Postmortem Toxicology

Very few fatalities have ever been reported (or studied), but it appears that the therapeutic index for ephedrine is very great. A 1997 case report described a 28-year-old woman with two prior suicide attempts, who died after ingesting amitriptyline and ephedrine. The blood ephedrine concentration was 11,000 ng/mL, and the liver concentration was twice that value (kidney, 14 mg/kg; brain, 8.9 mg/kg). The amitriptyline concentration was 0.33 mg/kg in blood and 7.8 mg/kg in liver (131). Values in a second case report (where methylephedrine concentrations were nearly 6000 ng/mL) may or may not be relevant to the problem of ephedrine toxicity, as the individual in question took massive quantities of a calcium channel blocker, and it is not known whether methylephedrine exerts all the same effects as ephedrine (132). Baselt and Cravey mention the case of a young woman who died several hours after ingesting 2.1 g of ephedrine combined with 7.0 g of caffeine, but tissue findings were not described. Her blood ephedrine level was 5 mg/L, whereas the concentration in the liver was 15 mg/kg (133).

A report from the European literature describes the findings in a 19-year-old woman who committed suicide by taking 40 LetigenĀ® tablets (200 mg of caffeine and 20 mg of ephedrine) amounting to 10 g of caffeine and 1 g of ephedrine. She developed severe toxic manifestations from the heart, CNS, muscles, liver, and kidneys leading to several cardiac arrests, and died subsequently of cerebral edema and incarceration on the fourth day of hospitaliza-tion. Postmortem blood concentrations were not given (134).

Pseudoephedrine concentrations, but not measurements for ephedrine or any of the other enantiomers, have been published by the National Association of Medical Examiners in their Annual Registry report. In 15 children diagnosed with sudden infant death syndrome, the mean blood pseudoephe-drine concentration was 3.55 mg/L, the median 2.3 mg/L, with a range of 0.07-13.0 mg/L (SD = 3.36 mg/L). The authors of the study take pains to point out that "The data do not allow definitive statements about the toxicity of pseudoephedrine at a given concentration" (129).

In the only autopsy study yet published (135), all autopsies in the San Francisco Medical Examiner's jurisdiction from 1994 to 2001 where ephedrine or any its isomers (E+) were detected were reviewed. Cases where ephe-

drine or its isomers were detected were compared with those in a control group of drug-free trauma victims. Of 127 ephedrine-positive cases identified, 33 were the result of trauma. Decedents were mostly male (80.3%) and mostly Caucasian (59%). Blood ephedrine concentrations were less than 0.49 mg/L in 50% of the cases, with a range of 0.07-11.73 mg/L in trauma victims, and 0.02-12.35 mg/L in nontrauma cases. Norephedrine was present in the blood of only 22.8% (mean concentration of 1.81 mg/L, SD=3.14 mg/L) and in the urine of 36.2% of the urine specimens, with a mean concentration of 15.6 mg/L, SD=21.50 mg/L). Pseudoephedrine (PE) was detected in the blood of 6.3% (8/127). More than 88% (113/127) of the decedents who tested positive for ephedrine or one of its isomers also tested positive for other drugs, the most common being cocaine (or its metabolites) and morphine. The most frequent pathological diagnoses were hepatic steatosis (27/127) and nephrosclerosis (22/127). Left ventricular hypertrophy was common, and coronary artery disease was detected in nearly one-third of the cases. The most common findings in the ephedrine-positive deaths reviwed were those generally associated with chronic stimulant abuse. There were no cases of heat stroke and no cases of rhabdomyolysis.

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