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For further information, see CMDT Part 38-15: Acetaminophen

Key Features

  • Toxic dose: 150–200 mg/kg, but not to exceed 8–10 g (acute) or > 4 g/day (chronic)

  • Nausea, vomiting shortly after ingestion

  • Hepatic necrosis evident after 24–48 h

Clinical Findings

  • Nausea or vomiting shortly after ingestion

  • Hepatic aminotransferase levels begin to increase 24–48 after ingestion; there are usually no other signs of toxicity

  • With severe poisoning, fulminant hepatic necrosis may occur, resulting in

    • Jaundice

    • Hepatic encephalopathy

    • Acute kidney injury

    • Death

  • Rarely, massive ingestion (eg, serum levels over 500–1000 mg/L [33–66 mmol/L]) can cause

    • Early onset of acute coma

    • Seizures

    • Hypotension

    • Metabolic acidosis unrelated to hepatic injury


  • The diagnosis after acute overdose is based on measurement of the serum acetaminophen level

  • Plot the serum level versus the time since ingestion on the acetaminophen nomogram shown in Figure 38–1

  • Ingestion of sustained-release products or coingestion of an anticholinergic agent, salicylate, or opioid drug may cause delayed elevation of serum levels which can make interpreting the nomogram difficult

  • The nomogram cannot be used after chronic or staggered overdose

Figure 38–1.

Nomogram for prediction of acetaminophen hepatotoxicity following acute overdosage. Patients with serum levels above the line after acute overdose should receive antidotal treatment. (Reproduced with permission from Daly FF, Fountain JS, Murray L, Graudins A, Buckley NA; Panel of Australian and New Zealand clinical toxicologists. Guidelines for the management of paracetamol poisoning in Australia and New Zealand—explanation and elaboration. A consensus statement from clinical toxicologists consulting to the Australasian poisons information centres. Med J Aust. 2008;188(5):296–301.)


  • Oral activated charcoal (if given within 1–2 hours of acute ingestion)

  • Oral N-acetylcysteine, 140 mg/kg oral loading dose, followed by 70 mg/kg every 4 hours

  • Traditional US oral regimen 72 hours (17 doses), although equivalent success has been achieved with 20–48 hours of treatment

  • Intravenous N-acetylcysteine (Acetadote)

    • Loading dose: 150 mg/kg administered over 60 minutes

    • Followed by 50 mg/kg over 4 hours

    • Then 100 mg/kg over 16 hours

  • Very large ingestions of acetaminophen (reported ingestions of > 30 grams or if the measured serum acetaminophen level is greater than twice the nomogram line)

    • May require higher dose N-acetylcysteine

    • Clinicians should contact a regional poison control center or medical toxicologist for assistance

  • Treatment with N-acetylcysteine is most effective if it is started within 8–10 hours after ingestion

  • Fomepizole, a cytochrome 2E1 inhibitor

    • Has been proposed as an adjunctive therapy

    • Not routinely used

  • Hemodialysis is rarely indicated but might be needed in some patients with massive overdose

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