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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

Diagnosis

  • 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 is not useful 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. (Adapted, with permission, from Daly FF et al. 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 Austr. 2008;188:296. © Copyright 2008 The Medical Journal of Australia. The Medical Journal of Australia does not accept responsibility for any errors in translation.)

Treatment

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

  • Oral N-acetylcysteine (NAC), 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 NAC (Acetadote), 150 mg/kg administered over 60 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hour (21-hour infusion)

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

  • Fulminant liver failure may require emergency liver transplantation

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

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