10 June - Acetaminophen poisoning

This AMs case was a 30ish year old female who had been injured in a car crash approximately 2 weeks prior to admission.   On this occasion she was admitted with significant nausea, vomiting, and abdominal pain.  She had a history of heavy alcohol consumption for several years prior to admit.  In the three days leading to this admission she had taken over 30 acetaminophen tablets (dose unspecified).  On admit her transaminases were elevated >2000, her INR was 1.7, and the bilirubin was 3.  There was no evidence of encephalopathy.  Her admit acetaminophen level was 0.9.

Pearls:

Acetaminophen toxicity occurs when liver sores of glutathione are depleted and the toxic metabolite NAPQI accumulates.  Administration of N-acetyl cysteine (NAC) replenishes glutathione and allows clearance of NAPQI.  Alcohol consumption is a well established risk factor for more severe toxicity.

The Rumack-Matthew nomogram helps predict when toxicity will occur, but this nomogram is only valid for single large ingestions with a known time.  Ingestion of multiple doses over several days or ingestion of extended release formulations can provide misleading results.  Also watch your units - confusing micrograms/ml with micromoles/ml when plotting on the nomogram will throw you off significantly!

Ideally, NAC should be given before the LFTs are elevated to be effective.  Not all poison control centers recommend its use once the acetaminophen level has dropped <20 or is undetectable.  This article from NEJM calls this into question.  They recommend more liberal use of NAC, especially when LFTs are elevated.  They refer to 2 studies that show reductions in mortality on the order of 20% in the setting of fulminant liver failure when intravenous NAC is used.  The cost of NAC is modest - only $50 for a full 72 hour treatment course. 

The FDA has taken steps to relable acetaminophen, remove higher dose formilations from the OTC market, and eliminate drugs such as Vicodin and Percocet that have combinations of high dose acetaminophen and opioids.  They have yet to set formal recommendations for max dosage, but anticipate doses of 3.25 grams for healthy individuals and <2.5 grams or outright avoidance for those who consume ETOH or have liver disease.