Free Oxycodone Concentrations in 67 Postmortem Cases from the Hennepin County Medical Examiner's Office

Abstract

Heart blood free oxycodone concentrations in oxycodone-related and mixed drug overdose deaths were compared with those found incidentally at autopsy in medical examiner cases. Between 2000 and 2005, 67 oxycodone-positive postmortem cases were identified. Thirty of 67 cases (44.8%) were determined to be drug overdoses. Oxycodone alone was responsible for 7 of the 30 (23.3%) overdose deaths. Mean (median) oxycodone concentrations were 1.060 mg/L (0.824 mg/L) with a range of 0.270-3.390 mg/L. Three cases were accidents, three were suicides, and one was undetermined. The remaining 23 were mixed drug overdoses. Mean (median) oxycodone concentrations in these cases were 0.820 mg/L (0.470 mg/L) with a range of 0.014-3.800 mg/L. Sixteen mixed drug overdoses were accidental, and seven were suicidal. Where oxycodone was an incidental finding, 24 were natural, 6 accident, 4 suicide, 1 homicide, and 2 undetermined. The mean (median) concentrations in the incidental finding group were 0.330 mg/L (0.150 mg/L) with a range of 0.017-1.300 mg/L. In conclusion, the findings substantiate the considerable overlap that exists with blood oxycodone concentrations in cases where oxycodone alone was determined to be the cause of death compared with mixed drug overdoses and incidental findings. Free oxycodone concentrations in postmortem cases must be interpreted in the context of the deceased's past medical history and autopsy findings.

Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone

“…Both ethanol and opioids cause respiratory depression and oversedation, potentially lethal adverse effects, and synergism can be supra-additive. Expanding the use of oxycodone has led to a higher count of unintentional overdose deaths [164]; simultaneous use of alcohol may further add to this risk [165].…”

Ethanol Reversal of Tolerance to the Antinociceptive Effects of Oxycodone and Hydrocodone

“…Multiple postmortem analyses have shown that individuals who consumed opioids such as heroin along with alcohol died from blood opioid concentrations measuring significantly lower than those who died from an opioid without alcohol consumption (Darke and Hall, 2003). Additionally, a separate study that specifically investigated oxycodone-related overdoses reported that deaths resulting from the combined intake of oxycodone and ethanol were ruled to be exclusively accidental, rather than intentional (Thompson et al, 2008). Although it is possible that a general lack of awareness exists among opioid users regarding the dangers related to coconsumption of ethanol with opioids, it is likely that these individuals experience some enhancement of opioid effects when used together, leading to riskier drug-taking behavior to offset the tolerance(s) developed to the opioids.…”

Heroin‐related Deaths from the Hennepin County Medical Examiner's Office from 2004 Through 2015

“…For drug analyses in the laboratory, all chemicals were of analytical grade (Sigma‐Aldrich, St. Louis, MO, USA) unless noted. Free and total opioids were quantified for codeine, morphine, hydrocodone, hydromorphone, along with free oxycodone and free oxymorphone, as previously described , using an Agilent GC/MS (6890/5973) equipped with a DB‐5 capillary column. Briefly, after glucuronide treatment (blood total opioids only) and solid‐phase extraction (Clean Screen, United Chemical Technologies, Inc., Bristol, PA, USA), samples were derivatized with N,O‐Bis(trimethylsilyl)trifluoroacetamide (BSTFA).…”

“…The interpretation of postmortem opioid concentrations in urine, blood, and tissues is complex, and numerous studies have examined this in various settings, including death investigations . Opioid concentrations measured following appropriate therapeutic, prescription use guided by providers can overlap with abusive or illicit use.…”