What is the treatment protocol for N-acetyl cysteine (NAC) in a patient with paracetamol (acetaminophen) poisoning?

N-Acetylcysteine Treatment for Paracetamol Poisoning

Administer N-acetylcysteine (NAC) immediately for any known or suspected paracetamol overdose—ideally within 8 hours of ingestion but beneficial up to 24 hours and beyond, even in established liver failure. 1, 2

Immediate Treatment Protocol

When to Start NAC Without Delay

• Start NAC immediately without waiting for laboratory confirmation in the following scenarios: 1, 2

  • Any known or suspected paracetamol overdose
  • Acetaminophen level plots above the "possible toxicity" line on the Rumack-Matthew nomogram (drawn 4-24 hours post-ingestion)
  • Unknown time of ingestion with detectable paracetamol levels
  • Established acute liver failure where paracetamol is suspected (transaminases "in the thousands," elevated INR/bilirubin)
  • Any elevation in AST or ALT above normal with suspected paracetamol exposure

• Give activated charcoal (1 g/kg) just prior to starting NAC if the patient presents within 4 hours of ingestion—do not delay NAC administration for this. 2, 3

Standard NAC Dosing Regimens

Intravenous Protocol (21-hour regimen)

• Loading dose: 150 mg/kg in 5% dextrose over 15 minutes 1, 2
• Second dose: 50 mg/kg over 4 hours 1, 2
• Third dose: 100 mg/kg over 16 hours 1, 2

Oral Protocol (72-hour regimen)

• Loading dose: 140 mg/kg orally or via nasogastric tube, diluted to 5% solution 1, 4
• Maintenance: 70 mg/kg every 4 hours for 17 additional doses (total 72 hours) 1, 4

The oral 72-hour regimen may be superior to the 21-hour IV regimen, particularly in delayed presentations, as modeling studies suggest the 21-hour infusion is often too short while the full 72-hour course provides more complete hepatocyte preservation. 5, 6 However, IV NAC offers advantages of shorter hospital stay and avoids issues with vomiting or charcoal interference. 6

Critical Timing Windows and Efficacy

• 0-8 hours post-ingestion: Maximum protection—only 2.9% develop severe hepatotoxicity when treated within 8 hours 2, 7
• 8-10 hours: Efficacy begins to diminish—6.1% develop severe hepatotoxicity 2
• 10-24 hours: Significantly reduced efficacy—26.4% develop severe hepatotoxicity, but still far superior to no treatment 2, 7
• >24 hours: NAC remains beneficial and should never be withheld, particularly in established liver failure where it reduces mortality from 80% to 52% 2, 3

The Rumack-Matthew nomogram does NOT apply to presentations >24 hours after ingestion—treatment decisions must be based on paracetamol levels, liver function tests, and clinical presentation. 2

Special Clinical Scenarios Requiring Modified Management

High-Risk Populations Requiring Lower Treatment Threshold

• Chronic alcoholics: Treat with NAC even with levels in the "non-toxic" range on the nomogram, as severe hepatotoxicity can occur with doses as low as 4-5 g/day 1, 2
• Fasting patients: At increased risk and may warrant NAC at lower paracetamol levels 1
• Malnourished patients or those with cirrhosis: Higher risk even at therapeutic doses 1

Extended-Release Formulations

• Serial paracetamol levels should be obtained as late increases may occur at 14 hours or beyond 2
• Standard dosing applies but monitoring and treatment duration may need extension 3

Repeated Supratherapeutic Ingestions

• Treat with NAC if: 2
  • ≥10 g or 200 mg/kg (whichever is less) during a single 24-hour period, OR
  • ≥6 g or 150 mg/kg (whichever is less) per 24-hour period for ≥48 hours, OR
  • Serum paracetamol ≥10 mg/mL, OR
  • AST or ALT >50 IU/L in high-risk patients

Established Acute Liver Failure

• Administer NAC immediately regardless of time since ingestion 2, 3
• Mortality reduction from 80% to 52%, cerebral edema reduction from 68% to 40% 2
• Contact liver transplant center immediately and provide ICU-level care 2
• Very high transaminases (AST/ALT >3,500 IU/L) are highly correlated with paracetamol poisoning even without confirmatory history 2

When to Extend or Discontinue NAC

Criteria for Safe Discontinuation

• NAC can be stopped when ALL of the following are met: 2
  • Acetaminophen level is undetectable
  • AST and ALT remain normal (no elevation above normal)
  • No coagulopathy
  • Normal INR

Mandatory Extended Treatment Beyond Standard Protocol

• Continue NAC beyond 21 hours (IV) or 72 hours (oral) if: 2, 3
  • Delayed presentation (>24 hours post-ingestion)
  • Extended-release formulation
  • Repeated supratherapeutic ingestions
  • Unknown time of ingestion with detectable levels
  • ANY elevation in AST or ALT above normal
  • Rising transaminases
  • Any coagulopathy present
  • Chronic alcohol use

Red Flags Requiring Immediate NAC Restart

• Restart NAC immediately if: 2
  • AST/ALT >1,000 IU/L (severe hepatotoxicity)
  • Rising transaminases
  • Development of coagulopathy
  • Detectable paracetamol level reappears
  • Clinical signs of hepatotoxicity emerge

Critical Pitfalls to Avoid

• Never delay NAC while awaiting laboratory confirmation—if paracetamol overdose is suspected, start immediately 2, 3, 4
• Low or absent paracetamol levels do NOT rule out poisoning if ingestion was remote or occurred over several days 2
• Do not rely solely on the nomogram for patients presenting <4 hours post-ingestion—the level may not represent peak concentration; obtain a second level 2, 4
• The standard treatment nomograms may underestimate risk for patients presenting within 8 hours—maintain a low threshold for treatment 5
• If the patient vomits within 1 hour of oral NAC administration, repeat that dose 4
• For persistent vomiting, consider duodenal intubation for oral NAC or switch to IV route 4

Adverse Effects and Management

• Overall incidence of adverse effects is low: nausea/vomiting <5%, skin rash <5%, bronchospasm 1-2% 1
• IV NAC adverse reactions occur in approximately 6% of patients but rarely prevent completion of treatment 6
• If generalized urticaria or allergic symptoms occur, discontinue NAC only if symptoms cannot be controlled and NAC is not deemed essential 4

Monitoring Throughout Treatment

• Baseline labs: Paracetamol level (drawn ≥4 hours post-ingestion), AST, ALT, bilirubin, INR/PT, creatinine, BUN, glucose, electrolytes 2, 4
• Repeat daily if paracetamol level is in potentially toxic range: AST, ALT, bilirubin, INR/PT, creatinine, BUN, glucose, electrolytes 2, 4
• For severe hepatotoxicity (AST >1,000 IU/L) or coagulopathy: ICU-level care with early transplant hepatology consultation 2