Identifying cases of heroin toxicity where 6-acetylmorphine (6-AM) is not detected by toxicological analyses

Abstract

PurposeHeroin has a half-life of 2–6 min and is metabolized too quickly to be detected in autopsy samples. The presence of 6-acetylmophine (6-AM) in urine, blood, or other samples is convincing evidence of heroin use by a decedent, but 6-AM itself has a half-life of 6–25 min before it is hydrolyzed to morphine, so 6-AM may not be present in sufficient concentration to detect in postmortem samples. Codeine is often present in heroin preparations as an impurity and is not a metabolite of heroin. Studies report that a ratio of morphine to codeine greater than one indicates heroin use. We hypothesize that the ratio of morphine to codeine in our decedents abusing drugs intravenously will be no different in individuals with 6-AM present than in individuals where no 6-AM is detected, and we report our study of this hypothesis.MethodsAll accidental deaths investigated by the Jefferson County Coroner/Medical Examiner Office from 2010 to 2013 with morphine detected in blood samples collected at autopsy were reviewed. Five deaths where trauma caused or contributed to death were excluded from the review. The presence or absence of 6-AM and the concentrations of morphine and codeine were recorded for each case. The ratio of morphine to codeine was calculated for all decedents. Any individual in whom no morphine or codeine was detected in a postmortem sample was excluded from further study. Absence or presence of drug paraphernalia or evidence of intravascular (IV) drug use was documented in each case to identify IV drug users. The proportion of the IV drug users with and without 6-AM present in a postmortem sample was compared to the M/C ratio for the individuals.ResultsOf the 230 deaths included in the analysis, 103 IV drug users with quantifiable morphine and codeine in a postmortem sample were identified allowing for calculation of an M/C ratio. In these IV drug users, the M/C ratio was greater than 1 in 98 % of decedents. When controlling for the absence or presence of 6-AM there was no statistically significant difference in the proportion of IV drug users when compared to non IV drug users with an M/C ratio of greater than 1 (p = 1.000).ConclusionThe M/C ratio in IV drug users, if greater than 1, is seen in deaths due to heroin toxicity where 6-AM is detected in a postmortem sample. This study provides evidence that a M/C ratio greater than one in an IV drug user is evidence of a death due to heroin toxicity even if 6-AM is not detected in the blood. Using the M/C ratio, in addition to scene and autopsy findings, provides sufficient evidence to show heroin is the source of the morphine and codeine. Listing heroin as a cause or contributing factor in deaths with evidence of IV drug abuse and where the M/C ratio exceeds 1 will improve identification of heroin fatalities, which will allow better allocation of resources for public health initiatives.

Corrected US opioid‐involved drug poisoning deaths and mortality rates, 1999–2015

“…Second, drug mentions on death certificates may contain errors. For instance, heroin use may sometimes be attributed to morphine or codeine . Third, some ICD‐10 codes lack desired specificity.…”

An analysis of issues in the classification and reporting of heroin‐related deaths

“…The re‐examination of unintentional drug overdose deaths in the United States led to the identification of a large number of heroin‐related deaths that had been attributed to morphine and codeine toxicity, as well as cases that were missed because of inconsistencies in the cause of death certification . Previous studies have demonstrated a reliance on 6‐AM detection, the generally limited use of alternate toxicological markers such as morphine and codeine ratios as evidence of heroin use which can contribute to variability in the attribution of a death to heroin . Fatal heroin overdose cases often involve multiple drug use; however, non‐specific death certification has been previously reported to significantly contribute to the under‐reporting of drug‐related deaths and was also identified as a major contributor to heroin‐related death under‐reporting in this study .…”

Methodological Complexities in Quantifying Rates of Fatal Opioid-Related Overdose

“…For example, epidemiologists can utilize toxicology data to improve estimates of heroin involvement in overdose deaths where the definitive heroin metabolite, 6-acetylmorphine (6-AM), was not detected by toxicological analyses, but other data indicate heroin ingestion. Heroin-specific analytes often go undetected due to the rapid metabolism of heroin to 6-AM, and the subsequent metabolism of 6-AM to morphine [ 61 ]. However, codeine is often present in heroin as an impurity.…”

“…However, codeine is often present in heroin as an impurity. Recent research has demonstrated that a morphine-to-codeine concentration ratio greater than 1 in toxicological data is a strong and probable indicator of heroin involvement and can be used to adjust the heroin-related overdose count/rate estimations [ 61 – 68 ]. Roxburgh et al provided flowcharts for distinguishing between morphine, codeine, and heroin deaths [ 69 ].…”