Are “Fatal” Opioid Concentrations Really Fatal?

When medical examiners conclude that the cause of death is opioid overdose, they rely primarily on the opioid blood concentration level in comparison to a pre-determined “fatal” cutoff. This approach is potentially inaccurate; the fatal ranges used are wide, and they overlap significantly with the ranges for living opioid users.

Numerous fatal ranges have been quoted for methadone: 220-3040μg/L (mean, 1371), 320-2980μg/L (mean, 772), and 600-3000μg/L. Baselt’s Disposition of Toxic Drugs and Chemicals in Man found fatal levels of 400-1800μg/L (mean, 1000) and 60-3100μg/L (mean, 280). These ranges are much too broad for determining cause of death because they include ranges experienced by many living users.

Worm et al. (1992) compared the methadone blood concentration levels of individuals who reportedly died from methadone toxicity while in treatment, out of treatment, or living: 30–1240μg/L (mean, 470), 30–990μg/L (mean, 270), and 30–560 μg/L (mean, 140). While the mean was lower for living methadone users, the ranges overlapped substantially.

Loimer and Schmid (1992) found a blood concentration range of 20–1308 μg/L (mean, 451.4) after a moderate oral methadone dose in 104 living addicts. Gagajewski and Apple (2003) found blood concentration ranges in deaths where methadone was an incidental finding of 180-3000 μg/L (mean, 1100 μg/L). In contrast, by Milroy and Forrest (2000) found the mean methadone range for those who reportedly died from methadone toxicity as 584–2700μg/L (mean, 584), with the majority under 500 μg/L.

Karch and Stephens (2000) compared the blood concentration levels between deaths “caused” by methadone toxicity and deaths where methadone was an incidental finding; they found no statistically significant difference.

Fatal morphine to blood concentrations from heroin use also vary widely. The minimum fatal concentration under North Carolina standards is 100μg/L, and Baselt has given fatal ranges of 50-3000 μg/L (mean, 430) and 10-1100 μg/L (mean, 300). Steven Karch, in his book Pathologies of Drug Abuse, examined twelve studies regarding fatal morphine concentrations and also found a wide range of fatal levels, from 100-2800 μg/L.

Darke et al. (1997) compared morphine concentration levels of current heroin users and heroin overdose deaths. Heroin-related deaths had a higher median concentration (350μg/L versus 90μg/L), but the concentrations overlapped substantially. In particular, a third of current users had morphine concentrations double the “fatal” level of blood morphine concentration.

Darke et al. (2007) compared the morphine concentration levels in deaths ruled morphine toxicity with those ruled homicide but with morphine in the body, finding no significant difference between the two groups.

With fatal toxic concentrations levels being so broad and overlapping with ranges that many addicts live with, a toxicology report is of little help when determining the cause of death. These broad ranges can skew medical examiner’s reporting and lead to an overrepresentation of heroin and methadone overdoses.

Theseus Schulze contributed to this blog post.