acetaminophen poisoning

Introduction

In acute acetaminophen overdose, the main site of injury is the liver. 1-10% of patients treated only with supportive care with suffer acute renal failure in conjunction withsevere hepatic failure.

Etiology

• toxicity occurs when the amount of acetaminophen ingested exceeds the liver's capacity of glucuronidation &sulfation
• metabolism of acetaminophen by hepatic microsomal enzymes results in a reactive intermediate which overwelmsthe detoxification capacity of glutathione S-transferase
• risk factors
  • 2.6 g/day may be toxic in a poorly nourished alcoholic
  • fasting reduces glutathione stores
  • critically illness
  • malnutrition
  • liver disease
  • chronic kidney disease
  • vegetarians

Epidemiology

• 1/2 of overdoses are unintentional
• individuals taking multiple acetaminophen-containing medications & elderly at risk
• female (80%)

Pathology

• hepatitis begins in phase 2
• hepatic necrosis occurs in phase 3
• complete resolution of hepatic dysfunction in phase 4 unless irreversible injury has occurred
• pyroglutamic acidosis

Clinical manifestations

• phase 1
  • may begin shortly after ingestion
  • duration 12-24 hours
  • nausea, vomiting, anorexia, diaphoresis
  • most patients will be asymptomatic
• phase 2
  • 24-72 hours after ingestion
  • right upper quadrant pain, nausea/vomiting, tachycardia, hypotension
• phase 3
  • 72-96 hours
  • resembles severe viral hepatitis
  • hepatic encephalopathy
• phase 4
  • 4 days to 2 weeks
  • resolution

Laboratory

• abnormal liver function tests (phase 2)
  • serum ALT may be > 6000 U/L
    • levels < 300 U/L suggest another diagnosis
• serum acetaminophen levels
  • serum levels > 200 ug/mL obtained at least 4 hours after ingestion mandate N-acetylcysteine administration
  • average levels
    • 840 ug/mL with intentional overdose
    • 160 ug/mL with unintentional overdose
  • for other labs, see acetaminophen
• elevated pyroglutamate in urine

Management

• gastric decontamination
  • ipecac: beneficial only within 2 hours of ingestion
  • gastric lavage
    • performed prior to administration of charcoal
    • 34-40 French orogastric tube (adults)
    • 150-200 mL aliquots of warm water or normal saline
    • 5-10 liters total
    • beneficial only within 2 hours of ingestion
  • activated charcoal
    • with & without sorbitol
    • beneficial within 4 hours of ingestion
• antidote: N-acetylcysteine
  • maximum benefit with 8 hours, but useful up to 24 hours after ingestion
    • start prior to serum acetaminophen results if presentation >= 8 hours after suspected ingestion
    • 12 hours of treatment sufficient
  • oral
    • load 140 mg/kg PO or NG, then
    • 70 mg/kg q 4h X 17
    • may be mixed in water or soda
  • intravenous:
    • 140 mg/kg infused into a peripheral IV over 1 hour using an in-line 0.2-m millipore filter
    • maintenance doses q4h of 70 mg/kg infused into a peripheral IV over 1 hour using an in-line 0.2-m millipore filter
    • IV solution made by diluting a 20% solution of acetylcysteine to 3% with D5W
    • modified acetylcysteine regimen
      • infusion of a total dose of 300 mg/kg over 12 hours, vs roughly 20 hours
      • lower initial dose (100 mg/kg over 2 hours, vs 150 mg/kg over 15 minutes in the U.K. & 1 hour in the U.S.)
      • less vomiting or the need for rescue antiemetics within 2 hours
  • average length of treatment is 48 h
  • treatment may be stopped after 5 initial doses of acetylcysteine (20 hours) when:
    • acetaminophen level is undetectable
    • ALT, AST & PT (INR) are normal
• sodium bicarbonate
• once severe hepatic toxicity has occurred, treatment is supportive

More general terms

• toxicity; poisoning; overdose

Additional terms

• acetaminophen (Tylenol, Paracematol, Panadol, Tempra, Datril, APAP, non-Aspirin)
• acetylcysteine (Mucomyst, Mucosol, Acetadote)