GHB. Club drug or confusing artifact?

GHB can be produced either as a pre- or postmortem artifact. The authors describe two cases in which GHB was detected and discuss the problem of determining the role of GHB in each case. In both cases, NaF-preserved blood and urine were analyzed using gas chromatography. The first decedent, a known methamphetamine abuser, had GHB concentrations similar to those observed with subanesthetic doses (femoral blood, 159 microg/ml; urine, 1100 microg/ml). Myocardial fibrosis, in the pattern associated with stimulant abuse, was also evident. The second decedent had a normal heart but higher concentrations of GHB (femoral blood, 1.4 mg/ml; right heart, 1.1 mg/ml; urine, 6.0 mg/ml). Blood cocaine and MDMA levels were 420 and 730 ng/ml, respectively. Both decedents had been drinking and were in a postabsorptive state, with blood to vitreous ratios of less than 0.90. If NaF is not used as a preservative, GHB is produced as an artifact. Therefore, the mere demonstration of GHB does not prove causality or even necessarily that GHB was ingested. Blood and urine GHB concentrations in case 1 can be produced by a therapeutic dose of 100 mg, and myocardial fibrosis may have had more to do with the cause of death than GHB. The history in case 2 is consistent with the substantial GHB ingestion, but other drugs, including ethanol, were also detected. Ethanol interferes with GHB metabolism, preventing GHB breakdown, raising blood concentrations, and making respiratory arrest more likely. Combined investigational, autopsy, and toxicology data suggest that GHB was the cause of death in case 2 but not case 1. Given the recent discovery that postmortem GHB production occurs even in stored antemortem blood samples (provided they were preserved with citrate) and the earlier observations that de novo GHB production in urine does not occur, it is unwise to draw any inferences about causality unless (1) blood and urine are both analyzed and found to be elevated; (2) blood is collected in NaF-containing tubes; and (3) a detailed case history is obtained.     

Methamphetamine-related deaths in San Francisco: demographic, pathologic, and toxicologic profiles

A study was undertaken to develop demographic, toxicologic, and pathological profiles of methamphetamine-related deaths. Anatomic and toxicologic findings in 413 deaths where methamphetamine was detected were compared with findings in a control group of 114 drug-free trauma victims. The number of cases per year did not change significantly over the course of the study. Mean age was 36.8 years, but 11% were over the age of 50. Decedents were overwhelmingly male (85.2%) and Caucasian (75%). Blood concentrations of methamphetamine and amphetamine were indistinguishable in cases where methamphetamine was related to the cause of death (MR) and cases where it was not (non-MR) (2.08 vs. 1.78 mg/L, p = 0.65, and 0.217 vs. 0.19 mg/L, p = 0.82). Coronary artery disease, ranging from minimal to severe multivessel, was identified in 79 of the 413 drug users, but in only six of the 114 drug-free controls (p = 0.0004), and MR decedents had enlarged hearts compared with controls. There were also ten cases of subarachnoid and intracranial hemorrhage in the MR group. Abnormalities of the liver (34%) and lungs (24.7%) were frequent. In 65% of these cases, death was due to accidental methamphetamine toxicity. In the remaining cases, methamphetamine was an incidental finding. We conclude that, in our jurisdiction, neither the rate of detection nor the number of methamphetamine deaths has increased significantly in the past 13 years. Decedents are almost all Caucasian males, and many were approaching middle-age. Methamphetamine use is strongly associated with coronary artery disease and with subarachnoid hemorrhage.     

HIV-infection in forensic autopsy cases

Sudden and unexpected death and violent death of persons with a high risk of acquiring HIV-infections, especially homosexual males and intravenous drug abusers, have to be investigated by forensic autopsies. Therefore every forensic pathologist has to be aware of this infection and should try to make the proper diagnosis. Three typical cases are described: (1) suicide by hanging, (2) homicide by cutting the throat and (3) intravenous heroin overdose. Merely retrospectively it could be cleared up that the deceased were homosexual but did not manifestly suffer from AIDS. The morphological findings in the lymph nodes and the postmortem serological findings are described in detail.     

Drug deposition in adipose tissue and skin: evidence for an alternative source of positive sweat patch tests

In a series of licit and illicit drug-related deaths, qualitative and quantitative analyses on extracts of adipose tissue and skin were performed by GC/MS. In all cases, the adipose tissue was found to contain drugs at concentrations lower than, approximately equal to, or even greater than the concentrations of the same analytes found in the blood, which may reflect a consequence of long-term chronic exposure, or acute intoxication, or some combination of both. Approximately one cubic inch of skin with adipose tissue was removed from the mid to lower abdominal region adjacent to the midline incision during autopsy. The drugs were recovered from the specimens following incubation and alkaline, acidic, and alkaline chloroform back extraction of one to three grams of tissue. Deuterated analogs of the analytes were added to the matrix at the beginning of the incubation period. Cocaine and free morphine (from heroin) were readily identified in several cases. The presence of these illicit drugs in adipose tissue raises significant forensic questions, especially the use of 'sweat patches' to monitor recent cocaine or heroin use in chronic drug users.     

National Association of Medical Examiners position paper on the certification of cocaine-related deaths

The National Association of Medical Examiners Committee on Cocaine-related Deaths recommends that the following guidelines be applied in the process of documenting, interpreting, and certifying potential cocaine-related fatalities. The committee cautions that the investigation of any drug-related death requires a complete investigation of the circumstances of death, the death scene, and past medical history. It is also necessary to have the results of the forensic toxicological analysis and those of a complete forensic autopsy examination prior to formulating an opinion as to the cause and manner of death. Cocaine should be considered the underlying cause of the death when 1 or more of the following is true: (1). the circumstances surrounding the death can be associated with an acute cocaine exposure and there are no supervening causes of death; (2). the immediate cause of death is directly due to a readily identifiable mechanism or disease such as a gunshot wound or a stroke, yet the acute use of cocaine was the direct underlying cause of the trauma or the disease process; and (3). chronic cocaine use leads to a disease that results in an ultimately fatal pathologic process leading to organ injury and death. The committee further cautions that reported drug levels may not directly relate to the toxic or lethal effects of the drug upon the patient. These guidelines are intended for use by practicing medical examiners and physicians who certify drug deaths, as well as providing education tools for students.     

Introduction to the forensic pathology of cocaine.

During the last several years, a clearer understanding of cocaine's effects on the body has emerged. Metabolism and tissue distribution are better understood. A diverse group of cocaine-related illnesses have been reported, but many appear to share the underlying mechanism of catecholamine toxicity. Knowledge of cocaine's metabolism makes possible certain conclusions about route of ingestion, time of use, and patterns of abuse in general. Knowledge of the histologic alterations known to be associated with cocaine use can pinpoint cocaine as the cause of death, even in cases where there are negligible blood levels. What follows is a brief review of recent observations that bear on the forensic aspects of cocaine abuse.     

Criteria for the interpretation of cocaine levels in human biological samples and their relation to the cause of death

The determination that cocaine is directly responsible for the immediate cause of death should be considered only when there is a reasonably complete understanding of the circumstances or facts surrounding the death. Another, more obvious and immediate cause of death must be absent, or, at least cocaine must be shown to be a significant contributing factor in the chain of medical findings that lead directly to the immediate cause of death. Not all death investigation requires the sequential steps described in this paper, but these steps must be considered early on in the investigation whenever there is scene, investigational, medical or a historical basis to believe that cocaine is directly related to the cause of death. A relatively high profile death when cocaine is known to be involved, or a death involving unusual behavior on the part of the deceased with police involvement are examples where these considerations may well apply. Information needs to be obtained as soon as possible to have the highest chance of successfully documenting the toxicologic basis for the diagnosis. These facts would include, but would not necessarily be limited to, a scene investigation (whenever possible), a careful review of the investigative reports from all involved agencies, the initial core temperature of the body as well as that of the environment at the time of the collapse or death, the past medical history of the individual, and the results of a complete forensic autopsy and toxicologic studies. Knowledge of and an understanding of the current relevant forensic literature on this subject should be available to the reviewer prior to any interpretation of the significance of cocaine upon a specific death.