Death by paracetamol poisoning

Abstrakt trykket i konferansebok:::: DEATH BY PARACETAMOL POISONING Nordrum IS (1,2), Viset T (2), Slørdal L (1,3), Vege Å (1,2). (1) Institute of Laboratory Medicine, Children’s and Women’s Health, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway (2) Department of Pathology and Medical Genetics, St. Olavs Hospital, Trondheim, Norway (3) Department of Pharmacology, St. Olavs Hospital, Trondheim, Norway The non-prescription agent paracetamol (acetaminophen) is the most commonly used analgesic and antipyretic drug in our part of the world. Paracetamol is metabolised to water-soluble inactive compounds by conjugation with sulfate and glucuronide. Depletion of hepatic glutathione causing accumulation of the hepatotoxic non-conjugated metabolite N-acetylbenzoquinoneimine (NAPQI) is the mechanism responsible for liver necrosis. The risk for hepatotoxicity increases in states of liver disease and malnutrition, and concomitant use of hepatic inducers such as some antiepileptic drugs as well as heavy alcohol consumption have been suggested as factors with a potential to increase the vulnerability for liver damage. The maximum therapeutic daily dose in adults is 6000 mg. A single dose exceeding 120 mg/kg or daily doses of more than 75-90mg/kg can adversely affect liver function. Hepatocellular damage may lead to death from massive liver necrosis after a few days. The indication for use of the antidote N-acetylcysteine is determined by the serum level of paracetamol and time passed after intake according to the Prescott nomogram. Overdoses of paracetamol are regularly encountered. In medico-legal autopsy practice death due to possible intoxication by paracetamol is seen several times annually. The findings at autopsy are typically non-specific with micro- or macroscopically liver necrosis as the most prominent. The cause of death is established by information about the circumstances of death, the findings of liver necrosis at autopsy and the post mortem blood paracetamol concentration, usually analysed in specimens obtained from the femoral artery. Sometimes it is difficult to ascertain the cause of death in cases with paracetamol ingestion prior to death. The dose supposedly taken may not explain the measured blood concentration (or vice versa), the influence of post-mortal redistribution may confound the issues, interaction with other substances such as ethanol or drugs might be present, and possible differences in tolerance due to chronic illnesses may have relevance. We will present cases from our medico-legal autopsy practice that emphasise these problems.