Karla A. Moore

Tissue distribution of tramadol and metabolites in an overdose fatality

Tramadol (Ultram) is a centrally acting, synthetic analgesic agent. Although it has some affinity for the opiate receptors, tramadol is believed to exert its analgesic effect by inhibiting the re-uptake of norepinephrine and serotonin. There are several published cases of tramadols involvement in drug-related deaths and impairment. Reports of deaths involving tramadol alone with associated tissue concentrations are rare. This report documents a case in which tramadol overdose was identified as the cause of death. The following tramadol concentrations were found in various tissues: blood, 20 mg/L; urine, 110.2 mg/L; liver, 68.9 mg/kg; and kidney, 37.5 mg/kg. Tissue distributions of the two primary metabolites, N-desmethyl and O-desmethyl tramadol, are also reported. In each tissue or fluid except urine, the tramadol concentration was greater than either metabolite, consistent with other reports of drug-impaired drivers and postmortem cases. The O-desmethyl metabolite concentration was greater than the N-desmethyl metabolite concentration in all tissues; this is in contrast to other postmortem reports, in which the majority of cases report concentrations of O-desmethyl as less than those of N-desmethyl. This may be useful as an indicator of time lapse between ingestion and death.

Tissue Distribution of Ketamine in a Mixed Drug Fatality

While reports of ketamine abuse are increasing, reports of ketamine deaths and tissue concentrations associated with fatalities are rare. We report here a case of a mixed drug fatality involving ketamine and ethanol. Ketamine analysis was carried out by gas chromatography with a nitrogen-phosphorus detector (NPD). We found the following tissue concentrations: blood 1.8 mg/L; urine 2.0 mg/L; brain 4.3 mg/kg; spleen 6.1 mg/kg; liver 4.9 mg/kg, and kidney 3.6 mg/kg. The blood ethanol concentration was 170 mg/dL. Because an empty nalbuphine ampule was found in the possession of the deceased, the blood was assayed for this opioid compound using a gas chromatography/mass spectrometry (GC/MS) method. None was detected at a limit of detection of 0.02 mg/L.

A comparison of ethanol concentrations in the occipital lobe and cerebellum

While many publications have addressed the issue of ethanol concentration in brain tissue as a better indicator of impairment than blood alcohol concentration (BAC), very few have looked at the regional distribution of ethanol in the brain and its possible significance in postmortem sampling. This paper reports on the analysis of occipital pole and cerebellar hemisphere for ethanol in 25/brain samples obtained at autopsy from the brain collection of the National Institutes of Mental Health/Stanley Foundation. When available, these concentrations were compared to BAC. The average ratio of occipital lobe alcohol concentration (OAC) to BAC for cases which also had blood samples (18/24) was 0.9, SD = 0.5, with a range of 0-1.8; the average ratio of cerebellar alcohol concentration (CAC) to BAC for these cases was 0.6, SD = 0.4, range = 0-1.2. When only those cases with a BAC > or = 0.04 g/dl (14/18 cases) were considered, the average OAC/BAC and CAC/BAC ratios were 0.8 (SD = 0.4) and 0.7 (SD = 0.4), respectively. These distribution ratios are well within the ranges reported by other authors and do not significantly differ from each other. The cortical brain region available or selected for postmortem ethanol analysis is probably not critical.