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Four young adults presented two days after one of them had received marzipan balls packaged in a box from an expensive candy manufacturer. Two ate one candy ball, while two others shared a third. The next day, variable gastrointestinal symptoms developed. On the third day, two patients developed painful paresthesiae of the hands and feet, an early but nonspecific clinical marker of thallium poisoning. A tentative diagnosis of thallium poisoning was made based on symptoms, and treatment was initiated. The remaining candies were radiographed. Metallic densities in the candies supported the diagnosis, and atomic absorption spectroscopy was used to quantitate thallium content. Each candy contained a potentially fatal dose. Five to seven days later, hypertension and tachycardia developed in the two patients who had ingested an entire candy. All patients developed alopecia but recovered without overt neurologic or other sequelae. While the diagnosis of thallium poisoning is often delayed until alopecia develops, an early diagnosis favors an effective treatment strategy.

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The illicit use of cocaine continues in epidemic proportions. Despite the incidence of life-threatening complications from cocaine use, little is known of the individual determinants of cocaine toxicity. In vitro analysis demonstrating that cocaine is poorly metabolized by the serum of patients with low plasma cholinesterase (PCh) activity (succinylcholine sensitivity) led to the hypothesis that altered PCh activity might modulate cocaine toxicity. An in vivo mouse model was created to test this theory. Mice were pretreated s.c. with either parathion [a mixed plasma and red blood cell cholinesterase (RBCCh) inhibitor], tetraisopropyl pyrophosphoramide (a selective PCh inhibitor) or placebo, and cholinesterase activity was determined at 24 hr. Incremental doses of i.p. cocaine were administered in a controlled and blinded fashion, and lethality was observed. Ten mg/kg s.c. parathion produced a mean suppression of 68 +/- 9 and 61 +/- 8% of PCh and RBCCh activity, respectively. One mg/kg s.c. tetraisopropyl pyrophosphoramide produced a mean suppression of 78 +/- 3 and 9 +/- 8% of PCh and RBCCh activity, respectively. Each pretreatment produced a statistically significant increase in cocaine lethality throughout the dose-response curve. Our results suggest that PCh activity is an important determinant of cocaine toxicity. This effect appears to be independent of either RBCCh activity or manifestations of organophosphate intoxication.

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STUDY OBJECTIVE: To determine whether plasma cholinesterase (pseudocholinesterase) activity is a marker for severe cocaine toxicity. DESIGN: A prevalence study in a cohort of cocaine users. SETTING: A large urban emergency department. PARTICIPANTS: During a three-month period in 1989, 187 patients who presented to the ED on 191 consecutive occasions with signs and symptoms consistent with cocaine intoxication were prospectively enrolled in the study protocol. METHODS AND MEASUREMENTS: All patients had plasma cholinesterase activity determined by the electrometric method. The patients who were cocaine positive were stratified into one of two groups: life-threatening toxicity (LT) and non-life-threatening toxicity (NLT), based on a predetermined set of criteria. Cocaine-negative patients served as controls for the LT group if criteria were otherwise met. RESULTS: Mean (+/- SD) plasma cholinesterase activities for the LT, NLT, and control groups were 682 +/- 277, 904 +/- 279, and 1,058 +/- 385 Michel units/L, respectively. All three groups were significantly different from each other (P less than .05 by analysis of variance). CONCLUSION: The data suggest that decreased plasma cholinesterase activity is associated with increased risk of life-threatening cocaine toxicity.

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A retrospective analysis of sedative-hypnotic overdoses reported to the New York City Poison Control Center (NYCPCC) for the years 1988 and 1989 was performed to evaluate the effects of the triplicate benzodiazepine (BZ) prescription program on the incidence and severity of sedative hypnotic overdoses. Although total BZ overdoses fell slightly, from 1,294 in 1988 to 1,265 in 1989, a statistically significant increase in non-benzodiazepine (NBZ) sedative-hypnotic overdoses, from 111 in 1988 to 144 in 1989, was noted. No difference in clinical outcomes between the two years could be demonstrated. These results suggest that the restriction of BZ failed to reduce the incidence or severity of sedative-hypnotic overdose, largely because of the substitution of similar nonrestricted agents.

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Whole bowel irrigation with polyethylene glycol electrolyte lavage solution has been recommended as an adjunct to traditional overdose management. Although combined activated charcoal and whole bowel irrigation could enhance the efficacy of both modalities, this improvement remains largely speculative. An in vitro experiment was designed to determine whether polyethylene glycol electrolyte lavage solution alters the adsorption of theophylline to activated charcoal. Theophylline was agitated with activated charcoal in either water or polyethylene glycol electrolyte lavage solution, at each of three activated charcoal:theophylline ratios; 1:1, 3:1, and 10:1. The concentration in the supernatant was determined by high pressure liquid chromatography, and the maximal adsorptive capacity of activated charcoal for theophylline was calculated from the Langmuir equation. The percent of theophylline adsorbed by activated charcoal in water was 16 +/- 4%, 67 +/- 5%, and 97 +/- 3% for the 1:1, 3:1, and 10:1 ratios, respectively. This was decreased to 17 +/- 5%, 37 +/- 3%, and 62 +/- 2% when polyethylene glycol electrolyte lavage solution was added. A statistical difference (p less than 0.05) occurred at the 3:1 and 10:1 activated charcoal:theophylline ratios. Similarly the maximal adsorptive capacity was decreased 23% from 264 mg/g to 203 mg/g when polyethylene glycol electrolyte lavage solution was added to activated charcoal prior to theophylline. Polyethylene glycol electrolyte lavage solution significantly decreases adsorption of theophylline to activated charcoal in vitro. In vivo studies are required to confirm these findings. If activated charcoal is to be used clinically for theophylline toxicity, the authors suggest the possibility of larger quantities of activated charcoal, and administering activated charcoal in a slurry of water before the initiation of whole bowel irrigation.

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The "crack" (cocaine alkaloid) epidemic has resulted in an increasing number of hospitalizations of "crack-vial body-stuffers," or patients who ingest "crack-vials" in an attempt to avoid prosecution. Management strategies for this type of ingestion are lacking because of the paucity of data. This report discusses the demographics and symptomatology of 23 patients with "crack-vial" ingestions, as well as the value of abdominal radiographs and the utility of varied strategies for decontamination in this patient population.

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Naloxone hydrochloride is extremely valuable for diagnosing and managing the opioid overdose. Due to naloxone's short half life and a long duration of action of most opioids, repeated naloxone dosing often is required to prevent the recurrence of respiratory depression. An alternative to repeated bolus administration is a continuous IV infusion. We conducted a two-phase study to determine the pharmacokinetics of naloxone and to develop a continuous dosing nomogram. In the first phase seven patients were given an IV bolus dose alone and serial plasma naloxone levels were determined. Naloxone elimination was found to be biexponential with the mean beta half life equal to 0.023 +/- 0.002 reciprocal minutes in two patients and 0.015 +/- 0.02 reciprocal minutes in five patients. In the second phase ten volunteers were given either a 2-mg or a 4-mg bolus dose followed by a 1.5-mg/hr or a 3-mg/hr continuous infusion. The mean volume of distribution of the central compartment was found to be 0.806 +/- 0.408 L/kg. The mean beta rate constant of elimination was found to be 0.036 +/- 0.027 reciprocal minutes. A computer simulation of the pharmacokinetic parameters determined in our study found that a continuous infusion of two-thirds of the bolus dose that resulted in reversal each hour will maintain the plasma naloxone levels equal to or greater than the naloxone levels that would have existed 30 minutes following the bolus dose.

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Approximately 70 per cent of all poisonings reported to poison control centers will be referred after home or hospital management to the primary care physician. When a patient presents to the physician's office following a poisoning, the care provider must know when hospitalization is needed, what equipment should be available, and where information about the toxin can be obtained.

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