Most Common Intoxication in Nephrology Ward Organophosphate Poisoning

Abstract

Objectives. In Taiwan, the widespread use of organophosphates (OPs) in agricultural and household environments results in numerous OP poisoning. To better understand the clinical significance of associated parameters on respiratory failure and patient outcome, we evaluate patients admitted to the Nephrology ward in our hospital with OP intoxication. Patients and Methods. Over a period of 2 years, a total of 42 consecutive patients with OP poisoning admitted to the nephrology ward or the Intensive Care Unit of Chang‐Gung Memorial Hospital were the subjects in the study. The diagnosis of poisoning was based on history of ingestion and characteristic clinical features of anticholinesterase agent poisoning. Prior to treatment, all symptoms recorded at emergency room and blood samples for blood chemistry including plasma amylase and plasma acetyl‐cholinesterase were collected from each patient immediately after the admission. Results. As clinical manifestations of OP show, nausea and vomiting and salivation were the leading manifestations, 45.2% and 33.3%, respectively. Patients who developed respiratory failure were older than those who did not (54.3 ± 6.9 vs. 43.1 ± 5.6, p < 0.05). The dosage of atropine administered for treatment was significantly higher in the patient group with respiratory failure compared to those without respiratory failure (29.7 ± 14.5 vs. 9.1 ± 10.2, p < 0.05). Plasma amylase level of the patient group with respiratory failure was significantly higher than those without respiratory failure (436.1 ± 87.1 vs. 181.3 ± 29.6, p < 0.01). Of course, mean days of hospitalization in the respiratory failure group are significantly longer than the other group (12.1 ± 2.1 vs. 5.4 ± 1.9, p < 0.05). Based on univariant analysis, bradycardia, hypotension, fasciculation and coma were significant factors associated with respiratory failure. The dose of atropine administered for treatment was significantly higher in the oral exposure group compared to nonoral exposure group (23.6 ± 12.6 vs. 10.6 ± 6.4, p < 0.05). The same is true for the pralidoxime treatment (9.6 ± 1.9 vs. 5.3 ± 1.4, p < 0.05). As for mean days of hospitalization (11.6 ± 3.9 vs. 6.4 ± 2.1, p < 0.05) and fatality (2 vs. 0, p < 0.05), those of oral exposure patients were significantly longer and higher than those with nonoral exposure. Conclusions. We demonstrate that elevated plasma amylase concentration was related to the development of respiratory failure in OP intoxication. It also provided us various important risk factors to identify those patients with OP poisoning who would ultimately require ventilatory support.

• Intoxication
• Organophosphate poisoning
• Respiratory failure

Introduction

Organophosphate (OP) is used worldwide as pesticides in agriculture.[1] Because of their ready availability, organophosphate is commonly consumed for the purpose of suicide. The toxicological effects of these compounds are caused by an excess of acetylcholine at cholinergic synapses, which initially stimulates and then paralyzes the synaptic transmission.[2] Poisoning may occur via skin exposure or inhalation (nonoral route), but severe cases of poisoning are commonly the result of ingestion in a suicide attempt. The cause of death in OP poisoning is respiratory failure due to combination of excessive bronchial secretions, pulmonary edema, bronchospasm and respiratory paralysis.[3] Populations specifically at risk of respiratory failure include those patients with severe poisoning assessed by clinical manifestations such as level of consciousness, profuse salivary and bronchial secretions and frequent muscle fasciculation.[4] Therefore, effective intensive care treatment and identification of these risk factors are imperative for the survival of patients.

In Taiwan, where the widespread use of OPs in agricultural and household environments results in numerous OP poisonings,[5] many intentional OP poisonings associated with respiratory failure have been seen.[6] To better understand the clinical significance of associated parameters on respiratory failure and patient outcome, we evaluated patients admitted to the Nephrology ward in our hospital with OP intoxication and have examined the association between laboratory findings and the occurrence of respiratory failure.

Patients and Methods

Over a period of 2 years, a total of 42 consecutive patients with OP poisoning admitted to the nephrology ward or the Intensive Care Unit of Chang‐Gung Memorial Hospital were the subjects in the study. The diagnosis of poisoning was based on history of ingestion and characteristic clinical features of anticholinesterase agent poisoning. Information from patients and their families as well as the examination of the container and its label confirmed each ingested material as OP. Prior to treatment, blood samples for blood chemistry, including plasma amylase and plasma acetyl‐cholinesterase, were collected from each patient immediately after admission. Bradycardia was diagnosed at a heart rate of less than 60 beats/min. Hypotension was defined if the patient's systolic blood pressure was less than 90 mmHg. Fasciculations were diagnosed in the presence of visible, repetitive, spontaneous contractions of muscle fibers over the same anatomic territory. Respiratory failure was diagnosed in the presence of respiratory distress, inadequate ventilation, and abnormal blood gas values including PaO₂ of less than 60 mmHg or PaCO₂ greater than 50 mmHg accompanied by acidosis. 19 patients needed tracheal intubations with mechanical ventilation on the day of admission or on the following days.

Management Procedure

Gastric lavage using administration of activated charcoal with cathartic via nasogastric tube was performed in all patients. For treatment, 2 mg atropine was administered intravenously every 15 min until signs of atropinization appeared, such as mydriasis, tachycardia, flushing and xerostomia. A maintenance dose of atropine was continued and boluses were given when the pulse rate was less than 100 beats/min. Pralidoxime was given to most patients. We used a dose of 1 g intravenously and followed by 3–5 g/day in the following days.

Statistic Analysis

All data were expressed as mean ± SD. Qualitative variables were compared using the Chi‐square or Fisher's exact test and quantitative variables were compared using the unpaired Student's t‐test. In all cases, p < 0.05 was considered significant.

Results

Clinical Manifestations of OP Intoxication

Clinical manifestations of OP poisoning shown are in Table 1. Nausea and vomiting and salivation were the leading manifestations, 19 (45.2%) and 14 (33.3%), respectively. Bronchorrhea was present in 12 (28.6%) and dyspnea in 11 (26.2%) subjects. Abdominal pain was present in 10 (23.8%) and sweating in 8 (19.0%). Bradycardia was noted in 9 (21.4%), whereas 8 (19%) had tachycardia, 7 (16.6%) subjects had fasciculations and 6 (14.3%) had coma.

Table 1. Clinical Manifestation of Organophosphate Poisoning in 42 Patients

Clinical manifestation	No	(%)
Nausea and Vomiting	19	(45.2%)
Salivation	14	(33.3%)
Bronchorrhea	12	(28.6%)
Dyspnea	11	(26.2%)
Abdominal pain	10	(23.8%)
Sweating	8	(19.0%)
Bradycardia	9	(21.4%)
Hypotension	8	(19.0%)
Fasciculation	7	(16.6%)
Coma	6	(14.3%)

Comparison of Various Variables Between Respiratory Failure Patients and Nonrespiratory Failure Patients

As shown in Table 2, no significant difference was found in sex. However, patients who developed respiratory failure were older than those who did not (54.3 ± 6.9 vs. 43.1 ± 5.6, p < 0.05). The dosage of atropine administered for treatment was significantly more in the patient group with respiratory failure compared with those without respiratory failure (29.7 ± 14.5 vs. 9.1 ± 10.2, p < 0.05). As for pralidoxime dose, there was no significant difference between these two groups. Plasma cholinesterase levels on the day of admission were not different between two groups; however, plasma amylase level of the patient group with respiratory failure was significantly higher than those without respiratory failure (436.1 ± 87.1 vs. 181.3 ± 29.6, p < 0.01). Of course, mean days of hospitalization in respiratory failure group were significantly longer than the other group (12.1 ± 2.1 vs. 5.4 ± 1.9, p < 0.05). As for fatality, there was no significant difference between these two groups.

Table 2. Clinical Variables in Respiratory Failure and Nonrespiratory Failure Patients

	Respiratory failure	Non‐respiratory failure	p
N	19	23
Age	54.3 ± 6.9	43.1 ± 5.6	p < 0.05
M/F	14/5	17/6	NS
Atropine (mg)	29.7 ± 14.5	9.1 ± 10.2	p < 0.05
Pralidoxime (g)	7.9 ± 4.6	5.3 ± 1.1	NS
Plasma cholinesterase (u/l)	116 ± 29	174 ± 51	NS
Plasma amyelase	436.1 ± 87.1	181.3 ± 29.6	p < 0.01
Hospitalization	12.1 ± 2.1	5.4 ± 1.9	p < 0.05
Fatality	1 (5%)	1 (4%)	NS

Factors Associated with Ventilator Support

Figures 1 and 2 depict the factors related with ventilator requirement. Based on univariant analysis, bradycardia (31.5%), hypotension (36.8%), fasciculation (36.8%) and coma (21.1%) were significant factors associated with respiratory failure. As for nausea, salivation, bronchorrhea and sweating, they did not significantly differ in the prediction of respiratory failure.

Figure 1. Factors associated with respiratory failure. As for nausea, salivation and bronchorrhea, they did not significantly differ in the prediction of respiratory failure. (Full color version available online.)

Figure 2. Factors associated with respiratory failure. Bradycardia (31.5%), hypotension (36.8%), fasciculation (36.8%) and coma (21.1%) were significant factors associated with respiratory failure. As for sweating, it did not significantly differ in the prediction of respiratory failure.

Comparison of Laboratory Variables Between Oral Exposure and Nonoral Exposure in OP‐Poisoned Patients

As shown in Table 3, no significant differences were found in sex and age. The dose of atropine administered for treatment was significantly more in the oral exposure group compared to nonoral exposure group (23.6 ± 12.6 vs. 10.6 ± 6.4, p < 0.05). The same is true for the pralidoxime treatment (9.6 ± 1.9 vs. 5.3 ± 1.4, p < 0.05). Plasma cholinesterase levels on the day of admission were not different between two groups. As for mean days of hospitalization (11.6 ± 3.9 vs. 6.4 ± 2.1, p < 0.05) and fatality (2 vs. 0, p < 0.05), oral exposure patients were significantly longer and higher than those with nonoral exposure.

Table 3. Demographic and Laboratory Difference Between Oral Exposure and Nonoral Exposure in OP Poisoned Patients

	Oral exposure	Non‐oral exposure	p
N	33	9
Age	47.3 ± 9.7	48.6 ± 11.2	NS
M/F	25/8	6/3	NS
Atropine (mg)	23.6 ± 12.6	10.6 ± 6.4	p < 0.05
Pralidoxime(g)	9.6 ± 1.9	5.3 ± 1.4	p < 0.05
Plasma cholinesterase (u/l) (3000–9300)	147.3 ± 5.2	172.9 ± 43.5	NS
Hospitalization (days)	11.6 ± 3.9	6.4 ± 2.1	p < 0.05
Fatality	2	0	p < 0.05

Discussion

This study on OP poisoning patients demonstrates that salivation, bronchorrhea and dyspnea were the common symptoms in our nephrology ward. According to previous reports, several target organs such as brain, lung, sympathetic and parasympathetic nervous systems were involved in the pathophysiology of OP poisoning. Interestingly, respiratory failure is brought by a combination of salivation, bronchorrhea, respiratory muscle paralysis and excessive bronchial secretion. In the present study, respiratory failure developed in the 45% of total patients. For plasma cholinesterase, no significant correlation with development of respiratory failure. Therefore, the decrease in plasma cholinesterase could be a confirmation of OP toxicity but could not be an indicator of severity of OP toxicity.

The usage of atropine in this study was found to be safe and we also found that clinical manifestations of atropinization are reliable criteria for the judgment of its dosage.[7] The requirement of a dose of atropine seems to be higher in respiratory failure patients. Therefore, prompt recognition and aggressive treatment of such acute intoxication is essential in OP poisoning patients with respiratory failure. In addition, patients who developed respiratory failure were older than those who did not.[8] In this case, age appears to be an important factor determining whether patients develop respiratory failure or not. This information provides us that we should be careful when we face an aged patient with OP intoxication.

It appears important to note a direct relation between serum amylase level and respiratory failure in our study. We can speculate that the salivation is commonly observed in our OP poisoning patients (Table 1) and it also could cause elevated serum amylase of salivary origin, because hypersalivation can cause elevated serum amylase. Furthermore, the previous report explains that hyperamylasemia in OP‐poisoned patients may be due to excessive muscarinic stimulation, severe acidosis, or shock with subsequent hypersecretion of salivary glands.[9] Since profuseness of salivation is one of the predisposing factors for severity of OP poisoning, elevation of serum amylase of salivary origin can be related to respiratory failure, which is one of the most severe complications of OP poisoning. In addition, some literature have also shown that severe OP intoxication can produce the conditions, which activate both parasympathetic and sympathetic nervous system and cause the massive salivation and the increase in the secretion of amylase.[10], [11] Therefore, we could also imply that plasma amylase level would be related to respiratory failure via the stimulation of autonomic nervous system.

There are other interesting findings shown in Figs. 1 and 2. We have proposed various risk factors to identify the need for definite or probable ventilatory support so that the available system of intensive care can be optimized in terms of maximum patient benefit.[12], [13] The following factors adversely affect the final respiratory outcome of the patient: bradycardia, hypotension, fasciculations and coma. Therefore, early and aggressive correction of bradycardia and hypotension appears reasonable in the management of OP poisoning. In this survey, coma seems to represent the poor prognosis in OP poisoning patients.

Further, the way of OP intoxication also plays an important role in the prognosis of OP poisoning patients. As shown in Table 3, oral exposure route shows significantly longer mean hospitalization and higher fatality than those with nonoral exposure route. We also noted that oral exposure OP intoxicated patient needs more aggressive treatment with atropine and pralidoxime.[14] Therefore, oral OP exposure remains an important clue to recognize high‐risk groups. Since adequate therapeutic facilities are available in most centers, our aim should pick up risk factors for early recognition of severe cases requiring intensive care monitoring and thus improve the outcome of these patients.

In conclusion, this study demonstrates that the elevated plasma amylase concentration was related to the development of respiratory failure in OP intoxication. It also provided us various important risk factors to identify those patients with OP poisoning who would ultimately require ventilatory support. In addition, oral exposure to OP also represents the poor prognosis of OP poisoning patients compared to those with non‐oral exposure.