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Toxicology: An annotated bibliography of the recent literature
The Literature of Emergency Medicine
Toxicology: An Annotated Bibliography of the Recent Literature THOMAS ACETAMINOPHEN Prediction of acetaminophen level from clinical history of overdose using a pharmacokinetic model. Edwards DA, Fish SF, Lamson MJ, et al. Ann Emerg Med 1986;lS: 1314-1319. This study analyzed the first levels drawn in 26 patients prior to spontaneous or induced gastric emptying. The measured level was compared with that predicted from a onecompartment pharmacokinetic model with first-order absorption and elimination. A good correlation was found in patients with levels drawn more than 2 hours after ingestion. The formula reduces to: plasma level at 4 hours = (0.59) (ingested dose in mg/kg). This study challenges the widespread belief that ingestion histories are unreliable in overdose patients. Coma and metabolic acidosis early in severe acute paracetamol poisoning. Flanagan RJ, Mant TGK. Hum Toxic01 1986;5: 179- 182. The cases of five patients with severe acetaminophen poisoning (levels >800 pg/mL between 4 and 12 hours after ingestion) are described. Four patients were deeply comatose, and two had a metabolic acidosis. Toxicologic analysis of the blood and urine revealed only one patient with a significant coingestion (serum salicylate level of 29 mg/dL). Halflives were prolonged with a mean value of 9.4 hours and range of 4.8 to 39 hours. The authors conclude that massive acetaminophen overdose without coingestants can present with coma and acidosis without signs of hepatic failure.
ALCOHOLS 4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man. Baud FJ, Bismuth C, Gamier R, et al. J Toxic01 Clin Toxic01 1986-7;24:463483. From the Department of Emergency versity Hospital, Washington, DC.
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4-Methylpyrazole (4-MP) is a potent inhibitor of alcohol dehydrogenase but is not approved for clinical use in the United States. 4-MP, 20 mg/kg * d, was used in three cases of ethylene glycol intoxication treated in France. In animal studies, 4-MP has not been found to be as toxic as the parent pyrazole compound. The elimination half-life of ethylene glycol was not determined before treatment with 4-MP and ranged from 11.5 to 14.75 hours after treatment in these cases. This corresponds to the half-life of 17 hours in patients blocked with ethanol. The renal ethylene glycol clearance during 4-MP treatment in one patient was 17 mL/min. Plasma oxalate levels were determined in two patients and returned to normal within 13 to 21 hours. Apparent side effects included a rash in one patient, eosinophilia in two patients, and mild elevations in the aspartate aminotransferase and creatinine phosphokinase levels in two patients. 4-MP appears to be a safe yet effective antidote for ethylene glycol intoxication, but more patients must be evaluated with scrutiny for allergic or hepatotoxic effects. Organic acids in ethylene glycol intoxication. Gabow PA, Clay K, Sullivan JB, et al. Ann Intern Med 1986;105:16-20. Ethylene glycol intoxication was evaluated in three patients to identify the organic acids responsible for the acidosis and the efficacy of hemodialysis with a bicarbonate dialysate. Animal studies have previously demonstrated that the major organic acid is glycolic acid, but this finding had not been verified in humans. At the time of analysis, the pH values ranged from 7.17 to 7.26. The analysis of the blood by gas chromatography with mass spectrometry revealed only lactic acid and glycolic acid. The pH increased markedly after the prolonged bicarbonate dialysis (5 to 14 hours duration). The authors conclude that glycolic acid and lactic acid were responsible for the acidosis in ethylene glycol intoxication and that dialysis with a bicarbonate bath is effective. These conclusions warrant validation with a larger sample and comparison with a control group. Because an internal standard was used only for glycolic acid, it appears uncertain that this assay was sensitive for other suspected organic acids. A selective imidazobenzodiazepine antagonist of ethanol in the rat. Suzdak PD, Glowa JR, Crawley JN, et al. Science 1986;234: 1243- 1247. New drug counters alcohol intoxication. 1986;234: 1198- 1199.
Kolat G. Science 65
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A new imidazobenzodiazepine, Ro 15-45 13, has been shown to block the behavioral effects of ethanol intoxication. Rats made comatose from ethanol appeared sober 2 minutes after receiving this drug. Ethanol acts on the yaminobutyric acid (GABA) receptor which facilitates chloride uptake via the chloride channel. This new drug completely blocks ethanol’s ability to stimulate this receptor, but it may not become available because of legal and ethical drawbacks. Ro15-4513 blocks only the behavioral effects of ethanol and not the other toxic or lethal effects.
ANTIASTHMATIC DRUGS Life-threatening theophylline toxicity is not predictable by serum levels. Aitken ML, Martin TR. Chest 1987;91: lo- 14. The authors studied 51 patients with theophylline levels greater than 40 pg/mL. All of the patients had chronic (iatrogenie) ingestions with a mean level of 50 ug/mL. Several previous authors have recommended hemoperfusion under these circumstances with levels greater than 40 kg/mL. In this series, life-threatening complications (serious ventricular dysrhythmias or seizures) developed in 15%, and death or permanent impairment in 12%. Although the age was significantly greater, the mean serum theophylline level was not different in these 15% from that in the remaining group of patients. Superficial examination of underlying medical problems did not seem to show a correlation with the risk of life-threatening complications. The authors conclude that the blood level is not a reliable predictor of life-threatening complications and that extracorporeal elimination be reserved for those with “serious manifestations” of toxicity. Theophylline toxicity 1986;108:538-542.
in children.
Baker
MD. J Pediatr
Data from 49 children during 65 episodes of theophylline toxicity were evaluated. Seizures occurred in 4 acutely intoxicated children, and all had levels less than 70 pg/mL. There were no cases of death or permanent impairment. The incidence of cardiac, gastrointestinal, and central nervous system symptoms increased with increasing doses. The authors conclude that blood levels alone should not be used as criteria for extracorporeal elimination.
ANTIBIOTICS Cardiac arrest apparently induced by penicilIln. Drug Intell Clin Pharm 1987;21:292.
Stumpf JL.
An 1l-month-old infant was inadvertently administered 500,000 U/kg of penicillin G over 2 minutes, instead of the prescribed 25,000-U/kg dose. This preparation also contained 8.5 mEq of potassium. The infant suffered ventricular dysrhythmias and eventually asystole. He was successfully revived with cardiopulmonary resuscitation and made an apparently uneventful recovery. In general, pediatric doses of greater than 25,000 U/kg should be diluted and administered over 20 minutes. The rapid infusion of potassium may lead to ventricular fibrillation which is often preceded by ventricular premature contractions and ventricular tachycardia. 66
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ANTIDEPRESSANTS Sudden death associated with switching monoamine oxidase inhibitors. Bazire SP. Drug Intel1 Clin Pharm 1986;20:954956. A 61-year-old woman was treated with orphenadrine, flupentixol, and isocarboxazid for 3 weeks for paranoid and delusional depressive symptoms. Because of failure to improve, she was switched from isocarboxazid to tranylcypromine. After four doses, she was found to have a masklike facies, cogwheel rigidity, hyperthermia, tachypnea, headache, photophobia, flushing, and sweating. The patient died within 9 hours of the onset of symptoms. Postmortem examination did not reveal any cause of death. Switching monoamine oxidase inhibitors has been reported in the past to cause severe adverse reactions. The authors also point out that this patient demonstrated many characteristic features of the neuroleptic malignant syndrome. The pathophysiologic basis for this reaction is not clear. Similar reactions have occurred with the initiation of cyclic antidepressant therapy to patients already on monoamine oxidase inhibitors. Level of consciousness as a predictor of complications lowing tricyclic overdose. Emerman CL, Connors Burma GM. Ann Emerg Med 1987;16:326-330.
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Data from 92 patients admitted for cyclic antidepressant overdose were reviewed. Thirty-seven patients (40%) sustained serious complications. Unresponsiveness to verbal stimuli or a Glasgow Coma Scale of less than 8 was the most sensitive and specific predictor of serious complications. The QRS complex was not increased greater than 0.1 second in 2 of 37 patients, but 1 had ingested propranolol and ethanol and the other had seizures on arrival. The serious complications began in less than 30 minutes after arrival in 73%. and in all patients by 2 hours. Tricyclic antidepressant overdose: emergency department findings as predictors of clinical course. Foulke GE, Albertson TE, WaIby WE Am J Emerg Med 1986;4:496500. QRS interval in tricyclic antidepressant overdosage: inaccuracy as a toxicity indicator in emergency settings. Foulke GE, Albertson TE. Ann Emerg Med 1987;16:160-163. These authors reviewed 139 cases admitted for acute cyclic antidepressant overdose. Complications were noted in 23% and included aspiration pneumonia, decreasing consciousness, cardiac dysrhythmias or block, seizures, hypotension, or respiratory failure. Two deaths occurred, one because of the respiratory distress syndrome and the other due to sepsis. No patient experienced major complications without evidence of toxicity in the emergency department. The data suggest that the following signs of toxicity are indications for hospital admission: dysrhythmias, altered consciousness, seizures, conduction blocks, hypotension, and depressed respirations. Patients with isolated QTc prolongation or tachycardia did not experience complications. The authors found no significant correlation between major complications, such as ventricular dysrhythmias and seizures, and the QRS interval. They conclude that a normal QRS interval cannot be relied on to rule out serious toxicity.
MARTIN AND LITOVITZ n TOXICOLOGY: ANNOTATED BIBLIOGRAPHY
Phenytoim does it reverse tricyclic antidepressant-induced cardiac conduction abnormalities? Mayron R, Ruiz E. Ann Emerg Med 1986;15:876-880. In a rabbit model, phenytoin did not delay the onset of conduction abnormalities, increase the lethal dose of antidepressant, or reverse the cardiac dysrhythmias or prolonged conduction. Their literature review supports the challenge of phenytoin efficacy in humans as well.
Late death in tricyclic antidepressant overdose revisited. McAlpine SB, Calabro JJ, Robinson MD, et al. Ann Emerg Med 1986;15:1349-1352. A 4Qyear-old woman presented with severe toxicity from an amitriptyline overdose. Initially, she was comatose, with hypotension, tachycardia, QRS prolongation, and acidosis. She responded to aggressive treatment, including gastric decontamination; multiple-dose charcoal, sodium bicarbonate, norepinephrine, and phenytoin infusions; and charcoal hemoperfusion. The initial serum level was greater than 1000 ng/mL. By 24 hours after admission, the QRS was no longer prolonged, treatment with pressor agents was discontinued, and the combined cyclic antidepressant levels were 337 ng/mL. By 51 hours after admission, the patient was awake with normal vital signs, was extubated, and had been weaned from all infusions. Multiple-dose charcoal treatment was discontinued when she had her first charcoal stool. By 56 hours after admission, she became agitated, with rapidly progressing bradycardia, hypotension, and hypoventilation. The patient arrested within the hour and could not be resuscitated. Postmortem examination did not reveal any other obvious cause of death. Skeptics of previously reported cases of late deterioration propose that these deaths were due to inadequate gastrointestinal decontamination, complications such as respiratory failure or hypoxic encephalopathy, or persistent severe toxicity. None of these factors seem to apply to this case.
Experimental amittiptyline intoxication: treatment of cardiac toxicity with sodium bicarbonate. Sasyniuk BI, Jhamandas V, Valois M. Ann Emerg Med 1986;15: 1052- 1059. In the canine model, these authors demonstrated that ventricular tachyarrhythmias were preceded by marked widening of the QRS complex. There was a significant correlation between the QRS duration and the amitriptyline level. In these animals with either ventricular tachycardia or supraventricular tachycardia with a wide QRS complex, sodium bicarbonate normalized the rhythm and blood pressure. Physostigmine was not effective in three cases of ventricular tachycardia, and although it did slow the heart rate in supraventricular tachycardia, it also dropped the blood pressure further. Propranolol was used in two cases of ventricular tachycardia and normalized the rhythm but also lead to severe hypotension and death. In vitro work is also presented to show the individual beneficial effects of sodium chloride, respiratory alkalosis, and metabolic alkalosis. Sodium bicarbonate was superior to sodium or hypocarbia alone, probably because of a combined effect of supplemental sodium and metabolic alkalosis.
ANTlHlSTAMINES/ANTICHOLINERGlCS Toxic encephalopathy caused by topically applied diphenhy dramhte. Filloux F. J Pediatr 1986;108: 1018- 1020. A 9-year-old boy developed varicella with a pruritic exanthem treated with topically applied 1% diphenhydramine (Caladryl lotion). Two full bottles, or 12 oz (3.6 g). were applied over 48 hours. The child experienced delirium with visual and auditory hallucinations, agitation, confusion, and disorientation. The vital signs revealed a normal temperature, pulse of 16O/bpm, and respirations of 28/minute. The results of a work-up including a spinal tap were nondiagnostic. A serum diphenhydramine level of 1.4 pg/mL was determined, with the toxic level being above 0.6 &mL. The symptoms resolved over 24 hours with discontinuation of the medication. Care must be used in recommending liberal topical diphenhydramine to patients. Diphenhydramine toxicity should be included in the differential diagnosis of the pruritic patient presenting with delirium.
Cardiogenic shock due to antihistamine overdose: reversal with hrtra-aortic balloon counterpulsation. Freedberg RS, Friedman GR, Palu RN, et al. JAMA 1987;257:660-661. This case report describes a 46-year-old woman who allegedly ingested 10 g of pyrilamine, from an over-thecounter sleep aid. The ingestion history was supported by a pyrilamine level of 121 ng/mL and an otherwise negative drug screen. Severe complications included grand mal seizures, oliguria, pulmonary edema, hypotension, and lidoCaine-resistant ventricular tachycardia. Invasive cardiac monitoring with a Swan-Ganz catheter revealed a high pulmonary capillary wedge pressure (26 mm Hg), high systemic vascular resistance (2240 dyne-s/cm5), and a very depressed cardiac index (1.2 Llmin - m2). All of these parameters worsened, and the patient became anuric in response to highdose, multiple-agent pressor therapy. A percutaneous intraaortic balloon pump was inserted under fluoroscopic guidance. Over the next 6 days, the dosages of pressers were tapered, and the balloon was removed on the sixth day after ingestion. By the seventh day the patient was off all pressors and was hemodynamically normal. The authors aptly demonstrate that invasive hemodynamic monitoring and mechanical cardiac assist devices may save critical overdose patients who are unresponsive to conventional therapy.
Clinical symptomatology of diphenhydramine overdose: an evaluation of 136 cases in 1982 to 1985. Koppel C, Ibe K. J Toxic01 Clin Toxic01 1987;25:53-70. This retrospective study reviews 136 cases of diphenhydramine overdose. The number of cases seems to have markedly increased since the drug became nonprescription, with diphenhydramine overdoses now representing 4.5% of all poisonings reported in West Germany. All of these cases were intentional overdoses, yet only one patient died. The death was associated with severe exposure hypothermia. Diphenhydramine levels ranged from 0.1 to 4.7 pg/mL (maximum therapeutic level, 0.1 pg/mL). Impaired conscious67
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ness was the most common symptom; psychotic behavior with catatonia and hallucinations was uncommon. Mydriasis, tachycardia, respiratory insufficiency, and seizures were also reported. A 96% extraction rate with charcoal hemoperfusion was reported in in vitro work, but the Iarge volume of distribution probably limits the usefulness of this modality. Hemodialysis and hemofiltration were performed in one patient with a 61% decrease in the blood level, but a rebound in the level did occur.
ANTUNFLAMMATORYAGENTS Ibuprofen overdose: 126 cases. Hall AH, Smolinske SC, Conrad FL, et al. Ann Emerg Med 1986;15:1308-1313. Ibuprofen overdose alone was evaluated in 126 cases, of which 19% became symptomatic. Adverse effects included central nervous system depression, seizures, acidosis, gastrointestinal disturbances, bradycardia, hypotension, apnea, and decreased renal function. Two children exhibited severe toxicity, and one died. No patients became symptomatic more than 4 hours after ingestion. No patients who ingested less than 99 mg/kg developed symptoms. A correlation between dose and toxicity was found for children but not for adults. Children with an ingested dose of greater than 400 mg/kg have the greatest risk for serious effects. Acute intoxication due to ibuprofen overdose. Lee CY, Finkler A. Arch Path01 Lab Med 1986;110:747-749. The case of a 48-year-old man who ingested over 20 g of ibuprofen alone is reported. The patient displayed a severe metabolic acidosis, hypotension, hemorrhagic gastritis, and acute renal and hepatic injury. The patient recovered with general supportive care. Death due to salicylate poisoning in Ontario. McGuigan MA. Can Med Assoc J 1986;135:891-894. A two-year review of salicylate deaths in Ontario. McGuigan MA. Arch Intern Med 1987;147:510-512. Fifty-one fatal cases of salicylate ingestion occurring from 1983 to 1984 were reviewed from records in the Chief Coroner’s Office. Although this database is limited, some useful facts are presented. Approximately one third of these deaths were classified as dead on arrival and not treatable. Charcoal was found in only 9% of the patients who presented alert and in none of those who presented comatose. Peritoneal dialysis was only attempted in two patients, and none received hemodialysis. Poison centers were only contacted in 21% of cases of patients who presented alive. The authors conclude that these deaths were frequently plagued with management difficulties that may have been avoided by consultation with a regional poison center.
CAUSTICS Digital hydrofluoric acid burns: treatment with intraarterial calcium infusion. Vance MV, Curry SC, Kunkel DB, et al. Ann Emerg Med 1986;15:890-896. Hydrofluoric acid exposure results in inhibition of various calcium-dependent intracellular processes, resulting in se68
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vere pain and tissue destruction. Traditional therapy of fingertip bums has involved nail removal and subcutaneous injections of calcium salts. Selective intraarterial infusion of calcium salts was evaluated in 10 patients. All patients had marked improvement with one to three infusions. Although a control group was not evaluated, intraarterial calcium appears as safe and effective as traditional therapy and is less painful. CARDIOVASCULAR AGENTS Charcoal hemoperfusion for the treatment of a combined diltiazem and metoprolol overdose. Anthony T, Jastremski M, Elliot W, et al. Ann Emerg Med 1986;15: 1344- 1348. A 49-year-old woman presented after allegedly ingesting 1.2 g of diltiazem and 0.5 g of metoprolol. The first sign of toxicity was first-degree block, which suddenly deteriorated to a severe bradycardia (25/minute) with a systolic pressure of 60 mm Hg. The bradycardia responded only to a pacemaker. The hypotension gradually worsened despite highdose pressor therapy. There was no response to glucagon and calcium injections. (The dose of glucagon was 5 to 10 times less than the recommended dose in this situation.) Because the metoprolol blood level was 20 times therapeutic and the diltiazem level only 5 times, metoprolol was thought to be the primary toxin. The patient did improve during and after hemoperfusion, but one cannot determine if she would have done so without the hemoperfusion or with the proper dose of glucagon. Acute pediatric digoxin ingestion. Lewander WJ, Gaudreault P, Einhorn A, et al. Am J Dis Child 1986;140:770-773. This retrospective study of 41 cases of acute digoxin toxicity was conducted at three major pediatric hospitals. The serum digoxin concentrations ranged from 0.2 to 11.6 ng/mL (0.3 to 14.9 nmol/L). Eight of the 10 cases in which peak levels could be estimated demonstrated a peak level in less than 6 hours after ingestion. Bradycardia and first- and second-degree heart block were observed, but no cases of serious ventricular dysrhythmias developed. Only one child had an elevated serum potassium level (5.4 mEq/L). The digoxin half-life was 3 hours in the initial phase and 20 hours in the second phase. Distribution of digoxin has previously been shown to take about 5 to 6 hours. These facts imply that the serum concentration determined less than 6 hours after ingestion may overestimate the severity of the ingestion. The absence of signs and symptoms during the initial presentation does not rule out serious toxicity when the initial level is greater than 3.0 ng/mL. The authors conclude that when the patient is asymptomatic and without electrocardiographic abnormalities for the first 6 hours and the serum level is less than 2 ng/mL, the patient may be safely discharged.
GASTRICDECONTAMINATION
'
In vitro adsorption of sodium pentobarhital by SuperChar, USP and Darco G-60 activated charcoals. Curd-Sneed CD, Parks KS, Bordelon JG, et al. J Toxic01 Clin Toxic01 1987; 25:1-11.
MARTIN AND LITOVITZ
SuperChar is a super-high surface area activated charcoal, the USP formulation a moderately high surface area, and Darco G-60 a low surface area charcoal. In aqueous solutions, the binding capacity of SuperChar (1141 pmol/g) was greater than that of USP (580 FmoVg) or Darco G-60 (381 pmol/g). In a 70% sorbitol solution, the binding capacity of USP and Darco G-60 were not affected, while SuperChar was reduced to 717 p,moYg. Sorbitol did not affect the dissociation constant for USP or Darco G-60 but did increase it for SuperChar. Although this study confirms that superactivated charcoals such as SuperChar have a greater binding capacity, it also suggests that the affinity of this binding is not as great and may be more adversely affected by the presence of cathartics such as sorbitol. Does alcohol absorb to activated charcoal? Hulten BA, Heath A, Mellstrand T, et al. Hum Toxic01 1985;5:211-212. The ability of activated charcoal to inhibit the absorption of ethanol was evaluated in humans. No significant differences were seen in ethanol absorption with or without charcoal. The authors contend that activated charcoal has no place in the treatment of isolated ethanol intoxication. Whole bowel irrigation as a decontamination procedure after acute drug overdose. Tenenbein M, Cohen S, Sitar DS. Arch Intern Med 1987;147:905-907. Whole bowel irrigation was evaluated in nine volunteers in a cross-over fashion 1 hour following the ingestion of 5 g of ampicillin. Polyethylene glycol electrolyte solution was infused via gastric tube by gravity at a rate of 2 L/h for an average of 4 hours. The endpoint of the infusion was the presentation of a rectal effluent similar in appearance to the infusion. This technique reduced the absorption of ampicillin by 67% and had no significant effect on serum electrolytes, hematocrit, osmolality, or body weight. This technique may be particularly well suited for ingestions of sustained-release preparations and iron. Having the patient seated on a commode or cholera bed during the infusion is highly recommended.
HEAVY METALS Pediatric lead poisoning in 1987: the silent epidemic continues [editorial]. Landrigan PJ, Graef JW. Pediatrics 1987;79: 582-583. An insightful update on lead poisoning is presented. Nine percent of preschool children (25% of blacks) have lead levels greater than 25 &dL. Subclinical lead poisoning can occur with levels as low as 5 to 10 &dL and has been shown to affect erythrocytes, peripheral nervous system, kidneys, immune system, bones, and central nervous system. Neuropsychological dysfunction without other clinical symptoms has been documented with levels between 25 and 45 &dL. The American Academy of Pediatrics’ Committee on Environmental Hazards recommends widespread screening of preschool children, including erythrocyte protoporphyrin and hematocrit determinations, along with continued vigorous abatement of all lead hazards. The definitions for lead toxicity have recently been tightened, with an elevated lead level now defined as greater than 25 pg/dL.
n TOXICOLOGY:
ANNOTATED
BIBLIOGRAPHY
Lead toxicity includes a toxic lead level with an erythrocyte protoporphyrin level of greater than 35 pg/dL.
HOUSEHOLD PRODUCTS Fatal outcome of methemoglobinemia in an infant. Johnson CJ, Bonrud PA, Dosch TL, et al. JAMA 1987;257:27962797. An infant who was fed powdered formula mixed with well water was first noted to be intermittently blue at age 2 weeks. When the infant was 4 weeks of age, the mother related a history of intermittent dyspnea, nausea, and vomiting to the physician. At 8 weeks of age, the infant experienced vomiting, severe diarrhea, and severe cyanosis. The family physician gave the child oxygen for 15 minutes and sent the child by car to a hospital 33 miles away. The child arrested enroute and could not be resuscitated in the emergency department. The well water was subsequently tested and found to contain 150 pg/mL nitrate as nitrogen (Environmental Protection Agency permits 10 cLg/mL). Wells used for drinking water are potential environment hazards and should be tested at least yearly for bacterial contamination and nitrates. The authors conclude that methemoglobinemia is preventable and treatable but continues to cause infant mortality. Acute ingestions of boric acid. Linden CH, Hall AH, Kulig KW, et al. J Toxic01 Clin Toxic01 1986;24:269-279. Acute boric acid exposure was evaluated in 364 cases reported to a poison center. Mild symptoms such as vomiting, diarrhea, and abdominal cramps were frequently noted. Systemic symptoms were notably absent. After a review of these cases and the pertinent literature, the authors conclude that serious poisoning from acute ingestion of boric acid is rare. Serum boric acid levels seem to correlate poorly with toxicity. Toxic pneumonitis from mixing household GR, Gammon RS. Chest 1986;89:49-52.
cleaners.
Reisz
Three cases of life-threatening adult respiratory distress syndrome following the inhalation of vapors from a mixture of household bleach and ammonia are described. All three occurred in patients over 53 years old, and short-term residual damage was noted. The toxicity of the mixture of household bleach and ammonia results from the formation of chloramines, which are more toxic than each agent alone. Hazardous effects due to alkaline button battery ingestion: an experimental study. Yasui T. Ann Emerg Med 1986;15: 901-906. This comprehensive investigation represents a significant contribution to the understanding of the mechanism of button-battery injury following ingestion. The role of an electrolytic current external to the battery is defined. The effects of surgical implantation of button batteries in Wistar rats on battery voltage, mucosal pH, and histopathology at the mucosal surface were evaluated. Initially, an electrolytic reaction occurred with a reduction in voltage, rise in mucosal pH, and ulceration or perforation of the mucosa. The 69
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electrolytic reaction was accelerated with lower mucosal pH but still occurred to significant degrees in alkaline pH.
HYDROCARBONS Dlagnosls of chlorinated hydrocarbon poisoning by x-ray examination. Dally S, Gamier R, Bismuth C. Br J Ind Med 1987;44:424-425. A construction worker inadvertently ingested a colorless liquid from an unlabeled bottle. His emesis and breath smelled heavily of a solvent, and symptoms included vomiting, abdominal pain, and diarrhea. Abdominal roentgenogram revealed a radio-opaque liquid in the stomach. Urine and blood analysis revealed chlorinated hydrocarbons. To confirm the radio-opacity of the probable parent chlorinated hydrocarbon, Sprague Dawley rats were administered 1,l , ltrichloroethane, which proved to be radio-opaque. Bottles of other solvents were radiographed, and the radio-opacity seemed to correlate with the degree of chlorination of the compound. Chronic cardiac toxicity after inhalation of l,l, l-trichloroethane. McLeod AA, Majot R, Monaghan MJ, et al. Br Med J 1987;294:727-729. ‘Iwo patients demonstrated chronic cardiac toxicity following repeat exposure to this chlorinated hydrocarbon. Suspicion began after signs of excessive ventricular irritability with administration of halothane anesthesia. The boy had abused (sniffed) trichloroethane for unknown periods, and the man was chronically exposed in his occupation. B-ichloroethane is a solvent used as a degreasing agent and is found in glue, typewritter correction fluid, and drycleaning aids.
NARCOTIC AGONISTS AND ANTAGONISTS Normeperldine toxicity. Armstrong Analg 1986;65:536-538.
PJ, Bersten
A. Anesth
Meperidine is metabolized to a potentially toxic metabolite, normeperidine. Circumstantial evidence suggests that normeperidine produces central nervous system excitation such as tremors, myoclonus, and seizures. Excretion of normeperidine is primarily renal. Naloxone does not reverse normeperidine toxicity. Two cases of apparent normeperidine toxicity from excess accumulation are described. The first occurred in a postoperative patient with disseminated carcinoma who had been given a total of 2800 mg of meperidine over 24 hours. She experienced a grand mal seizure, at which time her normeperidine level was 4.3 ug/mL. The seizure work-up was unrewarding. The second was in a postoperative patient who had received 1008 mg/d of meperidine for 2 weeks. At that time she complained of worsening pain, and myoclonic jerks and increasing agitation were noted. These symptoms resolved when morphine was substituted for the meperidine. Her normeperidine level was 1.6 pg/mL. The mean normeperidine level associated with grand ma1 seizures was 0.81 p,g/mL in a previous study by Kaiko. When prolonged narcotic administration is expected or renal insufficiency is present, a drug without an active metabolite (e.g., morphine) is desired. 70
Failure of nalbuphine to antagonize morphine: a double-blind comparison with naloxone. Bailey PL, Clark NJ, Pace NL, et al. Anesth Analg 1986;65:605-611. Nalbuphine has been touted as an agonist/antagonist with limited respiratory depression and analgesia. It has been suggested as an alternative to naloxone for narcotic-related respiratory depression. The effects of nalbuphine (Nubain) were compared with those of naloxone and placebo after a dose of morphine in a double-blind clinical study. Nalbuphine either did not affect or further depressed respiratory drive and did not alter the pain threshold. Thus, small to moderate amounts of opioid agonist may not be reversed and, indeed, may be potentiated by nalbuphine. Naloxone in the treatment of meperidine-induced seizures. Bontiglio MF, Mauro VE Drug Intel1 Clin Pharm 1986;21: 174- 175. Seizures associated with meperidine administration appear to be related to excess accumulation of normeperidine, the N-demethylated metabolite. Animal studies are reviewed that suggest naloxone does not reverse the seizure activity associated with meperidine use. ‘lwo case reports in humans are discussed, with mixed results regarding efficacy but no complications. The authors emphasize that general supportive care, routine short-term anticonvulsant therapy, and withholding further meperidine therapy comprise the fundamental management of meperidine-related seizures. They provide persuasive evidence that naloxone may not be effective in these cases. Hypertension associated with naloxone treatment for clonldlne poisoning. Gremse DA, Artman M, Boerth RC. J Pediatr 1986;108:776-778. Clonidine is an antihypertensive drug that stimulates alpha-adrenergic receptors in the peripheral vasculature and medulla oblongata, leading to decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature. Naloxone has been shown previously to have variable efficacy in reversing the lethargy and depressed respirations seen in clonidine intoxication. In this report, three children with clonidine toxicity were administered naloxone and developed significant hypertension 0 to 120 minutes after the first dose. The authors hypothesize that by inhibiting the central effects of clonidine, naloxone allows the peripheral vasoconstrictive effects to predominate. It is impossible to differentiate the occasional hypertension sometimes seen in clonidine overdoses from that due to naloxone in this study. These cases suggest that naloxone should be used cautiously with close hemodynamic monitoring in patients with clonidine toxicity. Abuse of pentazocine-naloxone combination. Schnoll SH. JAMA 1986;256:2562-2564.
Reed
DA,
Pentazocine and tripelennamine (T’s and blues) are frequently abused in combination as a heroin substitute. In response, the formulation of pentazocine was modified to include naloxone (‘Ihlwin Nx). Two cases of abuse of this new formulation are described. Both patients reported a rush similar to that following heroin. Three explanations were
MARTIN AND LITOVITZ W TOXICOLOGY: ANNOTATED BIBLIOGRAPHY
suggested for the apparent failure of this formulation: 1) Pentazocine is an agonist at the K and u receptor sites and an antagonist at the F receptor site. Naloxone is only an antagonist at the p receptor site. The rush effect may be from unopposed stimulation of the K or u receptors. 2) The dose of naloxone (0.5 mg/tablet) may not be sufficient. 3) Tripelennamine may produce euphoric or reward-enhancing effects of its own.
NEUROLEPTIC MALIGNANT SYNDROME Peripheral neuropathy as component of the neuroleptic malig nant syndrome. Anderson SA, Weinschenk K. Am J Med 1987;82:169-170. The cases of two patients who developed severe peripheral neuropathies following the classic manifestations of the neuroleptic malignant syndrome are described. Evaluation for other causes of the peripheral neuropathy was negative, and the neuropathies improved over several months. Successful treatment of neuroleptic malignant syndrome with bromocriptine. Janati A, Webb RT. South Med J 1986;79: 1567-1571. Neuroleptic malignant syndrome has been associated with the use of phenothiazines, butyrophenones, thioxanthenes, and sudden withdrawal of antiparkinsonian drugs. Four cases with characteristic manifestations of the syndrome were successfully treated with bromocriptine, 2.5 mg twice daily, increased by 2.5 mg/d to 7.5 mg three times daily. These patients displayed marked improvement within 24 hours. Therapy was required for at least 30 days.
PESTICIDES Clinical confirmation of organophosphate poisoning by serial cholinesterase analysis. Coye MJ, Barnett PG, Midtling JE, et al. Arch Intern Med 1987;147:438-442. Moderate organophosphate poisoning is confirmed by comparing postexposure erythrocyte and plasma cholinesterase activities to baseline preexposure values. Although California requires baseline preexposure testing of pesticide applicators, other states do not. The range of normal cholinesterase activity is wide, and the upper limit of normal may be 200% higher than the lower limit. Thus, if erythrocyte cholinesterase activity is 25% inhibited, 46 to 90% of the population would have activity measured within the normal range. With plasma cholinesterase activity 25% inhibited, 92 to 99% of the population would have activity within the normal range. When baseline preexposure activities are not available, false-negative results may occur frequently in mild to moderate organophosphate intoxication. To avoid these errors, serial cholinesterase levels are advised. Neurotoxic effects of organophosphorus insecticides: an intermediate syndrome. Senanayake N, Karalliedde L. N Engl J Med 1987;316:761-763. Changing profile of pesticide poisoning [editorial]. Davies JE. N Engl J Med 1987;316:807-808. This article and its commentary focus on an intermediate syndrome observed in 10 persons with organophosphate
poisoning in Sri Lanka. This syndrome is characterized by an onset at 24 to % hours; weakness of the proximal limb, neck flexors, and respiratory muscles; and cranial nerve motor dysfunction. It followed the appearance of classic cholinergic signs in all patients and was unresponsive to atropine. Four patients required mechanical ventilation for up to 15 days; 3 patients died from ventilatory failure. Electromyographic studies suggested a postsynaptic defect. Resolution followed a characteristic pattern, with cranial nerves recovering first and then respiratory, proximal limb, and neck flexor muscles. Four different organophosphates were responsible, with the highest incidence in monocrotophos exposures (22%).
STREET DRUGS Perinatal cerebral infarction and maternal cocaine use. Chasnoff IJ, Bussey ME, Savich R, et al. J Pediatr 1986;108: 456-459. A newborn developed a cerebral infarction shortly after delivery. The child’s mother had abused cocaine during the preceding 72 hours. Urine analysis revealed benzoylecgonine (a cocaine metabolite) in the infant’s urine for 4 days. Other well-documented obstetrical complications of maternal cocaine abuse include spontaneous abortion and abruptio placentae. New treatment for PCP toxicity? 1987;257:3188.
Macdonald
DI. JAMA
Phencyclidine (PCP)-specific goat Fab antibody fragments have been investigated in dogs. The affinity of PCP for this Fab fragment is 700 times greater than for its neuronal receptor. In dogs given tracer amounts of PCP, favorable changes in volume of distribution and bound fraction occurred. Experiments with higher doses of PCP are in progress. Previous work with digoxin suggests that the large volume of distribution and protein binding do not interfere with the efficacy of Fab antibodies. Botulism and botulism-like illness in chronic drug abusers. MacDonald KL, Rutherford GW, Friedman SM, et al. Ann Intern Med 1985;102:616-618. Six parenteral drug abusers were reported who had botulism suspected to be of wound origin. Wound botulism results from toxin production by Clostridium botulinum growing in the wound. Wounds harboring C. botulinum may not look infected, which may delay appropriate therapy. The syndrome starts with cranial nerve dysfunction (usually dysphagia), followed by a progressive descending paralysis. To be maximally effective, botulinal antitoxin must be given as soon as possible after the onset of symptoms (preferably ~24 hours). The diagnosis can be confirmed with a positive wound culture, while the serum tests are usually negative. The authors recommend that all abscesses on intravenous drug abusers be cultured for anaerobic organisms and incised and drained. Patients with these symptoms should receive appropriate antibiotics (usually penicillin) and botulinal antitoxin. 71
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Cocaine-associated myocardia ischemia: review of clinical and angiographic findings. Mathias DW. Am J Med 1986;81: 675-678. Acute cardiac events temporally related to cocaine abuse. Isner JM, Estes M, Thompson PD, et al. N Engl J Med 1986;315: 1438- 1443. Acute myocardial infarction temporally related to cocaine use: clinical, angiographic, and pathophysiologic observations. Smith HWB, Liverman HA, Brody SL, et al. Ann Intern Med 1987;107:13- 18. Cases from Milwaukee, Boston, and Atlanta of ischemic chest pain and myocardial infarction temporally related to cocaine use are reported. Chest pain was the presenting symptom, and the electrocardiogram revealed obvious signs of ischemia or infarction in almost all of these patients. Most of the patients were young, with a mean age of 31.4 years. Risk factors were present in the majority, but some patients had none. Men comprised the majority (90%) of the patients. When performed, coronary angiography revealed abnormalities in the infarct-related vessels in two thirds of cases. If angiography had been done closer to the time of infarction, the yield might have been even higher. In a few, coronary thrombosis was lysed with thrombolytic therapy, and normal underlying vessels were revealed. Those patients
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challenged with ergonovine did not demonstrate coronary spasm. Most patients survived this infarction, but recurrent infarction and sustained prolonged ischemia occurred in a few who continued to abuse cocaine. Cardiogenic shock and cardiac arrest were rare complications. These data are enlightening but may be biased by the retrospective nature of the studies. These studies indicate that complications are not limited to intravenous abusers and that fixed coronary artery disease or high risk factors are not prerequisites. A history of cocaine use should be sought in young patients with coronary ischemia-like symptoms.
PCP intoxication in seven young children. Schwartz RH, Einhorn A. Pediatr Emerg Care 1986;2:238-241. Seven children were treated at a large children’s hospital for phencyclidine (PCP) toxicity. The most common symptoms were neurologic and included lethargy, decreased responsiveness to stimuli (often associated with a blank stare), ataxia, nystagmus, and miosis. The authors suggest that children are very sensitive to PCP and may develop serious neurologic signs with minimal exposure. They recommend toxicologic screens routinely in children with unexplained coma, hypotonia, seizures, or a blank stare.
Toxicology: An Annotated Bibliography of the Recent Literature THOMAS ACETAMINOPHEN Prediction of acetaminophen level from clinical history of overdose using a pharmacokinetic model. Edwards DA, Fish SF, Lamson MJ, et al. Ann Emerg Med 1986;lS: 1314-1319. This study analyzed the first levels drawn in 26 patients prior to spontaneous or induced gastric emptying. The measured level was compared with that predicted from a onecompartment pharmacokinetic model with first-order absorption and elimination. A good correlation was found in patients with levels drawn more than 2 hours after ingestion. The formula reduces to: plasma level at 4 hours = (0.59) (ingested dose in mg/kg). This study challenges the widespread belief that ingestion histories are unreliable in overdose patients. Coma and metabolic acidosis early in severe acute paracetamol poisoning. Flanagan RJ, Mant TGK. Hum Toxic01 1986;5: 179- 182. The cases of five patients with severe acetaminophen poisoning (levels >800 pg/mL between 4 and 12 hours after ingestion) are described. Four patients were deeply comatose, and two had a metabolic acidosis. Toxicologic analysis of the blood and urine revealed only one patient with a significant coingestion (serum salicylate level of 29 mg/dL). Halflives were prolonged with a mean value of 9.4 hours and range of 4.8 to 39 hours. The authors conclude that massive acetaminophen overdose without coingestants can present with coma and acidosis without signs of hepatic failure.
ALCOHOLS 4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man. Baud FJ, Bismuth C, Gamier R, et al. J Toxic01 Clin Toxic01 1986-7;24:463483. From the Department of Emergency versity Hospital, Washington, DC.
Medicine,
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4-Methylpyrazole (4-MP) is a potent inhibitor of alcohol dehydrogenase but is not approved for clinical use in the United States. 4-MP, 20 mg/kg * d, was used in three cases of ethylene glycol intoxication treated in France. In animal studies, 4-MP has not been found to be as toxic as the parent pyrazole compound. The elimination half-life of ethylene glycol was not determined before treatment with 4-MP and ranged from 11.5 to 14.75 hours after treatment in these cases. This corresponds to the half-life of 17 hours in patients blocked with ethanol. The renal ethylene glycol clearance during 4-MP treatment in one patient was 17 mL/min. Plasma oxalate levels were determined in two patients and returned to normal within 13 to 21 hours. Apparent side effects included a rash in one patient, eosinophilia in two patients, and mild elevations in the aspartate aminotransferase and creatinine phosphokinase levels in two patients. 4-MP appears to be a safe yet effective antidote for ethylene glycol intoxication, but more patients must be evaluated with scrutiny for allergic or hepatotoxic effects. Organic acids in ethylene glycol intoxication. Gabow PA, Clay K, Sullivan JB, et al. Ann Intern Med 1986;105:16-20. Ethylene glycol intoxication was evaluated in three patients to identify the organic acids responsible for the acidosis and the efficacy of hemodialysis with a bicarbonate dialysate. Animal studies have previously demonstrated that the major organic acid is glycolic acid, but this finding had not been verified in humans. At the time of analysis, the pH values ranged from 7.17 to 7.26. The analysis of the blood by gas chromatography with mass spectrometry revealed only lactic acid and glycolic acid. The pH increased markedly after the prolonged bicarbonate dialysis (5 to 14 hours duration). The authors conclude that glycolic acid and lactic acid were responsible for the acidosis in ethylene glycol intoxication and that dialysis with a bicarbonate bath is effective. These conclusions warrant validation with a larger sample and comparison with a control group. Because an internal standard was used only for glycolic acid, it appears uncertain that this assay was sensitive for other suspected organic acids. A selective imidazobenzodiazepine antagonist of ethanol in the rat. Suzdak PD, Glowa JR, Crawley JN, et al. Science 1986;234: 1243- 1247. New drug counters alcohol intoxication. 1986;234: 1198- 1199.
Kolat G. Science 65
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A new imidazobenzodiazepine, Ro 15-45 13, has been shown to block the behavioral effects of ethanol intoxication. Rats made comatose from ethanol appeared sober 2 minutes after receiving this drug. Ethanol acts on the yaminobutyric acid (GABA) receptor which facilitates chloride uptake via the chloride channel. This new drug completely blocks ethanol’s ability to stimulate this receptor, but it may not become available because of legal and ethical drawbacks. Ro15-4513 blocks only the behavioral effects of ethanol and not the other toxic or lethal effects.
ANTIASTHMATIC DRUGS Life-threatening theophylline toxicity is not predictable by serum levels. Aitken ML, Martin TR. Chest 1987;91: lo- 14. The authors studied 51 patients with theophylline levels greater than 40 pg/mL. All of the patients had chronic (iatrogenie) ingestions with a mean level of 50 ug/mL. Several previous authors have recommended hemoperfusion under these circumstances with levels greater than 40 kg/mL. In this series, life-threatening complications (serious ventricular dysrhythmias or seizures) developed in 15%, and death or permanent impairment in 12%. Although the age was significantly greater, the mean serum theophylline level was not different in these 15% from that in the remaining group of patients. Superficial examination of underlying medical problems did not seem to show a correlation with the risk of life-threatening complications. The authors conclude that the blood level is not a reliable predictor of life-threatening complications and that extracorporeal elimination be reserved for those with “serious manifestations” of toxicity. Theophylline toxicity 1986;108:538-542.
in children.
Baker
MD. J Pediatr
Data from 49 children during 65 episodes of theophylline toxicity were evaluated. Seizures occurred in 4 acutely intoxicated children, and all had levels less than 70 pg/mL. There were no cases of death or permanent impairment. The incidence of cardiac, gastrointestinal, and central nervous system symptoms increased with increasing doses. The authors conclude that blood levels alone should not be used as criteria for extracorporeal elimination.
ANTIBIOTICS Cardiac arrest apparently induced by penicilIln. Drug Intell Clin Pharm 1987;21:292.
Stumpf JL.
An 1l-month-old infant was inadvertently administered 500,000 U/kg of penicillin G over 2 minutes, instead of the prescribed 25,000-U/kg dose. This preparation also contained 8.5 mEq of potassium. The infant suffered ventricular dysrhythmias and eventually asystole. He was successfully revived with cardiopulmonary resuscitation and made an apparently uneventful recovery. In general, pediatric doses of greater than 25,000 U/kg should be diluted and administered over 20 minutes. The rapid infusion of potassium may lead to ventricular fibrillation which is often preceded by ventricular premature contractions and ventricular tachycardia. 66
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ANTIDEPRESSANTS Sudden death associated with switching monoamine oxidase inhibitors. Bazire SP. Drug Intel1 Clin Pharm 1986;20:954956. A 61-year-old woman was treated with orphenadrine, flupentixol, and isocarboxazid for 3 weeks for paranoid and delusional depressive symptoms. Because of failure to improve, she was switched from isocarboxazid to tranylcypromine. After four doses, she was found to have a masklike facies, cogwheel rigidity, hyperthermia, tachypnea, headache, photophobia, flushing, and sweating. The patient died within 9 hours of the onset of symptoms. Postmortem examination did not reveal any cause of death. Switching monoamine oxidase inhibitors has been reported in the past to cause severe adverse reactions. The authors also point out that this patient demonstrated many characteristic features of the neuroleptic malignant syndrome. The pathophysiologic basis for this reaction is not clear. Similar reactions have occurred with the initiation of cyclic antidepressant therapy to patients already on monoamine oxidase inhibitors. Level of consciousness as a predictor of complications lowing tricyclic overdose. Emerman CL, Connors Burma GM. Ann Emerg Med 1987;16:326-330.
folAF,
Data from 92 patients admitted for cyclic antidepressant overdose were reviewed. Thirty-seven patients (40%) sustained serious complications. Unresponsiveness to verbal stimuli or a Glasgow Coma Scale of less than 8 was the most sensitive and specific predictor of serious complications. The QRS complex was not increased greater than 0.1 second in 2 of 37 patients, but 1 had ingested propranolol and ethanol and the other had seizures on arrival. The serious complications began in less than 30 minutes after arrival in 73%. and in all patients by 2 hours. Tricyclic antidepressant overdose: emergency department findings as predictors of clinical course. Foulke GE, Albertson TE, WaIby WE Am J Emerg Med 1986;4:496500. QRS interval in tricyclic antidepressant overdosage: inaccuracy as a toxicity indicator in emergency settings. Foulke GE, Albertson TE. Ann Emerg Med 1987;16:160-163. These authors reviewed 139 cases admitted for acute cyclic antidepressant overdose. Complications were noted in 23% and included aspiration pneumonia, decreasing consciousness, cardiac dysrhythmias or block, seizures, hypotension, or respiratory failure. Two deaths occurred, one because of the respiratory distress syndrome and the other due to sepsis. No patient experienced major complications without evidence of toxicity in the emergency department. The data suggest that the following signs of toxicity are indications for hospital admission: dysrhythmias, altered consciousness, seizures, conduction blocks, hypotension, and depressed respirations. Patients with isolated QTc prolongation or tachycardia did not experience complications. The authors found no significant correlation between major complications, such as ventricular dysrhythmias and seizures, and the QRS interval. They conclude that a normal QRS interval cannot be relied on to rule out serious toxicity.
MARTIN AND LITOVITZ n TOXICOLOGY: ANNOTATED BIBLIOGRAPHY
Phenytoim does it reverse tricyclic antidepressant-induced cardiac conduction abnormalities? Mayron R, Ruiz E. Ann Emerg Med 1986;15:876-880. In a rabbit model, phenytoin did not delay the onset of conduction abnormalities, increase the lethal dose of antidepressant, or reverse the cardiac dysrhythmias or prolonged conduction. Their literature review supports the challenge of phenytoin efficacy in humans as well.
Late death in tricyclic antidepressant overdose revisited. McAlpine SB, Calabro JJ, Robinson MD, et al. Ann Emerg Med 1986;15:1349-1352. A 4Qyear-old woman presented with severe toxicity from an amitriptyline overdose. Initially, she was comatose, with hypotension, tachycardia, QRS prolongation, and acidosis. She responded to aggressive treatment, including gastric decontamination; multiple-dose charcoal, sodium bicarbonate, norepinephrine, and phenytoin infusions; and charcoal hemoperfusion. The initial serum level was greater than 1000 ng/mL. By 24 hours after admission, the QRS was no longer prolonged, treatment with pressor agents was discontinued, and the combined cyclic antidepressant levels were 337 ng/mL. By 51 hours after admission, the patient was awake with normal vital signs, was extubated, and had been weaned from all infusions. Multiple-dose charcoal treatment was discontinued when she had her first charcoal stool. By 56 hours after admission, she became agitated, with rapidly progressing bradycardia, hypotension, and hypoventilation. The patient arrested within the hour and could not be resuscitated. Postmortem examination did not reveal any other obvious cause of death. Skeptics of previously reported cases of late deterioration propose that these deaths were due to inadequate gastrointestinal decontamination, complications such as respiratory failure or hypoxic encephalopathy, or persistent severe toxicity. None of these factors seem to apply to this case.
Experimental amittiptyline intoxication: treatment of cardiac toxicity with sodium bicarbonate. Sasyniuk BI, Jhamandas V, Valois M. Ann Emerg Med 1986;15: 1052- 1059. In the canine model, these authors demonstrated that ventricular tachyarrhythmias were preceded by marked widening of the QRS complex. There was a significant correlation between the QRS duration and the amitriptyline level. In these animals with either ventricular tachycardia or supraventricular tachycardia with a wide QRS complex, sodium bicarbonate normalized the rhythm and blood pressure. Physostigmine was not effective in three cases of ventricular tachycardia, and although it did slow the heart rate in supraventricular tachycardia, it also dropped the blood pressure further. Propranolol was used in two cases of ventricular tachycardia and normalized the rhythm but also lead to severe hypotension and death. In vitro work is also presented to show the individual beneficial effects of sodium chloride, respiratory alkalosis, and metabolic alkalosis. Sodium bicarbonate was superior to sodium or hypocarbia alone, probably because of a combined effect of supplemental sodium and metabolic alkalosis.
ANTlHlSTAMINES/ANTICHOLINERGlCS Toxic encephalopathy caused by topically applied diphenhy dramhte. Filloux F. J Pediatr 1986;108: 1018- 1020. A 9-year-old boy developed varicella with a pruritic exanthem treated with topically applied 1% diphenhydramine (Caladryl lotion). Two full bottles, or 12 oz (3.6 g). were applied over 48 hours. The child experienced delirium with visual and auditory hallucinations, agitation, confusion, and disorientation. The vital signs revealed a normal temperature, pulse of 16O/bpm, and respirations of 28/minute. The results of a work-up including a spinal tap were nondiagnostic. A serum diphenhydramine level of 1.4 pg/mL was determined, with the toxic level being above 0.6 &mL. The symptoms resolved over 24 hours with discontinuation of the medication. Care must be used in recommending liberal topical diphenhydramine to patients. Diphenhydramine toxicity should be included in the differential diagnosis of the pruritic patient presenting with delirium.
Cardiogenic shock due to antihistamine overdose: reversal with hrtra-aortic balloon counterpulsation. Freedberg RS, Friedman GR, Palu RN, et al. JAMA 1987;257:660-661. This case report describes a 46-year-old woman who allegedly ingested 10 g of pyrilamine, from an over-thecounter sleep aid. The ingestion history was supported by a pyrilamine level of 121 ng/mL and an otherwise negative drug screen. Severe complications included grand mal seizures, oliguria, pulmonary edema, hypotension, and lidoCaine-resistant ventricular tachycardia. Invasive cardiac monitoring with a Swan-Ganz catheter revealed a high pulmonary capillary wedge pressure (26 mm Hg), high systemic vascular resistance (2240 dyne-s/cm5), and a very depressed cardiac index (1.2 Llmin - m2). All of these parameters worsened, and the patient became anuric in response to highdose, multiple-agent pressor therapy. A percutaneous intraaortic balloon pump was inserted under fluoroscopic guidance. Over the next 6 days, the dosages of pressers were tapered, and the balloon was removed on the sixth day after ingestion. By the seventh day the patient was off all pressors and was hemodynamically normal. The authors aptly demonstrate that invasive hemodynamic monitoring and mechanical cardiac assist devices may save critical overdose patients who are unresponsive to conventional therapy.
Clinical symptomatology of diphenhydramine overdose: an evaluation of 136 cases in 1982 to 1985. Koppel C, Ibe K. J Toxic01 Clin Toxic01 1987;25:53-70. This retrospective study reviews 136 cases of diphenhydramine overdose. The number of cases seems to have markedly increased since the drug became nonprescription, with diphenhydramine overdoses now representing 4.5% of all poisonings reported in West Germany. All of these cases were intentional overdoses, yet only one patient died. The death was associated with severe exposure hypothermia. Diphenhydramine levels ranged from 0.1 to 4.7 pg/mL (maximum therapeutic level, 0.1 pg/mL). Impaired conscious67
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ness was the most common symptom; psychotic behavior with catatonia and hallucinations was uncommon. Mydriasis, tachycardia, respiratory insufficiency, and seizures were also reported. A 96% extraction rate with charcoal hemoperfusion was reported in in vitro work, but the Iarge volume of distribution probably limits the usefulness of this modality. Hemodialysis and hemofiltration were performed in one patient with a 61% decrease in the blood level, but a rebound in the level did occur.
ANTUNFLAMMATORYAGENTS Ibuprofen overdose: 126 cases. Hall AH, Smolinske SC, Conrad FL, et al. Ann Emerg Med 1986;15:1308-1313. Ibuprofen overdose alone was evaluated in 126 cases, of which 19% became symptomatic. Adverse effects included central nervous system depression, seizures, acidosis, gastrointestinal disturbances, bradycardia, hypotension, apnea, and decreased renal function. Two children exhibited severe toxicity, and one died. No patients became symptomatic more than 4 hours after ingestion. No patients who ingested less than 99 mg/kg developed symptoms. A correlation between dose and toxicity was found for children but not for adults. Children with an ingested dose of greater than 400 mg/kg have the greatest risk for serious effects. Acute intoxication due to ibuprofen overdose. Lee CY, Finkler A. Arch Path01 Lab Med 1986;110:747-749. The case of a 48-year-old man who ingested over 20 g of ibuprofen alone is reported. The patient displayed a severe metabolic acidosis, hypotension, hemorrhagic gastritis, and acute renal and hepatic injury. The patient recovered with general supportive care. Death due to salicylate poisoning in Ontario. McGuigan MA. Can Med Assoc J 1986;135:891-894. A two-year review of salicylate deaths in Ontario. McGuigan MA. Arch Intern Med 1987;147:510-512. Fifty-one fatal cases of salicylate ingestion occurring from 1983 to 1984 were reviewed from records in the Chief Coroner’s Office. Although this database is limited, some useful facts are presented. Approximately one third of these deaths were classified as dead on arrival and not treatable. Charcoal was found in only 9% of the patients who presented alert and in none of those who presented comatose. Peritoneal dialysis was only attempted in two patients, and none received hemodialysis. Poison centers were only contacted in 21% of cases of patients who presented alive. The authors conclude that these deaths were frequently plagued with management difficulties that may have been avoided by consultation with a regional poison center.
CAUSTICS Digital hydrofluoric acid burns: treatment with intraarterial calcium infusion. Vance MV, Curry SC, Kunkel DB, et al. Ann Emerg Med 1986;15:890-896. Hydrofluoric acid exposure results in inhibition of various calcium-dependent intracellular processes, resulting in se68
1 n January
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vere pain and tissue destruction. Traditional therapy of fingertip bums has involved nail removal and subcutaneous injections of calcium salts. Selective intraarterial infusion of calcium salts was evaluated in 10 patients. All patients had marked improvement with one to three infusions. Although a control group was not evaluated, intraarterial calcium appears as safe and effective as traditional therapy and is less painful. CARDIOVASCULAR AGENTS Charcoal hemoperfusion for the treatment of a combined diltiazem and metoprolol overdose. Anthony T, Jastremski M, Elliot W, et al. Ann Emerg Med 1986;15: 1344- 1348. A 49-year-old woman presented after allegedly ingesting 1.2 g of diltiazem and 0.5 g of metoprolol. The first sign of toxicity was first-degree block, which suddenly deteriorated to a severe bradycardia (25/minute) with a systolic pressure of 60 mm Hg. The bradycardia responded only to a pacemaker. The hypotension gradually worsened despite highdose pressor therapy. There was no response to glucagon and calcium injections. (The dose of glucagon was 5 to 10 times less than the recommended dose in this situation.) Because the metoprolol blood level was 20 times therapeutic and the diltiazem level only 5 times, metoprolol was thought to be the primary toxin. The patient did improve during and after hemoperfusion, but one cannot determine if she would have done so without the hemoperfusion or with the proper dose of glucagon. Acute pediatric digoxin ingestion. Lewander WJ, Gaudreault P, Einhorn A, et al. Am J Dis Child 1986;140:770-773. This retrospective study of 41 cases of acute digoxin toxicity was conducted at three major pediatric hospitals. The serum digoxin concentrations ranged from 0.2 to 11.6 ng/mL (0.3 to 14.9 nmol/L). Eight of the 10 cases in which peak levels could be estimated demonstrated a peak level in less than 6 hours after ingestion. Bradycardia and first- and second-degree heart block were observed, but no cases of serious ventricular dysrhythmias developed. Only one child had an elevated serum potassium level (5.4 mEq/L). The digoxin half-life was 3 hours in the initial phase and 20 hours in the second phase. Distribution of digoxin has previously been shown to take about 5 to 6 hours. These facts imply that the serum concentration determined less than 6 hours after ingestion may overestimate the severity of the ingestion. The absence of signs and symptoms during the initial presentation does not rule out serious toxicity when the initial level is greater than 3.0 ng/mL. The authors conclude that when the patient is asymptomatic and without electrocardiographic abnormalities for the first 6 hours and the serum level is less than 2 ng/mL, the patient may be safely discharged.
GASTRICDECONTAMINATION
'
In vitro adsorption of sodium pentobarhital by SuperChar, USP and Darco G-60 activated charcoals. Curd-Sneed CD, Parks KS, Bordelon JG, et al. J Toxic01 Clin Toxic01 1987; 25:1-11.
MARTIN AND LITOVITZ
SuperChar is a super-high surface area activated charcoal, the USP formulation a moderately high surface area, and Darco G-60 a low surface area charcoal. In aqueous solutions, the binding capacity of SuperChar (1141 pmol/g) was greater than that of USP (580 FmoVg) or Darco G-60 (381 pmol/g). In a 70% sorbitol solution, the binding capacity of USP and Darco G-60 were not affected, while SuperChar was reduced to 717 p,moYg. Sorbitol did not affect the dissociation constant for USP or Darco G-60 but did increase it for SuperChar. Although this study confirms that superactivated charcoals such as SuperChar have a greater binding capacity, it also suggests that the affinity of this binding is not as great and may be more adversely affected by the presence of cathartics such as sorbitol. Does alcohol absorb to activated charcoal? Hulten BA, Heath A, Mellstrand T, et al. Hum Toxic01 1985;5:211-212. The ability of activated charcoal to inhibit the absorption of ethanol was evaluated in humans. No significant differences were seen in ethanol absorption with or without charcoal. The authors contend that activated charcoal has no place in the treatment of isolated ethanol intoxication. Whole bowel irrigation as a decontamination procedure after acute drug overdose. Tenenbein M, Cohen S, Sitar DS. Arch Intern Med 1987;147:905-907. Whole bowel irrigation was evaluated in nine volunteers in a cross-over fashion 1 hour following the ingestion of 5 g of ampicillin. Polyethylene glycol electrolyte solution was infused via gastric tube by gravity at a rate of 2 L/h for an average of 4 hours. The endpoint of the infusion was the presentation of a rectal effluent similar in appearance to the infusion. This technique reduced the absorption of ampicillin by 67% and had no significant effect on serum electrolytes, hematocrit, osmolality, or body weight. This technique may be particularly well suited for ingestions of sustained-release preparations and iron. Having the patient seated on a commode or cholera bed during the infusion is highly recommended.
HEAVY METALS Pediatric lead poisoning in 1987: the silent epidemic continues [editorial]. Landrigan PJ, Graef JW. Pediatrics 1987;79: 582-583. An insightful update on lead poisoning is presented. Nine percent of preschool children (25% of blacks) have lead levels greater than 25 &dL. Subclinical lead poisoning can occur with levels as low as 5 to 10 &dL and has been shown to affect erythrocytes, peripheral nervous system, kidneys, immune system, bones, and central nervous system. Neuropsychological dysfunction without other clinical symptoms has been documented with levels between 25 and 45 &dL. The American Academy of Pediatrics’ Committee on Environmental Hazards recommends widespread screening of preschool children, including erythrocyte protoporphyrin and hematocrit determinations, along with continued vigorous abatement of all lead hazards. The definitions for lead toxicity have recently been tightened, with an elevated lead level now defined as greater than 25 pg/dL.
n TOXICOLOGY:
ANNOTATED
BIBLIOGRAPHY
Lead toxicity includes a toxic lead level with an erythrocyte protoporphyrin level of greater than 35 pg/dL.
HOUSEHOLD PRODUCTS Fatal outcome of methemoglobinemia in an infant. Johnson CJ, Bonrud PA, Dosch TL, et al. JAMA 1987;257:27962797. An infant who was fed powdered formula mixed with well water was first noted to be intermittently blue at age 2 weeks. When the infant was 4 weeks of age, the mother related a history of intermittent dyspnea, nausea, and vomiting to the physician. At 8 weeks of age, the infant experienced vomiting, severe diarrhea, and severe cyanosis. The family physician gave the child oxygen for 15 minutes and sent the child by car to a hospital 33 miles away. The child arrested enroute and could not be resuscitated in the emergency department. The well water was subsequently tested and found to contain 150 pg/mL nitrate as nitrogen (Environmental Protection Agency permits 10 cLg/mL). Wells used for drinking water are potential environment hazards and should be tested at least yearly for bacterial contamination and nitrates. The authors conclude that methemoglobinemia is preventable and treatable but continues to cause infant mortality. Acute ingestions of boric acid. Linden CH, Hall AH, Kulig KW, et al. J Toxic01 Clin Toxic01 1986;24:269-279. Acute boric acid exposure was evaluated in 364 cases reported to a poison center. Mild symptoms such as vomiting, diarrhea, and abdominal cramps were frequently noted. Systemic symptoms were notably absent. After a review of these cases and the pertinent literature, the authors conclude that serious poisoning from acute ingestion of boric acid is rare. Serum boric acid levels seem to correlate poorly with toxicity. Toxic pneumonitis from mixing household GR, Gammon RS. Chest 1986;89:49-52.
cleaners.
Reisz
Three cases of life-threatening adult respiratory distress syndrome following the inhalation of vapors from a mixture of household bleach and ammonia are described. All three occurred in patients over 53 years old, and short-term residual damage was noted. The toxicity of the mixture of household bleach and ammonia results from the formation of chloramines, which are more toxic than each agent alone. Hazardous effects due to alkaline button battery ingestion: an experimental study. Yasui T. Ann Emerg Med 1986;15: 901-906. This comprehensive investigation represents a significant contribution to the understanding of the mechanism of button-battery injury following ingestion. The role of an electrolytic current external to the battery is defined. The effects of surgical implantation of button batteries in Wistar rats on battery voltage, mucosal pH, and histopathology at the mucosal surface were evaluated. Initially, an electrolytic reaction occurred with a reduction in voltage, rise in mucosal pH, and ulceration or perforation of the mucosa. The 69
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electrolytic reaction was accelerated with lower mucosal pH but still occurred to significant degrees in alkaline pH.
HYDROCARBONS Dlagnosls of chlorinated hydrocarbon poisoning by x-ray examination. Dally S, Gamier R, Bismuth C. Br J Ind Med 1987;44:424-425. A construction worker inadvertently ingested a colorless liquid from an unlabeled bottle. His emesis and breath smelled heavily of a solvent, and symptoms included vomiting, abdominal pain, and diarrhea. Abdominal roentgenogram revealed a radio-opaque liquid in the stomach. Urine and blood analysis revealed chlorinated hydrocarbons. To confirm the radio-opacity of the probable parent chlorinated hydrocarbon, Sprague Dawley rats were administered 1,l , ltrichloroethane, which proved to be radio-opaque. Bottles of other solvents were radiographed, and the radio-opacity seemed to correlate with the degree of chlorination of the compound. Chronic cardiac toxicity after inhalation of l,l, l-trichloroethane. McLeod AA, Majot R, Monaghan MJ, et al. Br Med J 1987;294:727-729. ‘Iwo patients demonstrated chronic cardiac toxicity following repeat exposure to this chlorinated hydrocarbon. Suspicion began after signs of excessive ventricular irritability with administration of halothane anesthesia. The boy had abused (sniffed) trichloroethane for unknown periods, and the man was chronically exposed in his occupation. B-ichloroethane is a solvent used as a degreasing agent and is found in glue, typewritter correction fluid, and drycleaning aids.
NARCOTIC AGONISTS AND ANTAGONISTS Normeperldine toxicity. Armstrong Analg 1986;65:536-538.
PJ, Bersten
A. Anesth
Meperidine is metabolized to a potentially toxic metabolite, normeperidine. Circumstantial evidence suggests that normeperidine produces central nervous system excitation such as tremors, myoclonus, and seizures. Excretion of normeperidine is primarily renal. Naloxone does not reverse normeperidine toxicity. Two cases of apparent normeperidine toxicity from excess accumulation are described. The first occurred in a postoperative patient with disseminated carcinoma who had been given a total of 2800 mg of meperidine over 24 hours. She experienced a grand mal seizure, at which time her normeperidine level was 4.3 ug/mL. The seizure work-up was unrewarding. The second was in a postoperative patient who had received 1008 mg/d of meperidine for 2 weeks. At that time she complained of worsening pain, and myoclonic jerks and increasing agitation were noted. These symptoms resolved when morphine was substituted for the meperidine. Her normeperidine level was 1.6 pg/mL. The mean normeperidine level associated with grand ma1 seizures was 0.81 p,g/mL in a previous study by Kaiko. When prolonged narcotic administration is expected or renal insufficiency is present, a drug without an active metabolite (e.g., morphine) is desired. 70
Failure of nalbuphine to antagonize morphine: a double-blind comparison with naloxone. Bailey PL, Clark NJ, Pace NL, et al. Anesth Analg 1986;65:605-611. Nalbuphine has been touted as an agonist/antagonist with limited respiratory depression and analgesia. It has been suggested as an alternative to naloxone for narcotic-related respiratory depression. The effects of nalbuphine (Nubain) were compared with those of naloxone and placebo after a dose of morphine in a double-blind clinical study. Nalbuphine either did not affect or further depressed respiratory drive and did not alter the pain threshold. Thus, small to moderate amounts of opioid agonist may not be reversed and, indeed, may be potentiated by nalbuphine. Naloxone in the treatment of meperidine-induced seizures. Bontiglio MF, Mauro VE Drug Intel1 Clin Pharm 1986;21: 174- 175. Seizures associated with meperidine administration appear to be related to excess accumulation of normeperidine, the N-demethylated metabolite. Animal studies are reviewed that suggest naloxone does not reverse the seizure activity associated with meperidine use. ‘lwo case reports in humans are discussed, with mixed results regarding efficacy but no complications. The authors emphasize that general supportive care, routine short-term anticonvulsant therapy, and withholding further meperidine therapy comprise the fundamental management of meperidine-related seizures. They provide persuasive evidence that naloxone may not be effective in these cases. Hypertension associated with naloxone treatment for clonldlne poisoning. Gremse DA, Artman M, Boerth RC. J Pediatr 1986;108:776-778. Clonidine is an antihypertensive drug that stimulates alpha-adrenergic receptors in the peripheral vasculature and medulla oblongata, leading to decreased sympathetic outflow to the heart, kidneys, and peripheral vasculature. Naloxone has been shown previously to have variable efficacy in reversing the lethargy and depressed respirations seen in clonidine intoxication. In this report, three children with clonidine toxicity were administered naloxone and developed significant hypertension 0 to 120 minutes after the first dose. The authors hypothesize that by inhibiting the central effects of clonidine, naloxone allows the peripheral vasoconstrictive effects to predominate. It is impossible to differentiate the occasional hypertension sometimes seen in clonidine overdoses from that due to naloxone in this study. These cases suggest that naloxone should be used cautiously with close hemodynamic monitoring in patients with clonidine toxicity. Abuse of pentazocine-naloxone combination. Schnoll SH. JAMA 1986;256:2562-2564.
Reed
DA,
Pentazocine and tripelennamine (T’s and blues) are frequently abused in combination as a heroin substitute. In response, the formulation of pentazocine was modified to include naloxone (‘Ihlwin Nx). Two cases of abuse of this new formulation are described. Both patients reported a rush similar to that following heroin. Three explanations were
MARTIN AND LITOVITZ W TOXICOLOGY: ANNOTATED BIBLIOGRAPHY
suggested for the apparent failure of this formulation: 1) Pentazocine is an agonist at the K and u receptor sites and an antagonist at the F receptor site. Naloxone is only an antagonist at the p receptor site. The rush effect may be from unopposed stimulation of the K or u receptors. 2) The dose of naloxone (0.5 mg/tablet) may not be sufficient. 3) Tripelennamine may produce euphoric or reward-enhancing effects of its own.
NEUROLEPTIC MALIGNANT SYNDROME Peripheral neuropathy as component of the neuroleptic malig nant syndrome. Anderson SA, Weinschenk K. Am J Med 1987;82:169-170. The cases of two patients who developed severe peripheral neuropathies following the classic manifestations of the neuroleptic malignant syndrome are described. Evaluation for other causes of the peripheral neuropathy was negative, and the neuropathies improved over several months. Successful treatment of neuroleptic malignant syndrome with bromocriptine. Janati A, Webb RT. South Med J 1986;79: 1567-1571. Neuroleptic malignant syndrome has been associated with the use of phenothiazines, butyrophenones, thioxanthenes, and sudden withdrawal of antiparkinsonian drugs. Four cases with characteristic manifestations of the syndrome were successfully treated with bromocriptine, 2.5 mg twice daily, increased by 2.5 mg/d to 7.5 mg three times daily. These patients displayed marked improvement within 24 hours. Therapy was required for at least 30 days.
PESTICIDES Clinical confirmation of organophosphate poisoning by serial cholinesterase analysis. Coye MJ, Barnett PG, Midtling JE, et al. Arch Intern Med 1987;147:438-442. Moderate organophosphate poisoning is confirmed by comparing postexposure erythrocyte and plasma cholinesterase activities to baseline preexposure values. Although California requires baseline preexposure testing of pesticide applicators, other states do not. The range of normal cholinesterase activity is wide, and the upper limit of normal may be 200% higher than the lower limit. Thus, if erythrocyte cholinesterase activity is 25% inhibited, 46 to 90% of the population would have activity measured within the normal range. With plasma cholinesterase activity 25% inhibited, 92 to 99% of the population would have activity within the normal range. When baseline preexposure activities are not available, false-negative results may occur frequently in mild to moderate organophosphate intoxication. To avoid these errors, serial cholinesterase levels are advised. Neurotoxic effects of organophosphorus insecticides: an intermediate syndrome. Senanayake N, Karalliedde L. N Engl J Med 1987;316:761-763. Changing profile of pesticide poisoning [editorial]. Davies JE. N Engl J Med 1987;316:807-808. This article and its commentary focus on an intermediate syndrome observed in 10 persons with organophosphate
poisoning in Sri Lanka. This syndrome is characterized by an onset at 24 to % hours; weakness of the proximal limb, neck flexors, and respiratory muscles; and cranial nerve motor dysfunction. It followed the appearance of classic cholinergic signs in all patients and was unresponsive to atropine. Four patients required mechanical ventilation for up to 15 days; 3 patients died from ventilatory failure. Electromyographic studies suggested a postsynaptic defect. Resolution followed a characteristic pattern, with cranial nerves recovering first and then respiratory, proximal limb, and neck flexor muscles. Four different organophosphates were responsible, with the highest incidence in monocrotophos exposures (22%).
STREET DRUGS Perinatal cerebral infarction and maternal cocaine use. Chasnoff IJ, Bussey ME, Savich R, et al. J Pediatr 1986;108: 456-459. A newborn developed a cerebral infarction shortly after delivery. The child’s mother had abused cocaine during the preceding 72 hours. Urine analysis revealed benzoylecgonine (a cocaine metabolite) in the infant’s urine for 4 days. Other well-documented obstetrical complications of maternal cocaine abuse include spontaneous abortion and abruptio placentae. New treatment for PCP toxicity? 1987;257:3188.
Macdonald
DI. JAMA
Phencyclidine (PCP)-specific goat Fab antibody fragments have been investigated in dogs. The affinity of PCP for this Fab fragment is 700 times greater than for its neuronal receptor. In dogs given tracer amounts of PCP, favorable changes in volume of distribution and bound fraction occurred. Experiments with higher doses of PCP are in progress. Previous work with digoxin suggests that the large volume of distribution and protein binding do not interfere with the efficacy of Fab antibodies. Botulism and botulism-like illness in chronic drug abusers. MacDonald KL, Rutherford GW, Friedman SM, et al. Ann Intern Med 1985;102:616-618. Six parenteral drug abusers were reported who had botulism suspected to be of wound origin. Wound botulism results from toxin production by Clostridium botulinum growing in the wound. Wounds harboring C. botulinum may not look infected, which may delay appropriate therapy. The syndrome starts with cranial nerve dysfunction (usually dysphagia), followed by a progressive descending paralysis. To be maximally effective, botulinal antitoxin must be given as soon as possible after the onset of symptoms (preferably ~24 hours). The diagnosis can be confirmed with a positive wound culture, while the serum tests are usually negative. The authors recommend that all abscesses on intravenous drug abusers be cultured for anaerobic organisms and incised and drained. Patients with these symptoms should receive appropriate antibiotics (usually penicillin) and botulinal antitoxin. 71
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Cocaine-associated myocardia ischemia: review of clinical and angiographic findings. Mathias DW. Am J Med 1986;81: 675-678. Acute cardiac events temporally related to cocaine abuse. Isner JM, Estes M, Thompson PD, et al. N Engl J Med 1986;315: 1438- 1443. Acute myocardial infarction temporally related to cocaine use: clinical, angiographic, and pathophysiologic observations. Smith HWB, Liverman HA, Brody SL, et al. Ann Intern Med 1987;107:13- 18. Cases from Milwaukee, Boston, and Atlanta of ischemic chest pain and myocardial infarction temporally related to cocaine use are reported. Chest pain was the presenting symptom, and the electrocardiogram revealed obvious signs of ischemia or infarction in almost all of these patients. Most of the patients were young, with a mean age of 31.4 years. Risk factors were present in the majority, but some patients had none. Men comprised the majority (90%) of the patients. When performed, coronary angiography revealed abnormalities in the infarct-related vessels in two thirds of cases. If angiography had been done closer to the time of infarction, the yield might have been even higher. In a few, coronary thrombosis was lysed with thrombolytic therapy, and normal underlying vessels were revealed. Those patients
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challenged with ergonovine did not demonstrate coronary spasm. Most patients survived this infarction, but recurrent infarction and sustained prolonged ischemia occurred in a few who continued to abuse cocaine. Cardiogenic shock and cardiac arrest were rare complications. These data are enlightening but may be biased by the retrospective nature of the studies. These studies indicate that complications are not limited to intravenous abusers and that fixed coronary artery disease or high risk factors are not prerequisites. A history of cocaine use should be sought in young patients with coronary ischemia-like symptoms.
PCP intoxication in seven young children. Schwartz RH, Einhorn A. Pediatr Emerg Care 1986;2:238-241. Seven children were treated at a large children’s hospital for phencyclidine (PCP) toxicity. The most common symptoms were neurologic and included lethargy, decreased responsiveness to stimuli (often associated with a blank stare), ataxia, nystagmus, and miosis. The authors suggest that children are very sensitive to PCP and may develop serious neurologic signs with minimal exposure. They recommend toxicologic screens routinely in children with unexplained coma, hypotonia, seizures, or a blank stare.