What is the appropriate dosing of N-acetylcysteine (NAC) for a 68kg patient with a suspected acetaminophen overdose?

N-Acetylcysteine Dosing for 68kg Patient with Suspected Acetaminophen Overdose

Administer N-acetylcysteine using the standard weight-based intravenous 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) over 21 hours. 1, 2, 3

Immediate Administration Protocol

Start NAC immediately without waiting for acetaminophen levels if there is strong clinical suspicion of significant overdose, as treatment efficacy is critically time-dependent. 1, 2

Intravenous Dosing Regimen (Preferred)

For your 68kg patient, calculate the exact doses as follows:

• Loading dose: 150 mg/kg = 10,200 mg diluted in 200 mL of 5% dextrose, infused over 15 minutes 1, 2, 3
• Second dose: 50 mg/kg = 3,400 mg diluted in 500 mL of 5% dextrose, infused over 4 hours 1, 2, 3
• Third dose: 100 mg/kg = 6,800 mg diluted in 1000 mL of 5% dextrose, infused over 16 hours 1, 2, 3

Total treatment duration: 21 hours 1, 2, 3

Alternative Oral Dosing (If IV Not Available)

• Loading dose: 140 mg/kg = 9,520 mg orally or via nasogastric tube, diluted to 5% solution 1, 2
• Maintenance doses: 70 mg/kg = 4,760 mg every 4 hours for 17 additional doses (total 72 hours) 1, 2

The 72-hour oral regimen is as effective as the 20-hour IV regimen and may be superior when treatment is delayed. 1

Critical Timing Considerations

The window for maximal efficacy is 0-8 hours post-ingestion, where NAC provides the greatest hepatoprotection with only 2.9% developing severe hepatotoxicity. 1, 2

• Within 8 hours: 2.9% risk of severe hepatotoxicity 1, 2
• Within 10 hours: 6.1% risk of severe hepatotoxicity 1
• After 10 hours: 26.4% risk of severe hepatotoxicity 1

However, NAC should never be withheld even in late presentations (>24 hours), as it still reduces mortality from 80% to 52% in fulminant hepatic failure regardless of time since ingestion. 1, 2

Adjunctive Measures

If the patient presents within 4 hours of ingestion, administer activated charcoal (1 g/kg = 68 grams) just prior to starting NAC. 1, 2 Do not delay NAC administration even if activated charcoal has been given. 2

When to Extend Treatment Beyond 21 Hours

Continue NAC beyond the standard 21-hour protocol if any of the following apply:

• Acetaminophen levels remain detectable at 21 hours 1, 3
• ALT/AST continue rising or remain elevated 1, 3
• INR remains elevated 1, 3
• Delayed presentation (>24 hours post-ingestion) 1, 2
• Extended-release acetaminophen formulation 1, 2
• Repeated supratherapeutic ingestions 1, 2
• Unknown time of ingestion with detectable levels 1, 2
• Massive overdose (acetaminophen concentration above the "300-line" on nomogram) 1, 4

For massive overdoses with concentrations above the 300-line, consider step-wise increases in NAC dosing at the 300-, 450-, and 600-lines on the nomogram. 1, 4

Monitoring Requirements

Obtain the following labs before starting NAC and serially throughout treatment:

• Acetaminophen level (4-24 hours post-ingestion for nomogram use) 1, 2
• AST, ALT, bilirubin 1, 2, 3
• INR/PT 1, 2, 3
• Creatinine, BUN 2, 3
• Blood glucose, electrolytes 2, 3

Recheck labs at 12 hours and 21 hours to determine if treatment can be safely discontinued. 1, 3, 5

Special Populations Requiring Lower Treatment Threshold

Treat with NAC even if acetaminophen levels are in the "non-toxic" range for:

• Chronic alcohol users (hepatotoxicity can occur with doses as low as 4 g/day) 1, 2
• Fasting patients 2
• Patients taking enzyme-inducing drugs 1

Critical Safety Considerations

Monitor closely for hypersensitivity reactions, especially during the loading dose, as serious acute reactions including rash, hypotension, wheezing, and bronchospasm can occur. 3 If severe hypersensitivity occurs, immediately stop the infusion and initiate appropriate treatment. 3

Use with extreme caution in patients with asthma, as one patient with asthma developed fatal bronchospasm after IV NAC administration. 3

Acute flushing and erythema typically occur 30-60 minutes after initiating infusion and often resolve spontaneously despite continued infusion. 3 If the reaction involves more than simple flushing, treat as hypersensitivity with temporary interruption and/or antihistamines. 3

When NAC Can Be Safely Discontinued

NAC can be discontinued after 21 hours ONLY if ALL of the following criteria are met:

• Acetaminophen level is undetectable 1, 3
• AST and ALT remain normal (no elevation above baseline) 1, 3
• INR is normal 1, 3
• Patient presented early (<24 hours) with single acute ingestion 1

In carefully selected very low-risk patients with normal labs at presentation and 12 hours, a 12-hour NAC course may be safe, but this requires careful consideration. 1, 5

Common Pitfalls to Avoid

• Do not use the Rumack-Matthew nomogram for presentations >24 hours post-ingestion—base treatment decisions on acetaminophen levels and liver function tests instead. 1
• Do not delay NAC while awaiting confirmatory levels if there is strong suspicion of significant overdose. 2
• Low or absent acetaminophen levels do NOT rule out acetaminophen poisoning if ingestion was remote or occurred over several days. 1
• Do not use a maximum weight cutoff—use actual weight-based dosing even for patients >100 kg. 6
• For repeated supratherapeutic ingestions, the nomogram does not apply—treat if acetaminophen ≥10 mg/mL or if AST/ALT >50 IU/L. 1, 3