Clinical Problems in Organophosphate Insecticide Poisoning: The Use of a Computerized Information System

Transcription

1 FUNDAMENTAL AND APPUED TOXICOLOGY 4, S2O9-S214 (1984) Clinical Problems in Organophosphate Insecticide Poisoning: The Use of a Computerized Information System ASHER HlRSHBERG AND YEHUDA LERMAN Research and Development Branch, IDF Medical Corps, Israel Clinical Problems in Organophosphate Insecticide Poisoning: The Use of a Computerized Information System. HIRSHBERG, A., AND LERMAN, Y. (1984). Fundam. Appl. Toxicol. 4, S209- S214. A computerized medical information system has been constructed, which contains clinical data from 236 case records of organophosphate and carbamate insecticides poisoning in Israel. A computer program was used to retrieve, analyze, and cross-tabulate data contained in 162 variables per patient Clinical criteria were used to Hi-aingiiish mild (66%) from moderate (19%) and severe (1%) cases. The majority of exposures were occupational (8%), whereas the rest were accidental (31%) or suicidal (11%). Parathion was the toxic compound most frequently involved (13 cases). Grouping signs and symptoms according to the cholinergic synapse systems showed peripheral muscarink signs to be the most prevalent (92.% of cases), whereas involvement of all three synapse systems was rare (17%). Listing individual symptoms emphasized the high prevalence of nonspecific symptoms such as vomiting (142 cases) and abdominal pain (11 cases). The mean atropine dose given to adult patients during the first 24 hr after poisoning ranged from 6.0 ± 0.7 mg in mild cases to 49.8 ± 4. mg in severe cases. Evaluation of clinical decision making was demonstrated through analysis of the guidelines used by physicians to gauge atropine administration. Five of the eighteen fatalities were delayed deaths, one of which was due to a polymorphous ventricular arrhythmia. The same arrhythmia occurred also in four nonfatal cases. Other delayed effects included nonspecific EEG changes and neuropsychiatric symptoms. Matching individual cases with comparable cases in the data bank was demonstrated, using a previously published case report Computerized consultation may help inexperienced physicians to improve the quality of medical care given to cases of organophosphate insecticide poisoning in small hospitals located in rural areas. Organophosphate (OP) and carbamate insec- This paper describes an attempt to study ticides are highly toxic compounds which these problems by automated processing of cause systemic poisoning through inhibition clinical information. The method of conof cholinesterase in cholinergic synapse sys- structing a computerized bank of clinical data tems (Namba et al., 1971). This toxicological is described, and the use of this system as a emergency is frequently lethal and requires tool for clinical research is demonstrated, prompt diagnosis and treatment (Hamblin and Marchand, 192). METHODS In the management of these patients, the physician encounters problems which require oam base. Retrospective clinical information was obclinical judgment based on knowledge and ex- tained from 236 case records of OP or carbamate insecperience. Two such problems are antidotal ticide poisoning. These patients were treated in eight hos- m Israd therapy during the acute phase (especially ^ 198 and f^,?*j**" " OP.....,. j,, poisoning was confirmed by low blood chohnesterase levels atropine administration), and various delayed (in etytiaocyta ^ ^ pi^) Q ^ of aubanme ^ effects SUCh as cardiac arrhythmias (Kiss and soning were included only when unequivocal evidence of Fazekas, 1979). exposure to a carbamate could be obtained. S /84 $3.00 Copyrijtae 1984 by the Society of Tojucology. AD rijha of reproduction in my farm reaenvd.

2 S210 HIRSHBERG AND LERMAN The following items were collected from each case record; (a) patient's characteristics (age, sex, past medical history); (b) exposure conditions (type of poison, circumstances of exposure); (c) symptoms and signs; (d) clinical course and management; (e) complications and delayed effects. Information processing. Relevant information was collected from case records by means of coded questionnaires, which were designed to transform verbal information into numerical values. Variables, 162, were defined for each patient 90% of these variables were designated to items such as the clinical picture, management, course, and complications. Data was stored on a magnetic disc of an IBM 4341 computer and a simple computer program was used to retrieve and cross-tabulate these variables. Grades ofseverity of poisoning. Grades of severity were denned as follows: a. Mild cases patients who presented with mild muscarinic signs only, such as lacrimation, miosis, excessive sweating, and hypersalivation. b. Moderate cases patients in whom a partial or fullblown spectrum of symptoms appeared, but who were breathing unassisted. c. Severe cases patients who required assisted ventilation. RESULTS The age of the patients ranged from 1 month to 71 years (mean 24 years). Of the 236 patients, 189 (80%) were males. None of the patients had previously documented OP or carbamate insecticide poisoning. Two of every three patients were poisoned by parathion (13 cases, 6%), 20 patients were poisoned by malathion, and 8 patients by other OP insecticides. Five cases of carbamate poisoning were also included. More than half the exposures were occupational (137 cases, 8%). Accidental exposures accounted for 73 cases (31%) and attempted suicide by oral ingestion of the poison for 26 cases (11%). The great majority of the 192 adult patients (over 1 years) who were occupationally exposed were mild cases (80%) whereas most suicide attempts resulted in severe intoxication (62%). Analysis of Signs and Symptoms A general evaluation of the clinical picture according to grades of severity showed that 16 cases (66%) were mild, 4 cases (19%) were moderate, and 3 patients (1%) were severely poisoned. Grouping signs and symptoms according to the type of the cholinergic synapse involved (Table 1) showed that peripheral muscarinic signs (such as lacrimation, sweating, diarrhea, and miosis) appeared in almost all patients. Nicotinic signs (fasciculations, muscle tremor, and weakness) appeared in less than half the cases and (except for one case) were accompanied by peripheral muscarinic signs. Central nervous system involvement was observed in 40% of the patients. Symptoms included anxiety, confusion, convulsions, and disturbed consciousness. Involvement of all three synapse systems was uncommon (17% of the cases). Listing individual signs and symptoms (Table 2) showed that the two most prevalent symptoms were vomiting and abdominal pain. Miosis was the most prevalent specific sign, whereas lacrimation and rhinorrhea were uncommon. A surprising finding was the presence of mydriasis in 20 patients, 7 of which did not receive atropine prior to admission. Evaluation of Management The mean dose of atropine given to adult patients (over 1 years) during the first 24 hr ranged from 6 mg in mild cases to 0 mg in severe cases (Table 3). These figures include TABLE 1 SIGNS AND SYMPTOMS OBSERVED IN 236 CASES OF ANTKHOUNESTERASE INSECTICIDE POISONING GROUPED ACCORDING TO AFFECTED SYNAPSE SYSTEMS Group of signs Peripheral muscarinic Nicotinic Muscarinic + nicotinic CNS Muscarinic + nicotinic + CNS No. of cases Percentage

3 COMPUTER USE IN ORGANOPHOSPHATE POISONING S211 TABLE 2 PARTIAL LIST OF INDIVIDUAL SIGNS AND SYMPTOMS OBSERVED IN 236 CASES OF ANTICHOLINESTERASE IN- SECTICIDE POISONING Oximes were given to 12 patients. Of these 73 received pralidoxime chloride and 2 patients received obidoxime. Sign/symptom Vomiting Abdominal pain Miosis Fasci dilations Diarrhea L&crimation Rhinorrhea Mydriasis No. of patients * Percentage mydriatic patients received atropine before admission to the hospital. the atropine given to 46 patients before admission. The differences between the mean doses given to the three groups of patients are statistically significant (p < by twotailed / test). Guidelines used by physicians to gauge atropine administration appeared in the case records of only 32 patients. Atropinization (signs of mild atropine overdose) or dry skin and mucous membranes was the stated goal of treatment in 18 cases. However, in 14 cases the stated goal was tachycardia or mydriasis alone. Examination of the routes used for atropine administration during the first 6 hr after poisoning showed that in 3 cases a combination of all three parenteral routes was used. Two routes were used in 31 patients. TABLE 3 MEAN ATROPINE DOSE GIVEN DURING THE FIRST 24 hr TO 192 ADULTS (OVER 1 YEARS) POISONED BY AN- TICHOLINESTERASE INSECTICIDES Severity of poisoning Mild Moderate Severe Mean dose (mg ± SD) 6.0 ± ± ± 4. Complications and Delayed Effects (Table 4) Complications are clinical problems which arise during the acute phase of poisoning, whereas delayed effects appear after recovery from the acute phase. Both are not considered an integral part of the typical syndrome of OP or carbamate poisoning. Fever, which usually appeared more than 24 hr after poisoning, was the most prevalent complication. It could be attributed to causes other than the poisoning itself in only 1 cases. Atropine overdose, an iatrogenic complication, occurred in three cases. Of the 18 fatalities included in the data bank occurred at least 24 hr after the patient seemed to have recovered from the acute phase of poisoning (delayed death). The cause of death has been established in only one of these patients, who developed a polymorphous ventricular arrhythmia ("Torsade de Pointes"), followed by ventricular fibrillation and death. The same type of ventricular arrhythmia appeared in four nonfatal cases, and was successfully treated by ventricular pacing. Abnormal EEG tracings were found in 4 TABLE 4 COMPLICATIONS AND DELAYED EFFECTS OBSERVED IN 236 CASES OF ANTKHOUNESTERASE INSECTICIDE POI- SONING Clinical problem Fever (>37. Q Atropine overdose Acute death Delayed death Ventricular arrhythmia EEG abnormalities Neuropsychiatric symptoms No. of cases ' 9 Percentage 'Only 12 patients had an EEG examination before discharge from hospital.

4 S212 HIRSHBERG AND LERMAN of 12 patients who had an EEG examination before discharge from hospital. The abnormalities consisted of diffuse delta and theta activity, and were still present in two of the four patients 3 months later. Depression, confusion, and agitation were noted in nine patients after recovery from the acute phase of poisoning. Other complaints were insomnia and motor weakness without objective neurological deficits. Cross-tabulation of delayed effects and the grades of severity (Table ) showed that delayed death occurred only in severe cases, but polymorphous ventricular arrhythmia appeared in mild as well as severe cases. Abnormal EEG tracings and neuropsychiatric symptoms were observed mainly in mildly poisoned patients. No association could be found between the type of insecticide involved and a specific delayed effect, yet it is interesting to note that in the small group of patients exposed to carbamates no delayed effects were observed. Use of the System as a "Toxicological Consultant" The possible use of the information system as an automated "toxicological consultant" in the management of individual cases was demonstrated by matching cases from hospital records or case reports from the medical literature with similar cases in the data bank. A typical example is a detailed case report of severe malathion poisoning published by TABLE OBSERVED DELAYED EFFECTS OF ORGANOPHOSPHATE INSECTICIDE POISONING AS RELATED TO GRADES OF SE- VERITY OF POISONING Delayed effect Death Ventricular arrhythmia EEG changes Neuropsychiatric symptoms Mild Moderate 1 Severe Total 4 9 Richards (1964). A 46-year-old woman ingested malathion and was admitted to hospital in coma and respiratory distress, yet her cardiovascular status was stable. The computer program was used to find six comparable cases in the data bank. During the first 6 hr after poisoning these patients received an average atropine doses of 46 mg. The total atropine dose ranged from 90 to 320 mg in four women, but exceeded 600 mg in the other two. In comparison, the patient in the published report was given 40 mg of atropine during the first 6 hr, and the total dose was 840 mg. Evaluating outcome, one of the six patients from the data bank died during the acute phase (after 36 hr), and in another patient ventricular arrhythmia appeared on thefifthday requiring ventricular pacing. Of the six patients three developed fever, with evidence of pneumonia on X ray in two cases. In comparison, the patient in the published report did well except for fever, which was ascribed in part to lower respiratory tract infection. DISCUSSION Organophosphate insecticide poisoning is an important and common health problem, meriting a systematic and critical analysis. We present a new approach to this problem through the construction and use of a computerized bank of clinical data. Case records of poisoning due to cholinesterase inhibitors are especially suitable for automated processing because this disease entity is relatively stereotypical. It is characterized by a specific syndrome, a limited number of antidotes, and one pathognomonic laboratoryfinding (low blood cholinesterase) which allows the elimination of clinically false positive casesfromthe data base. All these features make it possible to use a small number of variables per patient, and to process, retrieve, and compare clinical data by a simple computer program. The study of clinical problems in the management of OP insecticides poisoning must

5 COMPUTER USE IN ORGANOPHOSPHATE POISONING S213 be based on a clear distinction between the various grades of severity of poisoning. Since the level of blood cholinesterase correlates poorly with the clinical picture (Freeman and Epstein, 19), grading of severity had to be based on clinical criteria. We chose to refer to the patient'srespiratorystatus to Histingiikh moderate from severe cases because a patient requiring assisted ventilation is indeed a critical case. Two methods were employed to analyze details of the clinical picture. Grouping signs and symptoms according to the type of the affected cholinergic synapse (Grob etal., 190) has the advantage of presenting the clinical picture in a systematic way. It also has therapeutic implications, since various antidotes exert their main effect on different synapse systems (Grob and Johns, 198). Peripheral muscarinic signs appeared in almost all the patients irrespective of the type of exposure. Therefore, when considering the diagnosis of poisoning due to cholinesterase inhibitors, looking for muscarinic signs is likely to be the most rewarding. The fruitfulness of listing individual signs and symptoms is emphasized by the finding of a surprisingly high prevalence of vomiting and abdominal pain. These symptoms should be considered an expression of systemic cholinergic stimulation and not a result of nonspecific gastrointestinal irritation, since they were present in many patients who were exposed to the poison by inhalation or through the skin. Although much less prevalent than miosis, mydriasis should also be considered a possible sign of OP poisoning (Dixon, 197). The focus of interest in antidotal treatment is atropine. That is so because atropine has to be carefully titrated according to the patients condition whereas oximes are given in standard doses at fixed intervals (Namba et al., 1971). The fact that significant differences were found between the mean atropine doses given to mild, moderate, and severe cases proves that the classification used (which was based on a retrospective analysis of clinical findings) has a sound pathophysiologjcal basis as well as practical value. The possible use of our system in the assessment of clinical decision making is demonstrated by the analysis of guidelines used by physicians to gauge atropine administration. Although only partial information was available, the use of tachycardia or mydriasis as a sole guideline indicates lack of clinical experience, since these two signs may be a direct effect of the poison. The tendency to use multiple routes for atropine administration may also be considered an indication of clinical inexperience since there is no objective reason to use more than one route during the first few hours. The complications and delayed effects observed in the present series have previously been described in the literature. Ventricular arrhythmias were described by Luzhnikov et al. (197) and later by others (Kiss and Fazekas, 1979; Ludomirsky et al., 1982). These arrhythmias may be the cause of delayed death in OP poisoning. EEG changes following acute exposure to OP have also been described (Holmes, 1964; Grob et al., 1947), but the changes are nonspecific and their clinical significance is not clear. Neuropsychiatric symptoms following recovery from the acute phase of poisoning have also been reported (Namba etal., 1971). The main advantage of a computerized analysis of complications and delayed effects is the possibility to evaluate the magnitude of the problem and to examine possible associations with other clinical data. One such example is the cross-tabulation of delayed effects with grades of severity of poisoning, which showed that these clinical problems appear in mild as well as severe cases. A detailed examination of the clinical course in specific cases is also possible, as was done in the patients with polymorphous ventricular arrhythmia. Since the system offers easy access to the accumulated clinical experience of many physicians treating OP insecticide casualties, it

6 S214 HIRSHBERG AND LERMAN was suggested to examine the possibility of using it as a comuterized "toxicological consultant" for the benefit of future patients. Automated toxicological consultation, which requires an interactive computer system, is based on matching the case in question with comparable cases in the data bank. Thus, the inexperienced physician can use the experience of others to help him make decisions. The example of matching a published case with six comparable cases from the data bank showed the predictions made by the system and the observations made in the published case to be considerably similar. We suggest that after furtherrefinementand enlargement of the data base, such a system may be of use in small hospitals located in rural areas, where OP insecticides poisoning is prevalent, but a clinical toxicologist is not always available. Thus, beyond being a convenient tool for clinical research, the computerized information system may also be of help in the management of individual cases. REFERENCES DTXON, E. M. (197). Dilatation of the pupos in parathion poisoning. J. Amer. Med. Assoc 163, FREEMAN, G., AND EPSTEIN, M. A. (19). Therapeutic factors in survival after lethal cholinesterase inhibition by phosphorus insecticides. A'. EngL J. Med. 23, GROB, D., GAKLJCK, W. 1_, AND HARVEY, A. M. (190). The toxic effects in man of the antkbolinesterase insecticide parathion. Bull. Johns Hopkins Hosp. 87, GROB, D., HARVEY, A. M., LANGWORTHY, O. R., AND LHJENTHAL, J. L, JR. (1947). The administration of diisopropylfluorophosphate (DFP) to man. HI. Effects on the central nervous system with special reference to the electrical activity of the brain. Bull. Johns Hopkins Hosp. 81, GROB, D., AND JONES, R. J. (198). Use of oximes in the treatment of intoxication by anticholinesterase compounds in normal subjects. Am. J. Med. 24, HAMBUN, D. O., AND MARCHAND, J. F. (192). Phosphate ester poisoning, a new problem for the internist Ann. Intern. Med. 36, 0-. HOLMES, J. H. (1964). Organophosphorus insecticides in Colorado. Arch. Environ. Health 9, Kiss, 21, AND FAZEKAS, T. (1979). Arrhythmias in organophosphate poisoning. Ada Cardiol. 34, LUDOMIRSKY, A., KLEIN, H. O., SARELU, P., BECKER, B., HOFFMAN, S., TETTLEMAN, U., BARZTLAI, J., LANG, R^ DAVID, D., DISEGNI, E., AND KAPUNSKY, E (1982). Q-T prolongation and polymorphous ("Torsade de Pointes") ventricular arrhythmias associated with organophosphate insecticide poisoning. Amer. J. Cardiol. 49, LUZHNIKOV, E. A., SAVTNA, A. S., AND SHEPELEV, V. M. (197). On the pathogenesis of cardiac rhythm and conductivity disorders in cases of acute insecticide poisoning. Kardiologiya (USSR) 1, NAMBA, R., NOLTE, C. T., JACKREL, J., AND GROB, D. (1971). Poisoning due to organophosphate insecticides: Acute and chronic manifestations. Amer. J. Med. 0, RICHARDS, A. C (1964). Malathion poisoning successfully treated with large doses of atropine. Canad. Med. Assoc. J. 91,