospital Batticaloa, Sri Lanka, from 1 July 2022 to 31 July 2023 among 200 consenting symptomatic patients admitted with acute oleander poisoning. Serum potassium and serum creatinine concentrations were assessed at recruitment and 6 hourly. Serial electrocardiograms were done at recruitment and 4 hourly, for 24 h. The model was developed through Multiple Logistic Regression (MLR) using backward elimination to select variables that demonstrated statistical significance at p < 0.05 in bivariate analysis as candidate predictors [1]. Of the 11 candidate variables, only 4 variables remained significant: hyperkalemia (serum potassium >5.5 mmol/L), bradycardia (heart rate <60 beats per minute) and high serum creatinine (SCr) (>1.35 mg/dL) and presence of reverse tick sign of digoxin toxicity. The regression coefficients for four predictors were assigned as weighted scores and rounded up to remove any decimal points. The consolidated score was developed by summing up the weighted scores. The consolidated score was used to anticipate an individual’s risk of developing a heart block. Analysis of the Receiver Operator Characteristic Curve was carried out to enhance the model.

Results

Among 200 consenting symptomatic patients recruited 63.5% (n = 127) were male. Overall, 31.5% (n = 63) developed hyperkalemia, 12.0% (n = 24) had high SCr concentrations (>1.35 mg/dL), 63.5% (n = 127) developed bradycardia and 12.5% (n = 25) presented with reverse tick sign of digoxin toxicity. Overall, 6.0% (n = 12), 8.0% (n = 16) and 4.0% (n = 8) of the patients developed 1st, 2nd and 3rd degree AVB, respectively. Temporary cardiac pacing (TCP) was performed in 8.0% (n = 16), and 1.5% (n = 3) died due to cardiac arrhythmias. A risk score, of 1 to 5 was developed. A cut-off value of 2.5 was used to distinguish "at risk" and "not at risk" patients to decide the need for intervention. The Area Under the Curve at p < 0.001 signified strong model performance, explaining 78.7% of patients developing heart block through the summary risk score. Prediction model achieved 75.0% sensitivity and 77.4% specificity.

Conclusion

The developed risk prediction model is valid to identify patients at risk of requiring interventions such as TCP or an antidote, following acute oleander poisoning. This model should be advocated as a simple, cost-effective tool to reduce healthcare burdens.

4. Precision cut lung slices in acetylcholinesterase reactivator research: assessing AChE activity and airway responsiveness

Abstract

Objective

The recent use of organophosphorus nerve agents (OPNA) has underscored the importance of effective medical countermeasures. OPNA exposure leads to the inhibition of acetylcholinesterase (AChE), resulting in an accumulation of acetylcholine (ACh), potentially causing a cholinergic crisis including bronchoconstriction. We, therefore, aimed to investigate the utility of precision cut lung slices (PCLS) as an ex vivo model for assessing AChE activity and airway responsiveness after OPNA exposure.

Methods

PCLS were prepared from the lungs of male Wistar rats. They were stored in an incubator overnight and used during the following day. A modified Ellman assay was employed to determine AChE activity in intact PCLS. PCLS were exposed to cyclosarin (GF), sarin (GB), or VX for 10 min, with subsequent addition of a phosphotriesterase to ensure a poison-free environment. As reactivators HI-6, obidoxime (OBI), and the experimental non-oxime reactivator NOX-6 were studied. AChE reactivation was assessed using 5,5′-dithiobis(2-nitrobenzoic-acid) and acetylthiocholine at 37 °C for 30 min. Airway area changes were monitored via video microscopy in a similar experimental setup, comparing the initial airway area (IAA) to the airway area (AA) after OPNA exposure and treatment.

Results

Despite low AChE activity in PCLS, this study successfully determined AChE activity by using four intact PCLS per measurement. Exposure to GB, VX, or GF led to significant AChE inhibition (≤12 ± 2%) and a corresponding decrease in airway area (≤13 ± 4%). The highest AChE reactivation after GB exposure was achieved with OBI (83 ± 6%) and HI-6 (64 ± 1%). After exposure to VX reactivation data were as follows: OBI 71 ± 3% > NOX-6 53 ± 4% ≥ HI-6 51 ± 1%. AChE activity was lowest for GF-inhibited AChE reactivated with OBI (13 ± 3%) and slightly higher with HI-6 (15 ± 3%). We also monitored changes in AA for selected conditions. After exposure to GB, following OBI treatment, the AA increased to 74 ± 6% of the IAA, whereas there was no significant increase in AA observed for OBI treatment after exposure to GF (11 ± 3% of IAA).

Conclusion

This study demonstrates the successful determination of AChE activity in PCLS and its correlation with airway responsiveness after exposure to OPNA and subsequent treatment with reactivators. Traditionally, bronchoconstriction resulting from OPNA poisoning has primarily been addressed using muscarinic receptor antagonists like atropine. Nevertheless, our present study demonstrates the effective reactivation of inhibited AChE in PCLS and their positive effect on airway reopening. This underlines the potential of AChE reactivators to alleviate life-threatening airway constriction as well.

5. Update from the EU Early Warning System on new psychoactive substances

Abstract

Objective

The European Union Early Warning System on new psychoactive substances (NPS) (EU EWS), operated by the EU Drug Agency (EMCDDA) is operational since 1997. It was the first regional early warning system to be established to monitor NPS and has been recognised as a model for national, regional and international early warning systems.

Methods

The EU EWS rapidly detects, assesses and responds to health and social threats caused by NPS. Data collected and analysed include event-based data on seizures by law enforcement, collected samples and serious adverse events linked to NPS. These data are complemented by annual reports, which include aggregated data on seizures and from poisonings.

Results

By September 2023, the EMCDDA was monitoring more than 940 NPS, 41 of which were first reported in 2022. The availability of NPS in Europe has reached a historic high, with more than 20 tons seized in 2022. This increase has been driven by a large increase in seizures of synthetic cathinones, in particular 3-CMC (3-chloromethcathinone), mostly trafficked from India. New threats continue to emerge; alongside hemp adulterated with synthetic cannabinoids over the past few years, cannabidiol has emerged as a precursor to make semi-synthetic cannabinoids that are sold openly as “legal” replacements to cannabis. Hexahydrocannabinol (HHC) was the first semi-synthetic cannabinoid that emerged on the European market in 2022 and since its emergence five further semi-synthetic cannabinoids have also been detected, suggesting commercial interest in this area. The trend towards highly potent substances continues, in some northern and Baltic countries, both fentanyls and nitazenes are a significant and growing threat in some cases causing outbreaks of poisonings and driving a rise in fatal overdoses. The first cases of adulteration of illicit opioids with xylazine (“tranq-dope”) or designer benzodiazepines (“benzo-dope”) have also been reported in Europe.

Conclusion

Currently, the NPS market is characterised by complexity and increased integration with the market for established controlled drugs. The market continues to grow, and is resilient and highly dynamic, rapidly adapting to attempts to disrupt it. There is a need to ensure that Europe continues to strengthen its ability to detect, assess, and respond to emerging threats in a timely and effective way in order to prevent or reduce the public health and social harms caused by NPS. The EU EWS plays a central role in supporting national- and EU-level preparedness and responses to NPS.

6. Involvement of new synthetic opioids in episodes of drug toxicity requiring emergency department attendance in the United Kingdom

Abstract

Objective

New synthetic opioids (NSO) include fentanyl and its analogues, 2-benzyl benzimidazoles (e.g., isotonitazene) and piperidine benzimidazolones (e.g., brorphine). Many are highly potent compounds that have been implicated in large numbers of drug-related deaths in North America [1]. Several have also been detected in drug seizures in Europe, although their role in drug related deaths is less clearly characterised. The Identification Of Novel psychoActive substances (NPS) study (IONA) tracked substances detected in samples from patients attending UK Emergency Departments (ED) after drug use between March 2015 and March 2023. Here we describe the NSO detected over this 8-year period.

Methods

IONA included patients (≥16 years) presenting to participating EDs with toxicity after suspected drug misuse who gave informed consent (or after agreement of a relative/representative if lacking capacity). Inclusion initially required a suspicion of NPS use but were expanded in January 2017 to include non-therapeutic opioid (e.g., heroin) use and in January 2020 to allow any drug use. Demographic and clinical features were recorded and blood and/or urine samples analysed using liquid chromatography-high resolution accurate mass full scan and full scan MS/MS mass spectrometry.

Results

Clinical and analytical data are available for 1815 patients in total. In this cohort, there were 1911 detections of established opioids or their metabolites and 151 detections of new synthetic opioids, demonstrating the sensitivity of the analytical methods. To ensure that detections of NSO in patient samples did not result from therapeutic use (for example for intubation and ventilation), 171 patients were excluded where fentanyl, alfentanil or remifentanil had been administered in hospital as part of treatment, or where this information was not provided. In the remaining 1644 patients there were 1607 detections of established opioids or their metabolites, most commonly methadone (565), diacetylmorphine (435), codeine (361), tramadol (60), noscapine (58) and buprenorphine (43), and 28 detections of the NSOs fentanyl (11), N-pyrrolidino-etonitazene (5), alfentanil (4), isotonitazene (4), remifentanil (2), acryloylfentanyl (1) and tetrahydrofuranylfentanyl (1). Heroin use and/or opioid toxicity was reported or clinically suspected in 306 of these 1644 patients.

Conclusion

NSOs have been detected infrequently in those attending emergency departments with toxicity related to drug use in the UK, including in those with analytical evidence or a history of heroin exposure.

7. Increasing detections of established and new psychoactive substance benzodiazepines in patients attending UK Emergency Departments after drug use

Abstract

Objective: The Identification Of Novel psychoActive substances (IONA) study analysed blood or urine samples from patients attending UK Emergency Departments (ED) after drug use to identify the substances involved, especially new psychoactive substances (NPS). Non-medical use of benzodiazepines and related compounds (BDRC) is common in the UK and has increasingly involved NPS compounds. In addition, deaths involving BDRC have increased substantially over the last decade. Here we report detection trends for BDRC, both individual and overall, in those attending UK EDs with drug toxicity between March 2015 and March 2023.

Methods: IONA included patients (≥16 years) presenting to participating EDs with toxicity after suspected drug misuse who gave informed consent (or with agreement of a relative/representative if lacking capacity). Demographic and clinical features were recorded and blood and/or urine samples analysed using liquid chromatography-high resolution accurate mass full scan and full scan MS/MS mass spectrometry.

Results: Clinical and analytical data is available from 1815 patients. There were 1992 detections of individual BDRC including 1488 for established and 504 for NPS examples. Annual rates (numbers of detections/number of patients) increased over the study period, especially for NPS BDRC (Table 1), despite generic legislation capturing psychoactive substances enacted in 2016 and control of individual NPS BDRC. For individual compounds detection rates increased until 2019 for etizolam, 2021 for flubromazolam (both controlled in the UK in 2017), and flualprazolam (controlled after 2020) and until 2023 for bromazolam (controlled in 2017). Patients exposed to BDRC were commonly also exposed to multiple other substances including those with sedative effects such as opioids and gabapentinoids.

Table 1 Annual rates of detection per patient of benzodiazepines and related compounds (BDRC), including their metabolites (compounds with at least 40 detections).

	2015*	2016	2017	2018	2019	2020	2021	2022	2023*
Patients included (n)	56	179	225	170	221	193	262	396	113
Detections per patient
Diazepam^1	0.36	0.34	0.47	0.43	0.54	0.64	0.57	0.60	0.73
Lorazepam	0.11	0.08	0.11	0.12	0.13	0.06	0.08	0.04	0.06
Etizolam**	0.00	0.01	0.00	0.03	0.14	0.13	0.19	0.06	0.06
Bromazolam**	0.00	0.00	0.00	0.00	0.00	0.00	0.09	0.12	0.21
Midazolam	0.05	0.03	0.04	0.09	0.06	0.05	0.06	0.04	0.02
Chlordiazepoxide	0.05	0.03	0.05	0.04	0.04	0.07	0.06	0.05	0.02
Alprazolam**	0.00	0.01	0.07	0.09	0.04	0.02	0.05	0.05	0.03
Zopiclone	0.00	0.01	0.02	0.01	0.03	0.00	0.01	0.11	0.12
Flubromazolam**	0.00	0.00	0.00	0.00	0.00	0.10	0.10	0.02	0.02
Flualprazolam**	0.00	0.00	0.00	0.00	0.05	0.06	0.06	0.03	0.02
Flubromazepam**	0.00	0.02	0.00	0.01	0.01	0.01	0.01	0.04	0.12
Other BDRC	0.09	0.11	0.03	0.04	0.04	0.05	0.08	0.07	0.08
Total – Established BDRC	0.66	0.58	0.75	0.71	0.84	0.91	0.89	0.89	0.97
Total – NPS BDRC	0.00	0.06	0.07	0.15	0.25	0.33	0.52	0.35	0.51
Total – All BDRC	0.66	0.64	0.82	0.85	1.10	1.24	1.40	1.24	1.49

*Incomplete year; **NPS BDRC; ¹includes temazepam and oxazepam as these may be metabolites of diazepam.

Conclusion: BDRC have been detected increasingly frequently in patients attending EDs with drug toxicity since 2015. Established compounds are most often involved, but detections of NPS BDP have increased steeply over that period. Changes for individual BDRC are not well explained by changes in drug control legislation in the UK.

8. Synthetic cathinone intoxications in Italy

Abstract

Objective: In 2022, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) confirmed synthetic cathinones (SC) as the second largest group of new psychoactive substances (NPS). The aim of this study is to evaluate the increasing trend and variability of SC intoxications in Italy through the data collected by the Coordinating Centre of the Italian Alert System for NPS (our Poison Control Centre-PCC).

Methods: All patients with history of SC abuse referred to our PCC during a 5-year period (October 2018-August 2023) were prospectively collected; only cases in which SC were analytically identified in biological samples were included. All cases were assessed for demographic data, circumstances of consumption, clinical course, and outcome.

Results: Overall, 66 patients (males 98%, median age 33.5 years, range 15–59) were included. Main clinical manifestations were severe psychomotor agitation (65%), tachycardia (33%), seizures and neuromuscular symptoms (25%), confusion (25%), hallucinations (24%), and aggression (15%). Many patients (65%) consumed SC in the context of chemsex. Multiple traumatic lesions and self-injury wounds were also frequently observed. Overall 66% of patients required sedation with benzodiazepines and 10% required endotracheal intubation. No lethal cases were reported. Fifteen different SC (in association in 6 cases) were identified (Table 1). A discrepancy between history and analytical results was recorded in 62% of cases (patients did not declare the abuse of cathinones or declared the use of a different cathinone that was not analytically confirmed).

Table 1 The synthetic cathinones detected in 66 patients over a 5 year period.

Synthetic cathinone	2011	2012	2013	2014	2015	2016	2017	2018	2019	2020	2021	2022	2023
α-PHP									4			3
α-PVP					2	1
3-CMC													4
3-MMC										1
4-MEAP							1
4-MEC	1	2
Bk-2C-B						1
Butylone	2
Chloroethcathinone								1
Cl-PVP											1
CMC												1	1
Ethylcathinone								1
Eutylone									1
MDPHP								2	5	1	7	12	18
MDPV	1	1	3	1	3				1
Mephedrone		1	1		1		1		3	2	4		2
Methylethylcathinone								1
Methylmethcathinone								1
Methylone				2	1	2
N-Ethylhexedrone											1
N-Ethylpentedrone								1			1
N-Ethyl-pentylone							1	3
Pentedrone		1
PV8										1
Compound not yet recognized							1

Conclusion: SC abuse is increasing in Italy. Despite the variability in the available SC molecules over the years, the clinical picture at emergency department admission is always similar. SC detected in previous years (2011–2017) differs from those detected after 2018 (e.g., MDPHP was never identified before 2018). Second level analysis is essential to identify the SC (and other NPS) used. Synthetic cathinones abuse could be suspected when a history of chemsex is reported.

9. Increase in O-desmethyltramadol (O-DSMT) poisonings reported to the Dutch Poisons Information Center

Abstract

Objective

In Europe, new synthetic opioids (NSOs) are commonly detected in consumer drug samples and forensic seizures. Over 70 NSOs have been newly identified since 2009. Up to 2020, the Dutch Poisons Information Center (DPIC) was rarely consulted on NSO poisonings (0–1 poisonings/year). However, this increased to 10 exposures in 2021 and 20 in 2022. Remarkably, nearly all poisonings involved O-desmethyltramadol (O-DSMT), an NSO that was not reported to the DPIC before 2021. NSOs are a public health concern because of the high risk of severe poisoning resulting from respiratory depression. Therefore, we performed a retrospective analysis on all O-DSMT poisonings reported to the DPIC.

Case series

Between 2021 and June 2023 the DPIC was consulted on 33 poisonings in 24 unique patients. Two patients were exposed repeatedly and involved in 11 poisonings. Analysis of patient characteristics showed a median age of 21 years (n = 23, range: 17–49 years) and that most were male (n = 13/24, 54%). Co-exposures were reported often (n = 28/33, 85%), mostly involving other sedatives including designer benzodiazepines (n = 16/28, 57%) and registered benzodiazepines (n = 9/28, 32%). Reported symptoms in patients poisoned with only O-DSMT (n = 5) included: hyper- or hypoventilation, apnea, sedation, coma, tachycardia, angina pectoris, paresthesia, gastrointestinal distress, perspiration, and miosis. Based on symptoms reported during consultation, 60% of patients poisoned with only O-DSMT (n = 3/5) required hospitalization (poisoning severity score (PSS) moderate to severe). The most severe case involved a female patient who ingested 9 grams of O-DSMT (30 tablets of 300 mg) purchased on the Internet. She developed miosis, apnea, and coma for which she was admitted to an intensive care unit (ICU). The severity of poisoning was moderate to severe in 57% of the cases with co-exposures (n = 16/28). The median reported dose in patients with co-exposures (150 mg, range 3–350 mg) was lower than the median reported dose in patients poisoned with only O-DSMT (2000 mg, range 300–9000 mg) (p < 0.0001, Mann-Whitney U test).

Conclusion

The number of O-DSMT poisonings is increasing in the Netherlands. The majority of patients with O-DSMT poisoning develop moderate to severe symptoms, often resulting in hospital admission. The proportion of moderate to severe poisonings was similar in patients with and without co-exposures (57% versus 60%), even though co-exposures are expected to aggravate the clinical course. This may be explained by the lower median reported dose in patients with co-exposures and the limited number of patients poisoned with only O-DSMT (n = 5).

10. Eight year trends in psychoactive substances detected in patients attending UK Emergency Departments after drug use

Abstract

Objective: The Identification Of Novel psychoActive substances study (IONA) was funded between March 2015 and March 2023 tracking substances detected in samples from consenting patients attending UK Emergency Departments (ED) after drug use, especially new psychoactive substances (NPS). Here we report trends in NPS detected over this 8-year period.

Methods: IONA included patients (≥16 years) presenting to participating EDs with toxicity after suspected drug misuse who gave informed consent (or with agreement of a relative/representative if lacking capacity). Demographic and clinical features were recorded and blood and/or urine samples analysed using liquid chromatography-tandem mass spectrometry.

Results: Clinical and analytical data are available for 1815 patients (1383 males, median age 32, range 16–79 years) recruited by 39 EDs including 285 (15.7%) admitted to intensive care and 25 (1.4%) who died. Overall, median length of hospital stay was 16.3 h. Detections totalled 1336 for NPS and 4329 for established substances. Annual NPS detection rates (corrected for patient numbers) fell after 2016. Synthetic cannabinoid receptor agonists (SCRA) were the most commonly detected NPS category (565 detections), but overall rates reduced substantially after 2016. Most common were 5F-MDMB-PINACA, AMB-FUBINACA, and MDMB-4en-PINACA. Less commonly identified were novel benzodiazepines (504 detections), most commonly etizolam, bromazolam and alprazolam with overall rates increasing up to 2021, opioids (151 detections) with fentanyl and isotonitazene the most common (excluding those likely to reflect therapeutic use after ED admission) and overall rates peaking in 2019 and cathinones (89 detections), most commonly mephedrone and N-ethylpentylone (ephylone), with overall rates falling after 2016 (Table 1).

Table 1 Annual numbers of NPS detections per patient by category.

	2015*	2016	2017	2018	2019	2020	2021	2022	2023*
Patients included (n)	56	179	225	170	221	193	262	396	113
NPS detections per patient
SCRA	0.68	0.89	0.46	0.41	0.29	0.31	0.18	0.06	0.01
Benzodiazepines	0.00	0.06	0.07	0.15	0.25	0.33	0.52	0.35	0.51
Opioids	0.11	0.06	0.08	0.10	0.19	0.08	0.06	0.06	0.03
Cathinones	0.07	0.12	0.06	0.06	0.04	0.04	0.04	0.02	0.04
Dissociatives	0.00	0.02	0.00	0.01	0.00	0.00	0.02	0.01	0.00
Stimulants (other)	0.00	0.00	0.00	0.01	0.00	0.00	0.02	0.01	0.00
NPS other	0.00	0.01	0.00	0.00	0.00	0.01	0.01	0.00	0.01
Total NPS detections	0.86	1.16	0.67	0.74	0.76	0.77	0.84	0.51	0.59

* Incomplete year.

Conclusion: IONA has provided 8 years of clinical and analytical data which can track the involvement of new and more established substances in ED presentations. Further work is needed to evaluate these trends taking into account changes in methodology over the course of the study.

11. Spider bite: an overestimated phenomenon in Italy that may be better managed

Abstract

Objective

The risk of autochthonous spider bites is overestimated in Italy, mainly in relation to unfounded fears transmitted via some media resulting in people attending the emergency departments (EDs) without real necessity. To better assess the real risk from spider bite, we evaluated Poison Control Centre (PCC) cases of suspected or confirmed spider bites in Italy.

Methods

All human spider bite cases collected by the PCC during 2019–2022 were retrospectively assessed for demographics, clinical manifestations, spider family, treatment, outcome and the effectiveness of the involved diagnostic network ED-PCC-arachnologists (experts from Italian Arachnologists Association). Confirmed cases were those with coherent clinical manifestations + spider observed/captured while biting + identification by arachnologist (when possible). Suspected cases had coherent clinical manifestations + spider not observed/captured while biting.

Results

Overall 1082 patients were collected (range 28–55 years-old); 328 (31%) were confirmed-cases (including 187 cases of verified identification of spider by arachnologists, 17.3% of total), and 754 suspected-cases (69.0%), respectively. The most frequently identified species were Zoropsis spinimana (20.9%), Loxosceles rufescens (20.3%), Cheiracanthium punctorium (17.1%), Steatoda spp. (4.3%) and Latrodectus tredecimguttatus (1.6%). Hyperaemia (72.4%), local oedema (47.5%) and local pain (35.9%) were the most frequent signs/symptoms; local necrosis occurred in 16.1% of cases. Systemic manifestations (nausea, vomiting, abdominal discomfort, fasciculations) were mainly related to Latrodectus tredecimguttatus envenomation (15 cases): Antivenin Latrodectus Mactans® was administered effectively and without adverse effects in 8/15 of these cases (72.7%), including five cases where the antivenom was urgently sent to another European country that lacked it. Loxosceles rufescens envenomation was diagnosed in 235 cases (suspected and confirmed): 66% manifested local necrosis, 20% of cases needed surgical toilet, and hyperbaric and vacuum-assisted closure treatments were applied in 2 and 1 patients, respectively. In cases where identification by the arachnologist was available (187 cases), clinical management of patients was maintained at home in 84%, and 42% of hospitalized patients were discharged home with active follow-up performed by our PCC.

Conclusion

Although the PCC has seen an increase in requests for advice from both hospitals and the public on spider bites in recent years, this clinical problem still remains misdiagnosed in many clinical aspects. Furthermore, our experience strongly emphasises the role of a multidisciplinary approach including the identification of biting species by an arachnologist. This can help reduce overcrowding in EDs and healthcare costs. Moreover, we believe that the availability of the antidote for Latrodectus tredecimguttatus envenomation should be implemented in the Mediterranean region.

12. Viper bites in France: a first multicentric approach to long-term patient follow-up

Abstract

Objective

In France, viperine envenomations pose a public health problem [1]. Although mortality is low due to the efficacy of antivenoms, there is a risk of prolonged functional disability and psychological repercussions. The aim of this study was to describe the physical and mental evolution of bitten patients, and to determine the factors associated with unfavorable outcomes.

Methods

We collected data from four French poison centers and followed patients up to one year after the bite. The variable of interest was the time to healing (in days), as self-assessed by the patient. Primary analysis by Kaplan-Meier (KM) analysis compared the evolution to recovery between groups. To compare the proportion of patients with full recovery of each time point, we used logistic regression. A Cox proportional hazards (CPH) model was performed to compare time to full recovery between groups.

Results

According to the study criteria, 170 patients were included between 2020 and 2022. The sex ratio (M/F) was 1.54 and the mean age was 45.2 ± 19.1 years (min: 12 years, max: 86 years). More than half of the patients received antivenom (59%) but 11% did not receive it when indicated. For all patients, the median recovery time was 21 days (95% CI: 15–28 days). At 14 days from the bite, 45.1% (n = 65) of all patients, regardless of envenomation grade or treatment received, were considered cured. At 1 month post-bite, 62.5% (n = 90) of patients had recovered, no matter what the grade of envenomation. At 6 months, 84% (n = 121) of patients were considered healed. The risk of non-recovery was 0.57 (CI95% = 0.50–0.65), 0.39 (0.32–0.48) and 0.16 (0.11–0.23) at 14, 30 and 180 days after the bite, respectively. Factors influencing recovery time included clinical grade of envenomation, gender, and inappropriate management. Psychological repercussions on patients were also observed, with some avoiding activities related to the biting incident and experiencing fear or thoughts about the episode, even after one year.

Conclusion

The results call for a reassessment of the follow-up of envenomed patients, beyond the initial treatment period. We should take account not only of the envenomation itself, but also the objective elements of management and the patients' psychological experience.

13. A case of Gaboon viper (Bitis gabonica) envenomation: clinical presentation and successful treatment with South African Institute for Medical Research (SAIMR) antivenom

Abstract

Objective

We report a case of Gaboon viper envenomation in which the patient’s symptoms progressed despite treatment with North American crotalid antivenom, but improved significantly after receiving species-specific antivenom.

Case report

A 59-year-old man presented to an emergency department immediately after being bitten by his pet Gaboon viper (Bitis gabonica). On arrival, he had normal vital signs, two puncture wounds proximal to the first metacarpophalangeal joint on his left hand, and edema distal to the wrist. The hospital contacted the local poison center (PC) for recommendations. The PC conveyed that Crotalidae Polyvalent Immune Fab (CroFab^®) would likely be ineffective and recommended obtaining B. gabonica-specific antivenom or transferring the patient to the regional snakebite center. Despite consultation with the regional snakebite center, the team chose monitoring instead of transfer. Initial platelet count was 77 × 10ⁱ/L; other laboratory tests were normal. The PC again recommended transfer to the regional snakebite center, which had access to B. gabonica-specific antivenom, but the patient was not transferred. He received six vials of CroFab® followed by three doses of two vials each. The next morning, swelling had progressed proximal to the elbow and platelets were 37 × 10ⁱ/L. He was finally transferred and received five vials of species-specific South African Institute for Medical Research (SAIMR) polyvalent antivenom. Six hours later, his platelets were 130 × 10ⁱ/L. By the next morning, his swelling significantly improved. He was discharged the following day.

Conclusion

The Gaboon viper, native to equatorial Africa, is a popular captive snake in the United States. Its potent venom causes tissue edema, coagulopathy, and in severe cases, hemorrhage, dysrhythmias, and death. We report a patient who developed edema and thrombocytopenia that worsened despite receiving crotalid antivenom, then resolved after treatment with species-specific antivenom. Bitis gabonica-specific antivenom is not widely available in the United States and envenomations generally require patient transfer or antivenom delivery from another location. This raises the question of whether crotalid antivenom, which is ubiquitous, can treat B. gabonica envenomation. One study suggests that crotalid antivenom delays onset of toxicity in mice, but human data are lacking [1]. This case highlights the need for prompt recognition of B. gabonica envenomation and consultation with a PC and snakebite center to facilitate administration of species-specific antivenom.

14. Severe cardiomyopathy due to Amanita proxima ingestion: a poorly recognized mushroom poisoning syndrome

Abstract

Objective

Cardiotoxicity is an uncommon and poorly defined toxic effect of Amanita spp. ingestion, reported to date in only a few case reports. A. proxima, a wild mushroom growing around the Mediterranean, was first recognized as poisonous in 1994 and associated with a toxic syndrome ("syndrome proximien") characterized by early gastrointestinal symptoms followed by acute renal failure and mild hepatic injury. In 2012, the first two cases of severe left ventricular dysfunction and cardiogenic shock after A. proxima ingestion were reported in France, followed by an additional case each from France (2014) [1] and Israel (2022) [2]. Our aim was to present a case series of patients with significant cardiac injury as manifestation of the toxic syndrome of A. proxima poisoning.

Case series

Using the Israeli Poison Center database, we identified five cases of mycologically verified A. proxima poisoning between 2012 and 2022, one of which had been reported previously [2]. Four patients developed signs of cardiotoxicity (e.g., reduced left ventricular ejection fraction, abnormal electrocardiogram (ECG), elevation of troponin and/or pro-brain natriuretic peptide serum concentrations). Two patients developed severe cardiogenic shock requiring veno-arterial extracorporeal membrane oxygenation (ECMO). Four patients developed acute renal failure requiring hemodialysis, accompanied by mild hepatocellular liver injury. In addition to supportive treatment, three patients also received N-acetylcysteine, one was treated by high-dose insulin euglycemia, and one received corticosteroids and ascorbic acid. Most complications were reversible until hospital discharge, but one patient still had substantially reduced renal function on discharge.

Conclusion

Myocardial injury manifested by acute left ventricular failure is a hallmark of severe A. proxima poisoning. In severe cases, the myocardial damage may require intensive life support, including ECMO, but is eventually fully reversible. The causative cardiotoxin(s) are yet to be elucidated.

15. Optimization of silibinin antidote use in amatoxin mushroom ingestions

Abstract

Objective: The increasing popularity of wild mushroom foraging increases the risk of untrained individuals confusing edible mushrooms with toxic species. Amatoxin, a highly hepatotoxic cyclopeptide, is the main toxic compound in Amanita phalloides, Amanita virosa, and Galerina marginata, all of which are native Danish fungi. Management of a suspected amatoxin mushroom poisoning includes a 3-day hospital treatment of activated charcoal, and either intravenously administered G-penicillin or the antidote silibinin, which is thought to reduce the risk of liver failure by inhibiting the amatoxin uptake in the hepatocytes. The availability of silibinin in the national antidote preparedness stock is sparse and the cost is high. We studied the importance of an optimized silibinin use by early specific mushroom identification.

Methods: We evaluated the number of consultations of mushroom ingestion to the Danish Poisons Information Centre over a 10 year-period. Parameters studied were suspected ingestion of amatoxin mushroom, confirmed identification by a mycologist, month, antidote initiation, and antidote cessation based on the confirmed identification.

Results: The main season was August to November, with climate related variations one year causing the season to start in July. The odd call in January was caused by ingestion of heated, frozen samples of the remains collected in the prior Autumn season. Specific mushroom identification by a professional mycologist massively reduced the number of suspected amatoxin mushroom ingestions (Table 1). Moreover, in most years 1–4 cases of antidote treatments were stopped very early after initiation due to the professional mushroom identification, which over a 10 year-period lead to cessation of 20% (16/79) of antidote treatments.

Table 1 Mushroom ingestion calls to the Danish Poisons information Centre, specifications on ingestions of amatoxin mushrooms, and the use of silibinin.

Year	2014	2015	2016	2017	2018	2019	2020	2021	2022	2023*
Total number of calls (N)	24,782	24,642	26,972	28,730	31,096	33,445	37,014	38,098	37,503	27,526
Mushrooms ingestion calls (N)	659	510	496	733	763	955	944	928	939	844
Suspected amatoxin ingestion (N)	99	45	28	70	83	96	91	95	116	27
Confirmed amatoxin ingestion (N) (Children 1–17 y/Adults ≥18 y)	5 (3/2)	4 (1/3)	2 (1/1)	13 (10/3)	12 (1/11)	7 (0/7)	7 (2/5)	7 (5/2)	9 (3/6)	4 (2/2)
Month specification
January	0	1	0	0	0	0	0	0	0	0
July	0	0	0	0	0	0	1	0	0	0
August	1	0	2	1	3	1	1	5	0	4
September	4	1	0	0	5	4	2	1	3	0*)
October	0	2	0	12	3	2	3	1	3	–*)
November	0	0	0	0	1	0	0	0	3	–*)
Antidote initiated based on suspicion (N)	7	4	2	13	13	7	9	10	11	3
Antidote dosing regimen continued based on confirmed identification (N)	4	4	2	11	12	7	6	7	7	3

* 1 January–4 September 2023. ^¤Mushroom identification confirmed by a professional mycologist.

Conclusion: Early specific mushroom identification optimised the use of silibinin antidote in amatoxin mushroom ingestions, with the potential of not only securing the antidote supply and reducing the antidote costs, but also by reducing length of hospital stay.

16. A retrospective study of case reports received by UK NPIS over a 10-year period (2012–2021) involving acute single ingestions of herbal preparations of Valerian officinalis

Abstract

Objective

Valerian (Valerian officinalis) is a perennial herb native to Europe and Asia, used to promote sleep and reduce stress. There are few reported adverse effects and safety data are limited. This review aims to explore the dose-response correlation and the safety of valerian.

Methods

This is a retrospective analysis of telephone enquires involving single acute ingestions of valerian herbal products reported to the UK National Poisons Information Service (NPIS) between 1 January 2012 and 31 December 2021. NPIS data were refined using Python programming to identify exposures concerning valerian. Single acute ingestions of valerian products were extracted and analysed. The Kruskal-Wallis test was used to analyse differences in median dose in cases with central nervous system features compared with asymptomatic patients. The Mann-Whitney test was utilised in the analysis for comparison of intentional exposures compared with unintentional exposures.

Results

The NPIS recorded 708 valerian related enquiries, of which 372 involved acute valerian-only exposure. The median number of enquiries was 31 per year (IQR 24–42), with a significant downward trend in the annual number of enquiries (p = 0.009). There was a female predominance of exposures to valerian with 254 (68%) female cases compared with 117 males (32%) and 1 unknown gender. The median age was 18 years (IQR 4–30) (range 0–89 years). Twenty-five percent of cases were under 5 years of age and 29% of cases occurred in adolescents (10–19 years). The product Kalms™ was involved in 192 cases (51%). Overall, 181 (48%) cases were intentional exposures, 132 (35%) accidental and 44 (11%) therapeutic error. The median dose ingested by patients with intentional exposure versus non-intentional exposure was significantly different (p = 0.006). The median dose ingested by patients with central nervous system features compared with asymptomatic patients was significantly different (p = 0.01). Somnolence was the most frequent clinical feature 35 (9%), with 281 (75%) cases asymptomatic.

Conclusion

Over a 10-year period there has been a downward trend in the number of cases of valerian exposures reported to the NPIS. Following exposure, 75% of enquiries remained asymptomatic, with only 9% experiencing somnolence. The results support classification of valerian as a low toxicity substance which rarely causes significant harm.

17. Poisonous mushrooms as food with special attention to Amanita pantherina: experience from the Netherlands

Abstract

Objective

Ingestion of misidentified wild-picked mushrooms can lead to significant toxicity. We aim to provide an overview of such cases reported to the Dutch Poisons Information Center (DPIC).

Methods

The DPIC database was retrospectively analyzed for symptomatic patients who ingested wild-picked mushrooms from 2020 to 2022. Data was collected regarding patient demographics, mushroom identification by a mycologist, reported clinical data, and outcome.

Results

A total of 53 events involving 66 patients were included; 50% were female, median age was 44 years (range 9–82 years). At least 35 patients were of a foreign background, mainly Eastern European (n = 15), Syrian (n = 10), or (South) East Asian (n = 5). For 16 events, mushroom remnants were available for determination by a mycologist, but proper identification was only possible in 11/53 cases (20.8%), involving 13 patients. The most frequently recognized species was Amanita pantherina (3 events/4 patients), followed by Boletus spp. (2 events/2 patients), Amanita phalloides (1 event/2 patients), Amanita virosa (1 event/1 patient), Scleroderma citrinum (1 event/1 patient), Macrolepiota procera (1 event/1 patient), Tricholoma spp. (1 event/1 patient), and Agaricus spp. (1 event/1 patient). Follow-up data on treatment and outcomes were limited. Forty-seven patients visited the emergency department. Four patients died, seemingly as result of amatoxin-containing mushroom ingestion, although no remnants were available for identification. Individual cases of the most frequently identified mushroom species (A. pantherina) are presented. 1) A couple aged 59 (M) and 53 (F) years ingested an unknown amount of boiled A. pantherina and developed serious clinical effects, including urinary and fecal incontinence, agitation alternating with decreased consciousness, followed by coma. The woman needed mechanical ventilation due to respiratory depression. After waking up from coma, both patients were agitated with hallucinations. Both recovered completely. 2) A 32-year-old man shared a meal containing four mushrooms with his wife. Within three hours, the man developed increasing drowsiness requiring hospital admission. His wife did not develop any symptoms and was excluded from this analysis. 3) A 40-year-old man ingested multiple mushroom species, of which only A. pantherina could be identified. He developed gastrointestinal symptoms (vomiting and diarrhea), but no neurological symptoms.

Conclusion

Determination of mushroom remnants by a mycologist was possible to a limited extent. Species from Amanita genus were most often identified, especially A. pantherina which contains potent neurotoxins including muscimol and ibotenic acid and can cause serious poisonings.

18. Confirmation of amatoxicosis in dogs with a rapid urine test for amatoxins: 4 cases

Abstract

Objective

Assessment of mushroom ingestion by dogs is difficult as the identity of the mushroom is often unknown, or the ingestion may be unobserved. In particular, amatoxin-containing species can lead to life-threatening poisoning. Diagnostic testing to help triage and manage these cases would be of great value. AMATOXtest is a commercially available urine assay which is affordable, simple, rapid (<10 min) and sensitive (threshold: 10 ng/mL total amanitins). Here, we present a case series of four dogs with a positive AMATOXtest.

Case series

1) A 5.7-year old (33 kg) Golden Retriever was presented with fulminant liver failure and severe coagulopathy of unknown origin. She had hypoglycaemia (2.4 mmol/L), increased lactate (13 mmol/L), bile acids (619 µmol/L), and alkaline phosphatase (AP) (132 U/L). Urine tested positive for amanitins. She was euthanised due to poor clinical condition. 2) A 4-month old (5.8 kg) Dachshund was seen biting wooden sticks, berries and mushrooms. Next morning, he developed vomiting, diarrhoea and shock. He had hypoglycaemia (2.6 mmol/L) and increased lactate (4.5 mmol/L). Urine tested positive for amanitins. Repeated activated charcoal administration and N-acetylcysteine (NAC) infusion was started but he developed fulminant liver failure with increased alanine transaminase (ALAT) (unmeasurable), AP (407 U/L), and bile acids (127.9 µmol/L) with severe coagulopathy. He was euthanised due to poor clinical condition and grave prognosis. 3) A 3-month old (8 kg) cross-breed developed lethargy, abdominal pain, vomiting with mushroom remnants in vomitus, and diarrhoea approximately 12 h after eating mushrooms. She had hypoglycaemia (2.1 mmol/L), increase lactate (10.5 mmol/L), and liver enzymes (AP 327 U/L, gamma- glutamyl transferase 13 U/L). Urine tested positive for amanitins. She was euthanised due to rapid deterioration. 4) Twenty minutes after eating a mushroom, a 10-month-old cross-breed (8.2 kg) vomited spontaneously. Thirty minutes later, emesis was induced successfully with mushroom remnants in the vomitus. Remnants were identified by a mycologist as possible Amanita phalloides. Activated charcoal was given. Approximately 10 h after ingestion, urine tested positive for amanitins, after which NAC and penicillin G infusion was started. Four days later, she was discharged in good health. During hospitalisation only the ALAT had risen slightly (142 U/L).

Conclusion

Aggressive decontamination and early treatment might improve the outcome of amatoxicosis. A rapid and simple diagnostic urine test for amanitins allows early identification of dogs at risk to develop amatoxicosis. Furthermore, it can help with decision making in (palliative) treatment of critically ill patients by confirming or excluding amatoxicosis in symptomatic patients.

19. Parathion bioactivation in HepaRG liver spheroids and monolayer cultures in vitro

Abstract

Objective

Phosphorothioate pesticides belong to the large group of organophosphorus compounds (OP) and require cytochrome P450-mediated oxidative biotransformation in the liver to form corresponding oxons, which are potent inhibitors of the enzyme acetylcholinesterase (AChE). The human hepatoma cell line HepaRG has been shown to maintain various phase I enzymes (CYP enzymes), phase II enzymes and nuclear transporters. The aim of this study was to investigate the parathion cytochrome P450-mediated bioactivation to paraoxon with two HepaRG cell-based models. This study should demonstrate the suitability of cell culture models for the investigation of the phosphorothioate bioactivation in the liver in vitro.

Methods

HepaRG liver spheroids and monolayer cultures were exposed to seven different parathion concentrations (1 µM–250 µM). The quantification of the corresponding paraoxon was performed after 5 h and 24 h with an AChE inhibition assay able to detect nM paraoxon concentrations. A standard curve was used to calculate the generated paraoxon. Interactions of paraoxon with AChE, butyrylcholinesterase and paraoxonase 1 were considered. Data are presented as mean ± SD.

Results

Our results showed the cytochrome P450 catalyzed bioactivation of parathion with HepaRG cell-based models. In monolayer cultures paraoxon formation increased in a time- and dose-dependent manner between 1 µM to 50 µM parathion and reached a plateau at about 50 µM. After exposure to 50 µM parathion, paraoxon concentrations of 545 ± 40 nM (5 h) and 700 ± 142 nM (24 h) were measured. With liver spheroids, paraoxon production was also time- and dose-dependent but generally lower than with monolayer cultures. At 50 µM parathion, paraoxon concentrations were 98 ± 8 nM (5 h) and 394 ± 24 nM (24 h). Paraoxon production reached a plateau in liver spheroids after 24 h at 100 µM and 250 µM parathion (472 ± 44 nM versus 444 ± 43 nM).

Conclusion

The drug metabolism capacity of both monolayer and three-dimensional cultures and the suitability of HepaRG models to study OP metabolism in the human liver were shown in this study. Monolayer cultures seemed superior to liver spheroids to generate relevant paraoxon amounts in the concentration range from 1 µM to 10 µM parathion.

20. Home continuous positive airway pressure (CPAP) machine use as a novel delivery method of inhaled “detergent suicide”

Abstract

Objective

We seek to describe a case of a detergent suicide utilizing a home CPAP machine for delivery.

Case report

A 45-year-old man with a history of depression reportedly mixed unknown concentrations of 4 liters of muriatic acid (hydrochloric acid) and 500 mL of lime cleaner (calcium sulfide) in an effort to produce hydrogen sulfide (hydrogen sulfide) in a “detergent suicide”. He placed the combined solution in his home CPAP water chamber and inhaled the liberated hydrogen sulfide gas. He was found with altered mentation and respiratory difficulty and the emergency medical services (EMS) were called. At the hospital he was promptly intubated. Post-intubation vitals were: pulse 94/min, blood pressure 115/67 mmHg, respiration 18/min, oxygen saturations on 40% FiO₂ intubated. Chest X-ray demonstrated diffuse bilateral interstitial infiltrates. Complete blood count (CBC) and a comprehensive metabolic panel (CMP) were normal. Arterial blood gas analysis showed pH 7.3, pCO₂ 40 mmHg, pO₂ 477 mmHg, bicarbonate 21 mmol/L, carboxyhemoglobin 0.5%, methemoglobin 0.8%, and lactate was 2.6 mmol/L. He remained intubated for approximately 24 h and on day two his chest X-ray improved and showed only a residual left basilar infiltrate. He was extubated and titrated off nasal cannula oxygen on day three and was transferred for psychiatric care.

Conclusion

This case is unique in that inhalational suicide efforts through the use of a home CPAP device are uncommonly reported in the literature, yet can potentially provide an effective means to deliver an inhaled toxin in a suicide attempt. Given the nearly closed circuit of a CPAP machine, nearly all liberated toxic gases are directly routed towards to the individual and are not lost to the surrounding environment. A single case report of a similar CPAP “detergent suicide” has was described using butane gas in a modified CPAP setup, however, chemicals were not mixed and placed in the CPAP water chamber [1]. Our patient sought to complete the following reaction: 2HCl + CaS → H₂S + CaCl. We suspect the patient survived this exposure due to low concentrations (usually <10%) found in household formulations of both the muriatic acid and lime cleaner that yielded a low concentration of hydrogen sulfide. “Detergent suicides” continue to be used by patients in suicide attempts, however, the use of a home CPAP machine is a relatively novel delivery method.

21. An Indian female with tonic-clonic seizures: a severe case of Ayurvedic saturnism

Abstract

Objective

In recent years, poisonings due to lead contamination of Ayurvedic remedies have been reported in Western countries. Chronic lead exposure can lead to weight loss, cramping abdominal pain and microcytic anaemia but lead encephalopathy in adults due to Ayurvedic medications is rare.

Case report

A 43-year-old female came to the emergency department (ED) with an history of abdominal pain and new onset generalized tonic-clonic seizures at home. She presented another seizure during hospital transportation and a third episode at the ED. History of drugs, substance of abuse and carbon monoxide exposure was excluded. Head computerised tomography (CT) scan was negative for acute findings and electroencephalogram (EEG) presented disorganized input with irritating signs. Laboratory data showed microcytic anaemia (hemoglobin 8.9 g/dL; mean corpuscular volume (MCV) 79 fL) and slight increase of alanine aminotransferase (ALT) 63 U/L (normal value 7–40). Midazolam IV bolus 0.2 mg/kg was promptly administered with resolution of the acute phase; a chronic therapy with levetiracetam 1000 mg/day was started for a suspected diagnosis of epilepsy. A detailed inquiry performed after consultation with the Poison Center with her parents revealed that over the previous 2 months, she had been taking an Ayurvedic powder sent from India by an Ayurvedic doctor to treat dysmenorrhea (5 g/day for 2 months). Blood lead concentration performed two days after admission was 153 µg/dL (normal value <3). Chelating therapy with sodium calcium edetate IV 1500 mg/m²/day was administered for 5 days followed by oral succimer for 19 days (2400 mg/day for 5 days; 1600 mg/day for 14 days). After the chelation cycle the blood lead concentration decreased (8.7 µg/dL) and laboratory data progressively improved. She was discharged after one week asymptomatic without further abdominal, neurologic manifestations and normal EEG. Levetiracetam was tapered progressively until discontinuation at one month from chelation cycle termination. Further investigations confirmed lead concentrations in the Ayurvedic preparation of 389 µg/g with an estimated oral intake of 192 µg/kg/week (WHO at-risk-weekly-intake is 25 µg/kg/week).

Conclusion

Chronic lead encephalopathy may present with memory/concentration disturbances, headache, psychiatric symptoms, diminished libido, syncope, tremor, seizure and ataxia. In western countries the use of alternative remedies may involve both Indian and Caucasian patients but it is often not reported because these products are considered “natural and safe”. Lead neurotoxicity due to the use of Ayurvedic remedies is rarely reported, it may be misdiagnosed as epilepsy or other neurological disease and it should be evaluated in a case of rapidly progressive encephalopathic signs with no apparent identifiable cause.

22. Pediatric methadone exposure and pediatric opioid use-associated neurotoxicity with cerebellar edema (POUNCE) syndrome

Abstract

Objective

Demyelinating neurotoxicity is associated with volatilized heroin, a pattern of use known as “chasing the dragon”. Affected adults exhibit bradykinesia, ataxia, and speech abnormalities with prominent cerebral and cerebellar lesions noted on neuroimaging. Rarely, children with opioid exposure develop a similar leukoencephalopathy known as the syndrome of pediatric opioid use-associated neurotoxicity with cerebellar edema (POUNCE). We report a case of POUNCE syndrome associated with confirmed methadone exposure.

Case report

A 31-month-old girl, with a medical history only notable for speech delay, was found by her mother floppy and unresponsive nearly 12 h after she was last observed as normal. The child was previously under the care of her grandparents, both known to have substance use disorder, with methadone, cocaine, and delta-9-tetrahydrocannabinol (THC) available in their home. Upon hospital arrival, naloxone was administered with a notable increase in alertness, as well as resolution of miosis. Fingerstick glucose was 60 mg/dL (3.3 mmol/L). Neurology was consulted with concern for seizures or meningitis, but both the electroencephalogram and the lumbar puncture were unrevealing. Computed tomography (CT) angiography of the head on the day of admission showed bilateral cerebellar loss of gray-white matter differentiation, favored to represent bilateral cerebellar edema secondary to toxic ingestion. Magnetic resonance imaging (MRI) of the brain performed 24 h after admission showed abnormal T2/FLAIR hyperintensity with associated restricted diffusion symmetrically involving the cerebellar hemispheres. Smaller foci of similar abnormal signal intensity were seen in the bilateral occipital subcortical white matter, and the centrum semiovale. There was no evidence of tonsillar herniation or hydrocephalus. Urine toxicology was notable for a methadone concentration of 5562 ng/mg creatinine, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP, a methadone metabolite) 8297 ng/mg creatinine, and THC 124 µg/g of creatinine. At the time of discharge, the neurological examination revealed hypertonicity of the lower extremities. A detailed visual assessment was not reported. Child Protective Services was involved during the admission.

Conclusion

Computed tomography and MRI findings were consistent with the limited existing literature describing pediatric opioid use-associated neurotoxicity with cerebellar edema (POUNCE). While radiographic abnormalities alone cannot offer a definitive diagnosis, the presence of these unusual cerebellar findings in young children should suggest opioid overdose and can help to redirect investigative efforts. The direct mechanism of toxicity is not fully understood, although cerebellar injury secondary to hypoxia is uncommon in the young pediatric population.

23. Risk factors for lung injury in acute poisoned patients aged 0–18 years: a 6 year case-control study

Abstract

Objective

To identify the incidence and risk factors of lung injury in patients with acute poisoning due to agents known to have pulmonary toxicity.

Methods

A case-control study of patients aged 0–18 years admitted to our clinic for acute poisoning. Patients were categorized by the substance involved, and a comparative analysis was performed using ANOVA, chi-square test, or risk ratio (RR) within each cohort. The control group comprised poisoned patients without lung injury and the study group patients with various degree of lung injury.

Results

Overall 4115 patients with acute poisoning were registered (2017–2022) and lung injury occurred in 1.75% (n = 72). The substances associated with a significantly higher risk of pulmonary involvement were smoke, chlorine, and hydrocarbons. Smoke inhalation led to lung injury in 32.4% (study group:control 11:23; RR =22), irrespective of age (p = 0.62) or time from exposure to admission (p = 0.61). Inhalation of chlorine gas caused lung injury in 66.7% (study group:control =14:7; RR =47) and was associated with older age (p = 0.02) and longer time from exposure to admission (p = 0.01). Intentional or unintentional ingestion of hydrocarbons led to lung injury in 56.9% (study group:control =33:25; RR =59) and was associated with younger age (p = 0.02) but was independent of time to admission (p = 0.55). The risk of lung injury due to intentional or unintentional detergent ingestion was low (2.7%; study group:control =6:216; RR =1.59) and independent of age (p = 0.23) or time to admission (p = 0.9). Pulmonary involvement occurred in <1% of cases poisoned with drugs, alcohol, pesticides, and local irritants. Patients with inhalation of smoke or chlorine gas in a collective setting had a higher risk of lung injury (p = 0.04, and p < 0.001, respectively). The presence of cough at admission was significantly associated with lung injury in all subgroups (smoke: RR = 3.35, p = 0.008; chlorine gas: RR = 1.75, p = 0.03; hydrocarbons: RR = 2.37, p = 0.001; detergents: RR = 4.08, p < 0.001). Vomiting after toxic ingestion was associated with a higher risk of lung injury in hydrocarbon poisoning (RR = 1.89, p = 0.008) but had no significant influence on detergent poisoning (RR = 1.34, p = 0.34). Fever at admission was predictive for lung injury only in patients with detergent poisoning (RR = 24, p = 0.005). The following biological parameters were associated with lung injury in one or more groups: leukocytosis (smoke RR = 2.55; hydrocarbons RR = 1.79; detergents RR = 1.9), and neutrophil-to-lymphocyte ratio (NLR) > 3 (smoke RR = 2.13; hydrocarbons RR = 3.15; detergents RR = 5.75). Venous blood gases (VBG) and C-reactive protein (CRP) concentrations were not associated with lung injury in any group.

Conclusion

Children poisoned by smoke, chlorine gas, or hydrocarbons have a high risk of pulmonary involvement. The presence of cough at admission is the only risk factor for toxic lung injury, irrespective of the incriminated substance. Leukocytosis and NLR >3 are more likely to predict pulmonary involvement than VBG analysis and CRP concentration.

24. When “pumping” iron leads to weakness: a case of ferric carboxymaltose leading to hypophosphataemia

Abstract

Objective

Iron (ferric carboxymaltose) infusion can cause renal phosphate wasting resulting in severe hypophosphataemia [1], mediated via inhibition of fibroblast growth factor 23 (FGF-23) degradation and resultant effects limiting phosphate reabsorption in the proximal renal tubules and intestine [2]. We report a case of severe hypophosphataemia secondary to repeated iron infusions.

Case report

On 26 June 2023, New South Wales Poisons Information Centre (PIC) was consulted regarding a 38-year-old female with severe hypophosphataemia. She had systemic lupus erythematosus (SLE) complicated by immune thrombocytopenia (ITP) treated with high dose prednisolone, rituximab and intravenous immunoglobulin (IVIG). In late March 2023, she was admitted with severe thrombocytopenia (platelets 5 × 10ⁱ/L) and treated with high-dose prednisolone 80 mg daily, mycophenolate 1000 mg bd and IVIG. She was discharged on weekly rituximab infusions for 4 weeks. The PIC call noted severe fatigue, malaise and myalgia with muscle weakness not suggestive of steroid-induced proximal myopathy. Her phosphate on 24 April was 0.35 mmol/L (0.75–1.50 mmol/L), from a March baseline of 1.13 mmol/L. A serum hypophosphataemia screen was normal without urine screen completion. Case review noted she had inadvertently received 3 × 1000 mg ferric carboxymaltose infusions weekly from 18 April–2 May instead of 500 mg total as per the Ganzoni formula and queried this as the aetiology of phosphate wasting. A urine fractional excretion of phosphate confirmed renal wasting. She received oral supplementation, but her phosphate was undetectable on 10 May and she commenced IV (20 mmol sodium dihydrogen phosphate) and then oral phosphate 1000 mg tds. She was dose reduced and then ceased oral supplementation in late June 2023 in favour of a high-phosphate diet and 0.5 mg calcitriol daily due to gastrointestinal complications. Her phosphate normalised in September 2023, five months after the initial treatment.

Conclusion

This patient had severe hypophosphataemia secondary to recurrent dosing, resolving after five months of therapy. Despite product labelling hypophosphataemia as a side effect, until recently it was thought to be asymptomatic and transient. The timeframe for resolution in our case however was more like recent studies [1,3].

25. Patterns of psychoactive substances in drivers involved in road accidents in the Italian province of Piacenza

Abstract

Objective

Road accidents are among the leading causes of death and injuries worldwide; therefore, the prevalence of psychoactive substance use by individuals involved is a matter of significant interest. The following study provides an in-depth examination of road accidents in the province of Piacenza, with a specific focus on the categorization of detected positive cases.

Methods

Between January 1, 2020, and December 31, 2022, analyses were conducted on urine and blood samples of drivers involved in road traffic accidents with suspected psychophysical impairment due to substance use. The analyses were performed employing high performance liquid chromatography-mass spectrometry (HPLC-MS) and results were categorized according to gender, age group and positivity to alcohol and/or drugs. A blood alcohol concentration of 5 g/L or higher indicated positivity to ethanol. Additionally, drug positivities were further classified based on substance class.

Results

Blood and urine samples of 871 drivers (677 males; 194 females) were analysed. Among men, 37.7% tested positive. Of the positive samples, 45.8% were for alcohol, 37.5% for drugs, and 16.7% for both. The most prevalent class of drugs was found to be cannabinoids (36.8%), followed by opioids (27.4%), cocaine (20.0%), and benzodiazepines (15.8%). In the age groups 18–29 years and 30–59 years, there was a prevalence of cannabinoid use (48% and 33%, respectively), while in 60–79 year olds, opioids were most prevalent (62%). Finally, in the 80–89 year age group, positivity was only detected for benzodiazepines. In women, a positivity rate of 24.7% was observed. Among positives, 39.6% were for alcohol, 43.8% for drugs, and the remaining 16.7% were positive for both. Opioids were the most frequently detected class of drugs (33%), followed by benzodiazepines (31%), cannabinoids (27%), and cocaine (9%). In the 18–29 year age group, a prevalence of cannabinoid use was observed (50%); benzodiazepines and opioids were equally detected in the 30–59 year group (40%); the only positivities in the 60–79 year age group pertained to opioids, while no samples in the 80–89 year age group tested positive for any class of drugs. In both genders, most positive results for benzodiazepines were attributed to therapeutic use (78%), whereas opioids were primarily linked to drug abuse (83%).

Conclusion

The data highlight a widespread prevalence of alcohol and drug consumption, with significant differences between genders and different age groups. It is therefore crucial to consider this information in the development of targeted prevention strategies, with the aim of reducing the risk of road accidents.

26. Exposure to malodorous mercaptans: novel in vitro biomarkers identified by mass spectrometry

Abstract

Objective

Malodorous mercaptans, i.e., alkyl thiols, exhibit an extensive stench and thus, their repulsive characteristics make them candidates to be used as riot control agents [1,2]. Since exposure to such chemicals may induce shortness of breath, nausea or vomiting [3,4], bioanalytical methods are needed in order to prove exposure.

Methods

During in vitro incubation of human plasma with iso-amyl mercaptan (SⁱAm), adducts with plasma proteins were formed. Modified proteins were subsequently proteolyzed by pronase and resulting biomarkers were detected and identified by microliquid chromatography (µLC) coupled to high-resolution tandem-mass spectrometry (MS/HR MS).

Results

Adduction of mercaptans to human serum albumin (HSA) occurred via disulfide formation between the thiol group of SⁱAm and the cysteine (Cys) residue Cys³⁴. During pronase-catalyzed proteolysis, SⁱAm-modifications were detected as peptide-adducts, namely as the modified dipeptide cysteine-proline, Cys³⁴(-SⁱAm)Pro. During µLC-MS/HR MS analysis, the precursor ion of Cys³⁴(-SⁱAm)Pro (m/z 321.131) resulted in product ions at m/z 217.064, m/z 200.038, m/z 170.081 and m/z 116.070, which could all be assigned to the dipeptide-backbone. The SⁱAm-adduct was identified by a product ion at m/z 304.104, resulting from loss of ammonia.

Conclusion

The identified novel disulfide-adduct might be used as a biomarker of exposure to the malodorous SⁱAm, and similar adducts were also formed with the three mercaptans ethyl mercaptan, n-butyl mercaptan and tert-butyl mercaptan. Furthermore, it is expected that various other plasma proteins undergo comparable adduction leading to comparable peptide-adducts.

27. Falsely elevated serum digoxin concentration secondary to enzalutamide-related immunoassay interference

Abstract

Objective

Immunoassays are used in clinical laboratories to determine digoxin concentrations for therapeutic drug monitoring, and in cases of digoxin overdose. Enzalutamide is a non-steroidal androgen receptor antagonist used in the treatment of metastatic castration-resistant prostate cancer. Enzalutamide has been reported to interfere with digoxin immunoassays, particularly the chemiluminescent microparticle immunoassay (CMIA) method despite not sharing a similar structure [1]. The mechanism of interference is hypothesized to be linked to an interaction between the antibody used for testing and its oxo-imidazoline function [2]. We report a case of falsely elevated serum digoxin concentrations in a patient using therapeutic doses of enzalutamide, secondary to analytical interference with the laboratory digoxin assay.

Case report

A 76-year-old male presented with two weeks of lethargy, lower limb weakness and dyspnoea. There were no complaints of nausea, vomiting, palpitations or visual disturbance. The patient denied taking an overdose of any medication. He had no clinical signs of digoxin toxicity on examination. A routine serum digoxin concentration was performed and was elevated at 14 ng/mL (therapeutic range 0.8–2.0). A repeat sample performed using the same CMIA on an Architect Abbott analyzer was 12 ng/mL. A 12-lead electrocardiogram (ECG) showed a normal sinus rhythm with no evidence of atrioventricular conduction delay, no downsloping ST/T wave changes and no other manifestations of digoxin toxicity. Medication reconciliation revealed that he was currently prescribed enzalutamide for prostate cancer and amiodarone, rivaroxaban, fludrocortisone, frusemide, clopidogrel, dutasteride and pantoprazole. He had previously been prescribed digoxin, but it had been discontinued more than 6 months ago.

Conclusion

Clinicians should be aware of the potential for enzalutamide to produce a falsely elevated serum digoxin concentration, which may lead to unnecessary administration of digoxin-specific antibody fragments or other therapies used to manage digoxin toxicity. In addition, this interaction may lead to a falsely elevated serum digoxin concentration and inappropriate cessation of digoxin therapy. In such cases, confirmatory testing using a different technique is recommended.

28. Deployment-related lung diseases caused by chemical substances exposition: the Ukrainian war experience

Abstract

Objective

Military personnel and civilians are exposed to toxic substances and environmental pollutants that cause a variety of respiratory system diseases (RSD) in the territory of hostilities [1]. The exposures include explosive compounds, combustion products, fuel vapors, consequences of fires, infrastructure damage, etc. The problem lies not only in acute intoxications, but also in the delayed consequences of toxic substance exposure to the respiratory system. The aim of the study was analysis of the structure and clinical features of RSD caused by chemical substances in the territory of war in Ukraine.

Methods

Analysis of statistical data of the State Labor Service of Ukraine, statistical report of the Ministry of Health of Ukraine, and an analytical review of scientific publications, using abstract databases (PubMed, Medline, BMJ group).

Results

More than 50,000 people are exposed to high concentrations of dangerous chemical substances in the territory of hostilities in Ukraine. Considering the specificity of atmospheric air pollution, in the zone of military operations, RSD includes diseases of inflammatory, allergic, fibrotic and immune origin depending on the prevalence of the etiological factor [2]. The most common chronic Deployment-Related Lung Diseases (DRLD) in the combat zone are bronchial asthma, bronchitis, constrictive bronchiolitis, eosinophilic pneumonia. Other pulmonology disorders such as interstitial lung diseases are infrequently reported, that may be associated with the post-exposure development of the disease. Massive destruction of old buildings containing asbestos may lead to an increase of lung cancer and mesothelioma prevalence in the future. It is important to emphasize, that not all deployment-related respiratory complaints may result from deployment chemical hazards and a broad differential should be considered.

Conclusion

A wide range of air pollutants in the war zone in Ukraine has a combined effect on the health of military personnel and civilians, leading to the development of DRLD. However, the association between chronic lung diseases and airborne hazard exposure requires further longitudinal research studies with objective pulmonary assessments.

29. The Munich Research Training Group “Targets in Toxicology – Deciphering Therapeutic Targets in Lung Toxicology”

Abstract

Objective

Twelve Munich-area research partners from the LMU Munich, Helmholtz Zentrum München, Technische Universität München, and the Bundeswehr Institute of Pharmacology and Toxicology collaborated to form the Munich Research Training Group (RTG) "Targets in Toxicology – Deciphering Therapeutic Targets in Lung Toxicology." The RTG, a structured MD/PhD program, engaged in training a new generation of lung toxicologists and fostered collaborations with the goal of developing a comprehensive mechanistic understanding of toxic lung injury in acute and chronic toxic lung injury using a new conceptual approach of "precision toxicology."

Methods

The RTG is built on three pillars. Innovation – The RTG investigates new therapeutic targets for lung toxicity. Chemical-induced toxic syndromes are often caused by direct interactions between the chemical and target receptor proteins, resulting in adverse cellular responses, including cell death and inflammation. Although targeted treatment is widely established in other disciplines such as cancer, the concept of "precision toxicology" is new. Our cutting-edge multidisciplinary and cross-disciplinary research will shed light on toxicant-targetable molecular and cellular responses. Excellence – We launched a truly interdisciplinary research collaborative and recruited scholars from a variety of contemporary life sciences domains. This included leading research groups in Munich with a long history of toxicological research, as well as researchers who have excelled in bioorganic chemistry, biochemistry, cell biology, and cellular signal transduction along with investigators specializing in the development of cutting-edge methodology such as "-omics" and single cell approaches. Internationality – The RTG's international program provides young researchers with excellent international science and qualifying measures early in their careers. Guest lectures and accompanying meet-the-speaker seminars, international symposia, and a laboratory exchange program (internships) that allows our PhD candidates to study specific aspects of their studies in top laboratories across the world are all part of the program.

Results

The RTG was kicked off in September 2018 with 12 projects. The structured MD/PhD program includes specialized training in lung pathophysiology and the full field of toxicology from world recognised experts. The RTG is a worldwide unique program with an exceptional scientific atmosphere and cutting-edge research infrastructure. Students are provided with individualized teaching curricula, worldwide networking opportunities, including an exchange program, and close supervision while working on cutting-edge research projects at the intersection of fundamental and clinical science.

Conclusion

For our PhD candidates, the RTG "Targets in Toxicology" offers as a springboard to a variety of job opportunities. Studies within our RTG have received significant worldwide attention, with 55 original publications to date in high-ranking international toxicology and respiratory journals, as well as notable multidisciplinary journals. Posters from selected projects illustrate some of the most recent outcomes.

30. Common characteristics and dilemmas in management of acute exposure to chlorine based products

Abstract

Objective

Observing common features of acute exposure to pulmonary irritants in our community and identifying factors that influenced hospitalisation.

Methods

Data were collected from medical records of patients exposed to pulmonary irritants treated at the Department of Emergency and Clinical Toxicology, Belgrade, over a 5-year period. Case records were reviewed for age, gender, type of agents and exposure, symptoms, clinical findings, treatment, admission and discharge criteria.

Results

There were 179 patients (female 76%, average age of 45.4 ± 14.46 years). All exposures were accidental, predominantly due to chlorine-based products (174; 97%), others were phosphoric and nitric acid inhalations. The main source of exposure was inappropriate use of cleaning products (159, 89%), the most common by mixing hydrochloric acid and products containing sodium hypochlorite due to bathroom cleaning (82; 46%). Other cases included incidents at pools (9; 5%), school accident during chemistry class (7; 4%) and industry incidents (4; 2%). Patients presented with one or more characteristic signs of mucosal irritation: irritating cough (86%), dyspnoea (64%), lacrimation, nose and throat irritation (44%), nausea and vomiting (16%), and retrosternal burning (14%). There were 9 (5%) asymptomatic patients that remain asymptomatic during the observation period. Depending on manifestations, initial treatment included oxygen, bronchodilators and corticosteroids. In most cases (119; 67%) symptoms and signs resolved in the emergency department within approximately 3 h from presentation, which was also the time when admission decisions were made. Once asymptomatic, patients were not recommended for the 6-h observation so they were discharged with appropriate instructions. Despite treatment, symptoms persisted in 51 patients (28%); 12 patients refused hospitalisation and 39 (22%) were hospitalized. The average SaO₂ on presentation of discharged and admitted patients was 95.9% and 91.4%, respectively. Among hospitalised patients, hypoxemia (28, 72%) was mild to moderate in 13 and 15 cases, respectively. History for one or more underlying conditions, smoking (20; 51%), respiratory and cardiovascular disease (22; 56%) was presented in 30 patients (77%). Chest X-ray showed consolidations in 5 and accentuated bronchovascular markings in 15 cases. There were no cases with signs of pulmonary oedema. The average length of hospitalisation was 2.4 days.

Conclusion

Mildly symptomatic and asymptomatic patients refusing the suggested length of observation must be given clear instructions in case of symptoms deterioration about delayed chlorine effects. In chlorine exposed cases lower oxygen saturations on presentation and underlying conditions can facilitate the admission decision. Prevention must still be targeted at proper use of cleaning agents.

31. Investigating disease-specific effects of cigarette smoke in interstitial lung disease-derived samples

Abstract

Objective

Cigarette smoke (CS) is a key risk factor for certain interstitial lung diseases (ILD) including idiopathic pulmonary fibrosis (IPF). Discovering disease- and cell type-specific mechanisms underlying the response to CS and pathogenesis of chronic lung diseases may lead to new treatment approaches. The overall aim is to identify novel molecular pathways induced by cigarette smoke (CS) that are specifically relevant to interstitial lung diseases (ILD).

Methods

Proteomic data from bronchoalveolar lavage fluid (BALF) [1] of a chronic lung diseases (CLD) patient cohort predominantly composed of ILD patients (n = 124: 16 idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP), 79 non-IPF ILD, 29 non-ILD) was compared for smoking history and changes classified as transient or persistent. Primary human bronchial epithelial cells (phBECs) were chronically exposed to CS extract (CSE) and the cellular response to assessed by proteomics and subsequent pathway enrichment analysis. Having identified nuclear protein 1 (NUPR1) as a potential novel key regulator in this context, cell barrier integrity and cytotoxicity were monitored after ZZW115-mediated NUPR1 inhibition in both normal and IPF-derived phBECs (+/− CSE) after 7 and 28 days of differentiation. Cellular localization and cell type composition were analysed by immunofluorescent (IF) staining, and gene expression using quantitative polymerase chain reaction.

Results

CS induced transient and persistent changes in the BALF proteome with an overlap between transient changes in CS-exposed phBECs and BALF. Macrophages were identified as a source of persistent changes, but none of these proteomic changes appeared to be specific to ILD. NUPR1 inhibition induced comparable cytotoxicity in control and CS-exposed phBECs but modulated the pro-ferroptotic gene ACSL4 in a CS-dependent manner. Notably, the half-maximal inhibitory concentration (IC₅₀) varied significantly between normal and IPF phBECs after full differentiation. Finally, IF staining revealed an increase of club cells in IPF-derived phBECs compared to normal phBECs.

Conclusion

Smoking triggers transient and persistent proteomic changes in BALF. Our findings suggest airway epithelial cells as transient and macrophages as persistent source. Inhibition of NUPR1 in phBECs led to significant cytotoxic effects and the upregulation of pro-ferroptotic genes, with the latter being partially influenced by CSE. IPF cells were more susceptible to cytotoxic effects of NUPR1 inhibition and displayed a different cell type composition after full differentiation. The results indicate that disease-specific differences are maintained in IPF phBEC culture and suggest an important protective role for NUPR1 in IPF-derived phBECs.

32. Ex vivo tissue perturbations coupled to single-cell RNA-sequencing to study multi-lineage cell circuit dynamics in human lung fibrogenesis

Abstract

Objective

Pulmonary fibrosis develops as a consequence of failed regeneration after injury or exposure to occupational and environmental agents such as toxic insults. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques.

Methods

Using human precision-cut lung slices (hPCLS) to experimentally dissect cell differentiation trajectories and gene regulatory networks during human lung fibrogenesis using multimodal and multiplexed time-resolved single-cell genomic profiling coupled to small interfering RNA (siRNA) and drug-mediated perturbations.

Results

In our previous work, we coupled ex vivo cytokine and drug perturbations of hPCLS with single-cell RNA sequencing (scRNAseq) and induced a multilineage circuit of fibrogenic cell states (regenerative intermediate cell states, RICS) in hPCLS, which we showed to be highly similar to the in vivo cell circuit in a multi-cohort lung cell atlas from pulmonary fibrosis patients. Cell-cell communication routes in patients were largely conserved in the hPCLS model and affected by anti-fibrotic drug treatments in a cell type-specific manner.

Conclusion

Our work provides an experimental framework for perturbational single-cell genomics directly in human lung tissue that enables analysis of tissue homeostasis, regeneration, and pathology, in addition to examining the mechanism of action of toxic compounds and candidate drugs. We anticipate that this novel approach will ultimately enable the simultaneous discovery and pre-clinical translation of novel pro-regenerative therapies for pulmonary fibrosis. hPCLS combined with single-cell analysis is a powerful model to study the mechanism of action for both toxic compounds and (candidate) drugs.

33. Use of naloxone in patients treated for opioid overdose at a primary care emergency clinic in Oslo, Norway, 2014–2021

Abstract

Objective

Naloxone is a lifesaving antidote for patients with respiratory depression caused by opioid overdose. We describe the use, and trends in use, of naloxone in patients treated for opioid overdose at a primary care emergency clinic in Oslo, Norway, from 2014 to 2021.

Methods

The study was an observational study, with data collected retrospectively at the Oslo Accident and Emergency Outpatient Clinic (OAEOC). All patients presenting between 1 January 2014 and 31 December 2021 with an acute recreational opioid overdose were included, excluding poisonings with suicidal intention and patients drugged against their will or without their knowledge. We registered drugs taken, if and where naloxone was administered, respiratory rate, Glasgow Coma Score (GCS), and whether the patient was transferred to hospital.

Results

From 2014 to 2021, a total of 6796 opioid overdoses were included. Naloxone was given in 1734 (25.5%) of the cases. The proportion given naloxone was stable during the study period, except for an increase in 2015 and 2016 (32.1% and 32.0%, respectively) and a decrease in 2018 (17.0%). When naloxone was given, 1223 (70.5%) received it before arriving at the clinic, i.e., mainly from ambulance personnel, 388 (22.4%) received it at the clinic, and 123 (7.1%) both before arriving and at the clinic. Among the patients who received naloxone, 14.6% had bradypnoea (respiratory rate <10/minute) at arrival, median GCS at presentation was 14 (IQR 12–15), median lowest GCS was 11 (8–14), and 19.1% were transferred to hospital. Naloxone was given in 27.8% of heroin overdoses, 13.8% of methadone and/or buprenorphine overdoses, and in 22.4% of overdoses with other opioids.

Conclusion

The proportion of opioid overdose patients given naloxone was fairly stable from 2014 to 2021. The registered clinical findings and types of drugs taken provided no obvious explanation for the observed fluctuations in naloxone administration.

34. Overdose involving opioid agonist treatment opioids in Oslo, Norway

Abstract

Objective

Opioid agonist treatment (OAT) is considered an effective treatment for opioid-dependent people, reducing both morbidity and mortality. Yet, overdose due OAT drugs, both fatal and non-fatal, is not uncommon. The main OAT drugs in Norway are methadone and buprenorphine. We describe patients presenting with overdose involving methadone or buprenorphine and compare them to patients presenting with heroin overdose.

Methods

In this retrospective observational study, we included patients presenting to the main primary care emergency clinic in Oslo with overdose involving methadone, buprenorphine and/or heroin from 1 October 2013 to 31 December 2021. Overdoses from suicidal intention were not included. Cases were grouped as M (methadone and not buprenorphine), B (buprenorphine and not methadone), or H (heroin and not methadone or buprenorphine). Cases involving both methadone and buprenorphine were excluded. Data were collected from the patient records at the Oslo Accident and Emergency Outpatient Clinic, using the variable set developed by the European Drug Emergency Network (Euro-DEN).

Results

In total, 5698 patients were included, 421 in the M group, 182 in the B group, and 5095 in the H group. The patients presenting with methadone overdose were older (M: 45 years, B: 37 years, H: 35 years, p < 0.001), more often female (M: 25.4%, B: 20.9%, H: 20.0%, p = 0.029), and more often admitted to hospital (M: 21.1%, B: 9.3%, H: 12.0%, p < 0.001), compared with patients presenting with buprenorphine or heroin overdose. Fewer patients in the buprenorphine group were brought by ambulance (M: 70.5%, B: 49.5%, H: 69.3%, p < 0.001), given naloxone treatment (M: 16.2%, B: 8.8%, H:28.0%, p < 0.001), and transferred to hospital, compared with the two other groups. The patients in the buprenorphine group also had a less affected conscious level, i.e., the lowest Glasgow Coma Score (M: 13, B: 14, H: 13, p = 0.023).

Conclusion

Overdoses involving methadone seem to be more severe than those involving buprenorphine or heroin.

35. Appropriateness of antidote use in the emergency setting

Abstract

Objective

To analyze the usage of specific antidotes (flumazenil, naloxone, N-acetylcysteine) in drug poisoning cases within an Emergency Department and assess the appropriateness of their utilization.

Methods

Observational study of indication-prescription based on a clinical record of poisonings in the emergency department. The appropriateness of antidote administration was assessed by the absence of contraindications and specific criteria for their indication [1–3].

Results

During the study period (January 2022–August 2023), 608 drug poisonings were recorded. In 471 cases (77.5%), the implicated drug was amenable to treatment with an antidote. Antidote therapy was administered to 85 patients (18.0%), with 36 of them receiving at least two antidotes. All three evaluated antidotes were readily available for prescription in the Emergency Department. From an indication perspective, in the 63 paracetamol cases, the use of N-acetylcysteine was deemed appropriate in 85.7% of cases. In 9 patients, its use was considered inappropriate, with 3 cases having no indication and 6 cases not being prescribed despite being indicated. Of the 23 opioid drug poisonings, the use of naloxone was considered appropriate in 82.6% of cases. In 4 patients, its use was considered inappropriate, with 1 case having no indication and 3 cases not being prescribed despite its indication. In the 421 benzodiazepine poisonings, the use of flumazenil was considered appropriate in 91.2% of cases. In 37 patients, its use was considered inappropriate, with 20 cases having no indication, 8 cases having contraindications, and 9 cases not being prescribed despite its indication. No fatal outcomes occurred in any cases where the antidote was not administered despite being indicated.

Conclusion

Antidote administration is infrequent and is primarily performed in accordance with recommendations. Nevertheless, the results leave room for improvement and support the need for ongoing training of healthcare professionals involved in the management of poisoned patients, as well as the promotion of Clinical Toxicology Units with multidisciplinary teams that can help enhance the management of drug poisonings.

36. New drug of abuse: hexahydrocannabinol (HHC) in Toxicology Information Centre calls

Abstract

Objective

Abuse of psychoactive substances is a wide social problem. Hexahydrocannabiol (HHC) is a new psychoactive substance, a cannabinoid, chemically similar to Δⁱ-tetrahydrocannabinol (THC) [1]. Products are offered through vending machines and e-shops. They include jelly (gummies), liquids, cookies or e-cigarettes, contain a broad range of HHC doses and toxicity data are lacking. In this retrospective study, based on the calls to the Toxicological Information Centre (TIC) we analyzed intoxications due to HHC.

Methods

Inquiries concerning HHC were searched in the TIC electronic record system up to 25 September 2023. Medical reports of exposed subjects were examined and symptoms were categorized based on Poisoning Severity Score.

Results

The first HHC call was recorded on 13 May 2022. We registered a total of 101 consultations, including 57 males and 44 females, aged (21 ± 12 years; range 2–64 years). The exposure was intentional in 85 subjects, unintentional in 16 subjects; seven concerned pre-school children, who had mistaken them for a candy. The most frequent HHC exposures were e-cigarettes (33), jellies (31, mean HHC content used 92 mg; range 25–300 mg), and cookies (23, mean HHC 148 mg, range 20–500 mg). The dose did not correlate with severity of symptoms. Physicians consulted in 86 cases and 37 medical reports were received; 23 subjects were hospitalized and 14 were treated on an outpatient basis. Additionally, 15 calls came from the patients. Symptoms developed a few minutes to 4 h after exposure: 45 subjects had mild, 42 moderate and 8 following severe symptoms: hallucinations (6, due to different dose and products), seizures (1; half a jelly) and ataxia (1; 2 jellies); symptoms were not reported in 6 subjects. Among 23 patients admitted to hospital, 15 subjects were hospitalized for 24 h, 5 for 2 days, 2 for 3 days, and one subject for 5 days (combined intoxication). They received fluids with crystalloids (21), anxiolytics (6), antiemetics (3), and charcoal (2). THC in urine was tested in 19 patients, positively in 18 patients.

Conclusion

Although HHC products may cause intoxication and addiction, they are freely available. They are especially popular with young adults, however, children were also intoxicated and needed hospital treatment. Even one 25 mg HHC jelly/cookie may cause symptoms regardless of age. The Czech Government has taken steps to limit the sales. Quality control is also needed.

Acknowledgements

Cooperatio 207041-3.

37. Infantile hypercalcemia induced by acute calcium carbonate ingestion

Abstract

Objective

To describe a case of calcium carbonate overdose in a young girl.

Case report

A 2.5-year-old girl, generally healthy and vaccinated, with no significant medical history, presented to the Emergency Department (ED) for a suspected drug overdose. She was left unsupervised at home and was found on the floor with a half-empty package of 750 mg calcium carbonate tablets (Tums^®, GSK, Missouri, USA) in her hands. Her caregivers did not see her swallowing the tablets. Her mother, who took the tablets for heartburn during pregnancy, remembers taking a relatively small number of tablets. The child was taken to the ED about an hour after she was found with the package. Upon arrival, she was in excellent general condition. Vital signs were normal, and physical examination was normal. The mother brought the package of tablets, and 27 were counted out of 60 in a complete package. Based on the patient's history, it was estimated that the dose consumed was 8.5–9 g (773–818 mg/kg). Three hours after the presumed time of ingestion, her calcium concentration was 12.4 mg/dL (normal for age ≤10.8 mg/dL) in the presence of albumin 47 g/L. Ionized calcium was 6.31 mg/dL (normal ≤5.08 mg/dL). Phosphate and magnesium were normal. Venous blood gas analysis showed, pH 7.359 pCO₂ 35.0 mmHg, bicarbonate 19.3 mmol/L, and base excess of 5.3. ECG showed normal sinus rhythm with a QTc of 377 ms and PR interval of 120 ms. The calcium creatinine ratio in a spot urine test was 1.9 (normal value ≤0.2). The girl was not treated with activated charcoal as it does not absorb calcium in its ionic form. She was hospitalized for monitoring and treated with 0.9% saline with 5% glucose (0.9% standard). Calcium concentrations normalized over 24 h. Throughout her stay in the hospital, she remained asymptomatic.

Conclusion

This is the first report of calcium carbonate poisoning in children. Over-the-counter antacids, especially calcium carbonate, are widely used and do not require a prescription. Their safety profile is considered to be high. Despite the impression that this drug is relatively harmless, it is essential to remember that there is a real possibility of hypercalcemia in intentional or accidental poisonings. Therefore, monitoring and following calcium concentrations with appropriate treatment is important.

38. A review of electronic cigarette exposures in children aged 5 years and younger

Abstract

Objective

E-cigarette devices have evolved since their introduction to the UK in 2003. They are available in various colours and shapes, and exist as either single-use or refillable designs. E-liquid nicotine concentrations in the UK are restricted to 20 mg/mL [1]. The common belief is that e-cigarettes are “safer” than conventional cigarettes since users inhale nicotine in a vapour, rather than smoke. Additionally, e-cigarettes do not burn tobacco, or produce tar or carbon monoxide. There is concern that users may not store devices and e-liquids safely.

Methods

A retrospective review of e-cigarette exposures in children aged 5 years and younger to the National Poisons Information Service (NPIS) was performed between 1 January 2008 and 30 June 2023. Enquiries concerning exposures to multiple agents were excluded.

Results

The NPIS received a total of 738 enquiries, increasing from one enquiry in 2008 to 63 in 2022. The highest number of enquiries in one year occurred in 2018 (n = 114; 20%). Three hundred and eighty-five enquiries (52%) involved male patients. Infants aged 1 year old represented nearly half (n = 360) of all exposures. Most exposures were acute (n = 734), accidental (n = 733) and occurred at home (n = 732). Two exposures resulted from a therapeutic error, by an adult, following unintentional e-liquid administration as nasal and ear drops. Most exposures (664, 90%) concerned ingestion of e-cigarette liquid, 79 cases involved inhalation of the e-cigarette, and 29 were concomitant skin/ingestion exposures. Other exposures involved eye contact alone (n = 9) or a combination of routes of exposures (ingestion/inhalation/skin/eye). Overall, 428 patients were referred for assessment; of these, 167 required further investigations, and 168 needed their vital signs monitored. One hundred and five patients were treated supportively. Thirty-one enquiries (4%) cited vomiting as a feature of toxicity, six described coughing, and four cases experienced abdominal pain. Poisoning Severity Score (PSS) at the time of enquiry reported PSS0 (asymptomatic) n = 615 (83%), PSS1 (minor) n = 96 (13%) and PSS2 (moderate) n = 10 (1%). One enquiry, concerning a 1 year-old child, documented a PSS3 indicating severe toxicity (bradycardia (heart rate 70’s), hypotension (BP 90/40 mmHg), and oxygen saturation 77%).

Conclusion

Acute exposures to e-cigarette liquids rarely results in severe toxicity. Nevertheless, a message highlighting the potential dangers of nicotine products and the importance of safe storage is recommended, to ensure that children are protected against accidental exposures to these devices.

39. Epidemiology, clinical profiles, and outcomes of acute isoniazid poisoning in children

Abstract

Objective

To assess the prevalence, clinical characteristics and outcomes of acute isoniazid poisoning in children, and to identify any potential correlations between demographic factors, symptoms and prognosis.

Methods

We conducted a retrospective, multicentre analysis of acute isoniazid poisoning in children over a 7-year period. Epidemiological, clinical and paraclinical data were collected from five pediatric poison centres and statistically analysed using DataTab statistical software.

Results

In total 26 patients diagnosed with acute isoniazid poisoning were identified between 1 September 2017 and 31 August 2023. Most (92.3%) patients were female, resulting in a male-to-female ratio of 12:1. The median age was 14 years (range 5–17 years) whilst the median hospitalization period was 4.5 days. A significant percentage of cases (69.2%) were intentional. Dosage information was available in 80.8% of cases, ranging from 400 mg to 9 g. Symptoms typically appeared within one hour after ingestion, including neurological symptoms in 84.6% of patients, mainly seizures (60.5%) and gastrointestinal symptoms, predominantly vomiting (61.6%). Metabolic disorders occurred in 42.3% of cases, with 30.8% developing metabolic acidosis. Liver dysfunction and rhabdomyolysis were each found in 23.1% of cases. Antidote administration was necessary in 88.5% of cases, with 7.7% requiring intensive care. Severity, as determined by the Poison Severity Score, classified 26.9% of cases as severe. A statistically significant negative correlation was observed between patient age and the probability of experiencing digestive symptoms (p = 0.16), metabolic disorders (p = 0.006), and seizures (p = 0.005).

Conclusion

Acute isoniazid poisoning primarily affected girls. Seizures, vomiting and metabolic acidosis are the main symptoms, the onset being within 1 h after ingestion in most cases [1]. Age is a significant factor that influences the clinical presentation, highlighting the importance of age-specific management guidelines.

40. Brief intervention for adolescents with acute alcohol intoxication: assessing efficacy at 6 months

Abstract

Objective

The aim of this study is to evaluate the effectiveness 6 months of a Brief Intervention (BI) implemented in the emergency department of a public hospital in reducing alcohol use.

Methods

We conducted a quasi-experimental, pretest-post-test single-group design study on patients under 18 years old who visited the emergency department (ED) of a paediatric hospital in Barcelona (Spain) for alcohol intoxication. Risk assessment and BI were conducted during follow-up visits. The study obtained the approval from the Clinical Research Ethics Committee and was conducted from November 2019 to September 2023. The score on the Alcohol Use Disorders Identification Test (AUDIT) was used for initial risk assessment and to measure the effectiveness of the BI. Telephone follow-ups were conducted at 1 and 6 months. We fitted a General Linear Model to predict AUDIT score at 6 months with AUDIT scores at baseline and month follow-up, gender, age, age of first use of alcohol and setting a target (alcohol use reduction or abstinence). The data were analysed using the open-source software Jamovi.

Results

Seventy-one patients were included in the study (62% women, mean age 14.5 years old (SD =1.1)). Girls were younger on average (t = 2.26, gl =69, p = 0.027) and the age of onset of alcohol consumption was also lower for girls (t = 3.29, gl =69, p = 0.002). All patients agreed to set a target, with 57.7% aiming for zero alcohol consumption. The average AUDIT score at baseline was 9.82 (SD =3.1) and AUDIT-C 2.92 (SD =1.8). Those considering abstinence showed a significantly lower AUDIT, at baseline (t = 2.61, gl =69, p = 0.009), month follow-up (t = 2.83, gl =63, p = 0.006) and follow-up at 6 months (t = 4.04, gl =46, p < .001). A significant effect was observed (F(7, 40) = 17.82, p = <0.001, η² = 0.757) which indicated that setting a target (b = −0.61, df =40, p = 0.003) and AUDIT scores both basal (b = −0.25, df =40, p = 0.002) and in the first follow-up (b = 0.57, df =40, p < 0.001) are statistically significantly related to the AUDITC score 6 months after the AAI.

Conclusion

Follow-up after the BI demonstrated a significant reduction in risk. Paediatric emergency departments play a crucial role in identifying these patients and initiating interventions to reduce alcohol use and prevent future intoxications.

41. Prolonged vitamin D overdosage in the paediatric population

Abstract

Objective: Vitamin-D intoxication is a rare but not irrelevant condition, almost exclusively caused by chronic overdosage due to mistakes in administration or consumption. This often involves the paediatric population, given the wide use of vitamin D supplements in these patients, usually at a daily dose of 400 IU. Clinical manifestations are hypercalcemia and its consequences. Repeated vomiting, malnutrition, and growth retardation are present in severe cases. We evaluate the features of the cases of paediatric chronic vitamin D overdosage.

Methods: A retrospective analysis of cases referred to our Poison Control Centre (PCC) from January 2020 to September 2023. All cases of repeated vitamin D overdose (daily overdoses for at least a week) in patients under 3 years of age were evaluated. Patient demographics, administered dose, clinical manifestations, and laboratory tests were analysed.

Results: In total 29 cases were included (15 females), with age ranging from 1 to 19 months. The average daily dose of 25OH-Vitamin D was 4550 IU (range 1400–20,000 IU), administered for an average time of 87 days (range 7–381 days). At the first medical assessment, 22 patients were asymptomatic (76%), and 7 were symptomatic (Table 1). Four patients had significant hypercalcemia (greater than 11 mg/dL). All patients who presented with symptoms received an overdose of vitamin D of more than 4-fold the therapeutic dose, and for at least two months. Notably, the three most severe cases received overdose for most or all their lives. This finding confirms that it is the duration of the overdosage that confers the greatest severity of the intoxication.

Table 1 Summary of children with chronic vitamin D overdose.

Patient	Age (month)	Gender	Administrated dose		Symptoms at clinical evaluation	Blood 25OH-vitamin D (ng/mL)	Serum calcium (mg/dL)
			Daily intake (IU)	Number of days
1	9	F	3750	270	Reduced growth	> 150	11.6
2	14	M	1000	360	Reduced growth	ND	ND
3	10	F	2550	210	Reduced growth	ND	ND
4	4.5	F	5000	135	Tremors	> 150	11.4
5	6	F	1750	60	Tremors	ND	11.7
6	5	M	5000	60	Irritability	ND	10.8
7	12	M	2900	90	Vomiting	> 150	10.9
8	4	M	20,000	70	None	> 150	11.2

Conclusion: Vitamin D intoxication in paediatric patients can cause significant symptoms and must not be underestimated. Therapeutic errors are often caused by the existence of formulations with different concentrations. Physicians and pharmacists should take this into account, always checking that caregivers have a clear understanding of the dosage to be administered.

42. A fatal case of “low toxicity” surfactant ingestion

Abstract

Objective: Surfactant toxicity is believed to result from the disruption of lipid membranes, including those of mitochondria, leading to the disruption of oxidative phosphorylation. Effects include gastrointestinal injury, acidosis, cardiotoxicity, pulmonary oedema and renal injury. We highlight a fatal ingestion of nonoxynol-9, an agricultural surfactant described as being of low toxicity in toxicology references.

Case report: A 76-year-old man accidently drank three mouthfuls of Wetter 600 (nonoxynol – 9 at 600 g/L) that had been decanted into a water bottle. The Poisons Information Centre (PIC) was contacted, and the product identified in the National Poisons Register (NPR) where it refers to the “Detergents and Soaps – Anionic and Ionic” monograph, indicating a low-risk exposure with only mild gastrointestinal symptoms expected. Reassurance was provided. Owing to vomiting and throat irritation, the patient presented to hospital and further PIC advice was sought. Anti-emetics and fluid replacement was advised and to expect symptoms to improve with time. Blood analysis, 1.5 h post ingestion, was notable for a lactic acidosis and elevated creatinine (Table 1). Thirty minutes later the patient passed a large bowel motion and collapsed. He was hypotensive (BP 70/50 mmHg) and hypoxic (SpO₂ 78%). Blood gas analysis revealed a worsening mixed acidosis. He deteriorated further, developing coma and circulatory shock despite fluid resuscitation and noradrenaline (10 µg/min). At 2.5 h post-ingestion he suffered a cardiac arrest with pulseless electrical activity. Resuscitation was unsuccessful. Toxicological testing of post-mortem blood confirmed the presence of nonoxynol-9 but was negative for other common herbicides and pesticides. Quantification of nonoxynol-9 was not performed.

Table 1 Blood results during presentation in an elderly male who accidentally ingested Wetter 600 (nonoxynol-9 at 600 g/L).

Parameter	Reference range	Time post-ingestion
		90 min	120 min	170 min (post arrest)
pH	7.32–7.43	7.26	7.08	6.95
pCO2	38–54 mmHg	57	64	79
Bicarbonate	22–33 mmol/L	26	19	18
Lactate	0.5–2.2 mmol/L	5.7	8.8	9.2
Creatinine	64–108 µmol/L	120	124	131

Conclusion: The potential life-threatening toxicity of this agent is not currently reflected in available references including the NPR or Product Safety Data Sheet (PSDS). We advocate these references are updated and for harm reduction measures such as safety caps be used in its packaging.

43. Retrospective analysis of anticoagulant rodenticide poisoning cases in Muratsan University Hospital, Armenia, 2016–2022

Abstract

Objective

Rodenticides are among the most toxic materials used in households. People, especially children, can be exposed to these toxins through eating, drinking, and skin contact. Long-acting anticoagulant superwarfarins, are known for their greater potency, half-life and delayed onset of symptoms. They work by inhibiting vitamin K-dependent clotting factors. In case of exposure, coagulopathy does not occur until the body’s existing reserves of vitamin K and active clotting factors are depleted. It usually appears within 48 h of ingestion. Bleeding symptoms usually occur 3–9 days later [1]. Symptoms may last weeks to months, depending on the exposure amount, and also high lipid solubility, hepatic metabolism and enterohepatic recirculation properties of the rodenticide.

Methods

We used the medical charts of patients with rodenticide poisoning admitted to “Muratsan” University Hospital during the period of 2016 to 2022.

Results

Overall 71 patients were admitted over the study period, 70 cases were accidental, with only 1 intentional poisoning. Ten of the patients were from Yerevan, and the remaining 61 were from regions. The average age was 6.2 years and the average length of stay was 3.1 days; 57 of the cases were individual poisonings, the main cause of which was the attractive appearance of rodenticide baits, such as colored granules that looked like candy. The remaining 14 were group poisoning cases where family members accidentally ingested the poison through food. Clinical symptoms were observed mainly in cases of intentional and food poisoning. The main symptoms were bleeding gums and oral mucosa (18), nosebleeds (12), bruises (10), lower back and muscle pain (7), joint pain and swelling (5), and urine color changes (3). In moderate and severe cases, laboratory tests revealed prolonged prothrombin time (22), prolonged International Normalized Ratio (INR) (15), hematuria (11), and anemia (9), thrombocytopenia (3), fecal occult blood (3). Treatment included vitamin K injections, fresh frozen plasma and red blood cell transfusions, and administration of repeated doses of activated charcoal.

Conclusion

The study found that poisoning with anticoagulant rodenticides is mainly manifested by impaired coagulation and requires long-term vitamin K treatment. Early diagnosis and timely treatment can prevent serious complications and lethal outcomes.

44. Severe lactic acidosis after intake of apricot kernels

Abstract

Objective

Apricot kernels are marketed for presumed health effects including lowering blood pressure and even to prevent or cure cancer, even though they contain amygdalin. This is a cyanogenic glycoside and which when plant material is chewing the glycoside is hydrolyzed via an enzymic reaction into hydrogen cyanide. The content of amygdalin is very variable and kernels from wild growing trees contains more amygdalin than kernels from cultivated trees. If the almond is not bitter, the content is low. We present a case of a woman who mistakenly ingested apricot kernels and was hospitalized requiring intensive care.

Case report

A 60-year-old woman ingested 30 bitter apricot kernels. Soon after the ingestion she became dizzy and breathless. When the ambulance arrived, she was unresponsive to commands. On arrival at the hospital, 1.5 h after ingestion, she had pale skin, was diaphoretic, unresponsive to commands and snoring. Heart rate and blood pressure were normal. Arterial blood gas measurement revealed pH 6.8 and lactate 22 mmol/L. She was administered hydroxocobolamin 5 g intravenously over 15 min, and thereafter sodium thiosulphate 15 g intravenously over 10 min and another 5 g hydroxocobolamin. She was intubated and sedated, and after gastric lavage received two doses of activated charcoal. Sodium bicarbonate and buffering fluids were given with improvement of pH to 7.06 and lactate 18 mmol/L. The following morning, she had bradycardia (32 bpm) and was given atropine without effect. The heart rate dropped to a minimum of 23 bpm and then increased slowly after another dose of atropine. About 12 h after ingestion of the kernels she was successfully extubated. The blood gas normalized after 1.5 days, and she improved gradually. Three and a half hours after the apricot kernel ingestion, the patient’s whole blood cyanide concentration was 0.19 µg/g (normal value for nonsmokers, 0.5 µg/g or less). Note that the concentration of cyanide in blood drops quickly so a high concentration can easily be missed.

Conclusion

There are many plants which contain amygdalin. Cyanide toxicity following ingestion of apricot kernels has been reported previously [1], but intoxications are rare because the cyanogenic compounds must be metabolized to release cyanide.

45. A case of Cerbera odollam (Pong Pong) seed ingestion

Abstract

Objective

Cerbera odollam is a common fruit found in Singapore along the coastline as well as in certain areas of Southeast Asia and India. Its seeds contain a toxin called cerberin which is highly cardiotoxic and binds to and reversibly inhibits the Na-K ATPase pump in myocardial cells [1]. This can be fatal and hence the tree is known as the “suicide tree”. The clinical presentation and mechanism of toxicity is similar to digoxin. Clinical management is similar, with supportive treatment of bradycardia and hyperkalaemia. Administration of digoxin immune fab can be considered as well. We report a case to improve awareness about the potential toxic effects of Cerbera odollam ingestion.

Case report

A 37-year-old female presented to the Emergency Department (ED) four hours after ingestion of Cerbera odollam, “Pong Pong” seed with intent to self-harm. She broke through the husk, pounded two seeds and mixed it with honey and ice cream. Subsequently, she ingested 3 spoonful of this mixture. There was no co-ingestion with any other drug or substance. She initially had perioral and facial region numbness, as well as some lethargy, nausea and vomiting. Her initial vitals were: temperature 37 °C, blood pressure 102/70 mmHg, heart rate 54 beats/minute, respiratory rate 20 breaths/minute, SpO₂ 100% (room air). The physical examination was unremarkable. Initial investigations showed digoxin concentration <0.4 µg/L, salicylate concentration <3 mg/L, paracetamol <5 mg/L, lactate 1.9 mmol/L. Blood gases were pH 7.559, pCO₂ 24 mmHg, and bicarbonate 21 mmol/L. Haemoglobin was 10.6 g/dL and urea, creatinine, serum sodium, potassium, glucose and liver function tests were within normal range. The patient was diagnosed with mild cerberin poisoning. The toxicology service was consulted and advised activated charcoal administration and admission to short stay unit under the Accident and Emergency department for observation with continuous electrocardiogram (ECG) monitoring. Overnight, she had intermittently bradycardia with heart range ranging between 45 and 55 beats per minute. The heart rate improved to about 75 beats/minute by the morning (about 15 h post-ingestion) and the patient was discharged well after psychiatry review. She did not require any digoxin-specific antibody therapy.

Conclusion

Cerbera odollam fruit ingestion caused nausea, vomiting, perioral numbness and sinus bradycardia with hypotension in this patient but she did not require digoxin-specific antibody therapy. Physicians should be aware of the potential mortality and morbidity and possible treatment options in patients that ingest Cerbera odollam seeds.

46. Delayed treatment of severe hepatitis in unrecognized phalloides syndrome

Abstract

Objective

Delayed or insufficient antidote treatment of patients with mushroom poisoning is a challenge for every toxicologist [1]. We present a case of delayed recognition of severe phalloides syndrome treated with an additional acetylcysteine dose to the standard protocol with favorable outcome.

Case report

A middle-aged man was admitted to the Clinic on the 4th day after ingestion of mushrooms he had picked and eaten under the assumption that they were parasol mushrooms (Macrolepiota procera). He had a medical history of diabetes mellitus type 2, coronary artery bypass graft x3 (only aspirin) and hypertension. Profuse gastroenterocollitis developed 16 h after ingestion (over a weekend) and for the first 2 days he was treated at a local medical center for infectious enterocolitis as an outpatient. Laboratory analyzes on the third day showed an increased transaminase activity with a progressive increase the next day, after which he was brought to the clinic. He was alert, blood pressure 100/60 mmHg, an electrocardiogram (ECG) showed sinus rhythm, heart rate 100/min, pain under the ribs in the right upper quadrant, with yellow discoloration of the sclera. Laboratory analysis revealed platelets 129 × 10ⁱ/L, gamma-glutamyl transferase (GGT) 199 U/L (later 608 U/L), alanine aminotransferase (ALT) 8389 U/L, aspartate aminotransferase (AST) 13804 U/l, lactate dehydrogenase (LDH) 7961 U/L, direct bilirubin 104 µmol/L, blood urea nitrogen (BUN) 17.1 mmol/L, creatinine 133.8 µmol/L, prothrombin time (PT) 29.3 s (11–14 s), and D-dimer 8183 ng/mL. Hepatitis viral marker negative. The patient was intensively rehydrated, treated with IV acetylcysteine (200 mg/kg over 4 h, followed by 100 mg/kg over 16 h, with additional 100 mg/kg dose), oral silymarin (100 mg 3 × 2) and supportive treatment. Abdominal ultrasound presented enlarged liver (not congested) with intensive steatosis. Progressive thrombocytopenia from day 2 of hospitalization was noted with a nadir of 58 × 10ⁱ/L (150–450 × 10ⁱ/L) on the 9th day of poisoning. He received dexamethasone and low molecular weight heparin (LMWH) and PT normalized on the 8th day of poisoning (14.2 s). The patient recovered after 10 days of treatment, with normalized transaminases after 3 months. The mushroom ingested was assumed to be Amanita phalloides, based on the clinical features, laboratory findings and recognition of the ingested mushroom with a look-alike poisonous mushroom from a mushroom atlas by the patient.

Conclusion

Data about the consumption of picked mushrooms should be seriously considered when determining the etiology of severe acute gastroenterocollitis. Delayed treatment of phalloides syndrome may worsen the clinical course and increase the potential risk of lethal outcome.

47. Coma and seizures induced by Amanita pantherina poisoning

Abstract

Objective

Amanita pantherina poisoning is a rare, poorly described event. The clinical picture is usually associated with A. muscaria, but A. pantherina contains more muscimol and more commonly causes coma [1]. We describe a case of severe coma and seizures after A. pantherina ingestion.

Case report

A 56-year-old woman was found at home unresponsive (Glasgow Coma Score (GCS) 3) with miosis, clonic movements of all limbs, normal respiratory and cardiovascular functions and without cerebral ischemic symptoms. Naloxone and flumazenil administration by emergency services were ineffective. Her husband reported mushroom ingestion 4 h earlier. They were picked from the home garden and believed to be Macrolepiota procera. The mushroom caps were cooked in the oven and the patient ingested 4 whole caps, whilst her husband ate only 2 little pieces. The latter remained asymptomatic. Unenhanced brain computerised tomography (CT) scan and cerebral CT angiography were normal. Blood tests were within normal range, including troponin I, creatine phosphokinase and lactate. Toxicological screening was negative for methadone, ecstasy, amphetamines, barbiturate, cannabinoids, cocaine, opioids and benzodiazepines. Suspecting ingestion of A. pantherina, gastrointestinal decontamination was performed and whole bowel irrigation was maintained up to the 5th day when rectal effluent became clear. Mycological examination of residual stems of the ingested mushrooms identified A. pantherina, and evaluation of photos of the same mushrooms growing in their garden confirmed the species. On the second day, an electroencephalogram showed epileptiform activity and levetiracetam 3000 mg/day was started. The patient remained hemodynamically stable but daily neurologic wake-up tests highlighted the presence of agitation and clonic movements of the limbs up to the 7th day of hospitalization. Brain magnetic resonance imaging (MRI) was normal and follow-up electroencephalogram showed partial improvement. Levetiracetam was tapered and stopped after two months based on neurological evaluation. The patient recovered without sequelae.

Conclusion

Amanita pantherina poisoning is a rare event and the clinical picture of convulsions and coma often guides the diagnosis towards organic pathologies such as brain stroke [2]. The latter should be excluded first but an accurate anamnesis should also consider mushroom consumption. Gastrointestinal decontamination may be the only therapy for reducing toxins absorption and clinical severity. Our patient had acute severe neurological effects lasting many days, but she completely recovered with intensive treatment and levetiracetam administration.

48. The pattern of neurorespiratory effects induced by the synthetic opioid U-47700 significantly differ from that related to morphine in the rat

Abstract

Objective

Emergence of novel synthetic opioids represents a major public health threat. The recreational use of U-47700 has been increasingly reported resulting in overdoses and fatalities. Our aim was to investigate U-47700-induced neurorespiratory toxicity in the rat.

Methods

Randomized male Sprague-Dawley rats were intravenously administered saline, U-47700, or morphine at 50% of their lethal dose 50% (1.5 mg/kg versus 23 mg/kg, as determined in our laboratory) using a jugular catheter. We used whole-body plethysmography, arterial blood gas analysis (after femoral artery catheterization), and diaphragm electromyography to assess the impact on sedation, body temperature and ventilation of the drugs. Plasma U-47700 concentrations were measured using liquid chromatography coupled with mass spectrometry in tandem. The pharmacokinetic profile and pharmacokinetic/pharmacodynamic (PK/PD) relationships were studied.

Results

U-47700 and morphine resulted in sedation (p < 0.01 and p < 0.05) but only U-47700 in decreased temperature (p < 0.05) in comparison to saline. Morphine and U-47700 increased inspiratory time (p < 0.05 and p < 0.01) but did not alter expiratory time nor tidal volume. Only U-47700 reduced the minute volume (p < 0.001). By contrast, only morphine decreased arterial pH (p < 0.001) and increased PaCO₂ and lactatemia (p < 0.001 and p < 0.01). Electromyography data showed no significantly altered diaphragm muscle contractility with both drugs. The PK/PD profile of U-47700 showed an counter-clockwise hysteresis.

Conclusion

The neurorespiratory toxicity profile of U-47700 in the rat differs from that of morphine, with fewer functional consequences despite more marked alterations in volumes and rates of respiration. The exact consequences of these experimental observations in humans remain to be determined.

49. The neurorespiratory effects induced by fentanyl and carfentanil in comparison to morphine in the rat

Abstract

Objective

The United States is facing a threatening crisis of opioid overdose fatalities, which has extended over the past two decades. Potent synthetic opioids including fentanyl and its analogs have become the primary drivers of the fatal overdose surge. Our aim was to investigate the neurorespiratory toxicity of carfentanil and fentanyl in the rat to identify synthetic opioid molecule-specific patterns.

Methods

Randomized male Sprague-Dawley rats received intravenous saline, morphine, fentanyl and carfentanil, using a jugular catheter at 23 mg/kg, 1.5 mg/kg, and 1.7 mg/kg, respectively (i.e., 50% of their lethal dose 50%, as determined in our laboratory). We used whole-body plethysmography, arterial blood gas analysis (after femoral artery catheterization), and diaphragm electromyography to assess the drug impact on sedation, body temperature, and ventilation. The areas under the curves were calculated to examine the overall impact of each drug on each parameter and each animal. One-way ANOVAs with multiple comparison tests were used for comparison. Plasma concentrations were measured using liquid chromatography coupled to mass spectrometry in tandem. The pharmacokinetic profile and pharmacokinetic/pharmacodynamic (PK/PD) relationships were investigated.

Results

Rats which received fentanyl and carfentanil were more sedated (p < 0.001) and presented lower body temperature in comparison to saline (p < 0.05 and p < 0.001, respectively). Immediate muscular rigidity associated with Straub tail was observed. Both drugs significantly increased inspiratory time (p < 0.001) whereas carfentanil additionally increased expiratory time (p < 0.01) and fentanyl increased tidal volume (p < 0.05). Consequently, decrease in minute volume was observed by both fentanyl (p < 0.05) and carfentanil (p < 0.001). Morphine did not significantly alter respiratory times and volumes. Fentanyl and carfentanil significantly increased PaCO₂ (p < 0.05 and p < 0.001) and blood lactate (p < 0.05 and p < 0.01) and decreased arterial pH (p < 0.001 and p < 0.05) and PaO₂ (p < 0.01 and p < 0.001) in comparison to the saline. Only morphine altered blood lactate (p < 0.05), fentanyl (p < 0.05), and carfentanil (p < 0.01). Additionally, the diaphragm contraction amplitude was increased in fentanyl-treated rats (p < 0.05) with no significant modification of the diaphragm contraction frequency. The PK/PD profile of fentanyl and sufentanil showed different counterclockwise hysteresis.

Conclusion

Fentanyl and carfentanil are responsible for sedative and ventilation depressant effects, with distinctive patterns not observed with morphine. Additional mechanistic studies are encouraged.

52. Plant poisonings in Estonia: a 5 year overview

Abstract

Objective

This study describes demographics and severity of plant poisoning and the most commonly involved species in Estonia during 5 years from 2018 to June 2023.

Methods

Calls to the Estonian Poison Information Centre (EPIC) hotline were analysed. The data collected included species involved (if known), age of victim, place of the event, intent of exposure and recommended observation place. Toxscore was calculated for each exposure. The total number was compared with cases of poisonings in Estonian hospitals based on data from the Health Insurance Fund.

Results

Overall, 190 calls were analysed. Most cases were in children 1–4 years (45%), and <1 year (13%). The least exposures with poisonous plants were among patients aged 65+ years (2%). Though there are several plants in Estonia containing substances with potential to cause severe illness or death, most calls were about mild exposures and 96% were accidental. Most (70%) had a Toxcore 0 at time of the call to EPIC (90% of 1–4 year olds). Most symptomatic cases were in the adult group (18–64 years, 62% of call). All patients aged 65+ years were symptomatic. There were no severe poisonings (Toxscore 2–3) among the callers in the study period. Home was the most common observation place (88%); 5% were sent to hospital and 4% to their family doctor. Among children, most cases involved Convallaria majalis (lily of the valley) and locally irritating plants. In adults, most cases related to Heracleum. Other common plants were tulips, dieffenbachia, Zamioculcas, yew, and common snowberry. Most of the accidents happened at home (83%) or in nature (15%). In the same period Health Insurance Fund data show there were 34 healthcare provider visits due to plant poisoning so the majority of such accidents were covered by EPIC.

Conclusion

Research shows that most accidental plant exposures in Estonia are mild, and usually it is enough to rinse the mouth or skin and observe at home. Parents of young children usually call for advice as soon as they notice the child’s contact with a plant. Adults usually only call for advice if they have developed symptoms or realised they have mistakenly eaten a poisonous plant. Dermal exposure to Heracleum in adults was usually due to actions like cutting long grass or riding an all-terrain vehicle (ATV), which explains why there are few cases among the elderly. Also, we may suppose older people know their plants better. The information gathered helps EPIC in targeting prevention work on poisonous plants.

53. Anticholinergic poisoning: ingestion of vegetables erroneously harvested or packaged in commercial products

Abstract

Objective

Many wild vegetables are traditionally harvested for culinary purposes, but can be confused with poisonous plants containing tropane alkaloids. The aim of our study was to describe the characteristics of this phenomenon in Italy.

Methods

We conducted a retrospective observational study from January 2007 to December 2022 including all consecutive patients with history of ingestion of edible vegetable and presenting with anticholinergic symptoms (PSS ≥1). Exclusion criteria were asymptomatic cases, and cases in which the causality was uncertain. For each case, we collected demographic data, temporal and geographical location, vegetables presumably ingested and their origin, clinical manifestations, treatment and outcome.

Results

We included 361 patients distributed in 196 clusters (52.4% males; mean age 48.9 ± 20.9 years) with a mean of 22.6 ± 8.3 cases/year. Most cases occurred in Sicily (72%) from October to January (65.6%). In 87.8% of the cases the vegetable eaten had been harvested as a wild plant, in 8% it had been bought at a local market, and in 2.2% it was a contaminated product from large-scale distribution. The most common allegedly ingested vegetables were borage (Borago officinalis) in 32.9% of cases, followed by Beta vulgaris (13.8%) and Spinacia oleracea (8.5%). The mean latency from vegetable consumption to the onset of symptoms was 1.9 ± 2.1 h; 70.9% of patients presented with both central and peripheral anticholinergic symptoms (AS) of which the most common were mydriasis (73.7%), hallucinations (50.9%), tachycardia (49.3%), psychomotor agitation (39.6%), confusion (31.1%), and xerostomia (34.2%). Coma and convulsions were found in 5.3% and 0.5% of patients, respectively. Considering treatments, 91.9% of patients underwent gastrointestinal decontamination, 32.7% received benzodiazepines, 29.4% physostigmine for central AS (mean administered dose: 2.10 ± 1.38 mg) and 8% neostigmine (prostigmine) for peripheral AS. Control of central AS was achieved in 90.6% of patients treated with physostigmine compared to 49% of patients treated with benzodiazepines. Physostigmine administration reduced the need for intensive care admission and orotracheal intubation compared to benzodiazepines alone (0.9% versus 25.5% and 0% versus 5.9%, respectively). We did not register any adverse effect after physostigmine administration. All patients recovered fully.

Conclusion

Poisoning by anticholinergic plants mistaken for edible vegetables is common in Italy, although poorly reported in the literature. Sicily has the highest prevalence, probably because of the confusion of edible borage with the poisonous mandrake (Mandragora officinarum), which is widespread in southern Italy. Physostigmine is a safe and effective antidote for the treatment of central AS, superior to benzodiazepine therapy alone.

54. Prevalence of new psychoactive substance (NPS) intoxications from the beginning of COVID-19 pandemic in Italy

Abstract

Objective

The new psychoactive substances (NPS) world is constantly and rapidly evolving, and this phenomenon pose a threat to public health. The signs and symptoms of NPS intoxications can be unpredictable and variable. This study aimed to assess the prevalence and the clinical characteristics of laboratory-confirmed NPS intoxications presented to the emergency department network (EDs) referring to Pavia Poison Centre (PPC) within the Italian Early Warning System.

Methods

All cases referred to the PPC since the beginning of COVID-19 pandemic (March 2020) until August 2023 with a history of NPS or atypical clinical pictures after overdose with “old drug of abuse” were included. Cocaine, opiates, cannabis, amphetamine/methamphetamine, methadone were defined as “old drugs of abuse”; ethanol, prescription opioids, 3,4-methylenedioxymethamphetamine (MDMA) and lysergic acid diethylamide (LSD) intoxications were excluded. All cases were assessed for age, history, acute clinical manifestations, outcome and analytical investigations.

Results

A total of 523 cases met the inclusion criteria during the study period; the mean age was 29.5 ± 11.9 years, 80.1% were males. In 187/523 cases (35.8%) NPS consumption was declared; 24.9% of patients were unable to report the substances taken. The most common clinical manifestations were: agitation (69%), drowsiness (31.2%), hallucinations (29.6%), tachycardia (26.8%), confusion (21.2%) and gastrointestinal symptoms (13.8%). Among hospitalized patients, 53.4% were admitted to intensive care units, and 31.1% to psychiatric units; 8 fatal cases were registered. The second level laboratory investigations (gas chromatography-mass spectrometry (GC/MS) or liquid chromatography-mass spectrometry (LC-MS)) were carried out in 93.7% of cases (490/523). Among the identified NPS (31% of cases), the most frequent were synthetic cathinones (56), arylcyclohexylamines (28), ketamine (26), atropine/scopolamine (14), psilocin/psilocybin (9), gamma-hydroxybutyrate/gamma-butyrolactone (GBH/GBL) (7), and nitrites (6). Co-consumption of several NPS was documented in 19.5% of cases, and in 49.7% biological samples were positive for “old drugs of abuse” too.

Conclusion

The use of NPS is common among males, particularly in the context of chemsex. Synthetic cathinones represent the most abused NPS class, unlike the pre-COVID period. Neurological manifestations and severe psychomotor agitation are the most common presenting symptoms and can lead to severe intoxication. Advanced toxicological analysis in emergency settings are essential in understanding the phenomenon of NPS abuse. Finally, we must consider the impact of the COVID-19 pandemic both on the drugs of abuse market and on the data collection by the PPC observatory.

Acknowledgements

Study carried out with the support of DPA – Presidency of the Council of Ministers.

55. Nitrous oxide associated pulmonary embolism

Abstract

Objective

To report a case of pulmonary embolism linked to nitrous oxide (N₂O) abuse.

Case report

A 33-year-old male, obese, smoker, without chronic comorbidities or regular medication treatment was referred to the emergency department due to dyspnea and pleuritic pain for 2 days. Upon admission he was alert, with mild tachypnea (RR 20/min), SO₂ 99%, BP 113/71 mmHg, HR 75/min. Oral temperature 36.6 °C. The rest of the physical examination including neurological assessment was unremarkable. Blood tests revealed elevated D-dimer (5202 ng/mL; normal <250) and C-reactive protein (CRP) (16.6 mg/dL; normal <0.5) concentrations. Serum troponin and blood count were in the normal ranges. Electrocardiogram (ECG) showed normal sinus rhythm. Bedside echocardiogram demonstrated normal cardiac function. Chest X-ray did not show any pathology. Computerised tomography (CT) angiography showed filling defects in the main pulmonary artery and in the right and left lobar arteries. The diagnosis was pulmonary thromboembolism. Treatment with enoxaparin (80 mg BID) was started. In follow-up questioning, the patient reported using nitrous oxide repeatedly for recreational purposes that intensified in the week before admission. Additional tests were ordered. Toxicological urine screen was negative. Serum folic acid concentration was low, 5.6 mmol/L (normal range 8.8–60.8) and vitamin B12 was close to the lower normal limit, 170 pmol/L (normal range 145–569). Serum homocysteine concentration was 96.3 µmol/L, about 6-fold higher than the upper normal limit (normal range 5–15). Testing for hypercoagulability revealed that the patient is heterozygotic for Factor II. Therapy with vitamin B12 (1000 µg QD) and folic acid (5 mg QD) was given. Enoxaparin was replaced with PO apixaban for prolonged treatment. The patient was educated about the risks of nitrous oxide and recommended to avoid its use. After 5 days in hospital, he was discharged in an improved condition for continuing treatment at home.

Conclusion

The presented case highlights the elevated risk of venous thromboembolism with nitrous oxide abuse through secondary hyperhomocysteinemia, especially in patients with associated risk factors. Hyperhomocysteinemia is an intermediate factor for vascular thrombosis, and nitrous oxide was likely a factor in the pathogenesis of thrombosis in the presented case. This uncommon, but potentially life-threatening effect of nitrous oxide, was previously reported to a limited extent. While nitrous oxide-related neurological complications are widely known, thrombotic effects are less appreciated. Higher awareness and appropriate intervention are needed. Stopping nitrous oxide abuse and supplementation with folic acid and vitamin B12 in patients at risk are highly recommended.

56. Poison centres should organize hunts for paramethoxymethamphetamine (PMMA) or PMMA-like novel psychoactive substances

Abstract

Objective

Some drugs in the amphetamine/cathinone class (i.e., 4-methoxymethamphetamine, PMMA) have a propensity to cause severe hyperthermia; likely because they are potent inhibitors of monoamine oxidase (MAO)-A [1]. Poison centres (PC) could serve an important function in limiting the spread of such highly toxic stimulants by coordinating efforts to identify the offending substance in cases of severe drug-induced hyperthermia.

Case report

A 40-year-old male psychiatric inpatient with a history of schizophrenia and mixed drug use collapsed after emerging naked, confused, and covered in sweat from his hospital room where a pill-bag marked “Vanilla Sky” was subsequently found. He was rushed to the emergency department (ED) where he had a body temperature of 42 °C. Severe serotonin toxicity was suspected, and he was immediately sedated with propofol, paralyzed with rocuronium, intubated, and given 10 mg olanzapine IV. His temperature normalized within 30 min. He developed only moderate hepatic injury, disseminated intravascular coagulation (DIC), rhabdomyolysis and an aspiration pneumonia and was discharged from the intensive care unit (ICU) neurologically intact after 36 h. Per instructions from the PC one “Vanilla Sky” pill was sent to the laboratory at the Swedish Medical Products Agency and analyzed with liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR). It contained the cathinones N-ethylpentedrone (NEP) and α-pyrrolidinoisohexanophenone (α-PHIP) in a 3:2 molar ratio. Blood and urine samples taken during the first hours were sent to the National Board of Forensic Medicine and screened for drugs of abuse using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF) technique. The blood was negative for all 229 substances included in the screen, and α-PHIP was the only drug detected in urine. NEP was not included as a reference substance at the time of analysis but was added after this case. No further cases of drug related heat stroke came to the attention of the PC during the following weeks.

Conclusion

The cathinones detected in this case are analogues to pentedrone and pyrovalerone, which usually cause dopaminergic overstimulation. Their molecular structures do not contain the ring-substitutions typically associated with MAO-A inhibition [1]. This isolated case of drug-related heat stroke probably represented an idiosyncratic or dose-related reaction, rather than a predictable response to a uniquely toxic substance. However, we argue that the highly malignant and comparatively rare clinical picture justified analytical efforts beyond routine practice. The early detection of PMMA or a PMMA-like NPS “in circulation” may be essential for averting epidemics of life-threatening serotonin toxicity.

57. Influence of the COVID-19 pandemic on consumer behavior and the acute medical care of patients with acute recreational drug intoxication

Abstract

Objective

The COVID-19 pandemic is a relatively recent phenomena, so data on whether it caused significant changes on the population’s alcohol and drug consumption are scarce. Furthermore, the impact of the pandemic on the treatment and care of patients with acute recreational drug toxicity is sparse. We assess whether changes in alcohol and drug consumption in patients treated in a clinic were observed during the COVID-19 pandemic and which factors could account for these differences.

Methods

Retrospective mono-center study using data from patient records from a tertiary university hospital in Germany one year before the pandemic (January to December 2019) versus, the first year of the pandemic (April 2020 to March 2021). The outcome measure and analysis were comparison of epidemiological and clinical characteristics, emergency department and hospital management of patients with acute recreational drug intoxication before and during the COVID-19 pandemic.

Results

Overall, 869 patients were included in our study with 71.3% male with a mean age of 41.6 ± 14.0 years. Pre-COVID-19, admissions occurred more frequently via emergency ambulance (p = <0.001) with significantly lower Glasgow Coma Scores (GCS) (p = <0.001) and a higher rate of opioid (p = 0.028) and novel psychoactive substances (NPS)/cathinone consumption (p = 0.024). Respectively, during COVID-19, there were significantly higher rates of self-admissions (p = <0.001). Sedatives had to be used more frequently for the treatment of acute intoxications during the pandemic (p = <0.001). During COVID-19, hospital discharge occurred more frequently to psychiatric facilities (p = 0.013).

Conclusion

The COVID-19 pandemic had an influence on the pattern of drug consumption, calling an emergency ambulance and the long-term treatment of patients with acute recreational drug toxicity.

58. A case of status epilepticus in a drug user

Abstract

Objective

A national survey on the extent and pattern of substance use in India shows that substantial numbers of people use psychoactive substances [1]. Alcohol (14.6%), cannabis (2.8%), opioids (2.1%), sedatives (1.08%), inhalants (0.7%), cocaine (0.1%), amphetamine-type stimulants (0.18%), and hallucinogens (0.12%) are the common substances used by the Indian population. People require medical help in harmful and dependent use and cause diagnostic and therapeutic difficulties in overdosage and withdrawal.

Case report

A 24-year-old male tattoo artist, DJ and sound engineer who was missing from home for a day, was brought to the hospital by police. He presented with complaints of abnormal behaviour and recurrent involuntary movements associated with loss of consciousness. He was an alcoholic, a smoker and had a history of drug abuse. He was unresponsive Glasgow Coma Score (GCS) 3/15, with tachycardia, tachypnoea, desaturating, facial twitching, oral bleeding and a tongue bite. He had multiple linear abrasions over chest and left forearm. A diagnosis of status epilepticus was made and the aetiologies considered were drug overdosage, withdrawn state, encephalitis, intracranial bleed or a metabolic cause. Investigations were: brain computerised tomography (CT) scan normal, white blood cell count 76.8 × 10ⁱ/L, sodium 154 mmol/L, potassium 5.3 mmol/L, aspartate aminotransferase (AST) 226 IU/L, alanine aminotransferase (ALT) 66 IU/L, creatinine 247.58 µmol/L, uric acid 1153.9 µmol/L, prothrombin time 20 s, International Normalized Ratio (INR) 1.6, and activated partial thromboplastin time (aPTT) 50 s. Arterial blood gas analysis showed metabolic and respiratory acidosis. He was given antiepileptics, vasopressors, IV fluids, mechanical ventilation, and other supportive measures. He continued to have bleeding from multiple sites and repeated seizures despite antiepileptics. Despite all measures he expired after 20 h of hospital admission. Toxicology analysis reported the presence of 3,4-methylenedioxymethamphetamine (MDMA) and the final diagnosis was MDMA overdose with hyperthermia, status epilepticus, disseminated intravascular coagulation (DIC) and multisystem dysfunction.

Conclusion

Substance abuse and withdrawal can cause seizures not responding to therapy. MDMA overdosage can cause hyperthermia and heat stroke, disseminated intravascular coagulation, status epilepticus and multiorgan dysfunction and can be fatal.

60. Additional morbidity of co-exposure to novel psychoactive benzodiazepines in Emergency Department patients with confirmed opioid overdose

Abstract

Objective

Although prescription and novel psychoactive substances (NPS) classified as benzodiazepines are structurally similar, NPS benzodiazepines can have different pharmacological characteristics. Additionally, NPS benzodiazepines may have potent clinical side effects [1]. The objectives of this analysis in emergency department patients with confirmed opioid overdose, were to examine the association with adverse clinical effects for NPS benzodiazepines compared to 1) prescription benzodiazepines and 2) all patients without NPS benzodiazepines.

Methods

The Toxicology Investigators Consortium (ToxIC) Fentalog Study is an ongoing prospective multicenter cohort study consisting of 9 medical centers across the US. Patients are enrolled if they present with acute suspected opioid overdose. Clinical data are obtained via chart review and blood samples are collected for qualitative toxicological analysis using liquid chromatography quadrupole time-of-flight mass spectrometry for the presence of over 1100 psychoactive substances. Laboratory analyses are performed by the Center for Forensic Science Research and Education. Adverse clinical effects included death, intubation, naloxone requirements, and neurological effects. Neurological effects included the presence of agitation, cerebral hemorrhage, coma/central nervous system depression, delirium, dystonia, hallucinations, hyperreflexia, hypoxic or anoxic brain injury, seizures, and/or slurred speech. Bivariate statistical tests were conducted for each comparison (chi square tests for categorical variables and Mann-Whitney U Tests for continuous variables). All analyses were conducted in R 4.2.2 and approved by a central institutional review board (IRB) (WIRB).

Results

Between 21 September 2020 and 13 May 2023, 1541 patients met the inclusion criteria, and 1266 cases had blood analytes. A total of 113 patients (8.9%) had at least one NPS benzodiazepine. The most common NPS benzodiazepines (N = 113) were bromazolam (40.7%), clonazolam (38.9%), etizolam (19.5%), and flubromazepam (15.0%). NPS benzodiazepine overdoses were significantly more likely to have neurological effects within 4 h of hospital presentation (77.0%) compared to neurological effects among those without NPS benzodiazepines (55.2%; p = 0.008). Furthermore, NPS benzodiazepines were also more likely to result in adverse neurological effects within 4 h of hospital presentation compared to prescription benzodiazepines (77.0% versus 63.4%; p < 0.001).

Conclusion

Neurological effects were much more likely in patients testing positive for NPS benzodiazepines among patients presenting after acute opioid overdose to emergency departments.

61. Clinical characteristics and mortality risk factors in non-trauma patients requiring resuscitation due to illicit substance use in Taiwanese emergency departments

Abstract

Objective

The rising global prevalence of new psychoactive substances (NPS) has drawn attention to the role of emergency departments (EDs) in monitoring and addressing the risks associated with illicit drug use [1,2]. This study seeks to explore the clinical characteristics of non-trauma patients in Taiwanese EDs who require resuscitation due to acute incidents linked to illicit substance use and to identify associated risk factors for mortality.

Methods

This retrospective observational cohort study involved patients in our EDs with conditions requiring non-trauma resuscitation between May 2017 and December 2022, associated with recreational drug use. Inclusion criteria mandated positive urine tests for illicit substances, verified through liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results

During the study period, 1215 cases in our EDs tested positive for at least one illicit drug. After excluding patients under the age of 10 and trauma cases, 93 patients necessitated resuscitation. Among them, 31 patients (33.3%) did not survive, with the noteworthy finding that this group was significantly younger in median age compared to the group that survived (p = 0.006). The most frequently detected drugs included methamphetamine in 53 cases, phencyclidine-type substances in 28 cases, and synthetic cathinones in 26 cases. Morphine and analogs were detected in 19 patients. Psychostimulant intoxication was the most common diagnosis, affecting 43 patients, followed by psycho-depressant intoxication in 17 patients. The group of patients who did not survive exhibited a higher prevalence of psychostimulant intoxication diagnosis (death group: 21 [67.7%], survival group: 22 [35.5%], p = 0.003). The multivariable logistic regression analysis revealed several significant risk factors for mortality. These included phenethylamine use (odds ratio (OR): 41.46, 95% CI: 3.27–518.16, p = 0.004), low blood pressure (OR: 9.41, 95% CI: 2.55–34.64, p = 0.001), hyperthermia (OR: 3.87, 95% CI: 1.03–14.56, p = 0.046), and lactic acidosis (OR: 4.26, 95% CI: 1.52–14.47, p = 0.020).

Conclusion

This study provides insights into the clinical characteristics and risk factors associated with mortality in acute illicit drug-related resuscitation cases. These findings underscore the need for tailored management strategies for patients associated with illicit substance use who require resuscitation, with particular attention to the management of hyperthermia.

62. Lessons learned from misinterpreted toxicological laboratory results

Abstract

Objective

In May 2023, three parents consulted the Taiwan Poison Control Center (PCC-Taiwan) suspecting their children had been given an unknown sedative by a kindergarten teacher. Despite the medical advice provided by the PCC-Taiwan, they later reported this to the police, leading to more than twenty similar accusations. These children underwent enzyme immunoassay (EIA) tests, some revealing quantitative results, e.g., serum phenobarbital concentration of 1.2 mg/mL, urine benzodiazepine concentration of 20 ng/mL, etc., and a media frenzy. Subsequently, both the New Taipei City Department of Health and two hospitals requested PCC-Taiwan to have drug confirmation tests for these samples.

Methods

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed in the testing of both serum and urine samples. Moreover, to address potential time delays in confirmatory testing of these biological matrices, a new LC-MS/MS method was developed for analyzing hair samples for phenobarbital using the SCIEX Triple Quad™ 5500+ LC-MS/MS System. The proximal segments of hair samples (0–6 cm from the root; each segment was 3 cm long) were analyzed. The hair sample was preprocessed and then incubated with methanol. Finally, the supernatant was dried, and dissolved in mobile phase. With regard to the development of hair analysis, the calibration curves were created and linearity from 0.05 to 2 ng/mg was obtained with correlation coefficients greater than 0.99. Phenobarbital was measured in hair samples collected from long-term prescription drug users as the positive control, and the results were consistent with a previous study [1].

Results

Confirmatory testing by PCC-Taiwan were negative for phenobarbital and benzodiazepines. Furthermore, hair samples revealed undetectable phenobarbital, based on the specimen we received.

Conclusion

Currently, therapeutic drug monitoring (TDM) is commonly used to measure drug concentrations. However, the results can be challenging to interpret, especially when miscorrelated with the clinical manifestations. In this case, TDM was not appropriate as the children were not using phenobarbital for epilepsy, and the concentrations near the detection limit should not have been interpreted as positive. Additionally, caution should be exercised when interpreting EIA test results, as they may yield false positives or negatives. When there is uncertainty in interpreting toxicological test results, LC-MS/MS, is regarded as the gold standard in laboratory confirmation, and should be used for confirmatory diagnosis rather than EIA.

63. The neurorespiratory effects of pregabalin alone or in combination with morphine in the naïve and morphine-tolerant rat

Abstract

Objective

Pregabalin (PGB) is increasingly identified in post-mortem toxicology analyses, frequently in association with opioids [1]. However, little is known about the contribution of PGB to fatal events involving opioids. To investigate the possible interaction between PGB and opioids, we hypothesized that PGB could alter tolerance to morphine-induced respiratory effects, as was suggested in mice [2]. We designed an experimental study in rats to investigate the possible alterations of morphine-induced respiratory effects by PGB in morphine-naive rats and in rats tolerant to the respiratory effects of morphine (morphine-tolerant rats).

Methods

We first developed a model of tolerance to the respiratory effects of morphine. Rats were treated by increasing subcutaneous morphine doses (10–60 mg/kg) twice daily for 8 days. To validate this model, we compared the respiratory effects, in plethysmography, of the subcutaneous administration of morphine 60 mg/kg in morphine-naive and morphine-treated rats. We then studied the respiratory effects of subcutaneous 41 mg/kg PGB, alone or in combination with 60 mg/kg morphine, in morphine-naive and morphine-tolerant rats. Areas under the curve for each parameter versus time were assessed. Comparisons between the groups were performed using one-way ANOVAs with Dunnett’s post-tests.

Results

Morphine 60 mg/kg significantly reduced the minute volume (V_E) in morphine-naïve compared to morphine-tolerant rats (p < 0.001), validating our model of morphine-tolerance. PGB 41 mg/kg alone did not induce a significantly different reduction in V_E in morphine-tolerant rats compared to morphine-naive rats. PGB combined with morphine induced a significantly greater reduction in V_E in morphine-naive rats compared to morphine-tolerant rats (p < 0.001).

Conclusion

PGB 41 mg/kg does not alter tolerance to morphine-induced respiratory effects in rats. The exact mechanism by which PGB contributes to opioid-induced respiratory depression remains to be elucidated.

64. Life-threatening caffeine poisonings. Is there a pitfall in regulations?

Abstract

Objective

This study aims to assess the potential dangers associated with the consumption of caffeine powder and tablets, categorized as food supplements in Europe. These products are readily available in various retail outlets, including supermarkets and pharmacies, without stringent regulatory oversight. In 2022 there were several severe caffeine poisonings in Estonia, making the Estonian Poison Information Centre (EPIC) look more closely into sales and regulations of caffeine-containing supplements. We found that over-the-counter caffeine products often contain an amount of caffeine per package exceeding the supposed adult lethal dose in literature.

Methods

Calls to EPIC about caffeine exposures 2010–2023 and Health Insurance statistics about cases treated were analysed. A round table meeting with other involved parties in Estonia was organized in December 2022 to discuss the possibility of restricting caffeine sale per purchase. In addition, European partner organizations were consulted about their regulation of caffeine-containing products.

Results

Overall 45 EPIC consultation cases were found (23 male, 22 female) peaking with 8 cases in 2022. The mean age was 21 years (from 3 to 62 years). Symptoms reported included gastrointestinal irritation (56%), tachycardia (30%), tremors (35%), headache (13%), hypotension (10%), seizures (2%), and ventricular fibrillation with successful resuscitation (2%). A third (33%) of exposures were suicide attempts. More serious symptoms were associated with caffeine tablets and powder. For the same period, there were 153 visits to healthcare providers related to caffeine exposures. The most common caffeine tablets in Estonia are sold as 100 mg tablets in a bottle of 100. Supplements sold in gyms sometimes contain even more caffeine per package. As a food supplement, sale of caffeine is regulated by the recommended daily dose not considering whole amount per package. From PICs in other Nordic countries and the European Food Agency we learned that oral caffeine is registered as a food supplement not medication all over the Europe, therefore its sale cannot be restricted if the daily dose does not exceed 400 mg (200 mg per intake).

Conclusion

Our cases show that caffeine can cause serious poisoning. Caffeine supplements are mostly used by teenagers and young adults who also are the most endangered age group in terms of suicide attempts. Therefore, it does not seem reasonable to sell them limitless amounts of a potentially deadly substance. We believe there is a need to register caffeine as a medication or otherwise change the restrictions for food supplement sale, so it not possible to buy deadly amounts of a substance per purchase.

65. Improving toxin classifications in a knowledge-based decision support system for the diagnosis of human exposures

Abstract

Objective

Utilizing data elements required by the National Poison Data System (NPDS), a knowledge-based system (KBS) is being developed. The KBS is capable of supplying computerized decision support to aid medical personnel when diagnosing human exposures to unknown toxins.

Methods

During development, the KBS was trained and tested using 10-fold cross validation. To train the KBS, data mining extracted 168,545 relevant single exposure cases from a database supplied by the Florida Poison Information Center Network. A subset of the extracted data was then used to train the KBS to generate differential diagnoses (i.e., ranked lists) using pre-test probabilities and likelihood ratios. For the remaining subset of cases, the clinical effects associated with each case were introduced to the system and the known cause compared to the computed differential diagnosis. System accuracy was calculated as the percentage of correct diagnoses in the top 10% of all trained diagnoses.

Results

Prior work demonstrated that system accuracy improved as the number of toxic exposure cases in the database increased. Additionally, the removal of cases resulting in death and the removal of ambiguous substance listings defined by NPDS, further improved system accuracy. However, it was noted that NPDS categories frequently do not group substances by similar clinical effects. For this study, clinically indistinguishable substances with the same management strategies were merged into appropriate diagnostic classes. For example, acetylsalicylic acid, salicylamide, and methyl salicylate were grouped together as salicylates. Using these new classes, the system attained accuracies of 82.0% when diagnosing exposures of minor severity or worse, 85.0% when diagnosing exposures of moderate severity or worse, and 85.3% when diagnosing exposures of major severity. These results represent an increase in system accuracy of 4.3% when diagnosing minor severity or worse and 1.0% when diagnosing moderate severity or worse. Unfortunately, system accuracy decreased by 1.1% when diagnosing only major severity cases.

Conclusion

The decrease in accuracy diagnosing major severity exposures may be explained by accuracy being calculated in the top 10% of all trained diagnoses. Grouping substances in classes reduced the number of possible diagnoses from ∼480 to ∼340, meaning the substance must now be identified in the top 34 diagnoses rather than the top 48. Taking this, and the improved accuracies at other severities, into consideration, the use of classes may be viewed as a success. Furthermore, the overall utility from the perspective of a user viewing the system's differential diagnosis is drastically improved.

66. Sodium nitrate poisoning with a fatal outcome

Abstract

Objective: To describe the management of a fatal sodium nitrate poisoning.

Case report: A 23-year-old male required urgent medical attention after experiencing two cardiopulmonary arrests at home following the deliberate ingestion of 25 grams of sodium nitrate orally, in a suicide attempt. Upon arrival at the Emergency Department, the patient was intubated and receiving an adrenaline infusion. He exhibited a pronounced cyanotic appearance of the skin and serohematic fluid exudation through the endotracheal tube. At this point, he experienced another cardiopulmonary arrest in the form of asystole.

An urgent arterial blood gas analysis revealed a pH of 6.7, a bicarbonate of 6 mmol/L, a glucose of 32 mg/dL, and 100% methemoglobinemia. An intravenous infusion of methylene blue [1] was immediately initiated with an initial dose of 100 mg. After the first administration of this antidote, the blood gas analysis was repeated, showing a methemoglobinemia level of 75.6%. Two additional doses of 50 mg of intravenous methylene blue were administered while resuscitation efforts continued. Blood analysis revealed elevated concentrations of sodium (155 mmol/L), potassium (6.1 mmol/L), alanine aminotransferase (ALT) (963 U/L), aspartate aminotransferase (AST) (1828 U/L), prothrombin activity (41%), INR (1.89), and fibrinogen (143 mg/dL). Despite resuscitation efforts lasting 35 min, including the administration of 7 mg of adrenaline, 150 mmol of intravenous 1 M bicarbonate, 2 ampoules of calcium gluconate, 2 ampoules of dextrose 50%, and 200 mg of methylene blue, the patient ultimately died.

Conclusion: In cases of sodium nitrate poisoning resulting in methemoglobinemia, hypoxia symptoms develop rapidly, in contrast to tissue hypoxia where hypoxemia may not be present. Symptoms can range from cyanosis and dyspnea to a picture of respiratory shock. The severity of poisoning often correlates with blood methemoglobin levels and can be exacerbated by factors such as anemia, cardiac, and pulmonary diseases. Most fatal outcomes occur when methemoglobin levels exceed 30–40%, as was the case here.

The antidote of choice is methylene blue, indicated in acute poisonings with methemoglobin levels above 20–30%. For intoxicated patients who are asymptomatic with levels <30%, close monitoring is usually recommended.

67. Navigating the blue abyss: successful treatment of extreme methemoglobinemia at 88.9% caused by intentional sodium nitrite poisoning

Abstract

Objective

Sodium nitrite is used as a coloring agent, fertilizer, preservative in food and as an antimicrobial agent in meat products. Sodium nitrite intoxication is a common cause of severe methemoglobinemia (MetHb) and MetHb levels of >70% are considered fatal [1]. In this report, we describe the successful treatment of a case of severe MetHb of 88.9% due to intentional sodium nitrite poisoning.

Case report

A 20-year-old woman with a Glasgow Coma Scale (GCS) score of 3 was presented to the emergency department. At the time of the initial examination, the patient was cyanotic, with insufficient spontaneous breathing at 8/min with SpO₂ 78%, blood pressure 92/47 mmHg, and heart rate 85/min. Minutes later, the patient was intubated, and intravenous vasopressors started at 0.22 -> 0.44 -> 0.66 (µg/kg/min). Initial arterial blood gas analysis showed pH 7.4; pCO₂ 22.5 mmHg; pO₂ 474.3 mmHg; normal electrolytes; glucose 16.3 mmol/L, lactate of 11.66 mmol/L and MetHb 88.9% (normal range 0–2%). Life-threatening methemoglobinemia was diagnosed, a clinical toxicologist was contacted, and it was decided to start a methylene blue infusion (2 mg/kg). An additional 7.5 g of ascorbic acid with 5% glucose solution was given. The patient was admitted to the Toxicology ICU for further treatment. After an hour of antidote treatment, MetHb was 11.0%, and a few hours later it reached a normal range of 1.1%. When she recovered, the patient explained that on that day of admission she drank a bottle of sodium nitrite for suicidal purposes after searching for information on the Internet. As was later known, the patient had a history of depression and anxiety and was on sertraline. As she started having stomach cramps, nausea and general weakness, she informed her brother, who then called the ambulance. After almost a month in the ICU, she was moved to the psychosomatic ward, hemodynamically stable, spontaneously breathing and without any neurological deficit, for further psychiatric treatment.

Conclusion

This case highlights the critical importance of rapid recognition and intervention in cases of life-threatening methemoglobinemia induced by intentional sodium nitrite poisoning. Severe methemoglobinemia may be fatal, therefore, accurate diagnosis is essential to ensure specific antidote treatment can be started as soon as possible.

69. Deliberate self-poisoning by car exhaust fume inhalation resulting in significant methemoglobinemia without carboxyhemoglobinemia

Abstract

Objective

Methemoglobinemia is an uncommon consequence of car exhaust fume inhalation. This is most likely from exposure to inadequately removed nitrogen oxides by catalytic converters, which normally remove significant amounts of carbon monoxide and nitrogen oxides. We present a case of significant methemoglobinemia without carboxyhemoglobinemia, resulting from deliberate self-poisoning with car exhaust fumes and poly-sedative ingestion.

Case report

A previously healthy 45-year-old man with history of depression, was found unresponsive in his sealed car cabin, with a pipe connected from the car exhaust (2013 Mazda-6 sedan), resulting in exposure to exhaust gases for an unknown period. Bystander cardiopulmonary resuscitation (CPR) was performed for unresponsiveness. On paramedic arrival, vital signs were: blood pressure 146/87, pulse 87/min, respiratory rate 20/min, blood glucose 6.1 mmol/L. He was initially comatose with Glasgow Coma Score (GCS) 3. This improved en route to hospital. He was cyanotic and pale in appearance with unrecordable pulse oximetry saturation, despite 15 L/min oxygen via non-rebreather mask. In the emergency department, he was drowsy and confused (GCS 13). Cyanosis was unresponsive to oxygen administration, respiratory rate 14/min, pulse oximetry 93% on 15 L/min of oxygen. Venous blood gas demonstrated respiratory acidosis (pH 7.21, pCO₂ 79 mmHg, bicarbonate 31 mmol/L, lactate 3.8 mmol/L), methemoglobin 32.8% (normal: 0–2.0%), carboxyhemoglobin 1.3% (normal: 0–2.0%). Methylene blue 1 mg/kg IV was administered with resolution of methemoglobinemia. Subsequently, he became increasingly sedated requiring endotracheal intubation for airway protection. Twelve-lead electrocardiogram (ECG) showed sinus rhythm. Serum troponin, electrolytes, renal and liver function, cranial computerised tomography (CT) scan were normal. Ethanol was undetectable. Drug of abuse immunoassay revealed amphetamines and benzodiazepines. He remained intubated for 36 h and was confused for 3 days post-extubation. On resolution of confusion, the patient was neurologically intact, and, in addition to car exhaust exposure, reported ingestion of pregabalin and “street” benzodiazepines. He denied exposure to methemoglobin-inducing substances and denied previous episodes of cyanosis or family history of methemoglobinemia. Glucose-6-phosphate dehydrogenase and haemoglobin electrophoresis screening were normal.

Conclusion

Central cyanosis unresponsive to oxygen therapy mandates methemoglobinemia confirmation as a diagnosis. Previous reports of acquired methemoglobinemia after car exhaust fume inhalation are infrequent. Three reported cases had similarly low carboxyhemoglobin percentage despite significant methemoglobinemia, after car exhaust inhalation. Our case was similarly successfully treated with methylene blue. Catalytic converters remove nitrogen oxides and carbon monoxide from car exhaust gases. Changes in engine air-fuel ratios may vary the ratio of removal of these two gases by catalytic converters and could explain these sporadic cases of methemoglobinemia.

70. Intractable gastrointestinal symptoms and neuropathies in a patient with ethylene glycol poisoning

Abstract

Objective

We present an ethylene glycol (EG) poisoned patient with intractable gastroparesis, long-lasting constipation and multiple cranial and peripheral neuropathies.

Case report

A 53-year-old man with a history of hypertension and schizoaffective disorder was brought to our department. He had ingested 0.3–0.4 L of 70% EG solution 5 days earlier in a suicide attempt. On admission he was awake, and oriented to time and place. He was tachycardic (136/min), but his physical examination revealed no other abnormalities. Venous blood gas showed metabolic acidosis (pH 7.234, bicarbonate 8.7 mmol/L, anion gap 32.8). His serum EG concentration was undetectable. Laboratory studies confirmed acute renal injury (serum creatinine 565 μmol/L) and the patient was anuric. He was started on intermittent haemodialysis (IHD). On day 13 of admission he complained of difficulty swallowing, 2 days later he noted tinnitus, hyperacusis, dizziness, numbness and weakness of lower limbs. Otolaryngological and neurological examination established bilateral palsies of cranial nerves VIII, IX, and X and diminished reflexes, tactile and algetic hypaesthesia, and ataxia of lower limbs with normal muscle force. Computerised tomography of the brain showed no pathology. On day 19 of admission he developed respiratory failure and required mechanical ventilation for 12 days in the intensive care unit (ICU). Tracheotomy was performed. The patient received antibiotics for bronchitis and transfusion. After he was discharged from ICU his hearing and movement improved significantly. He was able to swallow, but complained of persistent nausea and vomiting after meals [1]. His symptoms partially respond to antiemetics; hence he was given a motilin receptor agonist (erythromycin) for 10 days to accelerate gastric emptying [2]. His gastroparesis recovered, but he suffered from constipation and needed laxatives for months. IHD was ceased after 12 weeks, but his renal function remained abnormal, and the neuropathy of the lower limbs persisted. He was transferred to the psychiatric department.

Conclusion

Neuropathies and gastroparesis are known delayed neurological sequelae of EG toxicity, but physicians should consider long-lasting constipation as a delayed autonomic nervous system dysfunction. This case illustrates that intractable gastroparesis can be treated successfully with erythromycin in patients with EG poisoning.

71. Vitamin D macrodosing: two cases of unconventional treatment in pre-conception and pregnancy

Abstract

Objective

Vitamin D (colecalciferol) has an immune modulating role via interaction with the vitamin D receptor (VDR); it is used in prophylaxis and therapy of various diseases [1]. In 2013, the group of Cicero Coimbra proposed the “Coimbra protocol” (CP) [2], i.e., high dose vitamin D3 in patients with autoimmune disorders to overcome vitamin D receptor resistance. We report two cases of vitamin D3 macrodosing according to the CP.

Case reports

A 41-year-old woman planning a pregnancy through egg donation, affected by rheumatoid arthritis and Hashimoto's thyroiditis, treated with CP (colecalciferol 180,000 IU/day) showed a 25-hydroxyvitamin D value of 604.7 µg/L. The treatment was interrupted and after 1 year the 25-hydroxyvitamin D value was still 230 µg/L, reducing by only a third. Due to clinical worsening the patient resumed colecalciferol therapy and the medically assisted procreation project was abandoned. A 31-year-old woman affected by ulcerative colitis treated with colecalciferol 100,000 IU/day throughout pregnancy despite the indication to stop the CP, showed a serum 25-hydroxyvitamin D value far above toxicity (566 µg/L). A healthy baby girl was delivered at week 39. However, she also had a very high value of 25-hydroxyvitamin D (250 µg/L), phosphorus 7.4 mg/dL and creatinine 1.23 mg/dl. The concentration of 25-hydroxyvitamin D in the mother’s breastmilk was 7.59 ng/mL compared 4 ng/mL in a sample of pooled human milk. The baby was then fed with human milk from the Children's Hospital milk bank and treated with IV fluid therapy. Echocardiography showed microcalcifications at the papillary muscles of the left ventricle, not confirmed on a second examination. The baby was discharged on day 10 with a 25-hydroxyvitamin D value of 174 µg/L which slowly decreased to normal range. The growth was regular during the first 3 months. High levels of vitamin D taken during pregnancy lead to mild toxic effects in the newborn and despite a long afterbirth hospitalization the baby is now healthy.

Conclusion

Therapy with vitamin D macrodosing cannot be safely managed in certain periods of life and should be avoided in pre-conception period and pregnancy due to its extremely long elimination time and possible toxicity in both mother and baby.

72. Can benzodiazepines mask toxidromes induced by new psychoactive substances?

Abstract

Objective

New psychoactive substances (NPS), such as cathinones, ketamine, and amphetamine-type stimulants, often lead to poisoning causing a sympathetic toxidrome with symptoms including hypertension, tachycardia, and dilated pupils [1]. Polysubstance drug poisoning is common in the emergency department, and the toxidrome of patients may be obscured due to the concurrent use of benzodiazepines. Benzodiazepines are the first-line treatment for sympathomimetic toxidromes, despite not causing pupil constriction [2]. Our objective is to determine whether benzodiazepines mask the toxidrome induced by new psychoactive substances.

Methods

In a retrospective study at China Medical University Hospital, we analyzed data from September 2016 to October 2018. Excluded from the study were patients under 20 years old, those with insufficient specimens, or those exposed to non-NPS substances. The new psychoactive substances analyzed encompassed cathinone drugs, amphetamine-type stimulants, and ketamine. We conducted a comparative analysis, using the Independent Sample t-test, to assess pupil size, heart rate, body temperature, Glasgow Coma Score (GCS), and blood pressure in patients exposed to both new psychoactive substances and benzodiazepines, as opposed to those exposed solely to new psychoactive substances.

Results

Out of a total of 384 patients, 278 were excluded, leaving 106 patients for inclusion in our study. Among these, 59 patients were concurrently exposed to benzodiazepines, while 47 were not. Comparing patients exposed to new psychoactive substances with benzodiazepines to those without benzodiazepines, the average pupil size was 2.80 mm versus 3.57 mm (P-value 0.04), heart rate 107.7/min versus 103.4/min (P-value 0.46), body temperature 36.75 °C versus 36.82 °C (P-value 0.76), systolic blood pressure 127.81 mmHg versus 133.25 mmHg (P-value 0.33), and Glasgow Coma Score 12.36 versus 11.37 (P-value 0.21).

Conclusion

The study found that pupil size in patients exposed to new psychoactive substances with benzodiazepines was smaller than in those exposed to new psychoactive substances alone, potentially masking sympathetic toxidromes. However, there were no significant differences in heart rate, body temperature, systolic blood pressure, or Glasgow Coma Score.

73. Acute knockdown effect due to inhalational exposure to hydrogen sulphide in a leather tannery effluent worker: a diagnostic conundrum solved

Abstract

Objective

To describe a case of toxic inhalational hydrogen sulphide (H2S) exposure and its associated longitudinal outcomes. This case report is derived from a retrospective review of hospital electronic medical records of a clinical toxicology unit at a tertiary care referral center in South India.

Case report

A 52-year-old male working in a leather tannery wastewater effluent treatment plant, was found unconscious by his co-workers 10 min after entering an effluent treatment pit. He was immediately pulled out and taken to hospital. Within a few minutes his consciousness improved, but he developed rapidly worsening breathlessness. At a regional primary healthcare center, he was markedly hypoxemic with bilateral infra-axillary and infra-scapular crepitations. He was given IV diuretics for suspected pulmonary oedema and referred to a tertiary center for diagnostic evaluation and further management of a possible acute coronary syndrome with acute pulmonary oedema. Imaging of the brain was advised to rule out a subarachnoid hemorrhage in view of acute loss of consciousness. On arrival to the Emergency Department of Christian Medical College, Vellore, he was tachycardic, tachypneic and drowsy with oxygen saturation of 87% (room air). He had conjunctival injection with excessive lacrimation and bilateral infra-scapular and infra-axillary inspiratory crepitations. Laboratory investigations revealed severe lactic acidosis, normal renal and liver function tests and normal cardiac enzymes. Electrocardiogram (ECG) revealed only sinus tachycardia and chest X-ray was suggestive of pulmonary oedema. Plain brain computerised tomography (CT) scan was normal. In view of possible exposure to hydrogen sulfide which is commonly produced as a by-product in effluent treatment pits and a compatible clinical syndrome, the patient was clinically diagnosed to have hydrogen sulfide inhalational toxicity. The diagnosis was supported by a coin found in his pocket which had turned black, possibly due to formation of iron sulfide on H2S exposure. He was managed with mechanical ventilation and supportive care in the intensive care unit. Sodium nitrite was not available. He was discharged after marked clinical improvement. On review after 2 weeks, he was noted to have developed atypical Parkinsonism, requiring amantadine. A site visit 2 months later to the effluent treatment plant, confirmed the presence of hydrogen sulfide in the effluent collection pit using a hydrogen sulfide meter.

Conclusion

Hydrogen sulphide exposure is an occupational hazard in leather tannery effluent workers, which may be under recognized. Knowledge about the clinical manifestations and exposure sources will aid in clinical diagnosis thus avoiding unwarranted investigations and early initiation of appropriate therapy.

74. Intentional ingestion of a potentially lethal dose of caffeine: case report with plasma determination

Abstract

Objective

The availability on the Internet of tablets with high concentrations of caffeine, often used for weight-loss, increase the risk of poisoning by high dose-caffeine. There is no defined toxic dose/plasma concentration of caffeine that is derived from case reports/series, a lethal dose in adults is estimated at 150–200 mg/kg, and death is reported with serum concentrations above 80 µg/mL. We describe a case report of an attempted suicide by caffeine ingestion by a teenager.

Case report

A 16-year-old male, weight 75 kg. was accepted to a peripheral emergency department because of intentional ingestion, 3 h prior, of 70 tablets of caffeine 200 mg (estimated ingested dose 187 mg/kg), bought on the Internet. Clinical manifestations were vomiting, hypokalemia (2.6 mEq/L) and metabolic acidosis (lactate 6.6 mmol/L). Because of the estimated lethal dose and the clinical manifestations, he was immediately transferred to our pediatric hospital. Admitted to intensive care, the clinical picture was characterized by a worsening of metabolic acidosis (lactate 10.3 mmol/L), for this reason the patient was intubated and sedated, to prevent seizures and to perform an endoscopy for decontamination purposes (at 6 h after ingestion, minimal residual powder of tablets was retrieved), followed by whole bowel irrigation. Dialysis using the continuous renal replacement therapy (CRRT) technique was also carried out for a total time of 20 h. The clinical course was characterized by increase in creatine kinase, creatinine, amylase/lipase values up to 1191 U/L; 1.2 mg/dL and 157/136U/L, respectively. A determination of plasma caffeine was also obtained 6, 10, 16, 24, 27 and 29 h after ingestion, revealing concentrations of 53, 34.5, 26.5, 16.85, 14.9 and 9.7 µg/mL, respectively. The patient did not develop seizures and abnormal blood tests gradually improved, finally he was extubated and discharged asymptomatic 72 h after ingestion with scheduled psychiatric follow-up.

Conclusion

In our case, the initial plasma concentration confirmed the estimated lethal dose reported by the patient for which an interventional immediate approach was chosen. A slower decrease in plasma caffeine values was observed than expected with dialysis, this is possibly explained by a delayed gastric decontamination with a consequent prolonged absorption of caffeine from the gut in parallel with dialysis. At the same time, it is possible to speculate that dialysis, together with the sedation administered, prevented the achievement of higher concentrations that would have been responsible for seizures and a more severe clinical picture.

75. Treatment of toxic alcohol poisoning using fomepizole (off-label) in pediatric patients

Abstract

Objective

The antidotal treatment of toxic alcohol poisoning is based on ethanol and fomepizole administration. Fomepizole is the antidote of choice to avoid ethanol adverse reactions, particularly in pediatric poisoning. However, the leaflet of the three brands available in our country reports “Safety and effectiveness in pediatric patients have not been established”. This is a common problem in pediatric clinical practice in which many drugs/antidotes are used off-label. The aim of this study has been to evaluate efficacy and safety of the off-label use of fomepizole in poisoned pediatric patients.

Methods

A retrospective study including all patients <18 years in which fomepizole was administered for suspected/confirmed toxic alcohol poisoning was performed in our Poison Control Centre in the period 2010–2022.

Results

Fifty-four cases met the inclusion criteria (37M/17F), mean age 7.5 years (7 months-14 years). All cases were treated with fomepizole because of accidental ingestion of a maximum of 1–2 sips of products containing ethylene glycol/methanol (32 antifreeze; 21 paints thinner, 1 model engine fuel). The mean time between ingestion and emergency departments (ED) arrival, and between ingestion and fomepizole administration, was 1.8 h (30 min–8 h) and 5.6-h (1–24 h), respectively. At ED arrival, 33/54 patients were asymptomatic. The main clinical manifestations in 21/54 symptomatic patients were metabolic acidosis (52%), vomiting (28%), drowsiness (14%), and ataxia (14%). In 12/54 cases the antidote was promptly available, in 42/54 it was mobilized from other hospitals. In all cases the decision to administer the antidote was based on the amount ingested and the concentration of toxic alcohol in the product; fomepizole was administered at a dose of 15 mg/kg followed by 10 mg/kg every 12 h as in adult patients. The total doses needed were 1 in 5/54, 2 in 34/54, 3 in 12/54, and 4 in 3/54. The number of administered doses was guided by the presence of metabolic acidosis and the ethylene glycol/methanol plasma concentrations (obtained in 34/54 patients). No adverse reactions to fomepizole were registered. An improvement of metabolic acidosis was registered in the cases in which it was present before fomepizole administration. No clinical manifestations of toxicity appeared in asymptomatic patients, even when toxic alcohols plasma concentration was positive.

Conclusion

The off-label use of fomepizole in pediatric patients was safe and effective in preventing/treating toxic-alcohols poisoning. We hope that a greater number of antidotes will be studied and made available for pediatric poisoned patients.

76. Pediatric alpha-2 agonist exposures in the ToxIC Registry

Abstract

Objective

To describe outcomes following exposures to pediatric single agent alpha-2 agonist agents reported to the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) between 2010 and 2022.

Methods

We performed a retrospective review of cases of pediatric (<18 years) single agent alpha-2 agonist exposures in the ACMT ToxIC Registry from January 1, 2010 through December 31, 2022. Data in the ToxIC registry is prospectively collected by consulting medical toxicologists at participating sites using a standardized form. Descriptive epidemiology is reported.

Results

This retrospective cohort study analyzed 658 clonidine exposures and 231 other alpha-2 agonists: tizanidine, guanfacine and dexmedetomidine. There were no pediatric cases involving xylazine. Hypotension (defined as systolic blood pressure <80 mmHg) was documented in 126 (19%) cases of clonidine exposure and 175 (76%) cases of other alpha-2 agonists. Bradycardia (heart rate <50 beats per minute) was identified in 294 (45%) cases of clonidine exposure and in 123 cases of other alpha-2 agonists (53%). There were 74 (11%) cases of respiratory depression following clonidine exposure and 9 (4%) with other alpha-2 agents. Pressors were administered in 25 (4%) of clonidine cases and 6 (3%) of other alpha-2 agonists. Intubation was required in 75 (11%) cases of clonidine ingestion and 14 (6%) of other alpha-2 agonists. No deaths were reported in this cohort.

Conclusion

This data underscores the significant occurrence of hypotension in non-clonidine exposures, suggesting the potential for more dramatic cardiovascular effects with other alpha-2 agonists. Rates of bradycardia and pressor support were similar. However, clonidine exposures resulted in more cases of respiratory depression and intubation.

77. Sulfoxaflor poisoning and its association with delayed neurotoxicity: a case report

Abstract

Objective

Sulfoxaflor, a neonicotinic insecticide, has been considered a potential replacement for older neonicotinics due to its limited impact on mammalian nicotinic acetylcholine receptors (nAChRs). Although it primarily affects the nervous system and liver in rats, its human toxicity remains unexplored. We report the first case of oral sulfoxaflor ingestion, leading to consciousness disturbance and seizures.

Case report

An 82-year-old man with hypertension, diabetes, iron-deficiency anemia, and a previous left cerebral artery stroke ingested two mouthfuls of sulfoxaflor. Three hours later, he arrived at the Emergency Room (ER), conscious with stable vital signs. He reported mild shortness of breath but no other discomfort. Examination revealed small, reactive pupils, dry skin, and scattered chest rhonchi. Laboratory results showed leukocytosis, microcytic anemia, high anion gap metabolic acidosis, lactic acidosis, and deteriorating renal function. Liver function and electrolytes were normal. After four hours, he experienced muscle twitching and unconsciousness, necessitating intubation. Blood pressure dropped but improved with hydration. An electroencephalogram (EEG) showed cortical dysfunction and epileptic discharge, but brain magnetic resonance imaging (MRI) was normal. Levetiracetam controlled seizures, and he regained consciousness. Extubation occurred after 16 days, and he was discharged after 25 hospital days.

Conclusion

The patient showed no liver enzyme or function impairment. Human reactions to nicotine exposure, termed "nicotinic signs" vary. Sulfoxaflor primarily affects insect nAChRs but differs in its interaction with mammalian nAChRs. Muscle twitching in our patient may not result from muscle nAChR activation but from seizures triggered by specific central nervous system nAChR stimulation. A prior ischemic stroke may have increased seizure risk. The product ingested contained sulfoxaflor and propylene glycol, but metabolic and lactic acidosis with a high anion gap did not align with propylene glycol intoxication. This case represents the first report of oral sulfoxaflor intoxication in humans. Possible toxic effects include consciousness disturbance and seizures, managed with supportive care and anti-epileptic drugs. Further studies and case reports are needed to confirm sulfoxaflor's definitive toxicity in humans.

79. Avermectin related poisoning reported to Taiwan Poison Control Center, 1993–2022

Abstract

Objective

Pesticide ingestion is a frequently employed method for attempting suicide worldwide and was ranked as the third most common method of suicide in Taiwan [1]. In recent years, a growing concern has arisen regarding the increasing prevalence of avermectin poisoning. The objective of this study is to investigate the trend and the characteristics of avermectin poisoning in Taiwan.

Methods

We conducted a retrospective analysis of all cases of poisoning involving avermectins (including ivermectin, abamectin, and emamectin) reported to the Taiwan Poison Control Center (PCC-Taiwan) between 1993 and 2022. We then analyzed the annual number of cases to examine the trend of poisoning incidents reported to PCC-Taiwan. In addition, we conducted a descriptive analysis of the baseline characteristics of the poisoned cases.

Results

After excluding 131 cases that were lost to follow-up, had insufficient information to determine severity, or co-ingestion of more toxic pesticides such as paraquat, organophosphates, carbamates, and chlorfenapyr, a total of 524 cases were eligible for final analysis. The annual number of avermectin poisoning cases significantly increased during the study period (R² = 0.7006, p < 0.001), mainly due to an increase in the number of emamectin poisoning cases. Among the 524 cases, 465 had an oral exposure and 59 had a non-oral exposure. For cases with oral exposure, 88.4% of patients were intentionally exposed and 39 died, resulting in a case fatality rate of 8.4%. In contrast, among the 59 cases with non-oral exposure, most of them were accidentally exposed, and only one case experienced severe toxicity. Among the orally exposed cases, 50.8% experienced gastrointestinal effects (e.g., nausea and vomiting), 43.4% had neurological effects (e.g., altered mental status), 34.4% manifested cardiovascular effects (e.g., hypotension), and 24.1% presented with respiratory effects (e.g., dyspnea).

Conclusion

We have observed an increasing trend of avermectin, especially emamectin poisoning reported to PCC-Taiwan during the study period, which may be related to the ban of more toxic insecticides such as organophosphates and carbamates in Taiwan. Moreover, the majority of avermectin poisoning cases are orally and intentionally exposed, which is associated with more severe outcome and a higher case fatality rate as compared to the non-oral and accidental exposure.

80. Analysis of lethal cases by chemical poisonings registered in the Spanish Toxic Surveillance System (STSS) during the last 24 years

Abstract

Objective

To track the evolution of fatal cases involving chemical products recorded in the Spanish Toxic Surveillance System (STSS) since 1999. The STSS compiles data on acute poisonings caused by chemicals treated in Spanish hospital Emergency Departments (ED). Between 1999 and 2022, a total of 19,990 cases were collected from 30 hospitals.

Methods

Data are provided by members of the staff in the ED of the hospitals participating in the STSS. Each case's data file includes information such as sex, age, symptoms, treatment, outcomes, product identification, cause of exposure, and exposure route. Since 2011, an online form has been employed to collect case information. The primary chemical substances currently responsible for acute poisonings include toxic gases (systemic and irritants), corrosive liquids, solvents, pesticides, and detergents.

Results

There were 221 recorded fatal cases, resulting in a mortality rate of 1.1%, which is higher than the mortality rates for total acute poisonings, which are less than 0.5% in Spanish hospitals. The average age of fatal cases is 63 years, significantly higher than that observed in the total chemical cases (39 years). Gender distribution among fatal cases is uneven, with 62% being males and 38% being females, in contrast to the general group where cases are evenly distributed. The types of poisoning incidents include suicide attempts in 143 cases (65%), domestic accidents in 54 cases (24%), and occupational accidents in 7 cases (3%). The mortality rates by chemical family are as follows: pesticides 3.6%, caustics 1.8%, solvents 1.4%, and toxic gases 0.6%. For the most hazardous agents, the mortality rates are as follows: carbon monoxide (CO) 0.6%, methanol 15.5%, hydrochloric acid (HCl) 19.3%, and paraquat 62.5%. Cases of paraquat poisoning are concentrated in the first 7 years (92%) due to the EU's ban on this herbicide in 2007. Cases related to CO and HCl are spread throughout the study period. CO exposure is mainly associated with domestic accidents, while HCl exposure is linked to suicide attempts.

Conclusion

Poisoning by chemical agents still exhibits a higher mortality rate compared to all poisoning cases attended in our EDs. Lethal cases are more prevalent among men and the older population, primarily from suicidal gestures. The most dangerous agents include paraquat, HCl, methanol, and CO. The European Union's ban on highly toxic pesticides, such as organophosphate insecticides and paraquat, has demonstrated its effectiveness in reducing mortality associated with these substances.

81. Coagulopathy and potential disseminated intravascular coagulation following abamectin intoxication

Abstract

Objective

While agricultural avermectin poisonings are generally associated with mild clinical manifestations and are often considered safer compared to organophosphate poisonings, we present an atypical presentation of abamectin intoxication leading to coagulopathy.

Case report

An 83-year-old female with a medical history of rheumatoid arthritis, hypertension, and prior colorectal polypectomy presented to the emergency department after ingesting 250 mL of insecticide, which contained 2% abamectin and unknown solvent. She experienced vomiting shortly after ingestion and, upon arrival, exhibited mild somnolence, accompanied by complaints of throat pain and abdominal discomfort. Initial laboratory tests showed an elevated white blood cell count (WBC 12,500/µL) and low potassium (K 2.9 mmol/L). Coagulation parameters were within normal range, however, there was a change in clinical condition nine hours post-ingestion where she began to develop bloody stools. Subsequent coagulation studies showed prolonged prothrombin time (PT 20.0 s), elevated International Normalized Ratio (INR 1.71), extended activated partial thromboplastin time (APTT 43.7 s), and elevated fibrinogen (344.3 mg/dL); D-dimer concentration was elevated (2804.5 ng/mL) with thrombocytopenia (platelet count 80,000/μL). International Society of Thrombosis and Hemostasis (ISTH) disseminated intravascular coagulation (DIC) score was calculated to be 5. Notably, the gastrointestinal bleeding ceased spontaneously without any specific hemostatic interventions. Following a week of hospital care and close observation, the patient was discharged in stable condition.

Conclusion

The relationship between abamectin intoxication and coagulopathy appears to be atypical. The case report discussed presents an uncommon manifestation of abamectin poisoning leading to coagulopathy, which has not been traditionally reported in the literature [1,2]. The observed coagulopathic effects might be related to the solvent or other additives present in the pesticide rather than the abamectin itself. It is important for clinicians to consider the potential complication of DIC when dealing with significant abamectin ingestion, as highlighted by this case.

82. Prolonged symptoms following dermal exposure to alpha-cypermethrin, a type II pyrethroid

Abstract

Objective

To describe a case of prolonged symptoms following dermal exposure to alpha-cypermethrin, a type II pyrethroid insecticide.

Case report

A 45-year-old male farmer was exposed to a large amount of alpha-cypermethrin (1.25%) solution when he accidentally spilled it on his back, leg and foot while treating sheep for ectoparasites. Decontamination with soap and water was performed after 15–20 min. He developed generalized pruritus for two days, during which he contacted the Norwegian Poison Information Centre (NPIC) twice and the local emergency room physician prescribed antihistamines. On day 13, he was admitted to the hospital with progressive flu-like symptoms, restlessness, insomnia, paresthesia, myalgia and involuntary movements. Laboratory tests showed elevated creatine kinase (456 U/L), but were otherwise normal. Neurological examination revealed incomplete left-sided hemihypesthesia. His symptoms improved slightly by day 21, but he still had numbness in his left extremities and face, as well as muscle pain. On day 45, he reported no further improvement and complained of fatigue and recurrent muscle spasms and pain, especially after physical exertion. On day 145, he still suffered from muscle pain that interfered with his work.

Conclusion

This case report presents an unusual course of symptoms following dermal exposure to alpha-cypermethrin, which lasted for several months and affected the patient’s quality of life. Previous reports of dermal pyrethroid toxicity have not described such long-lasting effects [1]. Implementing a longer medical follow-up period after large dermal exposures could potentially identify similar cases and increase knowledge of the subsequent long-term effects. We suggest that the slightly delayed decontamination may have contributed to the severity and duration of the symptoms in this case.

83. A case of Cascabela thevetia (Thevetia peruviana) self-poisoning in Italy with analytical confirmation of the plant glycosides in blood and urine

Abstract

Objective

Yellow oleander (Cascabela thevetia previously Thevetia peruviana Juss) is a tropical and sub-tropical plant well known to contain a mixture of natural occurring cardiac glycosides structurally similar to digoxin. To our knowledge, none of the published cases of intoxication are laboratory confirmed through direct identification of the plant’s glycosides in biological fluids. We here report on a rare case of ingestion as self-harm poisoning in Italy with the first quantitative determination of yellow oleander glycosides in biological samples of a patient.

Case report

An 18-year-old female with a history of depressive disorder presented to the emergency department with diaphoresis, nausea, bradycardia (45 bpm), and blood pressure 100/70 mmHg. She revealed having intentionally ingested, 8 h earlier, half a glass where 9 crushed seeds of yellow oleander bought on the Internet were mixed in water. She had vomited at home. An antiemetic and activated charcoal were administered. Electrocardiogram (ECG) showed 2nd degree atrioventricular (AV) block type I. The serum potassium and digoxin concentration were respectively 4.2 mEq/L and 0.3 ng/L. Bolus doses of digoxin immune Fab (DigiFab^® 80–120 mg) were administered on day 1 with temporary rhythm normalization with negative T waves in inferior leads, and on days 3 and 5 as the ECG showed sinus/junctional rhythm (50 bpm) with retrograde P waves. A transient thrombocytopenia (60 × 10ⁱ/L) developed on day 7. She was discharged on day 11 following ECG normalization. Blood (collected on day 1 before DigiFab^® administration and day 3) and urine (day 3) samples were analysed using ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) with specific analytical standards for glycosides thevetin A, thevetin B and peruvoside. Thevetin A and thevetin B were below the detection limit in all samples. Peruvoside plasma concentration on day 1 was 2.27 ng/mL and below limit of quantification on day 3; urine concentration on day 3 was 14.52 ng/mL.

Conclusion

Peruvoside, a metabolite of the primary glycoside thevetin A obtained through hydrolytic cleavage [1], was the only glycoside recovered in biological fluids among those tested. The finding may support very early administration of activated charcoal to possibly prevent further formation of secondary glycosides (that are more potent Na/K-ATPase inhibitors) and limit toxicity. Future studies should also address the affinity of DigiFab^® for peruvoside and other main secondary glycosides to optimize antidote dosing strategy and shorten hospital stays.

84. The potential impact of a urine test for amatoxins on the management of mushroom ingestion in dogs

Abstract

Objective

Assessment of suspected mushroom ingestion in dogs is challenging. In particular ingestion of amatoxin-containing species can lead to life-threatening poisoning. Diagnostic testing with a quick and sensitive urine test for amatoxins, could improve triage and management of these cases. Our aim is to estimate the percentage of cases reported to the Dutch Poisons Information Center (DPIC) in which such a test could have been of value.

Methods

The DPIC database was retrospectively searched for inquiries concerning dogs suspected of ingesting wild mushrooms from 1 September 2022 to 1 September 2023. Collected cases were analysed for time between ingestion and first contact with the DPIC and the presence of clinical signs during this inquiry. Cases were scored on the time amatoxins are presumed to be present in the urine (>2 to ≤72 h) and time initial amatoxins-induced symptoms are to be expected (>6 to ≤24 h).

Results

Ninety-five inquiries involving 95 dogs were included; median body weight 10 kg (range 1–36 kg, n = 71) and median age 0.3 years (0.2–15 years, n = 54). In 24/95 cases the time between exposure and DPIC contact was unknown, 10/24 dogs were symptomatic, mostly gastrointestinal related. In 51/95 cases contact with the DPIC was established <2 h after ingestion (median 0.4 h, 0.1–2 h), 15/51 dogs were symptomatic (predominantly vomiting and diarrhoea). In 11/95 cases contact was established >2 to ≤6 h after ingestion (median 4 h, 2.5–6 h). All dogs were symptomatic, predominantly gastrointestinal related. In 5/95 cases contact was established >6 to ≤24 h after exposure (median 15 h, 7–24 h), all dogs were symptomatic and in at least one dog liver enzymes were elevated. There were 4/95 contacts with the DPIC >24 h after ingestion (median 48 h, 24–48 h) concerning one asymptomatic and three symptomatic dogs, including one with fulminant liver failure.

Conclusion

A diagnostic urine test for amatoxins was considered to be of value in all DPIC inquiries as there were no inquiries beyond the time amatoxins were expected to be in the urine. In >50% of the cases ingestion was so recent that decontamination measures were still applicable and urine collection would have had to be postponed to produce a reliable test result. Even in dogs developing gastrointestinal signs ≤6 h after mushroom ingestion, this test is of value as co-ingestion of amatoxin-containing mushroom species cannot be excluded. The value of the test lies predominantly with the early identification of dogs at risk to develop amatoxicosis, as aggressive decontamination, including repeated administration of activated charcoal and early start of liver protective treatments, may improve the outcome.

85. Recreational mushroom ingestion in adolescents reported to the UK National Poisons Information Service over a 10-year period

Abstract

Objective

Accidental mushroom ingestions are commonly reported in children as they can be easily exposed when exploring outdoor environments such as gardens. Cases concerning intentional mushroom ingestion in children for recreational purposes are rare. We analyse cases of recreational mushroom ingestions in adolescents reported to the UK National Poisons Information Service (NPIS) over a 10-year period.

Methods

A retrospective review of enquiries to the NPIS involving cases of recreational mushroom exposure in patients aged 18 and under was carried out for the period 1 January 2013 to 31 December 2022. Data were analysed by descriptive statistics and Pearson’s chi-squared test. An alpha <0.05 was considered significant.

Results

Twenty-six enquiries concerning 24 patients ingesting mushrooms recreationally were recorded, which accounted for 3% of the total enquiries involving mushroom ingestions in children for this period. Ten of the 26 enquiries were made in 2022. Twenty-one patients were male and 3 were female, p = 0.0002. The age ranged between 12 and 18 years with a median of 16. Twelve exposures occurred in a domestic setting, 7 in public areas, 4 in schools and 1 in a care home. Eighteen of the enquiries came from hospitals, three from NHS 111/NHS Direct/NHS 24, two from a primary care source and two from schools. The time since exposure was between 15 min and 6 days (median 5.25 h). The most common features were abdominal pain (n = 4), hallucinations (n = 3), mydriasis (n = 3), and agitation, headache, nausea, tachycardia, abnormal vision (all n = 2). The maximum Poisons Severity Score was none in 7 cases, minor in 13 and moderate in 4. The agents reported included unknown mushrooms (n = 11), magic mushrooms (n = 11), Amanita phalloides (n = 1) and Amanita muscaria (n = 1). Co-ingestions were reported in 7 cases. These included cannabis (n = 4), LSD (n = 2), MDMA (n = 1), morphine (n = 1), alcohol (n = 1), alprazolam (n = 1) and 2CB (n = 1).

Conclusion

The incidence of recreational mushroom use in adolescents is small. Most cases involve teenage boys. Magic mushrooms are often consumed with other recreational drugs, such as cannabis and LSD. Our data has limitations in that the service typically receives calls about more complex cases where callers require further discussion hence we suspect that this is an under-representation of the actual number of adolescent recreational exposures.

86. A case of severe Digitalis toxicity with an atypical response to DigiFAB treatment

Abstract

Objective

Digoxin-specific antibodies (DigiFAB^®) are used to treat toxicity from plant cardiac glycosides as well as pharmaceutical digoxin. While guidelines for digoxin toxicosis are well-established, plants contain numerous cardiac glycosides with less predictable pharmacokinetics. We report a case of severe toxicity following intentional foxglove ingestion with limited response to DigiFAB^® was limited.

Case report

A 53-year-old female presented 26 h following ingestion of a homemade paste containing four ground foxglove plants and 100 mg diazepam. She was found profusely vomiting and somnolent. The heart rate was 44 bpm and blood pressure (BP) 133/61 mmHg. The 12-lead electrocardiogram (ECG) demonstrated sinus bradycardia and first-degree heart block. Blood investigations demonstrated a serum digoxin of 2.2 μg/L, urea 6.5 mmol/L, creatinine 84 μmol/L and potassium 5.0 mmol/L, without acidosis (pH 7.35). She experienced intermittent bradycardia (26 bpm) and hypotension (systolic BP 80 mmHg), which rapidly responded to intravenous fluids. Forty-one hours post-ingestion she acutely decompensated with bradycardia (25 bpm) and hypotension (70/40 mmHg) before a brief loss of cardiac output. Cardiopulmonary resuscitation was commenced along with five vials (200 mg) of DigiFAB^® and 600 μg atropine. Haemodynamic stability was achieved with IV epinephrine (adrenaline) boluses. Five hours post-arrest, repeat blood tests demonstrated creatinine 52 μmol/L, potassium 3.6 mmol/L, and digoxin 10.2 μg/L. Due to ongoing bradyarrhythmias, she received a further 13 vials (520 mg) of DigiFAB^® over the following 36 h. Although initially associated with clinical improvement, subsequent dosing achieved minimal increases in heart rate. A glycopyrrolate infusion successfully achieved haemodynamic stability over the following five days. During this period, the patient developed profound diuresis (4–6 L/24 h) with a consistent negative fluid balance. Serum osmolality (280 mOsmol/kg) and urine osmolality (105 mOsmol/kg) suggested diabetes insipidus. Renal function remained normal. The patient recovered with supportive care and was discharged to a medical ward after five days.

Conclusion

We present a case of severe toxicity secondary to plant cardiac glycosides with associated features consistent with diabetes insipidus. DigiFAB^® is well-recognised for treatment of toxicity from plant cardiac glycosides, although higher doses are normally required [1]. In this case, increasing doses of DigiFAB^® were minimally effective. The precise cause of the diuresis remains unclear, although similar clinical features have historically been described [2].

87. A case report of Nerium oleander poisoning misidentified as bay laurel (Laurus nobilis) leaves: clinical challenges and management insights

Abstract

Objective

Nerium oleander (oleander) is a toxic plant containing cardiac glycosides, resulting in serious health risks following its ingestion. The clinical manifestations of oleander poisoning closely resemble those of digoxin toxicity, encompassing a spectrum of gastrointestinal symptoms, neuropsychiatric disorders, and cardiac disturbances. This report describes a case of accidental intoxication resulting from the consumption of an infusion of oleander leaves misidentified as bay laurel (Laurus nobilis) due to the similarity of their leaves.

Case report

An 84-year-old man with a history of triple coronary artery bypass, hypertension, and dyslipidemia ingested the misidentified oleander infusion, experiencing gastrointestinal symptoms within hours. Suspecting he has used the wrong plant for the infusion he contacted the poison control center (PCC), and on the advice received sought emergency care. Despite stable initial vital signs, the patient exhibited sinus bradycardia (heart rate: 55 bpm), grade I AV block, and frequent supraventricular extrasystoles on electrocardiogram, indicating a digitalis-like effect. Laboratory tests revealed a digoxin concentration of 0.75 ng/mL. While initially stable, the patient developed worsening bradycardia (heart rate: 37 bpm) and grade III AV block 19 h after ingestion, prompting the administration of digoxin-specific antibodies. Afterward, he required external transcutaneous pacing for three hours. Subsequent monitoring revealed a return to bradycardic sinus rhythm (heart rate: 50–59 bpm). The patient was discharged on the eighth day in a stable condition.

Conclusion

This case report highlights the critical importance of accurate plant identification and the potential dangers of misidentification. Oleander poisoning, which mimics digoxin toxicity, can lead to severe cardiac and gastrointestinal manifestations. Clinicians must be vigilant, especially when patients present with ambiguous symptoms. The case emphasizes the need for close monitoring, even in patients with an initial stable condition, as severe complications may be delayed. Moreover, the study emphasizes the limitations of standard assays, emphasizing the reliance on clinical evaluation.

88. Interdisciplinary therapy of Taxus poisoning

Abstract

Objective

Taxus intoxication presents a multifaceted challenge in the realm of toxicology and medical treatment. A high-dose ingestion of Taxus baccata (English yew) often results in death. Taxine alkaloids block sodium and calcium channels and disrupt sodium-potassium transport, consequently triggering a cascade of life-threatening events upon ingestion, necessitating swift and comprehensive medical intervention. Key obstacles include the rapid onset of symptoms, the absence of specific antidotes, and the potential for severe cardiac and neurological complications.

Case report

A 40-year-old patient collected Taxus leaves, dried and ground them. She then mixed them with yogurt and ingested approximately 150 g, which amounts to multiple lethal doses of ground Taxus leaves. Upon admission to the hospital she was hemodynamically stable, but quickly deteriorated during primary care. Electrocardiogram (ECG) showed wide QRS complexes, and despite sodium bicarbonate and calcium, episodes of ventricular fibrillation was detected. During the 2 h advanced life support, along with mechanical ventilation and fluid resuscitation, multiple DC shocks, sodium bicarbonate, calcium, magnesium sulphate, amiodarone, epinephrine (adrenaline), and norepinephrine (noradrenaline) were applied. Due to refractory arrhythmia, lipid emulsion and digoxin Fab were used. Ventricular arrhythmia progressed to pulseless electrical activity (PEA)/severe bradycardia several times, therefore an external pacemaker was used. After 2 h of resuscitation, she was hemodynamically stable and transported to an extracorporeal membrane oxygenation (ECMO) centre. Over the next 12 days arrhythmias recurred on several occasions and cardioversion was needed. To treat significant vasodilation and to facilitate taxine elimination CytoSorb^(R) treatment was also implemented. Due to partial hepatic impairment, hemostasis was corrected based on thromboelastometry measurements. Twelve days after the start of ECMO the patient was stable, and transferred to the local intensive care unit (ICU) and then to a rehabilitation center. Four months after the intoxication she was discharged from hospital without any permanent complications.

Conclusion

Combined therapy such as of ECMO, lipid emulsion, DigiFab^(R), and CytoSorb^(R) can be effective and life-saving in the management of Taxus poisoning in severe cases. An interdisciplinary approach in medical treatment is essential to improve the management of severe Taxus intoxication and ultimately reduce its associated mortality.

89. A fatal case of food poisoning from cucurbitacin-containing courgette

Abstract

Objective

Cucurbitacins are a group of bitter tasting toxins produced by the Cucurbitaceae family (courgettes (zucchini), cucumber, pumpkin and squash) to protect the plants against insects. High concentrations of toxin in plants could result from cross-pollination with wild or ornamental cucurbitaceae species, or high temperatures which cause growth stress [1]. We present a case of food poisoning involving home-grown courgettes.

Case report

An older, formerly healthy, couple ate an ovendish, containing courgette grown from their garden. The female ingested one bite and the male ingested two bites. Two hours after ingestion, the woman contacted the general practice (GP) service with symptoms of nausea, vomiting and diarrhea, more severe in her husband. She also mentioned a repulsive bitter taste. Food poisoning in the NTS (Dutch Triage Standard) is considered as bacterial gastroenteritis and the couple were given instructions conforming to the NTS protocol to maintain fluid balance and contact the GP service if symptoms worsened. The next day, the GP service was contacted twice more. The woman had recovered, but her husband was still suffering from severe gastrointestinal distress. A home-visit was planned, but by the time the GP visited the patient, he had already died from exhaustion and dehydration, less than 24 h after ingesting the courgette casserole. Food poisoning with cucurbitacins was suspected due to the fulminant course and reported bitter taste. Therefore, leftover material of the casserole and courgettes from the garden was preserved. The materials were analysed using liquid-chromatography with Q-Exactive Orbitrap mass-spectrometry. Both the casserole and home-grown courgette contained cucurbitacin-E, cucurbitacin-E-glucoside and cucurbitacin-I-glucoside, contrary to control courgettes obtained from another garden.

Conclusion

Retrospectively, the cause of death was poisoned food by cucurbitacin-containing courgette. We present this case to alert physicians of the existence of this rare but potentially fatal cause of food poisoning. The medical terminology “food poisoning” leads to diagnosis of bacterial gastroenteritis which is inadequate in the case of poisoned food.

90. Anticholinergic delirium after ingestion of salad leaves from a cultivated garden

Abstract

Objective

The potency of anticholinergic alkaloids in Datura stramonium is well-known and often involved in cases of intentional abuse for its hallucinogenic effects. Confusion of Datura species with edible plants is rare and was last reported in 2014 to the Danish Poison Information Centre (DPIC).

Case report

An elderly couple of 68 years (male) and 67 years (female) with no prior medical history shared a lunch in early July of mixed salad leaves picked from their own garden with edible rocket (Eruca sativa) and lamb's lettuce (Valerianella locusta). The female noticed a very bitter taste, but the male ate most of the salad. Within one hour of ingestion, they both developed dry mouth and over the next few hours, the male grew increasingly confused with intermittent incoherent speech and an ambulance was called. They both presented with mydriasis, tachycardia, and urinary retention, and other causes were ruled out. The DPIC was consulted and due to the couple’s anticholinergic symptoms presenting in a dose-dependent manner, accidental ingestion of Datura species was suggested, and treatment with activated charcoal, physostigmine and benzodiazepine was recommended. The couple were treated with activated charcoal, and all anticholinergic symptoms resolved in both within 20 h without further treatment, although the male had a longer duration of symptoms. Later, the couple photographed leaves of D. stramonium growing in their garden, which verified the exposure and explained the course of symptoms.

Conclusion

Poisoning with D. stramonium is well known and described in literature, but almost solely due to intentional intake. We describe a rare case of confusion of edible salad leaves with small leaves of D. stramonium in a cultivated garden bed causing anticholinergic symptoms in a dose-dependent relationship. There was full recovery of symptoms within 20 h after ingestion with one administration of activated charcoal without the use of specific antidote.

Table 1 Timeline of events, onset of symptoms, findings, and treatment in two patients with delirium after accidental ingestion of Datura stramonium.

Location	Home	Home	Ambulance	Hospital	Hospital	Hospital
Time (24 h)	12:00–13:00	14:00 (+1 h)	17:30 (+4.5 h)	18:30 (+5.5 h)	04:00 (+15 h)	09:30 (+20 h)
Event	Ingestion	Onset		Activated charcoal		Discharged
Clinical course of patient
Male 68 years	Most of the salad	Dry mouth	Confusion, agitation, intermittent incoherent speech	Confusion GCS 14 BP 174/91 HR 92 Mydriasis Urinary retention	Confusion GCS 14	GCS 15 Normalised
Female 67 years	A few bites	Dry mouth	Dry mouth, headache, nausea, gastrointestinal upset	GCS 15 BP 159/97 HR 115 Mydriasis Urinary retention	Normalised GCS 15	GCS 15 Normalised

91. Comparative evaluation of the modified cocaine HEART score, HEART pathway and original HEART score in patients with cocaine-associated chest pain presenting at the emergency department

Abstract

Objective

There are few studies identifying patients at risk for a major adverse cardiovascular event (MACE) in patients with cocaine-associated chest pain (CACP). This study aims to determine the rate of MACE among CACP patients triaged as low-risk by three risk stratification scores and to validate these scores; the HEART score (History, Electrocardiogram, Age, Risk factors, and initial Troponin), the modified cocaine HEART score and the HEART pathway.

Methods

In this single-centre retrospective study, data of patients admitted between January 2016 and December 2022 were extracted. All consecutive CACP patients were included and 1:2 age/sex-matched to non-CACP patients. The primary outcome was the rate of MACE within 30 days. For each risk stratification, score sensitivity, specificity, positive and negative predictive value, and likelihood ratio and Odds Ratio for MACE were determined. Logistic regression models were used to compare CACP to non-CACP patients.

Results

Of the 1653 included patients, 551 presented with CACP. Most were male (84%) and the mean age was 40 years (SD ±12.6). MACE occurred in 139 patients, 50 (9.1%) with CACP and 89 (8.1%) with non-CACP. The rate of MACE among low-risk patients by all three risk stratification scores ranged between 0% and 0.7%. Although the sensitivity, negative predictive value, and AUCs were very similar between the three risk stratification scores, the HEART pathway performed slightly better. When comparing MACE in low-risk patients with CACP and non-CACP, no significant differences were found.

Conclusion

All three risk stratification scores perform well in a low-risk population, with a MACE rate lower than 0.7%.

92. A pilot study to collect data on acute recreational drug toxicity from European Neighbourhood Policy Countries bordering the European Union

Abstract

Objective: There is a paucity of data on acute harms and other key indicators relating to recreational drug use in European Neighbourhood Policy (ENP) countries. The aim of this study was to look at the feasibility of data collection on acute drug recreational toxicity in sentinel centres in ENP countries.

Methods: Sentinel centres were recruited in ENP countries in the Western Balkans, Middle East and North Africa. The Euro-DEN Plus minimum dataset was used to capture key demographic, clinical and outcome variables in presentations with acute drug toxicity (related to the use of recreational drugs, new psychoactive substances and/or the misuse of prescription medicines) with the aim of collecting data for at least 6 months in each centre. Local ethical approval was in place in each centre for collection and sharing of the data.

Results: Data were collected on 741 presentations to seven centres in six countries (Albania, Algeria, Israel, Lebanon, Serbia and Tunisia) in 2021; and 571 presentations to five centres in five countries (Albania, Algeria, North Macedonia, Serbia, Tunisia) in 2022 (Table 1). There were no new psychoactive substances reported in the presentations; illicit drugs were the most common drugs, but a significant minority involved prescription medicines.

Table 1 Data collected using the Euro-DEN Plus minimum dataset from sentinel centres in 2021 and 2022. (EU4Monitoring Drugs (EU4MD) and Instrument for Pre-accession Assistance (IPA) 7 project).

	2021 EU4MD/IPA7 Pilot	2022 EU4MD/IPA7 dataset
Number and location of centres	7 Tirana, Albania; Bab El Oued, Algeria; Oran, Algeria, Haifa, Israel; Beirut, Lebanon; Belgrade, Serbia; Tunis, Tunisia	5 Tirana, Albania; Bab El Oued, Algeria; Skopje, North Macedonia; Belgrade, Serbia; Tunis, Tunisia
Number of presentations	741	571
% Male presentations	80.4%	83.0%
Median age (IQR) years	30 (23–37)	28 (23–35)
% Illicit drugs	59.5%	61.7%
% Prescription medicines	36.1%	31.4%
% New psychoactive substances (NPS)	0%	0%
Top 5 drugs	Cannabis (1)	Cocaine (1)
	Cocaine (2)	Cannabis (2)
	Heroin (3)	Heroin (3)
	Pregabalin (4)	MDMA (4)
	MDMA (5)	Benzodiazepine nk (5)
Top 5 prescription medicines	Pregabalin (1)	Benzodiazepine nk (1)
	Methadone (2)	Pregabalin (2)
	Clonazepam (3)	Methadone (3)
	Benzodiazepine (4)	Diazepam (4)
	Buprenorphine (5)	Opioid nk (5)
Top 5 illicit drugs	Cannabis (1)	Cocaine (1)
	Cocaine (2)	Cannabis (2)
	Heroin (3)	Heroin (3)
	MDMA (4)	MDMA (4)
	Amphetamine (5)	Amphetamine (5)
Length of hospital stay <24 h	76.3%	88.8%
% Medical discharge from the Emergency Department	69.0%	65.7%
% Self-discharge from the Emergency Department	17.4%	13.0%
% Psychiatric admission	11.6%	18.6%
% Critical care admission	6.9%	6.5%

Conclusion: We have demonstrated that it is feasible to collect data using Euro-DEN Plus methodology from sentinel hospitals in European neighbouring countries. Whilst retention of centres between 2021 and 2022 was not complete, and it was only possible in this pilot study to collect data from eight centres, these data provide valuable insight into local drug use and patterns of harm associated with this use in countries of the European Neighbourhood Policy (ENP). This is important given the paucity of data on other key indicators of drug use from these countries.

93. Frostbite injury – a common and potentially life-threatening side effect of recreational nitrous oxide use

Abstract

Objective

Recreational use of nitrous oxide is increasing both in Sweden and other countries. The most common side effect is nerve damage due to repeated exposure. Injuries in direct conjugation with acute exposure are rare. However, acute frostbite injuries from handling compressed metal gas canisters have been described and may be underreported [1]. We present a review of frostbite injuries reported to the Swedish Poisons Information Centre (PIC).

Methods

A systematic review of calls registered as suspected or confirmed nitrous oxide related frostbite between 1 January 2021 and 7 May 2023 were made from the Swedish PIC database. Case details were reviewed manually to determine the injury and means of exposure.

Results

During the study period, 606 calls about toxic side effects of nitrous oxide were registered. Of them, 64 calls consisted of suspected (public calls with typical findings, not assessed by healthcare professional, 29/64) or confirmed (hospital calls with typical findings, assessed by healthcare professional, 36/64) frostbite injuries. In addition, we found 16 possible cases with a typical patient story but no description of objective findings. The most common route of exposure was inhalation (41/64), followed by external exposure (23/64). The most frequently described symptoms were throat pain and swallowing difficulties (26/64), blisters and damaged mucosa in the oral cavity (22/64) and retrosternal pain (9/64). Other symptoms were blisters or discoloration in the facial area (7/64), hands (7/64) or legs (4/64) and a few persons experienced hoarseness (4/64) and/or difficulty speaking (5/64). Some patients had more than one symptom (16/64). To our best knowledge there were two life-threatening frostbite injuries during the observation time. There were an adolescent who had extensive injury in the oral cavity, pharynx and larynx and needed a tracheotomy and a young adult with pronounced esophageal damage and perforation requiring intensive care for weeks.

Conclusion

Frostbite injuries are a relatively common side effect of nitrous oxide abuse that may cause tissue damage and even life-threatening injuries.

94. Nitrous oxide presentations: the growing trend of nitrous oxide cylinder usage

Abstract

Objective

Chronic nitrous oxide (N₂O) use can result in neurological and/or psychiatric sequelae. N₂O can be inhaled from bulbs or cylinders (1–3.3 L tanks). Both are readily available in Australia over the Internet for immediate delivery. We evaluate the changing pattern of N₂O presentations and the effect of the recent availability of N₂O cylinders.

Methods

Retrospective review of patients presenting to two Sydney hospitals with N₂O use and neurological and/or psychiatric symptoms from November 2020 to October 2023. Patients identified from toxicology unit databases and medical records were reviewed for demographics, clinical details, and outcomes. Total daily use of N₂O was calculated assuming each bulb contains 8 g of N₂O and a 1 L cylinder 600 g.

Results

Overall, 51 presentations in 34 patients were identified, with 11 N₂O-related representations. Of the 34 patients, 19 (56%) were male with median age 25 years (IQR: 23.5–31). The majority were students (n = 18) and 19 were born in Asia. Of the 51 presentations, the median maximum N₂O use was 2400 g/day (IQR:1200–4000 g/day, range: 240–16000 g/day, n = 47), for median time of 4 months (IQR: 2–24 months, n = 46). Over time N₂O use changed from bulbs to cylinders. Prior to May 2022, all patients reported using bulbs (22 presentations). After this, 21 presentations reported use from cylinders, 6 cylinders, and bulbs, and 2 bulbs only. Those inhaling bulbs had a median maximum daily dose of 2000 g (IQR: 1200–2400 g, n = 23) versus 4000 g (IQR: 1200–8026, n = 25, p = 0.0472, Mann-Whitney U) for cylinders. Two re-presented with increasing use from bulbs to cylinders. Neurological symptoms including numbness, weakness, and/or decreased mobility were found in 37 patients, of which 24 had abnormal gait on examination. Psychiatric symptoms such as auditory hallucinations, psychosis, and depression were reported in 23. Two with psychotic symptoms reported >7000 g N₂O/day for a few days only. Vitamin B₁₂ and/or holotranscobalamin concentrations were normal in 28/42 and 32/35, respectively as most had prior vitamin B₁₂ supplementation. In contrast, homocysteine and methylmalonic acid were high in 25/26 and 7/8 tested, respectively. All were treated with intramuscular vitamin B₁₂.

Conclusion

This case series demonstrates the changing use of N₂O from bulbs to cylinders with an increase in daily use, likely due to the large volumes that can be purchased and the ease of use from cylinders. Furthermore, we had a high number re-presenting with ongoing use and symptoms. Of concern were two patients presenting with psychotic symptoms after only days of large-volume N₂O use.

95. Increasing detections of the novel benzodiazepines gidazepam and desalkylgidazepam in patients attending emergency departments in the UK

Abstract

Objective

Gidazepam is an anxiolytic benzodiazepine licensed in Russia and Ukraine. It exerts its pharmacological actions via the long-acting active metabolite desalkylgidazepam (bromonordiazepam) [1]. Both compounds were first detected in illicit drug markets internationally in 2022. Here we describe increasing detections of these compounds in patients attending emergency departments (ED) in the UK.

Methods

Consenting patients (≥16 years) presenting to participating hospital EDs with toxicity after suspected drug misuse were included in the Identification Of Novel psychoActive substances (IONA) study between March 2015 and March 2023. Demographic and clinical features were recorded and blood and/or urine samples analysed using liquid chromatography-high resolution accurate mass full scan and full scan MS/MS mass spectrometry.

Results

Desalkylgidazepam was detected in at least one sample (blood or urine) in 14 patients (median age 41 years, range 21–53 years; 9 males, 5 females) between July 2022 and March 2023, with gidazepam also present in 4 of the 14 patients. Desalkylgidazepam was detected in 13/99 (13%) recruited in Scotland, 1/4 (25%) recruited in Wales and 0/404 (0%) recruited in England in 2022–2023. Most (10) reported ingestion of a benzodiazepine (diazepam or “Valium” in 9, alprazolam with etizolam in 1) but none reported use of desalkylgidazepam or gidazepam. Other drugs reported included cocaine (6) heroin (4), methadone (2) pregabalin (3) and unidentified tablets (1). Analysis of blood or urine provided evidence of polydrug use in all cases; the median numbers of additional substances taken was 8, most commonly other benzodiazepines in 14 (most commonly diazepam (11), bromazolam (11), flubromazepam (7), alprazolam (5)), opioids in 14 (morphine or metabolites (11), methadone (10), codeine (7)), tetrahydrocannabinol (8), pregabalin (8) and cocaine and metabolites (8). Reduced conscious level was documented in 12 with Glasgow Coma Score <9 in 5, confusion in 8 and respiratory acidosis (pCO₂ > 6 kPa, pH <7.33) in 5 patients. Two patients were managed by intubation and ventilation. All patients survived to hospital discharge (median length of stay 20 h, range 6.6–172 h).

Conclusion

Desalkylgidazepam has appeared in ED patient samples in Scotland and Wales since mid-2022, but had not been detected in England by March 2023. In a few cases gidazepam was also detected. Those involved were unaware of exposure to these compounds. All had polydrug exposure likely contributing to observed clinical features.

96. Profiling emergency department presentations related to recreational illicit and prescription opioid use through a European Sentinel-Centre Based Registry

Abstract

Objective

For Europe, the scale and patterns of illicit versus prescription opioid misuse and their impact on emergency departments have been poorly investigated.

Methods

Emergency department presentations with recreational use of illicit versus prescription opioids were obtained from the Euro-DEN dataset from January 2014 to December 2021.

Results

Overall, 3888 prescription and 11,252 illicit opioid-related presentations to the emergency department were reported, representing 6.2% versus of 18.0% all Euro-DEN presentations. In 587 (0.9%) presentations, both were present. The most frequently documented prescription opioids were methadone (51.3%), buprenorphine (13.9%), morphine (9.3%), fentanyl (6.8%) and tramadol (6.7%). Oxycodone was only documented in 2.6% of presentations. Combined use of prescription opioids with benzodiazepines and Z-drugs (35.6% versus 20.6%) and gabapentinoids (6.6% versus 1.5%) was significantly higher than in the illicit opioid users (p < 0.001). Mortality rate related to prescription opioid misuse (1.2%) was significantly higher than mortality rate related to illicit opioid misuse (0.4%, p < 0.001). The most frequently encountered prescription opioids differed per country. The presentation rate related to prescription opioids is significantly related to the official consumption data in Defined Daily Doses [1].

Conclusion

Methadone and buprenorphine are the most frequently misused prescription opioid in the Euro-DEN database. Fentanyl and oxycodone represent only a minor portion of the prescription opioid misuse presentations by contrast to the US and Canada. Combined use of prescription opioids with benzodiazepines, Z-drugs, and/or pregabalin and mortality rate were significantly higher in the prescription than in the illicit opioid users.

97. Targeting design of snakebite rapid diagnostics in Asia: a preliminary report

Abstract

Objective: The World Health Organization (WHO) has identified snakebite envenoming as a neglected tropical disease, and set a goal to halve the global health burden of snakebite by 2030, particularly in Africa, Asia and Latin America. In addition to safe and effective antivenoms, reliable and widely available point-of-care diagnostic tests, instead of the speculatively syndromic approach, can be used to discriminate between various types of envenoming and snakes which is a great challenge in the clinical management of snakebite envenoming. Based on our previous studies [1], where we assessed an immunochromatographic kit to differentiate the venoms of Naja atra (NA) and Russell’s viper (RV), we investigated if the method could be extended and was applicable to the Asian region.

Methods: We created a highly specific, high-yield, economic and versatile antibody production platform from avian (goose and duck) eggs (IgY) to minimize interference from human specimens and improve the efficacy of antigen-based immunological point-of-care (PoC) tests. We produced IgY on venom of the Malayan pit viper (Calloselasma rhodostoma (CR)), one of the most important, wide-distributed vipers in the Asia, and combined IgY and horse IgG to assemble multiplex immunochromatographic kits for rapid snake identification in some regions of Asia.

Results: The multiplex kit for NA, RV and CR venoms showed good cross detection for other Asian cobra venom, but with good differentiation from these three venoms (Table 1).

Table 1 The use of multiplex kit for snake bites in Asia.

Multiplex Kit	Test for Naja atra (NA)	Test for Russell’s viper (RV)	Test for Calloselasma rhodostoma (CR)
Detection limit	5–50 ng/mL	5 ng/mL	50 ng/mL
Positive for	NA and other Naja	RV	CR
Negative for	Pit viper and RV	NA or pit viper	NA or RV

Conclusion: The kit would be feasible to make different testing assemblies depending on the characteristics of venomous snakes in most areas of Southeast Asia. Rapid diagnostics might guide correct and targeted antivenom therapy, reduce dosage and side effects. Country-based or area-available rapid tests could also guide antivenom design and production, making antivenoms more efficient and economical in the future.

98. Endoscopic gastric decontamination: a case series from a pediatric poison control center

Abstract

Objective

Gastrointestinal decontamination is one of the basic principles in managing poisoned patients and may include gastric lavage, activated charcoal and whole-bowel-irrigation: nevertheless, indications of these procedures are still debated [1]. Decontamination procedures are evolving according to new drug formulations and, in selected cases, gastroscopy may be useful. We describe our experience on the performance of endoscopic gastric decontamination (EGD) after gastric lavage (GL) in patients presenting with severe or life-threatening drug poisoning.

Case series

We retrospectively analyzed (2020–2023) 11 cases of intentional ingestion severe/life-threatening drug intoxication managed by EGD with the aim of evaluating residual drugs after GL (Table 1). The indications to perform EGD were: drug formulation (slow release), the clinical condition and other exams (based on the PSS) and recent meal. GL was performed within 3 h of ingestion. Solid drug was removed in seven cases (63.7%), food material in 2 patients (18.2%), and in cases 1 and 10 EGD was negative. Plasma/serum drug concentrations were performed in 7 cases, however, except for lithium sulfate, the results were obtained after >24 h and were therefore not useful for clinical decision making. All patients improved without any complications.

Table 1 Endoscopic gastric decontamination (EGD) after gastric lavage (GL) in patients presenting with severe or life-threatening drug poisoning.

Patient	Age/sex/ weight	Drug and dose (plasma concentration)	Clinical condition and exam	PSS	Hours before EGD	Endoscopic gastric decontamination
1	15 y/F 55 kg	Lithium sulfate 2490 mg (3.37 mmol/L)	Drowsiness, confusion, metabolic acidosis, elevated AST, ALT	3	17	Negative
2	15 y/F 70 kg	Isoniazid/rifampin 30000 mg/2400 mg (93.45 µg/mL/unknown)	Coma, convulsions, metabolic acidosis, elevated AST, ALT and CPK	3	12	Bezoar
3	16 y/M 51 kg	Eltrombopag 4200 mg (188 µg/mL)	Drowsiness and confusion	3	2.5	Solid tablets
4	14 y/F 95 kg	Quetiapine SR 1400 mg (unknown)	Drowsiness and confusion, increased QTc	2	3	Gastric material
5	17 y/F 56 kg	Biperiden/lithium sulfate 160 mg/1162 mg (unknown/1.37 mmol/L)	Drowsiness and confusion	1	2	Tablet residue
6	17 y/F 50 kg	Aripiprazole 125 mg (unknown)	Elevated CPK	1	3	Bezoar
7	13 y/M 72 kg	Lithium sulfate 4150 mg (2.7 mmol/L)	Agitation, elevated AST, ALT and CPK	3	11	Gastric material
8	13 y/F 50 kg	Acetylsalicylic acid 9750 mg (5.30 mg/dL)	None	0	4	Bezoar
9	14 y/F 45 kg	Quetiapine SR /fluoxetine uncertain amount (1784 ng/mL/235 ng/mL)	Coma, hypotension, metabolic acidosis	3	4	Bezoar
10	16 y/M 75 kg	Caffeine 14000 mg (53 µg/mL)	Vomiting, metabolic acidosis, AKI and elevated CPK	3	5	Negative
11	17 y/F 60 kg	Amitriptyline/chlordiazepoxide 112.5 mg/45 mg (unknown)	Drowsiness and confusion	3	6	Tablet residue

AKI: acute kidney injury; ALT: alanine aminotransferase; AST: aspartate aminotransferase; CPK: creatine kinase; F: female; M: male; PSS: Poisoning Severity Score; SR: slow release; Y: years.

Conclusion

From our experience, EGD may have a fundamental role in maximizing gastric decontamination. In this cases series, after GL, in over 80% of patients we found and removed solid drugs or food material with probable drug residues. No association was found between gastroscopy latency and efficacy: the drug, any co-administration and the presence of food material can influence the results. Further studies are desirable to define the role and indications for EGD.

99. Activated charcoal in gastrointestinal decontamination: a retrospective analysis of utilization

Abstract

Objective

Activated charcoal (AC) is the most common method used for gastrointestinal (GI) decontamination in poisoned patients. It adsorbs xenobiotics to prevent absorption. Multiple guidelines have recommendations on AC use [1]. Contraindications to AC are GI perforation/obstruction, unprotected airway, and need for endoscopy. Some substances do not adsorb to AC. The timeframe of administration is controversial, but earlier administration is more effective. This descriptive study evaluates AC use in emergency departments (EDs), specifically to determine the frequency in which AC is administered when it is contraindicated or there is no expected benefit.

Methods

A retrospective review of single dose AC as a modality for GI decontamination in a single poison center serving the 7 major EDs in the country. Patient records were reviewed to identify cases in which AC was used in the ED. Patient data included age, substance ingested, dose ingested, time since ingestion, signs of GI obstruction/perforation, risk of aspiration, level of consciousness, and complications post AC. Each case was assessed by two medical toxicologists and a poison specialist to determine if AC administration was 1) contraindicated due to 1.1) high aspiration risk; 1.2) suspected/confirmed GI obstruction/perforation; or 1.3) potential need for endoscopy, or 2) expected to have no benefit due to 2.1) lack of xenobiotic binding; 2.2) non-toxic dose; 2.3) used after 2 h of the substance ingestion; or 2.4) unknown substance or time of ingestion.

Results

A total of 220 AC treatments were identified from 1 January 2023 to 1 October 2023. Of the performed therapies; 70 (31.8%) were indicated, and 150 (68.2%) contraindicated and/or not indicated. Of the latter group, 18% had high risk of aspiration, none had signs of GI obstruction/perforation nor in need of endoscopy, 6.7% were for substances that do not adsorb to AC, and 19.3% for subtoxic doses. AC was given in 22% more than 2 h from the time of substance ingestion and in 4.7% of unknown time. Overall 8.7% had vomiting after AC with no signs of aspiration.

Conclusion

In this study, 68.2% of AC administration in the ED setting was given when contraindicated or of no expected benefit. Frequent AC administration for acute poisoning in the ED when it should not be administered occurs in the emergency medical system. We recommend poison center or medical toxicologist input for cases of poisoning prior to the administration of AC.

100. Pharmacobezoars and the holistic approach

Abstract

Objective

Potassium poisoning is not very common, and in patients with intact renal function a large amount of potassium has to be taken for the development of life-threatening hyperkalaemia. Certain pharmaceutical products, however, tend to conglomerate in the gastrointestinal tract [1] which affects the risk and severity of poisoning. We report a case of severe poisoning after pharmacobezoar formation.

Case report

A 47-year-old woman with negative past medical history was admitted to the toxicology department after self-administering 50 potassium chloride tablets in a suicide attempt 1.5 h earlier. It was not known whether the tablets were immediate or modified release as the patient had bought them via the Internet and no details were available. On admission she was alert, vital parameters were stable, physical examination was unremarkable. Arterial blood gas showed no acid-base disturbance, but moderate hyperkalaemia was detected (6.7 mmol/L). Normal sinus rhythm and peaked T-waves on the precordial leads were demonstrated by electrocardiography (ECG). Gastric decontamination did not retrieve any tablet fragments. Antero-posterior abdominal X-ray revealed a mass in the stomach as a conglomerate of a large number of tablets. Repeated gastric decontamination carried out in the Trendelenburg position was not successful. Repeated arterial blood gas analysis showed increased serum potassium concentration, and on the ECG T-waves became progressively worse. In spite of complex conservative therapy (calcium gluconate, sodium bicarbonate, glucose-insulin therapy, polystyrene sulfonate suspension, furosemide) the serum potassium concentration did not decrease. The decision was taken to perform intestinal decontamination and 39 whole intact tablets were removed by urgent upper panendoscopy. This intervention resulted in rapid improvement of the serum potassium concentration.

Conclusion

The potassium tablets in this case were radio-opaque and were seen on abdominal X-ray. In case of a mass overdose the possibility of a pharmacobezoar should always be considered. Potential life-threatening pharmacobezoars can be successfully removed by urgent gastroscopy. Multidisciplinary thinking and management can help in the holistic approach to treatment.

101. Better three hours too soon than a minute too late. The evacuation of ghost-pills in a case of hemodynamic collapse after bupropion overdose

Abstract

Objective: Between 2019 and 2022 the number of calls to the Swedish Poisons Information Centre concerning overdoses with bupropion increased by 84%, including several cases of life-threatening cardiovascular compromise. Early decontamination of swallowed tablets would be an attractive way of avoiding this feared complication of bupropion overdose. Use of gastric lavage in overdoses is controversial and is particularly likely to be ineffective in overdoses involving sustained release preparations (e.g., bupropion). In such cases, gastroscopic evacuation of tablets has been reported as an option [1]. We present a case of late evacuation of apparently intact bupropion tablets in a severe poisoning.

Case report: A woman presented unconscious after a mixed-drug overdose. The pharmaceuticals involved, dose and ingestion time were unclear, but bupropion had recently been prescribed to the patient. She was intubated, gastric lavage was performed (with no yield) and charcoal was administered. She was tachycardic, but electrocardiogram (ECG) and echocardiography were normal on admission. Her blood pressure was low, and she was treated with vasopressors whereupon hemodynamic stability was achieved. She deteriorated 18 h after hospital arrival with wide-complex arrhythmias rapidly progressing to cardiac arrest. After 35 min of cardiopulmonary resuscitation (CPR), she was put on venoarterial extracorporeal membrane oxygenation (ECMO). Her cardiac function gradually returned, QRS duration normalized and ECMO was discontinued 36 h after hemodynamic collapse. The patient subsequently made a complete recovery.

During ECMO-treatment a gastroscopy was performed (34 h after presentation, 16 h after hemodynamic collapse) revealing multiple tablets still present in the stomach. After extraction, all tablets could be identified as bupropion 150 mg through visible print. The total yield was 236 tablets (35.4 g of bupropion). The tablets were analysed by nuclear magnetic resonance (NMR) but no longer contained any active substance. Blood concentrations of bupropion and hydroxybupropion at 36 h after admission were 790 and 1300 µg/L, respectively.

Conclusion: In this case of life-threatening bupropion overdose apparently intact tablets were evacuated by gastroscopy at 34 h after presentation. However, the tablets were found to be completely drained of active substance at the time of extraction (“ghost pills”). Had the evacuation been performed earlier in the course it seems likely that the extent of cardiovascular toxicity could have been mitigated or avoided. An early abdominal computerised tomography (CT) scan could alert clinicians to the presence of large amounts of tablets in the stomach in similar cases.

102. Massive diphenhydramine overdose complicated by wide-complex dysrhythmia refractory to sodium bicarbonate successfully treated with lidocaine

Abstract

Objective

Diphenhydramine is a first-generation antihistamine with “sodium channel blocking” properties. More precisely, it binds inactivated cardiac sodium channels, delaying recovery to the open state and impairing intraventricular conduction. While wide-complex tachydysrhythmias in sodium channel blocker poisoned patients are usually aberrantly conducted sinus tachycardias, best treated with sodium bicarbonate, true ventricular dysrhythmias can occur. Based largely on animal studies, lidocaine is a potential treatment for these dysrhythmias, however data in humans, and for diphenhydramine poisoning specifically, are limited. We report a case of massive diphenhydramine overdose complicated by ventricular dysrhythmia successfully treated with lidocaine.

Case report

A 15-year-old male presented to the emergency department after intentional overdose of 7.5 g diphenhydramine. Vital signs on arrival were notable for tachycardia, tachypnea, and elevated temperature (38 °C). Initial electrocardiogram demonstrated sinus tachycardia with QRS 118 ms, QTc 446 ms, and terminal rightward axis deviation. He received a 1.85 mEq/kg sodium bicarbonate bolus followed by continuous infusion. Approximately two hours later, he had a generalized seizure complicated by emesis, aspiration, and subsequent hypoxia. He underwent a challenging intubation requiring several attempts. Shortly thereafter his QRS widened on the monitor, and a second 1.85 mEq/kg sodium bicarbonate bolus was administered with no change in QRS duration. Arterial blood gas drawn at this time demonstrated pH 7.12 and PaO₂ 63.9 mmHg. He became pulseless, received compressions and 1 mg/kg intravenous lidocaine, with subsequent QRS complex narrowing and return of spontaneous circulation. Lidocaine infusion (20 µg/kg/min) was initiated. QRS and blood pressure remained stable, and lidocaine and sodium bicarbonate infusions were discontinued 18 and 42 h later, respectively. He had a prolonged hospitalization ultimately requiring veno-venous extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) but never developed recurrent cardiotoxicity. Serial diphenhydramine concentrations demonstrated a peak concentration of 8100 ng/mL and apparent elimination half-life of 50 h (normal 3–9 h).

Conclusion

In this massive diphenhydramine overdose, a wide-complex dysrhythmia unresponsive to sodium bicarbonate was successfully treated with lidocaine. Lidocaine binds inactivated sodium channels with fast-off kinetics and is thus postulated to mitigate toxicity from sodium-channel-binding xenobiotics with relatively slower dissociation kinetics. This case suggests efficacy of lidocaine for treatment of diphenhydramine-induced ventricular dysrhythmias. The blood gas indicates that his dysrhythmia and cardiac arrest were unlikely a direct result of peri-intubation acidemia or hypoxemia, but rather due to diphenhydramine toxicity; though acidemia likely indirectly exacerbated this toxicity by increasing the ionized fraction available to bind sodium channels. Apparent half-life was significantly prolonged, likely in part due to muscarinic antagonism impairing gastrointestinal tract motility and auto-decontamination.

103. Cefepime-induced neurotoxicity with non-convulsive status epilepticus

Abstract

Objective

Cefepime is a broad-spectrum beta-lactam antibiotic, widely used in treating severe cases of infection caused by drug-resistant microorganisms. Cases of neurotoxicity in patients with impaired renal function have been reported [1]. We present a case of encephalopathy with associated non-convulsive status epilepticus subsequent to the treatment of urosepsis with cefepime despite renal function adjusted dose.

Case report

An 83-year-old male, afflicted with multiple comorbidities including arterial hypertension, acute exacerbation of chronic renal disease, and small fiber neuropathy was admitted due to Klebsiella aerogenes urosepsis. In accordance with the antibiogram, he was treated with cefepime. Initially, he received 2 g every 24 h for the first three days due to reduced renal function (estimated glomerular filtration rate (eGFR) 24 mL/min). As renal function improved (eGFR 48 mL/min), cefepime dosing was adjusted to 2 g every 12 h. Inflammatory markers exhibited a decrease during the treatment course, and the patient also showed clinical improvement. On the seventh day of cefepime therapy, the patient presented with altered mental status, including involuntary movements, and increased muscle tone without obvious lateralization. Computerised tomography (CT) imaging excluded acute ischemic or haemorrhagic pathology. Following electroencephalogram (EEG) confirmed the presence of neurotoxicity with non-convulsive status epilepticus, which responded favourably to intravenous antiepileptic agents. To accelerate cefepime elimination, two haemodialysis sessions were administered. The patient's cognitive function gradually normalised, and within two weeks, he regained the ability to sit independently and to self-feed. Other conceivable aetiologies of neurotoxicity, including electrolyte imbalances, uremia, and hepatopathy, were systematically ruled out, with cefepime emerging as the most plausible causative factor. Toxicological analysis of serum samples corroborated elevated cefepime concentrations. Trough concentration of cefepime at the lower dose were 7.1 mg/L, while after dose escalation, they reached 20 mg/L, exceeding the aimed trough concentration of <7.5 mg/L [1]. Several predisposing factors were observed, with kidney disease being the most notable, extending the cefepime half-life, thereby significantly amplifying the drug's exposure. Advanced age, inflammatory conditions, and pre-existing neurological conditions impacting the central nervous system have been proposed as potential contributors to cefepime toxicity as well.

Conclusion

Cefepime's potential for neurotoxicity, particularly in patients with predisposing factors, is underscored by this case. The complex interplay of medical comorbidities, dose adjustments, and pharmacokinetic alterations reveals the need for vigilant therapeutic monitoring and individualized dosing strategies when employing cefepime.

104. Life-threatening verapamil and flecainide overdose with a favorable outcome

Abstract

Objective

To describe a case of acute overdose involving mixed cardioactive drugs, emphasizing the importance of understanding drug pharmacokinetics, the role of intensive support care, and advanced cardiac monitoring.

Case report

A 41-year-old woman with a history of right ventricular outflow tachycardia arrived at the emergency department (ED) 75 min after ingesting 10.8 g slow-release verapamil and 2 g flecainide. She presented in vasoplegic shock with a systolic blood pressure of 61 mmHg, and Glasgow Coma Score 12 (E3M5V4). Her initial electrocardiogram (ECG) displayed a widened QRS complex (157 ms), and an echocardiogram revealed a hyperdynamic heart, consistent with predominantly flecainide toxicity. Her blood flecainide concentration was 1.4 mg/L (normal range: 0.2–1.0 mg/L) taken 21 h post-ingestion. In the ED, she received intravenous fluids, noradrenaline, sodium bicarbonate, calcium gluconate, activated charcoal, and whole bowel irrigation. Her hemodynamics stabilized over time, and she was intubated before being transferred to a tertiary medical center with extracorporeal membrane oxygenation (ECMO) capabilities due to anticipated refractory cardiogenic shock. Approximately 9 h post-ingestion, the patient experienced another episode of profound cardiogenic, vasoplegic shock and complete heart block requiring cardiac pacing. Pulse index continuous cardiac output (PiCCO) monitoring showed a low cardiac output of 2.25 L/min (normal range: 3–5 L/min). PiCCO was utilised in titration of high-dose vasopressors, ionotropic support and intravenous pacing up to a rate of 100 bpm. High-dose insulin (HDI) therapy was initiated, reaching a maximum rate of 8 units/kg/h with a maximal cardiac output of 5.3 L/min. Continuous renal replacement therapy (CRRT) was also initiated for her worsening metabolic acidosis and anuric acute kidney injury (AKI). This second wave of clinical deterioration was consistent with the onset of verapamil toxicity. Cardiac pacing, vasopressors, and inotropes were discontinued at 60 h and 80 h post-ingestion, respectively. HDI was gradually tapered and eventually discontinued at 75 h, with glucose requirement persisting for up to 25 h after HDI cessation. C-peptide and insulin concentrations were measured to review the correlation of endogenous insulin production and repeated C-peptide level was normalized (397 pmol/L) at 5 h after cessation of HDI. CRRT was ceased on day 5 of intensive care unit admission. The patient was eventually discharged in good health on day 8 of admission.

Conclusion

This case underscores the complexities of managing a combination overdose involving drugs with different pharmacokinetics and cardiac toxicities. It highlights the favorable outcome that can be achieved with high-level supportive care and the utilization of invasive cardiac monitoring in clinical management.

105. External use only: we mean it! Ten cases of intravascular administration of biguanide wound cleaning solutions

Abstract

Objective

We report ten cases of intravascular biguanide disinfectant administration reported to the UK National Poisons Information Service between 2008 and 2022.

Case series

Ten cases (ages 6–73 years, 70% female) of intravascular administration of biguanide wound cleaning solutions have been reported to the NPIS since 2008. In six cases, it was mistakenly used as a line flush. Central lines or dialysis catheters were involved in four and three cases, respectively. Poison centre advice was sought within one hour of administration in eight cases; six cases were referred to a clinical toxicologist. Symptom onset and resolution occurred rapidly in all but two cases. In one case, shortness of breath and cyanosis persisted for 40 min; in another, the patient had persistent tachycardia. Five patients developed systemic symptoms. One patient suffered a cardiac arrest with return of spontaneous circulation achieved after 40 s of CPR and IV fluids. Cardiovascular features including tachycardia (n = 3), hypotension (n = 2) and raised troponin concentration (n = 1) were noted in some patients; dyspnoea (n = 2) and cyanosis (n = 1) were also observed. Treatments included intravenous fluid for hypotension, supplemental oxygen for reduced oxygen saturations, antihistamines for local reactions and aspiration of blood/line contents to reduce exposure. All patients receiving Prontosan^® (n = 6) developed symptoms, and a higher proportion developed systemic features compared to chlorhexidine. It was noted that specific properties of Prontosan^® contributed to its inadvertent use; it looks similar to saline, the bottle is the same shape as is used for IV medications and it has a connector which can attach to IV lines.

Conclusion

Biguanides, particularly Prontosan^®, can cause severe symptoms when given intravascularly. When this occurs, patients should be monitored for respiratory dysfunction and hypotension. Symptoms are immediate and resolve quickly with supportive care. The design of treatments for external use should be able to be differentiated easily from parenteral solutions.

Table 1 Clinical details of patients with intravascular administration of biguanide wound cleansing solutions.

Patient	Formulation and quantity	Circumstances	Clinical features
48/F	5–10 mL chlorhexidine 2%	Via central line instead of saline	Tachycardia, strange taste in mouth, malaise.
73/F	5 mL chlorhexidine gluconate 0.5%	IV	Pain.
56/M	5–10 mL chlorhexidine 4%	Via shunt on renal unit	Nil.
Adult/F	10 mL chlorhexidine 20% (with denatured ethanol)	Via PICC line	Nil.
55/F	5 mL Prontosan^®	Via PICC line	Slight irritation noted (location not reported).
61/M	5 mL Prontosan^®	Via peripheral cannula instead of saline flush	Tingling in face and arms, loss of consciousness, cardiac arrest (responded to CPR and IV fluids); thereafter shivering, tachycardia, chest pain, raised lactate with normal pH, calcium and potassium.
25/F	Prontosan^®	Type of line not recorded, instead of saline flush	Hypotension (responded to fluids), tachycardia (persisted for hours, perhaps due to underlying painful condition). Patient was pregnant, fetal outcome not followed up.
61/F	Prontosan^®	Via dialysis line instead of saline flush	Slight injection site reaction.
66/F	10 mL Prontosan^®	Via femoral dialysis line instead of saline flush	Sudden tingling and numbness around mouth and hands, shortness of breath, wheeze, raised troponin-T (perhaps related to underlying condition).
6/M	3 mL Prontosan^®	Via central line instead of saline flush	Shortness of breath, cyanosis, pruritus.

Prontosan^® contains 0.1% polyhexanide and 0.1% betaine in water. PICC: peripherally inserted central catheter.

106. Gamma-hydroxybutyrate poisonings admitted to the intensive care unit: variability of presentation and investigation of the relationships between coma depth and plasma concentrations

Abstract

Objective

Gamma-hydroxybutyrate (GHB) and its precursor, gamma-butyrolactone (GBL) represent increasingly used recreational drugs at risk of life-threatening overdose. We report the presentation of GHB/GBL poisonings, investigate the prognostic value of plasma GHB concentration, and the variability of the coma depth/GHB concentration relationships.

Methods

We conducted a single-center prospective study including all GHB-poisoned patients admitted to the intensive care unit (ICU) (2018–2023). Diagnosis was based on plasma GHB concentration in the toxic range. When possible (in non-sedated patients), serial concentrations were measured and the relationships with the time-course of coma depth using the Glasgow Coma Score (GCS) were modelled (WinNonlin^®). Data are expressed as percentages or medians [percentiles]. Univariate comparisons were performed using chi-squared and Mann-Whitney tests.

Results

Overall 142 GHB-poisoned patients (30 years [26–38]; 123M (87%)/19F (13%); Caucasian (76%)/African (13%)/Maghreb (10%) origin; history of drug use (95%) and depression (18%)) were included. Exposure occurred at home (46%), outdoor (23%) or in a club/sauna (14%), as a recreational (80%) or chemsex use (13%). GHB (85%) versus GBL (15%) ingestion was involved. Co-toxicants included 3-MMC (28%), ethanol (25%), cocaine (11%), methamphetamine (6%), 3,4-methylenedioxymethamphetamine (MDMA) (5%), and poppers (5%). On admission, patients presented GCS of 3 [3–6], hypothermia (35.9 °C [35.1–36.6]), myorelaxation (49%), seizures (6%), mydriasis (9%)/miosis (42%), pyramidal syndrome (4%), and vomiting (25%). Electrocardiogram showed sinus rhythm (70/min [60–82]), QT_c of 416 ms [400–437], and QRS length of 92 ms [80–104]. The anion gap was 16.9 mmol/L [15.28–18.7]. Plasma GHB concentration on admission was 273 mg/L [136–439]. Management included mechanical ventilation (76%, performed in the prehospital setting except in three patients), sedation (80%), and vasopressors (6%). About 25% of the ventilated patients self-extubated. Complications included aspiration pneumonia (32%), rhabdomyolysis (21%), withdrawal syndrome (6%), and death (2%). No significant differences in presentation between GHB- and GBL-exposed patients were observed. Correlations between GCS (R² = 0.024) or anion gap (R² = 0.39) and GHB concentration on admission were weak, despite a trend to observe GBL users with larger anion gap and higher GHB concentrations. Coma depth/GHB concentration relationships fit the sigmoidal E_max model, with high Hill coefficient values, demonstrating that a small decrease in GHB concentration was associated with a dramatic consciousness improvement. Interindividual variability could be interpreted in relation to drug use history, development of tolerance to GHB in chronic GHB users, and co-used drugs.

Conclusion

GHB/GBL use may result in life-threatening neuro-respiratory depression. Outcome is rapidly favorable. Coma depth/GHB concentration relationships fit the sigmoidal E_max model with parameters subject to a high interindividual variability.

107. Clinical predictors of opioid exposure in Emergency Department presentations with hypoxaemia: analysis of 151 presentations with analytically confirmed illicit drug toxicity in Victoria, Australia

Abstract

Objective: Clinical features following toxic opioid exposure are characterised by sedation, bradypnoea and miosis. We examined the utility of these clinical features, in isolation and in combination, in predicting subsequent analytical confirmation of opioid exposure in emergency department illicit drug presentations with an initial observation of hypoxaemia.

Methods: Data were extracted from an ethics-approved clinical registry collecting de-identified clinical and analytical data on a convenience sample of illicit drug presentations to 17 emergency departments in Victoria, Australia. Blood samples were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) for 575 pharmaceutical and illicit drugs. Sensitivity, specificity, and positive predictive value (PPV) of single or combination clinical findings in relation to an analytically confirmed opioid detection were based on the following definitions: hypoxaemia as pulse oximetry <92% measured on 21% inspired oxygen, bradypnoea as respiratory rate of <10 breaths per minute; sedation as Glasgow Coma Score (GCS) of less than 9.

Results: Of 2129 presentations analysed (September 2020–September 2023), 187 were hypoxaemic on presentation. Complete data was available in 151 cases. Positive opioid detection in this cohort was 61% (n = 91). Common co-detections (number of presentations) included benzodiazepines (n = 105), methylamphetamine (n = 98), and gamma-hydroxybutyrate (n = 30). Miosis was absent in 36% of presentations with hypoxaemia and analytically confirmed opioid exposure. Positive likelihood ratio was highest for bradypnoea in isolation and in combination with other clinical features (Table 1).

Table 1 Sensitivity, specificity, and positive likelihood ratio of clinical findings associated with analytically confirmed opioid exposure in emergency department illicit drug presentations with hypoxaemia.

Clinical finding(s)	Sensitivity	Specificity	Positive Likelihood Ratio
Miosis	0.64	0.63	1.73
Respiratory rate (RR) < 10 breaths per minute	0.47	0.77	2.04
Glasgow Coma Score (GCS) < 9	0.64	0.37	1.02
Glasgow Coma Score (GCS) = 3	0.56	0.55	1.24
Miosis AND GCS <9	0.38	0.63	1.03
RR <10 breaths per minute AND GCS <9	0.41	0.85	2.73
Miosis AND RR <10 breaths per minute	0.35	0.89	3.18
Miosis AND RR <10 breaths per minute AND GCS <9	0.29	0.89	2.64

Conclusion: In this cohort, clinical findings had relatively poor sensitivity, specificity, and positive likelihood ratio in identifying the presence of an opioid in emergency department presentations with hypoxaemia. Naloxone should not be withheld in cases of hypoxaemia secondary to possible opioid exposure based on the absence of classical clinical signs of opioid toxicity.

108. Changing patterns of synthetic cannabinoid receptor agonists detected in patients attending emergency departments in the UK after drug use

Abstract

Objective: Synthetic cannabinoid receptor agonists (SCRAs) are new psychoactive substances that can cause severe adverse health effects. Large numbers of these compounds have been identified internationally and those used most frequently may be affected by changes in national and international legislation. SCRAs are commonly manufactured in China so legislation in that country is of particular importance. Here we report the SCRA most commonly detected in UK emergency departments (ED) since 2015 and relate changes observed to UK and Chinese legislative changes.

Methods: The Identification Of Novel psychoActive substances study (IONA) included patients (≥16 years) presenting to participating EDs with toxicity after suspected drug misuse who gave informed consent (or with agreement of a relative/representative if lacking capacity) between March 2015 and March 2023. Demographic and clinical features were recorded and blood and/or urine samples analysed using liquid chromatography-high resolution accurate mass full scan and full scan MS/MS mass spectrometry.

Results: Clinical and analytical data is available from 1815 patients. There were 565 detections of individual SCRAs with annual rates (numbers of detections/number of patients) falling since 2016. All SCRA with more than 20 detections (Table 1) have been controlled in the UK since 2016 or earlier and are also captured by generic effect-based legislation enacted in that year which made it illegal to import or sell psychoactive substances for human consumption. Reductions for individual SCRAs also occurred following Chinese legislation affecting them in 2015 (MDMB-CHMICA, 5F-AKB-48) and 2018 (5F-MDMB-PINACA, AMB-FUBINACA), while rates for the remainder have fallen after generic structure-based legislation was introduced in China in 2021.

Table 1 Annual SCRA detection rates for compounds with at least 20 individual detections in the IONA study.

	2015^a	2016	2017	2018	2019	2020	2021	2022	2023*
Patients included (n)	56	179	225	170	221	193	262	396	113
Detections per patient
5F-MDMB-PINACA	0.00	0.25	0.15	0.14	0.01	0.01	0.00	0.00	0.00
AMB-FUBINACA	0.05	0.12	0.15	0.03	0.04	0.00	0.00	0.00	0.00
MDMB-4en-PINACA	0.00	0.00	0.01	0.00	0.03	0.17	0.06	0.02	0.00
MDMB-CHMICA	0.29^c	0.12	0.06	0.05	0.00	0.00	0.00	0.00	0.00
5F-MDMB-PICA	0.00	0.00	0.00	0.02	0.09	0.03	0.00	0.01	0.00
FUB-NPB-22	0.02	0.12	0.01	0.01	0.01	0.00	0.00	0.00	0.00
4F-MDMB-BINACA	0.00	0.00	0.00	0.01	0.06	0.04	0.01	0.00	0.00
5F-PB-22	0.05	0.12	0.00	0.01	0.00	0.00	0.00	0.00	0.00
AB-FUBINACA	0.00	0.01	0.02	0.05	0.00	0.02	0.00	0.00	0.00
ADB-BUTINACA	0.00	0.00	0.00	0.00	0.00	0.00	0.04	0.02	0.01
Others	0.27	0.16	0.05	0.11	0.03	0.05	0.06	0.01	0.00
All SCRA	0.68	0.89	0.46	0.41	0.29	0.31	0.18	0.06	0.01

^a Incomplete year.

Conclusion: Legal controls enacted in the UK (2016) and China (2015, 2018, 2021) have influenced the numbers and patterns of SCRAs encountered in patients attending UK emergency departments. These findings illustrate the importance of international approaches to drug control measures.

109. Ketamine abuse with urologic complications on the rise in the Netherlands

Abstract

Objective

At sub-anesthetic doses, ketamine induces motor impairment and psychoactive effects, for which it is abused recreationally. Chronic ketamine abuse can cause urinary tract damage. The objective of this study was to analyze trends in the number of inquiries on ketamine abuse in the Netherlands.

Methods

We retrospectively queried the Dutch National Poisons Information Center (DPIC)-database retrieving all inquiries concerning ketamine abuse from 2018 to 2022. We also retrieved data on patients with urological complications from the first regional ketamine outpatient clinic in the Netherlands [1].

Results

See Table 1. DPIC data: Since 2018 the number of telephone inquiries concerning ketamine abuse related toxicity to the DPIC has increased, primarily from 2021 onwards. Nine patients (3%) reported urologic complaints. In addition, consultation of the DPIC website on ketamine exposures increased from 54 in 2018 to 353 in 2022 (total: 989 from 2018–2022). Ketamine outpatient clinic: In 2022, 32 patients with urologic complaints related to ketamine abuse presented at the regional ketamine outpatient clinic. Often reported urologic complaints were pain, hematuria, polyuria, incontinence and decreased bladder volume. Ketamine cessation was difficult for most of the patients due to increasing pain. Cessation, in combination with medical therapy, led to a substantial reduction of symptoms after 3 months in 73% of “clean” patients.

Table 1 Data on ketamine abuse in the Netherlands.

Year	Poisons center	Ketamine outpatient clinic
2018	33	–
2019	33	1
2020	46	2
2021	77	11
2022	81	32
TOTAL (2018–2022)	270	46
Descriptive statistics	2018–2022	Only 2022
Age in years
Median	23	25
IQR	20–29	22–28
Range	13–70	20–42
Sex
Male	180 (67%)	24 (75%)
Female	83 (31%)	8 (25%)
Ketamine use only	100 (37%)	11 (34%)
Unknown		3 (9%)
Other drug use (total)	170 (63%)	18 (57%)
Alcohol	73 (27%)
3,4-Methylenedioxymethamphetamine (MDMA)	33 (12%)
Cannabis	28 (10%)
Amphetamine	27 (10%)
3-MMC/4-MMC	25 (10%)
3 or more other drugs	75 (28%)
Ketamine abuse
Average amount used per week	–	20 grams
Duration of abuse (>1 gram/day)	–	32 months

Conclusion

Ketamine related health incidents are increasing in the Netherlands, with an increase in urological complications from heavy abuse, burdening the already strained healthcare system.

110. The Addiction's Clinical Care Suite: a dedicated medical unit for drug and alcohol detoxification in homeless patients within an acute NHS Trust

Abstract

Objective: Tri-morbidity (drug misuse, physical and mental health) is prevalent in the homeless community. Their treatment is heavily stigmatised leading to fragmented and inadequate care that makes creating appropriate care models challenging. To address the need of this group the Addiction Clinical Care Suite (ACCS) was proposed. At this time the ACCS is the only addictions inpatient unit in London (UK) operating as an integral part of an acute NHS Trust. With 5 beds for homeless patients, it arranges admissions focused around providing high standard medically assisted withdrawal/drug stabilisation from a range of recreational substances. The underlying premise of the service was to establish an inpatient unit within an acute hospital with close links to community drug and alcohol teams. Care is shared and co-led by a multidisciplinary team including Toxicology, Nursing, Psychiatry and Psychology colleagues.

Methods: Data from admissions across 12 months were collected. This included demographics and focus of admission, alongside medical and mental health interventions required during the hospital stay.

Results: Overall, 84 patients (mean (SD) age 42.6 ± 8.2 years, range 24–64, 71% male) were admitted across 21 different London boroughs. Patients reported a total of 17 substances being used regularly, with an average of 2.7/patient (range 1–6). The most common were alcohol (74, 88.1%), crack cocaine (37, 44%), heroin (36, 42.9), methadone (26, 31%), and cannabis (17, 20.2%). Table 1 outlines the treatment received (detoxification/drug stabilisation) and the leading mental and physical health comorbidity. In total 80% of patients completed treatment.

Table 1 Summary of the addictions, mental and physical health treatment received for patients admitted to the Addiction Clinical Care Suite (ACCS) (N = 84).

Reason for admission – n (%) (MAW* unless indicated)		Most frequent physical comorbidities treated (system categories) – n (%)
Alcohol	58 (14.5)	Gastroenterology (liver disease, bleeding, gastritis)	38 (45.2)
Methadone MAW: Stabilisation:	6 (7.1) 3 (3.6)	Metabolic (electrolytes)	19 (22.6)
Alcohol + methadone stabilisation	6 (7.1)	Musculoskeletal (haematoma, bone fractures)	17 (20.2)
Buprenorphine/Espranor	4 (4.7)	Neurology (delirium, CVA, intra-cerebral bleed)	16 (19)
Alcohol and buprenorphine	3 (3.6)	Cardiovascular (angina, arrhythmia)	14 (16.7)
Alcohol + methadone	2 (2.4)	Infection (STD, pneumonia, COPD)	14 (16.7)
GHB	1 (1.2)	Haematology (VTE, anaemia)	14 (16.7)
Methadone + pregabalin	1 (1.2)	Dermatology (eczema, psoriasis)	12 (14.3)
Most frequent mental health comorbidity treated – n (%)		Respiratory (COPD/asthma)	7 (8.3)
Depression	56 (66.7)	Obstetric/gynaecology	4 (4.8)
Post-traumatic stress disorder (PTSD)	11 (13.1)	Renal (acute kidney injury)	4 (4.8)
Personality disorder	9 10.7)	Ophthalmology (glaucoma)	1 (1.2)
Anxiety, behavioural	26 (31)	Overdose	1 (1.2)

COPD: chronic obstructive pulmonary disease; CVA: cardiovascular accident; GHB: gamma-hydroxybutyrate; MAW: medically assisted withdrawal; STD: sexually transmitted disease; VTE: venous thromboembolism.

Conclusion: The level of comorbidity among patients who are rough sleeping is demonstrated. The high levels of retention, completion of treatment, and number of individual health interventions collectively highlight that the ACCS offers both a feasible and effective model to provide the complex healthcare interventions needed for this patient demographic.

111. Fun I love but too much fun is of all things the most loathsome. Injuries by repeated nitrous oxide use, unexpected high rate of encephalopathy

Abstract

Objective

Recreational use of nitrous oxide is growing globally. As severe injuries related to acute exposure are rare, the use may seem insidiously safe. However, complications due to repeated use is an increasing problem. These injuries are mainly caused by an oxidation and inactivation of vitamin B692. Nitrous oxide thus causes a functional vitamin B692 shortage, and the symptoms of nitrous oxide abuse mimic, in many ways, the effects of true vitamin B692 deficiency (as pernicious anaemia). The most common symptoms include peripheral neuropathy and myelopathy, but encephalopathy is described as rare [1]. Here presented is a review of complications caused by repeated use of nitrous oxide reported to the Swedish Poison Information Centre.

Methods

Records of calls from hospitals to the Swedish Poisons Information Centre between 1 January 2022 and 13 October 2023, concerning injuries caused by repeated use of nitrous oxide were examined.

Results

A total of 211 cases (2022 n = 97, 2023 n = 114) were recorded. Median age was 22 years (range 14–48). There were 135 males and 76 females. In 80% (n = 169) of the cases there were symptoms of peripheral neuropathy or myelopathy (e.g., paraesthesia, numbness, weakness, gait disturbance) and 38% (n = 81) showed symptoms of encephalopathy (e.g., lethargy, confusion, cognitive disturbance, psychosis). Thromboembolic and hematologic complications were scarce, 2% and 0.9%, respectively (n = 5 and n = 2). During 2023 serum homocysteine concentration were collected and reported in 81 out of 114 cases and was elevated in all of these (average 102 µmol/L).

Conclusion

The most common complications were, as expected, symptoms of peripheral neuropathy or myelopathy. Encephalopathy was much more common than earlier reported, indicating that symptoms of cerebral involvement after recreational use of nitrous oxide may be underreported in the literature. In contrast to symptoms of vitamin B692 deficiency caused by pernicious anaemia, hematologic complications were rare. S-homocysteine is a sensitive marker of overconsumption of nitrous oxide.

113. A ten-year review of intentional paracetamol ingestions in children and adolescents – is there a distinct age separating intentional and unintentional overdoses in these populations?

Abstract

Objective

Paracetamol is a readily accessible medication and is the main pharmaceutical involved in poisoning in the UK. It is a cheap and widely available product. This study intended to determine the demographics of intentional and unintentional ingestions of paracetamol in individuals aged between 0 and 18 years.

Methods

Records of all UK telephone enquiries from hospitals to the National Poisons Information Service (NPIS) relating to intentional and unintentional paracetamol ingestions between 1 January 2012 and 31 December 2022 were analysed retrospectively. Data were analysed using descriptive statistics. Student’s T-test and Pearson’s chi-squared test were used for comparisons. A P-value of less than 0.05 was considered significant. Severity was graded according to the maximum Poisoning Severity Score (PSS).

Results

The NPIS received a total of 9969 enquiries relating to paracetamol ingestion, of which 6918 (69%) involved intentional ingestion (p < 0.001). The age of patients with intentional overdose ranged between 9 to 18 years. The mean age was 15 ± 1.5 years, compared with 6.9 ± 6.2 years (range 0–18 years) for unintentional overdose (p < 0.0001). Intentional overdose was not reported in females under 9 years old or males under 10 years old. Female patients accounted for 86% of all intentional overdoses compared to males (p < 0.0001). Females aged 12–17 years who ingested paracetamol intentionally, represented 55% of all paracetamol related enquiries. During 2012–2020, the peak age for intentional overdose in females was 15-years-old, compared to 14-years-old between 2021 and 2022. In females who ingested paracetamol intentionally, 33% scored MAXPSS0 (asymptomatic; n = 2341), 39% MAXPSS1 (minor; n = 2693), 8% MAXPSS2 (moderate; n = 559) and 2% MAXPSS3 (severe; n = 152). Four fatalities were reported (one male and three females). Most intentional paracetamol overdoses occurred during March (684), with 727 fewer overdoses occurring during April, July, August and December, compared to 2621 in January, March, June and November (p < 0.0001).

Conclusion

Intentional paracetamol ingestion occurred more frequently in adolescent females compared to males. Rates of intentional overdoses have historically increased with age. However, recent data suggests that the peak age of intentional paracetamol overdose in females has decreased from 15 to 14 years old. No reported intentional overdose occurred in females aged under nine years or males aged under ten years. The number of cases is not independent of the month, suggesting that intentional overdoses may be influenced by seasonal factors. These data indicate a need for more focused interventions to reduce cases of intentional paracetamol overdoses, specifically targeting females aged 12 and above.

114. Glucagon-like peptide 1 (GLP-1) agonists: a review of enquiries received by the UK National Poisons Information Service

Abstract

Objective

Glucagon-like peptide 1 (GLP-1) agonists have been approved for use in the UK for the treatment of type 2 diabetes since 2007. The use of GLP-1 agonists is likely to increase, as more recently, they have been approved for use to manage obesity in non-diabetic patients. The total quantity of GLP-1 agonists prescribed in general practice in England has increased from an estimated 3 million to 12 million items between 2018 and 2022 [1].

Methods

We retrospectively reviewed all telephone enquiries to the National Poisons Information Service (NPIS) involving GLP-1 agonists between 1 January 2009 and 31 August 2023.

Results

There were 197 enquiries involving 195 patients during this time, and 172 cases involved a GLP-1 agonist alone. Enquiries increased from 3 in 2010 to 38 in 2022. We restricted further analysis to the 166 (111 female and 55 male) cases of single agent injection. At least 35 of these were for weight loss (2 dulaglutide, 7 liraglutide and 26 semaglutide). Dulaglutide accounted for 41 exposures (25%). Twenty-seven (66%) of those exposed were female. The dose was known in 33 cases, median 3 (IQR 1.5–3) mg. A Poisoning Severity Score (PSS) [2] of none or minor was recorded in 40 cases (98%), and unknown in the remaining case. Liraglutide accounted for 68 exposures (41%). Forty-two (62%) of those exposed were female. The dose was known in 52 cases, median 2.4 (IQR 2.4–3.2) mg. A PSS of none or minor was recorded in 64 cases (94%), and moderate in 4 cases (6%). Semaglutide accounted for 57 exposures (34%). Forty-two (74%) of those exposed were female. The dose was known in 47 cases, median 1 (IQR 1–2) mg. A PSS of none or minor was recorded in 45 cases (79%), moderate in 10 cases (18%), and unknown in two. Prolonged episodes of vomiting were reported in all 14 cases of moderate toxicity. One case of (minimal) hypoglycaemia was recorded with a bedside blood glucose concentration of 3.3 mmol/L in a 33-year-old female who self-administered 2.5 mg of semaglutide purchased online.

Conclusion

The number of enquiries to the NPIS involving GLP-1 agonists is increasing. Our survey suggests that most overdoses are unlikely to be severely symptomatic but further surveillance is required.

115. Sodium glucose co-transporter 2 (SGLT2) Inhibitors: a retrospective review of the National Poison Data System 2014–2023

Abstract

Objective

Sodium glucose co-transporter 2 (SGLT2) inhibitors are a newer class of oral antidiabetic medications which have been prescribed in the US since 2013. Use of SGLT2 inhibitors has also broadened to include heart failure with mildly reduced or preserved ejection fraction. Prior studies have found acute ingestions of SGLT2 inhibitors to be well-tolerated without hypoglycemia and only minor effects. The primary purpose of this study was to describe characteristics in poison center calls related to SGLT2 inhibitors over a ten-year period.

Methods

We conducted a retrospective analysis using the National Poison Data System (NPDS), a data warehouse which collects information from all 55 US poison centers. NPDS was queried for all calls relating to SGLT2 inhibitors (code 0310102) between 1 January 2014 and 30 September 2023. Patient demographics, route and reason for exposure, clinical effects, therapies received, and medical outcome are reported descriptively.

Results

During the study period, 8435 calls involving SGLT2 inhibitors were reported to US poison centers, 3616 being single substance exposures. The number of exposures increased steadily from 172, and 425 in years 2014 and 2015 to 1713 in 2022 and 1792 in 2023 (up to September 30), respectively. Adult exposures (>19 years) represented 74.8% (n = 6308) and females 54.1% (n = 4564) of the calls. Therapeutic error (n = 5206; 61.7%), unintentional exposures (not otherwise specified) (n = 1908; 22.6%) and suspected suicide attempts (n = 875; 10.4%) were the most frequently reported reason for exposure. Medical outcome of single SGLT2 inhibitor ingestion were mostly judged non- to minimally toxic (n = 2009; 55.6%) and 31.3% resulted in no effect (n = 1135). Sixteen cases resulted in a major effect (0.4%) and one case of death was reported. The majority of single substance exposures were managed onsite and did not require referral to a healthcare facility (n = 2689; 74.4%), 13.7% (n = 497) were treated in the emergency department and 5.4% (n = 197) were admitted to a healthcare facility. Nausea (n = 86; 2.4%) and dizziness (n = 77; 2.1%) were the most frequently reported clinical effects. Food and snacks (n = 1077; 29.8%), intravenous fluids (n = 152; 4.2%) and activated charcoal (n = 75; 2.0%) were the top three therapies received in single substance ingestions.

Conclusion

SGLT2 inhibitor related calls to US poison centers are steadily increasing. Therapeutic errors represent the main reason for exposure and most exposures result in minimal toxicity. Poison center staff are able to keep most of those who ingest SGLT2 inhibitors out of healthcare facilities.

116. Presentation and outcome of the severely cyamemazine-poisoned patient in the intensive care unit: an observational cohort study

Abstract

Objective

Cyamemazine is a first-generation antipsychotic drug of the phenothiazine family marketed in France since the 1970s. Despite the emergence of new (or atypical) antipsychotics, showed to be more effective and safer, cyamemazine remains widely prescribed to treat anxiety-depressive and psychotic personality disorders at risk of suicidal attempt. Our aim was to report the features of severely cyamemazine-overdosed patients, to identify the factors associated with the requirement of mechanical ventilation, and to investigate the prognostic contribution of the plasma cyamemazine concentration measured on admission.

Methods

We conducted a single-center retrospective observational study including all cyamemazine-poisoned patients admitted to the intensive care unit (ICU) during the last 5 years (2017–2022). Diagnosis was based on a compatible history, clinical presentation, and plasma cyamemazine concentration in the toxic range on admission (>0.07 mg/L). Data are expressed as percentages or medians [percentiles]. Univariate comparisons were performed using chi-squared and Mann-Whitney tests, as requested. Coefficients of linear correlation were calculated.

Results

Eighty-four cyamemazine-intoxicated patients (31 years [22–50]; 25M (30%)/59F (70%); past depression (58%) and psychosis (45%); Sequential Organ Failure Assessment (SOFA) score 4 [2–7]) were included. Exposure resulted from suicidal ingestion in chronically cyamemazine-treated patients. Intoxication resulted from a multidrug ingestion (93%) including benzodiazepines (67%), antidepressant drugs (41%), other antipsychotics (17%), anticonvulsive drugs (11%), opioids (9%), acetaminophen (5%), and lithium (2%). On admission, patients presented Glasgow Coma Score (GCS) of 7 [6–11], agitation (16%), confusion (12%), seizures (4%), myorelaxation (19%), mydriasis (17%), and vomiting (8%). Electrocardiogram showed sinus tachycardia (95 bpm [80–111]) and marked abnormalities (24%) including impaired ST segment (21%) and QRS enlargement (10%). Plasma cyamemazine concentration on ICU admission was 0.247 mg/L [0.160–0.391]. Management included activated charcoal (20%), mechanical ventilation (63%), vasopressors (20%), hemodialysis (2%), and extracorporeal membrane oxygenation (ECMO) (1%). Complications included aspiration pneumonia (46%) and acute renal failure (6%). Two patients presented prehospital cardiac arrest and died. No malignant syndrome was observed. Length of ICU stay was 4 days [2–5]. The correlation between the plasma cyamemazine concentration and the GCS on admission was relatively weak (R² = 0.07), highlighting the contribution of the co-ingested toxicants to the alteration of consciousness. The necessity of mechanical ventilation was significantly related to the coma depth (p < 0.0001), aspiration pneumonia onset (p < 0.0001), vasopressor administration (p = 0.001), PaO₂/FiO₂ (p = 0.04), and plasma cyamemazine concentration on admission (p = 0.004).

Conclusion

Acute cyamemazine poisoning may result in severe complications requiring ICU admission. Mechanical ventilation is guided by the severity of neurorespiratory presentation and hemodynamic failure. Outcome is favorable in the absence of prehospital cardiac arrest. Prescribers should be aware of the risk of cyamemazine-attributed toxicity when prescribing this drug to patients at high-risk of suicide attempts.

117. A one-year prospective survey of propranolol enquiries to UK National Poisons Information Service

Abstract

Objective

The NPIS has previously reported on the prevalence of propranolol overdose and the unique opportunities Poison Centres have in prospectively capturing information to support safer prescribing [1,2].

Methods

We undertook a prospective survey of intentional overdoses involving propranolol reported to the NPIS between 1 January 2022 and 31 December 2022. All enquirers were asked prespecified questions, including whether the patient was prescribed propranolol (and if so the therapeutic indication) and whether the patient was known to have taken a deliberate overdose previously.

Results

There were 301 patients aged 12–86 years, including 201 females. Propranolol was the patient’s own medication in at least 186 (51 males and 135 females) cases and the indication was recorded in 132 (anxiety n = 117, hypertension n = 6, migraine n = 5, other indications n = 4). Attempts were made to follow up the 149 patients in hospital; outcome was ascertained in 48 cases. Thirty-four patients made a complete recovery; the dose ingested was known in 25, median (IQR) was 1120 (500–2800) mg. Fourteen patients (10 females) died. The dose ingested was documented in 9/14 cases, median (IQR) 2000 (800–3360) mg. In 9/14 fatal cases propranolol had been prescribed, specifically for anxiety in at least three. Of the 117 patients (31 males and 86 females) prescribed propranolol for anxiety, at least 49 (42%) were known to have taken deliberate overdoses previously. The dose ingested was known in 48/49 patients, ranging from 60 to 6400 mg. Fourteen of the 49 (29%) cases resulted in either moderate or severe [3] toxicity; seven patients made a complete recovery, and two died.

Conclusion

Intentional propranolol overdose continues to be reported almost daily to the NPIS. Many overdoses occur in patients with a history of overdose who are prescribed propranolol for anxiety, with a substantial proportion developing systemic toxicity. Targeted follow-up of Poison Centre enquiries and focused data collection may support assessment of drug toxicity and make prescribing safer.

118. The neurobehavioral effects of pregabalin: a mouse study

Abstract

Objective

Since it was marketed in 2004, pregabalin (PGB) has emerged as a recreational drug, particularly among opioid use disorder patients [1]. Its liability properties were demonstrated in mice. They might involve the dopaminergic and glutaminergic systems but are poorly understood [2,3]. The aim of this experimental study was to investigate the neurobehavioral effects and addictive liability of PGB and the impact of PGB administration on the addictive liability of morphine.

Methods

In all experiments, CD-1 mice were used and PGB (60 and 90 mg/kg) or saline (controls) administered intra-peritoneally. We studied PGB-induced neurobehavioral effects on locomotor activity, working memory, spatial orientation, and social interactions, after a single administration and repeated daily administration for 5 days. We investigated the addictive liability of PGB using conditioned place preference (CPP) tests in male and female mice. Using CCP in male mice, we investigated the impact of dopamine-1 receptor antagonist pretreatment on PGB-related reinforcing effects and the impact of PGB on morphine-related reinforcing effects (after the daily drug injection for 5 days).

Results

Hyperactivity was observed after single (p < 0.05) but not repeated PGB administration. Working memory or spatial orientation were not significantly altered with both administration patterns. Significant reinforcing effects were observed with 90 mg/kg PGB in female (p < 0.05) and 60 and 90 mg/kg PGB in male mice (p < 0.01). The reinforcing effect was abolished with dopamine-1 receptor antagonist pretreatment. PGB administered daily for five days sensitized mice to morphine-induced reinforcing effects.

Conclusion

In mice, PGB induces reinforcing effects involving dopaminergic pathways and allows sensitization to the reinforcing effects of morphine. Our findings suggest great vigilance is required if PGB and opioids are co-prescribed or PGB prescribed to opioid users.

119. Treatment challenges in massive acetaminophen overdose: does the route of administration of N-acetylcysteine matter?

Abstract

Objective

Currently there is no consensus on the definition of massive ingestion of acetaminophen (paracetamol), however, a dose greater than 32 g or a serum concentration of greater than 300 µg/mL at 4 h after exposure has been proposed. We review three cases treated in our emergency department (ED) and discuss the route of administration of N-acetylcysteine ​​(NAC) and its role in the outcome of each of them, considering that they were registered in a country where intravenous NAC is not readily available [1].

Case series

Case 1: A 53-year-old woman ingested an unknown amount of acetaminophen and clonazepam, arriving at the hospital 13 h post-ingestion. At this time, her serum acetaminophen concentration was 216 µg/mL. She underwent gastric lavage (GL), and received single dose activated charcoal (AC), and double-dose oral NAC (IV not available). Despite administration of ondansetron, she developed persistent vomiting, metabolic acidosis, hepatotoxicity, neurological impairment, gastric bleeding and shock, and died 22 h post-ingestion. Case 2: A 39-year-old male arrived at the ED 8 h after ingesting 75 g of acetaminophen and 16 mg of clonazepam. The acetaminophen concentration was 146.4 µg/mL. After GL and AC administration, he was treated with double-dose IV NAC. He recovered without liver failure and was discharged 48 h later. Case 3: A 40-year-old woman arrived at the ED 13 h after ingesting an unknown amount of acetaminophen and diphenhydramine. The acetaminophen serum concentration was 220 µg/mL. GL and AC administration were performed, and double-dose IV NAC was initiated. She was discharged without sequelae on day seven.

Conclusion

Intravenous NAC allows higher and more controlled dosing, which improves therapeutic outcome, in addition to avoiding gastrointestinal side effects, increasing treatment adherence [2]. The cases presented suggest that the oral NAC regimen may be less well tolerated in patients who present with vomiting refractory to treatment, especially when a massive dose of paracetamol is ingested, because it is necessary to administer a higher dose of NAC. Although comparative studies are necessary to determine whether cases of massive paracetamol ingestion should be treated exclusively with an intravenous NAC regimen, these cases renew the discussion about the need to have an intravenous presentation of NAC in our country.

120. Trends in fomepizole use for paracetamol poisoning: cases reported to US poison centers 2016–2022

Abstract

Objective: Fomepizole has been proposed as an adjunctive treatment in severe paracetamol (APAP) poisoning. Since its mention in 2016 [1], animal [2], and volunteer studies [3] have emerged to support its use. We describe nationwide trends of fomepizole use reported to America’s Poison Centers.

Methods: We queried the National Poison Data System (NPDS) for cases in which fomepizole was used and APAP was a listed toxicant. We compared these to cases of fomepizole use in which the listed toxicant was ethylene glycol (EG) or methanol (MeOH). Data are reported using descriptive statistics.

Results: Fomepizole use in APAP exposed patients increased from 121 cases in 2016 to 1014 cases in 2022 (Table 1). Over this span, the total number of cases involving fomepizole use increased from 2369 to 3188. Thus, the proportion of fomepizole use cases related to APAP increased from 5.1% to 31.8% of all cases over this span. In 2022, paracetamol poisoning was the most frequent toxicant treated with fomepizole.

Table 1 Use of fomepizole by listed toxicant reported to America’s Poison Centers.

Year	2016	2017	2018	2019	2020	2021	2022
Ethylene glycol (EG)	1204	1159	1073	1096	920	823	876
Methanol (MeOH)	287	227	238	267	242	263	254
Other	757	869	899	912	1281	1347	1044
Paracetamol (APAP)	121	108	128	144	256	681	1014
Total	2369	2363	2338	2419	2699	3114	3188
APAP % of total	5.11%	4.57%	5.47%	5.95%	9.48%	21.87%	31.81%

Conclusion: Fomepizole use in APAP poisoning is being increasingly reported to US poison centers. Although data are retrospective and lack confirmatory testing, they signal a large-scale shift in favor of using fomepizole for this indication. Further study is needed to determine the clinical benefit from this potential antidote.

121. Balancing act: digoxin antidote supply and demand in New South Wales, Australia

Abstract

Objective

Digoxin-Fab, a life-saving drug for digoxin poisoning, is expensive; each vial costs around US$1000 in Australia with a shelf-life of 3 years. With new clinical research evidence, the New South Wales (NSW) Life-Saving Register changed its guideline and recommends most hospitals stock 5 vials [1]. However, there is no information regarding the demand for digoxin-Fab in NSW Australia. Hospitals are divided into 6 categories with increasing level of emergency care [2]. We assessed the supply and demand for digoxin-Fab by comparing the stocking of digoxin-Fab across the hospitals in NSW and the advice provided by Clinical Toxicologists (CTs) at NSW Poisons Information Centre (NSWPIC) regarding administration of digoxin-Fab.

Methods

The current supply of digoxin-Fab documented by the Clinical Excellence Commission in NSW was used. Demand was estimated by advice provided by CTs regarding acute and chronic digoxin poisoning at the NSWPIC. Data included patient demographics, clinical details regarding the poisoning and management advice. CT advice for digoxin-Fab demand were categorised as “immediate” or “if clinically indicated”.

Results

Digoxin-Fab was unevenly distributed across NSW hospitals, totalling 394 vials. From 2017 to 2022, there were 149 chronic poisoning cases from 34 hospitals and 17 acute cases from 15 hospitals referred to the NSWPIC. Of the 34 hospitals that managed chronic cases, 25 received advice to give digoxin-Fab. Of these 25 hospitals, 3 were not registered to stock digoxin-Fab and all have Level 4 Emergency Departments (ED). Of the 15 hospitals that managed acute cases, 11 received advice to give dioxin-Fab. Of these 11 hospitals, 2 were not registered to stock digoxin-Fab; 1 was a private hospital and the other has a Level 4 ED. We propose a new stocking model whereby large EDs should keep 5 vials and smaller hospitals would hold 2 vials. This would amount to 246 vials available across all hospitals in NSW and reduce total stocks by 148 vials every 3 years, while still providing sufficient digoxin-Fab to treat all chronic poisoning cases and acute poisoning case with advice to source further vials from surrounding hospitals.

Conclusion

Our study showed the demand is mostly but not completely met by the supply of digoxin-Fab across NSW. Better utilisation of digoxin-Fab by more even and equitable supply across NSW hospitals would reduce costs substantially without compromising care to patients.

122. Systemic presentation of a Latrodectus tredecimguttatus envenomation successfully treated with Latrodectus mactans antivenom; a case report

Abstract

Objective

European black widow (Latrodectus tredecimguttatus) bite is a rare but potentially life-threatening event, especially in elderly, children and patients with multiple comorbidities. Only female spiders produce venom, containing the alfa-latrotoxin, which induces massive release of acetylcholine and noradrenaline on mammalian neuromuscular plates and neuroendocrine organs. The typical clinical picture is known as latrodectism. Grade 1–2 envenomation responds sufficiently to symptomatic treatment. We suggest that in grade 3 envenomation the L. mactans (the true black widow) antivenom could potentially be necessary and effective [1].

Case report

We present a case of L. tredecimguttatus bite in a 65-year-old Caucasian male, affected by arterial hypertension and diabetes mellitus type II, treated with metformin. Shortly after the bite at his elbow he developed a burning pain in the extremities and bruise-like pain in the trunk, unresponsive to benzodiazepines and intravenous morphine infusion. The typical latrodectism picture emerged, with diaphoresis, fasciculation of the extremities, facies latrodectismica, priapism, along with hypertension, tachycardia and tachypnea, mild oxygen desaturation and increased blood lactate concentration with mild increase in myoglobin and creatine kinase (CK). By 24 h after the bite and with no improvement in the clinical presentation, L. mactans antivenom was administered. An hour later most of the symptoms had disappeared, and the CK activity and renal function were restored by five days after the bite.

Conclusion

L. tredecimguttatus envenomation is a clinically significant medical event; it often requires hospitalization and intensive pain control, which is sufficient in grade 1 and 2 envenomation but not in 3rd grade envenomation. In grade 3 envenomation L. mactans antivenom has shown its efficacy and safety in the few reported cases to date [2].

123. Partial gastrectomy in a 4-year-old child after muriatic acid (hydrochloric acid) ingestion

Abstract

Objective

Our purpose is to illustrate the clinical presentation and the possible consequences due to caustic ingestion, underlining our diagnostic and therapeutic approach.

Case report

A 4-year-old boy was taken to the Emergency Department for the sudden appearance of hematemesis and abdominal pain. A probable accidental ingestion of muriatic acid (hydrochloric acid) a few hours earlier was reported; the substance was stored in a plastic bottle found in the kitchen. On clinical evaluation the child appeared apyretic, drowsy, with pale skin and antalgic position with bilateral flexion of hip. Regular bowel function and diuresis were reported. Blood exams, including hemoglobin values, were normal. Fasting and therapy with intravenous fluids and proton pump inhibitors were promptly started. Given the hemodynamic stability (as provided in the Society of Pediatric Gastroenterology Hepatology and Nutrition (SIGENP), and the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) Guidelines [1]) radiological images were immediately performed: chest radiography was negative, while abdominal radiography was suggestive for gastric perforation. He was then urgently taken to the operating room, where the radiological suspicion was confirmed, for which a partial gastrectomy was performed resulting in gastrostomy and jejunostomy. The esophagogastroduodenoscopy revealed grade 3a esophagitis according to the Zargar classification, while the laryngotracheobronchoscopy showed de-epithelization of the posterior oropharyngeal wall. The patient's post-operative course was complicated by bilateral pleural effusion, which required thoracic drainage, and difficulties in extubation caused by glottic edema. For the risk of infectious complications, intravenous antibiotic prophylaxis was administered; total parenteral nutrition was initiated. After 7 days, enteral nutrition via the jejunum was gradually started, with regular esophageal transit described by esophagogram. The patient was discharged in good general condition with a permanently dropping gastrostomy and enteral nutrition via jejunostomy over a 24-h period.

Conclusion

Caustic ingestion is a frequent cause of admission to hospital in children, often due to incorrect storage of household products. Such ingestions can cause necrosis of the gastrointestinal tract including perforation. An accurate medical history (aimed at identifying the nature and the quantity of the ingestion) and a detailed clinical examination are essential for the correct management. In case of an asymptomatic child, fasting and close clinical monitoring to identify complications early are strictly necessary while, in the suspicion of gastrointestinal perforation, an urgent radiography should be performed, followed by exploratory-therapeutic surgery.

124. Chlorine gas expositions due to mixing sodium hypochlorite with acids – a women’s issue?

Abstract

Objective

Sodium hypochlorite (NaOCl) is used as a disinfectant, cleaning or bleaching agent and mould remover. Products containing low concentrations (<5%) are available in many households. In our country, they must be labelled as follows: Do not mix with other products as dangerous gases (chlorine) may be released. Nevertheless, such exposures are common. The aim of the study is to describe the pattern of chlorine gas exposures due to accidentally mixing NaOCl with acids.

Methods

Retrospective analysis of calls to our national poison center from 1997 to 2022 with inhalational exposure to chlorine gas after mixing products containing NaOCl and acids. Patient characteristics, origin of calls (public or healthcare professionals) and site of exposure (workplace or residence) were evaluated. In cases with written medical follow-up (FUP), severity was graded according to PSS.

Results

There were 1119 calls involving exposure of 1060 patients; 723 calls (68%) were from the public and 396 (35%) from healthcare professionals. Of the 1060 patients, 1016 were adults (≥16 years), 39 children (<16 years), and 5 of unknown age. There were 685 females, 362 males, 13 of unknown sex. Exposures occurred at a residence in 866 cases (616 females, 241 males, 9 unknown), at the workplace in 186 cases (66 females, 117 males, 3 unknown), 8 exposures occurred at other or unknown sites. FUP with high causality assessment was available in 274 cases; 167 of the patients were exposed at a residence (FUP in 19%) and 101 at workplace (FUP in 54%). Three patients developed no symptoms. Mild, moderate and severe courses were observed in 188, 74 and 9 patients, respectively. There were no fatalities. Severity did not differ significantly between exposure at a residence or workplace: mild 69% versus 65%, moderate 26% versus 30%, severe 3% versus 3.6%. The female-to-male ratio for mild and moderate courses after exposures at residence was 1.7 and 3.9, respectively, after workplace exposures 0.6 and 0.5 respectively. Additionally, 5 of the 6 patients with severe symptoms after exposure at home were women, but none of the 3 severe cases after workplace exposure.

Conclusion

Most exposures took place at a residence (82%) with 71% females affected, while workplace exposures affected mostly men (63%). Most patients developed mild symptoms (69%), but moderate (27%) and rarely severe courses (3%) were also observed, irrespective of exposure site. Consumer education should take place to prevent exposures to chlorine gas emitted by mixing sodium hypochlorite containing products with acids.

125. A case of delayed diagnosis of a button battery ingestion

Abstract

Objective

Button batteries have devastating consequences when lodged in the esophagus [1]. Delayed diagnosis in children often leads to esophageal stricture, fistula, or perforation [2]. We present a case in which a child was diagnosed with a delayed button battery ingestion after a month of symptoms and was found to have significant mucosal injury on endoscopy.

Case report

A 2-year-old girl presented to her primary care physician after one month of poor oral intake. The pediatrician ordered a chest radiograph, which demonstrated a foreign body consistent with a button battery in the esophagus. The patient was immediately referred to the hospital where she was taken to the operating room for endoscopic retrieval. On endoscopy, the gastroenterologists noted the battery densely adherent to the anterior esophagus. Multiple attempts were made to retrieve the battery, all of which failed. Ultimately the team decided to push the battery into the stomach to allow it to pass through the gastrointestinal (GI) tract. A nasogastric tube was placed under direct visualization. The esophagus was found to have a large erosion with multiple discolored areas, without evidence of perforation. For the next two days, the battery continued to be visualized in the stomach on serial radiographs. Additionally, the patient pulled out the nasogastric tube and was unable to receive enteral nutrition. She had no bowel movement for four days and her stomach was noted to be newly distended on examination. Given the concern for further mucosal damage in the stomach, the poison center recommended gastrostomy for removal of the battery. She received the procedure the following day without evidence of further damage. The patient was placed on parenteral nutrition until an esophagram was performed on hospital day six, which showed no evidence of stricture. Her diet was slowly advanced, and the patient was discharged on hospital day nine with plans to follow up in the gastroenterology clinic.

Conclusion

Button battery ingestion can result in poor outcomes when intervention is delayed, thus rapid identification is paramount. This diagnosis should be considered in pediatric patients presenting with decreased oral intake.

126. A rare case of caustic skin burns from municipal tap water

Abstract

Objective

 We present a rare case of caustic skin burns from tap water caused by a high local concentration of sodium hydroxide used for pH adjustment in the municipal water supply. Caustic burns resulting from tap water is considered extremely unlikely, due to treatment technologies used in most water utilities, and the dilution of water treatment chemicals before reaching consumers. This case shows that caustic burns are possible when control mechanisms fail.

Case report

Within 2–3 min of showering a man experienced sudden skin pain and the water color changed to orange/brown. His skin immediately turned red with focal bleeding. He initiated skin irrigation within 20 min and continued for 2–3 h before transportation to hospital. There, he was diagnosed with widespread first-degree caustic burns to the head, neck, most of the upper body, and anterior parts of the extremities. The burns were treated with continued skin irrigation, analgesics, Vaseline^® and sulfadiazine cream. The following day he was discharged from hospital. During the first week he experienced sensitive and painful skin but recovered uneventfully. The municipality was alerted immediately and inspected the tap water in the house, measuring a high pH. Both a private warning on social media and an official warning was sent out. Several other consumers noticed abnormal color of the water, but no other adverse events were reported. The corrosive water came from the local water utility. To adjust pH, controlled amounts of sodium hydroxide were added directly into the water pipes containing running water in the water plant, by an automated mechanism. On the day of the incident, sodium hydroxide was added to stagnant water instead, and the water was sent out to the consumers with a “plug flow” of highly alkaline water.

Conclusion

 A technical malfunction at a water utility gave rise to a sudden elevated sodium hydroxide concentration and caused widespread first-degree skin burns during a shower. The case report illustrates the potential of serious poisonings to the public. A similar event has been reported from Germany [1]. Water utilities where treated water is delivered directly into drinking water mains directly connected to households pose a higher risk of adverse effects compared to facilities where water chemicals are diluted in a clean water storage tank before distribution.

127. Widespread esophageal mucosal injury following accidental ingestion of povidone-iodine: a case report

Abstract

Objective

Povidone-iodine (PVP-I) is a local broad-spectrum antiseptic commonly used for skin and wound disinfection. Complications associated with PVP-I use/abuse are rare but occasionally severe (acute renal failure, hypothyroidism), and in some cases, even fatal [1]. Toxicity is dose/concentration-dependent; therefore, accidental ingestion of PVP-I rarely leads to clinically significant alterations. Here, we present an exceptional case of accidental ingestion of PVP-I resulting in extensive esophageal mucosal injury.

Case report

A 64-year-old otherwise healthy woman accidentally ingested approximately 10 mL of 5% PVP-I solution. She presented to the Emergency Department complaining of epigastric-retrosternal pain. A toxicological consultation was sought from the Poison Control Center in Verona. After evaluating the patient (appearing distressed, persistent retrosternal pain, stable vital signs, intact oral cavity, normal abdomen, and within normal hematological and biochemical parameters), the decision was made to initiate high-dose proton pump inhibitor (PPI) therapy and perform urgent gastroscopy. The endoscopic examination revealed widespread superficial lesions of the esophageal mucosa, classified as type 2a according to the Zargar classification. The patient was admitted to the internal medicine department, kept nil by mouth, hydrated, and treated with PPIs, antibiotics, and corticosteroids. Renal and thyroid function remained unaltered during the hospitalization, and follow-up endoscopy showed significant improvement in the lesions. Consequently, the patient was discharged after five days. Subsequent gastroscopy three weeks post-ingestion revealed no residual lesions or complications.

Conclusion

Accidental ingestion of povidone-iodine, even in limited quantities (if the solutions are sufficiently concentrated), can cause severe esophagogastric mucosal injuries. Our recommendation is to consider iodopovidone ingestions (even accidental ones with high quantities/concentrations) on par with caustic ingestions, both in terms of management and subsequent follow-up.

129. Button battery enquiries to the Austrian Poisons Information Centre from 2016 and 2021

Abstract

Objective

Button battery ingestion and the seriousness of the possible damage is a growing toxicological burden. The severity of symptoms depends on several factors including size and chemical composition of the battery, the location and duration of mucosal or skin contact. Severe complications such as necrosis, perforation or strictures may occur if the button battery becomes lodged in the esophagus.

Methods

A retrospective and descriptive analysis of enquiries to the Austrian Poisons Information Centre (PIC) concerning button batteries from 2016 to 2021 was conducted.

Results

Between 2016 and 2021 the PIC received 268 enquiries regarding 260 persons. All cases involved ingestion except one, where a 5-year-old child stuck a battery up his nose. The majority (n = 202) were less than 15 years of age (6 months to 13 years; median age: 2 years; 116 male, 84 female, 2 unknown). In all cases, the exposure was unintentional. Most commonly, children up to the age of four were affected (n = 178). In children aged up to three years old, male children predominated (n = 101; female n = 65). In 58 cases, the individuals were 15 years of age or older, of which 18 were male and 40 were female. In the age group from 20 to 49 years (n = 13) only female individuals were affected. In four cases (age: 21–46 years) the button cells were taken with self-harm intent and in one of these cases additional medication was taken. An increase in cases was observed in the age group over 80 years (n = 35), with the oldest person being 97 years. Almost one third of these patients had dementia. In 2021, a kindergarten reported to the PIC a missing button battery from a book with a battery compartment and 51 children may have been affected; it was impossible to narrow down of the number of affected individuals. This case was summarized by the PIC to one affected person of unknown gender because it is not possible to enter 51 persons as one case in the database.

Conclusion

The age group most frequently exposed are children up to four years of age, followed by adults aged more than 80 years, especially patients with dementia. These data can be helpful in developing preventive measures.

130. Benzodiazepine enquiries to the Austrian Poisons Information Centre in the years 2014–2022

Abstract

Objective

Benzodiazepines are commonly prescribed to treat anxiety disorders, insomnia, and seizures. These medications have depressant effects on the central nervous system and can be misused. We analysed cases of benzodiazepine exposure reported to our poison centre.

Methods

Cases of benzodiazepine enquiries to the Austrian Poisons Information Centre (PIC) regarding the number of people and incidences from 2014 to 2022 are retrospectively analysed.

Results

In 2014 to 2022, the PIC advised on the treatment of 6977 intoxicated persons who had either taken benzodiazepines alone or in combination with other substances. In terms of the total number of people advised by the PIC, 3.5% of all had been exposed to benzodiazepines, with the highest proportion being 4% in 2021 and 3.9% in 2022. In the under 15-years of age group, there was no change in the number of benzodiazepine exposures in relation to the total number of PIC consultations. Exposure was mainly accidental (n = 180), followed by intentional (n = 83) and in 13 cases due to addictive behaviour. In 2021, there was the lowest number of accidental exposures (n = 12), but the highest number of young people who intentionally took benzodiazepines (n = 18). Among those aged 15-years and older, the number of people exposed to benzodiazepines increased in relation to the total number of people advised by the PIC. In 2014, 5.3% of persons were exposed to benzodiazepines, compared to 7.6% in both 2021 and 2022. Exposure was predominantly intentional (n = 4972), followed by addictive behaviour (n = 655) and incorrect use of benzodiazepines (n = 652). In 2021, the highest number of persons were exposed to benzodiazepines due to addictive behaviour (n = 125) and in 2022 due to self-poisoning (n = 689).

Conclusion

In 2021 and 2022, the largest increase in requests for benzodiazepine intoxication was in the group aged 15 years and over. In 2021, the most common intention was abuse and in 2022 it was self-poisoning. The COVID-19 pandemic occurred in these two years, and a possible link cannot be completely ruled out after analysing our data.

131. Paliperidone poisoning and measurable plasma concentrations 2.5 years after last administered dose: a case report

Abstract

Objective

To report a case of poisoning with paliperidone palmitate, a once‐monthly, long‐acting injectable antipsychotic.

Case report

A woman in her sixties diagnosed with bipolar disorder was admitted to the Psychiatric Department due to severe confusion and dystonia. Initially, severe depression, or a state of delirium, was suspected as the cause of her symptoms. The patient had been treated with long-acting intramuscular paliperidone for eight years and had received her last 100 mg paliperidone injection eight days prior to admission. On the fifth day of admission (12 days after the last injection of paliperidone) a blood sample revealed a highly elevated plasma paliperidone concentration of 605 nmol/L (normal therapeutic range 15–125 nmol/L), which was nearly five times higher than the upper reference range for this specific laboratory. The Danish Poison Information Centre was consulted and specifically asked for ways to increase the clearance of paliperidone. We aimed to increase paliperidone elimination by inducing p-glycoprotein through treatment with Saint John’s wort 300 mg ×3 daily for the rest of the hospital stay. This seemed to have a limited effect on paliperidone clearance. Plasma concentration concentrations decreased with time, as did the dystonia. All antipsychotic treatment was discontinued after this event, and the patient did not receive any prescriptions of paliperidone or risperidone. However, the plasma paliperidone concentration was in the low end of the normal therapeutic range 2.5 years after the last dose of paliperidone was administered, and the patient still had some symptoms of dystonia.

Conclusion

This clinical case report illustrates the perils of poisoning with long‐acting injectable antipsychotics. Paliperidone is a substrate of p-glycoprotein and we therefore aimed to increase its elimination by inducing p-glycoprotein through treatment with Saint John’s wort, with limited effect. The patient had a measurable paliperidone concentration in the normal therapeutic range 2.5 years after the last dose of intramuscular paliperidone was administered. We therefore hypothesise that prolonged treatment with paliperidone palmitate may cause a continuous, long-lasting absorption for up to 2.5 years in some patients.

132. Toxicity of ADHD drugs other than methylphenidate: an evaluation of follow-up reports

Abstract

Objective: Methylphenidate is frequently used for the treatment of attention-deficit hyperactivity disorder (ADHD), and its toxicity profile has been well studied. Much less is known, however, about the effects of overdoses of other drugs used to treat ADHD. We therefore aimed to establish toxicity profiles of these substances.

Methods: Retrospective analysis of cases with ingestion of dexmethylphenidate, lisdexamfetamine, dexamfetamine, atomoxetine, and guanfacine reported by physicians to Tox Info Suisse between 2006 and 2022. Cases with follow-up information were included if causality assessment was reasonable. Severity was graded according to the Poisoning Severity Score.

Results: Overall, 140 reports on humans were included; 61% (86 cases: 65 adolescents and adults ≥12 years, 21 children up to 12 years) had monointoxications with dexmethylphenidate, lisdexamfetamine, atomoxetine, guanfacine, and dexamfetamine in 40, 35, 8, 2, and 1 cases, respectively. Polyintoxications occurred in 54 cases (39%). After monointoxication with dexmethylphenidate, no symptoms occurred in 4 patients after doses up to 30 mg (in one case, no symptoms were reported after 400 mg). In 28 patients, mild symptoms were present after doses between 40 and 600 mg, while 4 patients had moderate symptoms after 100 to 1000 mg. Dose information was missing in 2 adults and 2 children with mild and 3 adults and 1 child with moderate symptoms. Moderate agitation (n = 6), mild restlessness (n = 14), and mild tachycardia (n = 21) were the most frequently reported symptoms. With lisdexamfetamine monointoxications, 9 patients showed no symptoms (30–900 mg). Mild and moderate symptoms were seen with 30–1260 mg (n = 14), and 50–1800 mg (n = 6), respectively. Dose information was missing in 6 patients with mild or moderate symptoms. Most frequently reported symptoms were moderate agitation (n = 7), mild restlessness (n = 9), and mild tachycardia (n = 9).

After monointoxications with atomoxetine, 2 patients showed no symptoms after 375 and 600 mg, respectively, while mild symptoms (most frequently headache and tachycardia) were present in 6 cases after doses between 16 and 3360 mg. One guanfacine monointoxication showed no symptoms (after 10 mg), the other mild drowsiness (8 mg). The patient who ingested 15 mg dexamfetamine showed mild thoracic pain and dyspnea.

Conclusion: No severe or fatal monointoxications occurred. For dexmethylphenidate in adults and adolescents, moderate symptoms (agitation) were observed in our dataset with doses starting from 100 mg. For lisdexamfetamine, doses and symptoms were not related. The number of reports for atomoxetine, guanfacine and dexamfetamine was too small for dose-toxicity relationship assessments.

133. A case of severe, treatment-resistant, neuroleptic malignant syndrome after paliperidone long-acting injectable

Abstract

Objective

Neuroleptic Malignant Syndrome (NMS) is a rare, life-threatening reaction to antipsychotic agents that presents with hyperthermia, rigidity, and altered mental status. We describe a case of NMS requiring multimodal therapy, with symptoms lasting greater than two months.

Case report

A 24-year-old male with schizophrenia presented to an outside facility with delirium after ingesting 120 mg of delta-9 tetrahydrocannabinol (THC) edibles. His medications included escitalopram, lisinopril, and monthly intramuscular paliperidone palmitate. His delirium improved and he was given his paliperidone injection nine days earlier than his scheduled dose. Over the next three days, he developed hyperthermia, tachycardia, hypertension, rigidity, and altered mental status. The regional poison center was consulted regarding the possibility of NMS, and he was transferred to our facility. On arrival, initial vital signs were: BP 140/51 mmHg; HR 128 beats/min; RR 33 breaths/min; temperature 39 °C; and O₂ saturations 95%. He was diaphoretic, with rigidity and clonus. He was intubated and sedated with midazolam, 15 mg/h. Bromocriptine was initiated at 2.5 mg three times daily. Laboratory studies included a white blood cell count of 13,000/µL, and a creatine kinase of 300 U/L. Broad workup including thyroid, computerised tomography (CT) head, CT angiography, magnetic resonance imaging (MRI) brain, and lumbar puncture were unremarkable. Initial paliperidone serum concentration was supratherapeutic at 65.4 ng/mL. Over the next 10 days, his sedation requirements escalated due to continued hyperthermia and rigidity. At maximal therapy, he was treated with oral bromocriptine 10 mg 4 times daily, oral amantadine 100 mg twice daily, dantrolene 1 mg/kg twice daily IV, midazolam 40 mg/h IV, propofol 80 µg/kg/min IV, as needed dexmedetomidine, along with oral diazepam 30 mg four times daily. After 72 days in the neurointensive care unit, he was weaned to a tracheostomy collar, and able to walk with assistance. He was discharged to a skilled nursing facility. One month post-discharge, he returned home with family assistance and walked independently.

Conclusion

We believe that our unique case was compatible with the diagnosis of NMS despite the atypical course and resistance to treatment. It is unclear whether the early administration of paliperidone was the culprit for precipitating NMS or if it was coincidental in an already established presentation. Furthermore, the depot preparation of paliperidone could have contributed to the prolonged course of our case due to the slow and prolonged release of the medication. Clinicians should consider this possibility and anticipate a longer disease course.

135. Digoxin over-exposures in hospitalized patients

Abstract

Objective

To evaluate and characterize digoxin over-exposure cases in hospitalized patients in recent years.

Methods

A single center retrospective chart review of hospitalized patients with elevated digoxin serum concentration (≥2 µg/L), between January 2020 to December 2022, was conducted. Cases were retrieved digitally and the medical records were manually reviewed. Exclusion criteria included cases in which blood sampling for digoxin concentration was inappropriately timed, not reflecting the true, clinically meaningful concentration. Demographic and clinical data were collected and subjected to descriptive and comparative statistical analysis.

Results

Of 171 patients that were evaluated for digoxin serum concentrations, 23 (13.4%) patients were eligible and included in the final analysis. The average age of patients was 81.6 years (median 82; range 67–94); 60.9% were female. Digoxin serum concentrations were in the range of 2–4.6 µg/L (average 2.74, median 2.4). Most patients (n = 16, 69.6%) were asymptomatic. Seven (30.4%) patients had associated clinical manifestations mostly mild to moderate, including symptomatic bradycardia (n = 6), weakness (n = 5), gastrointestinal symptoms (n = 3), and vision impairment (n = 2). Symptomatic patients had significantly higher digoxin concentrations (unpaired t-test, p = 0.027). The main cause for the over-exposures was a medication error: exaggerated loading (n = 9) and/or maintenance doses (n = 4), and interval errors (n = 2), such as twice per day instead of twice per week. Acute renal failure was a major factor in 8 more cases of digoxin over-exposure. No intentional acute overdose ingestion was recorded. Patients recovered successfully without antidotal treatment.

Conclusion

Based on the study, recently recorded digoxin over-exposures in hospitalized patients are mainly the result of various medication errors that caused a gradual increase in the drug serum concentrations. Better physician training, use of updated dosing protocols and appropriate monitoring of renal function and drug concentrations are pivotal for improving digoxin prescribing and administration practice and mitigating its over exposure in patients.

136. Never ending story – an extraordinary long duration of diazepam intoxication

Abstract

Objective

Diazepam is metabolised in the liver to active intermediates (mainly nordiazepam). Nordiazepam is renally eliminated with a longer elimination half-life than diazepam. Although diazepam poisonings generally are considered easy to treat there is considerable individual sensitivity to the effects of diazepam and nordiazepam. We present an iatrogenic diazepam poisoning with prolonged duration.

Case report

A 67-year-old male with a history of ethanol overconsumption and liver cirrhosis, presented to hospital. He developed delirium tremens and was treated with 370 mg of diazepam during the first week of hospitalisation. Subsequently, he became somnolent. Flumazenil was administered with prompt effect on his level of consciousness. During the following weeks he had several relapses of central nervous system (CNS) depression. He intermittently needed intubation, respiratory support and norepinephrine (noradrenaline) infusion, and developed aspiration pneumonia and kidney failure. Diazepam poisoning was suspected, and flumazenil was repeatedly administered, each time with a prompt effect on his level of consciousness and a flumazenil infusion was started. Blood analyses of diazepam and nordiazepam performed one month after the last administration showed 0.69 µmol/L and 2.0 µmol/L. Diazepam and nordiazepam concentrations were analysed weekly during the following month and declined over time. Two months after the last administration of diazepam the patient still required several doses of flumazenil daily. After three months of hospital stay the patient was discharged.

Conclusion

The prolonged CNS-depression in this patient may have been caused by an extended elimination half-life of diazepam and nordiazepam due to concomitant liver and kidney failure. Liver cirrhosis probably affects diazepam metabolism and renal failure may lead to accumulation of nordiazepam [1]. In addition, the age of the patient could have affected the course. Older patients are at risk of developing delayed elimination [2]. This case highlights the importance of considering underlying conditions, which might complicate the use of an otherwise well-known and considered safe drug.

137. Reasons for stroke code activations in patients presenting to hospital with self-poisoning

Abstract

Objective

Early diagnosis of cerebrovascular accidents (CVA) results in earlier delivery of cerebral revascularisation therapies and hopefully reduction in neurological deficit following stroke. Tools to rapidly diagnose CVA include non-specific signs including altered mental state, slurred speech, ataxia, and weakness. These may also be present after sedative drug overdose. We describe a retrospective cohort presenting to hospital with clinical signs resulting in “code stroke” activation with an ultimate diagnosis of drug overdose.

Methods

Toxicology unit referrals from 2013 to 2023 were searched for patients with “stroke code” assessments. Clinical details included, age, gender, reason for stroke code, whether overdose was suspected prior to stroke code activation, imaging performed, diagnosis, and substances implicated in overdose.

Results

There were 33 referrals following stroke code initiation (61%, n = 20 female) with median age 56 years (IQR: 45–64). Overdose was not initially suspected or mentioned in triage assessment in 67% (n = 22). Triage category was 1 or 2 out of 5 in 91% (n = 30) with code stroke initiated on arrival to the Emergency Department in 64% (n = 21) and delayed up to 11 h post-presentation in 25% (n = 8). Endotracheal intubation was performed on arrival in 30% (n = 10). The commonest documented reasons for activating stroke code were: altered conscious state 39% (n = 13), slurred speech 42% (n = 14), abnormal gait 21% (n = 7), and confusion 24% (n = 8). Unilateral facial droop and arm weakness was only documented at triage in one patient. No other patients had lateralising signs in this cohort. All patients underwent cerebral computerised tomography (CT) scanning. CT-angiography and cerebral magnetic resonance imaging (MRI) was performed in 73% (n = 24) and 15% (n = 5), respectively. Acute stroke was diagnosed in two patients following cerebral imaging. Median time to recognition of overdose was 2 h (IQR: 0–5) from presentation, however, delay was as long as 10 to 24 h in three cases. ICU admission was required in 40% (n = 13). There was one fatality resulting from hypoglycaemic brain injury. Overall, 84% (n = 26) of agents implicated in overdose had sedative effects and 42% (n = 13) were poly-drug ingestions. Substances included benzodiazepines 26% (n = 8), opioids 19% (n = 6), antidepressants 13% (n = 4), antihistamines and antipsychotics 13% (n = 4) and single cases of amphetamines, baclofen, ethanol, ethylene glycol, anticholinergics, and insulin.

Conclusion

Stroke code activation was primarily for non-lateralising signs of suspected CVA. Overdose was considered as an alternate diagnosis once cerebral imaging had excluded stroke in two-thirds of cases. Interestingly, one-third of cases presenting with history of overdose and non-lateralising signs still underwent initial code stroke evaluation.

138. Methylphenidate poisoning in Taiwan: a poison-center based study

Abstract

Objective

Methylphenidate is a drug primarily used in the treatment of attention deficit/hyperactivity disorder. This study aims to describe the demographic and clinical manifestations of cases with methylphenidate poisoning reported to Taiwan Poison Center (PCC-Taiwan) and to investigate the potential associations between the specific formulation of methylphenidate, pre-selected dosage thresholds, and the severity of poisoning.

Methods

This retrospective chart review study encompasses all documented cases of methylphenidate overdose reported to PCC-Taiwan from 1985 to 2022. Cases were categorized into two groups: asymptomatic and mild poisoning group versus moderate-to-severe poisoning group. Moderate poisoning is defined as a condition that is non-life-threatening but still requires medical treatment; whereas severe poisoning indicates the development of any life-threatening effects following methylphenidate exposure. The pre-selected dosage thresholds that might predict the severity were 2 mg/kg and 3 mg/kg, respectively [1]. The chi-square test was employed to assess potential relationships between methylphenidate formulation, various dosage thresholds, and the severity of poisoning.

Results

A total of 167 cases were identified. After excluding 13 cases due to incomplete data or duplication, 154 cases were eligible for further analysis. The median age was 13 years, with a slightly higher proportion of male (104, 67.5%). All cases were of acute exposure, with a slightly higher frequency of intentional exposure (94, 61.0%). Among the 154 cases, 79.9% had symptoms, yet the majority experienced only mild effects (64.9%). The most frequently observed clinical manifestations included tachycardia (34.2%), agitation (18.8%), and nausea (15.6%). None of the patients had severe toxic effects or died. Seven cases were further excluded from the analysis of predictors of severity of poisoning due to the lack of relevant information. Both the specific formulation of methylphenidate (p = 0.36) and the dosage thresholds (p = 0.31 for 2 mg/kg, p = 0.69 for 3 mg/kg) were not significantly associated with the severity of methylphenidate poisoning.

Conclusion

Most of the methylphenidate overdose cases reported to the PCC-Taiwan exhibited mild poisoning only, with tachycardia being the most frequently observed symptom. With the limited number of severely poisoned cases included in this study, neither the specific formulation of methylphenidate nor the dosage per body weight was found to exhibit a statistically significant association with the severity of methylphenidate poisoning.

139. Attempted suicide with a subcutaneous injection of liraglutide

Abstract

Objective

We present a case of a suicide attempt in a non-diabetic woman with a subcutaneous injection of liraglutide prescribed for weight loss. Liraglutide is a glucagon-like petide-1 agonist which increases insulin release from the pancreas and decreases excessive glucagon release as blood glucose concentrations rise.

Case report

A 37-year-old, non-diabetic woman of 75 kg self-injected 72 mg of liraglutide subcutaneously with a suicidal intent. Soon afterwards she developed continuous vomiting without other symptoms, for which she presented at the emergency department two hours later. After consulting the Belgian Poison Centre, asymptomatic treatment was started with continuous observation and monitoring of blood glucose concentrations and pancreatic function by serum lipase activity. During 36 h of stay in the emergency department, no abnormalities in glucose concentrations or lipase activity were detected with 83 mg/mL being the lowest detected blood glucose concentration. The vomiting continued for 36 h despite intravenous treatment with alizapride.

Conclusion

To the best of our knowledge [1–3], this is the first case report of a subcutaneous overdose of liraglutide in a non-diabetic patient. While blood glucose concentration monitoring was recommended, no signs of hypoglycaemia were detected. This is in line with liraglutide's pharmacological action and previous overdose reports. While pancreatitis is a known adverse effect in chronic users [4], no pancreatic abnormalities were present in our case. When drugs to lose weight are indicated, a good psychological risk assessment of the patient prior to administration is required.

140. Effects of incretin drugs in overdose: a collection of cases reported to the Swiss National Poison Center

Abstract

Objective

The discovery of the effects of incretins have prompted the development and utilization of a group of drugs for the treatment of diabetes mellitus type 2, as well as the management of obesity. Generally assumed to be safe, especially concerning the risk of hypoglycemia with therapeutic doses, not much is known about these drugs in overdose.

Methods

A case series of overdoses involving incretin drugs in adults and children is presented, either as monointoxications summarizing the type and severity of symptoms, or in combination with other drugs, estimating the risk of hypoglycemia. Cases were reported to our national poison center by physicians between 2008 and 2022. Cases were included if causality of symptoms was reasonable in monointoxications and if there was a clear (minimal) known dosage. Severity was graded according to the Poisoning Severity Score.

Results

Monointoxications: For glucagon-like peptide-1 (GLP1)-agonists, 8 cases were reported. These included injections of exenatide (150 µg, 300 µg), liraglutide (6 mg, 3 mg) and semaglutide (3 × 2 mg, 14 mg) in adults, as well as a child ingesting semaglutide (14 mg) orally. Frequently, gastrointestinal symptoms of mild to moderate severity occured, but hypoglycemia was not reported. With dipeptidyl peptidase (DPP)-4 inhibitors, only one case of sitagliptin (1.4 g) overdose was reported which did not result in any symptoms or hypoglycemia. Polyintoxications: GLP1-agonists in combination with other substances showed no hypoglycemia in the following cases: 4 cases of injections of liraglutide (2 mg, 10.8 mg, 18 mg, 36 mg) by adults and 1 case of a child ingesting 7 mg of semaglutide. DPP4-inhibitors in combination with other substances showed no hypoglycemia in the following cases: 24 cases of sitagliptin 150 mg-9 g by adults and 4 children that ingested 50–100 mg, as well as 6 cases of vildagliptin ingestion of 250 mg-1 g by adults.

Conclusion

Based on the limited data available, it appears that incretin drugs, especially DPP4-inhibitors, are relatively safe in cases of (up to moderate) overdoses concerning the risk of hypoglycemia. However, GLP1-agonists can lead to pronounced gastrointestinal symptoms. These findings align with the current understanding of the physiological effects of incretins. The potential side effect of acute pancreatitis was not observed in our case series. More reports are needed to strengthen these assumptions about the toxicity profile of incretin drugs.

141. Poisonings in Greenland with focus on medicine exposure

Abstract

Objective

Greenland is part of the Kingdom of Denmark. However, the infrastructure, the regulation and dispensing of drugs and the ethnicity of the population are different in Greenland compared with Denmark. The Danish Poison Information Centre (DPIC) is a national healthcare institution with 24/7 advisory service for healthcare professionals and the public about acute poisonings. The DPIC has more than 400,000 enquires in a database about poison exposures including enquiries from Greenland. The objective of this study was to examine whether poisonings in Greenland differs from poisonings in Denmark.

Methods

All enquiries to the DPIC registered in the period 2007–2022 with Greenlandic postal codes were extracted from the database. The extracted data were analysed for demography (age, gender, caller), toxic exposure, treatment and severity of the poisoning using a modification of the Poison Severity Score (PSS).

Results

The annual number of enquiries from Greenland to the DPIC has constantly risen since 2007, and the total number by the end of 2022 was 1827 enquiries over the 16-year period (individual patients). In 2022 0.8% of the total number of enquiries came from Greenland. However, the ratio between the number of enquiries and inhabitants in Greenland and Denmark was the same (4.6 versus 5.6 enquiries per 1000 inhabitants, respectively). The gender distribution showed a M/F ratio of 1:1.46, and the age distribution showed that a majority of the enquiries came from patients in the age group 20–29 years followed by the age groups 0–4 years and 15–19 years. This is clearly different from the pattern in Denmark in which the number of poisonings in the age group 0–4 years is twice as high, and the number of poisonings in the age groups 15–19 years and 20–29 years is only half the number in Greenland. As in Denmark, paracetamol is the most frequently used drug in overdosing, followed by ibuprofen, quetiapine and enalapril. Enalapril is not included on the Danish top ten list. PSS data shows a significantly increased proportion of moderate and life-threatening poisonings in Greenland compared with Denmark (18% versus 36% not or limited poisoned patients and 36% versus 12% moderate or life-threatening poisoned patients; p = 0.0004).

Conclusion

This is the first study of poisonings in Greenland. Compared with Denmark, our data shows that the poisonings are more severe, they more often involve adolescents and young adults, and the patients are to some extent poisoned with other drugs.

142. Not responding: a case of tricyclic antidepressant poisoning refractory to initial sodium bicarbonate therapy

Abstract

Objective

Tricyclic antidepressants (TCA) are prescribed for several conditions including major depressive disorder, and neuropathic pain. Often, electrocardiographic (EKG) changes associated with TCA toxicity improve after a 1–2 mEq/kg bolus of sodium bicarbonate (SB). We present a TCA overdose case where EKG changes were refractory to initial SB therapy.

Case report

A 41-year-old female was brought into an Emergency Department (ED) after being found unresponsive. The patient’s partner administered naloxone prehospital, which improved her mental status. Twenty tablets of nortriptyline and multiple olanzapine tablets were missing from her pill bottles, she also reported using cocaine and heroin prior to arrival. The patient arrived agitated, was given lorazepam, and subsequently intubated. Vital signs post-intubation were: heart rate 120 beats/minute, blood pressure 152/90 mmHg, temperature afebrile, oxygen saturation 97% on ventilator, and respiratory rate 16 breaths/minute. Prior to intubation, the patient had dilated reactive pupils, tachycardia, tachypnea with wheezing bilaterally, and a non-focal neurological exam. Initial labs showed a pH of 7.32, pCO₂ 46 mmHg, and lactate 4.7 mmol/L. Initial EKG showed a QRS of 200 ms and QTc of 385 ms. Subsequently, a 1 mEq/kg bolus of SB was given followed by an SB drip at 150 mEq/hour. A repeat EKG showed a QRS of 206 ms and QTc of 673 ms. A prior EKG displayed normal sinus rhythm with normal intervals. The patient received gastric lavage and activated charcoal, had a normal echocardiogram, and was transferred to an extracorporeal membrane oxygenation (ECMO) center. There, the patient received two 150 mEq SB boluses and the sodium bicarbonate drip was continued until hospital day 4 without improvement. Repeat labs showed a pH of 7.5 and serum bicarbonate of 30 mEq/L. By day 6, the QRS and QTc normalized. On Day 9 of her stay, the patient was extubated. She was discharged on Day 14. The patient’s serum nortriptyline concentration from hospital Day 1 was 945.0 ng/mL.

Conclusion

Although SB is integral in managing TCA poisoning, providing excessive SB may not improve patient outcomes in a hemodynamically stable patient, as in our case, the patient’s QRS did not respond to SB and narrowed only after SB was discontinued for 2 days. In this case other factors may have contributed to the abnormal QRS, including co-ingestants like cocaine, or intrinsic cardiac disease. In a hemodynamically stable TCA toxic patient with a wide QRS that is not responding to initial boluses of SB, repeated SB boluses and drip may be of low utility.

143. Severe atypical antipsychotic poisonings in the intensive care unit: clinical presentation, management and outcome

Abstract

Objective

Atypical antipsychotic drugs (AAD) are increasingly used to treat patients with various psychiatric diseases at risk of suicide. AAD marketing was supported by the hypothesis of a reduced toxic risk in overdose in comparison with the first-generation neuroleptics. Our aim was to report features of severely AAD-overdosed patients and to identify the predictive factors of mechanical intubation requirement.

Methods

We conducted a single-center retrospective observational study including all AAD-poisoned patients admitted during the last 5 years (2017–2022). Diagnosis was based on a compatible history, clinical presentation, and plasma AAD concentration in the toxic range on intensive care unit (ICU) admission. Data are expressed as percentages or median [percentiles]. Univariate comparisons were performed using chi-squared and Mann-Whitney tests, as requested.

Results

Sixty-four intoxicated patients (45 years [29–53]; 27M (42%)/37F (58%); Sequential Organ Failure Assessment (SOFA) score 4 [1–6]; Simplified Acute Physiology Score (SAPS) II score, 38 [29–51]) were included. Exposure resulted from suicidal ingestion except in two cases of unintentional overdose due to drug-drug interactions. Involved AADs were quetiapine (61%), risperidone (17%), olanzapine (14%), aripiprazole (6%), and clozapine (2%). On admission, patients presented Glasgow Coma Score (GCS) 11 [6–14], agitation (11%), confusion (13%), seizures (2%), hypotonic (23%) versus hypertonic (3%) presentation, mydriasis (14%) versus miosis (34%), and vomiting (2%). No prolongation of QRS complex on the electrocardiogram was observed. Intoxication resulted from a multidrug ingestion (87%) including benzodiazepines (36%), antidepressants (25%), ethanol (19%; blood concentration 0.74 g/L [0.26–1.15]), ZZ drugs (15%), and anticonvulsive drugs (3%). Complications included aspiration pneumonia (13%) and ventricular arrhythmia (2%). Management was based on activated charcoal (39%), mechanical ventilation (48%), vasopressors (20%), and hemodialysis (2%). No patient died and ICU stay length was 4 days [2–5]. Mechanical ventilation was significantly related to the coma depth (p < 0.001), blood bicarbonate concentration (p = 0.01), arterial pH (p = 0.05), and vasopressor infusion (p = 0.05).

Conclusion

Despite increased safety in comparison to the first-generation neuroleptics, AAD poisoning may lead to ICU admission. Mechanical ventilation is required in neurorespiratory and hemodynamic failure. Outcome is favorable if adequately managed in the ICU.

144. Metformin-associated/-induced lactic acidosis accompanied with hyperammonemia: a retrospective case series

Abstract

Objective

It is known that metabolic acidosis results in a net negative ammonia balance [1]. In diabetic cirrhotic patients, metformin use is associated with a decreased risk of hepatic encephalopathy, which might be related to the partial inhibiting effect of metformin on glutaminase activity [2]. We offer a case series of metformin-associated/-induced lactic acidosis (MALA/MILA) with hyperammonemia.

Case series

Three patients registered in the Taiwan Poison Control Centre were retrieved. The inclusion criteria are confirmed or clinically diagnosed MALA/MILA with hyperammonemia (ammonia >100 µg/dL). All the patients are reported from a single medical centre. None of the patients are recorded with any seizure episode or history of liver cirrhosis. Relevant lab data are summarised in the table.

Conclusion

MALA/MILA might be accompanied by hyperammonemia. In patients with MALA/MILA, the prevalence, outcome, and mechanism of hyperammonemia are pending further investigation.

Table 1 Summary of laboratory findings and treatment in three patients with metformin-associated/-induced lactic acidosis with hyperammonemia.

		Case A	Case B	Case C
Age		83	78	64
Gender		M	F	F
Metformin (history)		(+)	(+)	(+)^a
Metformin (serum)	mg/L	58.6	N/A	46.5
Sodium	mmol/L	134	129	135
Potassium	mmol/L	5.5	6.4	3.8
Chloride	mmol/L	85	96	83
Lactate	mg/dL	203.7	135.5	292
Bicarbonate	mmol/L	1.6	3.5	3.1
pH		6.818	6.734	6.917
Blood urea nitrogen (BUN)	mg/dL	62	88	43
Creatinine	mg/dL	5.15	9.97	3.72
Creatine kinase	U/L	115	48	1092
Alanine aminotransferase (ALT)	U/L	10	20	16
Total bilirubin	mg/dL	0.26	0.19	0.23
Ammonia	µg/dL	820	113	406
Glasgow Coma Score (GCS)		E4V4M5	E1V2M5	E4V5M6
Shock [3]		Yes	Yes	Yes
Extracorporeal treatment		CVVH	CVVHDF	CVVHDF

^aConfirmed with urine qualitative analysis. CVVH: continuous veno-venous hemofiltration; CVVHDF: continuous venovenous hemodiafiltration.

145. Massive warfarin self-poisoning: case report

Abstract

Objective: Although guidelines in the setting of a supratherapeutic International Normalized Ratio (INR) exist there are limited data about the approach for massive intentional warfarin overdose. We describe a case of massive acute warfarin ingestion (750 mg) with laboratory warfarin concentrations treated conservatively with phytomenadione (vitamin K₁).

Case report: An 84-year-old woman without previous history of psychiatric disease was admitted about 3 h after ingesting 750 mg of warfarin (150 tablets of warfarin 5 mg) in a suicide attempt. The patient had a past medical history significant for myocardial infarction, hypertension and diabetes mellitus. Warfarin was prescribed medication but she refused to use it. She clearly reported that she had collected and stored pills for suicide. On admission, she was alert, communicative, afebrile, mobile without signs of bleeding, heart rate 85/min, blood pressure 160/70 mmHg and SaO₂ 94%. Electrocardiogram (ECG) revealed first-degree atrioventricular block without other abnormalities. Owing to the ingested dose and the patient's condition, despite the time elapsed since exposure, gastric lavage was performed and single-dose activated charcoal was ordered. Suspicious tablet residues were seen in the gastric content. Warfarin blood concentration on admission was 119.10 mg/L and warfarin was confirmed in gastric content. Initial INR was 1.04, haemoglobin was 120 g/L, with normal renal and liver function parameters. Both INR and warfarin concentrations were regularly monitored and phytomenadione was administered intravenously according to the INR value and its trend (Table 1). There were no symptoms or signs of bleeding during the hospitalisation. Patient was discharged on day 14 with instruction for INR control in the following days.

Table 1 Daily INR, warfarin concentrations and phytomenadione doses in a patient following massive warfarin overdose.

Parameter	Day
	Admission	2	3	4	5	6	7	8	9	10	11	12
INR	1.04	1.12	4.41	6.11	8.84	1.52	6.1	5.22	>10	8.95	6.19	1.26
Warfarin blood concentration (mg/L)	119.10	68.63		14.23	19.8	13.34		7.31		5.16	2.05	4.45
Phytomenadione dose (mg)				5	10		5		10	10

Conclusion: Massive warfarin overdose could have a prolonged course due to warfarin's long half-life and unpredictable individual variability. Treatment of this condition in non-bleeding patients could be conservative with multiple doses of intravenous phytomenadione, but the patient's INR must be closely monitored, because of rebound increase risk.

146. Cardiovascular effects of high-dose insulin therapy: a randomised clinical trial

Abstract

Objective

High-dose insulin/glucose therapy (HIT) has gained interest as a treatment modality in severe overdoses with calcium-channel blockers and beta-adrenergic antagonists. Hemodynamic changes to insulin in these extreme supraphysiological doses have never been systematically studied in humans. HIT was investigated in a randomized controlled trial with blinded outcome assessment, and, as the primary endpoint, followed cardiac output from baseline, during and after 2 h of HIT with or without concomitant infusion of a beta-adrenergic antagonist.

Methods

A randomized, crossover, trial in 10 healthy male participants treated with a 2-h infusion of high-dose insulin (10 IU/kg/h) or placebo combined with intravenously administered a beta-adrenergic antagonist (esmolol infusion 0.25 mg/kg/min) or placebo on four separate days (EudraCT number: 2017-002553-11). We measured hemodynamics continuously with invasive arterial line and performed transthoracic echocardiogram (TTE) at specified timepoints during the trial days. TTE was measured in apical 4 chamber and 2 chamber view (iVenue, 12S probe, GE HealthCare) and analyses after end of trial in a blinded manner (GE EchoPAC Software). The primary endpoint was change in 4 chamber cardiac output from time 0 min to 120 min.

Results

Compared to placebo cardiac output increased significantly more from baseline on insulin-esmolol days (44.5% [95% CI: 20.8–72.9%] versus placebo-esmolol, p = 0.0007) and insulin-placebo days (31.7% [95% CI: 10.8–56.1%] versus placebo-placebo, p = 0.0040). Both heart rate and ejection fraction increased during the insulin days.

Conclusion

High-dose insulin infusion significantly increased cardiac output from baseline in healthy individuals compared to placebo.

147. Increase in tramadol poisonings in Denmark: a new misuse trend in adolescents

Abstract

Objective

Tramadol, a synthetic opioid analgesic, primarily exerts its effects through the metabolite O-desmethyltramadol, which has a higher affinity for the μ-opioid receptor compared to the parent compound. Additionally, tramadol is well-known for its role as a serotonin reuptake inhibitor. In Denmark, the overall use of tramadol increased two-fold from 2001 to 2013. Media coverage in 2017 prompted regulatory interventions, leading to a subsequent decline in tramadol consumption in the population. However, in recent years, concerns have been raised regarding opioid misuse among young Danish individuals, particularly tramadol. This study aimed to examine poisoning patterns and shifts in tramadol-related inquiries to the Danish Poisons Information Centre (DPIC), focusing on age distribution and the reasons for exposure.

Methods

We conducted a retrospective analysis of tramadol exposures reported to the DPIC from 2007 to 2022, including demographics, ingested dose, and symptoms. Data were extracted from the DPIC database.

Results

Covering a 16-year period, there were 3468 cases of tramadol-related inquiries to the DPIC, accounting for 1.0% out of a total of 341,000 inquiries. The proportion of tramadol-related inquiries increased from 0.6% in 2007 to 1.2% in 2014–2015, before gradually declining until 2020. However, a marked rise occurred in 2021 with an observed 49% increase in inquiries during 2021 and 2022. This increase was primarily due to tramadol exposures among individuals aged 15–24 years. In 2021–2022, tramadol exposures quadrupled among adolescents (aged 15–19), constituting 25% of all tramadol inquiries. Notably, in these young individuals, seizures resulting from misuse were a frequent reason for contacting the DPIC.

Conclusion

The substantial rise in tramadol-related inquiries to the DPIC among young individuals raises concerns about an increasing trend of tramadol misuse in the Danish youth population. Considering these findings, a multi-disciplinary approach involving clinicians, educators, and policymakers is urgently needed to address the escalating trend of tramadol misuse among Danish adolescents.

148. Pharmacovigilance of therapeutic errors: a retrospective analysis of data from a single poison centre

Abstract

Objective

Medication errors (MEs) have a great impact on health and public expense. Poison Control Centers (PCCs) provide therapeutic indications to the general public or hospitals about MEs and collect useful data to plan preventive strategies such as modification of the packaging or product recalls.

Methods

In the period between 1 January 2018 to 30 April 2023, a total 16,543 human cases of therapeutic errors that required the consultation of an Italian Poison Control Center were analyzed and follow-up calls were performed. Data about age, gender, active ingredients, dosage, cause of medical errors, and clinical outcome according to the Poisoning Severity Score (PSS) were obtained from patients’ medical records. Additional information was retrieved during a follow-up phase.

Results

In the study period a total 16,543 human therapeutic error cases were collected. Respectively: in 2018 (n = 3540), in 2019 (n = 3548), in 2020 (n = 2507), in 2021 (n = 2567), in 2022 (n = 3120), in 2023 up to April (n = 1261). The call site was from home in 65.4%, hospital in 18.5% and in 16.1% from other sites. Overall 9008 (54.5%) were female, 7324 (44.3%) males, and gender unknown in 211 (1.3%) cases. The age distribution was 0–4 years (n = 5725, 34.6%), 5–14 years (n = 2680, 16.2%), 15–39 years (n = 1451, 8.8%), 40–59 years (n = 1992, 12%), 60–79 years (n = 2852, 17.2%), > 80 years (n = 1434, 8.6%), and age unknown in 108 cases (0.6%). Exposure occurred mainly as a result of ingestion alone (n = 14196, 85.8%); other routes were rectal (n = 592, 3.6%), inhalation (n = 328, 2%), eye contact alone (n = 242, 1.5%) and skin contact alone (n = 25, 0.15%). The typology of ME was a dosage error in 9460 (57.2%) cases, wrong drug in 5829 (35.2%), wrong route of administration in 836 (5.1%), expired drug in 416 (2.5%), and not specified in 4 cases (0.02%). The most frequently involved drugs were acetaminophen, amoxicillin/clavulanate, cholecalciferol and ibuprofen. Overall, the most frequently reported clinical effects were vomiting, diarrhoea, irritation, tachycardia, hypotension and drowsiness. Most patients (83.3%) were asymptomatic, whereas the severity of the symptoms was mild in 9.8%, moderate in 3.7%, severe in 0.6% and not evaluated in 2.6%.

Conclusion

Monitoring therapeutic errors is important in order to avoid preventable mistakes. Children and people over sixty age are most commonly involved. The majority of the errors involved the wrong dosage. Non-steroidal anti-inflammatories and pain relievers were the most frequently involved drugs. This data provided an effective characterization and monitoring of the risks connected with the use of drugs by a single poison centre.

149. Angiotensin converting enzyme (ACE) inhibitor-induced angioedema: a case report from Pavia emergency department and Poison Centre

Abstract

Objective

ACE inhibitor-induced angioedema (ACEi-AE) is a local increased microvascular permeability, caused by inhibition of bradykinin metabolism induced by these antihypertensive drugs. The onset of this adverse reaction (ADR) can develop from days to years after starting therapy, and it may recur if ACE-inhibitor administration is not suspended. ACEi-AE particularly affects the tongue, lips and larynx, causing breathing difficulties, and can progress to airway obstruction. Symptoms develop over several hours and, if untreated, may last up to 48–72 h. Approved protocols for therapy are still lacking; first line strategies, including airway management, steroids, antihistamine and adrenaline, may not be effective. Recently proposed specific therapies are tranexamic acid (as upstream inhibitor of bradykinin activation), and bradykinin B2-receptor antagonist (e.g., icatibant), even if their efficacy is still debated.

Case report

A 76-year-old woman woke up with pronounced lip and tongue oedema. She did not have an allergic history nor recent therapy changes. In the prehospital setting, adrenaline, steroids and tranexamic acid were administered by the emergency staff, without improvement. At emergency department (ED) admission, the patient presented macroglossia, oedema of lips and neck tissues, and dyspnoea with mild oxygen desaturation. She reported perindopril and amlodipine therapy for 3 years. Based on anamnestic data and clinical presentation, the clinical toxicologists hypothesised an ACEi-AE, therefore icatibant (30 mg subcutaneous injection) was administered, with recommendation for another dose after 6 h. Twenty minutes after injection, the swelling decreased and oxygen saturation values stabilized (from 95% to 99%). The patient herself reported an improvement in breathing. After six hours the oedema was visibly reduced, hence the second icatibant injection was not administered. The patient was discharged the following day, with the indication to stop the administration of perindopril and change antihypertensive therapy. At outpatient clinical toxicological follow-up, haematochemical blood tests were performed in order to exclude hereditary angioedema or autoimmune disorders: C1-INH, C3, C4 fell within the physiological range, so the diagnosis of ACEi-AE was confirmed.

Conclusion

The pharmacological history and symptoms of the patient were highly suggestive for an ACEi-AE. In these cases, a first line approach should guarantee the airway patency, even with intubation, if needed. Then, considering the underlying mechanism of triggering of bradykinin B2-receptor, it is necessary to evaluate specific treatment with icatibant in order to antagonize the activation of B2-receptor. In the current case report, a single administration of icatibant was effective and safe.

150. Pregabalin-poisoned patients admitted to the emergency department: an observational cohort study and analysis of the prognostic contribution of the plasma concentration on admission

Abstract

Objective

Pregabalin misuse is a growing public health issue in Europe, mainly in the population of unaccompanied North African minor migrants. Whether pregabalin alone is responsible for respiratory depression in addition to coma or whether opioid or benzodiazepine co-exposure is required is unclear. Our aims were to describe the presentation of pregabalin poisoned patients; to analyze neurorespiratory depression in the presence or not of benzodiazepine/opioid co-exposure; and to investigate the contribution of plasma pregabalin concentration to evaluate severity.

Methods

We conducted a two-center retrospective observational study including all pregabalin poisoned patients admitted to the emergency department during the last 5 years (2017–2022). Diagnosis was based on a compatible history, presentation, and plasma pregabalin concentration in the toxic range. Data are expressed as percentages or medians [percentiles]. Univariate comparisons were performed using chi-squared and Mann-Whitney tests. Correlations between pregabalin concentrations and readily available surrogate parameters of respiratory depression were tested using Bartlett's tests of sphericity.

Results

Overall 168 pregabalin-intoxicated patients (25 years [20–38]; 142M (85%)/26F) were included. Patients were from Maghreb origin (71%) or Caucasians (25%). Exposure resulted from a recreational (92%) or suicidal use (8%). Patients were illicit drug users (63%), ethanol drinkers (30%), and presented depression (15%) or personality disorders (23%). Presentation included consciousness impairment (89%; Glasgow Coma Score (GCS) 7 [5–13]), agitation (19%), seizures (6%), headaches (3%), and vomiting (3%). Physical examination showed myorelaxation (9%), miosis (40%)/mydriasis (8%), and pyramidal syndrome (1%). Plasma pregabalin concentration on admission was 6200 ng/mL [3500–12,798]. Management included mechanical ventilation (26%; duration, 24h [15–26]), charcoal (7%), naloxone (12%) flumazenil (12%), and flumazenil + naloxone (12%). Complications included aspiration pneumonia (18%). Outcome was favorable except for two deaths. Patients were discharged (64%), sent to prison (9%), referred to the medical (7%) or psychiatric ward (5%) or escaped from hospital (14%). There were no significant correlations on admission between plasma pregabalin concentration and GCS, respiratory rate, PaCO₂, PaO₂/FiO₂, intubation requirement, and duration of mechanical ventilation. Severity of neurorespiratory depression and plasma pregabalin concentration did not significantly differ between patients exposed to pregabalin alone and patients exposed to pregabalin + benzodiazepines or opioids, except for a higher rate of ventilation in the patients co-exposed to opioids (p = 0.016).

Conclusion

Despite its recognized safety, pregabalin poisoning may lead to neurorespiratory depression, even if no opioid or benzodiazepine is co-used. Outcome is usually favorable. Plasma pregabalin concentration does not predict the severity of neurorespiratory depression due to multifactorial interindividual variability.

151. A case of tacrolimus intoxication due to the COVID-19 antiviral nirmatrelvir/ritonavir (Paxlovid^®)

Abstract

Objective

The COVID-19 antiviral, nirmatrelvir/ritonavir (Paxlovid^®), is given as a 5-day course to patients at high risk of progression to severe disease without requirement for supplemental oxygen. Ritonavir, a potent inhibitor of cytochrome P450 (CYP) 3A, is used to boost oral bioavailability of the protease inhibitor nirmatrelvir. Increased exposure of concomitantly administered CYP3A substrates with a narrow therapeutic window may lead to serious adverse drug interactions with this novel medication. We report a case of tacrolimus intoxication due to concomitant use of nirmatrelvir/ritonavir.

Case report

A 53-year-old kidney transplant patient with COVID-19 (Ct-value 33.31) was hospitalized due to severe diarrhea (up to 15 stools per day), vomiting, and tremor. The patient had received nirmatrelvir/ritonavir 300 mg/100 mg for 4 days prior to admission. Her immunosuppressive therapy included oral tacrolimus 3 mg twice daily, mycophenolic acid 720 mg twice daily, and methylprednisolone 4 mg/day. On admission, the plasma concentration of tacrolimus was 132.6 µg/L (target range 4–6 µg/L). The lab results revealed abnormal liver biochemistry (serum alanine aminotransferase 3 × upper limit of normal). Tacrolimus, mycophenolic acid and nirmatrelvir/ritonavir were stopped, and the patient was treated with loperamide, metoclopramide, and intravenous fluid. On the fifth day of drug withdrawal, the tacrolimus trough concentration was at 17 µg/L. The patient was discharged from hospital. A clear instruction was given, not to restart tacrolimus before reaching the target range. These results indicate a serious adverse drug interaction. The magnitude of tacrolimus intoxication was demonstrated by plasma concentrations and calculated pharmacokinetic parameters (e.g., mean residence time 55 h).

Conclusion

We recommend close therapeutic drug monitoring and dosage adjustment of tacrolimus in order to avoid over-exposure when combined with nirmatrelvir/ritonavir. In organ transplant recipients, some authors even advocate discontinuation of tacrolimus during treatment with nirmatrelvir/ritonavir [1]. Prescribers of Paxlovid^® should be aware of the extensive warnings in the product information resulting from irreversible CYP3A inhibition.

152. Unusual side effects of cytisine: a case report exploring beyond the common adverse reactions in smoking cessation therapy

Abstract

Objective

Cytisine, derived from Golden Rain (Laburnum anagyroides), is used in Europe as a smoking cessation alternative to varenicline [1]. Its pharmacologic effects involve the partial agonism of α4β2 nicotinic acetylcholine receptors, pivotal in controlling learning and central effects of nicotine. While predominantly safe, common literature-reported side effects include gastrointestinal symptoms, sleep disturbances, and restlessness, which, though self-limiting, can lead to treatment discontinuation [2]. This study presents an intriguing case of a young man experiencing an unanticipated side effect following cytisine intake.

Case report

A 28-year-old male, without prior medical history and medications, was prescribed 1.5 mg cytisine capsules for smoking cessation. The prescribed regimen involved one capsule every 2.5 h for the initial 3 days, followed by a tapered-dose schedule for 22 days. Following the first day of treatment, the patient reported symptoms, including epigastric burning, restlessness, and urinary incontinence. Clinical evaluations revealed a slightly elevated heart rate, but otherwise normal vital signs. The decision was made to discontinue cytisine, leading to the resolution of symptoms within 6 h after the last dose.

Conclusion

Cytisine continues to be an economically viable, safe, and well-tolerated option for smoking cessation. Common adverse reactions can be managed by adjusting the daily dose. While restlessness and gastritis are known cytisine-related side effects, our case suggests a potential involvement of other nicotinic receptors in micturition physiology, potentially attributed to genetic polymorphisms or altered drug elimination. Further comprehensive investigations are warranted to explore alternative pathways of cytisine action, especially concerning unexpected symptoms such as urinary incontinence. This study underscores the necessity for continued exploration and understanding of cytisine's complex pharmacological effects to enhance its clinical utility in smoking cessation therapies.

153. Hyperammonemic encephalopathy and deferasirox therapy. Hoc recolens in corde meo!

Abstract

Objective

Deferasirox (DFR) is an oral iron chelator whose use is preferred over parenterally administered deferoxamine. The adverse reactions reported in pediatrics are vomiting, transaminase increase, fever, diarrhea and hyperammonemia. We report the case of a 16-year-old girl suffering from sickle cell anemia, in chronic therapy with DFR, who developed a severe adverse reaction with hyperammonemic encephalopathy, coma, and Fanconi-type renal proximal tubular damage.

Case report

A 16-year-old patient with sickle cell disease, in therapy with DFR, presented to the emergency department with vomiting and persistent fever for 24 h with sensory decay (Glasgow Coma Score (GCS) 5). She was intubation and admitted to intensive care. A computerised tomography (CT) scan was normal. Blood tests showed hyperchloremic acidosis and rise in C-reactive protein (CRP) (10 mg/dL) and procalcitonin (PCT) (69 ng/mL) with normal neutrophil and lymphocyte count; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 77 and 59 U/L, respectively, INR (2.9), creatinine 2.15 mg/dL, azotemia 31 mg/dL, and renal failure due to Fanconi-type tubulopathy. Elevated plasma ammonium was detected (296.1 μg/dL) and therapy with sodium benzoate and arginine was started. Extensive metabolic studies documented secondary deregulation of urea cycle and mitochondrial respiratory chain. Since the state of coma persisted, continuous replacement therapy was started at the 54th hour after admission. The plasma DFR concentration at admission and at 22, 39, 63, and 77 h was 205, 192, 65, 30 mg/mL (normal range 0.16–40), respectively. The pharmacogenetic study excluded genetic defects of the urea cycle or polymorphism of uridine diphosphate (UDP)-glucuronosyltransferase (UGT), suggesting a diagnosis of hyperammonemic encephalopathy [1]. A progressive clinical improvement followed, with extubation on the fourth day. On the eleventh day, the patient was transferred to the hematology department, clinically stable.

Conclusion

This case shows the potential risk associated with deferasirox therapy. In case of sensory impairment, a possible hyperammonemic encephalopathy should be suspected and excluded by measuring ammonium concentrations and the blood concentration of the drug. Pharmacogenetic studies are indicated to exclude possible polymorphisms, which could cause reduced elimination of the drug. These tests should be performed before the start of therapy with DFR. Our patient showed a severe reaction from accumulation of the drug with multi-organ involvement, without genetic alterations, though the cause that triggered this event was not identified.

154. Severe and acute drug cutaneous adverse reactions (SCARs): how to prevent?

Abstract

Objective

Allopurinol is widely used in the treatment of hyperuricemia, gout and uric acid lithiasis. The correlation between allopurinol and severe cutaneous acute adverse reactions (SCARs) such as Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are reported. Complex genomic and immunopathological mechanisms are involved in developing SCARs, in which the HLA-B*5801 allele is strongly associated. This allele variant is most common among Asian subpopulations, notably in individuals of Korean, Han-Chinese (up to 20%) or Thai descent [1]. HLA-B*5801 screening is suggested before starting treatment with allopurinol (as reported in the leaflet). We describe the SCARs in a Chinese patient treated with allopurinol.

Case report

A 54-year-old Chinese woman was admitted to the emergency department for a generalized severe desquamating erythematous skin rash. Pharmacological history included insulin, bisoprolol, pantoprazole, allopurinol, linezolid, erythropoietin alfa, sodium-zirconium cyclosilicate, calcitriol, sodium bicarbonate, furosemide and a Chinese product named lianhua qingwen (for 2 months, self-medication, based on 12 plant types including 61 active ingredients as polyphenols/terpenes) taken during COVID infection). She was found to have acute renal failure and cholestatic hepatitis with significant transaminases increase. As she belonged to one of the above-reported susceptible ethnic groups, she was screened for the HLA-B*5801 allele and allopurinol administration was stopped, in order to exclude other drug-related causes. The screening tested positive for allele variant HLA-B*5801. She was treated with systemic steroids with improvement of the clinical skin condition and reduction of transaminases and cholestasis indices. Her clinical condition gradually improved and she was discharged one month later.

Conclusion

Despite the association between SCARs and allopurinol being well known, cases of severe cutaneous adverse reactions continue to occur, mainly due to the sporadic availability of HLA-screening. Moreover, the suggested indication to assess the HLA-B*5801 allele variant status is not well known by clinicians. Our case confirms that allopurinol-induced SCAR is associated with a genetic predisposition in Han Chinese sub-population; HLA-B*5801 is an important genetic risk factor for this life-threatening condition. Screening of HLA-B*5801 status should be strongly recommended before starting allopurinol therapy, especially when a subject belongs to a susceptible ethnic group, in order to avoid severe adverse reactions.

155. Vaccine side effects following COVID-19 vaccination and psychological correlates among Italian healthcare professionals

Abstract

Objective

COVID-19 vaccines have proven to be safe in clinical trials; nevertheless, reports of possible adverse reactions have increased and gained public attention. Post-COVID-19 vaccination adverse effect (ADR) and associated psychological factors in terms of vaccine relief, fear of COVID-19, and fear of vaccine side effects have been investigated in this study among healthcare professionals.

Methods

Two questionnaires were administered to 966 healthcare workers undergoing the first COVID-19 vaccine dose (Pfizer). The first one had to be filled out shortly before vaccine administration. Based on previous literature about factors influencing attitudes to vaccination [1,2], the following psychological domains were investigated: (i) fear of COVID-19 infection, (ii) fear of vaccine ADR, (iii) perception of COVID-19 vaccine as a relief. These factors were assessed using three ad-hoc items, asking participants to provide responses on a Likert scale ranging from 1 (not at all) to 4 (very much). In the second questionnaire, to be completed within the first week after vaccine administration, the ADRs experienced were investigated. Correlations, independent sample t-test, ANOVA and chi-square test were employed to study association between variables.

Results

Among the 966 subjects, females reported greater fear of COVID-19 (t = 5.37; p < 0.001) and vaccine side effects (t = 6.46; p <0.001). Individuals >40 years old manifested greater fear of COVID-19 (t = −2.02; p = 0.04) and participants with health problems (t = 2.13; p = 0.03) and receiving chronic therapies (t = 2.19; p = 0.03) showed higher fear of vaccine side effects. Overall 70% of participants declared to have experienced ADRs; the most frequently reported was pain at the injection site, followed by fatigue and headache. The average number of ADRs was 3.18 ± 1.58. Associations were found between side effects and psychological variables. Those who reported a larger number of ADRs was more afraid of COVID-19 (F = 7.67; p < 0.001) and of vaccine ADRs (F = 9.99; p < 0.001). Females (X² = 59; p < 0.001) and participants ≤40 years (X² = 6.27; p = 0.01) reported higher number of ADRs due to the vaccine.

Conclusion

Significant numbers of the respondents experienced side effects post COVID-19 vaccination. Women and younger people were more likely to report symptoms from vaccination. Fear of COVID-19 and fear of vaccine ADRs were associated with symptom reporting.

156. Acute kidney injury and severe gastrointestinal tract necrosis from mercury chloride after a suicide attempt

Abstract

Objective

We report a case of severe poisoning with an unknown amount of oral mercury chloride that responded to aggressive management.

Case report

A 27-year-old male without a somatic disease history but with unstable schizophrenia presented to a university hospital emergency department after a suicide attempt 5 h earlier. He had ingested an unknown quantity of an unknown white powder assumed to be mercury chloride. At the hospital the patient had prominent swelling in the mouth, slurred speech, vomiting, and diarrhea and was sedated for emergency tracheostomy due to respiratory difficulties. The patient had severe necrosis from the mouth to the stomach and a percutaneous endoscopic gastrostomy (PEG) tube was inserted for enteral nutrition. Further clinical effects included severe hemodynamic instability, acute kidney injury (total anuria, plasma creatinine increased to over 900 µmol/L) and acidosis. Chelation therapy with intravenous unithiol (dimercaptopropane sulphonate; DMPS) was started immediately with a loading dose (250 mg ×8/day) and samples for blood mercury concentrations were taken. Hemodialysis was started on the second day and was discontinued on week 4. The patient’s condition began to improve gradually and at the end of the second week he was hemodynamically stable, and diuresis started. After 2 weeks in the intensive care unit the patient was transferred to the nephrology ward. The first results for blood mercury concentration were delayed and were obtained after two weeks; 27,600 nmol/L. On week 5, he was able to start oral nutrition after good mucosal improvement in gastroscopy. The maintenance dose of unithiol was 500 mg/day intravenously which was changed to oral succimer (dimercaptosuccinic acid, DMSA) during week 7. The initial dose was 400 mg twice daily, but was reduced to 200 mg twice a day because of a rise in alanine aminotransferase (ALT) to 279 U/L.

Conclusion

Despite the severe poisoning, the patient’s condition improved and after 2 months his somatic condition was stable, and he was transferred to psychiatric care. Blood mercury concentrations, creatinine concentration and ALT activity were checked weekly and after 2 months of psychiatric care he was discharged.

157. Appropriateness of gastrointestinal decontamination in acute poisoning

Abstract

Objective

To analyze the use of gastrointestinal decontamination techniques (activated charcoal, gastric lavage, and total intestinal lavage) in the management of intoxicated patients in an Emergency Department and evaluate the appropriateness of their use.

Methods

A retrospective observational study based on a clinical record of intoxications in the emergency department. The suitability of each technique was assessed based on the absence of contraindications and specific criteria for their indication [1,2]. Activated charcoal was considered appropriate as a single dose within the first 2 h after ingestion and in multiple doses for drugs with enterohepatic circulation, such as carbamazepine. It was considered inappropriate in cases of reduced consciousness without airway protection, delayed presentation, the need for endoscopy, intestinal obstruction, or non-adsorbable toxins. Gastric lavage was considered appropriate in cases of massive ingestion of potentially lethal and non-adsorbable toxins by activated charcoal (as an exceptional indication) and early presentation (within the first hour) [2].

Results

From January 2022 to August 2023, 1027 intoxications were included in the registry, of which gastrointestinal decontamination was performed in 281 cases (27.4%); 192 patients received activated charcoal and gastric lavage, 85 patients received only activated charcoal, and 4 patients received only gastric lavage. In the 277 cases where activated charcoal was used, its use was deemed inappropriate in 37% (103 patients). The most frequent reasons for inappropriateness were its use in patients with reduced consciousness (38.8%) and its use more than 2 h after ingestion (35.9%). In 14 patients (13.6%), the dosing regimen was incorrect, as repeated doses should have been administered given the characteristics of the involved toxin. Gastric lavage as the sole decontamination measure was considered inappropriate in all cases. No patient underwent total intestinal lavage.

Conclusion

Despite the limitations of this registry-based study, a low percentage of appropriateness (62%) was observed in our setting, which is far from the recommended quality indicators for the urgent care of patients with acute intoxications (CALITOX-2006) [1]. This emphasizes the need for Emergency Departments to have the support of multidisciplinary clinical toxicology units that improve the care of intoxicated patients, participate in training, and the development of audit and research projects.

158. Feasibility of implementing a gastric point-of-care ultrasound course for junior residents to aid decision in gastric lavage

Abstract

Objective

Gastric lavage (GL) may have fallen out of favor in the last two decades but can still be indicated in potentially life-threatening ingestion of a toxic substance that is not well adsorbed by activated charcoal with a significant amount still present in the stomach [1,2]. Bedside ultrasound can play a role in decision making for gastric lavage especially if it detects large number of pills in the stomach [3]. This study aims to explore the feasibility of teaching junior residents the acquisition and interpretation of gastric ultrasound images for gastric lavage in a specially designed course as part of their ultrasound curriculum.

Methods

Ten first- and second-year junior residents posted to the emergency medicine department participated in the study. All were novices in the use of the ultrasound. The training was part of a half day ultrasound course (cardiac and abdomen) with 15 min of lecture dedicated in covering the theory of gastric ultrasound and hands-on training on 6 volunteers.

Results

Two of the 10 (20%) residents were able to demonstrate the gastric view on all 4 volunteers in the 2-min per station test; 40%, 30% and 10% managed to obtain satisfactory view in 3, 2 and 1 volunteers, respectively. Only 3 out of 10 residents were confident of performing a gastric ultrasound after the course and none of them was confident on determining if gastric lavage was indicated on ultrasound in a post-course survey.

Conclusion

Gastric ultrasound is technically challenging making it a difficult tool for determining the presence of pills in the hands of less experienced individuals. Interpretation of the gastric ultrasound images is also difficult in the presence of food or lack of water in the stomach. Despite the availability of ultrasound machines and emergency physicians being more adept at performing point-of-care ultrasound, the widespread utilization for this application may be limited due to its learning curve.

159. How to prevent accidents with chlorine-containing products for swimming pools

Abstract

Objective: Our Poisons Information Center (PIC) is consulted approximately 120 times per year on accidental exposure of humans and animals to chlorine-containing products for swimming pools, such as chlorine tablets and chlorine granules. Most exposures occur in summer, when temporary swimming pools are set up in private gardens. Reported symptoms range from mild (e.g., mucosal irritation, gastrointestinal symptoms) to serious (e.g., dyspnea, chest pain, unconsciousness), with inhalation more often leading to serious symptoms than ingestion. The objective of this study was to gain insight into the circumstances of these exposures, with the aim to prevent these exposures in the future.

Methods: Enquiries to the PIC in 2022 involving exposure to chlorine tablets or chlorine granules were selected from the database. Corresponding telephone recordings were replayed, and data on patient characteristics and exposure circumstances were retrospectively analyzed.

Results: In 2022, 131 exposures were reported; 86% of these concerned chlorine tablets and 14% chlorine granules. Most cases concerned either accidental ingestion of chlorine tablets/granules by young children (n = 47) or inhalation of chlorine vapor by adults (n = 34). These two scenarios were investigated in more detail.

Ingestion by young children (n = 47): The circumstances of exposure were known in 21 cases of ingestion of chlorine tablets/granules by young children (0–4 years old). In the remaining cases, it was not known how the child obtained the product. Chlorine tablets are often placed in pools in so-called chlorine floaters, from which the chlorine tablet slowly dissolves into the water. In 10 cases (48% of cases with known circumstances) children took a chlorine tablet from a chlorine floater. In 6 cases children removed chlorine tablets/granules from the original container. In the remaining cases (n = 5), children ingested a loose chlorine tablet or drank water in which a chlorine tablet was dissolved. Inhalation by adults (n = 34): In 22 cases (65%) of inhalation of chlorine vapor by adults, the exposure occurred while opening a container of chlorine tablets/granules. Sometimes exposure was the result of a broken container or dropping a container (n = 3), or of adding too much chlorine to the pool (n = 2). In the remaining cases (n = 7) the scenarios were diverse or unknown.

Conclusion: Child-proofing chlorine floaters and improving the child-safety of containers could reduce the number of accidental ingestions in young children. In addition, packaging chlorine tablets individually in (water-soluble or non-water-soluble) film could prevent most inhalatory exposures of adults, by preventing dust or vapor formation in the container.

160. Long symptom duration following chloramine gas exposure: a call-back study

Abstract

Objective

Exposure to toxic chloramine gases, formed when ammonia is mixed with hypochlorite-containing products, leads to a range of respiratory symptoms [1]. At low concentrations, a short exposure results in mild respiratory tract irritation. In contrast, at higher concentrations and longer exposure time, the exposure can cause corrosive effects and significant cellular injury of the respiratory tract. Only a few studies have been published on household exposures to chloramine. In a previous study, most patients experienced a resolution of symptoms within 6 h after exposure [2]. In this study, we aim to describe the course of the poisoning and the symptoms after chloramine gas exposure resulting from mixing household cleaners.

Methods

A retrospective study on symptomatic patients exposed to chloramine gas resulting from mixing household cleaners containing ammonia and bleach reported to the Norwegian Poisons Information Centre in the period from 4 June 2020 to 21 September 2022 was performed. Data on types of symptoms and onset, peak, and duration of symptoms, were collected by telephone interview using a standardized questionnaire. Results are presented as median (5–95th percentiles).

Results

Eighty-two patients were included in the study. The age range was 17 to 76 years (median 35 years), and 59 (72%) were female. Median exposure time was 0.6 h (0–10 h). The most frequently reported symptoms were cough (78%), and nasal (61%) and ocular (60%) irritation. The symptoms manifested almost immediately and within 2 min. The peak of symptoms was reported at a median of 5.5 h post-exposure (0–24 h). The median duration of symptoms was 48 h (2.5 h–14 days).

Conclusion

The duration of symptoms after chloramine gas exposure was considerably longer than previously reported. Our findings highlight the need for healthcare professionals to be aware of the potential for prolonged symptoms following chloramine gas exposure and to provide appropriate medical guidance.

161. “The pink-blue roulette”: repeated suicidal attempts with antifreeze among young women in Denmark

Abstract

Objective

To report a case series of repeated suicidal attempt by ingestion of antifreeze illustrating the diagnostic and therapeutic challenges of ethylene glycol poisoning in Denmark.

Case series

Between March and September 2023, the Danish Poison Information Center (DPIC) received 18 calls regarding two 18-year-old women, who attempted suicide by ingestion or intravenous/subcutaneous injection of antifreeze. This is a substantial increase in the number of cases of intentional ingestion of antifreeze reported to the DPIC (average of 10 cases per year). In 15 out of 18 times they presented at the hospital with severe metabolic acidosis and increased lactate requiring intensive care treatment and administration of antidote (fomepizole). Both women had several previous cases of contact with the DPIC due to suicidal attempts with painkillers, contraceptive, antipsychotics and antidepressants. We do not know the reason why they changed their intentional poisonings from medication to antifreeze. It is possible that the women know each other and/or they have been influenced by social networking promoting suicide by ingestion of antifreeze [1], but so far we could not confirm these hypotheses.

Conclusion

As it is not possible to measure blood concentrations of ethylene glycol in Denmark the indication for antidote is based on the patient’s own information or on the suspicion of ingestion of antifreeze. Furthermore, the duration of treatment is determined by repeated arterial blood gasses within 12–24 h after pausing fomepizole administration. These factors impose a risk of unnecessary or delayed and suboptimal treatment. The DPIC is therefore working with the Department of Clinical Biochemistry, Bispebjerg University Hospital – Copenhagen to implement the analysis of blood concentrations of ethylene glycol 24/7 and to make it available for all hospitals in the country.

162. My vision is blurry but I'm thirsty: a case report of accidental caustic ingestion

Abstract

Objective

Sodium hydroxide (caustic soda, lye) is highly alkaline (pH 12–14). Caustic substances are common ingredients in industrial and household products such as drain cleaners [1] and ingestion causes tissue injury. In adults, ingestion may be related to suicidal behaviour, or accidental poisoning while intoxicated. We report a patient who suffered significant gastrointestinal burns from accidental ingestion.

Case report

A 34-year-old male presented to the Emergency Department (ED) complaining of throat and abdominal pain, tongue swelling and difficulty breathing. He reported he was drinking alcohol and accidentally missed the bottle and drank cleaning detergent containing sodium hydroxide. Initially, he drank a liter of water and baking soda solution, which caused severe vomiting. After a few hours, he began to have difficulties breathing due to tongue and throat swelling. On examination, he was awake, with hoarse voice; SpO₂ was 97% (room air), respiratory rate 13/min, BP 141/82 mmHg, HR 107/minute. Edemic lips and tongue with bloody oral secretions were visible. Laboratory results showed leucocytosis, elevated lactate, and a blood alcohol concentration of 3.56 g/L. Corticosteroids and NSAIDs were administered and he was intubated with fibrobronchoscopy. Esophagogastroduodenoscopy demonstrated diffusely inflamed oesophageal mucosa with diffuse ulceration and necrosis throughout the entire oesophagus (Zargar 2b), and necrotic areas in the lower third and the posterior wall of the stomach (Zargar 3a). He was hospitalized in Toxicology ICU where treatment with intravenous antibiotics was initiated. He was ventilated for 7 days and then a tracheostomy was performed. After 28 days of parenteral nutrition, a nasoduodenal feeding tube was placed. Owing to oesophageal obstruction, the first attempt of tube placement was unsuccessful, and was performed under general anaesthesia. After 35 days in the ICU, he was transferred to the Toxicology Department. On the day of transfer, a second esophagogastroduodenoscopy showed partial oesophageal obstruction and bougie dilation for widening oesophageal strictures was suggested. After 40 days of hospitalization, he was discharged but then lost to follow up.

Conclusion

This case highlights the severe and life-threatening consequences of accidental sodium hydroxide ingestion. Prompt and aggressive medical intervention is crucial in managing such a case. This case underscores the importance of caution and safety when handling caustic substances and the need for rapid and comprehensive medical management in cases of caustic ingestions, especially those involving sodium hydroxide. Most surviving patients need long-term oesophageal stricture treatment.

163. Change of quality of life in patients with chronic pain with prescription opioid usage after opioid detoxification

Abstract

Objective

Long-term use of opioids for pain management leads to a range of adverse effects, including tolerance, dependence, significant societal costs, and a decline in overall quality of life (QoL) [1]. Despite these challenges, there is limited research on detoxification and its impact on the QoL for patients dependent on prescription opioids. This clinical study aimed to investigate the hypothesis that detoxification treatment can enhance the QoL for patients who are dependent on prescription opioids for chronic pain management and detoxification’s impact on pain scores.

Methods

This 2019–2023 study (study protocol approved by the Regional Bioethics committee license no. 2019/10-1153-644) included 45 patients who underwent elective detoxification from prescription opioids at the Toxicology Center of the Republican Vilnius University Hospital in Lithuania. In 41/45 cases detoxification was completed. QoL was assessed with SF-36v2™ questionnaires before detoxification, on the day of discharge, and remotely at least 6 months after detoxification. Visual Analogue Scale (VAS) pain scores were assessed before and after the detoxification. Full follow-up after the treatment was completed in 30/45 cases.

Results

There was a statistically significant difference between the estimates of the first and second SF-36v2™ questionnaires (p = 0.004) and between the first and third questionnaires (p < 0.001) and between the second and third questionnaires (p = 0.025). There was a statistically significant difference between VAS pain scores before and after detoxification (p < 0.001): VAS before detoxification is 6.57 [1–9] points. VAS after detoxification 2.17 [0–8] points.

Conclusion

After opioid detoxification, the majority of patients with chronic pain were observed to have QoL improvement (I 35 ± 14%; II 42 ± 19%; III 48 ± 22%), significant pain reduction (down 4.4 points on average) and opioid usage cessation (41/45 patients (91.1%). This leads us to believe that such a treatment can be safely administered and appropriate.

164. Digoxin-related BRASH syndrome: a case report

Abstract

Objective: BRASH syndrome is a combination of Bradycardia, Renal failure, AV node blockade, Shock, Hyperkalemia and is usually self-propagating in a vicious circle [1]. We present a case where the cause of this relatively new and underdiagnosed syndrome were related to digoxin accumulation.

Case report: A 66-year-old woman in treatment with digoxin, bisoprolol, ramipril, spironolactone and furosemide, presented to the emergency department complaining of worsening fatigue in the past 4 days.

She had a history of hypertension, atrial fibrillation, pulmonary hypertension, hepatic cirrhosis, and ascites from congestive hepatopathy. In the Emergency Department she appeared mottled, hypotensive, bradyarrhythmic, dyspnoeic and confused. She claimed to be anuric for 3 days. Arterial blood gas analysis revealed metabolic acidosis (pH 7.10) and severe hyperkalemia (8.9 mmol/L). On the first electrocardiogram (EKG) there was junctional bradycardia with ST changes consistent with digoxin toxicity. She was immediately started on specific treatment for hyperkalemia and an isoprenaline infusion. Transcutaneous pacing was implemented and the case was discussed with the poison control specialist as well as the nephrologist and intensive care physician. Laboratory test results were not still available, so she was treated empirically with Digifab^® 40 mg 2 vials for persistent bradycardia. No effect was elicited but later the laboratory revealed a digoxin value of 13.7 µg/L so another 5 vials of Digifab^® were administered. The potassium remained high (9.3 mmol/L) despite specific treatment and the digoxin antidote. A computerised tomography (CT) scan revealed a lung consolidation, pleural effusion and ascites. The patient was admitted to the Intensive Care Unit and started on continuous venovenous hemodiafiltration (CVVHDF). Ampicillin-sulbactam was administered for pneumonia. The serum potassium concentration improved over the following day (4.96 mmol/L), but serum digoxin slowly decreased to 1.36 µg/L in 14 days. The EKG slowly normalized to her baseline simultaneously with serum potassium. She started to urinate again with diuretic stimulation and she was later discharged at home with dialysis sessions twice a week, which she has stopped to date due to improved renal function.

Conclusion: BRASH syndrome is an underdiagnosed life-threatening condition due to the synergism between renal impairment and accumulation of AV nodal blocking medications. It requires prompt recognition and multidisciplinary management in order to identify the syndrome, treat each component of the disorder and its complications and may require invasive treatments such as hemodialysis or transvenous pacing.

165. A case of cardiac arrest after treatment with chlordiazepoxide in alcohol withdrawal symptoms

Abstract

Objective: Chlordiazepoxide is a long-acting benzodiazepine used as first line medical treatment of alcohol withdrawal symptoms in Denmark. Chlordiazepoxide is known to have several active metabolites with even longer half-lives. Chlordiazepoxide and its metabolites pose a risk of severe sedation and respiratory insufficiency lasting weeks with the need of antidote treatment and organ support [1]. This case illustrates the risk of respiratory insufficiency and hypoxic cardiac arrest following treatment with chlordiazepoxide.

Case report: A 74-year-old man with hypertension, atrial fibrillation, chronic obstructive pulmonary disease, hypothyroidism, and periodic alcohol abuse was hospitalized with a desire for alcohol detoxification. During the first 49 h after admission, a total of 950 mg chlordiazepoxide was administered. On days 4, 8 and 9 the patient was treated with flumazenil due to sedation and respiratory insufficiency with desaturation.

He suffered an unwitnessed cardiac arrest of possibly hypoxic cause 2.5 h after the last flumazenil dose on day 9. Primary rhythm was pulseless electric activity (PEA), the patient was cardiopulmonary resuscitated and had return of spontaneous circulation after 20 min. He was intubated and admitted to the intensive care unit (ICU) for organ support. The day after ICU admission, he was extubated and treated with flumazenil infusion to day 28. Due to depressed consciousness, respiratory distress, and secretion stagnation he was re-intubated and mechanically ventilated from day 13 to day 19. Full blood concentrations of chlordiazepoxide and metabolites were measured at day 9 and day 12 and the half-life of chlordiazepoxide and the two metabolites, demoxepam and nordazepam, was found to be 17.7 h, 65 h, and 148 h, respectively. The day 9 concentrations were 0.3 mg/kg, 2.7 mg/kg and 0.5 mg/kg, respectively. The patient was hospitalized for 32 days of which 21 days were in the ICU. He died of unknown cause the day after hospital discharge.

Conclusion: The use of chlordiazepoxide carries a risk of prolonged sedation with the need of antidote treatment. This case illustrates the shorter effect of flumazenil compared to chlordiazepoxide and its metabolites and emphasizes the importance of extended monitoring when antidote treatment is indicated.

166. A young woman presenting with blurry vision after sexual enhancement supplement overdose

Abstract

Objective

In the era of widespread Internet access, male sexual enhancement drugs are readily available online, posing potential risks. We present a case highlighting an instance of visual impairment resulting from an overdose of an unidentified male enhancement drug.

Case report

A 31-year-old female with no significant medical history presented to our emergency department after ingesting 16 aphrodisiac tablets following a dispute with her boyfriend. She complained of blurred vision, color perception impairment, and restricted color vision (black and white). Initial vital signs revealed hypotension (99/56 mmHg) and tachycardia (114 bpm), with normal body temperature and unremarkable breathing. Pupillary examination showed symmetrical pupil size (5/5) with no relative afferent pupillary defect (RAPD). There were no extraocular movement limitations. The patient denied other symptoms. Initial labs were unremarkable. Intravenous fluid resuscitation improved her blood pressure and heart rate, and her vision gradually improved within three hours. She was discharged in stable condition.

Conclusion

Online vendors often advertise natural source male enhancement drugs that are commonly found to be phosphodiesterase type 5 (PDE5) inhibitors, with a potential risk of contamination by other substances [1,2]. PDE5 inhibitors, prevalent for nearly two decades, are primarily prescribed for erectile dysfunction but are also used in the treatment of pulmonary arterial hypertension. Known side effects of PDE5 inhibitors include cardiovascular effects and possible visual disturbances. Previous research has documented ocular toxicity associated with PDE5 inhibitors, including ischemic optic neuropathy and retinal artery occlusion. Case reports resembling the present case have reported symptoms such as cyanopsia. This is mainly hypothesized that PDE5 inhibitor cross-reacts with PDE6 receptors in high sildenafil dosages, while PDE6 receptors are present in the retina and play a role in color vision [3]. While serum sildenafil concentration were not determined in this patient, the clinical presentation aligns with sildenafil toxicity, raising reasonable suspicion of sildenafil poisoning over other PDE5 inhibitors.

167. Severe adverse drug reactions due to injection of paliperidone long-acting formulations: two cases

Abstract

Objective

Patient adherence to antipsychotic drug treatment is crucial, and long-acting injectable (LAI) formulations, eliminate the need for daily oral intake and assure more stable serum concentrations [1]. Three formulations of paliperidone LAI exists: once-monthly (PP1M), 3-monthly (PP3M) and 6-monthly (PP6M). The administration schedule of PP1M involves two initial doses given one week apart (150 and 100 mg, respectively) followed by 75 mg monthly. Several studies demonstrated safety and efficacy of all formulas. However, serious adverse drug reactions (ADRs) have been reported [2], demonstrating the need to investigate risk factors. Two severe cases of ADRs to LAI paliperidone palmitate PPM1 are described. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine paliperidone serum concentrations (PC) which were compared to PP1M standard pharmacokinetics trends for the reported administration schedule [3].

Case series

Male, 64-year-old, 70 kg, polytherapy with lithium carbonate, pramipexole, valproic acid, benzodiazepines. Catatonia and prolonged QTc appeared after correct Xeplion^® (PP1M) administration. PC was twice the expected concentration (83.1 versus 40.2 ng/mL), increasing in the following weeks, reaching a peak of 247.9 ng/mL 7 weeks after discontinuation. The patient died two months later from septic complications. Male, 53-year-old, 75 kg. Neuroleptic Malignant Syndrome developed five days after second Xeplion^® administration, following orthopedic surgery. PC was about four times higher than expected mean (89.0 versus 20.5 ng/mL), despite delayed administration (about two weeks). Values slowly declined to 24 ng/mL 9 weeks after discontinuation. He had slow recovery with relevant sequelae.

Conclusion

Some factors affecting paliperidone pharmacokinetics are needle length, site of injection (deltoid versus gluteal muscle) and body mass index [1]. These had been taken into consideration by the physicians in these cases. We excluded drug-drug interactions as a leading cause of the reported ADRs, while surgery-induced stress may have influenced the pharmacokinetics in the second patient. The crucial role of therapeutic drug monitoring clearly emerged. In line with previous literature, the important factor could be a genetic polymorphism and further analysis will be conducted on patients’ samples.

168. Serious psychiatric adverse effects after a single dose of ofloxacin: explained by the concentration in cerebrospinal fluid (CSF)

Abstract

Objective

To report a severe adverse effect after ofloxacin, confirmed with early sampling and measurement in blood and CSF.

Case report

A 33-year-old Caucasian male (no past history) presented to our Emergency Department, complaining of sweating, chills, and spontaneous hematuria. He received infusions of ofloxacin 200 mg and gentamicin. One hour later, he was anxious, agitated, and aggressive, needing sedation with loxapine 150 mg. Septic shock was documented with tachycardia without arterial hypotension. Temperature was 36.4 °C. Laboratory tests were as follows: C-reactive protein 102 mg/L, procalcitonin 43.9 µg/L, white cells 10.9 × 10ⁱ/L, platelets 280 × 10ⁱ/L, coagulation unremarkable with International Normalized Ratio (INR) 66%, creatinine 87 µg/L, creatine kinase 1192 UI/L, aspartate aminotransferase (ASAT) 49 UI/L, alanine aminotransferase (ALAT) 38 UI/L, fibrinogen 4 g/L, increased cortisol (894 nmol/L) and glucose 5.7 mmol/L. A cerebral scan was unremarkable. A CSF sample showed protein 371 mg/L and lactate 2.4 mmol/L. One hour after the infusion, the ofloxacin concentration was 0.9 mg/L (blood) and 0.78 mg/L (CSF) and gentamicin 0.4 mg/L (blood). Antibiotic therapy was modified and third generation cefalosporins were administered. E. coli was identified in the urine. He was discharged on day 3 with no further psychiatric effects.

Conclusion

Fluoroquinolones are known to cause psychiatric effects, most commonly ofloxacin which is involved in 28% of cases [1]. Adverse effects are dose-related with few cases with blood or CSF concentrations. The low ofloxacin concentration can explain anxiety in this patient, while a high concentration can explain a sudden psychiatric disorder. A GABA antagonist effect is suggested, but psychiatric history, young age, and altered renal function are commonly reported factors. A single dose of ofloxacin 200 mg IV yielded a peak CSF concentration of 0.4–1.0 µg/L 2 h post dose [2]. Due to increasing reports of adverse effects with fluoroquinolones, the European Medicines Agency advised restricting prescribing of these drugs [3]. Biological sampling in septic cases may be helpful to understand the cause of adverse effects in therapy.

169. Neuroleptic malignant syndrome: accidental or intentional haloperidol poisoning

Abstract

Objective

Neuroleptic malignant syndrome (NMS) is a rare but potentially life-threatening reaction to almost any antipsychotic drug or major neuroleptic. It is characterized by high fever, muscle stiffness, altered mental status and autonomic dysfunction. Other symptoms include kidney failure, hyperkalemia and rhabdomyolysis [1,2].

Case report

A 13-year-old girl was admitted to the toxicology department with symptoms of fever, weakness, and abnormal behavior. The symptoms began a week earlier after she ingested cypermethrin to prevent mosquito bites. Her medical history was unremarkable. Upon admission, the child displayed apathy, resistance to examination, unresponsiveness to questions, and exhibited signs of suspicion and anxiety. Physical examination disclosed sluggish movements, dyskinesia, tongue tremors, horizontal nystagmus, pale skin with excessive sweating, cold extremities, tachycardia, and involuntary urination. Visual hallucinations and mutism were also observed. Midazolam and oral risperidone were prescribed by a psychiatrist. However, after two days, the mother discontinued the risperidone due to a worsening of visual hallucinations. Despite a fever reaching 41 °C, antipyretics proved ineffective, and laboratory markers indicated rhabdomyolysis. No elevated infection markers or causative agents were identified. Extrapyramidal symptoms, intractable fever, and rhabdomyolysis raised suspicion of neuroleptic usage. A urine toxicochemical test confirmed the presence of haloperidol metabolites. Diphenhydramine treatment was initiated, resulting in some clinical improvement. However, the parent subsequently declined further inpatient care. Consequently, the child was discharged and treatment discontinued.

Conclusion

This case emphasizes the need for prompt recognition and intervention in NMS cases, especially in young individuals exposed to neuroleptics. Healthcare providers should remain alert to ensure timely treatment and monitoring for better patient outcomes.

Table 1 Laboratory and diagnostic data in a patient with NMS after haloperidol.

White blood cell count (WBC)	C-reactive protein (CRP)	Cerebrospinal fluid analysis	Hemoculture	Cytomegalovirus (CMV) IgM	Epstein-Barr virus (EBV) IgM	Human immunodeficiency virus (HIV)	Creatine kinase	Brain magnetic resonance imaging (MRI)
10.1 × 10^i/L	0.38 ng/L	WBC <3 Gram stain-negative	No growth	Absent	Absent	Absent	6606 µg/L	Cytotoxic lesions of the corpus callosum (CLOCCs)

170. High risk of respiratory failure requiring mechanical ventilation when admitted to ICU after treatment with chlordiazepoxide for alcohol withdrawal symptoms

Abstract

Objective: Chlordiazepoxide is a long-acting benzodiazepine with several active metabolites with the potential to cause respiratory depression requiring ICU admission. We have previously described four cases of prolonged sedation with the need for antidote treatment up to 42 days after treatment with chlordiazepoxide [1]. This study aimed to describe the reasons for ICU admission, the frequency of mechanical ventilation, and the clinical outcome when patients were admitted to ICU after treatment with chlordiazepoxide for alcohol withdrawal symptoms.

Methods: A retrospective study of all patients admitted to the ICU at Bispebjerg Hospital after treatment with at least 200 mg of chlordiazepoxide between 1 January 2018 to 31 December 2020. Data was extracted from the electronic medical record and reported with descriptive statistics.

Results: One hundred and thirteen patients with a total of 133 admissions were included. Chlordiazepoxide was administered in a total of 2824 admissions in the same period. Hence, administration of any dose of chlordiazepoxide during admission resulted in a 4.7% risk of ICU admission. The total chlordiazepoxide dose before ICU admission was 800 mg (300–1100 mg; 5–95 percentile); 40% of admissions were due to respiratory failure, 39% were due to somnolence and 4.5% were post cardiac arrest. Mechanical ventilation was used in 71% of admissions of which 80% were invasive. In addition, 48% were readmitted to hospital within 90 days and 90-day mortality was 13% (Table 1).

Table 1 Patient characteristics, management, and outcome in 113 patients with 133 ICU admissions after chlordiazepoxide for alcohol withdrawal treatment.

Parameter	Values are mean ± SD or median [5–95% range]
Age, years	56 ± 12
Male	96 (85%)
Total dose of chlordiazepoxide before ICU admission, mg	800 [300–2210]
Number of chlordiazepoxide administrations before ICU admission	8 [3–20]
Reason for ICU admission
Respiratory failure	52 (39%)
Agitation	5 (3.8%)
Somnolence	52 (39%)
Refractory withdrawal symptoms despite high doses of benzodiazepines	41 (31%)
Cardiac arrest	6 (4.5%)
Other	6 (4.5%)
Hospital length of stay, days	15 [2.9–42]
ICU length of stay, days	5.2 [0.7–22]
Mechanical ventilation	95 (71%)
Non-invasive ventilation	18 (14%)
Invasive ventilation	73 (55%)
Continuous positive airway pressure	22 (17%)
Duration of mechanical ventilation, days	3.3 [0.4–18]
Mechanical ventilation at admission	55 (41%)
Use of flumazenil during ICU admission	26 (20%)
Infusion	12 (9.0%)
Duration of flumazenil infusion	1.9 [0.2–8.4]
Readmission within 90 days
Hospital readmission	48 (36%)
ICU readmission	18 (14%)
90-day mortality	17 (13%)
Time from ICU admission to death, days	6.8 [1.6–38]

Reason for ICU admission is calculated per admission; the remaining values are per patient.

Conclusion: Admission to ICU after treatment with chlordiazepoxide for alcohol withdrawal symptoms occurred in high numbers and was most commonly due to somnolence and/or respiratory insufficiency requiring mechanical ventilation in more than two-thirds of admissions. The risk of readmission and a fatal outcome was high.

171. Acute toxicity profile of domperidone in overdose: a consecutive case series

Abstract

Objective: Domperidone, a phenothiazine, is a dopamine 2-receptor antagonist with antiemetic properties. In many countries it is approved for oral use in patients >12 years and ≥35 kg. Maximal daily oral dose is 30 mg. The parenteral formulation was withdrawn from the market in 1986 because of cardiotoxicity. Since 2019 domperidone is no longer authorized for children ≤12 years because of lack of efficacy. Information on the toxicity profile of acute domperidone poisoning is lacking. The aim of this study was to investigate clinical features of acute domperidone overdose, with special focus on QTc- prolongation and extrapyramidal symptoms.

Methods: Retrospective review of acute single-substance oral domperidone overdoses reported to our poison centre from 1997 to 2022 with known follow-up and high causality assessment. Severity was graded according to the Poisoning Severity Score.

Results: Overall, 101 patients (57 females, 40 males, 4 unknown) met the inclusion criteria. There were 22 adults (median 26.0, mean 34.3, range 18–84 years) and 79 children <16 years (median 3.0, mean 4.0, range 0.1–15.5 years). Ingestion was accidental in 3 adults and 77 children, intentional in 19 adults and 2 children.

Ten adults and 68 children had no symptoms, minor effects developed in 10 adults and 11 children. Two adults with intentional ingestion had moderate and severe symptoms, respectively. Minor effects were predominantly gastrointestinal (nausea, vomiting, diarrhea, abdominal pain) or central nervous system effects (somnolence, lethargy, headache, restlessness). The patient with moderate effects had agitation. The patient with severe effects had aspiration pneumonia and agitation, requiring sedation and intubation. Extrapyramidal symptoms were seen in two patients (one child, one adult). No QTc-prolongation was observed. In contrast, in our database two polyintoxications (domperidone plus drugs without cardiotoxic effects) are documented with significant QTc-prolongation, both involving adults with intentional ingestion.

Asymptomatic children ingested 0.1–12.5 mg/kg (median 2.8, mean 3.6, dose known in 40/68), and children with minor effects 2.3–13.3 mg/kg (median 5.6, mean 6.0, dose known in 8/11). Asymptomatic adults ingested 60–300 mg (median 150, mean 162, dose known in 9/10), adults with minor effects 80–1500 mg (median 250, mean 397, dose known in 7/10). The two patients with moderate and severe symptoms ingested 120 mg and 300 mg, respectively.

Conclusion: Domperidone in acute overdose has a favorable toxicity profile, 98% of patients showed no or minor symptoms. No prolongation of QTc was seen in monointoxications and extrapyramidal symptoms were rare. We suggest that patients with accidental ingestions of domperidone, especially toddlers, can be safely monitored at home.

172. Analytically confirmed acute overdose of the antidepressant vortioxetine

Abstract

Objective

Vortioxetine is an antidepressant used as a third-line treatment of major depressive episodes in the UK. Its actions are across a range of different targets: i) 5-HT3, 5-HT7 and 5-HT1D antagonist; ii) 5-HT1A agonist; iii) 5-HT1B partial agonist; and iv) serotonin transporter blocker. Currently, there is limited information on risks associated with acute overdose of vortioxetine.

Case report

A 32-year-old white male with a medical history of depression, previous self-harm, type-1 diabetes, diabetic retinopathy and low testosterone, treated with insulin, ramipril, diazepam, vortioxetine, testosterone cypionate, human chorionic gonadotropin and exemestane, was found drowsy by a family member after intentional self-harm related ingestion of vortioxetine (estimated ingested maximum 1260 mg) and diazepam (estimated ingested maximum 350 mg) approximately 12 h previously. After transfer by ambulance to hospital, his initial observations were: heart rate 74 bpm, blood pressure 156/89 mmHg and temperature 37.5 °C. On examination, he was alert and orientated, although he made little eye contact and had quiet monotonic speech. Cardiovascular, respiratory, abdominal and neurological examinations were normal. An electrocardiogram (ECG) showed sinus rhythm with a rate of 62 bpm, QRS duration of 61 ms and QTc duration of 372 ms. Admission blood tests (renal function, liver function and full blood count) were normal apart from a raised ALT (126 IU/L); his capillary blood glucose was 21 mmol/L. He was admitted to hospital for 8 h of monitoring and the hyperglycaemia secondary to previously not taking his insulin was managed; following review by the mental health team, he was discharged from hospital. A blood sample taken at the time of presentation was prepared for analysis using reversed phase solid phase extraction and analysed using ultra performance liquid chromatography (UPLC) interfaced to high resolution accurate mass spectrometry. Vortioxetine was detected at a concentration of 457 ng/mL. Also detected were sub-therapeutic concentrations of diazepam (100 ng/mL; therapeutic range 0.7–1.5 µg/mL) and metabolites and pregabalin (540 ng/mL; therapeutic range 1–5 µg/mL).

Conclusion

Maximum plasma concentrations of vortioxetine after single and multiple dosing of 20 mg vortioxetine is 8.1 ng/mL and 33.0 ng/mL, respectively [1]. Our patient had a significantly elevated vortioxetine concentrations, but these were associated were minimal clinical features despite the potential risks of severe toxicity based on vortioxetine’s pharmacological actions.

173. Acute toxicity profile of pregabalin in overdose: a consecutive case series

Abstract

Objective

Pregabalin is a gamma-aminobutyric acid (GABA) analog binding to the alpha₂-delta site of calcium channels in the central nervous system (CNS). It is approved in adults >18 years and widely used in the treatment of neuropathic pain, anxiety disorder and epilepsy. The daily adult oral dose is 150–600 mg. The maximum (off-label) dose in children is 6 mg/kg/day [1]. The aim of this study is to investigate the demographic and clinical features of acute pregabalin overdose.

Methods

Retrospective review of single-substance acute oral overdoses with pregabalin in adults and children (<6 years), reported by physicians between 2006 and 2022 to our poison center and with a high causality assessment. The severity was classified according to the Poisoning Severity Score.

Results

Overall, 77 patients (median age 27, range 0.8–82 years) were included with 58 females (75%), 19 males (25%). There were 66 adults (86%) and 5 adolescents (6%, range 12–15.9 years), who were included in the adult group. Six small children under 6 years (8%, range 0.8–5.4 years) were assessed in a separate group. There were 64 cases with intentional intake (51 suicidal, 5 abuse, 8 other), 12 accidents and 1 unknown situation. In the adult group, no symptoms were reported in 11 of 71 patients (15%). The dose range was 0.735–3 g. Mild symptoms were seen in 45 adults (63%) with a dose range of 0.4–12.6 g. Moderate symptoms occurred in 14 adults (20%) with a dose range of 2–10.2 g. A 15-year-old had severe symptoms (coma) with an unknown dose. There were no fatalities. In the group with mild courses, CNS symptoms were most common with somnolence (69%), vertigo (16%), and drowsiness (9%). Further symptoms were tachycardia (13%), nausea (9%), vomiting (13%), abdominal pain and headache. Moderate symptoms were agitation (4/14), disorientation and confusion (4/14), seizures (1/14), myoclonus (3/14), rhabdomyolysis (1/14) and syncope (2/14). In the small children group, 4 children showed no symptoms (dose range 5–20 mg/kg). One 5.4-year-old developed mild symptoms (drowsiness) with 7.5 mg/kg. One 3.4-year-old child had moderate symptoms (sopor) with 10 mg/kg.

Conclusion

Pregabalin showed no clear dose-toxicity relationship in our data, so that no toxic threshold dose could be established. While CNS depression is the main symptom in mild courses, CNS excitation seems to be more common in moderate courses. Severe symptoms appeared to be rare in the dose range studied (up to 12.5 g in adults and 20 mg/kg in children).

174. Two cases of intravenously administered simethicone

Abstract

Objective

Simethicone (simeticone) is a mixture of dimethicone (dimeticone) and silicon dioxide. It effectively prevents formation of foam by reducing the surface tension of aqueous secretions. Simethicone is called a non-toxic substance and is excreted unchanged after passing through the gastrointestinal tract. The defoaming property of simethicone is beneficial in oral detergent poisoning. However, it is intended for oral use only. We describe two cases of poisoning after accidental intravenous simethicone administration.

Case report

A 51-year-old woman was accidentally given 3 mL simethicone intravenously during a routine gastroscopy in a doctor's office due to a mix-up of syringes. The patient immediately showed acute dyspnea with pronounced tachycardia. After being admitted to the intensive care unit, the Poisons Information Centre was contacted. The patient's oxygen saturation was 60% and she had to be intubated. A lung computerised tomography (CT) scan showed a peripheral pulmonary embolism with bilateral infiltrate. Antibiotic therapy was started. After one night the patient showed pronounced hemiparesis on the right side. She was transferred to a neurological intensive care unit. Cranial magnetic resonance imaging (MRI) showed multiple small ischemic emboli in the left middle cerebral artery and in the left cerebellum with secondary hemorrhage. Clinically, the patient presented a complete left media syndrome. She was heparinized and transferred to the early rehabilitation ward after 19 days. In the second case, an 82-year-old patient was admitted to the hospital with acute gastrointestinal symptoms and recurrent stenocardia. In preparation for an abdominal ultrasound examination, the patient was to be given simethicone orally, but due to an error, 10 mL was administered intravenously. She was immediately agitated with pronounced dyspnea and was transferred to the intensive care unit. The patient had to be intubated and the Poisons Information Centre was contacted. Hemoperfusion was started and on the following day she was hemodynamic stable. On day five it was possible to switch to assisted spontaneous ventilation and to stop the sedation. Despite heparinization she had a pulmonary embolism with subsequent decline in respiratory function. She required mechanical ventilation once again and antibiotic therapy was given because of elevated inflammation markers. The patient died due to renal insufficiency and respiratory deterioration.

Conclusion

In both cases, intravenous simethicone administration caused immediate acute respiratory failure, due to pulmonary embolism. In one case, cerebral embolism was also documented. Due to its chemical properties, intravenous administration of even a small volume of simethicone can lead to vascular occlusion with associated complications.

175. Prediction of hematotoxicity in acute valproic acid overdose

Abstract

Objective

Valproic acid is a drug used for convulsive diseases and emotional stabilization. Acute intoxication can lead to gastrointestinal disorders, neurologic symptoms, and hematologic toxicity. This study aims to investigate factors that can predict the patient’s prognosis.

Methods

In this single center retrospective observational study, patient medical records from 1st January 2013 to 31st December 2022 were reviewed. The initial clinical features, laboratory tests, and serum valproic acid concentration in patients with acute valproic acid intoxication who visited the emergency room were analyzed. The patients were divided into two groups – those who showed hematologic toxicity (hematotoxicity group) and those who did not (non-hematotoxicity group).

Results

A total of 115 patients were included in the analysis; 23 patients (20%) presented hematotoxicity. The median age was 39 years (IQR, 32.0 ∼ 50.5) and was higher than the non-hematotoxicity group (p = 0.001). The Glasgow Coma Score (GCS) was lower in the hematotoxicity group with a median of 12 points (IQR 9.0 ∼ 14.5) (p = 0.013). Hospitalization to the ICU was more frequent in the hematotoxicity group (p = 0.003). The hematotoxicity group had a higher incidence of developing pneumonia, acute kidney injury, rhabdomyolysis, metabolic acidosis, and hyperlactatemia compared to the non-hematotoxicity group (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p = 0.009, respectively). The initial valproate blood concentration in the hematotoxicity group was higher than the non-hematotoxicity group at a median concentration of 121.6 mg/dL (IQR, 9.8 ∼ 154.3) (p < 0.001). As a result of multivariate analysis, the odds ratio for developing hematotoxicity was 6.20 (p = 0.018) when metabolic acidosis was present, and 8.32 (p < 0.001) when the initial valproate concentration was higher than 115.0 mg/dL.

Conclusion

In patients suspected of acute valproate poisoning, it is crucial to assess the initial arterial pH and obtain a serum valproic concentration to predict the prognosis of poisoned patients.

176. Predicting serum paracetamol concentration in acute poisoning for safe termination of N-acetylcysteine in a resource-limited environment

Abstract

Objective

The Prescott nomogram has been utilized to forecast hepatotoxicity from acute paracetamol poisoning. In developing countries, emergency medical centers lack the resources to measure paracetamol concentrations, so the commencement and cessation of treatment is based on a reported dose. The purpose of the study is to investigate risk factors that can predict paracetamol detection after 15 h for safe termination of treatment.

Methods

Data were collected from an urban emergency medical center from 2010 to 2020. The study included patients ≥14 years with acute paracetamol poisoning within 15 h. The correlation between risk factors and detection of paracetamol 15 h after ingestion was evaluated using logistic regression and the area under the curve was calculated.

Results

One hundred and eighty-one patients were included in the primary analysis; median dose was 150.9 mg/kg and 35 patients (19.3%) presented 15 h after ingestion. The dose per weight and the time to visit were significant predictors for paracetamol detection after 15 h (dds ratio =1.002; 1.003). The areas under the curve were 0.628 with 135.4 mg/kg cut-off value and 0.658 with 455 min; that of the combined model was 0.714 with a sensitivity of 45.7% and specificity of 91.8%.

Conclusion

Where paracetamol concentrations are not reported during treatment following the UK guidelines, if patients are ≥14 years and visit within 15 h after acute poisoning, it is safe to start N-acetylcysteine immediately for patients who have taken ≥135.4 mg/kg and consider additional N-acetylcysteine doses for patients that present after 8 h.

177. Adherence to EXTRIP recommendations in lithium intoxication. Presentation of the SILITOX study

Abstract

Objective

To compare the degree of adherence to current recommendations (EXTRIP criteria [1]) for the management of lithium intoxication in the participating centers.

Methods

This is a multicenter international cohort study involving 10 Spanish and Irish hospitals. All patients aged 17 and older, diagnosed with lithium intoxication and treated at participating centers from 2012 to 2022, were included in this study.

Results

At the time of this analysis, 112 patients had been included in the study. The median age was 64 years (IQR 52–71), 74.1% were female. Ninety-three patients were included in the analysis. Of these, 54.8% had chronic intoxication, 26.9% had acute intoxication, and 18.3% had acute-on-chronic intoxication. The mean (SD) serum lithium concentration at admission was 2.07 mEq/L (0.94), with a peak concentration of 2.46 mEq/L (1.03). Fifty percent of patients experienced renal impairment during their emergency department stay. Sixty-nine patients (74.2%) presented at least one symptom, with confusion (62.4%) and decreased level of consciousness (37.6%) being the most common. Thirty-one patients (33.3%) received renal replacement therapy (RRT). Fifty-two patients (55.9%) required admission to a hospital, and 15 patients (16.1%) required admission to ICU/HDU. Two patients (2.2%) died. The degree of adherence to current recommendations (EXTRIP criteria) was 36.6%. In 37 patients, RRT was recommended, and of these, 17 (45.9%) underwent the same. In this cohort, serum lithium concentrations at admission were significantly higher in the group of patients who received treatment according to EXTRIP recommendations compared to those who did not follow the recommendations (3.06 versus 2.05; p = 0.005). Significant differences were also observed in peak lithium concentration (3.37 versus 2.20 mmol/L, p = 0.003). In 35 patients, EXTRIP suggested the use of RRT, and of these, 10 (28.6%) underwent the same. In 21 patients, RRT was not indicated, and of these, 4 (19.0%) were treated with RRT. In this cohort, patients who were dialyzed despite not meeting the RRT criteria in the guideline had a significantly higher peak lithium concentration than patients treated in accordance with the recommendations (3.26 versus 2.23 mmol/L; p = 0.036).

Conclusion

In our population, adherence to the recommendations of the EXTRIP workgroup was low (approximately 1 in 3 patients who had an indication for it).This work demonstrates that the indication for RRT in clinical practice appears to be more influenced by analytical criteria, specifically serum lithium concentrations, than clinical criteria (presence of symptoms).

178. Time correlation between prescribing and intoxication trends for selected psychotropic drugs: a 7-year observational study

Abstract

Objective: Changes in the intoxication rates for prescription drugs may occur with a delay following changes in prescribing patterns. Unused medication may be stored for a long period before being used in intentional or unintentional intoxication [1]. The purpose of this study was to determine the best method for time correlation between prescribing rates and intoxication events.

Methods: We conducted a 7-year (2015–2021) observational study of intoxication events in adults, identified from the registered phone calls to the national poisons control centre. Cases related to the ingestion of prescription antipsychotics, anxiolytics, hypnotics/sedatives, antidepressants and antiepileptics were included. We tested the time correlation between the prescribing and intoxication rates using Pearson Correlation coefficient. The prescribing rates were expressed in defined daily doses and compared with intoxication rates as shown in Table 1.

Table 1 Methods of time correlation assessment between prescribing rates and intoxication events

Prescribing year(s) in relation to the intoxication events	Prescribing year(s) – example for the intoxication events in 2015
Actual year of the intoxication events	2015
One year prior to the intoxication events	2014
Two years prior to the intoxication events	2013
Actual year + one year prior to the intoxication events	2014–2015
One year + two years prior to the intoxication events	2013–2014
Actual year + one year + two years prior to the intoxication events	2013–2015

Results: There were 2640 intoxication cases involving prescription psychotropic drugs during the 7-year period. The best time correlation was demonstrated using a two-year difference between the prescribing period and the time of intoxication events. This correlation was significant for antipsychotics (R = 0.766, p = 0.045), antiepileptics (R = 0.946, p = 0.001), and antidepressants (R = 0.828, p = 0.021). There was no time correlation detected between prescribing and intoxication events for anxiolytics and hypnotics/sedatives, regardless of the method used. A sum of the past two of three years for the prescribing rates did not provide a better correlation. The slope of the correlation was different for specific psychotropic drug groups. A change of 1,000,000 defined daily doses prescribed was related to a change of 50 intoxication events for antipsychotics, 20 events for antiepileptics, or 5 events for antidepressants.

Conclusion: The best time correlation was achieved when comparing the prescribing period of two years before the intoxication events. The correlation was statistically significant for antipsychotics, antiepileptics and antidepressants.

179. Iatrogenic muscle relaxant overdoses reported to the UK National Poisons Information Service (NPIS) over 15 years 2008–2023

Abstract

Objective

Muscle relaxants are widely used in clinical practice. Indications include bolus injections for paralysis during intubation and therapeutic infusions, such as for ventilatory failure [1] or facilitating safe transfer. Despite widespread use, limited data are available on features in overdose. We investigate the incidence of telephone enquiries received by the UK National Poisons Information Service (NPIS) following iatrogenic muscle relaxant overdose.

Methods

A retrospective analysis was conducted of NPIS enquiries involving atracurium, rocuronium, suxamethonium, pancuronium, vecuronium or sugammadex received between 1 January 2008 and 31 July 2023.

Results

Thirty-seven telephone enquiries were received by the NPIS involving 35 patients. Seven patients received muscle relaxants as a therapeutic adjunct to intubation, five patients suffered extravasation and three patients had taken intentional overdoses. These 15 patients were excluded from further analysis. Twenty cases of iatrogenic overdose were identified (two adults, two patients aged 5–9 years and 16 patients aged <5 years); four (including one adult) took place in operating theatres, one in adult intensive care (ICU), four in paediatric ICU and 11 in neonatal units. Enquiries involved atracurium (n = 6), vecuronium (n = 6), pancuronium (n = 4) or rocuronium (n = 4). Fourteen overdoses occurred with bolus dosing and six with infusions. Most cases were discussed with the NPIS contemporaneously. However, three cases were discussed more than 24 h after administration. The dosage was documented in 17 cases, and was at least 10 times the therapeutic dose in 12 patients. The most common effect reported was prolonged paralysis. Supportive management and monitoring were recommended for most patients (n = 11), but specific peripheral nerve stimulation monitoring was never discussed. In five patients (one adult, four aged <5 years) neostigmine was advised as an antidote, while sugammadex was never recommended.

Conclusion

While rare, muscle relaxant overdoses can have serious adverse effects. In this series, the majority of iatrogenic errors occurred in paediatric and neonatal patients, possibly related to the preparation of fractional doses with a small margin for error. Measures to increase awareness amongst clinical toxicologists of the role of nerve monitoring [2] and the role of reversal agents such as neostigmine and/or sugammadex in muscle relaxant overdose should be considered.

180. Prolonged central nervous system depression and neurologic findings in an adolescent after ingestion of a moderate perampanel ingestion

Abstract

Objective

Perampanel is a selective, non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist with a therapeutic half-life of 105 h; it is used to treat partial and tonic-clonic seizures. Initial dosing is 2 mg/day with maintenance dosing of 8–12 mg/day. Toxicity has been reported with doses as low as 0.25 mg/kg [1]. There are several case reports of ataxia and prolonged CNS depression lasting up to 14 days [2], mostly in young children and adults. We describe the prolonged toxicity of perampanel in an adolescent after overdose.

Case report

A 52.5 kg 16-year-old female with a history of seizures was found by her family agitated with erratic behavior. She was found with a new bottle of perampanel with ten 8 mg tablets missing (80 mg total, 1.52 mg/kg). The patient had stopped perampanel monotherapy six months previously and was not currently taking this medication. Upon arrival at the emergency department she was not following commands and required mechanical restraints and lorazepam IM, followed by required sedation and intubation for her agitation. Initial vital signs were: pulse 145/min, respiratory rate 22/min, blood pressure 126/72 mmHg, oxygen saturations 98% (room air). Electrocardiogram showed sinus tachycardia at 145/min, QRS 66 ms, QTc 431 ms. A comprehensive metabolic panel (CMP) was normal except for serum bicarbonate of 16 mmol/L, anion gap 21 mmol/L, and blood glucose 151 mg/dL. Serum acetaminophen, salicylate, and ethanol were undetectable. After intubation, she demonstrated rigidity and abnormal movements, but electroencephalogram (EEG) did not show seizure activity. She failed several attempts at extubation due to inability to follow commands but was successfully extubated on hospital day seven. After extubation she demonstrated additional dysarthria, word-finding difficulties, and truncal ataxia which resolved completely by hospital day eight.

Conclusion

We report a case of an adolescent after an acute ingestion of perampanel 1.5 mg/kg. Toxicity in this age group is not well described in the literature but appears similar to limited reports in young children and adults and includes agitation, truncal ataxia, and very prolonged CNS depression – even at therapeutic serum concentrations. Clinicians should have a low threshold for hospital referral and anticipate prolonged effects even with seemingly small to moderate exposures.

181. Multidrug-related insidious serotonin syndrome in an adolescent

Abstract

Objective

Serotonin syndrome (SS) is the result of an increased activity of 5-hydroxytryptamine (5-HT) at its receptors. It is characterized by mental status alterations, autonomic dysfunction, and neuromuscular abnormalities. While most cases recover within 24 to 72 h following drug cessation, administration of new serotonergic agents may favor the insidious behavior of this syndrome. We present a case of overdose involving sertraline, tramadol and fentanyl resulting in insidious SS.

Case report

A 17-year-old female with history of depression, ingested 1.4 g of sertraline, 25 mg of clonazepam and 2 g of tramadol. On arrival, she presented cyanotic, unresponsive, with Glasgow Coma Score 3/15, blood pressure 145/72 mmHg, heart rate 168 bpm, respiratory rate 7 rpm, oxygen saturation 68% and temperature 37.8 °C. She was intubated, developed seizures and progressively worsened. She suffered a cardiac arrest, with return of spontaneous circulation and subsequent hemodynamic instability for which vasopressor and intra-aortic balloon counter pulsation was required. Subsequently, the hemodynamic status improved and two days after exposure, medical toxicology was consulted since the patient presented persistent mydriasis, and anxiety, despite infusions of midazolam and fentanyl. During the evaluation, it was discovered that the patient also had hyperthermia (39 °C), tremors, hyperreflexia, diaphoresis and elevated creatine kinase (CK), for which a diagnosis of serotonin syndrome was established according to Hunter criteria, so fentanyl was suspended and cyproheptadine initiated after which the serotonergic manifestations ceased. Four days later, after a failed attempt to extubate her, the fentanyl infusion was restarted and 24 h later the serotonergic manifestations recurred and persisted despite the fact that no serotonergic drugs were used thereafter and that treatment with cyproheptadine was maintained, presenting only brief periods of improvement. Definitive remission was reached after 4 weeks. In addition, a toxicological profile, cortisol concentrations, thyroid profile, blood and urine cultures, as well as brain magnetic resonance imaging were reported normal. Patient was extubated in week 4, requiring physical therapy before discharge.

Conclusion

In the present case, we observed a pharmacological interaction between the serotonergic agents that the patient ingested in overdose and fentanyl, that was used therapeutically. This highlights the importance of considering patients' previous medication before administering drugs that may result in drug-drug interactions, in addition, medical staff need to be familiar with SS and its triggers. Finally, the importance of promptly notifying the toxicology service is highlighted in order to begin addressing patient management in a timely manner.

182. Vasoplegic shock associated with dihydropyridine calcium channel blocker poisoning in Australia: a retrospective study of treatment modalities and patient outcomes

Abstract

Objective: Amlodipine poisoning was the commonest cause of cardiovascular drug death in the US in 2021 [1]. A US Poison Centre study noted amlodipine was the most common cause of death from calcium channel blocker (CCB) poisoning (61%; 37/61 cases), with treatment including vasopressors (97%) and high dose insulin (HDI; 81%) [2]. HDI up to 10 U/kg/h is reported in managing amlodipine poisonings, and is associated with the use of more vasopressors in amlodipine poisoning compared to non-dihydropyridine poisoning [3]. HDI causes vasodilation, so could exacerbate vasoplegic shock from dihydropyridine poisoning. This study aims to determine treatments and outcomes from dihydropyridine CCB poisoning in Australia.

Methods: Retrospective study of patients managed by the New South Wales and Queensland Poisons Information Centre and three toxicology units (January 2020 to July 2023). Patients ≥15 years with deliberate dihydropyridine poisoning developing hypotension (MAP <65 mmHg or SBP <90 mmHg) were included. Patients ingesting non-dihydropyridine, alpha- or beta-blockers were excluded. We recorded demographics, drug and dose, vital signs, treatments and outcome.

Results: Fifty patients (42 amlodipine) met inclusion criteria: 41 (82%) co-ingested angiotensin axis antagonist drugs (Table 1). Median lowest SBP and MAP were 75 mmHg (IQR:65–82) and 53 mmHg (IQR:47–59), respectively. Noradrenaline, metaraminol, vasopressin or adrenaline were used in 39 (75%) of patients: 34, 24, 17 and 15 patients, respectively; 27 patients (54%) received more than one vasopressor. HDI was used in 10 patients (20%), median dose 1 U/kg/h(IQR:0.5–3). There was one fatality.

Table 1 Demographics, other treatments and outcomes of dihydropyridine (DHP) calcium channel blocker (CCB) poisonings with shock [medians (IQR) or n (%)].

Parameter	DHP CCB with shock
Median age (years)	57 (IQR 42–67)
Female	31 (62%)
Ingested dose (DDDs)	34 (IQR 20–57)
Intravenous fluid volume (Litres)	2.5 (2–3)
Received activated charcoal	12 (24%)
Received intravenous calcium	37 (74%)
Received thioninium blue (methylene blue)	7 (14%)
Intubation and ventilation	14 (28%)
Median length of stay (days)	3 (IQR 2–5)

Defined daily doses (DDDs): amlodipine 5 mg, felodipine 5 mg, lercanidipine 10 mg, nifedipine 30 mg.

Conclusion: We observed favourable outcomes from dihydropyridine with or without angiotensin axis antagonist overdose with vasopressors, and relatively low dose HDI was used in a small proportion of patients.

183. Paracetamol overdoses: delays in treatment across a single NHS Trust in the West Midlands

Abstract

Objective

Paracetamol is a readily available over-the-counter medication that accounts for a third of all admissions relating to intentional overdoses presenting to Emergency Departments across England [1]. TOXBASE^® guidance states that patients admitted following an acute paracetamol overdose should have N-acetylcysteine (NAC) started within 8 h of their last ingestion and that all patients should be started on NAC immediately following a staggered overdose [2]. We aim to assess the adherence to these recommendations by emergency physicians across two hospital sites.

Methods

A retrospective analysis of patients admitted following paracetamol overdose to Sandwell and West Birmingham Hospital between April and July 2023 presenting within 8 h of last ingestion and requiring intravenous NAC.

Results

Fifty admissions met the inclusion criteria, 33 were acute overdoses (23 of whom ingested ≥150 mg/kg) and 17 were staggered overdoses. Acute overdose (n = 33): NAC was commenced after 8 h post ingestion in 36% (n = 12) of patients presenting with acute overdoses. Reasons for this were a delay in blood results (n = 6), a delay in escalation of blood results to a clinician (n = 4) and patients absconding from hospital prior to clinical assessment (n = 2). The median delay between last ingestion and prescription for acute overdoses was 544 min (IQR: 521 – 569). Staggered overdose (n = 17): Staggered overdoses accounted for 34% of admissions, 11 of these had toxic (≥ 150 mg/kg) ingestions of paracetamol within a 24-h period. NAC prescriptions were delayed in 82% (n = 9) of patients admitted with a toxic staggered overdose. Delays in escalation to clinicians for patients presenting with toxic staggered overdoses was the main identified cause (n = 7). The median delay between last ingestion and prescription for staggered overdoses was 359 min (IQR: 330–459).

Conclusion

Many patients admitted following a paracetamol overdose had delays in commencing treatment, mostly in patients who have taken a staggered overdose. The delay in NAC prescription may reflect a delay in escalation to a clinician suggesting a suboptimal understanding of staggered paracetamol overdose management. Poison Centres should consider whether there are opportunities to support healthcare professionals in the timely triage and subsequent management of the poisoned patient.

184. Iatrogenic liver injury following treatment of massive insulin overdose

Abstract

Objective

Acute hepatic steatosis is a known complication of massive insulin overdose in combination with prolonged high dose dextrose administration [1]. High circulating insulin concentrations, in the presence of hyperglycaemia promote excessive production and storage of glycogen, inhibition of glycogenolysis, and increased lipogenesis with triglyceride accumulation in hepatocytes. Known as glycogenosis, or glycogenic hepatopathy, patients typically develop right upper quadrant pain, hepatomegaly, and elevated serum aminotransferases [2]. We report a case of a massive insulin overdose complicated by treatment-induced acute liver injury.

Case report

A 27-year-old female, with a history of type 2 diabetes mellitus, presented after an intentional insulin overdose. She self-administered 3150 IU insulin glargine and 6000 IU insulin aspart subcutaneously over multiple sites on her abdomen. In hospital she required multiple (n = 5) intravenous 50 mL boluses of 50% dextrose for hypoglycaemia. Oral complex carbohydrate intake was limited due to ongoing gastroparesis and a 50% dextrose infusion was required to maintain blood glucose concentration whilst in the intensive care ward. On Day 3 of admission (72 h post commencement of dextrose infusion) the patient developed right upper quadrant pain. Liver function tests, which were normal on presentation were deranged (AST 1400 IU/L, ALT 1000 IU/L). The Poisons Information Centre was contacted and recommended administration of octreotide and steroids to facilitate down-titration of dextrose. Transaminitis improved over 48 h after reduction and cessation of dextrose infusion.

Conclusion

In the setting of massive insulin overdose necessitating high volume/high concentration dextrose supplementation, clinicians need to be cognisant that acute liver injury can occur. As the degree of liver injury is related to the duration and dose of dextrose administered, adjunctive therapies such as octreotide or hydrocortisone should be considered in cases requiring prolonged high-concentration dextrose infusion to reduce dextrose requirements and to prevent glycogenic hepatopathy.

185. Fatality following intentional overdose of cenobamate: a case report

Abstract

Objective

Cenobamate is used as an adjunct in the treatment of focal onset seizures. The mechanism of action is not fully understood but may involve sodium channel inhibition and enhancement of GABA_A channel transmission. Cenobamate is usually prescribed in adults whose seizure activity has not been adequately controlled despite treatment with at least two antiepileptics [1]. The maximum dose in the UK is 400 mg once daily [2] and prescription items in England have increased from 18 in March 2022 to 1537 in July 2023 [3].

Case report

A 50-year-old female (estimated 50 kg) with a history of refractory epilepsy contacted her mental health crisis team following reported ingestion of 8400 mg of her prescribed cenobamate. Documentation was scant and it was unclear whether there were any co-ingestants. Upon arrival of paramedics, she was comatose (Glasgow Coma Score (GCS) 3). At the Emergency Department, she was hypothermic (temperature 34.0 °C), bradycardic (48 bpm) and hypotensive, which improved with fluid resuscitation (to 93/55 mmHg) shortly after arrival. Aspiration was suspected and she was subsequently intubated and ventilated. The National Poisons Information Service was consulted who advised management should focus on symptomatic and supportive care. At enquiry follow up 30 h following the initial NPIS consultation, she remained hypotensive (80/60 mmHg), despite inotropic support with noradrenaline and vasopressin, and acidotic (pH 7.24, lactate 7 mmol/L, base excess -7.8). Transfer to a regional extracorporeal membrane oxygenation (ECMO) centre was considered but not felt suitable in this case. She was commenced on high-dose insulin dextrose (10 U/kg/hour), but died 43 h post-ingestion.

Conclusion

Cenobamate is a relatively new drug and little is known about its effects in overdose. Prior to this case, the NPIS has received only 4 (all adults) patient related enquiries involving cenobamate since December 2021. All cases involved an accidental double-dose of prescribed medication and Poisoning Severity Score was either none (n = 3) or minor (n = 1) [4]. Poison Centres are well placed to capture information to support post-marketing surveillance.

186. Loperamide-associated electrocardiographic changes in medically prescribed supratherapeutic exposures compared to high-dose abuse

Abstract

Objective

Loperamide is an over-the-counter antidiarrheal opioid with a favorable safety profile at therapeutic dose due to its low bioavailability. However, recent reports have raised concerns about cardiac dysrhythmias, ranging from isolated QTc prolongation to ventricular arrhythmias in the context of high-dose loperamide abuse, predominantly in individuals with substance use disorders. These concerns extend to patients with intestinal failure and chronic diarrhea syndromes, who may be prescribed loperamide at doses exceeding the recommended maximum of 16 mg daily.

Methods

A retrospective chart review of patients at a tertiary care university hospital was conducted to identify inpatients on medically prescribed supratherapeutic loperamide with available electrocardiogram (ECG) recordings during exposure (group A). This group was compared to individuals in published reports of loperamide abuse, identified through a systematic review of the literature (group B). Parameters of interest were QTc duration, QRS duration, incidence of ventricular arrhythmias and other ECG abnormalities.

Results

A total of 106 patients were included (group A: 15, group B: 91). Patients in group A, mainly with intestinal failure syndromes, were significantly older (median age 66 years) and had a significantly lower loperamide exposure (median dose, 24 mg) compared to individuals in group B (median age 31 years, p < 0.0001; median dose 200 mg, p < 0.0001). Higher rates of risk-increasing co-morbidities (e.g., cardiac disease, other significant organ damage) and problematic co-medications (e.g., CYP3A4/2C8 or p-glycoprotein inhibitors, cardiotoxic or sedative medication) were seen in group A than in group B. QTc and QRS duration were lower in group A than in group B (median QTc: 411 ms versus 640 ms, p < 0.0001; median QRS: 91 ms versus 168 ms, p < 0.0001). Importantly, no life-threatening arrhythmias occurred in group A, despite being very common (64%) in group B. In the pooled dataset, moderate positive correlations were observed between ingested dose and QTc duration (p < 0.0001) and between dose and QRS duration (p < 0.0001).

Conclusion

ECG abnormalities were less common in patients prescribed supratherapeutic loperamide than previously reported in the context of high-dose abuse, despite a more concerning baseline cardiotoxicity risk profile in this population. Exposure to lower doses and potential disease-associated pharmacokinetic alterations may have contributed to this disparity.

187. Pharmacokinetic profile of phenytoin in a massive ingestion: a case report

Abstract

Objective: Given its relatively high pKa (8.3), phenytoin solubility is limited at gastric pH and oral absorption can be delayed unpredictably during overdose [1,2]. Here, we report a patient with massive phenytoin and valproic acid ingestion, highlighting the peculiar pharmacokinetic profile of phenytoin, with progressively increasing blood concentrations.

Case report: Florence PCC received a call from an emergency department. The Emergency Department (ED) doctors who oversaw the patient communicated the data and followed our instructions. A 27-year-old patient presented to the emergency department reporting a self-harm gesture one hour earlier by ingesting 197 tablets of phenytoin 100 mg and 39 tablets of valproic acid extended release 500 mg. Subsequently, the patient showed psychomotor agitation and delirium as well as hypotension, thus ED colleagues proceeded with intubation in order to start decontamination techniques and a noradrenaline infusion to support blood pressure. Valproic acid in the blood increased to 974 mg/L (therapeutic range 50–100 mg/L) associated with an ammonium concentration of 56 μg/dL (normal range 15–60 μg/dL). Therefore, due to the clinical picture and the high value of blood valproic acid, continuous venovenous hemofiltration (CVVH) was started as a purifying technique using a high cut-off dialyzer. Valproic acid blood concentration decreased to 186 mg/L on the second day, and to 22 mg/L on the third day; the ammonium concentration remained within the normal range. However, despite blood valproic acid purification, the patient continued to be neurologically unresponsive. Blood phenytoin concentrations showed a day-by-day increase, reaching the highest value of 80 mg/L (therapeutic range 10–20 mg/L) on the seventh day of hospitalization. No drug bezoar was detected in the gastrointestinal tract. Therefore, CVVH was re-started in order to reduce phenytoin blood concentrations, which normalized in four days with a concomitant improvement in the patient's neurological symptoms. According to EXTRIP guidelines, we suggested high-efficiency intermittent haemodialysis (HD) as a purification method [3,4]. However, due to the critical patient's circulatory condition, CVVH was preferred.

Conclusion: This report underlines the importance of the erratic absorption phase after phenytoin overdose as well as the importance of phenytoin blood monitoring and CVVH as a purification technique in critical patients following massive phenytoin ingestion.

188. Pure amiodarone overdose by ingestion: a case series

Abstract

Objective

Amiodarone is a Type III antiarrhythmic drug that acts primarily by blocking potassium channels (resulting in a QT-interval prolongation). It has also weak α and β adrenergic antagonist activity and can block both calcium and sodium channels, leading to I, II, and IV antiarrhythmic effects. Since its approval as an antiarrhythmic drug (1985), only a few cases of acute intoxication by oral intake without co-ingestants have been reported in the literature [1,2]. We conducted a retrospective study evaluating the clinical characteristics of pure amiodarone acute overdose by ingestion.

Methods

We enrolled all patients with voluntary ingestion of amiodarone tablets (only) for self-harming purposes referred to our Poison Control Centre from August 2008 to July 2023. Age, sex, ingested dose, clinical manifestations, treatment and outcome were evaluated for each patient.

Results

A total of 13 patients were collected (M = 5, F = 8). Four (M = 2, F = 2) were excluded due to lack of information in the clinical outcome (M = 2, F = 1), or late presentation to the emergency department (48 h) resulting in missing clinical data related to the first hours of intoxication (F = 1). The final series included 9 patients (M = 3, F = 6, median age 75 years). The average amiodarone dose ingested was 2000 mg. During clinical observation, only 22% (2/9) of the patients presented a slight prolongation of the QTc interval, 466 ms (at 1.5 h after ingestion) and 473 ms (at 3 h after ingestion), respectively, in the absence of clinical symptoms. In both cases, the QTc interval returned spontaneously to physiological values in the following hours. Most (88%, 7/9) patients remained asymptomatic during the observation period. Concerning treatments: all the patients underwent gastrointestinal decontamination without any other specific treatment. No lethal cases were recorded, and all patients fully recovered.

Conclusion

Our data are in accordance with literature data, reporting cardiovascular symptoms associated with electrocardiogram (ECG) alterations (tachyarrhythmia and prolongation of the QTc interval) as the main clinical complications [1,2]. Even in the literature cases, most complications resolved spontaneously. One of the main limitations of this study was the missing quantification of plasma amiodarone concentrations due to the current unavailability of a specific test in emergency settings.

189. Acute deferoxamine overdose due to administration error: not a problem?

Abstract

Objective: Deferoxamine is a parenteral chelator used to treat iron and aluminum toxicity. Based on early case series, the intravenous infusion rate is recommended not to exceed 15 mg/kg/h, however the maximum safe rate of administration remains unclear. We report a case of an unintentional acute deferoxamine overdose with a benign clinical course.

Case report: A 5-year-old, 13.3 kg, girl with transfusion-dependent beta-thalassemia complicated by iron overload was admitted to the hospital for a regularly scheduled deferoxamine chelation treatment. In a medication error, 800 mg (60 mg/kg) deferoxamine was inadvertently administered over 1 h instead of over 12 h. The error was recognized approximately 30 min thereafter. Vital signs at this time were within normal range for her age group. She was asymptomatic with an unremarkable physical examination. Serial chemistries demonstrated a mild uptrend in serum creatinine which resolved without intervention (Table 1). Chelation was resumed the following week.

Table 1 Serial chemistry studies at hour (h) relative to time (T) of completion of deferoxamine bolus given over 1 h instead of 12 h.

Chemistry (reference range, units)	T-1h	T + 3h	T + 9h	T + 17.5h	T + 36.5h	T + 59.5h
Blood Urea Nitrogen (2.5–8.9 mmol/L)	4.6	3.6	2.5	1.8	1.8	3.2
Creatinine (62–115 mmol/L)	<18	18	18	35	27	18

Conclusion: This unintentional intravenous overdose of 60 mg/kg deferoxamine over one hour was well-tolerated without clinically significant adverse effects. Prior reports describe rate-related hypotension in two children administered 80 and 150 mg/kg intravenous deferoxamine over 15 min each [1], and acute renal failure following unintentional overdoses of 38 mg/kg intravenous deferoxamine for 18 h [2] and 87.5 mg/kg intravenous deferoxamine for 8 h [3]. Our patient had normal vital signs and physical examination 30 min after the overdose. The slight uptrend in her serum creatinine, which remained below the normal laboratory reference range, was unlikely related to deferoxamine given rapid resolution without intervention. We report this case to add to the scant literature on acute deferoxamine overdose.

190. Sleeping benzodiazepine beauties: too much of a good thing

Abstract

Objective: Benzodiazepines are the cornerstone of management for ethanol withdrawal, and occasionally higher doses are necessary to achieve sufficient inhibitory tone due to downregulated gamma-aminobutyric acid (GABA) receptors. Our poison center has previously reported a patient demonstrating atypical elimination kinetics following treatment of ethanol withdrawal with large doses of diazepam [1]. We report two further cases of patients who developed prolonged obtundation following treatment with large doses of diazepam.

Case series: A 77-year-old male received a total of 1040 mg diazepam over nine days for presumed ethanol withdrawal. He remained obtunded for nine days thereafter, complicated by aspiration pneumonia. The treating team was uncomfortable administering flumazenil, and the patient required intubation for airway protection. He remained intubated (off sedation) until 28 days after last diazepam administration. The apparent half-lives of diazepam and nordiazepam were calculated to be 53 and 278 h, respectively.

A 67-year-old male received a total of 660 mg diazepam over 27 h for presumed ethanol withdrawal. He remained obtunded for 22 days thereafter, complicated by frequent airway concerns. Shortly before planned transition to comfort care, 0.2 mg flumazenil was administered yielding immediate alertness. In consultation with the poison center, he received a daytime flumazenil infusion (0.3 mg/h) to allow for enteral intake, physical therapy, and family interaction, and intubation was not required. During hospitalization the patient developed radiographic and laboratory findings of cirrhosis which were not present on admission. The apparent half-lives of diazepam and nordiazepam were calculated to be 124 and 156 h, respectively. Genotyping demonstrated normal activity of CYP3A4 and CYP2C19, the two primary metabolizers of diazepam. Thirty-seven days after last diazepam administration, flumazenil was discontinued for spontaneous alertness.

Conclusion: These remarkable cases demonstrate variably prolonged elimination half-lives of diazepam and nordiazepam without development of acute tolerance. While the long half-life of diazepam and its active metabolite are considered therapeutically beneficial properties in the treatment of alcohol withdrawal, we highlight the potential risks associated with administration of excessively high doses. Providers should exercise caution with high-dose diazepam administration, especially among patients with underlying health risks or advanced age, and consider a maximum dosage of long-acting benzodiazepines in hospital protocols. These cases also underscore the diagnostic and therapeutic value of flumazenil; we suggest closely monitored daytime flumazenil to mitigate sequelae of prolonged coma.

191. Trends in the frequency of bites by Vipera berus and the impact of Covid-19 national lockdown on the number of snakebites

Abstract

Objective

Vipera berus is the only venomous snake native to the Czech Republic. The aim of this study is to describe trends regarding snakebite enquiries to the Czech Toxicological Information Centre (TIC) between 2019 and 2023.

Methods

Data from the Czech TIC in Prague were analysed retrospectively for trends in the frequency of bites by Vipera berus in children (0–15 years) and adults from 1 January 2019, to 30 September 2023. Only cases with compatible symptoms and circumstances of the exposure were included. Data collected included age group, sex, year of the call, and antivenom treatment.

Results

In total, 190 cases with the diagnosis of Vipera berus bite were registered during the study period, of which 45 (23.7%) were children, and 145 (76.3%) adults; 104 (54.7%) were males, and 86 (45.3%) females. Fifty-nine (31.0%) patients were administered antivenom (antibodies made by hyper-immunising sheep with Vipera berus venom) over five years. Thirty-seven were adults (25.5% of all adults) and 20 children (44.4% of all children). No adverse reactions to the antivenom were reported and no patient died because of snakebite during the observation period. In 2020, a significant increase in reported cases, as well as in administered antivenom was found compared to 2019, 2021, 2022 and 2023, predominantly in adults. This could be explained by an increase in outdoor activities since the COVID-19 lockdown started and restrictions limited other leisure activities and international travel.

Conclusion

In recent years, the average number of bites by Vipera berus in the Czech Republic has been 33.5 ± 3.4 and the average number of antivenom administered was 9.7 ± 2.3 per year, except in 2020. During the Covid-19 lockdown, in 2020, we registered 56 snakebite enquiries and 20 packs of antivenom were administered.

Acknowledgements

Cooperatio 207041-3 Pharmacology.

192. Seizures in acute poisoning in children and adolescents – clinical and evolutive characteristics

Abstract

Objective

To assess the main characteristics and clinical outcome of seizures in acute poisoning in children and adolescents.

Methods

We performed a 6-year retrospective study of acute poisoned patients aged between 0 and 18 years who presented seizures as the main clinical manifestation. The following variables were analyzed: age, sex, involved agent, type of seizures, associated symptoms, treatment, and clinical outcome. Data analysis was performed using Microsoft Excel software and Fisher’s exact test.

Results

Out of the total of 3794 patients aged 0–18 years old who were diagnosed with acute poisoning between 2017 and 2022, 49 (1.3%) presented seizures. The median age was 12 years old and the male to female ratio was 1:1. Intentional poisoning was reported in 19 (38.8%) cases, the main agents involved being psychotropic drugs. Accidental poisoning was reported in 30 (61.2%) cases, of which 21 were caused by carbon monoxide exposure. High dose atropine was used in 5 patients as an antidote in acute poisoning with cholinesterase inhibitory insecticides. Analyzing the type of seizures, tonic-clonic generalized crises were found in 32 (65.3%) patients, hypotonia or hypertonia in 8 (16.3%) cases each and focal seizures in 1 child. The associated symptoms were acidosis (46.9%), vomiting (36.7%), mydriasis/miosis (22.4%), and cyanosis (20.4%). The majority of cases had favorable outcomes, but 18.4% of them experienced recurrent seizures and 16.3% prolonged seizures (over 15 min). Overall, 5 (10.2%) required orotracheal intubation, and one patient died. The probability of developing coma was shown to be greater in multidrug intentional poisonings (p < 0.05). The main therapeutic measures consisted of benzodiazepines administration and oxygen therapy.

Conclusion

Seizures represent a rare but severe event in acute poisoning in children and adolescents. The most frequent agent in our study was carbon monoxide followed by psychotropic drugs, which is similar to previous research [1]. The probability of developing coma in acute poisoned patients with seizures is significantly higher in acute intentional multidrug poisoning.

193. Thallium poisoning: Pavia Poison Centre clinical experience (2000–2022)

Abstract

Objective

Thallium poisoning is a rare and often misdiagnosed condition characterized by a nonspecific and insidious clinical onset, delaying appropriate treatments. In fact, the clinical suspicion may be made at the late stage of poisoning when alopecia or polyneuropathy appear. Thallium is often used with criminal intent and the poisoning may involve more than one victim. The main aims of our study are (i) to identify the clinical manifestations useful for early suspicion of poisoning, (ii) to evaluate the clinical response to antidote treatment and (iii) to identify possible correlation between thallium concentration (serum/urine) versus clinical severity versus outcome.

Methods

All laboratory confirmed thallium poisoned patients collected from 2000 to 2022 at the Poison Control Centre (PCC) were retrospectively evaluated concerning circumstances of poisoning, demographic data, clinical manifestations, thallium concentrations, antidote treatment and outcome. Inclusion criteria: positive history for thallium ingestion and/or coherent clinical findings associated with thallium concentration in serum >2 µg/L and urine >5 µg/L (inductively coupled plasma mass spectrometry (ICP-MS)). Index-case definition: first identified case in a cluster.

Results

Nineteen patients were studied [54.4 ± 21.0 years; 11 females (57.9%)]. In 18 cases thallium was used with criminal intent and only one case was accidental. Three fatal cases (15.8%) were registered. Early clinical manifestations in index-cases were gastrointestinal discomfort (57.9%), abdominal pain and chest pain (52.6%); no statistically significant relation between these clinical findings and thallium concentrations in serum/urine was found. Paraesthesia and alopecia appeared late in 18/19 (94.7%) and in 13/19 cases (68.4%), respectively. Prussian blue was administered to all patients and the duration of the treatment [mean duration 55 (3–131 days)] was statistically related with the decrease of thallium concentrations in both serum and urine. In six cases (6/16; 37.5%) the polyneuropathy was persistent at 6 months without statistical correlation with thallium concentrations; permanent peripheral neuropathy was recorded in 2 of them. A statistically significant correlation was found between serum (>3400 µg/L) and urine (>16,300 µg/L) thallium concentration and unfavourable outcome.

Conclusion

Thallium is a poison of choice for criminal purposes. Due to non-specific early manifestations, clinical suspicion is always a challenge, partly facilitated when more than one person is involved. Laboratory support plays a key role and is crucial for the final diagnosis. The antidote is safe and effective. Neurological sequelae are possible (in our experience 11% of cases). Probably, repeated consumption of thallium in food or drink may also influence the poor outcome in some poisoned patients.

194. Crossing borders of poison: a comparative analysis of call statistics and exposures between Dutch and UK poisons information services in 2022

Abstract

Objective: Globally, poison centres (PC) provide evidence-based management advice to both healthcare professionals and members of the public. The UK (NPIS) and Dutch PIC (DPIC) are unique in that they provide advice solely to healthcare professionals. We compared characteristics on telephone enquiries to the DPIC and NPIS.

Methods: Anonymous aggregated data were retrospectively collected on call statistics, enquirers and reported exposures to the DPIC [1] and NPIS between 1 January 2022 and 31 December 2022.

Results: Both the DPIC and NPIS receive a similar number of human exposure enquiries annually (Table 1) while serving a population that differs nearly 4-fold. The NPIS observed a shorter waiting time and fewer hang-ups, but a longer handling time (almost 2 min more) compared to the DPIC. The number of Specialists in Poison information (SPIs) dedicated to telephonic operations at the DPIC is half of that of NPIS during day and evening times. The DPIC received the greatest number of enquiries from primary care professionals, as did the NPIS. However, the NPIS received more enquiries from hospitals and the ambulance service. Paracetamol was (one of) the most frequently reported agents in both age groups (<13 and ≥13 years), and in both countries. Household products, vitamin preparations and over-the-counter medications also featured prominently.

Table 1 Call characteristics of Dutch and UK Poisons Information Centers in 2022.

Year: 2022	NPIS (UK)	DPIC (Netherlands)
Population served	67.33 million	17.81 million
Call statistics
Annual calls (N)	44,659	50,163
Population call rate	0.06%	0.28%
Annual hang-up calls (N)	2264 (5.1%)	4978 (9.9%)
Annual processed calls (N)	42,395	45,185
Mean handling time of call (sec)	359 (±257)	252
Mean waiting time caller of processed calls (sec)	66 (±109)	95
Callers
General practitioner and/or Telephone triage service (%)	59	56
Hospital (%)	25	7
Veterinarians (%)	Not applicable	20
Ambulance/EMS (%)	11	7
Top 5 agents <13 years
UK (n = 9967 patients) Multivitamins 710	Netherlands (n = 13,538 patients)  Paracetamol		771
Paracetamol 689	Vitamin D supplements		749
Reed diffuser 257	Multivitamins and/or minerals		442
Hand sanitiser 249	Dishwasher detergents		337
Ibuprofen 215	Laundry detergent pods		273
Top 5 agents ≥13 years
UK (n = 26,002 patients) Paracetamol 4846	Netherlands (n = 18,784 patients)  Paracetamol		2157
Ibuprofen 2806	Alcoholic beverages		1325
Paracetamol + codeine 1411	Quetiapine		1006
Naproxen 879	Lorazepam		940
Sertraline 778	Ibuprofen		874

Conclusion: Clear differences were observed between two PCs that only serve healthcare professionals. Explanation could be differences in the healthcare systems resulting in a different call rate as well as how resources are allocated within Poison Centres for answering of telephone enquiries. PCs can learn and improve based on each other’s services and should consider reviewing operating models in more detail to better understand where mutual exchange of ideas could support the provision of poisons information advice.

195. Severe subacute inorganic arsenic poisoning caused by a folk medicine for treatment of psoriasis: a case series

Abstract

Objective

To describe the clinical manifestations of a cohort of patients with subacute arsenic poisonings from consumption of anti-psoriatic folk medicine (FMed) allegedly made of realgar (an arsenic sulfide mineral) and describe the chelation efficacy of succimer (dimercaptosuccinic acid, DMSA) and unithiol (2,3-dimercapto-1-propanesulfonic acid, DMPS).

Methods

From August to October 2015, we prospectively collected data on all consecutive patients with FMed exposure reported to our centre. Arsenic exposure was estimated by the amount and duration of FMed consumption and the content of arsenic measured from the FMed sample. The frequency of the clinical features and laboratory abnormalities were recorded. Symptomatic patients or asymptomatic patients with elevated urine arsenic concentrations for spot urine samples (>68 nmol/mmol Cr) were treated with succimer (30 mg/kg/d orally for 5 days). Twenty four-hour urine samples (24hU) were collected for arsenic measurements on the day before (D0_DMSA) and after the commencement of succimer (D1_DMSA). In light of the reported effectiveness of unithiol in the literature, patients were further treated with unithiol (400 mg/d orally for 7 days after a drug holiday of 3-week period). Similarly, 24 hU were collected for arsenic measurements before (D0_DMPS) and after commencement of unithiol (D1_DMPS). Seafood intake was restricted during the treatment and urine measurement. A comparison of mean changes of the 24 h urinary arsenic excretions with succimer and unithiol was made by the Wilcoxon Rank Sum Test.

Results

Thirty-one patients were recruited. Arsenic content was 42,657 µg/mg in the FMed sample. The estimated mean daily arsenic exposure was 259.8 mg/day (range 90.6–494.5). The mean duration of exposure was 132.9 days (range 7–1098). Clinical manifestations included nausea/vomiting (55%); significant weight loss (40%); melanosis (60%); keratosis (25%); macrocytosis (50%); and sensory neuropathy (50%). The mean spot urine arsenic/Cr concentration was 578.9 nmol/mmol Cr (range 68–4730). Sixty-five percent of patients had elevated 24 hU arsenic concentrations with a mean of 4337.3 nmol/day (range 959–15,026). Overall 18 and 15 patients were treated with succimer and unithiol, respectively. The 24 hU of 12 patients were available for measurement and comparison of urinary arsenic excretion following chelating therapy. The mean changes of 24 h urinary arsenic excretion with succimer and unithiol were −32.9 ± 375.5 nmol/day and 221.6 ± 258.8 nmol/day, respectively (p = 0.24).

Conclusion

Adverse reactions and laboratory abnormalities were common in subacute arsenic poisoning following use of realgar FMed. Response to chelation therapy with unithiol appeared more effective than with succimer. Further studies are needed to confirm the findings.

196. Patient knowledge regarding paracetamol at an internal medicine outpatient clinic in Switzerland

* Contributed equally to abstract.

Abstract

Objective

Paracetamol is a common over-the-counter (OTC) analgesic and antipyretic, typically used for mild to moderate pain [1]. Although generally considered safe at therapeutic doses, paracetamol can cause severe hepatotoxicity in supratherapeutic doses or in the presence of risk factors such as malnutrition, co-medication with inducers of cytochrome P450 and chronic alcohol abuse [2]. The aim of this study was to investigate patients’ knowledge regarding the use and risks of paracetamol.

Methods

Over the course of one month in 2023, patients in the waiting area of the outpatient clinic of the internal medicine department at a Swiss University Hospital were invited to participate in an anonymous survey. The survey consisted of a 15-item questionnaire including knowledge questions about paracetamol (maximal daily dose, adverse effects, potency, indications, risk factors for intoxication) and a list of ten medicinal products (including OTC and combi-preparations) to identify which ones contain paracetamol. A knowledge score was calculated (maximum 15 points, characterized as “good” (≥12), “satisfactory” (≥9 to <12), or “inadequate” (<9)) and compared based on sex, age group and educational level.

Results

Among the 250 participants (54% older than 45 years, 45% women), 169 (68%) answered all questions and were included in the total score evaluation. The median score was 4 (range 0–15) and 88% achieved <9 points, indicating an inadequate knowledge level. Most of the participants identified the indications of paracetamol pain and fever correctly (90% and 52%, respectively), while only 37% selected the correct answer for the maximum daily dose (4 g). Younger participants (≤ 45 years) had higher scores than older age groups (median 4.5 versus 3.5, p = 0.02) and men lower scores than women (median 3.5 versus 4.5, p = 0.002), while no statistically significant differences were observed based on the educational level. Only for two preparations was it correctly identified by the majority of participants that they contained paracetamol.

Conclusion

The survey demonstrated gaps in patients’ knowledge regarding the use and risks of paracetamol. In particular, the identification of products containing paracetamol was insufficient in most cases. By identifying these gaps, strategies such as better labelling, boxed warnings or package size restrictions could be developed to improve patient awareness and safety and reduce the risk of accidental paracetamol intoxication.

197. From guidelines to practice: clinical toxicologists’ decision-making in digoxin poisoning

Abstract

Objective

Traditionally it is recommended that a patient should be treated with 10–20 vials of digoxin-Fab for acute and 2 vials for chronic digoxin poisoning. Since 2016, research has shown that acute digoxin poisoning can be managed with small, titrated doses while chronic digoxin poisoning can be managed with supportive care or just 1 vial of digoxin-Fab [1]. In August 2020, the therapeutic guidelines in Australia recommended changes in the management of both acute and chronic digoxin poisoning, as reflected by the clinical research findings. We aimed to determine if the new clinical guidelines changed advice given by clinical toxicologists (CTs) regarding the management of digoxin poisoning.

Methods

This is a retrospective, multi-centre study (2017–2022) that evaluated the advice given by clinical toxicologists at the New South Wales Poisons Information Centre (NSWPIC) to clinicians regarding the management of acute and chronic digoxin poisoning by a single researcher. The data included patient demographics, clinical details regarding the poisoning and management advice as recorded by the NSWPIC and case records of CTs. Advice given was compared to the new clinical guidelines.

Results

From 2017 to 2022, CTs at NSWPIC provided advice to 476 enquiries (including recalls) regarding acute and chronic digoxin poisonings. There were 149 chronic and 17 acute digoxin poisoning cases across 34 and 15 hospitals respectively. CTs adopted the new guidelines in 60.5% and 95.2% (difference: 35%, 95%CI: 23 to 49%, p < 0.0001) for chronic digoxin poisoning and 83.3% and 80% (difference −3%, 95%CI: −34% to +55%) for acute digoxin poisonings, before and after August 2020, respectively. Recommendations to administer digoxin-Fab decreased for chronic and acute poisonings from 39.5% to 31.8% (difference 7.8%, p = 0.39) and 75% to 60% (15%, p = 0.60), respectively.

Conclusion

There was a change in CTs’ advice and very high compliance with new clinical guidelines in the management of chronic digoxin poisoning. There were too few cases of acute digoxin poisoning to draw any conclusions. It is likely that there was considerable change in advice prior to the official guideline release and an even larger change might be demonstrated from earlier clinical data.

198. Risk perceptions of nicotine and nicotine products among Swiss healthcare professionals

Abstract

Objective: Nicotine is the underlying cause of sustained tobacco use, however, most smoking-related toxicities are caused by pyrolytic products or other chemicals present in tobacco. Healthcare professionals’ need to be knowledgeable about this subject to adequately provide information in the context of smoking cessation counseling. However, misperceptions regarding nicotine and tobacco-related risks have been uncovered in previous studies from the US [1,2]. This survey-based study aimed to investigate potential misperceptions among healthcare professionals within a large Swiss hospital group.

Methods: An anonymous online survey was conducted targeting all physicians and pharmacists within the hospital group. The survey included ratings on 0–100 visual analogue scales, ranging from agreement to disagreement or not harmful to harmful, depending on the question. For analysis, the scale was divided into three equal segments, with the middle part representing “unsure” or “moderately harmful”, respectively.

Results: The survey was distributed to 2026 participants and 279 (14%) responded. Among the responders, 53% were male, 69% were ≤40 years old and 74% regularly advised their smoking patients to quit. The results obtained are summarized in Table 1.

Table 1 Results of a survey of hospital physicians and pharmacists on risk perceptions of nicotine and nicotine products (279 respondents).

Statement or question in survey	Disagree	Unsure	Agree
Nicotine is the main substance in tobacco that makes people want to smoke (N = 279)	25 (9%)	40 (14%)	213 (76%)
Nicotine on its own causes… (N = 279)
birth defects	124 (44%)	74 (27%)	81 (29%)
cancer	204 (73%)	31 (11%)	44 (16%)
cardiovascular disease (CVD)	114 (41%)	57 (20%)	108 (39%)
chronic obstructive pulmonary disease (COPD)	193 (69%)	44 (16%)	41 (15%)
How harmful do you think the following products are for users? (N = 203)	Not harmful	Moderately harmful	Harmful
Tobacco cigarettes	0 (0%)	11 (5%)	192 (95%)
Electronic cigarettes	6 (3%)	86 (42%)	111 (55%)
Heated tobacco products	3 (1%)	74 (36%)	126 (62%)
How harmful do you think the following products are for bystanders in the immediate vicinity? (N = 203)
Tobacco cigarettes	2 (1%)	17 (8%)	184 (91%)
Electronic cigarettes	59 (29%)	80 (39%)	64 (32%)
Heated tobacco products	31 (15%)	85 (42%)	87 (43%)

Conclusion: The majority of the participants were aware that nicotine does not directly cause cancer, in sharp contrast to previous studies from other countries [1]. Opinions were more divergent with regard to topics such as birth defects and cardiovascular diseases. To address these knowledge gaps future curricula should put more emphasis on these aspects and specific training programs for healthcare professionals should be integrated.

199. Physic nut (Jatropha curcas) poisoning: characterization of three cases

Abstract

Objective

Jatropha curcas (physic nut, purging nut) is an evergreen plant from the Euphorbiaceae family, which grows in tropical regions from Mexico, Central America, Asia and Africa. Its uses vary from hedges to applications in traditional medicine [1] moreover, in recent years, it is being studied as a biofuel. J. curcas has toxic properties as it contains, predominantly but not exclusively, toxalbumins in the seeds [2]. Medical literature concerning the incidence of Jatropha curcas poisoning in pediatric populations in North and Central America is scarce, we present a series of three clinical cases and highlight the incidence of exposure as the plantations of Jatropha curcas increase.

Case series

Three 5-year-old female children, were admitted to the emergency department following ingestion of J. curcas seeds 2 h earlier. One of them had nausea, vomiting, and diarrhea secondary to ingesting 5 seeds. The second child was documented to have ingested 10 seeds, resulting in abdominal pain, nausea, vomiting, diarrhea, and mild dehydration. The third child presented nausea, vomiting, diarrhea, drowsiness, severe dehydration with hypovolemic shock secondary to the ingestion of 14 seeds. All children required intravenous fluid resuscitation. Their biochemical profile revealed leukocytosis with neutrophilia; electrocardiograms were normal, and no neurological alterations were found in any of the patients. The children were discharged 48 h after admission with all symptoms resolved and no complications.

Conclusion

Children are at higher intoxication risk due their natural behavior and curiosity, J. curcas seeds are sweet to the taste, which predisposes them to accidental ingestion. There is no specific toxic dose, however, ingesting more than 10 seeds would be dangerous if not treated promptly, as previously exemplified in the child with hypovolemic shock. Research on the energetic potential from the seeds, increases the risk not only in the pediatric population, but for the communities within the reach of these plantations; individuals should be aware of the risks associated with this exposure. Healthcare providers must recognize, assess, and initiate appropriate management in patients with J. curcas poisoning. Although this intoxication can be self-limiting, it can also trigger potentially life-threatening consequences in children since they are highly susceptible to hydroelectrolyte alterations and acid base disorders.

200. Analysis of the queries received on an antidote management online platform

Abstract

Objective

The Spanish Antidote Network (www.redantidotos.org), a virtual platform designed for the management of antidotes [1], has a section dedicated to resolving non-urgent toxicological queries. This tool is available to any healthcare professional who wishes to ask a question about availability or use of antidotes. The objective of our study is to analyse the questions received.

Methods

A descriptive study carried out from July 2015 to September 2023. The questions were answered by pharmacists or doctors who are experts in clinical toxicology, including paediatrics. Questions received were classified by topic and date. We excluded the queries related to the online platform functioning, because they were not scientific and those not asked by a healthcare professional.

Results

In this period, 221 queries were answered, with 20–52 annual consultations. The subject of the queries were as follows: Availability and shortage problems (54; 24.4%); antidote stock (43; 19.5%): provision of certain antidotes according to the characteristics of the hospital; scientific evidence (28; 12.7%): antidote effectiveness (20), lead poisoning (2), bioterrorism (1), oleander toxicity (1), ricin toxin (1), smallpox (1), skin decontamination (1) and toad venom (1); specific treatment for intoxications (26; 11.8%); antidote administration (26; 11.8%): N-acetylcysteine (4), lipid emulsion (3), carnitine (2), dantrolene sodium (2), protamine (2), glucagon (2), botulinum antitoxin (1), ascorbic acid (1), deferoxamine (1), dimercaprol (1), EDTA (1), ethanol (1), calcium folinate (1), calcium gluconate (1), methylene blue (1), polyethylene glycol (1) and silibinin (1); decontamination (14; 6.3%): ipecac syrup (9), sodium sulfate versus magnesium sulfate (2), Fuller’s earth (1), activated charcoal (1) and Diphoterine^® (1); antidote composition (10; 4.5%): snake venom antiserum (9), EDTA (1); and other queries (20; 9%): co-operation with official organizations (5), network design (3), antidotes for exotic snakes (3), antidotes stability (2), bioterrorism (2), economic queries (2) additive notification (1), pharmacokinetics (1) and antidotes’ sample (1).

Conclusion

Antidotes availability and adequacy of antidotes stocking according to the characteristics of each hospital, are the main concerns for doctors and hospital pharmacists. In this regard, one of the key focuses of the Spanish Antidotes Network is to promote the publication of updated clinical guidelines on the availability and use of antidotes [1].

201. Intentional poisoning in adolescents admitted to a toxicology department: a retrospective study

Abstract

Objective

The aim of this study was to analyse the characteristics of intentional poisoning in adolescents, admitted to the Pediatric Toxicology Department, Toxicology Clinic, UMHATEM “N.I.Pirogov”.

Methods

A retrospective review of all cases of suicide attempt or intentional self-poisoning, admitted to the Pediatric Toxicology Department, from August 2022 to August 2023 was performed. Demographic data, presenting syndromes, laboratory tests, previous illness and psychiatric associated disorders were obtained retrospectively from the patients’ charts. The cases of poisonings were evaluated with respect to clinical course, therapy and outcome.

Results

A total of 42 adolescents with acute intentional poisoning were treated in the department over the study period. Patients were aged between 11 and 17 years. There were 36 girls (85.7%) and 6 boys (14.3%). Age group ratio: 11–13 years old – 10 (23.8%), 14–15 years old – 19 (45.2%) and 16–17 years old – 13 (31.0%). All patients had pharmaceutical intoxication. The medicines included analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, antiepileptics, antidepressants, neuroleptics, antipyretics, vitamins, antihypertensive drugs, etc. Eighteen of the patients (42.9%) were poisoned by only one drug. In 24 (57.1%) of the cases, more than one drug, was involved in the poisoning. Ten (23.8%) of the children were diagnosed with psychiatric disorders including bipolar affective disorder, personality disorder, anorexia, depression, hyperactive disorder, and epilepsy. The severity of poisonings varied from moderate to severe. Cerebral toxic syndrome (altered consciousness) was noted in 27 (64.3%) cases, general toxic syndrome in 7 (16.7%), gastritis manifestations in 18 (42.9%), and cardiotoxic syndrome (hypotension, bradycardia) was presented in 6 (14.3%) cases. There were no deaths. Management in all cases was supportive with the main treatment modality being gastrointestinal decontamination by gastric lavage and activated charcoal, intravenous fluids, antidotal therapy and symptomatic treatment.

Conclusion

Acute self-poisoning in adolescents has become an important cause of admission to a toxicology department. The number of cases has increased in the last few years, so close monitoring of this age group is a real necessity.

202. Acute alcohol poisoning among children and adolescents: a retrospective analysis

Abstract

Objective

To analyze the characteristics of acute alcohol poisoning among children and adolescents, admitted to the Pediatric Toxicology Department, Toxicology Clinic, UMHATEM “N.I.Pirogov”.

Methods

We studied patients under 18 years old with acute alcohol poisoning, who were hospitalized during the period January 2023 to September 2023 in the Pediatric Toxicology Department. Data were retrieved from hospital records and we considered the following criteria: age, gender, home environment, blood ethanol concentration, clinical course, treatment and outcome. The blood ethanol concentration was measured by thin-layer chromatography.

Results

The study included 90 children and adolescents; 48 (53.3%) boys and 42 (46.7%) girls. Patients were aged between 1 and 17 years. The age distribution was as follows: 1–8 years old 4 cases (4.4%), 12–13 years old 26 cases (28.9%), 14–15 years old 39 cases (43.3%) and 16–17 years old 21 cases (23.4%). The youngest age was 1 year and 4 months in a child with accidental poisoning. The ethanol blood concentration ranged widely from 1.3–4.6 g/L. The highest concentration was measured in a 6-year-old girl, admitted to the hospital in a coma. The most frequent reason for alcohol consumption among adolescents in our study was meeting with friends and they most often used one type of alcoholic beverage. The patients’ parents predominantly were employed. The severity of poisonings varied from moderate to severe. Cerebral toxic syndrome (altered consciousness) was presented in all patients (100%), somnolence in 53 (58.9%), obnubilation in 15 (16.7%), sopor in 21(23.3%), coma in 1 (1.1%), and gastrointestinal manifestations in 39 (43.3%). All the poisonings were successfully managed. Patients received intravenous fluids, nootropic and antiemetic agents, as appropriate.

Conclusion

Alcohol consumption among children and adolescents has risen during the last few years and acute alcohol poisoning has become an important cause of admission in a Pediatric Toxicology Department. This phenomenon demands increasing public awareness.

203. Methamphetamine-related presentations to the emergency departments over seven years (2016–2022)

Abstract

Objective

Methamphetamine is one of the most commonly used recreational drugs in Slovakia. Monitoring of Emergency Department (ED) presentations with acute toxicity associated with methamphetamine is important to improve understanding of the harms related to methamphetamine use.

Methods

Retrospective analysis of cases presented to the monitored EDs in Bratislava with acute recreational drug toxicity over the years 2016–2022 with a focus on methamphetamine.

Results

During the study period, 490 presentations were directly related to acute toxicity of substances used recreationally. Out of 490 cases, 197 (40.2%) involved methamphetamine, used alone (81, 41.1%) or with other substances (116, 58.9%). Among the methamphetamine cases, urine drug screening using an immunoassay was available in 145 cases (74.1%). Most of the patients (153, 74.1%) were transported to the ED by ambulance. Alcohol co-ingestion was reported in 47.4%, tetrahydrocannabinol (THC) in 26.4%, 3,4-methylenedioxymethamphetamine (MDMA) in 23.9% and benzodiazepines in 14.2% of the cases. Mean age of the patients was slightly higher than in non-users of methamphetamine (25.7 years versus 23.8 years, p < 0.02). The majority of the presentations (127, 64.5%) involved males. Females were significantly younger than males (median age 19 years versus 26 years, p < 0.01). A large majority of patients (73.3%) were alert at presentation (Glasgow Coma Score (GCS) = 15), 27.4% of the patients had impaired consciousness (GCS <15), among them 0.7% were unconscious (GCS <8). Other frequent symptoms were agitation/aggression (54.8%), tachycardia (41.8%), anxiety (26.4%), vomiting (19.8%), palpitations (17.8%), chest pain (16.8%), seizures (16.2%), psychosis (13.2%) and hallucinations (12.7%). One-third of patients required sedation. Almost half of the patients (47.8%) were referred to specialized departments, with almost 10% to critical care; 41.6% were medically discharged directly from the ED and 10.2% left the hospital at their own decision (self-discharged). The mean length of hospital stay for those who used methamphetamine was 43 h 29 min, which was significantly more than 26 h 43 min for those who did not have methamphetamine in urine. Two patients died in the hospital due to irreversible asystole. Patients who used methamphetamine were significantly more frequently admitted to psychiatric care (20.7%) than those who did not use the substance (6.7%).

Conclusion

Medical problems related to recreational use of methamphetamine were mainly characterized by sympathomimetic toxicity and mental disorders. Patients were often agitated and aggressive. The methamphetamine users had a longer stay in hospital and were admitted to psychiatric care more frequently.

204. Retrospective survey on cases of essential oil exposure

Abstract

Objective

Essential oils are potentially dangerous substances. Considering this, we examined the incidence of exposure to essential oils in the Slovak Republic.

Methods

Intoxication cases were analysed on the basis of data gathered from phone consultations and medical reports forwarded to the National Toxicological Information Centre (NTIC) in Bratislava from the whole of Slovakia between 2013 and 2022. Age, sex, purpose of exposure, type of essential oil, and clinical severity of the poisonings were examined. Cases were graded according to the Poisoning Severity Score (PSS).

Results

We reported 274 cases of essential oil intoxication during a 10-year period. Between 2013 and 2022 the number of consultations increased 3.5 times. Essential oil exposures in males made up 51% of cases. The most frequent route of exposure was by ingestion (95%). The majority of intoxicated patients were children (78%), 80% of them were less than 5 years old. Most of the poisonings (86%) were purely accidental, mistaking a bottle of essential oil for another pharmaceutical such as a cough syrup. Inadvertent administration by parents accounted for 14% of cases. Eucalyptus (30%), tea tree (17%), citrus and cinnamon oils were most frequently misused. Most patients reported no symptoms or had only minor effects (85.4% and 14.2%, respectively). Minor symptoms were mostly linked to eucalyptus and tea tree oil ingestion. Nausea, vomiting, diarrhoea and mucous membrane irritation made up the majority of the symptoms. We also observed dizziness and flushing. Throughout this 10-year period of observation, just one child (0.4%) displayed symptoms of severe intoxication; an 18-month-old boy with respiratory disease was administered 10 drops of sage essential oil by his mother as an alternative to prescribed antibiotics and experienced generalized tonic-clonic seizures.

Conclusion

Most ingestions in children were not associated with the development of symptoms because only miniscule amounts of essential oils were consumed. Nevertheless, children should always be closely monitored after ingesting toxic oils, because the intoxication can result in serious adverse effects such as epileptic seizures. Since essential oils are generally not regulated, it can be difficult to determine the exact content of the essential oil bottle, including plant species, concentration of active ingredients or possible contaminants. We suggest that all toxic essential oils should have child-resistant closures.

205. A qualitative content analysis of social media posts regarding access to sodium nitrite for suicide

Abstract

Objective

Sodium nitrite (SN) is a meat preservative increasingly used for suicide by poisoning. This trend appears to be driven by pro-suicide websites and social media communications that instruct potential users on how to obtain and use SN for self-harm. To better assess the nature of these communications, we performed a qualitative content analysis of social media posts concerning SN and suicide on Twitter and Reddit (commonly used social media platforms), with a focus on posts that discuss access to SN.

Methods

We scraped Twitter and Reddit from 2018 to 2022 for tweets or posts containing mentions of SN and suicide, collecting 1192 tweets and 112 Reddit posts. Tweets and posts were screened for inclusion and coded for themes (such as access to SN) using an a priori deductive coding scheme developed by our team. We coded 396 tweets and 43 Reddit posts as relevant to access and explored their subthemes. Frequency of subthemes among tweets/posts was used as a proxy for salience.

Results

There were no tweets found concerning SN and suicide prior to the year 2021, whereas Reddit posts were found throughout the timeline of the study. The frequency of both tweets and Reddit posts increased throughout the study period. In 396 tweets about access to SN, 89 (22.5%) discussed SN being sold as part of a suicide kit, 86 (21.7%) referenced various lawsuits against Amazon.com for selling SN, and 51 (12.9%) alluded to the role of Amazon’s algorithm in recommending pro-suicide items with SN. In 43 Reddit posts about access to SN, 15 (34.9%) described successful access of SN, 8 (18.6%) reported inability to access SN, and 6 (14%) noted that access to SN was lost or taken away before they could use SN.

Conclusion

We observed conversations about SN and suicide on Reddit dating back to 2018, prior to prominent news and medical literature publications about this topic. Tweets regarding access were mostly reactions to current events by users not intending to obtain SN, whereas Reddit posts about this topic generally documented user experiences in attempting to obtain SN. Healthcare providers can use these data to drive educated patient conversations about lethal means access in vulnerable patients; similarly, public health advocates can use it to drive advocacy efforts for lethal means restriction as well as surveillance efforts to identify new trends in self poisoning.

206. A five year (2018–2022) retrospective analysis of vitamin enquiries to the National Poisons Information Centre in Ireland

Abstract

Objective: A retrospective analysis of vitamin enquiries received by the National Poisons Information Centre (NPIC) from 2018 to 2022.

Methods: NPIC enquiries regarding vitamins from 1 January 2018 to 31 December 2022 were collated. Statistical analyses were conducted using chi-squared, analysis of variance (ANOVA) tests and Tukey post-hoc analysis (using RStudio).

Results: Median patient age (years) in 2018 was 3 (IQR 1.4–5), 3 (IQR 2–5) in both 2019 and 2020, 3 (IQR 2–6) in 2021 and 3.5 (IQR 2.5–6) in 2022. ANOVA revealed a statistically significant difference in monthly total vitamin enquiry numbers across five years (p = 0.0002) (Table 1). Post-hoc analysis identified significant differences in monthly enquiries between the following years: 2018 and 2020 (p = 0.0005), 2019 and 2020 (p = 0.002), 2020 and 2022 (p = 0.001). Monthly vitamin D enquiries showed no significant difference (p = 0.304). Monthly multivitamin product enquiries displayed significant differences (p = 0.001) with post-hoc analysis indicating significant differences between 2018 and 2020 (p = 0.0008), 2019 and 2020 (p = 0.007), and 2020 and 2021 (p = 0.025). Most (88.2%) vitamin enquiry patients were asymptomatic, with no significant change in the proportion of asymptomatic/symptomatic cases over 5 years (p = 0.07). Similar proportions remained asymptomatic in the vitamin D group (88.4%) and multivitamin group (89.9%), with no significant change in the proportion of asymptomatic/symptomatic cases (p = 0.23 and p = 0.289, respectively). Patients aged <1-year represented 21.9% in 2018, 16.4% in 2019, 8.9% in 2020, 6.1% in 2021 and 4.0% in 2022 of all vitamin enquiries. There was a significant difference in all age groups across the five years (p = 5.04 × 10^l).

Table 1 Vitamin enquiries to the National Poisons Information Centre in Ireland over a 5-year period (2018–2022).

	2018	2019	2020	2021	2022
All vitamin enquiries	412	433	615	489	426
% of all enquiries to NPIC	3.84%	3.66%	5.26%	4.39%	4.14%
Vitamin D and analogues	165	144	160	143	122
Multivitamin products	212	241	379	289	251

Conclusion: Multivitamin enquiries to the NPIC increased substantially in 2020 compared to previous years and have somewhat returned to normal levels since, possibly due to greater multivitamin use during the COVID pandemic.

207. Analytically confirmed carbon monoxide exposures reported to the UK National Poisons Information Service (NPIS) 2009–2022

Abstract

Objective

To review incidence and nature of confirmed carbon monoxide exposures reported to the National Poisons Information Service (NPIS) between 1 January 2009 and 31 December 2022.

Methods

The study involved retrospective analysis of data collected between 1 January 2009 and 31 December 2022.

Results

The NPIS received enquiries relating to 2021 patients who had a carboxyhaemoglobin concentration measured. The median (IQR) measured carboxyhaemoglobin concentration in 1679 of 2021 patients was 5.4% (2.3–15.1). In the remaining patients, the carboxyhaemoglobin concentration was either given as a range (n = 104); measured but the result not known to the enquirer (n = 107); or measured using a breath or finger probe analyser (n = 131). The maximum Poisoning Severity Score (MAXPSS) was determined in 1911 of 2021 patients: 426 patients had a MAXPSS of 0; 1037 had a MAXPSS of 1 (minor toxicity); 166 had MAXPSS 2 (moderate toxicity), 252 were graded MAXPSS 3 (severe toxicity); 30 patients died (PSS 4). The median (IQR) measured carboxyhaemoglobin concentration in each of these PSS groups (0, 1, 2, 3 and 4) was 3.1% (2.0–7.9), 3.9% (1.9–9.5), 11.0% (3.6–20.2), 22.6% (11.8–33.0) and 37.0% (24.2–50.5), respectively. Where the sex of the patients was known (n = 1782), males accounted for 50.8%. Clinical features were recorded for 1925 patients. Four hundred and twenty-three patients were recorded as being asymptomatic. The most common reported features were headache (n = 603, 29.8%), followed by acidosis (n = 277, 13.7%), nausea (261, 12.9%), dizziness (n = 227, 11.2%) and coma (n = 209, 10.3%). Of the 30 fatalities, 25 were exposed in house fires, so thermal injury and smoke inhalation may have contributed. The remaining five were intentional exposures to carbon monoxide from a barbecue (n = 3) or vehicle exhaust fumes (n = 2). The circumstances of exposure were known in 1904 (94.2%) exposures. Exposure was accidental in 1725, intentional in 179 and was unknown in 117. Of the 179 intentional exposures, sex was known in 178 patients with a male preponderance (n = 147, 82.6%). The largest source of intentional exposure was exhaust fumes (from both vehicles and non-vehicles (n = 107, 59.8%)), followed by barbecues (n = 24, 13.4%). The location was known in 1911 patients, and mainly occurred in the home (n = 1616, 84.6%), the workplace (n = 181, 9.5%) and public areas (n = 89, 4.7%). The suspected source of carbon monoxide was known in 1795 cases, with faulty appliances being the most commonly implicated (n = 1034, 57.6%).

Conclusion

Carbon monoxide exposure remains an important preventable cause of morbidity and mortality in the UK.

208. Overview of moderate and severe poisoning due to inhalation exposure reported to the German Federal Institute for Risk Assessment from 2003 to 2022

Abstract

Objective

On the basis of the German National Chemicals Act, the German Federal Institute for Risk Assessment (BfR) receives reports on poisonings with chemical substances or products from physicians and institutions for statutory accident insurance and prevention or public sector accident insurers. All cases notified to the BfR are validated and registered in a standardised manner in BfR’s national poisonings database. Severity is assessed according to the Poisoning Severity Score (PSS) [1].

Methods

All moderate and severe cases with inhalation exposure registered between 2003 and 2022 were analysed for patient data, product categories and clinical course.

Results

In the years 2003 to 2022, the BfR received a total of 105,570 case reports of poisonings. In 9602 of these cases (9.1%) it was an inhalation exposure; 1492 of these cases (15.5%) had a moderate and 194 cases (2%) had a severe health disorder. All further evaluations refer to these moderate and severe cases. The BfR received 1106 reports (65.6%) from the institutions for statutory accident insurance and prevention or public-sector accident insurers describing occupational accidents. Overall 580 cases (34.4%) were reported by physicians from clinics or outpatient doctors. In total 1575 adults (93.4%) and 97 children (5.8%) were affected. In 14 cases (0.8%) the age group was not known. Exhaust gases, smoke or combustion gases were most often the cause of inhalation poisoning (n = 541; 32.1%), followed by chemical substances (n = 354; 21%). Inhalation of cleaning agents (n = 212; 12.6%) or paints or thinners also led to moderate or severe poisonings (n = 56; 3.3%). The main clinical symptoms were irritation of the respiratory tract with difficulty breathing, sometimes with dyspnoea, and impaired consciousness. However, nausea, vomiting, coughing, headaches, fainting, dizziness, weakness and other symptoms also occurred. In the case of inhalation poisoning, the eyes and/or skin were also often affected.

Conclusion

Cases of poisoning due to inhalation exposure occur at home as well as in the workplace. In our reports with moderate or severe health disorders, the cases with exhaust gases, combustion and smoke gases dominate. Compared to the total number of case reports, moderate and severe poisonings following inhalation exposure occur only rarely.

209. Oxycodone overdose is associated with the intention to self-harm among emergency department patients

Abstract

Objective

The intention to self-harm via overdose (OD) is a major cause of morbidity and mortality for emergency department (ED) patients. Factors associated with the intention to self-harm after opioid overdose can help inform clinical treatment and proper linkage to mental health resources. The objective of this study is to determine the association between qualitative toxicology results and the intention to self-harm among a cohort of patients presenting after opioid overdose to participating EDs across the US.

Methods

This is a secondary data analysis from the Toxicology Investigators Consortium (ToxIC) Fentalog Study, an ongoing prospective multicenter cohort at 9 participating medical centers in the US. Patients with suspected acute opioid OD are enrolled, clinical data is gathered, and residual blood samples collected as part of routine clinical care were analyzed qualitatively by liquid chromatography quadrupole time-of-flight mass spectrometry for the presence of over 1100 psychoactive substances. For this analysis, we included only patients who were categorized as “self-harm” intent versus “misuse/abuse” intent. Intention of overdose was collected via chart review. Multivariable logistic regression analysis was used to determine the association between self-harm intent (outcome) and analytes detected, adjusting for age, sex, race, and ethnicity. All analyses were conducted in R 4.2.2 and approved by a central institutional review board (IRB) (WIRB).

Results

Between 21 September 2020 and 13 May 2023, 1541 patients met inclusion criteria, and 836 cases had analyte results with either 1) self-harm intent or 2) misuse/abuse intent. Cases were categorized into self-harm intent (N = 103; 12.3%) or misuse/abuse intent (N = 733; 87.7%). In the multivariable analysis for the odds of the intention to self-harm, oxycodone was associated with 12% higher odds of presenting with the intention to self-harm compared to those without oxycodone present (aOR: 1.12; 1.02, 1.23). Additionally, the presence of fentanyl was 21% less likely to be associated with the intention to self-harm (aOR: 0.79; 0.75, 0.84) compared to those with misuse/abuse.

Conclusion

Oxycodone was associated with a higher adjusted odds of an intention to self-harm among patients presenting to the emergency department after an opioid overdose. Clinicians should be aware that those presenting with apparent oxycodone overdose (as opposed to illicit opioids) may be related to the intention to self-harm rather than misuse/abuse.

211. Use of cyproheptadine for the treatment of serotonin toxicity: a 10-year review of enquiries to the National Poisons Information Service (NPIS)

Abstract

Objective

Serotonin toxicity manifests with a range of clinical features, including neuromuscular hyperactivity, autonomic instability and altered mental status [1]. Cyproheptadine, an antihistamine with 5-HT_2A antagonist properties, has been used in the treatment of serotonin toxicity despite limited evidence for improved clinical outcomes [1]. We reviewed enquiries to the UK NPIS where the use of cyproheptadine was discussed.

Methods

We performed a retrospective analysis of enquiries to the NPIS between 1 June 2012 and 31 May 2022 involving cyproheptadine.

Results

There were 503 enquiries involving 446 patients. Median age was 30 (IQR 20–43) years and males accounted for 58.5% of exposures. A single serotonergic agent was ingested in 125 (28%) cases, and polypharmacy exposures were recorded in 199 (44.6%) cases. The agent(s) involved in 122 (27.4%) cases were unknown. Enquiries predominantly originated from Intensive Care (n = 204, 45.7%) and Emergency Departments (n = 188, 42.2%). Of the 446 patients, cyproheptadine had been administered prior to contact with the NPIS in 48 (10.8%), the NPIS recommended its immediate use in 84 (18.8%), cyproheptadine was advised to be considered in 168 (37.7%) and cyproheptadine was not recommended in 146 (32.7%) cases. We performed a statistical analysis of the 132 patients who were given/advised to give cyproheptadine and the 146 patients where its use was not recommended. Cyproheptadine was more frequently administered or recommended in those patients with a peak temperature of ≥39 °C (76/101, 75.2%) compared to those with a peak temperature of ≤38.9 °C (34/117, 29.1%) (p < 0.001). In addition, cyproheptadine was more frequently administered or recommended in those with a peak creatine kinase (CK) ≥ 1000 IU/L (47/74, 63.5%), compared with those with a CK <1000 (21/40, 52.5%), although this was not statistically significant (p = 0.253). An outcome was documented in 135/446 (30%) cases, of which 25 (18.5%) died. The age in fatal cases ranged from 17 to 55 years. A single agent was ingested in 12 (48%) fatal cases, more than one agent was ingested in 5 (20%) and the agent was unknown in the remaining 8 cases. Methylenedioxymethamphetamine (MDMA) was the substance most commonly implicated in fatal cases (n = 8).

Conclusion

Cyproheptadine is often discussed in calls to the NPIS for the management of serotonin toxicity. We demonstrated a statistical association between patients with a temperature ≥39 °C and the recommendation to use cyproheptadine. Further research into efficacy of cyproheptadine in serotonin toxicity is needed.

212. A 5-year review of blood mercury concentrations reported via the National Poisons Information Service (NPIS) or a Supraregional Assay Service (SAS)

Abstract

Objective: Mercury poisoning is a topic of confusion for healthcare practitioners and a source of many Poison Centre consultations. Whole blood mercury concentration is the recommended analysis for suspected acute poisoning [1]. Poison Centres are well placed to advise whether laboratory analyses are necessary and advising on indications for chelation [2].

Methods: We reviewed cases of suspected mercury poisoning reported to the NPIS and the Black Country Pathology Services SAS laboratory between 1 April 2018 to 31 March 2023.

Results: The NPIS received 316 enquiries regarding 254 patients and the SAS laboratory processed blood samples from 211 patients for mercury analysis during this time. Overall, there were 465 patients; 399 adults (aged ≥18 years) and 66 children. The NPIS and SAS laboratory were both utilised in 11 (2.4%) cases.

Blood mercury concentrations were available in 278/465 patients (59.8%). In 91 patients, blood mercury concentration was <5 nmol/L and concentrations in the remaining 187 ranged from 5 to 8542 nmol/L (1–1713 µg/L). Only 87 patients with blood mercury concentration exceeding 25 nmol/L (5 µg/L) underwent further data analysis (79 adults; 8 children) [1]. The exposure source was recorded in 55 cases; predatory fish consumption was most common (n = 33, 60.0%). Fifty-five adults had blood mercury concentrations ≥50 nmol/L including seven cases ≥250 nmol/L. The highest (8542 nmol/L) was recorded in a 28-year-old male who developed gingivitis, rectal bleeding and acute kidney injury following intentional ingestion of 1000 mg mercuric chloride. He was chelated with unithiol. At least 6 adults required chelation (unithiol n = 2, succimer n = 2 or a combination regimen n = 2). The median (IQR) blood mercury concentration in these cases was 2778 (671–4109) nmol/L. Cases involved intentional ingestion of mercuric chloride (n = 3), intentional ingestion/injection of elemental mercury (n = 2) and excessive predatory fish consumption (n = 1). In children, blood mercury concentrations exceeded 50 nmol/L in seven cases and exceeded 250 nmol/L in four (suspected exposure source; excessive predatory fish consumption n = 2, contaminated land n = 1 and unknown n = 1).

Conclusion: Limitations were that data from only one of seven UK SAS laboratories were reviewed, and in many NPIS cases a blood mercury concentration was unavailable. Poison Centres and SAS laboratories should consider ways to harmonise pathways for sample analysis and clinical interpretation in order to optimise the care of those suspected to have mercury poisoning.

213. A 5-year review of urine arsenic concentrations reported via the National Poisons Information Service (NPIS) or a Supraregional Assay Service (SAS)

Abstract

Objective

Arsenic poisoning is a topic of uncertainty for healthcare practitioners and a source of Poison Centre consultations. Urine arsenic corrected for creatinine is the recommended analysis for suspected poisoning but does not differentiate between non-toxic arsenobetaine from fish/seafood and toxic inorganic arsenic [1]. Poison centres are well placed to advise whether laboratory analyses are necessary and on the need for chelation [2].

Methods

We reviewed cases of suspected arsenic poisoning reported to the NPIS and the Black Country Pathology Services SAS laboratory between 1 April 2018 and 31 March 2023.

Results

The NPIS received 116 enquiries regarding 106 patients and the SAS laboratory processed 157 samples from 130 patients during this time. These involved 185 adults (aged ≥18 years) and 48 children; in 3 cases patient age was unknown. In only 8 (3.3%) cases were both services utilised. Of the 236 patients, a measured urine arsenic/creatinine ratio (with units) was available in 89 patients (38%) ranging from 1.5 nmol/mmol creatinine to 8619.6 nmol/mmol creatinine. Further data analysis focused on 57 cases (40 adults and 17 children) where the urine arsenic/creatinine ratio exceeded 17 nmol/mmol creatinine [1]. The source was known in 26/57 cases (17 adults, 9 children); dietary exposure to non-toxic arsenobetaine in 15 (ten adults, five children), contaminated water in five (two adults, three children), Ayurvedic/herbal medicines in two adults and miscellaneous (three adults and one child). In the 17 children where the urine arsenic/creatinine ratio exceeded 17 nmol/mmol creatinine the median (IQR) urine arsenic/creatinine was 92.5 (26.5–188.5) nmol/mmol creatinine. The highest concentration was in a 7-year-old child (1036.8 nmol/mmol creatinine) following exposure to non-toxic arsenobetaine. The median (IQR) urine arsenic/creatinine ratio in 40 adults was 60.3 (32.6–142.7) nmol/mmol creatinine. The highest concentration (8619.6 nmol/mmol creatinine) was recorded in a 58-year-old male treated with succimer following intentional ingestion of a hair removal product containing arsenic.

Conclusion

Limitations of this study were that data from only one of the seven UK SAS laboratories were reviewed, and in many cases a urine arsenic/creatinine ratio was unavailable or not documented with units to aid interpretation. Poison centres and SAS laboratories should consider ways to harmonise pathways for sample analysis and clinical interpretation to optimise patient care for those suspected to have arsenic poisoning.

214. N-acetylcysteine (NAC) in the management of increased cobalt concentrations derived from a metal-on-metal (MoM) hip prosthesis: a case report

Abstract

Objective: Systemic cobalt toxicity is a rare but potentially life-threatening complication of ill-fitting metal-on-metal (MoM) hip prostheses [1]. Most cases are associated with blood cobalt concentration in excess of 250 µg/L. The most effective management is prosthesis removal, though chelation with acetylcysteine has been proposed as a bridging treatment before surgery [2].

Case report: A 53-year-old male who underwent bilateral MoM hip resurfacings in 2001 was referred to the toxicology clinic for assessment of potential cobalt poisoning. He presented with non-specific symptoms including headache, poor memory, intermittent tinnitus and mild deterioration in visual acuity. There was no objective evidence of the classic manifestations of cobalt poisoning (peripheral neuropathy, cardiomyopathy or hypothyroidism) and no radiological or clinical evidence of an ill-fitting prosthesis. He was nevertheless concerned by an increase in blood cobalt concentration from 23 µg/L in August 2012 to 92 µg/L in July 2022. With full awareness of the limited evidence for acetylcysteine as a cobalt chelator, the patient was keen to undergo a trial of acetylcysteine to potentially slow the increase in blood cobalt concentration. The treatment regimen and results are detailed in Table 1. The patient experienced no adverse effects of treatment, with some improvement in headaches and tinnitus. He remains under toxicological and orthopaedic follow-up.

Table 1 Blood cobalt concentration, 24-h urine cobalt excretion and acetylcysteine regimen with a metal-on-metal (MoM) hip prosthesis.

Date	Blood cobalt concentration µg/L	24 h Urine cobalt excretion µg /24 h	Treatment regimen
02/11/2022	72	442
03/11/2022	49	795	Intravenous NAC 300 mg/kg over 12 h. Treatment duration: 3 days.
04/11/2022	44	343
05/11/2022	39	245
06/11/2022		150	24 h washout period.
07/11/2022		276	Oral NAC 300 mg/kg per day. Treatment duration: 3 days.
08/11/2022	38	228
09/11/2022	40	262
10/11/2022	36
24/11/2022	40
01/12/2022	43
09/12/2022	55
14/12/2022		268
15/12/2022	48	435	Oral NAC 300 mg/kg per day. Treatment duration: 3 days.
16/12/2022	42	295
17/12/2022		230
18/12/2022			48 h washout period.
19/12/2022
20/12/2022	35	355	Intravenous NAC 300 mg/kg over 12 h. Treatment duration: 3 days.
21/12/2022	28	225
22/12/2022	27	262
23/12/2022	30
05/01/2023	40
19/01/2023	56

Conclusion: These limited data provide some evidence that acetylcysteine may have a role in the management of modestly increased blood cobalt concentrations in patients with MoM prostheses.

215. Iron overdose in pregnancy

Abstract

Objective

Acute iron overdose in pregnancy can be fatal, and stage 3 toxicity can be associated with adverse perinatal outcome [1]. The use of deferoxamine, an iron chelator, is often withheld in pregnant women on the basis of theoretical fetal effect, even when indicated. We report a case of acute self-poisoning, which was managed with deferoxamine without adverse consequences.

Case report

A 30-year-old, 26 weeks gravida ingested 50 tablets of Neo-Ferro-Folgamma (each tablet contains 37 mg elemental iron, total dose 20.8 mg/kg elemental iron, and 0.8 mg folic acid). A few hours after ingestion she developed nausea, continuous vomiting and intense abdominal cramps. On admission her physical status was satisfying, and fetal evaluation by ultrasound was normal. The patient’s laboratory results included an initial serum iron concentration of 93.0 µmol/L (4 h after ingestion), and peak serum iron concentration of 118.0 µmol/L (normal 10–28 µmol/L). Her electrolytes, liver enzymes and renal function tests were all within the normal ranges. Four hours after ingestion gastric lavage was performed, then whole bowel irrigation was started, and she was treated with supportive care. Deferoxamine therapy is indicated for individuals with symptoms and for those ingesting more than 20 mg/kg elemental iron or serum iron concentration more than 90 µmol/L. Based on these criteria we began deferoxamine therapy (15 mg/kg/h intravenously), which the patient tolerated well. Deferoxamine was continued until symptoms resolved, serum iron concentration returned to a normal range, and vin rose coloration of urine was cleared. The total duration of deferoxamine therapy was 20 h. During her observation we could detect only mildly low International Normalized Ratio (INR) and mildly elevated alkaline phosphatase. She was discharged on hospital day 5. At home she was checked by a gynecologist, her pregnancy continued normally, and she delivered a healthy baby at term.

Conclusion

Acute iron intoxication can cause multi-organ complications and can be fatal. Treatment is well-defined, based on the patient’s symptoms, amount of elemental iron consumed and serum iron concentration. In this case, we treated a pregnant iron-intoxicated woman with appropriate supportive care, effective early decontamination and chelation (deferoxamine) therapy. Deferoxamine was given intravenously with no side effects. Our patient did not develop any lasting consequences of the overdose or treatment. In this case deferoxamine was safe and effective in late pregnancy.

216. Determining hospital text-based consult request feasibility for poison centers: a pilot study

Abstract

Objective

Global hospital demand on poison centers (PC) is increasing with cases becoming more complex. This has lengthened call handling and wait times, leading to increased abandonment rates, reduced caller satisfaction, and inappropriate clinical decisions by nonspecialists. Rather than calling, hospital text-based consultation requests to PC-based toxicologists potentially results in more timely clinical recommendations, enhances hospital provider satisfaction, and decreases initial consult call volume and strain on specialists in poison information (SPIs). Therefore, the purpose of this study was to determine the operational impact of hospital-based text consultation on a PC.

Methods

A retrospective chart review from 1 August 2023 to 15 October 2023 was conducted. Throughout the study period, the University Hospital (UH), for which our PC provides phone and bedside consults, directly texted consultation requests via Epic electronic medical record (Epic) to PC-based on-call toxicologists’ mobile phones for text or call response rather than calling the PC. The on-call toxicologist Epic consult encounter documentation was copied into the PC medical record. These charts in Epic were identified and records extracted. Data collected included demographics, poisons involved, disposition, recommended interventions, outcomes, and time to initial recommendations. Descriptive statistics were employed, with operational comparisons made to the same period in the previous year to account for seasonal call variation.

Results

During the study period, 56 texts for a consult were sent to the on-call toxicologist mobile phone through Epic. Of these, the consulting toxicologist gave initial recommendations via text in 41 cases (73%), by phone in 15 cases (27%), and 27 (48%) received subsequent bedside evaluation. The mean time from consult request text to initial recommendation was 62 s. For comparison, during the same time period the previous year, the mean time of telephonic pick up by SPI for calls from the UH was 132 s. Once picked up by SPI, the mean duration for the on-call toxicologist to respond to a SPI page regarding the case was 158 s. The aggregate mean time to initial recommendations given when a physician was involved was 290 s. Overall, 672 min (40,320 s) of SPI time was saved. There were no deaths or recommendation miscommunications from texts.

Conclusion

The text-based consult model resulted in a 228-s reduction in mean time to initial recommendation for hospital-based consults. This likely improved outcome, enhanced hospital provider satisfaction when consulting the PC, and eased SPI burden. Surveys targeting hospital providers, on-call toxicologists, and SPIs are needed.

217. Should modern telemedicine concepts also be used by Poison Control Centers?

Abstract

Objective

Telemedicine programs in emergency and intensive care medicine have increased significantly, particularly during the COVID-19 pandemic. Evolving from the telemedical project ERIC (“Enhanced Recovery after Intensive Care”) [1], experts from our tele-Intensive Care Unit (tele-ICU) team in Berlin discuss clinical cases together with cooperation partners worldwide on a regular basis. The project consists of a telemedical hub, which is connected via camera-equipped carts to the bedsides of different remote hospitals. This enables medical exchange, training, and special consultations. By presenting our case we show how modern telemedical concepts could also be used by clinical toxicologists to provide the best possible care for critically poisoned patients.

Case report

During a telemedical consultation a hospital in Tashkent, Uzbekistan presented a 3-year-old child who had been acutely admitted after ingestion of unknown amounts of an insecticide containing chlorpyrifos and cypermethrin. The patient showed typical signs and symptoms of an organophosphorus exposure (vomiting, foamy secretion from the mouth, bradycardia, Glasgow Coma Score (GCS) 10) and was transferred to the ICU. Atropine was started and progressive respiratory failure prompted intubation and mechanical ventilation. The tele-ICU team communicated with the bedside physicians and assessed the patient via high resolution audiovisual multichannel connection. Clinical symptoms, vital parameters, laboratory findings, respirator settings, etc. were displayed in real-time. The tele-ICU team consulted the Poison Control Center (PCC) Berlin to ensure adequate and timely treatment for the patient. Specific toxicological issues were addressed. After discussing and adjusting the therapy plan together with the remote physicians, the patient recovered without any deficits and was discharged 14 days after admission.

Conclusion

Although PCCs have been pioneers in using computerized support in the field of clinical medicine, many still operate by telephone today and do not use advanced communication technologies. However, the information transfer by telephone is limited, while modern telemedicine systems could be beneficial when assessing patients with acute poisoning. Telemedicine in critical care is increasingly being used as a vehicle to deliver high-quality medical content to remote medical facilities and has already become a fundamental element in many critical care settings. Clinical toxicologists and PCCs should learn from and participate in existing telemedicine programs to integrate modern communication technologies into their consultation strategies.

218. Outcomes in paracetamol overdose: is acetylcysteine enough?

Abstract

Objective: Paracetamol remains one of the most important poisonings worldwide, based on case numbers and severity of poisoning. New treatments are being explored, but there remains limited data on the outcomes in different groups of patients administered acetylcysteine. We aimed to determine the proportion of patients with hepatotoxicity following delayed treatment (>8 h).

Methods: We extracted cases of paracetamol poisoning presenting to the Hunter Area Toxicology Service from January 2010 to September 2023, treated with acetylcysteine. Extracted data recorded prospectively in a clinical database included demographics, dose, alanine transaminase (ALT), International Normalised Ratio (INR), complications, treatments and outcomes.

Results: Over a 14 year period, 749 paracetamol overdoses were administered acetylcysteine, median age 31 years (Interquartile range [IQR]: 21–48 years); 500 females (67%). The median paracetamol dose was 17.5 g (IQR: 12–25 g). The median length of stay was 27 h (IQR: 22–38 h), 49 patients (6.5%) were admitted to intensive care and four died (0.5%). Sixty (8.3%) had a peak ALT >1000 U/L (hepatotoxicity), 102 patients (14%) had a peak ALT >150 U/L and 35 patients (4.7%) had a peak INR >2.0. Hepatotoxicity occurred in 1.7%, 15%, 12% and 25% of patients receiving acetylcysteine within 8 h, 8–16 h, 16–24 h and >24 h, respectively (Table 1). The median peak ALT between these four groups was significantly different (Kruskal-Wallis test; p < 0.001). The proportion with hepatotoxicity was slightly higher excluding patients who were non-toxic. Median acetylcysteine dose was 22.5 g (IQR: 17.5–30 g); 140 patients (19%) received the 3-bag acetylcysteine protocol. Acetylcysteine was ceased within 8 h in 88 patients (12%) with non-toxic paracetamol concentrations or normal ALT. Gastrointestinal adverse effects occurred in 221 patients (30%) and anaphylactoid type reactions in 35 (4.7%).

Table 1 Time to acetylcysteine, hepatotoxicity and outcome in patients with paracetamol overdose.

Time to acetylcysteine	<8 h	8–16 h	16–24 h	>24 h	Unknown	RSTI
Number of patients	344	145	61	49	100	51
Median (IQR) peak ALT (U/L)	22 (15–38)	28 (20–88)	29 (19–87)	85 (25–1240)	44 (21–104)	40 (20–85)
ALT >1000	6 (1.7%)	23 (16%)	7 (12%)	12 (25%)	13 (13%)	2 (3.9%)
ALT >1000 (exclude non-toxic)	6 (9.5%)	23 (19%)	7 (13%)	12 (28%)	13 (15%)	2 (4.4%)
ALT >150	11 (3.2%)	29 (20%)	13 (21%)	20 (41%)	21 (21%)	8 (16%)
INR >1.4	6 (1.7%)	11 (8%)	6 (10%)	5 (10%)	9 (9%)	1 (2%)
Died	0	1 (0.7%)	0	0	3 (3%)	0
Acetylcysteine stopped early	30 (8.7%)	22 (15%)	9 (15%)	6 (12%)	14 (14%)	6 (12%)

ALT: alanine transaminase; RSTI: repeated supratherapeutic ingestion.

Conclusion: We confirm that the later acetylcysteine is administered, the larger the proportion of patients developing hepatotoxicity, increasing from 12% to 15% to 25%, higher if non-toxic patients are excluded. This shows that there are a considerable number of patients in which adjunct therapy may be beneficial, and clinical trials of newer therapies should be focused on these patient groups.

219. Calls related to occupational poisoning accidents in the data of the Finnish Poison Information Center

Abstract

Objective

We analyzed information about occupational poisoning accidents in Finland in order to contribute to better occupational working safety.

Methods

We retrospectively investigated the Finnish Poison Information Center (FPIC) call database concerning enquiries related to occupational poisoning accidents. Calls concerning suspected or confirmed occupational accidents were included from 1st January to 31st August 2023.

Results

The FPIC received 390 calls concerning occupational poisoning accidents. The victim was male in 49% and female in 37% of the cases. In 4% of the cases there were multiple victims. In 10% of cases, the gender was not registered. The age structure of the victims: younger than 20 years (5%), 20–29 years (20%), 30–39 years (20%), 40–49 years (8%), 50–59 years (5%), 60–69 years (2%). The age was not registered in 37% of the cases. The route of exposure was inhalation in 40%, skin 33%, eye 26% and oral 10% of the cases. Some cases involved multiple routes of exposure. The majority (81%) of the calls concerned exposure to a chemical. The most common chemicals were drain cleaners and heat transfer fluids. Exposure to a biocide or plant protection agent, most commonly disinfectants or algaecides, comprised 10% of the calls. In addition, 5% of the calls concerned exposure to a medicine. In 2% of the cases the substance was not known. Single individual calls concerned exposure to natural products, medicinal products, plants, lamps, batteries or cosmetics. The victim was symptomatic in 68% and asymptomatic in 29% of cases. In 3% of the cases the existence of symptoms was not known. In 34% of the cases the victim was referred to the emergency department (ED). In 47% of the cases the FPIC advice was to observe at home and reach out to the ED if necessary. Overall, 19% of the cases were determined as harmless.

Conclusion

Occupational accidents were more common in men, and the age group of 20–39 years had the most accidents. In occupational accident calls to the FPIC, exposure route via inhalation, skin or eye were the most common, differing from the general profile of poisonings, where oral exposure is prevalent. The majority of victims were exposed to chemicals.

220. “Unexpected” acute carbon monoxide poisoning in a chemical plant

Abstract

Objective: Potential exposure to carbon monoxide (CO) (the “silent killer”) in chemical plants is well-known, but sometimes the source is unexpected. We describe a case of acute CO poisoning in a worker at a chemical plant for production of organic anhydrides, additives for food and animal feed.

Case report: A 57-year-old male, a very experienced chemical technician, was called out to repair a ruptured disk, damaged by overpressure, on the top of the dosing tank (liquid acetic acid and nitrogen gas) for a reactor. He used personal protective equipment (PPE), including a full-face gas mask with charcoal filter for acetic acid. Two other workers were present, one dressed in PPE standing 1 meter from the patient and the other standing at 4–5 meters away. After 20 min, the patient became confused, and very weak, with dizziness. On transport by his colleagues to the plant infirmary, he experienced a brief loss of consciousness. No irritant symptoms were present. The patient was taken to the hospital where the emergency department physician contacted our Poison Center. Based on the symptoms, unrelated to acetic acid exposure, carboxyhemoglobin was assessed resulting in a level of 22.7%. Normobaric oxygen was increased to high flux with nonrebreathing face mask, and the patient was transferred to the hyperbaric chamber for 45-min 100% oxygen treatment at 2.8 ATA. After the procedure the patient was completely asymptomatic without signs of myocardial ischemia. He was discharged after 24 h. The patient was evaluated after three weeks and no delayed neurological sequelae were found. The lack of the expected symptoms of acetic acid inhalation and the symptoms of moderate CO poisoning were the key to the correct diagnosis in this case. Using the Tikuisis’ equation, estimating an initial carboxyhemoglobin level of 35%, the concentration of inhaled CO was about 3322 ppm or 0.33% (lethal within 30–40 min). A technical evaluation of the plant was conducted, and the accident was explained by an overpressure in the reactor with the passage of residual gases (nitrogen, acetic acid, oxygen and CO) to the dosing tank.

Conclusion: The risk of CO poisoning can pose a threat anywhere. Even chemical workers with expertise could be unaware or misguided by the usual content in tanks, and PPE may be not adequate for CO exposure. Consulting a poison center is helpful, especially when the symptoms do not correlate with the hypothetically involved substance or with those that are nonspecific and confounding.

222. Bloom 2023: a novel poisons centre public outreach and awareness-raising campaign

Abstract

Objective

The National Poisons Information Centre (NPIC) of Ireland sponsored an exhibition garden at Bloom, a national gardening and lifestyle 5-day festival, in June 2023 to raise awareness of our service and the importance of poison prevention. “The Know, Act, Prevent Garden” represented a family home with a kitchen/laundry, garden, and shed. The NPIC collaborated with a garden designer, the Health and Safety Authority and the Health Service Executive to raise awareness of chemical safety, the importance of reading labels, and keeping children safe from potential poisons. The garden featured low toxicity plants and was awarded a Silver medal. We describe the output, value and staff assessment of this public outreach activity.

Methods

A steering group (n = 7) developed the garden concept and safety themes over 7-weeks. New website content, educational messages, and coordinated social media posts were prepared. Spokespeople participated in media interviews (coordinated via a public relations company) to raise awareness.

Results

Over 100,000 visitors attended Bloom from 1st to 5th June, 2023 and 81% stated they came to visit the Show Gardens [1]. A team of staff (n = 7) and volunteers (n = 24) manned the garden and engaged with the public during the event. From 31 May to 5 June 2023, the NPIC website had 2612 page views compared to 813 page views for the same period in 2022. The most visited pages were the Bloom page (32.9%), Home page (13.9%), Contact us page (12.1%), and Low toxicity plant list (4.4%). In addition, 31 posts on Facebook and Instagram generated an organic reach of 339,761 (3264 for the corresponding time in 2022) and 1444 (compared to 373 in 2022), respectively; 69 posts on Twitter generated 33,484 organic impressions (reach in 2022 not available). Seven radio interviews and 2 print features (national newspaper and lifestyle magazine) that were also shared online generated a total reach of 2,331,633. A NPIC staff survey (n = 8) revealed that 87.5% described the experience as excellent, 75% strongly agreed and 25% agreed that the event met their expectations, 62% strongly agreed and 48% agreed that NPIC achieved our goals, and 50% strongly agreed and 50% agreed they enjoyed engaging with the public.

Conclusion

Attending a national festival was a valuable public relations outreach activity for poisons centre staff that raised awareness of the NPIC in the media and generated increased engagement via social media reach and website traffic.

223. Calls related to intentional poisonings by adolescents in the data of the Finnish Poison Information Center

Abstract

Objective

Recently, it has been observed that the wellbeing of young people has decreased, and mental health problems increased according to national surveys (e.g., school health promotion study) in Finland [1]. At the same time, the calls to the Finnish Poison Information Center (FPIC) related to intentional poisonings among young people have increased. The objective of this study was to evaluate trends and characteristics of the calls related to intentional poisonings among young people (aged 13–17 years).

Methods

The data was collected retrospectively from the Finnish Poison Information Center call register. Calls related to intentional poisonings of medicines among 13–17-year-olds were included from 1 January 2018 to 30 June 2021.

Results

The data consisted of 2479 calls. The number of annual calls was 610 (2018), 716 (2019), 695 (2020), and 492 (until 30 June 2021). Overall, 69.3% (n = 1717) concerned females and 16.5% (n = 409) males. Sex was unknown in 14.2% of calls (n = 353). The number of calls regarding females increased during the study period whereas the numbers among males did not change significantly. In total 217 different substances were identified in the data. The most common medicines were quetiapine (n = 466), ibuprofen (n = 391), paracetamol (n = 345), fluoxetine (n = 296), sertraline (n = 197), melatonin (n = 162), methylphenidate (n = 127), clonazepam (n = 101), escitalopram (n = 67) and hydroxyzine (n = 63). Quetiapine was involved in 19% of all calls. Mixed use was identified in 36% of calls and alcohol was included in 7% (n = 180) of cases [2].

Conclusion

Calls related to intentional poisoning in adolescents have increased since 2018 and the trend is upwards. The majority of cases were related to psychoactive medicines used in mental health problems. The increased number of calls may reflect a decrease in the well-being of adolescents, and that females are more likely to express their unwellness by overdose.

224. Infant botulism: Pavia Poison Centre clinical experience (2009–2022)

Abstract

Objective

Infant botulism (IB) is related to the in situ production of neurotoxins by Clostridia colonizing the intestinal lumen of young children (<1-year-old). IB is characterized by insidious onset, and clinical suspicion can only be advanced when the typical neuroparalytic syndrome (floppy baby) appears. Severe cases of IB may require assisted ventilation (AV) and antitoxin treatment. The main objectives are to assess (i) the clinical course of IB to identify key signs/symptoms useful for early clinical suspicion, and (ii) clinical efficacy and safety of antitoxin treatment.

Methods

All laboratory confirmed IB cases collected from 2009 to 2022 at the Poison Control Centre (PCC) were retrospectively assessed for demographics, clinical manifestations, toxin type, acute/delayed adverse reactions, and outcome. Clinical severity was classified using the IB score (IB1: mydriasis, ptosis, constipation, difficulty suckling; IB2: dysphagia, weak crying, head lag, tirage; IB3: floppy baby).

Results

Twenty-seven patients were studied (mean 17 weeks; body-weight 3270–3560 g.; normal/uneventful delivery in 17/27 (62.96%); breast-feeding in 19/27 (70.37%); history of honey ingestion in 8/27 (29.63%)). The most frequent symptoms reported by parents during at least 1 week before PCC evaluation were difficulty suckling (96.3%) and constipation (88.9%). The IB score at first evaluation was 1 in 11% (3/27), 2 in 26% (7/27), and 3 in 63% of cases (17/27). In the following 72 h, 5 patients achieved the worst score (IB3) (22/27; 81.5%). All patients IB3 (n = 22) were treated with antitoxin: 10 patients were already intubated when treated, while 12 (54.5%) did not require AV after antitoxin administration. Seven patients received the trivalent and 15 the heptavalent botulism antitoxin, respectively. No differences in hospital stay were recorded between the groups. Mild hypotension (n = 1) and transient skin rash (n = 2) were recorded. Five patients (IB2) were not treated with the antitoxin and remain clinically stable. Botulinum neurotoxin (BoNT) type-A (n = 4) and type-B (n = 20) were more frequently related to severe constipation and need for tube feeding; mechanical ventilation was applied in 25% of BoNT-B and 50% of BoNT-A, respectively. In BoNT-E positive cases (n = 3), constipation was reported in only 1 case, but all patients required intubation and AV. All patients fully recovered.

Conclusion

Clinical suspicion with the support of the PCC, was made early in 37% of cases in the absence of generalized hypotonia. Treatment with antitoxin is suggested in the floppy baby stage of botulism (IB3), and in more than 50% of cases it can stop progression of neuroparalysis avoiding intubation and AV. Increased awareness of IB may facilitate early diagnosis.

225. Launching a poisoning information centre (EPIC) in the 21st century: the first 15 years of experience in Estonia

Abstract

Objective

The Estonian Poison Information Centre (EPIC) was created with the opening of the information hotline after 18 months of preparation on 6 October 2008. The mission of the EPIC was set to reduce illness, health damage and mortality caused by poisoning, and to promote the availability of information on poisoning. Metrics were established: to reduce the number of ambulance calls, and visits to the emergency department due to poisonings. Five emergency medicine nurses and two doctors were hired, and a local database was acquired for work with calls and treatment instructions. Due to limited resources, a strategic communication action plan was drawn up with mapping of target-related groups and ways of sharing information. EPIC also conducted training for healthcare professionals and the public.

Methods

A retrospective study analyzing the process, data from the EPICs hotline 2018–2023. The achievement of the set goals and the impact on the country's healthcare system were assessed.

Results

Calls to the helpline increased until 2020, reaching a plateau of nearly 4000 yearly, which is significantly lower than the number expected at the beginning (9000) and the number of calls to PICs in the Nordic countries compared to the population. Starting in 2020, more people with poisonings can get help on the EPICs hotline than in all the country's hospitals and family doctors (3888 calls/3084 patients). The number of patients treated in hospital is on a downward trend. The number of ambulance calls has dropped from 2500 visits in 2009 to 600 visits in 2022. The cost of treatment in hospitals is in a downward trend, despite rising prices. Population/hospital calls to the hotline are in the ratio of 75% and 25%. The residents' first aid skills in case of poisoning have improved. Continuous prevention activities have been launched across the country. The center's team expanded with administrative experts, including acting as CBRN (chemical, biological, radioactive, nuclear) event experts. The IT tools of the center have been modernized.

Conclusion

An efficient EPIC is a cost-effective unit for the State, whose benefits will be to promote, through a 24-h hotline and consistent training, modern evidence-based treatment for poisoned patients, and to reduce spending by focusing health budgets on promoting quality of life for the population. The association of achieving a plateau effect lasting nearly 3 years, saving 5000 yearly poisoning patients through early prevention over 15 years, needs to be investigated.

226. Chronic exposures concerning medical drugs in adults reported to a German Poison Center

Abstract

Objective

Most calls to our poison center (PC) are related to one off or short time exposures or acute or chronic, e.g., overdose of the usual medication. This study focuses on chronic exposures of adults with special focus on medicinal drugs. The aim of the retrospective study was to identify the most frequent pharmaceuticals involved in chronic exposures and the ones, which were the main causes for major outcomes.

Methods

Retrospective analysis of reports about chronic exposures to medical drugs in the poison centers database. The database was searched for exposures coded as chronic concerning patients 18–64 years of age in the years 2013 to 2022.

Results

In the ten years from 2013 to 2022 the PC received 241,158 calls related to human exposures, 83,373 of them concerning adults. Of these 1175 (2.2%) were chronic exposures, i.e., duration of exposure was over one month and 419 of these were related to medical drugs. Lithium was the most often reported medication (n = 93; 22.2%), followed by colecalciferol (n = 18; 4.3%), and clozapine (n = 14; 3.3%). Considering only patients with symptomatic exposures and the symptoms assessed as at least possibly related to exposure, there were 257 exposures with 31.5% (n = 81) lithium, 3.5% (n = 9) clozapine and 3.5% (n = 9) colecalciferol as the most frequent substances. In total, 112 patients displayed major symptoms (Poisoning Severity Score moderate, severe or fatal, MMP). Most often reported substances related to MMP were lithium (n = 48, 43% of MMP), carbamazepine (n = 4; 3.6%), and quetiapine (n = 3; 2.7%). In 359 patients with chronic exposure to medical drugs and documented age the mean age was 45.4 years. Patients on chronic lithium therapy had a mean age of 54.6 years.

Conclusion

Only a small proportion of calls to our PC concerned chronic exposures to medications. Out of these lithium was by far the most important drug responsible for exposures and also for moderate and/or severe poisoning.

227. Systemic adverse reactions from topical administration of cycloplegic eye drops in paediatric patients

Abstract

Objective

Cycloplegic drugs, such as atropine, cyclopentolate and tropicamide, are used routinely for accurate refraction and fundus examination in children. Despite ocular administration, their use may be associated with systemic adverse effects/reactions (ADR) consisting of anticholinergic symptoms, both peripheral and involving the central nervous system (CNS).

Methods

We conducted a retrospective study including all paediatric patients who developed ADR after ocular administration of a cycloplegic drug referred to our Poison Control Centre between March 2007 and April 2023. The objective was to analyse the main ADR after intraocular administration of cycloplegic eye drops. The inclusion criteria were: all patients aged between 0 and 10 years old who developed a systemic adverse reaction after administration of cycloplegic eye drops.

Results

Forty-nine patients were included (mean age 4 years; male 55.1%). Most patients belong to the age groups of 0–3 (23; 46.9%) and 4–6 years old (21; 42.9%). The cycloplegic drugs used were atropine (61%), cyclopentolate (35%) and tropicamide (4%). In 42 patients (85.7%) the drug was administered at the prescribed dose, while in 7 children a higher erroneous dose was given. Thirty-four children (69.4%) developed CNS symptoms such as agitation (17/49), hallucinations (14/49), delirium (13/49), confusion (9/34) and drowsiness (9/34). Peripheral adverse effects were present in 39 patients (79.6%): flushing (24/49), xerostomia (10/49) and tachycardia (9/49). Both central and peripheral symptoms occurred in 24 patients. The mean symptom onset was 1 h and their mean duration was 13 h. CNS involvement was more frequent in female patients (p = 0.011) and when cyclopentolate was used (p = 0.003). Hallucinations were more frequent in older patients (p = 0.017). Most patients required only clinical observation without pharmacological treatment (77.6%), one patient was treated with benzodiazepines and one with physostigmine. All patients fully recovered.

Conclusion

Ocular administration of cycloplegic drugs in children may lead to anticholinergic adverse reactions with CNS involvement, statistically more frequent with cyclopentolate and in female patients. Hallucinations are statistically more frequent in older children, perhaps because of their greater ability to report them, while in toddlers the hallucinations manifest as agitation. In conclusion, the lowest effective dose of drops should always be used and for the shortest possible time, especially for cyclopentolate. Proper education of caregivers about the mode of administration is relevant.

228. Box jellyfish envenomation in an Italian tourist returning from Borneo

Abstract

Objective: Box jellyfish (class Cubozoan) represent the most significant hazard among the jellyfish classes, responsible for painful lesions and even fatalities in Pacific waters. Local signs of envenomation are intense skin pain with oedema/erythema, followed by blisters and necrosis. Outcomes may be hyperpigmentation or scarring. Systemic reactions may include hypotension, arrhythmias and cardiopulmonary arrest. Some Cubozoan specimens have also been signalled in the Mediterranean Sea. We describe management of box jellyfish envenomation in a patient returning from holiday.

Case report: Our PCC was consulted for a 48-year-old woman admitted at the Emergency Department (ED) 48-h after cutaneous contact with a jellyfish in Borneo. She referred that, immediately after the painful contact, the lifeguard recognized the jellyfish as a box species, locally endemic, and initially applied vinegar, trying to remove the remaining tentacles, with temporary pain improvement. She was then transferred to a local clinic where she was treated with oral steroids, antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and topic application of papain (local remedy). She was discharged after 12 h, with the described therapy, in order to take her planned flight back to Italy. At her arrival in Italy she went to the ED, complaining of intense pain and itch on her left leg where a characteristic whip-like (flagellate) linear wheals lesion was present with an extension from knee to ankle, accompanied by oedema and vesicles. In order to exclude a delayed systemic involvement electrocardiogram and blood tests (blood count/troponin/hepatic and renal function/lactate dehydrogenase/creatine kinase) were performed, all normal. She never developed systemic symptoms and was discharged after 24 h with scheduled telephone follow-up by the PCC and therapy with oral/local steroids, antibiotic, and antihistamine. At every follow-up she reported a progressive improvement of the oedema and pruritus, but linear lesions never completely healed, and residual deep scars persist to this day. At the last follow-up, one month after the jellyfish contact, she reported the appearance of paraesthesia in the whole leg with cyclic burning pain during the day, she is now waiting for an electromyography/neurography that has been prescribed. Follow-up is ongoing.

Conclusion: Considering increased travel possibilities and the occurrence of invasion by alien species in the Mediterranean Sea, physicians will more frequently face cases like the one described, even in areas where Cubozoans are not endemic. Therefore, is important to signal cases to improve knowledge on clinical characteristics/treatment options.

229. Fatal death cap (Amanita phalloides) poisoning in 5-month-old puppy

Abstract

Objective

Amanita phalloides contain cyclopeptide compounds including amatoxins which are hepatotoxins, binding to RNA polymerase II, preventing protein synthesis and causing cell death. Amatoxins undergo enterohepatic circulation and one cap contains enough to cause lethal poisoning in a human or pet. We report a fatal case in a dog.

Case report

A 5-month-old male 11.5 kg whippet presented just over 24 hours after eating mushrooms. He had developed progressive gastrointestinal signs the day after ingestion and presented that evening. On arrival he was subdued, with pink, tacky mucous membranes, moderately tachycardic (170 bpm), and painful on abdominal palpation. A sample of the mushrooms was identified as Amanita phalloides using an online app. He was started on IV fluids and analgesia. He had marked eosinophilia and hypoglycaemia, with bleeding and haematoma formation at the venepuncture site. Images of the mushroom were sent to a mycologist who confirmed the dog had most likely eaten Amanita phalloides. Treatment included glucose boluses, fluid therapy, maropitant, acetylcysteine and analgesia. His demeanour improved slightly, and he was able to eat a small meal with activated charcoal, but later vomited. In the morning his mucus membranes were pale and tacky, with prolonged APTT/PT; renal values were normal, bilirubin and ALP were moderately raised, and ALT was off the scale. During a visit from the owner that afternoon his demeanour improved, and treatment was continued but that he evening he deteriorated, progressed to haematemesis, and passed frank blood rectally. At 1 am he became unresponsive and rigid, and was euthanised.

Conclusion

Not all cases of A. phalloides ingestion in dogs are fatal [1–3]. Survival is more likely with witnessed consumption and prompt decontamination, with worse outcomes following delayed presentation. Supportive care with intravenous silybinin and acetylcysteine, have been the mainstay of treatment. Recent evidence suggests percutaneous cholecystocentesis and a strict nil by mouth regimen may improve outcome by inhibiting toxin enterohepatic recycling [3]. Our patient followed a classical progression. We lacked intravenous silybinin, attempted to give medications orally unsuccessfully, and were unable to prevent progression of his condition ultimately leading to death.

230. Saltwater emetic in pets: an inappropriate and potentially fatal treatment

Abstract

Objective

Saltwater emetic as a means of gastric decontamination is not recommended in human or veterinary medicine because of the risk of hypernatraemia, however, there are Internet resources that advise owners to make their pets sick using salt (sodium chloride). We examined the cases of saltwater emetic use reported to the Veterinary Poisons Information Service (VPIS).

Methods

A retrospective study of all cases involving saltwater or salt emesis in animals reported to the VPIS (1986–September 2023).

Results

There were 579 cases of saltwater or salt emetic use (543 dogs, 35 cats, 1 sheep), comprising 0.1–0.3% of annual cases. Where specifically recorded (n = 184), the saltwater was commonly given by the owner (or recommended by relatives/friends, 94%) and rarely recommended by veterinary staff (6%). The amount given varied from “a pinch of salt” to a litre of salt water. Of the 579 cases, there was follow-up on 240 cases with 7 fatal cases in dogs (3%); 6 dogs died and one was euthanised (1994–2018). In two cases the outcome was likely due to the agent ingested (aldicarb and suspected Gyromitra esculenta mushroom ingestion). In the other five cases, the outcome appeared to be directly or indirectly due to administration of a saltwater emetic. A 24 kg crossbreed was euthanised after it had eaten “2 chunks” of brodifacoum rodenticide and was given “1 L of very salty water”. It became very dull with weak pulse and acute kidney injury. The sodium concentration was not obtained due to a faulty machine. The four dogs that died had eaten a laundry capsule (and aspirated, dog was epileptic and had seizures); one baclofen tablet (electrolyte imbalance and collapse, sodium 165 mmol/L, normal 141–152 mmol/L); milk chocolate (23 g/kg, polyuria/polydipsia, aspiration pneumonia and died 84 hours after ingestion); and diclofenac (<50 mg/kg, vomited 7 tablets, and died suddenly 3 hours after ingestion). A serious limitation was the very small number of cases where sodium was reportedly measured (n = 25) and the time to analysis infrequently reported.

Conclusion

Saltwater emetics are never warranted in the management of suspected poisoning due to the risk of adverse effects including hypernatraemia and aspiration, and potentially death. In some of the cases reported to the VPIS, use of an emetic was contraindicated due to the substance ingested or not required as the risk of poisoning was low. More needs to be done to raise awareness of the risk of saltwater emesis in pet owners.

231. The adder strikes back: severe symptoms in a dog after his fight with the European viper (Vipera berus)

Abstract

Objective

The European viper (Vipera berus) is the only poisonous snake native to the middle, eastern and northern part of Germany – the main area of responsibility of the Poisons Information Centre (PIC) Erfurt. Enquiries regarding adder bites are common, especially during the warm summer months. However, the incidence of animal poisonings by Vipera berus is with about one tenth of all adder envenomation cases reported to our PIC comparatively low, and cardiovascular symptoms are rarely seen. We report a case of a dog that required antivenom after developing severe symptoms.

Case report

A Hunting Terrier was bitten in his armpit during a fight with an adder, and rapidly developed severe symptoms. Approximately one hour after the bite he showed collapse, panting, and ventricular tachycardia of over 200 beats per minute. The leg was massively swollen and he was in significant pain. Due to his rapidly deteriorating general condition despite symptomatic treatment with IV fluids, corticoids and antibiotics, antivenom was obtained and finally administered about four hours after the bite (Biomed Viper Venom Antitoxin, one vial). Subsequently, his condition improved and he was able to walk and use his leg again on the following day.

Conclusion

Dogs bitten by the European viper mainly develop local symptoms, like oedema and pain. According to a recent study, cardiac arrhythmias including ventricular tachycardia are also common, but usually resolve without treatment [1]. Although primarily approved for human use, adder antivenom can also be used to treat envenomation of pets. In our case, treatment with antivenom became necessary due to the severity of the symptoms. It seems possible that the site of the bite also contributed to symptom severity, as well as the fighting context.

232. “Bite-to-Door Time” in snakebite victims presenting to a tertiary care level hospital in South India

Abstract

Objective

We explore the concept of "Bite-to-Door Time" (BTDT) in snakebite victims attending a tertiary care center in South India. The aim is to determine the average delay in snakebite victims seeking appropriate medical care and understand how various factors influence this delay.

Methods

A prospective observational study was carried out over one year at a tertiary care center in Kerala, India. A total of 354 snakebite victims were interviewed. Data regarding delays in seeking medical care due to social, cultural, logistical, and geographical factors were collected using a structured questionnaire. The term "Bite-to-Door Time" was employed to quantify this timeframe. The study obtained institutional ethical and research committee approval (Ref. No: 07/19/IEC/JMMC&RI). Continuous variables were analyzed using mean, median, and mode. The relationships between various factors and BTDT were assessed using the Mann-Whitney test to identify significant delays. SPSS version 25 was used for statistical analysis.

Results

The median BTDT was found to be 56 min (IQR: 25–90 min). The study population included snakebite victims aged between 1 and 78 years, with 69% (n = 246) being male and 31% (n = 108) female. Cultural factors, such as the use of herbal medicines, traditional non-scientific practices, and tourniquet application, were found to be statistically significant in causing delays. Among social and logistic factors, only witnessed bites and visits to other medical facilities showed statistical significance. Delays in presenting snakebite victims to healthcare facilities are often attributed to socioeconomic reasons, poor accessibility, lack of awareness, cultural beliefs, and poverty.

Conclusion

A study from Sri Lanka reported a median delay of 45 min (IQR: 20–120 min) [1], and in our study it was 56 min. Early presentation to the healthcare system following snakebites is a key strategy in preventing and managing snakebite envenomings. The World Health Organization emphasizes empowering and engaging communities in this regard [2]. Outreach programs, educational initiatives, and life support courses can enhance public awareness and preparedness in the fight against snakebite envenoming. Addressing these issues can lead to a reduction in morbidity and mortality associated with snakebite in affected regions.

233. Skin lesions and loxoscelism: a critical analysis through the report of two cases

Abstract

Objective

The diagnosis of loxoscelism, a toxic condition induced by the bite of spiders of the Loxosceles genus, poses a significant clinical challenge. Its symptomatology can be easily confused with various dermatopathies, including those of infectious, allergic, and autoimmune etiology [1]. Accurate identification of loxoscelism is thus critical for effective clinical intervention. This study presents two cases of loxoscelism that were initially misdiagnosed, underscoring the challenges and key considerations for accurate diagnosis.

Case reports

An 8-month-old infant presented to the emergency department with a focal necrotic lesion on the distal phalanx of the right index finger, with 48 hours of evolution. He received antibiotic treatment and debridement, culminating in amputation of the distal phalanx, two weeks later. No fabotheraphy was applied. Biochemical analyses, including renal and hepatic function tests as well as complete blood counts, showed no abnormalities. In the second case, a 52-year-old male arrived at the toxicology department with a necrotic ulcer and perilesional edema on the lower right extremity, evolving for 72 hours following an unidentified arachnid bite. Upon administration of anti-Loxosceles fabotherapeutic within the first 24 hours of hospital admission, the lesion showed significant improvement.

Conclusion

The diagnosis of loxoscelism demands rigorous clinical scrutiny due to its propensity to be confounded with multiple entities that also induce dermonecrosis. Necrosis induced by Loxosceles bites is distinguished by a red-white-blue coloration pattern and rapid symptom progression in the absence of effective treatment. These features differentiate it from other causes of skin necrosis, such as garlic-induced chemical burns, autoimmune dermatopathies or infectious processes [2]. The lesion's evolution time and specific signs and symptoms are crucial for differential diagnosis and to minimize associated morbidity and mortality [3].

234. Emergency poisoning registry as a key tool in clinical toxicology: analysis of the last 2 years

Abstract

Objective

To analyze the profile of intoxicated patients attended to in a hospital emergency department and their clinical management.

Methods

An observational study based on an emergency poisoning registry with progressive inclusion of cases was conducted. This is a prospective registry of cases involving patients with acute poisonings presenting to our emergency department. This registry encompasses more than 40 clinical, analytical, and demographic variables.

Results

From January 2022 to August 2023, 1027 poisonings were identified in our emergency department. The median age was 34 years (IQR 22–51); 55.5% were women. Overall, 61.1% had psychiatric pathology, and 50.7% had a history of previous poisonings. Self-harm ideation was the reason for poisoning in 55.4% of cases, followed by recreational use of toxins (31.5%). The most common cause of poisoning was medication-related (59.2%), with benzodiazepines being the most commonly implicated drug class (41.0%), followed by alcohol (39.4%) and recreational drugs (26.8%). In 44.7% of patients, there were at least two substances involved. Most patients (867, 82.3%) presented at least one symptom, with psychiatric symptoms (36.5%) and neurological symptoms (34.3%), primarily agitation and decreased level of consciousness, being the most common clinical presentations. Overall 51 patients (5.0%) required admission to a hospital ward, and 37 patients (3.6%) required admission to the intensive care unit; 7 patients (0.7%) died.

Conclusion

This study demonstrates the wide range of poisonings treated in the context of hospital emergencies. Having a local registry has the advantage of helping to monitor the specific profile of intoxicated patients who visit that emergency department and to audit the practice itself with the aim of improving the quality of care. Additionally, having a poisoning registry facilitates collaboration in multicentre studies that contribute to increasing knowledge in clinical toxicology, both at the national (AMICO [1], DIGITOX [2]) and international (SILITOX) levels. The creation of clinical toxicology registries is of vital importance in order to integrate clinical knowledge with a solid methodological research base that ensures rigorous data collection, analysis, and interpretation of poisoning data.

235. Human exposures to animals reported to the Poison Information Centre Erfurt from 2013 to 2022

Abstract

Objective

In Germany, human exposures to animals are infrequent but can result in severe symptoms. Exposure to privately held exotic pets, however, are also possible. Recent information on this topic is rare.

Methods

We retrospectively analyzed all human exposures to animals and as a subgroup to exotic pets registered by the Poisons Information Centre (PIC) Erfurt from 2013 to 2022 for frequency and severity of symptoms as well as for age groups and sex of persons concerned.

Results

Exposures to animals (n = 1799) discontinuously increased from 132 in 2013 to 221 in 2022 while exposures to exotic pets (n = 158) stayed at a trendless low level between 7 to 22 cases (mean 15.8) per year. Children were affected in 36.4% and adults in 62.2% of cases. The proportion of males (49.6%) exposed to animals was higher than that of females (43.6%) and even more pronounced in exposures to exotic pets (males 66.5%; females 22.8%). Cases with moderate and severe symptoms were more often seen in males (all animals 9.3%, exotic pets 0.7%) than in females (6.2%, 0.5%), and more often occurred in adults (10.1%, 1.0%) than in children (3.2%, 0%). The frequency of symptomatic cases was comparable in exposures to all animals and exotic pets (mild 54.8% versus 53.8%, moderate 7.6% versus 8.9%, and severe symptoms 0.6% versus 1.3%). Severe symptoms occurred after exposures to Vipera berus (adder, n = 4), Crotalus (n = 2). Severe anaphylactic reactions were observed after stings by Vespa crabro (European hornet, n = 2), Vespula/Dolichovespula (n = 1), and Insecta unknown (n = 1). A bite of Cheiracanthium resulted in secondary infection. No case of animal exposure with fatal outcome was detected.

Conclusion

Exposures to animals slightly increased from 2013 to 2022 while exposures to exotic pets stayed at a trendless low level. Risk groups for moderate and severe symptoms were adult males. Severity of symptoms was comparable in exposures to all animals and exotic pets. Severe symptoms, anaphylaxis or secondary infection occurred in only a small number of cases. No fatal outcome was observed.

236. Toxicovigilance in the elderly population over a 5-year period

Abstract

Objective

Intoxications in the elderly population tend to be more serious due to the number of medications, comorbidities and decreased physiological functions of the body in this age group. The aim of this study is to find out the type of substances causing intoxications in the elderly population and to identify substances causing severe or fatal intoxications.

Methods

Retrospective analysis of consultations concerning patients 65 years and older over a 5-year period (2018–2022) consulted with National Toxicological Information Centre (NTIC) in Slovakia. The variables of gender, route of exposure, reason of acute intoxication, type of substance, causes of severe or fatal intoxications were analysed. Severity of consulted intoxications was based on the Poisoning Severity Score (PSS).

Results

During the 5-year period, 1453 consultations were analysed including patients 65 years and older. The majority of patients were female (n = 830; 59.2%). The most frequent route of exposure was by ingestion (n = 226; 59.2%) followed by inhalation (n = 115; 30.1%). Accidental intoxication (n = 718; 51.6%) was the most common reason for consultation, followed by suicidal intoxication (n = 467; 33.5%) and therapeutic errors caused by a non-healthcare professional (n = 126; 9%). Intoxications were mostly caused by medications (n = 764; 51.7%) and chemicals (n = 380; 25.7%). Zolpidem (n = 78; 10.2%) and alprazolam (n = 51; 6.7%) were the most consulted medications. Gasoline (n = 41; 10.8%) and products with sodium hypochlorite (n = 31; 8.2%) prevailed among consulted chemicals. The majority of patients had minor (PSS1; n = 518; 44.4%) or no symptoms at all (PSS0; n = 466; 39.9%). Severe (PSS 3; n = 26; 2.2%) or fatal intoxications (PSS 4; n = 21; 1.8%) were mostly caused by medications (alprazolam n = 5; 15.6% and digoxin n = 5; 15.6%). Corrosive substances (n = 5; 62.5%) caused the majority of severe or fatal intoxications involving chemicals (n = 8). Therapeutic error with methotrexate caused severe and fatal intoxication in two consulted cases. These therapeutic errors involved the dosing of methotrexate by patients and caused severe pancytopenia.

Conclusion

The majority of intoxications in the elderly population in this study were due to medications and chemicals. Zolpidem was the most frequent consulted substance among medications and gasoline the most common substance among chemicals. Of the pharmaceuticals, alprazolam and digoxin, and in the chemicals, corrosive substances, caused the majority of severe or fatal intoxications. Despite dosing warnings in the methotrexate patient information leaflet, one severe and one fatal intoxication occurred as a result of therapeutic error with this drug.

237. UK National Poisons Information Service data as a source of toxicovigilance to identify drugs with misuse potential

Abstract

Objective

Pregabalin and gabapentin are controlled under the Misuse of Drugs Act 1971 as Class C substances, and quetiapine is recognised for its potential for misuse and abuse [1,2]. We aim to assess whether cases reported to the National Poisons Information Service can support identification of drugs with the potential for misuse.

Methods

A retrospective search of the UK Poisons Information Database (UKPID) between the 1 January 2017 to the 31 December 2022, was undertaken for enquiries relating to pregabalin, gabapentin or duloxetine, as well as atypical antipsychotics (quetiapine, amisulpride, aripiprazole, asenapine, clozapine, lurasidone, olanzapine, paliperidone, risperidone). Recreational abuse was compared with other circumstances, including accidental, adverse reaction, intentional, malicious, medical or therapeutic error, other or unknown. The chi-square test was used to assess the differences in frequency of cases and odds ratios (with standard error) were calculated. Pearson’s test was used for correlation. A p < 0.05 was considered significant.

Results

A total of 2292 cases involved pregabalin, 1212 gabapentin and 255 duloxetine. For recreational abuse cases, 110 involved pregabalin, 15 gabapentin and 2 duloxetine. An increase in recreational abuse cases with pregabalin was identified; 2017 (7 cases), 2018 (10), 2019 (19), 2020 (20), 2021 (27), 2022 (27), r = 0.97, p = 0.0004. A difference was observed in the frequency of recreational abuse cases versus other circumstances for pregabalin compared with gabapentin and duloxetine, p < 0.0001. Odds ratio =4.3 (± 1.3). A total of 2454 cases involved quetiapine and 2355 involved other antipsychotics. Quetiapine was involved in 42 recreational abuse cases (or cases with another drug of abuse), whilst other antipsychotics were involved in 24 cases. An increase in recreational abuse cases with quetiapine was identified: 2017 (3), 2018 (2), 2019 (9), 2020 (10), 2021 (5), 2022 (13), r = 0.74, p = 0.06. A difference was observed in the frequency of recreational abuse cases versus other circumstances for quetiapine compared with other antipsychotics, p < 0.01. Odds ratio =1.9 (± 1.3).

Conclusion

The proportion of recreational abuse cases involving pregabalin or quetiapine was significantly greater than comparators. Reporter bias cannot be excluded from the study. This study suggests Poison Centre data can support identification of drugs with misuse potential.

238. Evolution of cases associated with cocaine abuse attending the Emergency Department in the last 5 years

Abstract

Objective

Our Clinical Toxicology Unit (CTU), attached to the Emergency Department (ED), has maintained a continuous and prospective registry of all cases of acute poisoning treated at our ED over the past 30 years, totaling approximately 30,000 cases. This registry allows us to monitor changes in the epidemiological profile. Cases related to substance abuse have undergone significant changes during this period, with heroin being the primary agent in 1995, cocaine in 2005, and cannabis in 2015. Given the apparent resurgence in cocaine-related cases, we conducted an analysis of their trends and characteristics over the past five years.

Methods

We extracted the cases attending in our ED in which an analytical confirmation of cocaine has been performed from the 1 January 2019 to 31 August 2023. We evaluated their chronological evolution, demographic characteristics, substance associations, clinical picture, treatment, and evolution.

Results

The number of cases related to cocaine was 345, accounting for 8.2% of the total acute poisoning cases (N = 4211) in the period. There was an increase tendency from 7.0% in 2019 to 10.8% in 2023. The mean age was 38 years (SD 11), and 64% were aged between 20 and 50 years. The sex distribution was clearly uneven, males representing 76.0% of the cases in the whole study period, although we have detected a rise in the female group from 2019 to 2022, going from 14% to 35%. Monthly distribution of the cases shows a high incidence in the summer period, but cases present an even distribution on the weekdays. The main associated substances were ethanol (49%), benzodiazepines (37%), and cannabis (34%). Opioids were associated in 12 cases (3.5%). The most common symptoms were anxiety/agitation (46%) and tachycardia (35%). The main treatment was symptomatic based on benzodiazepines and neuroleptics. Overall, 86.4% of the cases were discharged from the ED in the first 24 hours, 8 required ICU admission, and no lethal cases were registered.

Conclusion

Cases associated with cocaine abuse have been rising slowly but steadily over the last five years. Most patients were young adult males, and the cocaine was often taken with commonly consumed substances in our country, such as ethanol, benzodiazepines, and cannabis. Associations with more threatening substances are anecdotal. The clinical picture was usually not severe and quite easily treated with a good prognosis. The type of continuous register available in our CTU is an essential tool to detect epidemiological variations and, therefore, be aware of potentially threatening events.

239. A study of the culprit species, clinical manifestations, and severity among patients with marine animal related stings reported to the Taiwan Poison Center

Abstract

Objective

To understand the types of venomous marine species in Taiwan and related information such as the clinical manifestations, severity and the associated sea temperature, so as to provide reference for future diagnosis and treatment of patients.

Methods

The cases of sting by venomous marine species from the Taiwan Poison Control Center (1985–2021), and the sea temperature in Taiwan (2000–2021) were analyzed to find possible prognostic factors and predict them by logic regression model. The differences of categorical variables were analyzed by chi-squared test and Fisher's exact test, and the differences of continuous variables were analyzed by independent sample t-test and ANOVA test.

Results

A total of 603 venomous marine species sting cases were included in this study, including 29 venomous marine species. Stingray poisoning was most common in the fish (n = 138, 22.9%), and jellyfish in the non-fish categories (n = 88, 14.6%); the severity of envenomation was mostly mild (n = 397, 65.8%), with one fatal case. The odds ratios of moderate to severe and mild sting injuries were highest for stonefish (OR 6.8, 95% CI 2.0–23.0), followed by sea urchin (OR 5.9, 95% CI 1.5–22.6), stingray (OR 3.4, 95% CI 1.1–10.8), jellyfish (OR 3.1, 95% CI 0.9–10.5), catfish (OR 3.0, 95% CI 0.9–9.6), lionfish (OR 1.4, 95% CI 0.4–5.0), butterfish (OR 1.2, 95% CI 0.1–14.1), and rabbitfish (reference group). The Pearson correlation coefficient between the number of sting cases and sea temperature in different months was 0.86 (P value < 0.001).

Conclusion

The ranking of species severity found in this study is not the same as the risk perception of the public. There was a correlation between the number of sting cases in a month and sea temperature, so the results of this study may aid in public understanding of the severity of stings by venomous marine species in Taiwan to help avoid serious envenomation caused by a venomous marine animal sting.

240. The use of fomepizole in the management of toxic alcohol ingestions reported to the UK National Poisons Information Service: a 3-year study

Abstract

Objective: The objective of this study was to evaluate telephone enquiries relating to the use of fomepizole in the management of toxic alcohol ingestions reported to the UK National Poisons Information Service (NPIS).

Methods: A retrospective search of the UK Poisons Information Database identified enquiries where the use of fomepizole was discussed 1 September 2020 to 31 August 2023.

Results: During the 3-year period, a total of 536 cases were discussed, treatment with fomepizole had been initiated in 166 patients prior to discussion with NPIS and continuation of treatment was advised in 96 of these patients. In 231 cases, NPIS advised that treatment with fomepizole was commenced. Treatment was recommended in 74.1% of cases (around 15 cases per month). In 139 cases treatment was discussed but not indicated. Cases involved exposures to a variety of products: ethylene glycol-based antifreeze (29.1%), ethylene glycol (19.0%), antifreeze with unknown ingredients (14.2%), Fabulosa^® Disinfectant (8.6%), contaminated/illicit alcoholic drinks (5.0%), methanol (3.5%), alcohol-based hand sanitisers (3.4%), screen wash (3.0%), reed diffusers (2.4%), coolants (2.1%) and others (9.7%). The ages of patients were: <5 years: 58 (10.8%); 5–14 years: 16 (3.0%); 15–49 years: 332 (61.9%); >49 years: 118 (22.0%); unknown: 12 (2.2%). In 356 cases (66.5%), exposure was intentional (deliberate self-harm or product ingested intentionally as a substitute for alcohol), accidental exposures accounted for 135 cases (25.2%); in 45 cases (8.4%) the reason was unclear.

Following accidental exposure, Maximum Poisoning Severity Scores (MAXPSS) [1] were as follows: 53 asymptomatic (39.1%); 61 minor MAXPSS (45.2%); 11 moderate MAXPSS (8.1%); 7 severe MAXPSS (5.2%) and 3 unknown (2.2%). A greater proportion of patients presented with moderate or severe features following intentional exposures: 33 asymptomatic (9.3%); 125 minor MAXPSS (35.1%); 86 moderate MAXPSS (24.2%); 94 severe MAXPSS (26.4%) and 18 unknown (5.1%). In cases where the circumstances were unknown most patients presented with MAXPSS Severe (32 patients; 71.1%). A total of 6 fatalities were recorded, all following the ingestion of antifreeze/ethylene glycol (5 intentional and one unknown circumstances); all patients were treated with fomepizole.

Conclusion: Reassuringly, following accidental ingestion of products containing toxic alcohols around 85% of patients were asymptomatic or presented with minor symptoms. A significantly greater proportion of intentional exposures resulted in severe toxicity compared to accidental exposures (26.4% versus 5.2%, p < 0.0001).

241. Melatonin overdoses in Taiwan, 1985–2022

Abstract

Objective

A recent study indicates an increase in melatonin overdoses among pediatric patients in the US [1]. Taiwan has regulated melatonin as a prescription drug since 1996. Our objective is to investigate the patterns, trends, and severity of melatonin overdoses in Taiwan.

Methods

We conducted a retrospective study to identify all cases of melatonin overdose reported to the Taiwan Poison Control Center (PCC-Taiwan) from 1985 to 2022. After an initial screening of 171 cases, 156 of them had sufficient information and were thus included for further analysis. All data of the 156 cases were abstracted from the medical chart; the severity of the cases was determined by clinical toxicologists. We examined the trend of poisoning incidents by analyzing the number of annual cases. Additionally, we performed a descriptive analysis of the baseline characteristics of the poisoned cases.

Results

All cases of melatonin overdose occurred through oral ingestion. The annual number of melatonin overdoses showed a gradual decline between 1996 and 2017, followed by a slight increase after 2018. Adult cases (78.2%) outnumbered pediatric cases (19.9%), with women (69.2%) being more frequently affected than men (29.5%). Intentional ingestion represented 78.8% of the cases. Co-ingestion with other substances was observed in 25% of cases, with alcohol (13 cases, 8.3%) and benzodiazepines (12 cases, 7.7%) being the most commonly co-ingested substances. Among the 156 reported cases, melatonin overdose did not lead to severe or fatal outcome. Most cases had minor effects (64.1%) or were asymptomatic (32.1%), and only a few cases experienced moderate effects (3.8%). The clinical manifestations focused primarily on the central nervous system (51.9%), followed by cardiovascular symptoms (12.2%), gastrointestinal symptoms (8.3%), and other symptoms (9.0%).

Conclusion

Regulation of melatonin as a prescription drug in Taiwan has the potential to limit the number of melatonin overdoses. Furthermore, melatonin overdose cases in Taiwan predominantly involve adults attempting suicide, and most cases manifested only mild effects. Therefore, melatonin overdose does not seem to be a substance of significant concern in Taiwan.

242. Results of poisoning by chemical products during 2022 detected by a toxicovigilance program in a tertiary hospital in the Community of Madrid

Abstract

Objective

Toxicovigilance is the active process of identification and evaluation of existing toxic risks in a Community, as well as the study of possible measures aimed at their reduction [1]. In 2010, our center successfully developed and validated a toxicovigilance search tool (SAT-HULP) [2]. The objective of this work is to examine the epidemiological profile of adult patients intoxicated by chemical products during the year 2022.

Methods

A descriptive epidemiological analysis was carried out based on the data obtained from the intoxicated patients attended in the Adult Emergency Service of La Paz University Hospital during the year 2022, through the validated search tool SAT-HULP [2]. The cases were verified manually through the electronic medical record system and cases of intoxication due to chemical products selected. Intoxications due to medications, drugs of abuse, poisonous plants, mushrooms and animals were excluded.

Results

During 2022, 1243 intoxicated patients were treated in the Emergency Department, of which 119 (9.5%) were attended due to chemical product poisoning. The median age was 44 years and the mean 44.9 years (range of 18–91 years). The distribution by sex was 58.8% women and 41.2% men. Domestic poisonings represented the majority of cases (68.1%) followed by work accidents (16.8%). According to their intention, 86.6% had an accidental cause and 13.4% had a self-harm intent. The agents were toxic gases 37%, caustic products 29.4% and irritating gases 9.2%. Regarding the distribution of poisonings in days of the week, almost all days of the week had a similar frequency, with Saturday being slightly higher (21.8%). In the monthly distribution, a certain predominance was observed in the coldest months, with December being the month with the highest number of cases (16.0%). In the overall evolution of the cases, 86.6% resolved in the Emergency Department and 11.7% were admitted to the hospital ward. Two patients requested voluntary discharge from the Emergency Department. No fatal cases were detected.

Conclusion

Domestic poisonings represented more than two-thirds of the cases and the most frequent reason was accidental. The toxic agents most frequently involved were toxic gases, caustics and irritating gases. The majority of these cases were resolved in the Emergency Department.

243. Phenazopyridine toxicity reported to US poison centers: a 22-year retrospective analysis

Abstract

Objective

Phenazopyridine is an over-the-counter azo dye utilized for alleviating discomfort from lower urinary tract infections. Literature characterizing phenazopyridine toxicity is limited. This study aims to characterize the demographics, clinical effects, management, and outcomes of phenazopyridine exposure as reported to the US National Poison Data System (NPDS).

Methods

A retrospective analysis was conducted using data from the NPDS from 1 January 2000 to 31 December 2022. Cases involving single-substance phenazopyridine exposure were extracted and analyzed to identify demographics, clinical effects, management, and outcomes. Descriptive statistics were utilized to summarize the data among pediatric (<20 years) and adult (≥20 years) cases.

Results

During the study period, a total of 25,293 single-substance phenazopyridine exposures were reported. Pediatric exposures were notably high (n = 20,629; 81.5%), with a significant portion (n = 19,092; 75.4%) involving children aged 5 and under. Adverse drug events accounted for 21.7% of phenazopyridine toxicity in adults (n = 1015), therapeutic errors for 48.4% (n = 2258) and suspected suicide for 11.2% (n = 522). Most pediatric (n = 20,027; 97.1%) exposures were coded as unintentional without further classification. Suspected suicide attempts comprised 26.3% (n = 201) of teenage exposures. Clinical effects were documented in 16.1% (n = 3321) of pediatric and 50.5% (n = 2354) of adult exposures, with gastrointestinal symptoms being most common. Methemoglobinemia was reported in 23 (0.11%) pediatric and 50 (1.07%) adult patients, while renal failure was noted in 4 pediatric (0.02%) and 33 (0.71%) adult patients. Methylene blue was administered in 239 (7.3%) adult patients and 101 (0.61%) pediatric patients. N-Acetylcysteine (NAC) was administered in 3 (0.018%) pediatric and 9 (0.27%) adult patients. Hemodialysis was performed in 13 (0.28%) adults and 1 pediatric patient. Of exposures seen in the emergency department (n = 3719 pediatric and 1014 adult), 13% (n = 483) of pediatric patients and 48% (n = 487) of adults were admitted. Outcomes were generally mild, with 1% (n = 200) of pediatric and 10.5% (n = 665) of adult cases experiencing more than minor effects. One death was reported in an adult.

Conclusion

This study highlights a significant, sustained incidence of phenazopyridine exposures, particularly among children. Severe outcomes were rare but underscore the potential complications. There are no current recommendations for phenazopyridine toxicity management or the mitigation of adverse complications such as renal failure. Future research should focus on identifying contributing factors to exposures and developing appropriate interventions and clinical management guidelines.

244. Use and effectiveness of physostigmine in Taiwan: a retrospective review of the data reported to the National Poison Control Center

Abstract

Objective

A national antidote network was established by the Taiwan Poison Control Center (PCC-Taiwan) in 2000. This study was conducted to better understand the use and effectiveness of physostigmine in Taiwan.

Methods

Patient data were collected from all physostigmine-treated cases reported to PCC-Taiwan between 2017 and 2022. The cases were categorized into four groups based on the culprit substances, namely medicine, traditional Chinese medicine, plants, and others. Data were analyzed by using Fisher's exact test, ANOVA and logistic regression analysis. R statistical software (version 4.3.1) was used for all analyses, with a statistically significant level set at p < 0.05.

Results

A total of 78 cases were identified. After excluding non-related and misuse cases, 73 cases were analyzed. The median age of 73 cases receiving physostigmine treatment for anticholinergic toxidrome was 57 years old (range 2–88 years old). Among them, 42% were male. The distribution of different culprit substance exposures was as follows: medicine (35, 48%), traditional Chinese medicine (22, 30%), plants (12, 16%), and other substances (4, 6%). There was no statistically significant difference in age and sex between the 4 groups (P value =0.18 and 0.52, respectively). Most cases (65, 89%) had a good response to physostigmine treatment. Cases with traditional Chinese medicine or other substance exposures had a 100% response rate to physostigmine, whereas cases with plants or medication exposure had a lower response rate (92% and 80%, respectively). The percentage of repeated administration of physostigmine in cases with medicine, traditional Chinese medicine, plants and others substance exposures were 23%, 14%, 42% and 0%, respectively. In the logistic regression analysis, by using the medicine group as the reference group, the odds ratio of traditional Chinese medicine and other substance could not be calculated because of the 100% response rate in both groups, whereas the OR for plant exposure was 2.75 (95% CI 0.30–25.03, p = 0.37).

Conclusion

Physostigmine was effective in 89% of 73 cases reported to PCC-Taiwan between 2017 and 2022. Moreover, a 100% response rate was observed in cases involving exposure to traditional Chinese medicine, a finding that was unique as compared to a previous study conducted in the US [1]. A larger scale study is warranted in the future to better evaluate the response to physostigmine and its associated predictors of various substances.

245. Incidence of kratom-related poison control calls before and after kratom legalization in Thailand: current trends

Abstract

Objective

Kratom (Mitragyna speciosa), is an indigenous tree in Southeast Asia. Currently, kratom is popular and easily available worldwide, especially in Europe and the US via shops or the Internet to use as a substance of abuse, opioid alternative, or painkiller. In Thailand, kratom was illegal until August 24, 2021, but is now legal to possess and use. The data of impact after legalization is limited. This study was performed to describe and evaluate the incidence, clinical characteristics, and consequences of use and the trend of kratom-related poison center calls before and after legalization in Thailand.

Methods

We performed a retrospective cross-sectional study by analyzing data from the Ramathibodi Poison Center for 3 6-month periods: the first period (6 months after legalization 24 August 2021–23 February 2022), the second period (6 months before legalization 24 February 2021–23 August 2021), and the third period (the same period (months) as the first period but in the previous year 24 August 2020–23 February 2021).

Results

There were 173 calls or cases consulted to our poison center: 96, 38 and 39 cases in the 1st, 2nd and 3rd periods, respectively. The mean age of patients overall, and cases in the 1st, 2nd and 3rd periods were 29.4, 29.7, 29.0 and 28.9 years, respectively. Overall, most patients (84.4%) and those in each study period were male. Both the overall group (about 60%) and those in each study period had used or co-ingested kratom with other substances. The common clinical manifestations included palpitation (35.8%), nausea/vomiting/abdominal pain (22.5%), seizure (22.0%), agitation (18.5%), tremor (11.6%) and dystonia (5.2%). Interestingly 2 cases developed status epilepticus. The abnormal vital signs were tachycardia (43.4%), high blood pressure (22.5%) and high body temperature (6.9%). No patients presented with obvious respiratory depression or low oxygen saturation. Forty-six cases (26.6%) were admitted. Two cases (in the 1st period) were intubated due to drowsiness. No fatal cases occurred in the study groups. We compared the clinical characteristics of cases among 3 periods. No significant differences were found in age, sex, regions, co-ingestion and clinical effects including seizure among these 3 periods. However, cases in the 1st period were admitted (37.5%) more statically significantly when compared to the previous 2 periods (15.8%, 10.3%) (p < 0.001).

Conclusion

Kratom-related calls increased about 2 times after legalization. The trends of consultation and hospitalization were on the rise. Most enquiries involved young males who used kratom with other substances. Seizure was reported commonly in every period; however, its incidences showed no differences between the three study periods.

246. Alkyl nitrite (“poppers”) exposures in the United States: are poppers popping up more?

Abstract

Objective

Alkyl nitrites or “poppers” are recreational drugs that are used for their short-acting vasodilatory properties and purported ability to enhance sexual intercourse. While inhalation is the typical route of administration, ingestions have recently become more common in our catchment area and may be associated with an increased risk of developing methemoglobinemia. To investigate trends of poppers exposures in the US, we analyzed poison center reports over a ten-year period.

Methods

This is a retrospective review of aggregate poison center data collected by the US National Poison Data System (NPDS) from 2013 to 2022 on cases coded as related to amyl or butyl nitrites (street drugs), generic code 0034810. Route of exposure, user demographics, disposition, and clinical outcome were assessed.

Results

From 2013 to 2022, the total number of reports of alkyl nitrite exposures in the US increased from 138 to 365, and the total number of cases that presented to healthcare facilities (HCF) increased from 59 to 185. During the study period, 344 out of 942 patients (36.5%) who presented to a HCF were admitted, including 209 patients (22.2%) who were admitted to critical care units. Out of 2034 cases across the study period, 883 cases reported inhalation (43.4%) and 1098 cases reported ingestion (54.0%) as the route of exposure. Though the ratio of male-to-female patients who reported exposures remained stable at 4:1 on average over the study period, 206 out of 1098 ingestion cases (18.8%) involved females, whereas 94 out of 883 inhalation cases (10.6%) were female. Patients who ingested poppers had 94 major adverse events (8.6%) and 255 moderate adverse events (23.2%) out of 1098 reported exposures; patients who inhaled poppers had 68 major adverse events (7.7%) and 227 moderate adverse events (25.7%) out of 883 reported exposures. Of all patients who presented to a HCF, 202 out of 465 patients (43.4%) who ingested poppers were admitted to either non-critical or critical care units, and 156 out of 495 patients (31.5%) who inhaled them were admitted.

Conclusion

US alkyl nitrite exposures more than doubled from 2013 to 2022, although routes of exposure and demographics of users remained stable. Patients who ingested alkyl nitrites were more likely to experience major outcomes and hospitalization. Healthcare providers and public health authorities should consider harm reduction campaigns to encourage safer use patterns in alkyl nitrites, such as inhalation over ingestion.

247. Characterization of animal exposure calls captured by the National Poison Data System, 2013–2022

Abstract

Objective

This sought to characterize the data from all animal exposure calls reported to the National Poison Data System (NPDS) from 1 January 2013 through 31 December 2022. This investigation sought to identify recent patterns in poison center (PC) usage related to animal-related incidents and identify the resources and interventions associated with such exposure calls.

Methods

This study analyzed descriptive statistics characterizing animal type, exposure substance, route of exposure, reason for exposure, medical outcome, therapy provided, year and month of call, and caller site location for all animal exposure call data in NPDS from 1 January 2013 to 31 December 2022. Computational analysis was executed using RStudio.

Results

There were 582,426 animal exposure calls out of 21,958,424 (2.7%) total human and animal exposure calls in NPDS during the study period. The majority involved companion animal exposures with 90.0% canine, 8.6% feline, 2.9% bird, and 2.4% rodent/lagomorph exposures. Ingestion accounted for 91.3% of exposure routes (n = 545,004), followed by dermal (n = 24,942; 4.2%), and inhalation/nasal exposures (n = 13,296; 2.3%). Out of 1026 total exposure substances recorded, “other types of insecticides” (n = 52,162; 8.6%) were the most prevalent, followed by pyrethroids (n = 26,256; 4.3%). The most frequently reported medical outcome was “Not followed, minimal clinical effects possible (no more than minor effect possible)” (n = 262,355; 45.0%), followed by “Unable to follow, judged as a potentially toxic exposure” (n = 166,113; 28.5%). The most common caller site was the own residence (n = 517,010; 88.8%). Calls from veterinarians steadily declined over the study period (p < 0.001). The greatest number of calls occurred in July, with a seasonal distribution peaking in the summer months, and the fewest number of calls received in February. Most cases required no therapy (63.5%). Few specific pharmacological antidotes were administered, with phytonadione (n = 473) being the most frequent. There were 1323 deaths reported.

Conclusion

US PCs continue to receive calls pertaining to potential toxic exposures to animals, though the number has dropped from 4.7% (2000–2010) [1] to 2.7% of total calls received during the study period. Continued calls related to animals underscores the necessity of incorporating veterinary expertise and resources into PCs services. With the majority of exposure calls originating from the owner's residence, there continues to be a need for education on the prevention and treatment of toxic exposure threats to animals.

248. US poison centers utilization by mental health treatment facilities over the past decade

Abstract

Objective

Poison centers in the US provide free expert recommendations on the treatment of a diverse range of toxicological emergencies. Prior research has demonstrated the positive impact of poison centers in reducing hospital visits for calls originating from non-healthcare settings, as well as decreasing length of hospital stays and associated expenditures for patients within a health system. Considering the prevailing mental health crisis and the shortage of psychiatric inpatient beds, we hypothesize that poison centers could assume a pivotal role in the management of overdose cases in mental health facilities. The primary purpose of this study was to describe poison center utilization by mental health treatment facilities over a ten-year period.

Methods

We conducted a retrospective analysis using the National Poison Data System (NPDS), a data warehouse which collects information from all 55 US poison centers. NPDS was queried for all calls originating from mental health treatment facilities between 2013 and 2022. NPDS provides de-identified data with coded fields for each case. Data includes patient demographics, substance(s), route and reason for exposure, management site, and medical outcome. Characteristics of cases are reported descriptively.

Results

During the study period, 33,086 calls originating from mental health treatment facilities were reported with an average of 3300 calls per year ranging between 3189 and 3413 calls. These calls represented 0.15% of all calls made to US poison centers. Females represented 50.9% (n = 16834) of the cases. Adult and teenager (13–19 years) cases represented 59% (n = 19,643) and 35% (n = 11,427) of total calls, respectively. Ingestion was the most frequent route of exposure (n = 30,619, 92.5%). Most of the cases were successfully managed on site (n = 22,591, 68%) and 32% (n = 10,495) were transferred to a medical facility for management. Suspected suicide attempts (n = 8857; 27%) accounted for the highest proportion of exposures, followed by therapeutic errors (6347, 19%), intentional misuse and abuse (n = 4685, 14% and n = 3200, 10%, respectively). Among pharmaceutical substances, atypical antipsychotics were most frequently involved in exposure (n = 2785; 8.4%), followed by benzodiazepines (n = 1889; 5.7%) and acetaminophen in isolation or combination (n = 1525; 4.6%). Foreign body related calls (n = 845; 2.6%), hand sanitizers (n = 1378, 4.2%) and ethanol (beverages) (n = 831; 2.5%) were the most frequent non-pharmaceutical exposures.

Conclusion

Poison center services are under-utilized by mental health institutions across the US. There is a need to promote the role poison centers can play in preventing harm and reducing the cost of medical care following a potential toxic exposure.

249. Increase in clotiazepam cases in Chile: analysis by the major poison center in Chile

Abstract

Objective

Poisoning is a public health problem in Chile, with more than 30,000 cases per year recorded by the Centro de Información Toxicológica (CITUC), which is the principal Poison Control Center in Chile. There has been a perceived increment in some drugs in the past five years, such as clotiazepam, which is used widely in Chile; it is used during social media challenges among teenagers. The changes in clotiazepam cases has not been measured previously, so the objective of this study was to analyze clotiazepam cases.

Methods

Analysis of the incidence of clotiazepam cases in teenagers (12–18 years) registered by CITUC between January 2019 and September 2023. The cases are described by sex, exposure circumstance, and severity of symptoms. We used the ANOVA test of monthly cases by year to compare if there are differences in the monthly mean of cases registered between years. To explore possible risk factors, we calculated the Odds Ratio (OR) by sex and stratified by exposure circumstance and presence of symptoms.

Results

In the study period, 1035 cases were registered, 110 in 2019, 118 in 2020, 225 in 2021, 337 in 2022, and 245 until September 2023. Most cases (871, 84.2%) involved females, with 164 (15.8%) males. Most (96.8%) of the total cases were suicide attempts, followed by medication errors (1.4%) and accidental exposures (1.3%). The severity of symptoms were 60.7% minor, 6.0% moderate, 0.1% severe, and 29.6% of the cases did not have symptoms at the time of the call. The monthly mean by year was: 2019 = 9.1 (6.7–11.6); 2020 = 9.8 (8.1–11.5); 2021 = 18.75 (14.8–22.6); 2022 = 28.0 (24.4–31.7); 2023 = 27.2 (22.2–32.1), with an ANOVA test p <0.0001, that is statistically significant. Females had an OR of 0.9 (0.3–2.3) for suicide attempts and sex was not a risk factor for having symptoms, with an OR of 1.20 (0.84–1.72).

Conclusion

These results demonstrate there is an increment in the incidence of clotiazepam cases in the period 2019–2023. The most common cause of exposure was a suicide attempt. Although there are no differences in risk by sex, it is interesting that female was a protection factor for suicide attempt in clotiazepam cases, which is contrary to the common phenomena.

250. Epidemiology of poisoning with quetiapine by a poison center in Chile

Abstract

Objective

Poisoning is a public health problem in Chile, with more than 30,000 cases per year recorded by the Centro de Información Toxicológica (CITUC), which is the principal Poison Control Center in Chile. There is a perceived increment in some drugs in the past five years, such as quetiapine, but this has not previously been measured, so the objective of this study is to analyze quetiapine cases.

Methods

Analysis of the incidence of quetiapine cases registered by CITUC between January 2019 and September 2023. The cases are described by sex, exposure circumstance, and severity of symptoms. We used the ANOVA test of monthly cases by year to compare the monthly mean of cases registered between the years. To explore possible risk factors of being exposed to quetiapine, we calculated the Odds Ratio (OR) by sex and stratified by exposure circumstance and presence of symptoms.

Results

In the study period, 9097 cases were registered, 1431 in 2019, 1375 in 2020, 1828 in 2021, 2424 in 2022, and 2039 up to September 2023. Most (6975, 76.6%) involved females and 2123 (23.3%) were males. Overall 90.8% of the total cases were suicidal attempts, followed by accidental exposures (4.9%) and medication errors (4.9%). Severity of symptoms was 57.6% minor, 21.3% moderate, 1.5% severe, and 21.3% of the cases did not have symptoms at the time of the call. The monthly mean by year was: 2019 = 119.2 (112.4–126.0); 2020 = 114.5 (104.9–124.2); 2021 = 152.3 (137.0–167.5); 2022 = 202.0 (183.2–220.7); 2023 = 226.5 (202.7–250.3), with an ANOVA test p < 0.0001, this increase is statistically significant. Females had an OR of 3.1 (2.6–3.5) for suicidal attempts. However, sex was not a risk factor for having symptoms, with an OR of 1.07 (0.95–1.20).

Conclusion

These results demonstrate there is an increment in the incidence of quetiapine cases in the period 2019–2023. The most common cause of exposure was intentional self-harm and females have a greater risk of attempted suicide with quetiapine, however, males and females have the same risk of developing symptoms after exposure. Awareness of the changes in poisoning in Chile are essential in order to adopt control interventions.

251. SGLT-2 inhibitor-associated euglycemic ketoacidosis in Denmark

Abstract

Objective: In recent years, there has been growing evidence for an association between the use of sodium-glucose co-transporter-2 (SGLT-2) inhibitors and ketoacidosis with normal plasma glucose concentrations. We aim to describe the risk, characteristics, and outcomes following hospitalization with SGLT-2 inhibitor-associated euglycemic ketoacidosis.

Methods: In Danish registries, we identified all biochemistry-confirmed cases of euglycemic ketoacidosis while treated with SGLT-2 inhibitors in Denmark until 2021. The diagnosis was confirmed pH <7.3, serum bicarbonate <18 mEq/L, and plasma glucose <11 mmol/mol. Treatment was defined as having redeemed at least one prescription six months prior to hospitalization.

Results: In total, we identified 80,418 individuals who initiated treatment with SGLT-2 inhibitors, totaling 151,286 treatment-years. We confirmed 16 cases of euglycemic ketoacidosis, consisting of 9 males and 7 females. Table 1 presents patient characteristics. Considering death as a competing risk, analysis reveals a 5-year absolute risk for hospitalization with euglycemic ketoacidosis of 0.03% (95% CI 0.02 to 0.05%). No patients died during hospitalization.

Table 1 Characteristics of patients with SGLT-2 inhibitor-associated euglycemic ketoacidosis.

Characteristics (median (IQR) or N (%))	N = 16
Females	9 (56%)
Age (years)	64 (52, 71)
Years with diabetes	10.5 (7.8, 13.3)
Days treated with SGLT-2 inhibitors	626 (360, 963)
Days hospitalized	6 (5, 11)
Biochemistry at admission
pH	7.25 (7.24, 7.27)
Glucose (mmol/mol)	9.7 (8.7, 10.1)
Serum bicarbonate (mEq/L)	11.4 (9.2, 13.9)
Biochemistry prior to admission
Hemoglobin (mmol/L)	9.2 (8.2, 10.1)
HbA1c (mmol/mol)	59 (53, 84)
eGFR >90 mL/min/1.73 m^2	11 (69%)
eGFR 50–90 mL/min/1.73 m^2	5 (31%)
eGFR <50 mL/min/1.73 m^2	0 (0%)
Comedication
Antidepressives	5 (31%)
Antithrombotics	7 (44%)
Antihypertensives	9 (56%)
DPP-4 inhibitors	6 (38%)
Furosemide	6 (38%)
GLP-1 receptor agonists	6 (38%)
Metformin	13 (81%)
Statins	13 (81%)

DPP-4: dipeptidyl peptidase; GLP-1: Glucagon-like peptide-1; SGLT-2: Sodium-glucose co-transporter 2; eGFR: estimated glomerular filtration rate.

Conclusion: SGLT-2 inhibitor-associated euglycemic ketoacidosis events are rare, and we did not identify any cases resulting in in-hospital deaths.

252. High dose buprenorphine titration in severe chronic obstructive pulmonary disease (COPD) and the risk of significant respiratory depression

Abstract

Objective: Buprenorphine, as a partial μ-opioid receptor agonist with high binding affinity, has less potential to cause respiratory depression as treatment for opioid use disorder (OUD) compared to methadone. Little guidance exists on the initiation of buprenorphine in COPD and concerns exist around precipitated withdrawal and respiratory depression. This case study describes a successful buprenorphine titration in a patient with OUD and severe COPD admitted to the only dedicated Addiction's and Toxicology unit for illicit drug treatment located in an acute NHS hospital (London, UK).

Case report: A 66-year-old male with severe COPD was admitted for buprenorphine (Espranor^® oral lyophilisate) titration due to the risk of respiratory arrest if initiated in the community. He reported injecting £60 of heroin twice daily having last injected 14 hours previously. He was housebound due to breathlessness and could mobilise 2 m. Examination revealed chest hyper-expansion, reduced air entry and wheeze, a respiratory rate 18, SO₂ 91% (room air) and BMI 17.6 kg/m². Investigations included a chest X-ray demonstrating emphysema, arterial blood gases revealed pH 7.38, PO₂ 7.24 kpa, PCO₂ 8.3 kpa, base excess 4.7, bicarbonate 32.7 mmol/L, haemoglobin 171 g/L and normal renal/liver function. Espranor^® 2 mg was administered as required according to the Objective Opiate Withdrawal Score (OOWS) performed 4-hourly. Buprenorphine was then increased based on the preceding 24-h dose and ongoing withdrawal symptoms while the patient was closely observed for respiratory depression (Table 1). On Day 4 the patient desaturated to 85% requiring 2 L oxygen. Due to further desaturations and a raised D-dimer (0.73 mg/L) a computerised tomography pulmonary angiogram (CTPA) was completed which excluded pulmonary embolism but demonstrated emphysematous change throughout the lungs. Other than a worsening cough, he remained asymptomatic and received treatment for an infective exacerbation of COPD.

Table 1 Buprenorphine dosing in a patient with severe COPD and opioid use disorder (OUD).

Day	Time	Buprenorphine dose	Total 24-h buprenorphine dose	Pulse oximetry range (%) (on room air)
1	20:00	2 mg	6 mg	91–94%
	00:00	2 mg
	06:00	2 mg
2	13:00	6 mg	10 mg	91–96%
	18:00	2 mg
	22:00	2 mg
3	07:00	10 mg	12 mg	88–94%
	13:30	2 mg
4	08:30 23:30	12 mg 2 mg	14 mg	85% on air 88–91% on 1L to 2L O2 O2 used intermittently between Day 4 to 11
5	10:00	12 mg	14 mg	89–91%
	00:30	2 mg
6	10:30	14 mg	16 mg	88–92%
	23:30	2 mg
7	12:00	14 mg	16 mg	88–92%
	21:00	2 mg
8	07:00	14 mg	14 mg	88–92%
9	09:00	16 mg	16 mg	89–92%
10	09:00	16 mg	16 mg	90–91%
11	09:00	16 mg	16 mg	90–91%
12	09:00	16 mg	16 mg	90–91%
13	09:00	16 mg	16 mg	90–91%
14	09:00	16 mg	16 mg	Discharge SO2 91% on air

Conclusion: Titration with buprenorphine in OUD and severe COPD is completed on a patient-by-patient basis. It risks significant respiratory compromise and should be conducted in units able to deliver both medical and addictions support.

253. Non-significant effect of post-surgery unithiol on cobalt intoxication

Abstract

Objective: There is no certainty about the effect of chelation in patients with cobalt intoxication caused by a damaged cobalt-chromium (CoCr) hip prosthesis, as the data are limited. We present a new case.

Case report: A 76-year-old male underwent total hip arthroplasty ceramic-on-ceramic type in 2003, in June 2020 his broken ceramic head was replaced by CoCr alloy head. Two years later increasing hearing loss, cardiomyopathy, and lowered psychomotor speed were found. X-ray (January 2023) showed a deposit of metal debris and Co intoxication was suspected. During the surgery (February 2023) about 500 mL of metal debris were removed and the acetabular component and the femoral head were exchanged. Due to high Co concentration, two series of treatments with unithiol (2,3-dimercaptopropane-1-sulfonate, DMPS) 400 mg/day were used (firstly for 15 days, second course only two days due to allergic eczema). An X-ray on 12 May showed good healing and a small (5 × 10 mm) residual metal abrasion near the joint in the vicinity of large vessels and nerves, where it was not possible to operate with sharp instruments. Serum analysis showed a significant decrease of both Co and Cr by 6 days post-surgery to 18% and 39%, respectively (Table 1). This occurred before the chelation and further decrease was milder despite unithiol treatment.

Table 1 Metal concentrations in biological samples and joint debris in a patient with a cobalt-chromium (CoCr) hip prosthesis.

Date	Sample	Cobalt	Chromium	Titanium	Units
23 February 2023 (Surgery)	Joint debris	2290	1800	4.5	mg/L
	Serum	910	50.7		µg/L
3 March 2023 (Pre-treatment)	Serum	164	19.2		µg/L
	Urine	308	33.7		µg/L
Unithiol treatment 3–19 March 2023
13 March 2023 (10 dayś treatment)	Serum	113	17.0		µg/L
	Urine	195	37.4		µg/L
31 March 2023 (Pre-treatment)	Serum	69.4	11.7		µg/L
Unithiol treatment 31 March to 2 April 2023
3 April 2023 (Last treatment)	Serum	51.3	14.5		µg/L
	Urine	61.2	11.6		µg/L

Conclusion: Unithiol treatment did not result in a significant decrease in serum cobalt concentration and improvement in neurological problems and severe hearing loss. Pericardial exudate disappeared and cardiology finding improved. Removal of metal deposits during the surgery was most effective due to a 2500-fold concentration of Co as compared with serum. This result does not support unithiol treatment post-surgery [1], however it may be useful while waiting for surgery.

Acknowledgements

Cooperatio 207041-3.

254. Blind spot: the silent threat of closantel toxicity

Abstract

Objective

We report a rare case of closantel toxicity causing irreversible visual loss to increase awareness of this severe complication to facilitate early recognition and management. Closantel is a broad-spectrum anthelminthic agent commonly used for parasitic infestation in sheep and cattle [1]. Human closantel exposure is uncommonly reported, and is ophthalmotoxic, neurotoxic and hepatotoxic [1–3].

Case report

A 73-year-old male accidentally ingested 40–80 mL of Avomec Sheep Drench (abamectin 1 g/L, closantel 50 g/L). He immediately spat out half the substance and called the NSW Poisons Information Centre (PIC). He was advised to maintain oral hydration and seek medical attention for any vomiting, diarrhoea, drowsiness or dizziness. He had minimal vomiting but profuse diarrhoea over eight hours and progressive bilateral vision loss over the next two days, without further PIC consultation during that time. Extensive outpatient investigations including pathology, carotid ultrasound and brain magnetic resonance imaging (MRI) with angiography were unremarkable. Ophthalmology clinical examination demonstrated bilateral cataracts, possible pale optic nerve with normal maculae and intraocular pressures. No treatment was initiated at this time. At 20 days post-exposure, neuro-ophthalmologist review with retinal imaging and optical coherence tomography confirmed diffuse loss of retinal layers with loss of ellipsoid zone and retinal oedema. After PIC consultation, he commenced IV methylprednisolone 1 g for 3 days then high dose oral prednisone (1 mg/kg) for 7 days, despite likely futility given the treatment delay. On discharge there was subjective visual improvement, with increased brightness and colour perception. Repeat testing 5 weeks post-exposure revealed foveal contour loss and mild bilateral visual field improvement. This is consistent with other treatment delay case reports [1–4].

Conclusion

This case highlights the devastating consequence of bilateral vision loss after minor accidental closantel exposure. Treatments including plasmapheresis and systemic steroids show mixed success in vision loss, further reduced with treatment delay. A high degree of awareness is required to ensure any exposure is rapidly treated to minimise ophthalmic complications.

255. Occupational accidents involving animals and plants: an observational study of cases recorded in a poison control center

Abstract

Objective

Our work consisted of determining the species involved in bites and stings and plant exposures occurring in an occupational setting, as well as the circumstances of exposure, the occupations involved and the type of collective and individual prevention used at the time of the accident.

Methods

A retrospective observational study was conducted for all cases involving animals or plants in an occupational context, from 2012 to 2022. Cases were taken from the National Database of Intoxication Cases (BNCI). Inclusion criteria were as follows: calls involving an animal or a plant; cases occurring in the PCC's area of competence; cases of probable or very probable imputability. Biological infectious agents were excluded, as were cases for which the profession was not specified.

Results

Over the study period, 244 cases were analyzed. The mean age of the victims was 36.0 years (min 15 years; max 68.3 years). There were 57 women (23.4%) and 187 men (76.6%), giving a sex ratio of 3.3. There were 10 high severity cases (6.0%, PSS 3) involving only animals, and 52 medium severity cases (23.6%, PSS 2). The animals and plants involved are listed in Table 1. Certain professions were more exposed to accidents involving animals and plants, notably gardeners (52 cases, 21.3%), landscapers (32 cases, 13.2%), farmers (18 cases, 7.3%), nurserymen (12 cases, 4.9%), insect control specialists (9 cases, 3.7%), beekeepers (8 cases, 3.3%), market gardeners, pruners and fishermen (7 cases respectively, 2.9%), fishmongers and firefighters (6 cases respectively, 2.5%).

Table 1 Occupational accidents involving plants and animals, 2012–2022.

Animals and plants	N (%)
Insects, including Hymenoptera (52 cases) and Lepidoptera (16 cases)	73 (30.0)
Snakes, including autochthonous vipers (57 cases)	66 (27.0)
Aquatic animals	19 (7.8)
Other non-venomous animals	4 (1.6)
Spiders	2 (0.8)
Plants responsible for dermatological disorders, including Euphorbia species (41 cases)	58 (23.8)
Plants responsible for phytophotodermatitis	17 (7.0)
Plants responsible for skin injury (thorns, glochids)	9 (3.7)
Plants responsible for systemic toxicity	5 (2.0)

Conclusion

The problem of natural hazards in the workplace is little-known, even though it is a source of potentially serious cases. The importance of prevention, and of wearing personal protective equipment, is crucial in limiting the number of cases.

256. Reports of fatal work accidents to the German Federal Institute for Risk Assessment (BfR) in the last twenty years

Abstract

Objective

In Germany, all poisonings must be notified to the German Federal Institute for Risk Assessment (BfR) by the attending physicians or the responsible statutory accident insurances on a legal basis. In fatal cases, notification must be made after the autopsy. All notifications to the BfR are validated and registered in a standardised manner in BfR’s national poisonings database. For this study, the BfR evaluated reports on work accidents with a fatal outcome.

Methods

All deaths notified to the BfR from 2004 to September 2023 in relation to work accidents were evaluated according to the reported noxious agents, the route of exposure, the aetiology, the reported clinical course and/or the results of the medicolegal examination.

Results

In the last 20 years, 15 fatal work accidents were reported to the BfR. Three events resulted in the deaths of several people. All accidents involved men. The majority (13 cases) occurred after inhalational exposures, one case was caused by ingestion and one by severe chemical burns. The most common noxious agent was hydrogen sulfide. Seven incidents occurred during maintenance work, in 4 cases decanting into incorrect containers led to the accident (4 cases: other or unknown reasons). Ten of the persons concerned died at the scene of the accident, while 5 died in hospital due to complications related to the poisoning, e.g., by sepsis or hypoxic brain damage. According to the reports, the majority of cases were caused by human error. In some incidents, necessary safety precautions were not observed.

Conclusion

The study presented here shows that fatal workplace poisonings are primarily caused by toxic gases. Since the causes often lie in non-observance of the necessary safety precautions, companies should pay even more attention to comprehensive training for employees.

257. Consultations for gamma-hydroxybutyrate (GHB) poisoning recorded at the National Poisons Information Centre of Ireland from 2013 to 2022

Abstract

Objective

To describe the profile of gamma hydroxybutyrate (GHB) or its derivative intoxication consultations received by the National Poisons Information Centre of Ireland (NPIC).

Methods

A retrospective review of consultations at NPIC from 2013 to 2022 was conducted. NPIC collects and analyzes epidemiological data on acute poisonings, providing support to healthcare professionals for managing intoxicated patients. Data on the circumstances and type of intoxication, patient demographics, reported co-ingestion of other toxins, Poison Severity Score and outcome were collected and analyzed.

Results

A total of 27 consultations were recorded with most cases related to an acute exposure to GHB (96.3%). The median age was 30 years (IQR 25–33), and 85.2% were male. Recreational use was the reason for intoxication in over 50% of cases. Co-ingestion with other toxins was reported in 37%. Only 3 cases of withdrawal were recorded. Coma was the most frequently reported clinical presentation (25.9%). Among withdrawal cases, two patients presented with tremors and one with agitation. Regarding the Poison Severity Score, one case (3.7%) was fatal, nine (33.3%) were severe, and six (22%) were moderate. In over 50% of cases, recovery was complete. One patient died. The National Poisons Information Centre of Ireland recommended vital sign monitoring and supportive measures in the majority of cases (85.2%). In the remaining cases, patients were asymptomatic or the consultation related to interactions with other medications or the availability of an antidote.

Conclusion

GHB poisoning is severe, and recurrent use can lead to withdrawal cases that are serious and often require hospital management. This is likely an under representation of GHB admissions to hospital as this type of poisoning is not detected in routine toxicological analyses.

258. Get another hobby: the cost of antivenom and antivenom logistics in a Crotalus atrox bite in Sweden

Abstract

Objective

Vipera berus (European adder) is the only venomous snake endemic to Sweden, however, at least 130 different species of exotic snakes (many highly venomous) are kept in private homes as pets, and the Swedish Poisons Information Centre (PC) is involved in 2–6 exotic snake envenomations (ESE) annually. The Pharmacy CW Scheele (CWS), situated in Stockholm maintains a national stockpile of 14 polyvalent snake antivenoms (AV). In cases of ESE the PC is typically contacted by the receiving hospital and gives instructions to the CWS on which AV product to dispatch. The logistics and costs of this service are described in this case report.

Case report

A 33-year-old man arrived at a hospital in Gothenburg (470 km from CWS) within 15–30 min after suffering a bite to the right hand by his pet diamondback rattlesnake (Crotalus atrox). On arrival at 6 pm the entire hand was swollen, he had vomited once, was pale and nauseous but had stable vital signs. The PC was contacted at 6:10 pm and instructed the CWS to dispatch its entire supply of CroFab (8 vials, 33 200 EUR) by blue-light after-hour transport (2700 EUR). The AV left Stockholm at 7:10 pm and arrived in Gothenburg at 11 pm. The patient received all 8 vials in repeated doses during the following 12 hours. His vital signs and coagulation parameters remained stable, but his arm was now swollen to the shoulder, and he was in severe pain. Per instructions from the PC the CWS dispatched its entire supply of Antivipmyn Tri (10 vials, 15500 EUR) by immediate normal hour transport (1340 EUR). However, the patient remained stable and was not judged to need the Antivipmyn Tri, which was sent back to CWS seven days after the bite (normal delivery 975 EUR, AV cost refunded). According to Swedish regulations, pharmaceuticals dispatched from a pharmacy to a hospital may not be sent in return. However, exotic snake AVs are exempt if they are kept refrigerated. The CWS therefore packs the AVs in transport refrigerators together with digital thermometers at a cost of 1300 EUR per dispatch.

Conclusion

The cost of antivenom + antivenom delivery logistics in this case was 33,200 + 7615 = 40,815 EUR. The cost is borne entirely by Swedish taxpayers. The regulatory exemption permitting the return of Antivipmyn Tri saved 13,300 EUR. For comparison, the AV cost for treating an endemic viper bite is 3100–6200 EUR, with minimal logistic costs as antivenom is stocked locally at 70 Swedish hospitals.

259. Chronic exposures to medication drugs in the elderly: data from a poison centre

Abstract

Objective

Due to altered pharmacodynamics and pharmacokinetics in old age, the risk of adverse drug reactions and interactions is increased. The aim of this retrospective evaluation of chronic exposures to pharmaceuticals reported to a poison centre (PC) is to identify the medications that most often led to moderate and/or major poisoning (MMP) and inpatient treatment after chronic ingestion. In addition, we wanted to know whether these drugs are mentioned on the list of potentially inappropriate medications (PIM) published in Germany in 2010 [1].

Methods

Human exposure data collected by a German PC between 2006 and 2020 were retrospectively analysed. Only elderly patients (≥65 years) chronically exposed to medications were included. Excluded were exposures to an unknown medical drug and symptomatic exposures with a causality assessment of "unlikely" or "unassessable". The rate of MMP was determined for PIM and other pharmaceuticals.

Results

Overall 688 patients in the age of 65–98 years (median 76) were included; 429 patients were female (62%) and 356 patients displayed MMP (51.7%). The intake of at least 1 PIM was reported in 91 cases (13.2%) with 597 non-PIM cases (86.8%). MMP occurred in 45 (49.5%) PIM and 311 non-PIM (52.1%) cases. The five most often reported pharmaceuticals were lithium (n = 193; 28%), digitoxin (n = 52, 7.5%), digoxin (n = 17, 2.5%), methotrexate (n = 16, 2.3%), and paracetamol (n = 14, 2.0%). These five pharmaceuticals accounted for 292 exposures and for 207 MMP (71%). The proportion of MMP was highest for digitoxin (83%), lithium (71%), amitriptyline (70%), methotrexate (68%), and digoxin (65%). Out of these, only amitriptyline and digoxin are listed as PIM.

Conclusion

PIMs accounted only for one tenth of chronic poisonings and for 13% of MMP. Pharmaceuticals not listed as PIM dominated as causes of MMP in the elderly. Out of these, lithium most often led to MMP after chronic intake. That fits with reports of a higher incidence of lithium toxicity in the elderly than in the young [2]. In addition, the data raise the question of whether lithium should be added to the list of PIM.

260. Analysis of intoxications that required the activation of an online platform to ensure antidote availability

Abstract

Objective

Antidote availability is a main concern. In our country, a virtual platform was designed to share information about antidotes and to facilitate movements between centres [1]. The objective of this study was to describe the intoxications that required the use of the virtual platform to ensure availability.

Methods

A descriptive study was carried out from January 2020 to September 2023. Each time an antidote was requested through the platform, a questionnaire was sent to register the information. The data collected were age and sex of the patient, toxin, route of intoxication, antidote requested, medical service that requested the loan, indication of the antidote, clinical impact and user’s satisfaction with the online tool.

Results

In this period, 57 antidote requests were made through the platform. The most requested antidotes were digoxin antibodies (11), dantrolene (10), snake venom antiserum (8), ethanol (8), idarucizumab (4), silibinin (4), botulism antitoxin (BAT) (4), EDTA (3) and others (5). In 33 cases (57.9%) the patients were men and eight intoxications occurred in paediatric patients. The underlying toxics were drugs (43.8%), animal toxins (15.8%), heavy metals (7%), solvents (7%), mushrooms (7%), plants (1.8%), toxic gases (1.8%) and other substances (15.8%). The most common route of intoxication was oral (63.2%). The clinical conditions that justified the treatment were: alcohol toxicity (15.8%), reversal of snake envenomation (14%), hemodynamic instability (14%), malignant hyperthermia or neuroleptic malignant syndrome (14%), heart rhythm disorder (12.3%), heavy metal toxicity (7%), and others (22.9%). The antidote was not used in 14% of the patients but in 22.8% of the cases it was considered that it had a decisive impact on the patient and in 52.6% of the cases it provided a clinical benefit. The global analysis showed that antidote treatment was successful in 63.2% of the cases and avoided other therapeutic measures in 28.1% of the situations. In 10.5% of the intoxications, it was estimated that the antidote helped to reduce the Emergency Department stay. Finally, the average rating given by the platform uses was 9.16/10.

Conclusion

The online platform might help to improve antidote availability. The most requested antidote was digoxin antibodies. Most of the intoxications that required an antidote loan between hospitals were of pharmacological origin. In general, the antidote treatment positively contributed to the patient evolution.

261. Deliberate self-poisonings (DSPs) reported to Poison Information Centers (PICs) in four European Countries between 2017–2022: an EAPCCT pilot project

Abstract

Objective: Reports from the US, Canada and some European Countries recently indicated a rise in deliberate self-poisonings (DSPs), more specifically in adolescents and young adults, possibly due to the COVID pandemic. This pilot study describes recent trends in DSPs reported to Poison Information Centers (PICs) in four European countries.

Methods: We retrospectively collected the number of DSPs (excluding recreational poisonings) registered in French, German (Freiburg, responsible for Baden-Württemberg), Dutch and Swiss PICs from 2017 to 2022. Monthly aggregated data (age groups and gender) were collected on DSPs. The number of DSPs were expressed as percentage relative to the number of all poisonings and to all DSPs. Temporal trends were studied using SARIMA modelling based on pre-pandemic data (2017–2019).

Results: The rate of DSPs varied from 8% to 23% between PICs. Within DSPs, females represented approximately 70% in all countries. Within DSPs, the age groups 13–17 years and 18–24 years represented between 12–36% and 14–24%, respectively. Of all poisonings in the age groups 13–17 years and 18–24 years, 41–58% and 19–60%, respectively involved a DSP (Table 1). Time-trend analysis showed an increase in DSPs in the post-pandemic period for all countries collectively and for individual countries. This increase was mainly related to the significant increase in DSPs in 13–17 year olds. DSP increased in both men and women, but earlier (from 2021) and to a greater extent in women. Within specific age groups, the rate of DSPs increased significantly only in the 13–17 year-olds, and to a greater extent in females than in males.

Table 1 Epidemiology of deliberate self-poisonings (DSPs) reported to four European Poison Information Centers, 2017–2022.

	France	Germany (Baden-Württemberg)	The Netherlands	Switzerland
Population (in million)	68.04	11.28	17.59	8.81
N poisoning PIC cases	1,211,754	167,208	205,921	198,975
‍N DSP PIC cases	91,241	20,377	46,527	19,771
DSP rate among all PIC cases	8%	12%	23%	10%
DSP in specific groups relative to all poisonings (PIC cases)
DSP rate among females	14%	16%	31%	13%
DSP rate among males	6%	9%	15%	6%
DSP rate among 13–17 y	42%	41%	58%	44%
DSP rate among 18–24 y	19%	39%	60%	43%
Groups relative to all DSPs
‍ Females rate among DSP	69%	66%	69%	71%
Males rate among DSP	31%	34%	27%	29%
‍ 13–17 y rate among DSP	36%	12%	14%	18%
13–17 y female rate among DSP 13–17 y	84%	84%	79%	85%
18–24 y rate among DSP	14%	19%	24%	18%
18–24 y female rate among DSP 18–24 y	68%	72%	75%	74%

Conclusion: Females aged 13–17 years old are increasingly at risk for DSP. Harmonized data collection enables toxicovigilance at a European level.

262. Common substances used in deliberate self-poisonings (DSP) reported to Poison Information Centers (PICs) in four European Countries from 2017 to 2022: an EAPCCT pilot project

Abstract

Objective: The increase in deliberate self-poisonings (DSPs) in Western countries is a notable concern. Epidemiological data comparing the substances used in DSPs between European countries is missing. In this pilot study, we compared the substances used in DSPs reported to Poison Information Centers (PICs) in four European countries.

Methods: We retrospectively collected the number of DSPs (excluding recreational poisonings) registered in PICs in France, Germany (Freiburg PIC), the Netherlands and Switzerland from 2017 to 2022. For each PIC, the top 5 substances used in DSP were determined, for all patients, and for patients <18 years and ≥18 years. The number of exposures were expressed relative to the number of patients with DSP.

Results: The most common substances used in DSPs were paracetamol and alcoholic beverages (ranked first and second in all but one PIC, used by ≥30% of patients (Table 1). Only in the Freiburg PIC dataset, did ibuprofen outnumber paracetamol. In patients <18 years, paracetamol and ibuprofen were most frequently used and involved in approximately 50% of all DSPs in all four PICs. Alcoholic beverages were also within the top 5 in three out of four PICs in patients <18 years (not France). In patients aged ≥18 years, apart from paracetamol and alcoholic beverages, the substances used in DSP were more country-specific. In three out of four PICs (not France), alcoholic beverages were the most involved and quetiapine was in the top 5. Paracetamol and sedatives were in the top 5 in all four PICs.

Table 1 Substances involved in deliberate self-poisoning (DSP) reported to Poison Information Centers (PICs) from 2017 to 2022.

	France	%	Germany (Freiburg)	%	The Netherlands	%	Switzerland	%
Substances used in DSPs in patients <18 years
	n = 35,989 Patients		n = 2559 Patients		n = 6963 Patients		n = 3720 Patients
1	Paracetamol	40%	Ibuprofen	25%	Paracetamol	38%	Paracetamol	31%
2	Ibuprofen	10%	Paracetamol	18%	Ibuprofen	14%	Ibuprofen	16%
3	Cyamemazine	8%	Fluoxetine	6%	Methylphenidate	7%	Quetiapine	11%
4	Alprazolam	7%	Alcoholic beverage	5%	Alcoholic beverage	6%	Sertraline	7%
5	Hydroxyzine	6%	Quetiapine	5%	Fluoxetine	5%	Alcoholic beverage	6%
Substances used in DSPs in patients ≥18 years
	n = 54,255		n = 17,749		n = 39,547		n = 14,528
1	Paracetamol	19%	Alcoholic beverage	22%	Alcoholic beverage	17%	Alcoholic beverage	15%
2	Alcoholic beverage	14%	Ibuprofen	11%	Paracetamol	16%	Zolpidem	15%
3	Alprazolam	8%	Quetiapine	9%	Oxazepam	12%	Quetiapine	15%
4	Oxazepam	7%	Lorazepam	8%	Lorazepam	12%	Paracetamol	13%
5	Zopiclone	6%	Paracetamol	7%	Quetiapine	12%	Lorazepam	12%
Substances used in DSPs in all patients
	n = 91,241		n = 20,379		n = 46,527		n = 19,771
1	Paracetamol	27%	Alcoholic beverage	22%	Paracetamol	19%	Paracetamol	17%
2	Alcoholic beverage	10%	Ibuprofen	12%	Alcoholic beverage	15%	Alcoholic beverage	17%
3	Alprazolam	8%	Quetiapine	9%	Oxazepam	11%	Quetiapine	13%
4	Ibuprofen	6%	Paracetamol	7%	Quetiapine	11%	Lorazepam	12%
5	Cyamemazine	6%	Lorazepam	7%	Lorazepam	11%	Ibuprofen	9%

Conclusion: Similar substances were involved in DSPs in all four PICs. However, differences in preferences between countries and between age groups were observed, which may be used for the development of specific DSP prevention strategies. These pilot data show that harmonized data collection enables toxicovigilance at a European level.

263. Information calls to the Belgian Poison Centre concerning teratological risk

Abstract

Objective

The reporting of information calls to the Belgian Poison Centre (BPC) concerning the teratological risks of use of certain agents during pregnancy.

Methods

All information calls concerning pregnancy and teratological risks to the BPC from 2018 to 2022 were analyzed. Non-medical agents were first classified according to use and medicines following the ATC classification. These agents were then classified whether their use is known to be dangerous or safe during pregnancy based on the online databases Cybele.be and Lareb.nl or whether an estimation is not possible due to lack of data. The last step was to check whether the timing of these calls coincided with normal working hours where it is easy to contact a specialised medical professional or outside these hours.

Results

There were calls for 565 agents. Of these agents, 63.7% (N = 360) were medicines, 9.7% (N = 55) biocides and 26.5% (N = 150) were other agents such as phytotherapeutic pharmaceuticals, illicit drugs, food, or not otherwise specified agents. Within the group of medicinal products, those with action on the nervous system accounted for 31.9% (N = 115), for the respiratory system 21.7% (N = 78), for the digestive system 13.3% (N = 48), for antiparasitic medicines together with anti-infective drugs 17.8% (N = 64) and for the other groups 15.3% (N = 55). For 72.2% (N = 408) of these agents the use during pregnancy was rated as safe and for 6.5% (N = 37) as dangerous. In 6.5% (N = 37) data were missing to estimate the teratological risk. The call came in at a time when it is difficult to consult a specialist medical professional for 56.5% (N = 319) of these agents.

Conclusion

Our results show that there is a necessity for immediate teratologic information in Belgium. Existing hesitancy or unavailability of specialised medical professionals might encourage people to contact the BPC for these of inquiries. This is particularly the case as the BPC is available 24/7 free of charge and teratology could be seen as closely related to or even a part of toxicology. Further, our results can encourage the debate about the possible need for a distinct teratology information service in Belgium and, if so, they can help to outline the features of such a service and its relationship with other medical professionals and services as the BPC.

265. Poisoning Information Bureau Data in Lithuania for 2022

Abstract

Objective

To analyze consultations regarding poisoning cases in Lithuania conducted by specialists from the Department of Pharmacological Vigilance and Poisoning Information at the State Medicines Control Agency under the Ministry of Health.

Methods

Case data collected during 2022 was analyzed tabulating specific indices gathered by our specialists.

Results

In 2022 we provided 2566 consultations to residents and healthcare professionals, marking a 1% increase compared to 2021. Poisoning cases accounted for 89% of consultations, while 5% were inquiries, 3% were reports of poisoning cases, and 3% were erroneous calls. The majority of calls sought advice on potential health risks, specific poisonings, treatment strategies, and substance toxicity. When examining the ages of those affected by poisoning, adults were the most common group seeking consultations (56%). Calls related to child poisonings constituted 43%, while 1% had an unspecified age. The primary reasons for seeking consultation were accidental poisonings (64%), intentional poisonings (23%), unknown causes (10%), side effects (1%), and other reasons (2%). These consultations also extend to healthcare institution specialists, with 44% of calls directed at assisting in cases of poisoning. The general public accounted for 56% of consultations. Among the calls regarding poisonings, 50% were related to male individuals, 45% to females, and 4% were unspecified gender cases. Additionally, 1% of consultations involved poisoning in animals. The primary reasons for seeking consultation were accidental poisonings (64%), intentional poisonings (23%), unknown causes (10%), side effects (1%), and other reasons (2%). The analysis of poisoning cases in 2022 reveals that consultations were mainly sought for poisonings by medications, household chemicals, other substances, pesticides, and food. Consultations about poisonings in various therapeutic groups of medications were also prominent.

Conclusion

In conclusion, the data suggests a consistent slow rise in the number of consultations regarding poisoning cases in Lithuania, with an increasing trend in outpatient consultations. Additionally, the reduction in poisoning-related fatalities and the considerable number of consultations on medication and alcohol poisonings emphasize the importance of poison control centers in addressing public health issues.

266. Spanning the ocean: a comparison of adolescent suicide exposures from a US and an Italian poison center

Abstract

Objective: Since the pandemic and before, pediatric suicides have been increasing worldwide. We compared closed human exposure cases for suspected suicides in children and adolescents aged 10–19 years old between a four-state poison center (PC) in the US covering approximately 11.3 million people to the Milan Poison Center serving 59 million people with other independent PCs.

Methods: We queried the US National Poison Data System (NPDS) for closed human exposures age 10–19 years for the period 1 January 2016 to 31 August 2023.

Results: Total exposures from the US PC were 68,375. Of these 30,993 (45.3%) were intentional suspected suicides. Females numbered 24,099 (77.8%), males 6784 (21.9%), pregnant females 94 (0.30%) and unknown gender 87 (0.28%). Age distribution by group was: 10–12 years 2245, 13–15 years 1364, 16–17 years 9170, and 18–19 years 6114. The most frequently reported clinical effects were tachycardia (6192), vomiting (5258), nausea (4282), minor central nervous system (CNS) depression (3157), and drowsiness (2520). From the US PC, adolescent suspected suicides increased by 47% from 2016 (3349) to 2021 (4915) but decreased by 8.5% from 2021 to 2022 to 4499 exposures, whereas cases from the Italian PC increased by 26.2% from 2020 (638) to 2021 (865) and by 38.8% to 2022 (1043). Total exposures from the Italian PC were 5628 suspected suicides. Of them, 4579 were female, 1021 were male and 28 were unknown. The age distribution was as follows: 10–12 years 194 cases, 13–15 years 1829, 16–17 years 1925, and 18–19 years 1680. The most frequently reported clinical effects were in order of highest frequency: minor CNS depression (680), vomiting (709), drowsiness (348), heartburn (297), nausea (179), tachycardia (137), abdominal pain (132) and agitation (104). Table 1 shows the most common substances involved in suspected suicide exposures by age group.

Table 1 Common substances in suicide exposures in adolescents comparing data from a US poison center (Rocky Mountain Poison and Drug Center) and an Italian poison center (Milan).

All ages (10–19 years)		Age 10–12 years		Age 13–15 years		Age 16–17 years		Age 18–19 years
RMPC	MILAN PC	RMPC	MILAN PC	RMPC	MILAN PC	RMPC	MILAN PC	RMPC	MILAN PC
Analgesics (12015, 0.4%)	Analgesics (1488, 34.9%)	Analgesics (865, 40.5%)	Analgesics (42, 39.6%)	Analgesics (5494, 42.7%)	Analgesics (591, 47.9%)	Analgesics (3482, 39.4%)	Analgesics (521, 35.7%)	Analgesics (2174, 6.9%)	Antidepressants (952, 65%)
Antidepressants (7085, 3.8%)	Antidepressant (2362, 52.8%)	Antidepressants (401, 18.8%)	Antidepressant (52, 45.6%)	Antidepressants (2939, 22.9%)	Antidepressants (551, 42.%)	Antidepressants (2238, 25.3%)	Antidepressants (807, 52.3%)	Antidepressants (1507, 25.5%)	Analgesics (334, 22.9%)
Antihistamines (3959, 3.3%)	Sedative/Hypnotics/Antipsychotics (412, 9.14%)	Antihistamines (275, 12.9%)	Sedative/Hypnotics/Antipsychotics (12, 10.5%)	Antihistamines (1707, 13.3%)	Sedative/Hypnotics/Antipsychotics (91, 7%)	Antihistamines (1174, 13.3%)	Sedative/Hypnotics/Antipsychotics (133, 8.6%)	Sedative/Hypnotics/ Antipsychotics (872, 4.8%)	Sedative/Hypnotics/ Antipsychotics (176, 11.2%)
Sedative/ Hypnotics/ Antipsychotics (3161, 10.6%)	Others (248, 8%)	Cardiovascular agents (150, 7%)	Others (8, 7%)	Sedative/Hypnotics/ Antipsychotics (1140, 8.9%)	Other (75, 5.7%)	Sedative/Hypnotics/ Antipsychotics (1011, 11.4%)	Others (82, 5.3%)	Antihistamines (803, 3.6%)	Anticonvulsants (112, 7%)

Conclusion: Adolescent suspected intentional suicide cases showed marked similarities. Females predominated 4:1 in both centers. Our findings indicate more suicide education and prevention efforts are necessary.

267. Alpha-chloralose intoxication in cats and dogs

Abstract

Objective

Alpha-chloralose is a very effective rodenticide. It has stimulating and depressive effects on the central nervous system, which can lead to an inability to maintain homeostasis. Free-ranging pets and wild animals are at risk of poisoning from alpha-chloralose baits.

Methods

Cases of alpha-chloralose intoxication in cats and dogs were evaluated from the Austrian Poisons Information Centre (PIC) database from 2018 to 2022.

Results

The PIC documented 82 cases (69 dogs, 13 cats) of oral intake of alpha-chloralose. At the time of PIC consultation two cats were asymptomatic, two had mild symptoms (Poison Severity Score PSS1: drowsiness, muscle fasciculations), five had moderate symptoms (PSS2: ataxia, hypothermia, unconsciousness, convulsions), three had severe symptoms (PSS3: deep coma, convulsions, tremor) and one cat died (PSS4). Overall 42 dogs were asymptomatic, 14 dogs had mild symptoms (PSS1: ataxia, drowsiness, somnolence, hypersalivation, muscle fasciculations, tremor, agitation) and 12 dogs had moderate symptoms (PSS2: convulsions, hypothermia, sinus tachycardia). We describe a severe intoxication (PSS3) of a dog. A 2-year-old female Australian Shepard dog (17 kg) was taken to the vet with hypersalivation, miosis and facial muscle fasciculation spreading to the body and resulting in tonic-clonic convulsions. Temperature was 41.2 °C. The dog was treated with diazepam, glucocorticoids and maropitant (antiemetic). The dog received phenobarbital due to ongoing convulsions. She was fully conscious and was additionally treated with ketamine, medetomidine (sedative), and butorphanol (analgesic). Since the effect was very short, phenobarbital was given several times, and the patient was cooled to 40.8 °C with ice packs. Despite sedation, severe body spasms occurred in response to physical handling and even minor sensory stimuli. After 4.5 hours of treatment, the dog developed respiratory depression with mydriasis and nystagmus. Temperature dropped to 36 °C and the dog had to be warmed with heating pads. Phenobarbital was reduced. After 17 hours of treatment, the pet showed only mild twitching but was unable to stand or walk and exhibited a head tilt with an improvement in nystagmus. Five hours later she vomited the swallowed bait and improved shortly thereafter. After 25 hours of treatment, she was able to stand and the body temperature remained at 38.5 °C. The dog was able to walk and was discharged in a stable condition after 48 hours.

Conclusion

Alpha-chloralose intoxication is a serious situation that requires immediate and intensive veterinary treatment due to the pronounced and persistent symptoms. Treatment can be very cost-intensive.

268. Revenge of a Gila monster: first reported case to the Austrian Poisons Information Centre

Abstract

Objective

The Gila monster (Heloderma suspectum) is a desert dweller, who lives in arid regions of southwestern North America. Some people keep this reptile in private collections, so that bites by these lizards may increase. A firm bite and chewing movements can lead to envenomation. The symptoms are local pain, inflammation, muscle relaxation, hypotension, and metabolic disorders. We describe the first case of a Gila monster bite reported to the Austrian Poisons Information Centre.

Case report

At a zoo a 54-year-old man was bitten on his hand by a Heloderma suspectum for a duration of 20 s. He was an animal breeder, who held the animal for the zoo veterinarian, so he could determine the gender of the animal by ultrasound examination. The patient was taken to the hospital because he was tachypnoeic, tachycardic (130/min), and suffered from nausea and vomiting (4 times). The bite mark was clearly visible. Erythema and swelling covered the arm and movement was painful. He rapidly developed respiratory insufficiency with relatively high oxygen demand (8 L/min) with a pO₂ of 63–58 mmHg without X-ray correlation or other respiratory symptoms. Laboratory tests showed initial leucocytosis (12.7 × 10ⁱ/L) and an increased creatine kinase (CK 255 U/L) activity. The C-reactive protein concentration increased after 8 hours (7.4 mg/L) and on the next day to 27.4 mg/L. The patient developed fever (38.5 °C). He received intravenous fluids, antiemetics and antibiotics. The wound was cleaned, and he received cooling local therapy. In the following hours, the high oxygen demand decreased, and oxygen administration could be stopped after about 28 hours. The patient was discharged to outpatient care on day two, and after one week the swelling had resolved.

Conclusion

Although no metabolic disorder such as hypoglycaemia occurred, the poisoning was severe, with respiratory insufficiency for a duration of 28 hours. Since there is no antidote, this patient was treated symptomatically. Like other animal toxins, Heloderma venom consists of enzymes (hyaluronidase, phospholipase A2), various hormones and bioactive peptides, the most interesting is the exendin-4 peptide, with hypoglycaemic effect. Exenatide as an injectable suspension, is a synthetic analogue of this peptide and is used in the therapy of Type 2 diabetes.

EAPCCT abstracts author index 2024, by abstract number

A

Abouchedid, Rachelle 27, 107

Abraham, Siju V 232

Abston, Stephanie 60, 209

Accogli, Agnese 167

Aegerter, Jasmine M 196

Agajany, Netanel 37

Agami, Ahmed 32

Agosti, Antonio 25

Agoston, Viktor A 88

Aguilar-Salmerón, Raquel 200, 260

Alboni, Andrea 53

Aldy, Kim 60, 209

Allen, Monica T 160

Aloumi, Abdullatif 99

Alsakha, Ahmed 133

Álvarez, Miguel 242

Amaducci, Alexandra 60, 209

Anniballi, Fabrizio 224

Antonova-Šiaudvytė, Viktorija 67, 162

Antony, Tina 58

Antrobus, Jonathan D 86

Anvarov, Khikmat 217

Archer, John RH 110, 172, 252

Ardenghi, Nicola 53

Arena, Giovanna 25

Arif, Tara 129, 130, 174, 267, 268

Arillotta, Davide 187

Arnold, Justin K 20, 180

Arvidsson, Jenny 258

Arvidsson, Stefan 258

Auer, Reto 198

Avendaño-Solá, Cristina 35

B

Babulovska, Aleksandra 46

Bacchion, Matilde 87, 127, 152, 164

Bacis, Giuseppe 21, 47, 220

Badaras, Robertas 67, 162, 163

Bakken, Gry V 160

Bakos, Ágnes 70

Balachandran, Amith 73

Banerji, Shireen 266

Bång Arhammar, Jenny 44, 93

Banholzer, Sarah 196

Barlow, Nicola L 212, 213

Basanets, Anzhela 28

Bates, Nicola 229, 230

Battagliola, Mario 25

Bátyi, Anna 88

Baumann, Fabienne N 132, 140

Baumgartner, Christine 196

Bautista Albiter, Mayré I 119, 199, 233

Begemann, Kathrin 208, 256

Behr, Jürgen 31, 32

Bekka, Elias 186

Belli, Gilda 71

Benturquia, Nadia 63, 118

Benussi, Cristina C 11, 41, 75, 154, 167

Bercow, Asher 22

Berkowicz, Katarzyna 5

Bernasconi, Lucia 11, 53, 155, 193

Bernstorff, Dania F 119

Bettini, Marli 249, 250

Biary, Rana 1, 13, 22, 125, 142

Bissoli, Maurizio 148

Blomgren, Andreas 56, 101

Bloom, Joshua 142, 190, 205, 246

Blumberg, Stephen 22

Bøgevig, Søren 131, 141, 146, 147, 251

Bojikova, Ralitza A 201

Bonney, Caitlin 76

Bonzano, Marco 149

Boragno, Paola 155

Borobia, Alberto 177, 242

Bottari, Gabriella 98

Bradberry, Sally M 16, 38, 85, 105, 113, 114, 183, 211, 212, 213, 214, 237, 240

Brekke, Mette 33, 34

Brent, Jeffrey 60, 209

Brett, Jonathan 94

Brolli, Benedetta 8, 11, 41, 75, 122, 155, 167, 188, 193, 227

Brønden, Andreas 147

Bronstein, Alvin 266

Brookes, Rachael C 185, 213

Browning, Faith 252

Brownlow, Matthew 69

Brvar, Miran 103, 178

Buchanan, Jennie 60, 209

Buckley, Nicholas A 121, 197

Burbiene, Egle 265

Burgstaller, Gerald 32

Burke, Devin 133

Burmeister, Undine 259

Buscaglia, Eleonora 8, 54, 149, 193

Butera, Raffaella 21, 47

C

Caballero-Bermejo, Antonio F 35, 66, 157, 177, 234, 257

Cagáňová, Blažena 203, 204, 236

Cairns, Rose 121, 197

Calello, Diane 60

Callebert, Jacques 48, 49

Callelo, Diane 209

Calleo, Vincent J 13

Calpe-Delgado, Philippe 35, 66, 157, 234

Campleman, Sharan 60, 209

Canavese, Ambra 228

Capilla-Pueyo, Rosa 66, 157, 234

Capita, Claude-Alice 116

Caprioli, Daniele 83

Carcas, Antonio 242

Carnovale, Monica 11, 41, 053

Carosio, Valentina 75

Carpenter, Joseph 60, 209

Carter, Gill 194

Casey, Patricia 222

Cassidy, Nicola 222

Cecchetti, Corrado 74

Čečrle, Michal 36

Celentano, Anna 148, 266, 266

Cha, Kyungman 176

Chakraborty, Ashesh 31

Chamoun, Karam 48, 49

Chan, Aaron 205

Chan, Betty SH 94, 104, 121, 182, 197

Chan, Chun Man Jones 195

Chanchal AB, Vijay 232

Charlton, Nathan P 115

Cheah, Li Wei 166

Chen, Chun-Hung 72, 77

Chen, Guan-Yuan 61

Chen, Hsiang-Ling 138, 244

Chen, Ju-Yu 61

Chen, Nai-Yu 79, 138, 239, 241, 244

Cheng, Kai-Wen 144

Cheung, Ted 207

Chevillard, Lucie 48, 49, 63, 118

Chiew, Angela L 94, 218

Chiu, Yiting 62

Chiusolo, Fabrizio 153

Cho, Hyung-Gyo 189

Christen, Samuel E 198

Christensen, Mikkel B 146, 251

Christie, Rachel 5

Chu, Weilan 62

Cirronis, Marco 21, 47, 220

Clark, Clair LT 86

Climent, Benjamín 177

Cohen, Emily T 1

Coman, Irina 192

Conforti, Andrea 123

Contessa, Maria Gioia 21, 47, 220

Conti, Tommaso 148

Córdoba, Francisca 177

Costantini, Ilaria 87, 127, 152, 164

Coulson, James M 16, 85, 113, 237

Coutiño Fitzner, Ingrid 226

Crema, Francesca 8, 149, 227

Cremaschi, Carlotta 228

Crevani, Marta 122, 148

Cristaldi, Sebastian 123

Culbreth, Rachel E 60, 209

D

Dalhoff, Kim P 131, 141

Daneshmend, Adam 172

Dankel II, Douglas D 65

Dargan, Paul I 2, 92, 96, 108, 110, 172

Das, Bornnali 207

Dawson, Andrew H 104

De Angelis, Paola 98, 123

De Baerdemaker, Klara 92

de Lange, Dylan W 9, 18, 84, 91, 109, 159

de Morais, Joanna 5

De Paepe, Peter 96

De Sadeleer, Laurens 32

de Vries, Luc MA 89

Degrandi, Colette 124, 132

Del Angel González, Natanael 119, 181

Del Giudice, Luigi 153

Delgado, Emilio 150

Della Bella, Lorenzo 150

Della Grotta, Giada 83

Demirel, Petrus 56

Descatha, Alexis 12

Deters, Michael 235

Di Meglio, Lavinia 98

Di Nardo, Matteo 98

Díaz, Lucía 242

Dick, Elisabeth 31

Dietz, Jason 22

Dijkman, Marieke A 17, 18, 84

Dilger, Karin 151

Dimasi, Valeria 148

Dines, Alison M 92, 96

Djerada, Zoubir 168

Djordjevic, Dragana 145

Dobaja Borak, Mojca 103

Dobravc Verbic, Matej 103, 178

Dommasch, Michael 57

Dorner-Schulmeister, Susanna 130, 174, 267

Doyle, Sinead 222

Dragomirescu, Ana 39

Dufayet, Laurene 63, 118

Duggan, Edel 206, 222, 257

E

Eagling, Victoria A 240

Eddleston, Michael 7, 95, 108

Edel, Andreas 217

Edwards, Ella P 85, 86

Edwards, Nick 230

El Hadi, Hussein 106

Elamin, Muhammad EMO 179, 207

Eleftheriou, Georgios 21, 47, 220

Elek, István 70, 88, 100, 215

Eriyawa, Asanka 3

Eronen, Anna-Kaisa 223

EU4MD/IPA7 Research Group 92

Eugelio, Fabiola 83

Evans-Brown, Michael 5

Eyer, Florian 57, 96

F

Faber, Katrin 132, 261, 262

Falkowitz, Daria 102

Fang, Cheng-Chung 61

Fanti, Federico 83

Farah, Rita 115, 243, 247, 248

Faraoni, Lorella 21, 47, 220

Federici, Tatiana 123

Feistkorn, Esther 208, 256

Feliu, Catherine 168

Felix Bernstorff, Dania M 181, 199, 233

Fentalog Study Group 60, 209

Fernández, Camila 249, 250

Fernández De Gamarra-Martínez, Edurne 200, 260

Fernandez Ovalle, Antonia 189

Ferner, Robin E 114, 117

Ferrer Dufol, Ana 80, 238

Ferruzzi, Marcello 148

Fiabane, Elena M 155

Filip, Ari B 120

Flores, Elena 40

Fonio, Silvia 149

Foster, Howell R 120

Founaud Placer, Belen 238

Franceschini, Paola 153

Francis, Arie 190

Francis, Rajeevan 3

Fransen, Eric JF 91

Fraser, Clare 254

Freiberg, Cynthia 37

Frigerio, Tommaso 41

Frohwirth, Lori 205

Frosio, Laura 21

G

Gabanelli, Paola 155

Galardo, Gioacchino 83

Galicia, Miguel 177

Gallegos, Ana 5

Gallo, Mariapina 21, 47, 220

Gambassi, Francesco 187

García-Hernández, Raquel 35, 66, 157, 234

García-Peláez, Milagros 200, 260

Garland, Jack 42

Genser, Dieter 129

Genuini, Leonardo 74

George, Krupa 73

Gerckens, Michael 32

Gervilla, Elena 40

Ghannoum, Marc 17, 18, 84

Giampreti, Andrea 21, 47, 220

Giarda, Paola 154

Giardina, Daniella 133

Giardini, Ilaria 54, 75

Gigliotti, Cinthia 150

Gilberts, Maarten 18, 84

Gillich, Cedric 186

Giossi, Riccardo 148

Giraudon, Isabelle 92, 96

Gispert-Ametller, Maria Angels 177, 200, 260

Glaser, Nina 208, 256

Glatstein, Miguel 14

Gnirke, Marlis 102, 189, 190

Goffredo, Bianca Maria 98, 153

Goldwasser, Bernard 22

Gölitz, Fee MV 4

Gollmann, Mandy 231

Gomez, Astrid 143

Gote-Schniering, Janine 32

Gould, Allon 2, 172

Grabnar, Iztok 178

Grama, Andreea 39

Graudins, Andis 69, 137

Gray, Laurence A 16, 38, 85, 105, 113, 114, 117, 179, 207, 211, 212, 213, 237, 240

Grazioli, Cristina 11, 155, 188, 227

Greb, Ingo 217

Greene, Shaun 27, 107, 184

Greenwood, Matthew 24

Grenet, Guillaume 12

Gresnigt, Femke MJ 91

Grigoryan, Marine 43, 169

Grossenbacher, Francis 168

Gudermann, Thomas 29

Gutauskaite, Daiva 265

H

Hach, Jan 253

Hajj, Aline 48, 49

Halász, Judit 70

Hammann, Felix 196, 198

Hammer, Paula EC 161

Hampf, Dirk 217

Hampton, Sarah 184

Han, Diane 76

Handford, Jasmine 252

Hannoush, Rawan 99

Hansen, Johanne M 141

Harmouche, Elie 142

Harris, Keith 42

Haschke, Manuel 186, 196

Hatten, Benjamin 76

Hauck, Stefanie M 31

Hayman, Chelsea V 1

Henke, Des 207

Hennen, Elisabeth 31

Herbert, John X 206, 257

Hermanns-Clausen, Maren 226, 259, 261, 262

Heumos, Lukas 32

Heyerdahl, Fridtjof 96

Hilgendorff, Anne 31

Hill, Simon L 6, 7, 10, 95, 108

Ho, Yang 144

Hodgson, Sarah 27, 107, 184

Hoffman, Robert J 99

Hoffman, Robert S 1, 13, 22, 125

Høgberg, Lotte CG 15, 146, 147

Holmes, Peter 185, 194

Holstege, Christopher P 243, 247, 248

Holzer, Angelika 268

Hondebrink, Laura 9, 194, 261, 262

Horn, Gabriele 19

Horwitz, Henrik 131

Horwitz, Yuval 14

Houzé, Pascal 106

Hovda, Knut Erik 96

Howland, Mary Ann 190

Hoyte, Christopher O 216, 266

Hsu, Chung-Wei 241

Hudson, Simon 6, 7, 10, 95, 108, 172

Hughes, Adrienne 60

Hughes, Bethan W 237

Hunault, Claudine C 91

Hung, Dong-Zong 72, 77, 81, 97

Huusom, Anja J 15, 90

I

Ieri, Alessandra 71, 187

Ilenic, Petra 103

Ionita, Ioana-Catalina 23

Isbister, Geoffrey K 218

Isoardi, Katherine Z 42, 182

J

Jagarlamudi, Bash 94, 254

Jagpal, Pardeep S 114, 117, 179, 185, 194, 211, 212, 213

Jambugulam, Mohan 73

James, Anoop 232

Jayamanne, Shaluka 3

Jayawardane, Pradeepa 3

Jenkins, Shane 218

Jeong, Julia H 197, 121

Jeridi, Aicha 31

Jetter, Alexander 132, 140, 171, 173

Jimenez Solem, Espen 147

Johansson, Karl Sebastian 251

John, Harald 26

Jordan, Michael 229

Jorge, Rita 5

Jovic Stosic, Jasmina 30, 145

Judge, Bryan 60, 209

Junier, Lenneke AT 89

Jutley, Gurpreet S 114, 183, 211

K

Kägi, Seraina 132, 171

Kälble, Florian 151

Kallenberger, Stefan 151

Kant, Abhay 45

Kastanje, Ruth 52, 64

Kennedy, Cormack 177

Kerester, Samantha 246

Kerns, Abigail F 115, 247, 248

Kessler, Asa 14

Kettelz, Nicola N 90

Kettenring, Franca 57

Keymer, Nathaniel I 105

Khachikyan, Ruzanna 43

Khan, Aleha 212, 213, 214

Kibuka Musoke, Paula 205

Kim, Dahae 176

Klein, Samantha S 22, 125

Kneidinger, Nikolaus 32

Kotikova, Katerina 191

Kotoula, Christina 196

Koutsogiannis, Zeff 107

Kozer, Eran 37

Kristl, Anja 103

Krogh, Anita Von 160

Kronenfeld, Nirit 37

Krotulski, Alex 60, 209

Krueger, Birgit 173

Krzanowski, Jacob 110, 252

Kulczycki, Alessandro 11

Kurnik, Daniel 14

L

Labat, Laurence 106

Lach, Karel 253

Lampe, Elisabeth O 82

Lang, Niklas 32

Lanzi, Cecilia 71

Laporte, Geoffrey 255

Larréché, Sébastien 12

Laubner-Sakalauskienė, Gabija 67, 162, 163

Lavon, Ophir 55, 135

Le Roux, Gael 12, 255

Lee, Berlin 158

Lee, Hong-Wei 61

Lee, Jiwon 175

Lee, Kaiju 62

Lee, Wei Feng 158

Legeay, Marion 12, 255

Leggiero, Eleonora 193

Legittimo, Carlo M 11

Leguizamo, Federico 40

Lerta, Margherita 224

Lescaie, Andreea 23

Levine, Michael 60, 209

Li, Shao 60, 209

Liakoni, Evangelia 186, 196, 198

Liechti, Matthias E 96

Lilius, Tuomas O 156, 219

Lim, Steven HC 45

Lin, Chia-Ho 138

Lin, Jing-Hua 72, 97

Lin, Nung-Sheng 79

Lindeman, Erik 56, 101, 258

Lintula, Miika 223

Litmanen, Sanne K 156

Lobo-Antuña, Victoria 177

Locatelli, Carlo A 8, 11, 41, 53, 54, 75, 122, 149, 154, 155, 167, 188, 193, 224, 227, 228

Logan, Barry 60, 209

Lokunarangoda, Niroshan 3

Lonati, Davide 8, 11, 53, 54, 149, 154, 193, 224, 228

Looms, Jonathan 179

Losso, Lorenzo 87, 127, 152, 164

Lucaci, Cristian 39

Ludot, Berenger 168

Lukic, Vladan 145

Luongo, Dahlia 205

Lurie, Yael 14

Lyphout, Cathelijne 96

M

Madhavan, Indira 58

Maggi, Matteo 148

Magócs, Dávid 100

Mahonski, Sarah G 13, 133

Maida, Francesca 122, 148

Mancera Castillo, Lorena 119, 199, 233

Manini, Alex F 60, 209

Mannaioni, Guido 71, 187

Mantelli, Giovanni 87, 127, 152, 164

Marano, Marco 74, 98, 123, 153

Marcu, Maria A. 192

Mariani, Francesco 25

Marinelli, Cristiano 83

Markovits, Noa 14

Marozzi, Roberto 21

Martin, Helena M 183

Martín, Susana 242

Martinelli, Diego 153

Martínez-Sánchez, Lidia 40, 200, 260

Martiñón Ríos, Rocio 199

Mason, George 24

Mastalerz, Michal 31

Mattiuzzo, Elena 75, 154, 188, 228

Mayr, Chistoph H 31

Maystrova, Olha 11, 188

Mayur, Jayenth 142, 205

McDonald, Conner T 248

Medel-Jara, Patricio 249, 250

Mégarbane, Bruno 48, 49, 63, 96, 106, 116, 118, 143, 150

Menses, Rikkert S 194

Mercurio-Zappala, Maria 205, 246

Merl-Pham, Juliane 31

Meyer-Massetti, Carla 198

Meyhoff, Christian Sylvest 170

Miguel-Águila, Macarena L 177

Mihalcea, Ana-Maria 192

Milanesi, Giovanni 148

Milella, Michele S 83

Miró, Òscar 96

Miškinytė, Sigutė 163

Missanelli, Andrea 71

Moens, Jonas 139, 263

Møller, Linda S 90

Monica, Carnovale 227

Moranchel García, Leslie 233

Morando, Elia 87, 127, 152, 164

Morin, Emilie 12

Moro, Paola 148

Moyns, Emma 211, 212

Mu, Han-Wei 72, 81, 166

Mulder-Spijkerboer, Henneke N 17, 18, 084

Muldoon, Laura I 137

Mullins, Michael E 120

Murray, Austin C 243

Muselli, Federico 11

Musolino, Anna M 123

Musolino, Antonio 123

N

Natale, Luca 25

Neafu, Thomas 92

Negoita, Adriana 23

Negrini, Valentina 149, 154, 167, 228

Nersesjan, Mariam 131

Nic Ionmhain, Una 104

Nilsson, Ulrika 136

Nitescu, Viorela 23, 39, 192

Nixon, Emma 69

Nogué-Xarau, Santiago 200, 260

Nordmark Grass, Johanna 56, 93, 101, 111, 136

Nugteren-van Lonkhuyzen, Annette JJ 109

Nugteren-van Lonkhuyzen, Johanna J 9

Nunziata, Joseph 74

Nuutila, Noora 223

O

ÓLaoi, Ruadhan 177

Occupati, Brunella 71

Oder, Mare 52, 64, 225

Officer, Jane 7, 10, 108

Oliva, Eleonora 83

Ong, Sook Har 104, 182

Oteo, Alberto 6, 7, 10, 108

Otrubová, Ol’ga 203, 204, 236

P

Pahud De Mortanges, Aurélie 196

Pallás-Villaronga, Oriol 177

Palmqvist, Dorte Fris 165

Pan, Chi-Syuan 72

Pap, Csaba 88

Papa, Pietro 54

Pardo, Ramón 242

Pattupara, Archana 190

PCC-Taiwan Study Group 144

Pelclová, Daniela 36, 253

Perdichizzi, Salvatore 153

Pereska, Zanina 46

Pérez Hernández, Juan C 181

Pérez Tuñón, Jorge G 119, 181, 199, 233

Perkovic Vukcevic, Natasa 30, 145

Perlini, Stefano 41, 149, 228

Perminas, Marius 265

Petersen, Tonny S 131, 141, 146, 147, 165

Petkovski, Dushan 46

Petrolini, Valeria M 155, 167, 193, 224, 227

Phan, Hilda 136

Pignatiello, Francesca 21

Pineda-Torcuato, Álvaro 35, 66, 157, 177, 234, 257

Pires, Kyle D 1

Pi-Sala, Nuria 200, 260

Pisani, Mara 74, 98, 123, 153

Pistelli, Alessandra 71

Pitterling, Ulla 231

Plačková, Silvia 203, 204, 236

Planchuelo, Gregorio 5

Plenier, Yannick 168

Pohjanoksa-Mäntylä, Marika 223

Ponampalam, R 45

Ponce De Leon, Arturo G 119, 199, 233

Popazu, Andreea 192

Porkka, Päivi 219

Porras-Gonzalez, Diana 32

Potrebic, Olivera 30, 145

Prakki, Sai Rama Sridatta 32

Prasa, Dagmar 235

Priestman, Carly 229

Prodanchuk, Mykola 28

Pucci, Mark 211

Puchoň, Erik 203, 204, 236

Pugliese, Francesco 83

Puiguriguer-Ferrando, Jordi 177

Pujol, Elia 23

Puma, Alessia 154

Q

Quashie, Shantelle 110

Quelch, Darren 214

Quezada Miriel, Sofia L 181

R

Radenkova-Saeva, Julia V 201, 202

Ralph, Ravikar 73

Ramió, Cristina 177

Rashidov, Davlat 217

Razafimpanana, Nirinalisera 83

Re, Azzurra 154

Reichert, Cornelia 124, 132, 171

Reiter, Nanna 165, 170

Reiter, Nanna Roed 170

Renymol, B 58

Resenberger, Stefanie 29

Reuser, Michael 208, 256

Ricci, Giorgio 87, 127, 152, 164

Riezebos, Robert K 91

Riis, Troels 146

Rijal, Shikha 189

Ríos, Juan Carlos 249, 250

Rizvi, Khizer 142

Robben, Joris H 18, 84

Roberts, Darren M 182

Roberts, Suzanne 22

Roda, Elisa 8, 167

Rodríguez, Neus 177

Rodríguez-Miranda, Belén 35, 66, 157, 177, 234, 257

Rogozina, Olga 242

Romano, Alessia 227

Ronchi, Anna 193

Ronda-Roca, Gerard 157, 234

Rothenberg, Roger 13

Ruiz Ruiz, Francisco 80, 238

Ruiz-Antorán, Belén 35, 66, 157, 177, 234, 257

S

Sacco, Irene 71

Sætre, Ingrid 34

Šalabajeva, Anastassija 52

Salgado-Garcia, Emilio 200, 260

Salimova, Maya 122, 148

Salter, Mark D 24, 254

Sancho-López, Aránzazu 35, 234, 257

Sandakumari, Nilangika 3

Sandilands, Euan A 16, 38, 85, 86, 105, 113, 114, 117, 179, 185, 207, 211, 212, 213, 237, 240

Sarc, Lucija 103

Sargsyan, Manya 43, 169

Scaglione, Francesco 122, 148, 266

Scalfaro, Concetta 224

Scanniello, Elisabetta 198

Scaravaggi, Giulia 53, 193, 227, 228

Schaffer, David H 243

Scharffenberg, Tora AZ 126

Schauben, Jay L 65

Schenardi, Paolo 148

Schicchi, Azzurra 54, 74, 75, 193, 224, 228

Schiel, Helmut 130

Schievenin, Maria Grazia 122

Schillaci, Serena 123

Schiller, Herbert B 31, 32

Schipper, Joel D 65

Schmalzried, Scott G 247

Schmid, Otmar 31

Schmitt, Corinne 12

Schumann, Jennifer 107

Schwartz, Lauren 205, 246

Schwarz, Evan 60, 209

Secil, Zuhal 129

Sedefov, Roumen 5

Sergi, Manuel 83

Serrano Ferrer, Ana 80

Serrano Ferrer, Clara 238

Sesana, Fabrizio 148, 266

Setsaas, Erle JB 33

Sharma, Aniket 190

Shulman, Joshua 60, 209

Sieber, Helena P 26

Silva, Lorena 249, 250

Silverberg, Joshua Z 13

Simeon, Enrico 11

Simeoni, Elisabetta 8, 54

Simon, Lukas M 31

Simonovska, Natasha 46

Šipylaitė, Jūratė 163

Sisson, Charles 229

Skarupova, Katerina 92

Skjerdal, Jartrud W 126

Slincu, Laura 39

Smith, Jennifer 107

So, Byung Hak 175, 176

Solari, Sandra 249, 250

Son, Suro Stella 69

Sørensen, Anne Mette Skov 147

Souihi, Sofia 150

Spillum, Barbro J 126

Sriapha, Charuwan 245

St Francis, Hannah 13

Staab-Weijnitz, Claudia A 29, 31

Stanczyk-Feldges, Joanna 171

Stedtler, Uwe 226, 259

Steinberg, Marianne 126

Steindl, David 217

Steinecke, Karin 217

Steinritz, Dirk 26, 29

Stella, Francesco 148

Stoleriu, Mircea-Gabriel 32

Stoppa, Francesca 74

Stratula, Andreea 23

Stražnickaitė, Indrė 163

STSS Group of Collaborators 80

Stuerzebecher, Anne 231

Sturkenboom, Marieke GG 89

Su, Mark K 1, 102, 189, 190, 205, 246

Sumpa, Dani 58

Sun, Wei-Chen 239

Supervia-Caparrós, Augusto 177

Syrjanen, Rebekka 107

T

Tabasso, Giorgio 187

Taglieri, Silvia 224

Tan, Elizabeth MJ 45

Tang, Jonathan 27, 184

Tansuwannarat, Phantakan 245

Tay, Ying Pei 81

Taylor, Capwell E 13

Thanacoody, Ruben HK 16, 38, 85, 105, 113, 114, 117, 179, 207, 211, 212, 213, 237, 240

Thanki, Danica 203

Theis, Fabian 32

Thomas, Alison 185

Thomas, Eleri 38, 113, 194

Thomas, Simon HL 6, 7, 10, 95, 108

Timofticiuc, Diana 192

Tongpoo, Achara 245

Torroni, Filippo 98

Trakulsrichai, Satariya 245

Tran, Linda H 82

Turcu, Teodora 39, 192

Turner, Nicholas 110

U

Ularu, Ioana 23

Ulmeanu, Coriolan 23, 39, 192

Urbán, Ildikó 215

Urroz, Mikel 177, 242

Uten, Andreas 18

V

Vaid, Raizada A 13

Vallersnes, Odd Martin 33, 34, 96

Valli, Antonella 8, 53

Van Baelen, Jonas 139, 263

van den Hengel-Koot, Irma S 9

van der Sanden, Wouter MH 109

van Essen, Jelle JW 91

van Riel, Antoinette JHP 9, 109, 159

van Riemsdijk, Tessa E 194

van Velzen, Agnes G 159

Venkova, Alexandra I 202

Vidler, Dan 7, 10, 108

Vignola, Alessandro 164

Villani, Alberto 123

Visser, Corine C 9

Vivino, Gabriella 83

Vodovar, Dominique 63, 118, 261, 262

Vroon, Natalie 247

Vucinic, Slavica 30, 145

Vukovic Ercegovic, Gordana 30, 145

W

Wamberg, Christian Aage 165, 170

Wananukul, Winai 245

Warsi, Aamna 214

Watt, Annie 194

Wax, Paul 60, 209

Weber, Courtney 107

Wegscheider, Felix 57

Weiler, Stefan 186, 198

Weiss, Björn 217

Welfoot, Callum W 16

Weng, Te-I 61

Wessling, Jennifer 235

Westerbergh, Jenny 44, 93

Westergerling, Parisa 151

Wiener, Sage W 142

Wille, Timo 4

Williams, David 257

Williams, Grace 214

Williams, Hayley A 114, 117

Wood, David M 2, 7, 92, 96, 110, 172

Worek, Franz 4, 19, 26

Y

Yang, Chen-Chang 62, 79, 138, 239, 241, 244

Yang, Kai-Wei 72

Yang, Lin 32

Yates, Christopher 96

Yildrim, Ali Ö 31

Yu, Jiun-Hao 72

Z

Zaffino, Francesca 224

Zammit, Mark L 261, 262

Zampini, Giorgio 74

Zellner, Tobias 57

Zöller, Marie 31

Zoppellari, Roberto 25

Zuccaro, Francesco 122

EAPCCT keyword index 2024, by abstract number

3-CMC (3-chloromethcathinone) 5

3Rs 4

A

Abamectin 81

Acetaminophen 113, 119, 120, 176, 183, 196, 218

Acetylcysteine 35, 46, 119, 176, 214, 218

Acid 123, 124

Activated charcoal 99, 157

ADHD drugs 132

Adherence to guidelines 177

Adolescents 40, 74, 85, 113, 147, 180, 192, 201, 202, 223, 261, 266

Adverse drug reaction 133, 152, 153, 154, 155, 165, 167, 168, 227

Agitation 168

Alcohol intoxication 40, 202

Alcohol withdrawal symptoms 165

Alcoholic ketoacidosis 1

Alien species 228

Alkyl nitrites 246

Alpha-2 agonists 76

Alpha-chloralose 267

Alpha-cypermethrin 82

Alpha-PHIP 56

Amanita pantherina 17, 47

Amanita phalloides 46, 229

Amanita proxima 14

Amatoxins 15, 18, 84, 229

Amiodarone 188

Amlodipine 182

Ammonia 144, 160

Amygdalin 44

Analgesics 196

Analytical toxicology 62, 212, 213

Animal bites and stings 122, 235, 255, 268

Antiarrhythmic drug 188

Antibiotic 103

Anticholinergic delirium 90

Anticholinergic drugs 227

Anticholinergic poisoning 53, 90, 227, 244

Anticoagulant rodenticides 43

Anticoagulant, oral 145

Anticonvulsant drugs 175, 185

Antidepressant drugs 142, 172

Antidote 15, 33, 35, 46, 75, 86, 120, 121, 146, 149, 176, 183, 189, 193, 197, 200, 218, 121, 240, 244, 260

Antidote supply 121

Antifreeze 161

Antihistamine 102

Antipsychotic drug 116, 131, 143

Antitoxin, botulinum 224

Antitubercular drugs 39

Antivenom 13, 191, 231, 258

Antiviral drug 151

Apricot kernel 44

Arachnologists 11

Arsenic 195, 213

Arterial blood gases 49

Atomoxetine 132

Atracurium 179

Atrioventricular block 3

Attention deficit hyperactivity disorder (ADHD) drugs 132

Avermectin 79

Awareness campaign 222

Ayurvedic medicine 21

B

Battery 125, 129

Benzodiazepine 7, 72, 95, 130, 136, 170

Betaine 105

Biguanide 105

Bioanalytical verification 26

Biotransformation 19

Bite and stings 255

Bite to Door Time 232

Bites and stings 122, 235, 255, 268

Black widow spider 122

Botulism 224

Bradypnoea 107

BRASH syndrome  164

Bronchial epithelium 31

Buprenorphine 34, 252

Bupropion 101

Button battery 125, 129

C

Caffeine 64, 74

Calcium carbonate 37

Call statistics 194

Cannabinoid 36

Carbon monoxide 69, 207, 220

Carboxyhaemoglobin 207

Cardiac arrest 165

Cardiac glycosides 45, 87

Cardiotoxicity 14, 76, 83, 87, 88, 102, 104, 142, 182, 186

Carfentanil 49

Cascabela thevetia (previously Thevetia peruviana) 3, 83

Case registry 234, 238

Cats 230, 267

Caustic 123, 126, 162

Cefepime 103

Cenobamate 185

Cerbera odollam 45

Cerebrospinal fluid (CSF) concentration  168

Cerebrovascular accident 137

Chelation 189, 214, 253

Chemical plant 220

Chemical poisoning 80, 242

Child 23, 37, 38, 39, 41, 43, 75, 76, 98, 113, 123, 125, 153, 159, 169, 192, 202, 224, 227

Chloramine 160

Chlordiazepoxide 165, 170

Chlorhexidine 105

Chlorine 30, 124, 159

Chlorine tablets/granules 159

Chronic drug intoxication 226

Chronic obstructive pulmonary disease (COPD) 252

Chronic pain 163

Cigarette smoke 31

Cleaners 30, 124

Closantel 254

Coagulopathy 58, 81

Cobalt 214, 253

Cocaine 91, 238

Cocaine-associated chest pain 91

Code stroke 137

Colour vision changes 166

Coma 47, 106, 116, 143, 150

Comorbidity 110

Computer-assisted patient care 65

Conditioned place preference  118

Constipation 70

Continuous positive airway pressure (CPAP) route of exposure 20

Courgette 89

COVID-19 54, 57, 151, 191

COVID-19 vaccine 155

Criminal poisoning 193

Cucurbitaceae 89

Cucurbitacin 89

Cyamemazine 116

Cyanide 44

Cyanogenic glycoside 44

CYP3A inhibition 151

Cyproheptadine 211

Cytisine 152

D

Data harmonisation 261, 262

Datura stramonium 90

Decision support 65

Deferasirox 153

Deferoxamine 189, 215

Delayed diagnosis 125, 137

Deployment-related lung diseases 28

Depot formulation 167

Dermal exposure  82

Desalkylgidazepam 95

Desferrioxamine 189, 215

Detergent suicide 20

Detoxification 163

Dexmethylphenidate 132

Dextrose 184

Diabetic drug 114, 139, 140, 251

Diagnostic kit 97

Diazepam 136, 190

Differential diagnoses 65

Digitalis species 86

Digoxin 27, 45, 86, 135, 164, 197

Digoxin-Fab 121, 164, 197

Diphenhydramine 102

Disseminated intravascular coagulation (DIC) 81

DMPS (unithiol) 156, 253

Dog 18, 84, 229, 230, 231, 267

Domperidone 171

DPP4-inhibitors 140

Drug-drug interaction 151, 181

Dulaglutide 114

E

E-cigarettes 38, 198

Education 29, 158, 198

Elderly 236, 259

Electronic vaping devices 2

Elimination kinetics 190

Emamectin benzoate 78

Emetic, salt water 230

Encephalopathy 21, 111

Envenomation 11, 13, 27, 97, 122, 239

Epidemiology 7, 10, 80, 92, 108, 205, 238, 240, 249, 250

Essential oils 204

Ethanol 40

Ethanol withdrawal 190

Ethylene glycol  70, 161

Eucalyptus oil 204

Euglycemic ketoacidosis 251

Euro-DEN 96

European viper 12, 231

Exhaust fumes 69, 207

Exotic pets 235

EXTRIP criteria 177

F

Fatal 42, 66, 80, 256

Fentanyl 49

Fentanyl analogues 6

Ferric carboxymaltose 24

Flecainide 104

Floppy baby 224

Flumazenil 35, 190

Fluoroquinolone 168

Fomepizole 75, 120

Food poisoning 89

Food supplement 64

Foxglove 86

Frostbite injury 93

Functional impairment 12

Fungus 14, 15, 17, 18, 46, 47, 84, 85, 229

G

Gaboon viper (Bitis gabonica) 13

Gamma hydroxybutyrate (GHB) 106, 257

Garden 90

Gastrectomy 123

Gastric decontamination 98, 100

Gastric lavage 157, 158

Gastric perforation 123

Gastrointestinal decontamination 99, 101, 157, 158

Gastroparesis 70

Gastroscopy 98, 101

Ghost pills 101

Gidazepam 95

Gila monster 268

Glucagon-like petide-1 (GLP1) agonists 114, 139, 140

Guanfacine 132

Guidelines, treatment 177, 197

Gut decontamination 99, 101, 157, 158

H

Haematemesis 123

Haematotoxicity 175

Haloperidol 169

HEART pathway 91

HEART score 91

Heavy metals 21, 156, 193, 195, 213, 253

Heloderma suspectum 268

HepaRG 19

Hepatic steatosis 184

Hepatotoxicity 15, 119, 184, 196, 218

Herbal 16

Hexahydrocannabinol 36

High-dose insulin 104, 146, 182

High-resolution tandem-mass spectrometry 26

Hip prosthesis 214

Homeless 110

Homocysteine 111

Household product 20, 30, 124, 160

Human precision-cut lung slices (hPCLS) 32

Hydrogen sulphide 20, 73, 256

Hypercalcaemia 37

Hyperkalaemia 164

Hyperthermia 58

Hypochlorite 160

Hypoglycaemia 140

Hypophosphataemia 24

Hypoxaemia 107

I

Identification (plant/fungus) 15

Idiopathic pulmonary fibrosis 31

Immunoassay  27

Incretin drugs 114, 139, 140

Inhalant abuse 94, 246

Inhalation exposure 23, 160, 208, 256

Insecticide 19, 77, 82

Insulin 184

Intensive care 143, 217

Interference in immunoassay 27

Internet 2

Interpretation of toxicological analysis 62

Intestinal failure 186

Intravenous administration, inappropriate 105, 174

Iron 215

Irritants 30

Isoniazid 39

Isotonitazene 6

J

Jatropha curcas 199

Jellyfish 228

K

Ketamine 109

Ketoacidosis 251

Knockdown effect 73

Kratom 245

L

Lactic acidosis 144

Latrodectus mactans 122

Latrodectus tredecimguttatus 122

Lead 21

Leather tannery 73

Lidocaine  102

Liraglutide 114, 139

Lisdexamfetamine 132

Lithium 177, 226

Liver injury  15, 119, 184, 196, 218

Liver spheroids 19

Logistics 258

Long acting injectable antipsychotics 131

Long-term follow up 12

Loperamide 186

Loxosceles venom 233

Lung injury/toxicity 4, 23, 28, 124

M

Macrodosing 71

Major adverse cardiovascular event (MACE) 91

Malignant hyperthermia 169

Marine envenomation 228

Marine stings 238, 239

Mass spectrometry 7, 10, 95, 108

Means restriction 205

Mechanical ventilation 116, 143, 170

Medically assisted withdrawal 110

Medication error 41, 135, 148, 189, 259

Melatonin 241

Mental health facilities 248

Mercaptans 26

Mercury 156, 212

Mercury chloride 156

Metal poisoning 21, 156, 193, 195, 213, 214, 253

Metformin 144

Methadone 22, 34

Methaemoglobinaemia 66, 67, 69, 205

Methamphetamine 203

Methylene blue 66, 67, 69, 182

Methylphenidate  138

Miosis 107

Misuse, drug 237

Mitragyna speciosa 245

Modelling 106, 150

Morphine 118

Morphine tolerance 63

Mortality 80

Multidisciplinary team 88, 100

Multivitamins 206

Muscimol 47

Muscle relaxants 179

Mushroom 14, 15, 17, 18, 46, 47, 84, 85, 229

Myelopathy 111

N

Naloxone 33, 35

National Poison Data System (NPDS) 115, 243, 247, 248

Necrosis, dermal 233

Neonicotinic insecticide 77

Nerium oleander 87

Nerve agent 4

N-Ethylpentedrone 56

Neuroleptic drugs 169, 171

Neuroleptic malignant syndrome (NMS) 133

Neurotoxicity 70, 94, 103, 180

New psychoactive substances (NPS) 5, 7, 8, 9, 10, 36, 54, 56, 60, 72, 95, 108

New synthetic opioids 8, 9

Nicotine 38, 198

Nicotinic acetylcholine receptors (nAChRs) 77

Nirmatrelvir/ritonavir 151

Nitrite 66, 67, 205

Nitrous oxide 55, 93, 94, 111

Nordiazepam 136

N-Pyrrolidino-etonitazene 6

O

Occupational exposure 73, 219, 220, 255, 256

Ocular medication 227

O-Desmethyltramadol (O-DSMT) 9

Oesophago-gastric injury 127

Off label antidote 75

Oleander 3, 83, 87

Ophthalmotoxic 254

Opioid 8, 9, 33, 34, 48, 49, 60, 96, 107, 147, 163, 209

Opioid agonist treatment 34

Opioid use disorder (OUD) 252

Organophosphate insecticide 19, 217

Organophosphorus nerve agents 4

Osmol gap 1

Outdoor activities 191

Outreach 222

Over-exposure 135

Oxides of nitrogen 69

Oxycodone 209

P

Paliperidone 131, 133

Pancuronium 179

Paracetamol 113, 119, 120, 176, 183, 196, 218

Parathion 19

Patient knowledge 196

PDE5 inhibitor 166

Perampanel 180

Peripheral neuropathy 111

Peruvoside 83

Pesticides 19, 43, 77, 79, 82

Pets 18, 84, 229, 230, 231, 247, 267

Pharmacobezoar 100

Pharmacogenetics 154

Pharmacovigilance 148, 149, 167, 226

PhD programme 29

Phenazopyridine 243

Phenytoin 187

Phosphodiesterase type 5 (PDE5) inhibitor  166

Physostigmine 244

Plants 3, 44, 45, 52, 53, 83, 88, 89, 90, 199, 255

Plethysmography 48, 49

Poison centre activity 216, 222, 225, 261

Poison centre data 11, 16, 52, 53, 54, 85, 105, 109, 114, 115, 117, 120, 124, 129, 130, 132, 140, 141, 148, 154, 171, 173, 194, 206, 211, 212, 213, 219, 223, 235, 236, 237, 239, 240, 241, 243, 244, 245, 249, 250, 255, 257, 262, 263, 265, 266

Poison centre utilisation 247, 248

Polyhexanide 105

Poppers 246

Potentially inadequate medications (PIM)  259

POUNCE 22

Povidone-iodine 127

Precision cut lung slices (PCLS) 4, 32

Pre-conception 71

Pregabalin 63, 118, 150, 173, 237

Pregnancy 71, 215, 263

Prescribing rates 178

Prevention 25, 52, 64

Prognostic indicator 3, 106, 150

Propranolol 117

Protein-adducts 26

Prussian blue 193

Psychoactive substance use 25

Psychostimulant intoxication 61

Psychotropic drugs 178

Pulmonary embolism 55, 174

Pulmonary toxicology 29

Pulse index continuous cardiac output (PiCCO) 104

Pyrethroid 82

Q

Quality of life 163

Quetiapine 237, 250

R

Rat study 48, 49, 68

Reactivators 4

Recreational drugs 2, 5, 6, 7, 8, 9, 10, 25, 36, 48, 55, 56, 57, 60, 61, 64, 72, 85, 92, 93, 95, 96, 107, 109, 111, 147, 150, 186, 203, 238, 246

Regulations 64

Renal injury 103, 164

Renal replacement therapy 177

Respiratory depression 48, 49, 63, 170, 252

Retina 166

Risk perception 198

Risk prediction 3

Road accidents 25

Rocuronium 179

Rodent study 48, 49, 63, 118

Rodenticides 43

S

Salt water emetic 230

Schizophrenia 133

Sea temperature 239

Sedation 107

Sedative overdose 137

Seizure 47, 192

Semaglutide 114

Semi-synthetic cannabinoids  5

Serotonin toxicity 181, 211

SGLT-2 inhibitors 115, 251

Sickle cell disease 153

Simethicone 174

Smoke inhalation 207

Smoking cessation therapy 152

Snake bite 12, 13, 95, 191, 231, 232, 258

Social media 205

Sodium bicarbonate 102, 142

Sodium channel blockade 102

Sodium chloride 230

Sodium hydroxide 126, 162

Sodium hypochlorite 124

Sodium nitrite 67, 205

Sodium-glucose co-transporter-2 (SGLT-2) inhibitors  115, 251

Spider bite 11, 122, 233

Status epilepticus 58

Sulfoxaflor 77

Supratherapeutic doses 186

Surfactant 42

Swimming pool products 159

Synthetic cannabinoid receptor agonists 2, 10, 108

Synthetic cathinones 8

Synthetic opioids 5

T

Tacrolimus 151

Taxus species 88

Telemedicine 217

Teletoxicology 217

Teratology 263

Text-based consult request 216

Thallium 193

Therapeutic drug monitoring 131

Therapeutic error in route of administration 105, 174

Thevetia peruviana (now Cascabela thevetia) 3, 83

Thevetin A 83

Thrombosis 55

Time correlation 178

Titration 252

Tobacco 198

Toxalbumins  199

Toxic alcohols 1, 240

Toxic gas 256

Toxic heat stroke 56

Toxicologist 197

Toxicovigilance 237, 242

Toxidromes 72

Toxinology 18, 84, 233

Toxscore 52

Traditional medicine 21

Tramadol 147

Treatment delay 183

Trends 120

Tricyclic antidepressant 142

Trimorbidty 110

Tropane alkaloids 53

Tropical disease 232

U

U-47700 48

Ultrasound 158

Unithiol (DMPS) 156, 253

Urologic complications 109

Use disorder 118

V

Valerian 16

Valproate/valproic acid 175

Vaping 2

Vasoplegic shock 104, 182

Vasopressor 182

Vecuronium 179

Verapamil 104

Veterinary toxicology 18, 84, 229, 230, 231, 247, 267

Vipera berus 191, 231

Virtual platform  200, 260

Visual loss 254

Vitamin D 41, 71

Vitamins 206

Vortioxetine 172

W

War 28

Warfarin 145

Water treatment 126

Wetter 42

Withdrawal  110

Wound disinfectant 105

Y

Yellow oleander 3, 83

Yew 88