Acetaminophen Overdose

KEY FEATURES

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

• Nausea, vomiting shortly after ingestion

• Hepatic necrosis evident after 24–48 hours

CLINICAL FINDINGS

• Nausea or vomiting shortly after ingestion

• Hepatic aminotransferase levels begin to increase 24–48 hours 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 > 500–1000 mg/L [33–66 mmol/L]) can cause

  • Early onset of acute coma

  • Seizures

  • Hypotension

  • Metabolic acidosis unrelated to hepatic injury

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 40–1

• 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

TREATMENT

• 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