Acetaminophen overdose: workup and management
Acetaminophen poisoning is common and treatable. Plot a 4–24 hour level on the Rumack–Matthew nomogram for a single acute ingestion; start IV N-acetylcysteine for any level above the treatment line, for unknown timing or repeated supratherapeutic ingestion with abnormal labs, and for any liver injury. Watch for acute liver failure and refer early to a transplant center.
Working diagnosis
Adult · US guidelines
Draft · awaiting physician review
01Orient
What's new in the evidence
- 2023 US/Canada consensus statement on acetaminophen poisoning: standardized risk assessment, NAC regimens (including two-bag) and stopping criteria
- ACG 2023 acute liver failure guideline: IV NAC preferred and started immediately when toxicity is suspected; continue beyond the standard protocol if INR >1.5 or encephalopathy
- Fomepizole for massive ingestions is under study; not yet standard
Differential diagnoses
- Acute single ingestion
- Repeated supratherapeutic ingestion (often with alcohol or fasting)
- Co-ingestion (opioids, salicylates, anticholinergics) (can't miss)
- Other causes of acute liver injury: ischemic, viral, drug-induced, mushroom
- Intentional self-harm (can't miss: psychiatric assessment)
02Assess
Risk scores and decision tools
- Rumack–Matthew nomogram (US treatment line 150 mcg/mL at 4 h) for single acute ingestion with known time
- King's College criteria for transplant referral (pH <7.30 after resuscitation, or INR >6.5 + creatinine >3.4 + grade 3–4 encephalopathy)
- MELD and lactate in acute liver failure
Key history questions
- Time, amount and formulation (extended-release, combination products)
- Single vs repeated ingestion; co-ingestants
- Alcohol use, malnutrition, enzyme-inducing drugs
- Intent and current suicidality
- Vomiting, RUQ pain, confusion
Examination findings
- Often normal early
- RUQ tenderness, jaundice (day 2–3)
- Encephalopathy grade, asterixis
- Signs of co-ingestants
03Investigate
Initial investigations
- Acetaminophen level at 4 hours after ingestion (or on arrival if later)
- AST/ALT, bilirubin, INR, BMP, glucose, lactate, blood gas
- Salicylate level, ECG, ethanol, pregnancy test
- Repeat acetaminophen level and LFTs before stopping NAC
Advanced investigations
- Phosphate (high phosphate predicts poor outcome)
- Ammonia and CT head if encephalopathy
- Transplant evaluation labs
04Treat
Immediate management
- Activated charcoal 1 g/kg within 4 hours if airway is protected (benefit possible later with large or extended-release ingestions)
- Start IV NAC immediately if ingestion time is unknown, ingestion >8 hours ago, or level above the treatment line
- Treat co-ingestants; psychiatric safety precautions
First-line treatment
- IV NAC 21-hour regimen: 150 mg/kg over 1 h, then 50 mg/kg over 4 h, then 100 mg/kg over 16 h (or two-bag: 200 mg/kg over 4 h then 100 mg/kg over 16 h)
- Continue NAC (at the last infusion rate) until acetaminophen is undetectable, AST/ALT falling and INR <2 with no encephalopathy
- Glucose monitoring and correction
Second-line treatment
- Acute liver failure: ICU, early transplant center referral, treat cerebral edema risk, CRRT for AKI or hyperammonemia
- Massive ingestion (levels far above the line): higher NAC dose and toxicology input; hemodialysis for coma with metabolic acidosis
Specialist referrals
- Poison control center (1-800-222-1222)
- Toxicology
- Hepatology/transplant for liver failure
- Psychiatry for intentional ingestion
05Disposition
Admission criteria
- Any patient needing NAC
- Liver injury, acidosis or encephalopathy
- Intentional ingestion pending psychiatric assessment
Safe discharge criteria
- Level below the treatment line at ≥4 h with normal AST, or NAC completed with stopping criteria met
- Medically cleared and psychiatric assessment complete
Follow-up timing
- Psychiatric follow-up after intentional ingestion
- LFTs in a few days if mild injury
Patient instructions
- Check combination products for hidden acetaminophen; limit to package maximums
Monitoring
- AST/ALT, INR, creatinine, glucose every 12–24 hours
- Mental status
Clinical pearls and pitfalls
- The nomogram does not apply to repeated ingestions, unknown timing or extended-release products
- NAC is nearly 100% protective if started within 8 hours
- Anaphylactoid reactions to IV NAC are usually rate-related; pause, treat and restart
RefGuidelines and landmark evidence
For education only. Typical adult starting points; confirm doses against renal function, allergies, interactions and your institution's protocols. Not a substitute for clinical judgment or senior review.