Toxicology and pathology of deaths related to methadone: retrospective review

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Abstract
To clarify the mechanisms and risk factors of methadone toxicity and to describe the findings of deaths related to methadone use Design Retrospective review of case notes in the records of the San Francisco Medical Examiner comparing the findings in cases where methadone was deemed the cause of death with findings in decedents where methadone was an incidental finding, and with 50 age-matched, disease and drug free, trauma victims. 38 cases out of the 3317 processed by our office during 1997-1998 were identified in which methadone had been detected. Cases were mostly male 28/38 (74%) and white, 28/38 (74%). In 17 of 38 cases death was deemed to have been caused by methadone toxicity. For the group the mean blood methadone concentration for all 38 patients, was 957 ng/ml SD = .681, SE = .14). The mean blood concentration of the main methadone metabolite (EDDP) was 253 ng/ml, SD = 529 ng/ml, SE = .089. The mean ratio of methadone in the blood to EDDP in the blood was 13.6:1 Values were not significantly different between cases in which methadone toxicity was the cause of death and in those in which it was an incidental finding. Cocaine, or the cocaine metabolite benzoylecgonine, was detected in the blood or urine of 16/38 cases (42%); morphine in one-third (13/38) and methamphetamine in only one. Pulmonary edema was evident in all cases, coronary artery disease in 9/38 (24%) and cirrhosis in 7/38 (18%) of the methadone users. Necrotizing fasciitis was the cause of death in 4 of the 38 methadone users (11%). Nationally, a sizeable percent of methadone deaths are from drugs diverted from treatment programs. The presence of methadone is often an incidental finding during postmortem examination which is unrelated to the cause of death. Postmortem measurements of methadone or its metabolite, or both, cannot be used in isolation to identify which deaths are associated with methadone toxicity.