Morphine concentrations in fatalities after palliative treatment of acute burn injury

Abstract

The evaluation of a morphine concentration in postmortem blood is routine for a forensic toxicologist. We here report three fatal cases where we found high morphine concentrations with 7.96, 4.30, and 5.82 mg/l in femoral blood that have to be estimated as unusually high. All these individuals died due to severe burn injuries and obtained morphine in the context of their palliative care in the last hours of their lives. According to the autopsy results, the cause of death in case 1 was burn disease with burns of about 90% of the body surface area (BSA), case 2 burn trauma, and case 3 burn shock. Besides morphine, propofol, fentanyl, sufentanil, midazolam, diazepam, lorazepam, cefazolin, and rocuronium were detected in femoral blood. The findings fitted well with the detailed clinical documentation. Further evidence of therapeutic concentrations of quetiapine, duloxetine, and melperone could be matched to preexisting medication of the individuals. Physiologically based pharmacokinetic modelling (PBPK) was applied, developed for the intravenous administration of morphine, to find an explanation for the high morphine concentrations in femoral blood. Quantification of morphine in body fluids and tissue was performed to calculate morphine tissue concentration ratios to the morphine concentration in femoral blood. The presented cases show that pharmacokinetic simulations can reflect decreased renal clearance and decreased hepatic metabolism in general. However, this prediction is not sufficient to explain the high morphine concentrations in femoral blood measured here. It can be assumed that burn shock in particular leads to altered pharmacokinetics, namely decreased distribution of morphine.