causes of seizures reported to the Poison Control Center were cyclic antidepressants (55 cases ..... poisons with which the caller is less familiar. However, it.
Erra turn In the article entitled “Seizures Associated With Poisoning and Drug Overdose” by Olson et al. (Am J Emerg Med 1993;6:565-568), the second column head-
ing in Table 3, on page 567, should have read “No complications.” The article, with the corrected table, is reprinted below.
Seizures Associated With Poisoning and Drug Overdose KENT R. OLSON, MD,*t# THOMAS E. KEARNEY, PHARMD,*$II JO ELLEN DYER, PHARMD,*II NEAL L. BENOWITZ, MD,*t§ PAUL D. BLANC, MD, MSPH*$§ A retrospective review of cases consulted by the San Francisco Bay Area Regional Poison Control Center during a 2-year period was performed to determine the causes and consequences of seizures associated with poisoning and drug intoxication. Of 233 charts coded as involving seizures, 191 occurred in humans and were avallable for analysis. The leading causes of seizures reported to the Poison Control Center were cyclic antidepressants (55 cases, 29%); cocaine and other stimulants (55 cases, 29%); diphenhydramine and other antihistamines (14 cases, 7%); theophyiline (10 cases, 5%); and isoniazid (10 cases, 5%). Stimulants and diphenhydramine were more likely than other drugs to produce brief, self-limited seizures. in contrast, poisoning by cyclic antidepressants, cardiodepressant antiarrhythmic agents, or theophyiiine was more likely to be associated with death. Seizures in elderly patients were more likely to result in complications and death. The frequency of seizure-related cases by substance type was also compared with the results of an earlier survey performed in 1981, and found a striking increase in the proportion of seizures caused by cocaine and (23% in 1988 to 1989 compared with 4% in 1981). Poison Control Center data can provide valuable information about the causes and consequences of drug-related medical compiications, as well as highlight changing trends in drug-related injury. (Am J Emerg Med 1993;11:585-588. Copyright 0 1993 by W.B. Saunders Company)
Numerous drugs are known to cause seizures with therapeutic use or overdose.‘,’ However, the relative frequency of such complications has rarely been studied, and little is known about the relationship of drug-induced seizures to From the *San Francisco Bay Area Regional Poison Control Center, the tciinical Pharmacology Unit of the Medical Service, and the *Injury Center for Prevention and Research, San Francisco General Hospital, and the $Department of Medicine, School of Medicine, and the ItDivision of Clinical Pharmacy, School of Pharmacy, University of California, San Francisco, CA. Manuscript received January 26, 1993; revision accepted April 3, 1993. Supported in part by grant no. R49CCR903697 from the National Center for Injury Prevention and Research, Centers for Disease Control, Atlanta, GA. Address reprint requests to Dr Olson, Medical Director, San Francisco Bay Area Regional Poison Control Center, San Francisco General Hospital, 1001 Potrero Ave, San Francisco, CA 94110. Copyright 0 1993 by W.B. Saunders Company 0735-6757/93/1106-0001$5.00/0 392
eventual medical outcome. Although the federal government’s Drug Abuse Warning Network (DAWN) provides statistical data about emergency department visits for drug abuse, it does not report data on specific complications such as seizures, coma, or cardiovascular problems.3 Poison control centers (PCCs) in the United States provide consultation on more than 1.8 million human poisonings each year, including 280,000 calls from health care facilities.4 They provide a unique opportunity to monitor specific drug-related complications. We used data collected at one regional PCC during a 2-year period to determine the most common causes and medical consequences of drug-induced seizures. The results were also compared with those of a previous survey we performed a decade earlier to look for changing patterns of drug-related seizures.
METHODS At the San Francisco Bay Area Regional Poison Control Center (SFPCC) each human exposure chart is coded at the time of the case and during follow-up for the drug or drugs involved and common medical complications including seizures, coma, shock, respiratory arrest, and serious electrocardiographic (ECG) abnormalities. The staff also document reported history of exposure, clinical presenting signs, results of laboratory and toxicological testing, and their assessment of the case, including whether or not it appears to be related to the suspected drugs. In addition, all hospitalized cases are followed-up to recovery by PCC staff and faculty, and if new information is uncovered, the data are edited appropriately. All charts from 1988 and 1989 that were human exposures and were coded as involving seizures were reviewed, and pertinent data (age, reason for exposure, substances involved, number or duration of seizures, clinical data, treatment, and medical complications) were extracted onto a customized data collection form. Statistical analysis was performed using x2 and Fisher’s exact tests. For analysis by substance, the substance in question was compared with the total value for all other substances combined. This was done similarly for each analyzed medical complication by substance. RESULTS Of 223 cases coded as involving seizures in 1988 to 1989, 191 occurred in humans and were available for review. Re-
OLSON ET AL w SEIZURES AND POISONING/OD
TABLE1.
Causes of Drug- and Poison-Induced
393
Seizures No. of Cases With Seizures
Primary Drug(s) Antidepressants Tricyclics/tetracyclics Amoxapine Fluoxetine’ Stimulants Cocaine Amphetamine/methamphetamine Ephedrine/pseudoephedrine lsometheptene Phencyclidine Diphenhydraminet Theophylline lsoniazid Cardiodepressant antiarrhythmic agents Diltiazem Mexiletine Procainamide Verapamil Other Sedative-hypnotic withdrawal Lidocaine Lithium Other/unknown* Total cases
55 47 4 4 55 42 6 4 2 1 14 10 10 4 1 1 1
1 43 5 3 3 32 191
*All four fluoxetine cases involved coingestion with other drugs that may have caused the seizures (ie, diphenhydramine, thioridazine, thiothixene, and/or desipramine). T Two cases also involved other antihistamines (hydroxyzine, pyrilamine). $ One to two cases each involved the following: acetaminophen (liver failure); AZT; boric acid; carbamazepine; DPT immunization; LSD; monoamine oxidase inhibitors; nitrous oxide; nonsteroidal antiinflammatory agents; opioids; organophosphates; phenothiazines; salicylates; strychnine; and unknown.
sults are illustrated in Tables 1 through 4. The most common causes of seizures were cyclic antidepressants (55 cases, 29%); cocaine and other stimulants (55 cases, 29%); diphenhydramine and other antihistamines (14 cases, 7%); theophylline (10 cases, 5%); and isoniazid (10 cases, 5%). Other drugs and poisons (1 to 3 cases each) included acetaminophen (with liver failure), azidothymidine (AZT), boric acid, calcium antagonists, camphor, carbamazepine, DPT injection, lidocaine, lindane, lithium, mexiletine, nitrous oxide, nonsteroidal antiinflammatory agents, opioids, organophosTABLE2.
phates, penicillin, phenothiazines, procainamide, salicylates, sedative hypnotic agents (withdrawal), and strychnine. Fifty-eight cases involved exposure to more than one drug. Stimulants and diphenhydramine were more likely than other drugs to produce only brief, self-limited seizures (Table 2). In contrast, patients with cyclic antidepressant overdose were more likely to have multiple or prolonged seizures, to require endotracheal intubation, and to experience other medical complications (Table 3). Multiple or prolonged seizures and medical complications were also common in patients with theophylline-induced seizures. Although seizures were often multiple or prolonged in patients with isoniazid overdose, they rarely were associated with medical complications. Patients with seizures associated with antidepressant or antiarrhythmic overdose were more likely to die. Seizures in elderly patients, seizures occurring as a result of a suicide attempt, and multiple or prolonged seizures were also more likely to be associated with other medical complications (Table 4). However, seizures associated with drug abuse were usually uncomplicated. The most frequent complications were respiratory compromise necessitating endotracheal intubation (65 cases, 34%). cardiac arrhythmias including significant sinus tachycardia (43 cases, 22%), and hypotension (31 cases, 16%), hyperthermia (14 cases, 7%), rhabdomyolysis (11 cases, 6%). and death (18 cases, 9%). We also compared the frequency of seizure calls by substance type with the results of an earlier survey performed in 1981, and found a striking increase in cocaine-related cases (4% of cases in 1981 compared with 23% in 1988 to 1989). DISCUSSION Seizures associated with poisoning or drug overdose generally indicate a significant exposure and an increased probability of medical complications, both from the seizure itself and other pharmacological effects of the drug or poison. A variety of agents may cause seizures; when a patient with poisoning or drug overdose has a seizure, certain common substances should immediately be suspected. The results of this study suggest that these should include cyclic antidepressants, cocaine and amphetamines, theophylline, diphenhydramine, and isoniazid. This has important implications for the emergency physician because determination of the specific drug or poison involved may lead to selection of specific laboratory tests and possibly administration of a specific treatment or antidote. For example, seizures in a
Number and Duration of Seizures by Drug Class
Drug Class
No. of Cases
1 to 2 Brief Seizures
55 55 14 10 10 4 43 191
29 (53%) 43 (78%) 13 (93%) 4 (40%) 4 (40%) 1 (25%) 26 (60%) 118 (62%)
Antidepressants Stimulants Diphenhydramine Theophylline lsoniazid Antiarrhythmics Other/unknown Total ABBREVIATION: NS, not significant.
Multiple/Prolonged 16 (29%) 7 (13%) 0 4 (40%) 5 (50%) 3 (75%) 6 (14%) 41 (21%)
Unknown
P
10 (18%) 5 (9%) 1 (7%) 2 (20%) 1 (10%) 0 11 (25%) 30 (16%)
NS 60 years Number/duration of seizures* 1-2 Brief Multiple/ prolonged
12, Number
Endotracheal lntubation
Any
No Complications
Antidepressants Stimulants Diphenhydramine Theophylline lsoniazid Antiarrhythmics Other/unknown Total
TABLE 4. Complications Number of Seizures
n Volume
MEDICINE
by Drug Class
Drug Class
NOTE. Complications included rhabdomyoiysis, or death. *P < .Ol. t P < ,001.
OF EMERGENCY
Antidepressants Stimulants Antihistamines Theophylline lsoniazid Other/unknown Total
1981 17 2 4 7 11 12
(32%) (4%) (8%) (13%) (21%) (23%) 53
ABBREVIATION: NS, not significant.
Seizures,
1988-l 989 55 55 14 10 10 47
(29%) (29%) (7%) (5%) (5%) (25%) 191
1981
P NS
