What is the recommended IV dose of N-acetyl-cysteine (NAC) for a 68kg patient with paracetamol intoxication?

IV N-Acetylcysteine Dosing for 68kg Patient with Paracetamol Intoxication

For a 68kg patient with paracetamol intoxication, administer IV N-acetylcysteine using the standard 21-hour protocol: 150 mg/kg (10,200 mg) loading dose over 15 minutes, followed by 50 mg/kg (3,400 mg) over 4 hours, then 100 mg/kg (6,800 mg) over 16 hours, for a total dose of 300 mg/kg (20,400 mg). 1, 2

Standard IV NAC Protocol

The FDA-approved and guideline-recommended intravenous regimen consists of three sequential infusions 3:

Loading Dose (First 15 minutes):

• 150 mg/kg = 10,200 mg for 68kg patient
• Dilute in 200 mL of 5% dextrose
• Infuse over 15 minutes 1, 2

Second Dose (Next 4 hours):

• 50 mg/kg = 3,400 mg for 68kg patient
• Dilute in 500 mL of 5% dextrose
• Infuse over 4 hours 1, 2

Third Dose (Final 16 hours):

• 100 mg/kg = 6,800 mg for 68kg patient
• Dilute in 1000 mL of 5% dextrose
• Infuse over 16 hours 1, 2

Critical Timing Considerations

Initiate NAC immediately—do not wait for confirmatory acetaminophen levels if there is strong suspicion of significant overdose. 2 The efficacy of NAC is highly time-dependent:

• Treatment within 8 hours: only 2.9% develop severe hepatotoxicity 2, 4
• Treatment within 10 hours: 6.1% develop severe hepatotoxicity 2
• Treatment after 10 hours: 26.4% develop severe hepatotoxicity 2
• Even if presentation is >24 hours post-ingestion, NAC still reduces mortality and should be administered immediately 1, 2

When to Extend Treatment Beyond 21 Hours

The standard 21-hour IV protocol may be insufficient in certain scenarios. Continue NAC beyond 21 hours if any of the following are present 1, 2:

• Acetaminophen level remains detectable
• AST or ALT remain elevated or are rising
• INR remains elevated
• Delayed presentation (>24 hours post-ingestion)
• Extended-release acetaminophen formulation
• Repeated supratherapeutic ingestions
• Unknown time of ingestion with detectable levels
• Massive overdose (>30g or >500 mg/kg) 5

For established hepatic failure (AST/ALT >1000 IU/L), continue NAC until transaminases are declining and INR normalizes, regardless of time since ingestion—this reduces mortality from 80% to 52%. 1, 2

Special Considerations for This Patient

For a 68kg patient, calculate whether this represents a high-risk ingestion 2:

• If ingestion >10g (or >150 mg/kg = >10,200 mg for 68kg), this is potentially hepatotoxic
• If patient has risk factors (chronic alcohol use, malnutrition, enzyme-inducing drugs), toxicity threshold is lower 1, 2

Monitoring During Treatment

Obtain baseline and serial laboratory studies 2, 3:

• Acetaminophen level (4-hour post-ingestion level for nomogram plotting)
• AST, ALT
• INR/PT
• Creatinine, BUN
• Electrolytes, glucose
• Repeat liver function tests and INR daily if acetaminophen level is in toxic range 3

Common Pitfalls to Avoid

• Do not delay NAC while awaiting acetaminophen levels if strong suspicion exists 2
• Do not stop NAC at 21 hours if acetaminophen is still detectable or transaminases are elevated 1, 2
• Activated charcoal (if given within 4 hours) should not delay NAC administration 2
• The Rumack-Matthew nomogram does NOT apply to presentations >24 hours post-ingestion or repeated supratherapeutic ingestions 2
• Anaphylactoid reactions to IV NAC occur in ~6% of patients but rarely require discontinuation—slow or temporarily stop the infusion and treat symptomatically 6

IV vs Oral NAC

While both routes are effective, IV NAC is preferable for most patients due to shorter hospital stay, guaranteed bioavailability (not affected by vomiting or activated charcoal), and patient convenience. 6 The oral 72-hour regimen (140 mg/kg loading, then 70 mg/kg every 4 hours for 17 doses) may be superior for very late presentations (>15-24 hours), but IV remains the standard of care in most settings 1, 7, 6.