Fatal diphenhydramine intoxication in infants

Diphenhydramine is an antihistamine available in numerous over-the-counter preparations. Often used for its sedative effects in adults, it can cause paradoxical central nervous system stimulation in children, with effects ranging from excitation to seizures and death. Reports of fatal intoxications in young children are rare. We present five cases of fatal intoxication in infants 6, 8, 9, 12, and 12 weeks old. Postmortem blood diphenhydramine levels in the cases were 1.6, 1.5, 1.6, 1.1 and 1.1 mg/L, respectively. Anatomic findings in each case were normal. In one case the child's father admitted giving the infant diphenhydramine in an attempt to induce the infant to sleep; in another case, a daycare provider admitted putting diphenhydramine in a baby bottle. Two cases remain unsolved; one case remains under investigation. The postmortem drug levels in these cases are lower than seen in adult fatalities. We review the literature on diphenhydramine toxicity, particularly as it pertains to small children, and discuss the rationale for treating these cases as fatal intoxications.     

Acute intoxication with orphenadrine and clozapine.

This report describes a fatal intoxication with two different drugs: clozapine and orphenadrine. A 38-year-old man was found dead in the bedroom of his residence. Near the body were found various empty pharmaceutical boxes, employed in schizophrenic therapy, two of them containing clozapine and orphenadrine. High concentrations of clozapine and orphenadrine detected in blood, urine and gastric content were related to death. These compounds were identified and quantitated by liquid-liquid extraction followed by gas chromatographic/mass spectrometry (GC/MS) analysis.     

Acute fatal intoxication with narcotic substances during their intracavitary transportation

The authors describe a case of sudden death of a passenger on the train from Uzbekistan bound for Russia via Kazakhstan. The death was attributed to the poisoning with an illegally transported narcotic substance that was detected in the subject's stomach and intestines.     

Acute flurazepam intoxication: a case report

A fatality due to ingestion of flurazepam is reported. Flurazepam is a benzodiazepine, a widely prescribed hypnotic drug for use in sleep disorders. There are only few documented reports of the disposition of flurazepam in deaths due to overdose. A 68-year-old woman was found deceased at home with no evidence of trauma or asphyxia. Toxicologic analyses were performed and drug levels measured by means of gas chromatography coupled to mass spectrometry. The flurazepam concentration in each specimen was as follows: heart blood 2.8 microg/mL, bile 323 microg/mL, and urine 172 microg/mL. Presence of flurazepam into gastric content was observed too. Based on the autopsy findings, patient history, and toxicologic results, the cause of death was determined to be acute intoxication of flurazepam and the manner, suicide.     

Acute lethal alcohol intoxication (author's transl)]

In 14,744 autopsy cases from an 18-year period 92 cases (of which 7 were ruled out because of decomposition were observed in which death was supposed to be due to direct acute alcoholic intoxication. In the police reports 81 persons were designated as chronic alcoholics or abusers of spirits. The blood alcohol level ranged between 2.04 and 4.92 o/oo. The cases studied were divided into two groups, one with low and the other with high lethal alcohol level. Fatty liver and cirrhosis were found with identical frequency in the two groups, whereas cardiac hypertrophy of obscure origin occurred markedly more often in the group with low lethal blood alcohol level. On the basis the possible mechanism of death in the cases with cardiac hypertrophy is discussed. Finally, the relation between the blood and urine alcohol concentrations observed in 72 cases is discussed. On the assumption that the water phase of the blood was 75 per cent of the total blood, death occurred in the persons without cardiac hypertrophy with fairly identical frequency either in the phase of absorption or the phase of elimination, whereas in the persons with cardiac hypertrophy death most often occurred in the phase of absorption. These statements should, however, be taken with some reservation, partly because the water phase of the blood may vary considerably post mortem (60-90 per cent) and partly because the urine alcohol concentration depends on serval variable factors.     

Hypothermia and undressing associated with non-fatal bromazepam intoxication.

A 42-year-old woman with a history of depression was found unconscious, lying near her car in an early autumn morning. The lower part of her body was undressed and there were multiple purple spots and excoriations on the body suggesting at first a sexual assault. On admission to the intensive care unit, she presented a hypothermia with a central temperature of 28.4 degrees C. The biological samples obtained at the hospital were analysed. Blood concentration of bromazepam was 7.7 mg/l, which is above the highest level reported till now in a case of fatal intoxication.     

Acute arsenic intoxication: forensic and toxicologic aspects (an observation).

The authors report on an acute suicidal arsenic intoxication (di-arsenic-trioxide). Death can occur one week after ingestion, despite intensive care. The forensic, anatomopathological and toxicologic aspects are reported. Forty titrations are realized at the level of the biologic fluid in viscera, by absorption spectrophotometry. These data are compared with those in standing literature, especially with the rates determined in normal subjects, following simple environmental impregnation.     

Anxiety,alcohol intoxication,and aggression

Purpose. Research into alcohol‐related aggression has typically focused on perpetrators’ externalizing characteristics. The purpose of this exploratory review is to examine the contribution of anxiety to alcohol‐related aggression. Arguments. Anxiety disorders are associated with externalizing disorders in childhood, but anxiety appears to protect against extreme antisocial behaviours. In contrast, in adolescence and early adulthood, anxiety appears to be associated with increased risk of antisocial behaviour. One possible explanation for this disjunction may be alcohol use, which typically starts in adolescence. Alcohol is an anxiolytic drug, which may appeal to certain young people who are socially anxious but not socially avoidant. Alcohol myopia, the cognitive mechanism whereby alcohol exerts an anxiolytic effect, is also a mechanism by which alcohol serves to increase aggression. Therefore, in anxious antisocial people, drinking to cope with anxiety is likely to increase aggression. Conclusions. Interventions that flow from the research on anxiety, alcohol, and aggression are suggested.     

Report of a fatal, acute tripelennamine intoxication.

A death resulting from tripelennamine overdose in a 19-year-old male Caucasian is reported. The patient died 7 h after ingesting approximately twenty 50-mg tripelennamine tablets. A concentration of 1.0 mg/100 ml was found in the blood. All tissue concentrations were measured by ultraviolet spectroscopy and verified by gas-liquid chromatography. Significant findings included pulmonary edema and multiple small petechial hemorrhages in the soft tissue of the scalp.     

Fatal intoxication with a selective serotonin reuptake inhibitor, lorazepam, and codeine

Selective serotonin reuptake inhibitors were introduced in 1987 as an alternative treatment option for patients with depression or certain anxiety disorders. Unfortunately, this greater use has prompted a corresponding increase in reports of more severe side effects and fatalities, with a majority of fatalities occurring due to coingestion of selective serotonin reuptake inhibitors with other substances or serotonergic drugs. We report a case which exemplifies one such fatality related to sertraline, lorazepam, and codeine coingestion. A brief discussion of the presumed mechanism by which death occurred will be offered.     

Fatal intoxication with melperone

Melperone is judged to be a safe neuroleptic drug. Until now there has been no report of a melperone fatality, though it has been used in suicide attempts. We report on a case of a 36-year-old woman where no cause of death could be established at autopsy. Criminological investigation pointed to a homicide by poisoning but also the possibility of a suicide had to be taken in account. The toxicological analysis of blood, cerebral spinal fluid and urine revealed extremely high concentrations of melperone which had never been reported before. Furthermore, diazepam, nordazepam and carbamazepine were detected. To our knowledge, this case is the first melperone fatality. Possible interactions with diazepam and carbamazepine are discussed.     

Lithium intoxication. A case study

This study reports a fatal ingestion of lithium carbonate and its distribution in tissues and biological fluids.     

Bupropion and alcohol fatal intoxication: case report.

A fatality due to the ingestion of bupropion and ethanol is presented. Bupropion and its metabolites were extracted from several tissues and identified using gas chromatography with nitrogenphosphorus and mass spectrometry detection. The concentrations of bupropion, hydroxybupropion and the erythroamino and threoamino alcohol metabolites in heart blood were 4.2, 5.0, 0.6 and 4.6 mg/l, respectively. The heart blood ethanol concentration was 0.27 g/dl. In addition, bupropion was distributed as follows: subclavian blood, 6.2 mg/l; bile, 1.4 mg/l; kidney, 2.4 mg/l; liver, 1.0 mg/kg; stomach contents, 16 mg and urine, 37 mg/l.     

A case of fatal intoxication with ammonium sulfate and a toxicological study using rabbits.

Agricultural fertilizers such as ammonium sulfate are widely used in house gardens as well as in agriculture, but few case reports or toxicological studies of ingested fertilizers have been reported. This paper investigates a fatal case of ammonium sulfate poisoning and demonstrates its clinical and biochemical findings in rabbits. An 85-year-old woman was found dead lying on the ground outside her house in the middle of March, but the autopsy could not determine the cause of her death. Examination at the police laboratory of the solution in the beer can found next to her showed that it was very likely ammonium sulfate. Our measurement showed a significant increase of ammonium and sulfate ions in serum and gastric contents. The cause of her death was determined as poisoning by ammonium sulfate. The total dose of 1500 mg/kg of ammonium sulfate was administered to three rabbits, all of which showed similar symptoms such as mydriasis, irregular respiratory rhythms, local and general convulsions, until they fell into respiratory failure with cardiac arrest. EEG showed slow, suppressive waves and high-amplitude slowing wave pattern, which is generally observed clinically in hyperammonemia in man and animal. There was a remarkable increase in the concentration of ammonium ion and inorganic sulfate ion in serum, and blood gas analysis showed severe metabolic acidosis. These results, mainly findings by EEG, have shown that a rapid increase in ammonium ions in blood can cause damaging the central nervous system without microscopic change. When the cause of death can not be determined, measurement of ammonium ion, inorganic ion and electrolytes in blood as well as in stomach contents at forensic autopsy is necessary.     

Fatality from diphenhydramine monointoxication: a case report and review of the infant, pediatric, and adult literature

As an antihistamine, diphenhydramine (DPH) is well known for its use in allergy treatment. Since its introduction in 1946, it has been marketed under various trade names, the most popular being Benadryl. Three years after its introduction, the first fatality due to DPH toxicity was reported in 1949.To better understand the incidence of fatalities due to DPH monointoxication, we reviewed deaths that were reported from 2 data sources: (1) the English-language literature using PubMed, from 1946 through 2003; and (2) the Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System (ARAAPCCTESS), from 1983 through 2002. The results were then tabulated using age, gender, clinicopathologic findings, and toxicology results.Combined results from both data sets show the following mean (and range) for age and DPH levels: Adult, 35.6 years (18-84) and 19.53 mg/L (0.087-48.5); pediatric, 8.6 years (1.25-17) and 7.4 mg/L (1.3-13.7); infant, 31 weeks (6 weeks-11 months) and 1.53 mg/L (1.1-2.2), respectively.Most deaths were certified as accident or suicide; however, 6 infant homicides were reported. The most common symptoms for all cases were cardiac dysrhythmias, seizure activity, and/or sympathetic pupil responses. The most common autopsy finding was pulmonary congestion.     

Fatal intoxication with amisulpride and presentation of organ distribution

Amisulpride is a substituted benzamide used as an atypical antipsychotic drug. It antagonizes dopamine D2 and D3 receptor-mediated effects with greater affinity for the limbic system suggesting better neurological tolerance than classical neuroleptics. However, occasionally amisulpride intoxications associated with seizures, comatose conditions and agitation, hyperthermia, tachycardia, prolongation of the QT interval and extrapyramidal features have been described. A 27-year-old female with a medical history of psychosis and amisulpride therapy was found dead at home. By means of high performance liquid chromatography coupled with mass spectrometry (LC/MS) an amisulpride concentration of 13.4 mg/l was found in the peripheral blood. A lower concentration in the brain and an extremely high concentration in bile can be explained by the polarity and hydrophobic character of the substance. After macroscopic and histological exclusion of other causes of death the results of the toxicological analysis were consistent with the assumption of a fatal amisulpride overdose.