Journal of Toxicology Clinical Toxicology

Toxicity of 1,4-butanediol, an industrial solvent and a substance of abuse, is still misunderstood and not well documented. To date, only supportive treatments are used in this poisoning. The case of a 43-year-old man who ingested 30 mL of a homemade 1,4-butanediol solution and who developed general seizures and coma has been reported here. An intravenous loading dose of fomepizole 10 mg/kg was started on admission and followed by two other doses of 10 mg/kg every 12 hour. He awoke shortly after fomepizole administration. Initial plasma 1,4-butanediol and gamma-hydroxybutyric acid concentrations, measured by gas chromatography-mass spectrometry, were 24 and 222 mg/L, respectively. Subsequent 1,4-butanediol and gamma-hydroxybutyric acid determination suggest that there was some further formate of gamma-hydroxbutyric acid after fomepizole was administered. Fomepizole administration appeared safe in this 1,4-butanediol-intoxicated patient. It is unknown whether fomepizole influenced his clinical course, but the rapid awakening observed suggests that it may have been usefuL Further experience is needed, however, to define the efficacy of this antidotal therapy in 1,4-butanediol intoxication.

Carbamazepine (amizepine) is a widely used psychotropic agent. A much easier accessibility of this drug, observed during the recent years, may account for an increasing number of acute intoxications with carbamazepine. The aim of this study was to determine the elimination kinetics of carbamazepine and its metabolite carbamazepine 10,11-epoxide, and to identify the quantitative relationship between concentrations of these compounds, in serum. The subjects were 41 patients with acute carbamazepine intoxication. Serum carbamazepine and carbamazepine 10,11-epoxide concentrations were determined every 6 hours during thefirst 24 hours of hospitalization, and then every 12 hours. At the same time, urinalyses were performed for each patient to confirm or exclude homogeneity of poisoning. Depending on the type of intoxication (homogenous or combined), three groups of patients, and on the method of treatment (symptomatic, charcoal administration), two groups of patients were distinguished. The statistical analysis of the results revealed that among the investigated parameters (time-integrated concentrations of carbamazepine and carbamazepine 10,11-epoxide in serum, the presence of drugs, and/or ethanol, charcoal treatment) only carbamazepine concentrations had statistically significant effect on the duration of coma regarded as a critical effect. The kinetics of carbamazepine elimination was determined on the basis of the mean carbamazepine concentrations at the same timing of sampling for each patient in all the three groups; the mean carbamazepine elimination in serum followed zero-order kinetics. In individual groups, the decrease in serum carbamazepine concentrations ranged from 0.5 to 0.8 mg L(-1) hour(-1). Contrary to the suggestions found in the literature, carbamazepine 10,11-epoxide determination does not seem to enhance the possibility of anticipating the course of intoxication or the time of recovery.

The toxicological interpretation of blood and urine concentrations of drugs affecting the digestive system and metabolism, as with other groups of pharmaceutical specialties, is complicated. As a continuation of our published studies on the concentrations of drugs of abuse, drugs affecting cardiovascular and hematopoietic systems, and respiratory system, we have reviewed the published data relating to the concentrations of drugs affecting the digestive system and metabolism in clinical and forensic cases. We have selected them on the basis of conservative criteria and our own experience. A table with concentrations of 101 drugs in whole blood, serum/plasma, and urine, corresponding to therapeutic, toxic, or lethal concentrations, is presented. The data can help interpret analytical results of patient or postmortem samples when there is a suspicion of poisoning with this group of drugs.

Poisoning caused by drugs of abuse or commonly used addictive medicines occurs with relative frequency and often leads, either directly or indirectly, to death. The interpretation of the blood and urine concentrations is, however, a complex and difficult problem. We have reviewed the published data and subjected them to selection and unification on the basis of conservative criteria and our own experience. A compilation of the concentrations of 103 drugs of abuse in whole blood, serum/plasma, and urine, during habitual or therapeutic use and as found in toxic or lethal poisoning is given. The table presented can be helpful in interpretation of the drug concentrations encountered in clinical, toxicological, and forensic cases.

Verification of abstinence from cannabinoid use after initial identification requires documentation of falling quantitative levels of urinary 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) over an extended time period. We present a case in which normalization of quantitative urinary THC-COOH results to urinary creatinine is required to correctly interpret a series of quantitative levels and confirm abstinence from marijuana smoking. © 1989 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

In West Germany, the antihistaminic diphenhydramine is marketed as a non-prescription hypnotic. Results of toxicological screening in cases of drug overdose indicate that poisoning with diphenhydramine represents a substantial part (4.5%) of the total number of intoxications. A total of 136 cases of diphenhydramine poisoning in 1982-1985 were evaluated with respect to age, ingested dose, plasma level, and clinical symptomatology. All patients had taken diphenhydramine with suicidal intent. Two-thirds of the patients were aged 14-30 years. In about 50% of the cases, between 6 and 40 times a therapeutic dose was ingested. Diphenhydramine plasma levels showed a wide range (0.1-4.7/micrograms/ml) due to differences in ingested dose and time between ingestion and admission to hospital. Impaired consciousness was the most common symptom. Psychotic behavior similar to catatonic stupor--often combined with anxiety--was highly specific for diphenhydramine poisoning. Further symptoms included hallucinations, mydriasis, tachycardia, and less frequently diplopia, respiratory insufficiency, and seizures. Primary treatment included gastric lavage, administration of activated charcoal and sodium sulfate. In one case, hemodialysis and ultrafiltration were performed which had only limited effect on diphenhydramine plasma elimination kinetics. This patient died of diphenhydramine overdose and extreme hypothermia. All intoxications except the one mentioned before had an uncomplicated clinical course. In vitro experiments indicate that diphenhydramine may be almost completely removed from the plasma compartment by hemoperfusion. Routine analysis of urine samples in diphenhydramine overdose led to the identification of 4 previously unknown metabolites and artifacts of diphenhydramine.

Lithium kinetics were studied in 14 patients with lithium poisoning. Three patients were treated by hemodialysis. Serum lithium peak concentrations ranged between 1.4 and 9.6 mmol/L. The apparent mean serum half-life was 23.16 +/- 9 h, the mean total clearance was 26.5 +/- 13.3 mL/min and the mean renal clearance was 17.2 +/- 5.4 mL/min. The kinetic parameters were dependent on the duration of the study and on the type of the poisoning: acute, acute upon chronic or chronic. During the first 12 h after admission ten patients were in a distribution phase, three were in an elimination phase and one was in an absorption phase. The serum half-life during hemodialysis ranged from 3.6 to 5.7 h and hemodialysis clearance was 63.2 to 114.4 mL/min. The mean volume of distribution calculated in six cases was 0.63 +/- 0.09 L/kg. The evolution of the lithium pools showed a different kinetic pattern between the extra- and the intracellular pool which decreased more slowly. During hemodialysis the decrease of the extracellular pool was about twice that of the cellular pool. Among the factors which may modify lithium toxicity and kinetics, are the type of the poisoning, the presence of an underlying disease and renal impairment. No general and rigid indication for hemodialysis can be set, but the need for hemodialysis should be based on clinical and kinetic data determined during the 12 h following admission.

One hundred forty-nine (149) consecutive cases of arsenate-containing ant killer reported to the Minnesota Regional Poison Center over 4 1/2 months were retrospectively reviewed with a follow-up (1 week to 3 months) completed in 132 (89%) of the population studied. One hundred and forty eight (99%) of the ingestions were accidental. The majority of cases involved children 3 years of age and younger. Only three patients accidentally ingesting the product were symptomatic (mild episodes of vomiting and diarrhea which cleared in all patients within 12 hours). No patient was referred to a medical center for treatment and no patient reached on follow-up reported any additional ill effects as a result of the exposure. In addition to the 149 patients in this series, we describe two representative patients who accidentally ingested similar amounts of sodium arsenate-containing ant killer, resulting in urine arsenic of 3500 micrograms/24 h and 5819 micrograms/24 h. They required no chelation treatment and had no evident sequelae during 4-6 months of medical follow-up. This experience supports poison center directed home management for the majority of single, acute, and accidental ingestions of small quantities (< 5 mL) of arsenate-containing ant killers as a safe alternative to medical center referral and adverse reactions to chelation.

Review was made of the symptoms, treatment and outcome of 151 cases of severe envenomation by the scorpion Centruroides sculpturatus treated with antivenom, 1988-1989. The most frequent symptoms were restlessness, nystagmus, paresthesiae, hypersalivation, fasciculation, blurred vision and dysphagia with an average of four symptoms. Medications before antivenom, given to about half of the subjects, included antihistamines, sedatives, analgesics and epinephrine. In 71% of patients, symptoms were relieved within 30 minutes of receiving one vial. Immediate hypersensitivity reactions occurred in 8%, but were generally mild. Skin tests had a sensitivity of 96% and specificity of 68%. Delayed reactions were not addressed. In conclusion, the antivenom appears safe and effective.

Ciguatera is a disease caused by the ingestion of fish containing the toxins of Gambierdiscus toxicus. This dinoflagellate is frequently found in damaged coral reef systems. Previously rare in Europe, this disease entity is now seen in tourists returning from tropical countries. Eighteen patients were examined between 1997 and 2002. Nine poisonings occurred in Atlantic Ocean islands, eight in Pacific Ocean islands, and one in the Egyptian Red Sea coast. Gastrointestinal signs were always present in the Atlantic areas, but were less severe or absent in the Pacific areas. All patients had sensory disturbances, and two of them had motor disturbances affecting the respiratory muscles and leading to the death of a 73-year-old man in Cuba. The 17 surviving patients returned to France and for 2 to 18 months suffered from arthralgias, myalgias, or pruritus. Ciguatera is a newly imported intoxication in Europe. As the number of international tourists grows each year, this type of poisoning will be seen more frequently. Furthermore, as the condition of coral reefs declines around the world and the prevalence of G. toxicus increases, physicians in non-tropical countries should be prepared to manage such poisoned patients.

Case histories of the last nine fatalities (1969-1984), in which the cause of death on the State of Arizona Certificate of Death was snakebite, were reviewed. Six males and three females ranged in age from 2 to 77 years, and were bitten between 0800-2100 hours from April to September. Bites in three adult males were "illegitimate" and of these, two were by captive Mojave rattlesnakes, Crotalus s. scutulatus. The latter two victims had been bitten previously and remained at home, refusing treatment. In the other seven victims, the snakes involved were not identified. However, all localities where bites occurred were within the geographical and altitudinal range for Crotalus atrox and C. s. scutulatus. The apparent cause of death was prolonged hypotension with major organ system failure in five, intestinal hemorrhage in one, and was unknown in three. Major organs were involved as follows: cardiac failure (two); noncardiac pulmonary edema (two); renal failure (two); unconsciousness with airway obstruction and brain damage (two); and coagulopathy with multiple hemorrhage sites (one). Seven of the nine deaths appeared to be preventable. Four delayed going to a medical facility and six did not have hypotension corrected. Antivenin was not administered early (first four hours) or in adequate amounts (10 vials or more) because of delayed arrival in five or physician's decision in four. Pre-existing cardiac disease contributed to death of two victims. Rattlesnake bite victims should not delay travel to a medical facility and hypotension must be treated aggressively and appropriately.

A collaborative study of 273 treated poisonings at three regional poison control centers showed a significant decrease in salicylism from 19% of all cases in 1970 to 9% in 1975 and 11% in 1980. A temporal correlation with safety packaging was also seen in the decrease in poisonings by household products from 36% and 42% of all treated poisonings in 1970 and 1975 to 21% in 1980. Poisonings by non-salicylate medications increased from 45% to 68% of treated ingestions. Therapeutic mishaps were relatively constant at 27%, 20% and 20% of all poisonings by medications. In children under one year of age 59% of medicinal poisonings were therapeutic mishaps, significantly higher than the 27% incidence for ages 1 to 5 years. Therapeutic mishaps and ingestions of household products resulted in significantly longer hospitalizations than accidental ingestion of medications. Additional data from two other regional centers permitted analysis of a total of 47 cases of treated salicylism. Therapeutic mishaps showed a possible upward trend from 27% of salicylate poisonings in 1970 to 36% in 1980. Almost all of the therapeutic mishaps with salicylates involved repeated overdose; 18 of the 19 mishaps due to other medications were allergic reactions.

In the seven year period 1978-1984, 40,847 registered cases of poisonings were treated in hospital wards in Finland. 73.9% of the poisonings were due to drugs and 26.1% were due to technochemical products. The patients were primarily treated in internal medicine wards (65%) and in pediatric wards (16.3%). Seasonal variation was seen for agents such as oils, carbon monoxide, solvents, psychotropics, mushrooms and pesticides. Poisonings due to psychotropic drugs occurred at a steady rate during the period. For example, in 1984 there were 21.3 admissions per 100,000 inhabitants per year. Neuroleptics were the most common psychotropic drugs. Antidepressants caused fewer poisonings than did sleeping pills, which increased steadily to 13.9/100,000 inhabitants. Poisonings due to cardiovascular drugs declined, paralleling a decrease in digoxin prescriptions. During the period studied there were 13 to 14 admissions/100,000 inhabitants/year due to alcohol. The rate of cases of corrosive and solvent intoxication was steady at about 3 admissions/100,000 inhabitants/year.

In the Netherlands since 1980, 16 situations have been identified in which man might be exposed to environmental pollutants. This paper provides an overview of these incidents and describes how health risk assessments, public studies and provision of individual medical toxicological care are dealt with. The importance of involving general practitioners and other primary health care personnel at an early stage is stressed. © 1985 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.

The Taiwan National Poison Center has received more than 30,000 telephone calls since its establishment in July 1985. To obtain more information about poisoning exposures in Taiwan, a retrospective analysis was conducted of all telephone calls to the center concerning human poisoning exposures July 1985 through December 1993. The following data were tabulated: age, sex, intent of exposure, route of exposure, substances ingested and clinical severity. During the eight years (1985-1993), 23,436 telephone calls concerning human poisoning exposure were recorded. Adults accounted for most cases (75.2%) and exposures involving males (54.2%) were somewhat more prevalent than female poisoning exposures (44.7%). Intentional poisonings (54.6%) were more common than unintentional poisonings (40.1%), with an inverse relationship in pediatric poisoning exposures. After amphetamines, the most frequently ingested poisons were pesticides, benzodiazepines, and cleaning products. Fatalities occurred most frequently following ingestion of pesticides. The mortality rate was 5.7% for all exposures. Human poisoning is a serious problem in Taiwan. The reduction of suicide attempts is a major objective. Childhood poisonings are underreported and of high mortality.

To characterize beta blocker-related deaths. This is a retrospective review of beta blocker-related exposure data and fatality case abstracts reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System during the 11 year period, 1985 to 1995. Historical and laboratory data were used to determine those fatalities which resulted primarily from beta blocker intoxication. Of 52,156 reported beta blocker exposures, 164 were fatal. In 38 cases, beta blockers were implicated as the primary cause of death. Propranolol was responsible for the greatest number of exposures (44%) and implicated as the cause of death in a disproportionately high percentage of fatalities (71%). Patients were generally young women; 63% were female and 92% were less than 50 years old. The dysrhythmias most often noted in fatal cases were bradycardia and asystole. Cardiopulmonary arrest did not develop until patients were in the care of health care personnel in 59% of cases. Though glucagon was initiated more often than any other intervention in fatal intoxications (83%), optimal dosing and maintenance infusions appear to have been underutilized. The predominance of fatalities associated with propranolol compared to other beta blockers reflects both its greater frequency of use over the time period studied and its greater toxicity. Since 59% developed. cardiac arrest after reaching health care personnel, further study should focus on identifying medical intervention that can reduce mortality in this group.

This study analyzed 9,086 human exposures involving N,N-diethyl-m-toluamide--containing insect repellents that were reported to Poison Control Centers from 1985-1989. Nearly two-thirds of those exposed had no adverse effects or only experienced minor symptoms that resolved rapidly. Symptoms were more likely to occur after ocular or inhalation exposures and least likely to occur if the product was ingested. The only reported death occurred in a patient who suicidally ingested 8 oz of an insect repellent containing N,N-diethyl-m-toluamide. Five patients may have experienced a serious or potentially life-threatening effect but the poison center record did not provide unequivocal substantiation of the effect or clearly establish N,N-diethyl-m-toluamide as the causative agent. From the analysis of those patients calling Poison Control Centers, it appears the risk of serious medical effects with the labeled use of N,N-diethyl-m-toluamide-containing insect repellents is low in comparison with its reported annual use by about 30% of Americans. For patients contacting Poison Control Centers, the occurrence of adverse effects appears to be related to the route of exposure rather than age or gender of the patient or the concentration of N,N-diethyl-m-toluamide in the product.

Injuries involving chemicals occur aboard merchant ships, since such agents are carried commonly on board either as cargo or as needed for running the ship. In case of events involving chemicals, the crew may seek advice from the Medical First Aid Guide for Use in Accidents Involving Dangerous Goods published by the International Maritime Organization. The Guide is currently under revision. To improve knowledge of what is relevant in such a guide, a study was undertaken to identify all intoxications and corrosive incidents occurring aboard Danish merchant ships. A retrospective study of all intoxications and corrosive incidents reported to the Danish Maritime authorities between 1988 and 1996. A total of 177 injuries were identified, of which 66 were systemic poisonings and 111 were due to corrosive damage to the eyes and skin. Thirteen of 66 systemic poisonings were fatal and almost three out of four corrosive injuries involved the eyes. This study and others show that the majority of injuries aboard merchant ships involving dangerous goods are amenable to first aid and symptomatic measures. Specific antidotes seem to have a limited role aboard merchant ships.

An analysis of mushroom case exposures reported in 1989 to the American Association of Poison Control Centers "National Data Collection System" by poison centers in the United States was conducted to obtain a clearer view of mushroom poisoning epidemiology and outcome in the United States.