Paracetamol Toxicity

The answer first

Paracetamol (acetaminophen) remains a leading cause of severe acute liver injury. Mechanism papers from 1973 showed that hepatotoxicity is caused by a toxic intermediate epoxide metabolite normally detoxified by glutathione but which, in excess, binds covalently to hepatic enzymes and proteins. The clinical name for that metabolite is N-acetyl-p-benzoquinone imine (NAPQI). [7][17]

Three rules govern the long case. [7][11][3]

1. Treat from the clock and the concentration, not from how well the patient looks. Early recognition and prompt N-acetylcysteine (NAC) can prevent hepatic injury; the early phase is often silent. [17][2]
2. The Rumack-Matthew nomogram applies to a single acute immediate-release ingestion with a known time. Australia and New Zealand, with the United States, use a treatment line starting at 150 mg/L at 4 hours, extending to 24 hours with a half-life of 4 hours. The United Kingdom lowered that line to 100 mg/L at 4 hours for all patients in 2012 and ceased separate risk-factor lines. Staggered, repeated-supratherapeutic, modified-release, and unknown-time ingestions are not plotted — they are treated on clinical and biochemical grounds. [7][8][11]
3. Once acute liver failure is established, the question is transplant triage. O'Grady's acetaminophen cohort linked poor prognosis to arterial pH below 7.30, prothrombin time greater than 100 s, and creatinine greater than 300 micromol/L. Arterial lactate identifies non-survivors earlier than those King's College Hospital (KCH) criteria. Keep giving acetylcysteine — Keays showed it still improves survival after fulminant hepatic failure has declared itself. [3][5][4]

DCE trap: Name the ingestion pattern first. "Single acute, known time — plot the 4-hour level on the ANZ 150 mg/L line" is a different patient from "staggered over days — nomogram invalid, start NAC, consider early liver-centre transfer." [6][8][11]

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References17Show ledgerHide ledger

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2. [2]Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985) N Engl J Med, 1988.PMID 3059186
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