Abstract
Introduction
Poison centers provide free expert recommendations on the treatment of a wide variety of toxicological emergencies. Prior studies have called attention to the increasing complexity of cases reported to poison centers. We aimed first, to evaluate the trends in medical outcome severity, over a 15-year period in both the adult and pediatric populations. Second, we described the most frequently reported substances associated with major effect or death.
Methods
This is a retrospective review of exposures reported to the National Poison Data System from 1 January 2007 through 31 December 2021. All closed cases, for human exposures, reported during the study period were included. We assessed trends in frequencies and rates of medical outcomes and level of care received, among the adult (age greater than 19 years) and pediatric (age 19 years and younger) populations by reason for exposure.
Results
During the study period, the number of adult unintentional exposures resulting in major effect (37.4 percent) and death (65.3 percent) increased. The number of adult intentional exposures resulting in death increased by 233.9 percent and those resulting in a major effect increased by 133.1 percent. The rates of exposures resulting in major effect and death increased among both intentional and unintentional adult exposures. The number of pediatric unintentional exposures resulting in a major effect increased by 76.6 percent and the number of pediatric intentional exposures resulting in death and major effect increased by 122.7 and 190.1 percent, respectively. Moderate, major effect, and death rates increased in pediatric unintentional exposures and moderate and major effect rates increased in pediatric intentional exposures.
Conclusions
We found a worsening severity of medical outcomes in adult and pediatric cases reported to poison centers. Poison centers are increasingly managing complex cases. Monitoring trends in which substances are associated with severe outcomes is imperative for future strategic prevention efforts.
Introduction
Drug overdose deaths continue to rise, despite continued national prevention efforts. In 2021, there were 106,699 drug overdose deaths in the United States (US), increasing five-fold over the past two decades [Citation1]. Poison centers in the US provide free expert recommendations on the treatment of a wide variety of toxicological emergencies. Specialists in poison information manage calls from the lay public and healthcare professionals. Depending on case complexity, specialists in poison information may consult the on-call toxicologist before providing the caller with case management recommendations. Data published by US poison centers reveal that the number of poison centers calls peaked in 2008 and since then has been steadily decreasing [Citation2]. However, prior studies have called attention to the increasing complexity of cases being reported to poison centers [Citation2,Citation3]. Increasing complexity requires poison centers to utilize more resources per case [Citation3].
The 2022 Annual Report of the National Poison Data System (NPDS) showed a yearly increase in the overall number of cases with more serious outcomes (moderate effect, major effect, death) since 2000 [Citation4]. However, the report did not examine the granularity of the change such as trends in severity by age group and by reason for exposure [Citation4].
Therefore, in the present study, we aimed to evaluate the trends in medical outcomes reported to US poison centers over a 15-year period involving intentional and unintentional exposures in the adult and pediatric populations. Second, we aimed to describe the most frequently reported substances associated with a major effect or death in each of these categories.
Methods
Study design
This is a retrospective review of exposures reported to the NPDS from 1 January 2007 through 31 December 2021. The NPDS is the data warehouse for the 55 US poison centers. When a member of the public or a health care professional makes a call to a regional poison center and consults with a specialist in poison information, the information exchanged during the initial and any follow-up calls are entered into an electronic medical record and uploaded, de-identified, to NPDS in near real time.
Case selection and data collection
All closed cases, for human exposures, reported by poison centers during the study period were included in the analysis. Specialists in poison information, using coding standards set forth in the NPDS coding manual, code information collected during the call. Data on the origin of the call (lay public versus healthcare facilities), the patient (age and gender), exposure (substance, reason, and route), management of the case (level of care and therapies received), and the medical outcome were included in the study.
Medical outcome definition
The medical outcome is the final determination made by the specialist in poison information, based upon all the information available at the conclusion of the case. Exposures followed to a known outcome can result in no effect, minor, moderate, major effect or death. The NPDS defines major effects as life threatening or resulting in significant disability or disfigurement (e.g., status epilepticus, ventricular fibrillation). Moderate effects are pronounced, prolonged, or systemic, and usually require some form of treatment, but are not life threatening (e.g., acid-base disturbance, hypoglycemia with confusion). Minor effects are minimally bothersome and resolve rapidly (e.g., sinus tachycardia without hypotension, mild gastrointestinal symptoms without dehydration). No effect is reserved for patients who develop no symptoms as a result of the exposure [Citation4].
Analyses by reason for exposure
Analyses of intentional exposures: we included cases coded as suspected suicide, intentional abuse (exposures resulting from the intentional improper or incorrect use of a substance in which the patient was likely attempting to gain a euphoric or other psychotropic effect), intentional misuse (exposures resulting from the intentional improper or incorrect use of a substance for reasons other than the pursuit of a psychotropic effect), and intentional-unknown reason.
Analyses of unintentional exposures: we included cases coded as unintentional–general, unintentional misuse (unintentional improper or incorrect use of a non-pharmaceutical substance), therapeutic errors, environmental and occupational exposures, bites and stings, food poisoning and unknown unintentional exposures.
Statistical analysis
We assessed trends in frequencies and rates of medical outcomes (per 1,000 human exposures, except for death rates per 100,000 human exposures) among adult (age >19 years) and pediatric (age ≤19 years) populations by reason for exposure and age categories using Poisson regression methods. In addition, we assessed trends in level of care received critical care unit; non-critical care unit; treated and released (non-admission). We presented percent changes in frequencies with the corresponding 95% confidence intervals (CI) and reported rates with the corresponding 95% CI. We presented study outcomes in years 2007, 2017 and 2021 to allow an assessment over a 15-year period and during the last 5 years of the study. We graphically presented the yearly rates of exposures with more serious outcomes (moderate effect, major effect and death) and less serious outcome (minor effect, no effect) by age and reason for exposure. We described the most frequently reported substances (single and multi-substance exposures) associated with major effect or death among adult and pediatric cases, separately and by reason for exposure. We divided substances into three, five-year blocks (2007–2011, 2012–2016, and 2017–2021) for categorization, and without making statistical inference. More than one substance can be reported in each exposure case; we reported substances frequencies. We analyzed data using SAS statistical software (version 9.4; SAS Institute). The study was conducted on de-identified NPDS data and was exempt from comprehensive Institutional Review Board review.
Results
During the study period, there were 33,796,185 human exposures reported to US poison centers. This included 7,988,856 (23.6%) unintentional adult exposures, 3,891,569 (11.5%) intentional adult exposures, 18,706,890 (55.4%) unintentional pediatric exposures, and 1,637,841(4.8%) intentional pediatric exposures. There were 387,953 calls from healthcare facilities in 2007 (15.6% of total calls) and 490,521 calls in 2021 (23.4% of total calls) representing a 26.4% increase (95% CI: 25.9–27.9%).
Trends in medical outcome severity: adult population
Between 2007 and 2021, the number of unintentional exposures in the adult population slightly declined (−0.8%), however the number of unintentional exposures resulting in major effect (37.4%) and death (65.3%) increased, during the same time period (). Major effect and death rates increased between 2007 and 2021 while minor effect decreased ( and ).
Figure 1. Trends is medical outcome in adult and pediatric populations by reason of exposure – United States poison centers, 2007–2021.
Table 1. Frequency and rates of medical outcomes in adult and pediatric populations – United States poison centers, 2007–2021.
Between 2007 and 2021, the number of adult intentional exposures increased by 11.0%. The number of deaths increased by 233.9% and the number of exposures resulting in a major effect increased by 133.1% (). Rates in exposures resulting in moderate, major effect and death increased among adult intentional exposures. ( and ). The increase in severity of medical outcomes was observed across all age groups (Supplementary Table 1).
Trends in medical outcome severity: pediatric population
During the study period, the number of pediatric unintentional exposures decreased 33.0%. However, the number of unintentional exposures resulting in a major effect increased by 76.6% (). Moderate, major effect, and death rates in pediatric unintentional exposures increased between 2007 and 2021 ( and ).
Between 2007 and 2021, intentional exposures in the pediatric population increased by 59.0%. The number of exposures resulting in moderate effect increased by 117.2% and those resulting in major effect increased by 190.1%, and the number of deaths increased by 122.7% (). Moderate and major effect rates in pediatric intentional exposures increased during the study period ( and ). The increase in severity of medical outcomes was observed across all age groups (Supplementary Table 2).
Admission to hospital units
Between 2007 and 2017, admission rates to critical care units rose in pediatric intentional exposures During the same period, admission rates to critical care units slightly increased in adult unintentional exposures and declined in adult intentional exposures. Compared to 2007 and 2017, admission rates to critical care units in 2021 declined in all groups except for pediatric unintentional exposures. Between 2007 and 2021, the rates of non-critical care unit admissions increased in adult and pediatric populations, intentional and unintentional exposures ( and ).
Figure 2. Trends is level of care received in adult and pediatric populations by reason of exposure – United States poison centers, 2007–2021.
Table 2. Frequency and rates of level of care received by the adult and pediatric populations – United States poison centers, 2007–2021.
Most frequently reported substances associated with major effect or death
During the study period, 424,025 single and multi-substance exposure cases resulted in a major effect or death, of which, 31,978 (7.5%) were unintentional adult exposures. For unintentional adult exposures, carbon monoxide and paracetamol (acetaminophen) – alone (excluding combination) were the two most frequently reported substances throughout the three five-year blocks (). There were 285,960 (67.4%) intentional adult exposures. For adult intentional exposures, ethanol was the most frequently reported substance in the three five-year blocks and paracetamol (alone) was the second most frequently reported substance during 2007–2011 and 2012–2016 and the third most frequently substance reported during 2017–2021. There were 17,431 (4.1%) unintentional pediatric exposures. Clonidine and carbon monoxide ranked the first and second most frequently reported substances, respectively; across the three five-year blocks. Methadone was among the five most frequently reported substances in unintentional pediatric exposures, during the three five-year blocks. Buprenorphine ranked fifth during 2012–2016, and third during 2017–2021 (). There were 41,785 (9.9%) intentional pediatric exposures. During the study period, paracetamol alone, diphenhydramine, ibuprofen and ethanol were among the most frequently reported substances involved in intentional pediatric exposures. Bupropion ranked first and second during the 2012–2016 and 2017–2021 periods, respectively (). The list of generic codes of the most frequently reported substances is presented in Supplementary Table 3.
Table 3. Most common substances associated with major effect or death – United States poison centers, 2007–2021.
Discussion
While the exposure case volume data decreased during the 15-year study period, the severity of medical outcomes in both adult and pediatric intentional and unintentional exposures increased. All age subgroups, within adult and pediatric populations, saw more severe medical outcomes (moderate, major, and death). The increasing severity of outcomes over time, indicates that a larger proportion of exposures that poison centers are consulted on are of a more complex nature. While the majority of cases continue to be from the lay public, health care facility exposure cases are steadily increasing.
Prior studies have illustrated the cost effectiveness of poison centers and their impact on reducing healthcare spending [Citation5–8]. These savings occur due to the poison centers’ ability to manage cases out-of-hospital, thereby preventing unnecessary visits to the emergency department, by decreasing length of hospital stay, and through appropriate antidote utilization [Citation8–10]. When a toxicologist is directly involved in bedside care of a hospitalized poisoned patient, the result is a decrease in the length of stay as well as higher reimbursement for the hospital [Citation11]. As the medical outcomes of exposure cases trend towards an increase in severity, the importance of involvement of a poison centers or inpatient toxicology service to provide direct bedside assessment becomes of critical importance.
The rates of exposures resulting in major effect increased by 21% (adult unintentional), 57% (adult intentional) and death rates increased by 47% (adult intentional) between 2017 and 2021. Despite the rising severity of cases and increased healthcare admissions, NPDS data did not reveal a consistent increase in admissions to critical care units over the course of the study period. The insufficient number of available intensive care unit beds and the shortage of intensivists in many healthcare facilities may have constrained physicians to care for poisoned patients in the emergency department or in a lower level of care within the hospital [Citation12,Citation13]. Our hypothesis is further supported by the sharp decrease in admissions of poisoned patients to critical care units during the COVID-19 pandemic (2020–2021), period when the healthcare systems were overwhelmed, intensive care unit physical space and staffing were insufficient, and non-COVID-19 care processes were greatly compromised [Citation14]. The corresponding trend was not noted in the pediatric population, which, in comparison to the adult population, did not see an increase in COVID-19 related critical care unit admissions to the same extent during the initial wave in 2020 and remained fairly constant with subsequent variants [Citation15,Citation16]. Pediatric intentional exposures had the largest increase in non-critical care unit admissions, compared to all other groups. Pediatric suicides are increasing at an alarming rate, a national trend that has been noted to increase during the COVID-19 pandemic [Citation17]. Furthermore, pediatric unintentional exposures had the greatest decline, compared to all other groups. This could be in part due to the success of preventative efforts including general public education regarding the safe use and storage of drugs (e.g., up and away) and implementation of child resistant packaging [Citation18–21]. This decline may also be due in part to a new generation of parents of young children who are consulting web-based forums rather than calling the local poison center. The decrease in the overall unintentional encounters in the pediatric population cannot fully explain the increase rate of more serious outcomes. Analysis of trends showed that while the overall encounters decreased by 33%, the number of cases resulting in major effect and death increased 76% and 51%, respectively. This increase may be due in part to children gaining increased access to highly toxic substances such as edible cannabis products and opioids [Citation22,Citation23].
Limitations
Our study has several limitations. The NPDS is subject to reporting bias, with the accuracy of data being subject to correct input and coding of medical outcomes and the highest level of care received during the case encounter. Reporting to poison centers is voluntary and therefore is not representative of all poisoning cases occurring in the US. As various substances become more prevalent in society, healthcare professionals become more adept at recognition and treatment and may not routinely seek out expert advice or report these cases to poison centers. Therefore, part of the increase in severity of cases observed in the current study could be due to poison centers getting consulted more often on unfamiliar or severe toxicities and less often on classic clinical presentation of well-known toxic exposures. When cases are reported, measuring the complexity of the cases is multifactorial and the current study only evaluated a few aspects. Furthermore, interpreting changes in case volume and medical outcome during the COVID-19 pandemic is challenging due to global changes in resource utilization. We described the most frequently reported substances in major effect and death cases. The retrospective nature of our study cannot prove causation. In addition, we included single and multi-substance exposure cases, and it is possible that commonly encountered but low toxicity substances were involved in many cases, while less common and highly toxic substances contributed more to the worse medical outcome. For example, gabapentin may have been a co-ingestion in four different opioid overdoses with major effect (e.g., fentanyl, heroin, methadone, and codeine) which would cause gabapentin to be counted four times, but each opioid to be only counted once, despite being the cause of the major effect. Furthermore, in many cases, confirmatory testing is not performed, and substances associated with major effect or death may only be presumed based on patient’s history and clinical characteristic of poisoning. Reported opioids such as methadone or heroin could have actually been fentanyl or fentanyl analogs. Further analysis is warranted to assess change in substance trends by age and reason for exposure and taking into account the number and sequence of substances involved in each encounter.
Conclusions
The total number of exposures reported to poison centers decreased between 2007 and 2021. However, we found a worsening severity of medical outcome in adult and pediatric cases, and across all age groups. Management of more complex cases requires more time and effort from poison center staff. On-call toxicologists are an integral part of the management team as the severity of cases increases. Studies assessing the time poison center staff and toxicologists spend managing poisoned patients are warranted to further assess the change in cases complexity and need for future resource allocation. Monitoring trends in which substances are associated with severe outcomes is imperative for future strategic prevention efforts.
Supplemental Material
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The authors reported there is no funding associated with the work featured in this article.
Disclosure statement
No potential conflict of interest was reported by the author(s). America’s Poison Centers maintains the NPDS, which houses de-identified case records of self-reported information collected from callers during exposure management and poison information calls managed by the country’s poison centers. The NPDS data do not reflect the entire universe of exposures to a particular substance as additional exposures may go unreported to poison centers; accordingly, NPDS data should not be construed to represent the complete incidence of US exposures to any substance(s). Exposures do not necessarily represent a poisoning or overdose and America’s Poison Centers is not able to completely verify the accuracy of every report. Findings based on NPDS data do not necessarily reflect the opinions of America’s Poison Centers.
Data availability statement
Data are available from America’s Poison Centers, National Poison Data System.
Additional information
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