SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

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LOW DOSE ACETAMINOPHEN DEATHS
Olaf H. Drummer*, Victorian Institute of Forensic Medicine, Department of Forensic Medicine, Monash
University, 57-83 Kavanagh St, Southbank 3006 AUSTRALIA, e-mail olaflal,yifin.org
Acetaminophen (paracetamol) is a commonly used over the counter analgesic. It is well known that use of
excessive doses can lead to the development of liver toxicity. This is mediated through the formation ofthe
toxic metabolite N-acetyl benzoquinone imine. In adults single doses required to initiate liver necrosis is
believed to start from 6 to 10 grams, which is about 12 to 20 500-mg tablets. Typically blood
concentrations are well over 200 mgIL. This presentation describes acetaminophen toxicity in three women
following doses within therapeutic guidelines.
Case 1. The deceased was a 28 year old female of age with a history of an eating disorder, depression and
alcoholism. While in hospital for an unrelated condition she became drowsy, weak, ataxic, and had slurred
speech. She died some hours later. She had received about ten tablets over the previous 3-4 days. Her
maximum acetaminophen concentration was 38 mgIL.
Case 2. The deceased was a 21-year-old healthy woman. She developed a laceration after falling on glass.
Three days later she presented to hospital with severe headache associated with vomiting and mild
photophobia. A few days later she was weak, was vomiting and had a high heart rate. She was diagnosed
with hepatic encephalopathy and her acetaminophen concentration was 46 mglL. She had taken about 10
acetaminophen tablets over a few days. Other causes of liver necrosis were excluded by exhaustive
toxicology, serology and virology testing.
Case 3. This 45-year old woman had undergone surgery for an obstructed bowel. A few days later she was
confused and agitated. This worsened until her death on day six. The day previously she had been
diagnosed with liver failure. Her maximum acetaminophen concentration was 46 mgIL. She had been
given one gram acetaminophen two to three times daily for several days prior to her death.
All cases showed typical liver necrosis at post-mortem and had clinical changes consistent with
acetaminophen toxicity. None of the cases had circumstances suggesting recent abuse of acetaminophen.
The low acetaminophen concentration and absence of other causes of liver necrosis suggests that some
persons may be sensitive to this drug, perhaps because of low glutathione concentrations due to diet or
genetic factors and/or were genetically predisposed to the development of the toxic metabolite. A full
account ofthe toxicology and post-mortem findings will be presented.
Keywords: acetaminophen, low-dose, toxicity, post-mortem
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