What is the management for paracetamol (Acetaminophen) poisoning?

Management of Paracetamol (Acetaminophen) Poisoning

Administer N-acetylcysteine (NAC) immediately to all patients with acetaminophen levels above the treatment line on the Rumack-Matthew nomogram or when hepatotoxicity is suspected, as this is the only proven antidote that reduces mortality and prevents liver failure. 1

Initial Assessment and Risk Stratification

History and Laboratory Evaluation

• Obtain detailed history including the amount ingested, timing of ingestion (single acute vs. repeated supratherapeutic), formulation type (immediate vs. extended-release), and any co-ingestions 1, 2
• Draw baseline laboratory tests: AST, ALT, bilirubin, INR, creatinine, BUN, blood glucose, and electrolytes 1, 2
• Obtain plasma acetaminophen concentration at least 4 hours post-ingestion (earlier levels are unreliable and may not represent peak concentrations) 1, 2

Toxic Dose Thresholds

• Adults: Ingestions ≥10 grams or ≥150 mg/kg (whichever is lower) are potentially hepatotoxic 3, 4
• Children <6 years: Refer to emergency department if ≥200 mg/kg ingested acutely 5, 4
• High-risk patients (chronic alcohol use, malnutrition, CYP2E1 inducers): Toxicity can occur with doses as low as 4-5 g/day 1, 3

Gastrointestinal Decontamination

• Administer activated charcoal 1 g/kg orally if the patient presents within 4 hours of ingestion 1, 6
• Give activated charcoal just prior to starting NAC in patients with known or suspected overdose 1
• Most effective within 1-2 hours but may provide benefit up to 4 hours post-ingestion 1
• Critical caveat: Ensure airway protection is adequate, especially with co-ingestions (e.g., sedatives, alcohol) 1

Use of the Rumack-Matthew Nomogram

When to Use the Nomogram

• Only applies to single acute ingestions with known time of ingestion 1, 5, 2
• Plot acetaminophen level obtained 4-24 hours post-ingestion 1
• Do NOT use for: repeated supratherapeutic ingestions, unknown time of ingestion, or presentations >24 hours post-ingestion 1, 5

Treatment Thresholds

• Initiate NAC if acetaminophen level plots at or above the "possible toxicity" treatment line (the lower line on the nomogram) 1, 2
• The nomogram may underestimate risk in high-risk populations (chronic alcoholics, malnourished, patients on enzyme-inducing drugs like isoniazid)—treat these patients even with levels in the "non-toxic" range 1, 2

Extended-Release Formulations

• If initial 4-hour level is below the treatment line, obtain a second level at 8-10 hours post-ingestion 2
• If the second value is at or above the treatment line, initiate NAC immediately 2

N-Acetylcysteine (NAC) Administration

Standard Dosing Regimen

• FDA-approved three-bag regimen: Total dose of 300 mg/kg IV over 21 hours 1, 2

  • Loading dose: 150 mg/kg over 1 hour
  • Second dose: 50 mg/kg over 4 hours
  • Third dose: 100 mg/kg over 16 hours 2

• Alternative two-bag regimen (recommended by Australian/New Zealand guidelines): 200 mg/kg over 4 hours, then 100 mg/kg over 16 hours—this has similar efficacy but significantly reduced adverse reactions 6

Timing is Critical

• Within 8 hours: Severe hepatotoxicity risk is only 2.9% 1
• Within 10 hours: Risk increases to 6.1% 1
• After 10 hours: Risk jumps to 26.4% 1
• After 15 hours: 44% develop hepatotoxicity even with treatment 2, 7

Special Scenarios Requiring Immediate NAC (Do Not Wait for Labs)

Treat immediately without waiting for acetaminophen levels in these situations:

• Unknown time of ingestion with detectable acetaminophen level 1, 2
• Presentation >8 hours post-ingestion with known toxic dose 1, 2
• Clinical evidence of hepatotoxicity (elevated transaminases, right upper quadrant tenderness, vomiting) 1, 2
• Acetaminophen level unavailable within 8-hour window 2
• Fulminant hepatic failure from acetaminophen (regardless of time since ingestion) 1

Massive Overdose Management

• For ingestions ≥30 g or ≥500 mg/kg, use increased doses of NAC 6
• For acetaminophen concentrations more than double the nomogram line, increase NAC dosing 6

Repeated Supratherapeutic Ingestion (RSTI)

Definition and Thresholds for Treatment

Children <6 years—refer to emergency department if: 5, 4

• ≥200 mg/kg over a single 24-hour period, OR
• ≥150 mg/kg per 24-hour period for 48 hours, OR
• ≥100 mg/kg per 24-hour period for ≥72 hours

Adults and children ≥6 years—refer to emergency department if: 1, 4

• ≥10 g or 200 mg/kg (whichever is less) over 24 hours, OR
• ≥6 g or 150 mg/kg (whichever is less) per 24-hour period for ≥48 hours

High-risk patients—lower threshold: 4

• 4 g or 100 mg/kg per day in patients with alcoholism, prolonged fasting, or isoniazid use

Treatment Approach for RSTI

• Nomogram does NOT apply to repeated supratherapeutic ingestions 1, 5
• Initiate NAC if serum acetaminophen ≥10 mg/mL OR if AST or ALT >50 IU/L 1
• Do not use activated charcoal for RSTI 4

Late Presentations (>24 Hours Post-Ingestion)

• Administer NAC immediately without waiting for laboratory confirmation 1
• NAC remains beneficial even with delayed treatment, though efficacy is significantly diminished 1
• Between 16-24 hours, hepatotoxicity occurs in 41% of high-risk patients (compared to 58% with supportive care alone) 1
• The nomogram is invalid for presentations >24 hours—base treatment decisions on acetaminophen levels, liver function tests, and clinical presentation 1

Management of Established Hepatotoxicity

• All patients with fulminant hepatic failure from acetaminophen must receive NAC regardless of time since ingestion (Level B recommendation) 1
• NAC in fulminant hepatic failure reduces mortality from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48% 1
• Early NAC treatment (<10 hours) in fulminant hepatic failure results in 100% survival 1
• Late NAC treatment (>10 hours) in fulminant hepatic failure results in 37% mortality and 51% requiring dialysis 1

Criteria for ICU Admission and Transplant Consultation

• AST >1000 IU/L 1
• Coagulopathy (elevated INR) 1
• Encephalopathy or other signs of fulminant hepatic failure 1

Monitoring During Treatment

• Repeat AST, ALT, INR, and acetaminophen levels to assess for developing hepatotoxicity 1
• Continue monitoring until transaminases are declining and patient is clinically improving 1
• Watch for hypersensitivity reactions during NAC infusion (hypotension, wheezing, bronchospasm)—these are more common with rapid initial infusion rates 2, 8

Common Pitfalls to Avoid

• Do not rely on patient-reported ingestion amount—history is often inaccurate 2
• Do not draw acetaminophen levels <4 hours post-ingestion unless it's to guide immediate treatment decisions 1, 2
• Do not use the nomogram for repeated supratherapeutic ingestions or unknown time of ingestion 1, 5
• Do not withhold NAC in late presentations (>24 hours)—it still provides benefit and does not worsen outcomes 1, 2
• Do not assume therapeutic doses are safe—even 4 g/day for 14 days causes ALT elevation >3× normal in 31-41% of healthy adults 3
• Patients may develop hepatotoxicity despite being in the "no risk" zone on the nomogram due to inaccurate history or increased susceptibility 1

Disposition

• Immediate emergency department referral for: any stated self-harm, toxic doses ingested, unknown ingestion amounts, or signs of hepatotoxicity 4
• Patients can be observed at home only if: age <6 years, confirmed ingestion <200 mg/kg, single acute ingestion, and asymptomatic 4
• If initial contact occurs >36 hours post-ingestion and patient is well, no further evaluation needed 4