Toxicology and pathology of deaths related to methadone: retrospective review

Abstract

Toxicology and pathology of deaths related to methadone: retrospective review ABSTRACT ⅷ Objectives 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. ⅷ Results 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. ⅷ Conclusions 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.

Demographic, pathologic, and toxicological profiles of 127 decedents testing positive for ephedrine alkaloids

“…No significant differences in ephedrine concentrations were found either in central blood or peripheral blood, in the trauma or non-trauma cases. This same pattern has been observed with other abused drugs, where it has been found that blood drug concentration measurements do not reliably differentiate between cases where the presence of a drug is an incidental finding, and cases where it is the cause of death [25,26]. It is interesting to note that even in the presence of other stimulants including cocaine and methamphetamine, ephedrine blood concentrations in trauma and non-trauma deaths were indistinguishable.…”

Methadone and methadone metabolites in postmortem specimens

“…Previous investigators have commented that fatal and nonfatal levels of methadone overlap and that determination of the metabolite, EDDP, did not assist interpretation [1][2][3][4]. We have measured a second methadone metabolite, EMDP, in postmortem cases to gain a better understanding of the accumulation/distribution of this metabolite and also of the overall process of METH demethylation.…”

“…It is also used in management of chronic pain. These applications are longterm, involve escalating dosages, and persons in treatment often become tolerant to the desired and/or toxic effects of methadone [1][2][3][4].…”

“…For example, after a retrospective review of medical examiner cases involving methadone, Karch and Stephens [1] wrote that ''postmortem measurements of methadone or its metabolite, or both, cannot be used in isolation to identify which deaths are associated with methadone toxicity.'' Similarly, Milroy and Forrest [2], Gagajewski and Apple [3], and Wolf et al [4] reported overlapping methadone concentrations in postmortem tissues in cases where methadone toxicity either was or was not, the cause of death.…”

Methadone Deaths: Risk Factors in Pain and Addicted Populations

“…[19][20][21] These findings are consistent with reports in the US, in which the number of methadonerelated deaths have risen markedly. 6,7,22 Opioid-dependent patients with polysubstance use appear most vulnerable to methadone fatalities, 23 and the role of polysubstance use in methadone overdoses underscores the potential role of pharmacological interactions in these fatalities.…”