Edward P. Krenzelok

CARBAMAZEPINE OVERDOSE: A PROSPECTIVE STUDY OF SERUM LEVELS AND TOXICITY

A cooperative prospective study of consecutive cases of carbamazepine overdose was conducted to determine if serum levels were predictive of toxicity and if risk factors such as age, chronic exposure, or previous disorder or cardiovascular disease could be used as prognostic indicators. Seventy-three consecutive cases were collected from two regional certified poison control centers from January 1989 to August 1989. There were 25 exposures in children less than 6 yrs., 11 exposures in adolescents, and 37 exposures in adults. Ten adult cases and one adolescent case were excluded from the study due to the presence of coingestants or inadequate information. Peak measured serum levels ranged from 0.3 to 56 mcg/ml. Using the presence of coma, seizure activity or respiratory depression requiring mechanical ventilation as measures of toxicity, we found poor correlation between rising serum levels of carbamazepine and toxicity. Increased serum levels of carbamazepine did appear to correlate with increased hospital stay, but not with ICU stay. History of a seizure disorder appears to pose increased risk of a seizure in carbamazepine overdose. In this series chronic exposure to carbamazepine did not appear to increase the risk of coma or respiratory depression for a given toxic serum level and may add some protective effect. Serum levels below 40 mcg/ml do not appear to accurately predict the severity of toxicity. Cardiac conduction defects were rare (one child). Anticholinergic findings, as evidence by decreased bowel motility and sinus tachycardia were common. Previous cardiovascular disease and age did not appear to be important prognostic indicators.

Contribution of sorbitol combined with activated charcoal in prevention of salicylate absorption

The use of cathartics and activated charcoal in treating toxic ingestions has become a standard treatment modality. Sorbitol has been shown to be the most rapidly acting cathartic, but its therapeutic significance has been debated. Using a previously described aspirin overdose model, ten healthy volunteers participated in a crossover design study that investigated the effect of activated charcoal alone versus that of activated charcoal and sorbitol in preventing salicylate absorption. In phase 1 of the study, subjects consumed 2.5 g aspirin followed by 25 g activated charcoal one hour later. Urine was collected for 48 hours and analyzed for quantitative salicylate metabolites. Phase 2 was identical except that 1.5 g/kg sorbitol was consumed with the activated charcoal. The mean amount of aspirin absorbed without the use of sorbitol was 1.26 +/- 0.15 g, whereas the mean absorption was 0.912 +/- 0.18 g with the addition of sorbitol. This is a 28% decrease in absorption of salicylates attributable to the use of sorbitol. The difference is significant at P less than .05 by the paired Students t test. This study demonstrates that the addition of sorbitol significantly decreases drug absorption in a simulated drug overdose model. Effects on absorption in actual overdose situations and on patient outcome should be the subjects of further study.

Gastrointestinal transit times of cathartics combined with charcoal

Oral activated charcoal usually is administered in toxic ingestions along with a cathartic. A study was done in volunteers to determine the rapidity of gastrointestinal transit when activated charcoal was administered with various cathartics. A control of activated charcoal was compared to the gastrointestinal transit times of activated charcoal plus the cathartics magnesium citrate, magnesium sulfate, or sorbitol. Activated charcoal alone produced a mean transit time of 23.5 hours; magnesium citrate catharsis occurred in 4.2 hours, magnesium sulfate catharsis occurred in 9.3 hours, and sorbitol catharsis occurred in 0.9 hours. Sorbitol clearly was the most rapidly acting cathartic.

Successful donation and transplantation of multiple organs from a victim of cyanide poisoning

AbstractDemand for viable human organs for transplantation continues to exceed the supply. To expand supply, the criteria for identification and management of suitable donors must continue to evolve. Poisoned patients are often excluded as potential organ donors due to perceived risks of transmittable agents and/or physiologically compromised organs. In this report, a patient succumbed after an intentional ingestion of cyanide and multiple Pharmaceuticals. Donor organ viability was determined by lack of significant injury beyond the central nervous system. Following standard procurement procedures, the heart, liver, corneas, 16 skin grafts and 16 bone grafts were deemed suitable and successfully transplanted. All organ recipients were doing well eight months post transplantation. The focus of procurement personnel should be on tissue injury and not on the mere presence of clinical effect of a toxic agent. With the paucity of organs available, poison centers need to be cognizant of this dilemma when faced ...

Cimetidine protection against alpha-amanitin hepatotoxicity in mice: a potential model for the treatment of Amanita phalloides poisoning.

The ingestion of the mushroom Amanita phalloides is associated with hepatic necrosis appearing clinically two to three days after ingestion. The mechanism of this toxicity is unknown, and no reliable antidote is available. Because of the similarity of Amanita poisoning to other toxins affecting cytochrome P450, we investigated the use of cimetidine (as a P450 cytochrome inhibitor) as an antidote against a primary toxin of the mushroom alpha-amanitin. Mice injected with alpha-amanitin and given cimetidine either prophylactically or within six hours showed histologic protection from the hepatic damage seen in control mice. Control animals displayed significant mitochondrial changes when examined by electron-microscopy, while the mitochondria of the cimetidine-treated animals were preserved, suggesting a possible site for toxin action. Further trials will be necessary before treatment of human cases with cimetidine is indicated.

Delayed Life-Threatening Reaction to Anthrax Vaccine

Background: Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Due to the current world threat of unpredictable biological terrorism, the Department of Defense has mandated the systematic vaccination of all US military personnel against this warfare agent. Many may experience a mild flu-like illness and soreness at the injection site, but systemic reactions are rare. Case Report: We report a delayed and potentially serious life-threatening adverse reaction to anthrax vaccine. A previously healthy 34-year-old male was transported to the emergency department with dyspnea, diaphoresis, pallor, and urticarial wheals on his face, arms, and torso after the administration of the third dose of anthrax vaccine. All symptoms resolved after pharmacological intervention and the patient was discharged. Pharmaco-epidemiological data indicate that 30% of anthrax vaccine recipients experience mild local reactions. With large numbers of military personnel being vaccinated, emergency physicians may encounter more vaccine-related adverse reactions.

Clinical Evaluation of Pediatric Ethylene Glycol Monobutyl Ether Poisonings

Ethylene glycol butyl ether, CAS 111-76-2, an ingredient in many popular commercial window/glass cleaners, is known to produce equal if not greater toxicity than ethylene glycol when administered to animals. Treatment recommendations for human poisonings are based upon animal data and include the use of ethanol therapy to inhibit the production of toxic metabolites. No human experiential data exist to accurately assess human toxicity or to verify treatment modalities. A 5 month retrospective review of all glass cleaner ingestions reported to a regional poison information center disclosed 24 pediatric patients, ages 7 mo to 9 y, who ingested 5-300 mL of a liquid glass cleaning product containing ethylene glycol butyl ether. All ingestions were reported within 5 min of ingestion, and all 24 children were asymptomatic at that time and subsequently. The product concentrations of ethylene glycol butyl ether ranged from 0.5% to 9.9%. Two of the 24 children ingested > 15 mL and were treated by gastric emptying and 24 h hospital observation. Neither hospitalized child suffered symptoms consistent with hemolysis, nervous system depression, acidosis, or renal compromise. Dilution with oral fluids at home is considered appropriate treatment of pediatric ingestions of < 10 mL of a commercial liquid glass/window cleaners containing < 10% ethylene glycol butyl ether.Ethylene glycol butyl ether, CAS 111-76-2, an ingredient in many popular commercial window/glass cleaners, is known to produce equal if not greater toxicity than ethylene glycol when administered to animals. Treatment recommendations for human poisonings are based upon animal data and include the use of ethanol therapy to inhibit the production of toxic metabolites. No human experiential data exist to accurately assess human toxicity or to verify treatment modalities. A 5 month retrospective review of all glass cleaner ingestions reported to a regional poison information center disclosed 24 pediatric patients, ages 7 mo to 9y, who ingested 5-300 mL of a liquid glass cleaning product containing ethylene glycol butyl ether. All ingestions were reported within 5 min of ingestion, and all 24 children were asymptomatic at that time and subsequently. The product concentrations of ethylene glycol butyl ether ranged from 0.5% to 9.9%. Two of the 24 children ingested > 15 mL and were treated by gastric emptying an...

Survival of a child despite unusually high blood ethanol levels

A 30-month-old, 13-kg child reportedly ingested up to 16 ounces of a wine containing 20% ethanol. The child was brought into the emergency department by paramedics, and upon arrival was found to be comatose and unresponsive to deep stimuli but breathing spontaneously. The patient remained unconscious and unresponsive for three hours after admission. Despite an initial blood ethanol level of 98.78 mmol/L (455 mg/dL), recovery was complete without sequelae. Treatment consisted of prompt gastric decontamination and maintenance of adequate hydration and euglycemia. Elimination of ethanol was rapid in this child and appeared to follow first-order kinetics instead of the zero-order kinetics usually observed. To our knowledge, this is the highest initial blood ethanol level reported in a child with survival. Additionally, no significant metabolic or cardiorespiratory derangement occurred. Ethanol toxicity, elimination kinetics, and treatment are discussed.

Liquid automatic dishwashing detergents: A profile of toxicity

The recent introduction of liquid automatic dishwashing detergents (LADDs) has resulted in numerous calls to poison information centers and, subsequently, a large number of referrals to emergency departments. As with their traditional granular counterparts, LADDs contain alkaline builders that contribute to the pH of these products. Exposure to granular automatic dishwashing detergents has been associated with caustic injury similar to the pathology produced by other alkaline corrosives. Do LADDs produce similar toxicity? There is no published information that profiles the toxic manifestations associated with exposure to LADDs. To determine their toxicity, all LADD exposures reported to a regional poison information center over a 12-month period were collected. One hundred ninety-two human exposure cases were reviewed. Pediatric patients accounted for 76% of the exposures; 76% were ingestions, 12% were dermal exposures, and 12% were ocular exposures. Seventy-nine percent of the patients were exposed to a full-strength product, and 21% contacted a dilute product or one that had already been through the dishwashing cycle. Of the patients who ingested a LADD, 91.1% remained asymptomatic, 8.2% had minor symptoms, and only one (0.7%) suffered moderate toxicity. In contrast, 91.3% of all patients who had an ocular exposure developed minor or moderate toxicity (73.9% vs 17.4%). Of dermal exposures, 69.6% were asymptomatic, and those with symptoms were the result of inappropriate use. Overall, 78.7% remained asymptomatic, 18.2% developed minor toxicity, and 3.1% developed moderate toxicity. Small oral and dermal exposures usually do not result in toxicity and do not necessitate referral to an ED. Ocular exposures are associated with a high incidence of at least minor toxicity and require ED evaluation.

Environmentally-Induced Methemoglobinemia in an Infant

Acquired methemoglobinemia results from the exposure to various chemicals and drugs able to oxidize hemoglobin at a rate exceeding the normal enzymatic capacity for hemoglobin reduction. Levels of methemoglobin exceeding 60-70% may be associated with coma and death. We describe a case of complete, uneventful recovery involving a 10 week-old infant who presented to the Emergency Department with profound sudden onset of cyanosis, irritability, metabolic acidosis, and a lethal methemoglobin level of 71.4%. Intravenous administration of 12 mg methylene blue resulted in immediate resolution of the cyanosis and reduction of measured methemoglobin to 1.3%. The carboxyhemoglobin was negative. Sodium bicarbonate successfully corrected the acidosis. RBC reductase measurement was within normal limits, ruling out congenital methemoglobinemia. Family history revealed a wood-burning stove which emitted pine tar fumes as the potential environmental methemoglobin-producing source. The infants cradle was situated five feet from the stove. The infant was discharged on day three of hospitalization with a methemoglobin level of 0.2%.