What is the recommended dose of N-acetyl cysteine (NAC) for a patient with acetaminophen overdose?

N-Acetylcysteine Dosing for Acetaminophen Overdose

For acetaminophen overdose, administer N-acetylcysteine (NAC) using either an oral regimen of 140 mg/kg loading dose followed by 70 mg/kg every 4 hours for 17 doses (72-hour protocol), or an intravenous regimen of 150 mg/kg over 15 minutes, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours (21-hour protocol). 1, 2

Standard Dosing Regimens

Oral NAC Protocol

• Loading dose: 140 mg/kg by mouth or nasogastric tube, diluted to 5% solution 1, 2
• Maintenance dose: 70 mg/kg every 4 hours for 17 additional doses 1, 2
• Total duration: 72 hours 1, 3
• Dilute the 20% solution with diet cola or other diet soft drinks to achieve 5% concentration; water may be used if administering via gastric tube 3

Intravenous NAC Protocol

• 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
• Total duration: 21 hours 2, 4

Critical Timing Considerations

Start NAC immediately—do not wait for acetaminophen levels if overdose is suspected. 2, 5 The efficacy of NAC is highly time-dependent:

• 0-8 hours post-ingestion: Maximum hepatoprotection with only 2.9% developing severe hepatotoxicity 2, 4
• 8-10 hours: Hepatotoxicity increases to 6.1% 2, 4
• 10-24 hours: Hepatotoxicity jumps to 26.4% 2, 4
• 16-24 hours: Among high-risk patients, 41% develop hepatotoxicity (still better than 58% in untreated historical controls) 2, 4

NAC should still be administered even beyond 24 hours after ingestion, as it reduces mortality and hepatotoxicity regardless of delay. 1, 2, 3

Special Clinical Scenarios Requiring Modified Dosing

Massive Overdose (Acetaminophen Levels Above 300-Line)

For patients with extremely high acetaminophen concentrations, consider step-wise increases in NAC dosing 5, 6:

• 300-line: Consider increased dosing beyond standard protocol 5
• 450-line: Further dose escalation may be warranted 5
• 600-line: Maximum dose escalation 5

One case report successfully used intravenous NAC at 12.5 mg/kg/hour plus oral NAC at 70 mg/kg every 4 hours during continuous veno-venous hemofiltration for a massive 125g ingestion 7

Acute Liver Failure

For established hepatic failure from acetaminophen, administer NAC regardless of time since ingestion. 1, 2, 5 This reduces mortality from 80% to 52%, cerebral edema from 68% to 40%, and need for inotropic support from 80% to 48% 2

Extended Treatment Scenarios

Continue NAC beyond standard protocols for 2, 5:

• Delayed presentation (>24 hours post-ingestion)
• Extended-release acetaminophen formulations
• Repeated supratherapeutic ingestions
• Unknown time of ingestion with detectable acetaminophen levels
• Any elevation in AST or ALT above normal
• Chronic alcohol use (lower threshold for hepatotoxicity)

Route Selection: Oral vs. Intravenous

The 72-hour oral regimen is as effective as the 20-hour IV regimen and may be superior when treatment is delayed. 2, 4 However, use IV NAC when 1:

• Active gastrointestinal bleeding is present
• Worsening mental status precludes oral administration
• Persistent vomiting prevents oral retention
• Patient cannot protect airway

Discontinuation Criteria

NAC can be discontinued when ALL of the following are met 2, 5:

• Acetaminophen level is undetectable
• AST and ALT remain normal (no elevation above baseline)
• No coagulopathy present
• INR normalizes if previously elevated

Do NOT stop NAC if any of these red flags are present 2, 5:

• Any elevation in AST or ALT above normal
• Rising transaminases
• Any coagulopathy
• Detectable acetaminophen level
• Clinical signs of hepatotoxicity

Critical Pitfalls to Avoid

• Never delay NAC while awaiting acetaminophen levels—start immediately if overdose is suspected 2, 5, 3
• Low or absent acetaminophen levels do NOT rule out poisoning if ingestion was remote or occurred over several days 2
• The Rumack-Matthew nomogram does NOT apply to presentations >24 hours after ingestion, repeated supratherapeutic ingestions, or extended-release formulations 2, 5
• Activated charcoal adsorbs NAC—if charcoal was given, perform gastric lavage before starting NAC 3
• If patient vomits within 1 hour of oral NAC dose, repeat that dose 3
• Chronic alcoholics require treatment even with "non-toxic" acetaminophen levels due to hepatotoxicity occurring at doses as low as 4g/day 2, 5

Adjunctive Measures

• Give activated charcoal (1 g/kg) just prior to starting NAC if patient presents within 4 hours of ingestion 1, 2
• For massive overdoses unresponsive to standard therapy, consider fomepizole (inhibits cytochrome P450) and hemodialysis or continuous veno-venous hemofiltration 7
• Monitor AST, ALT, INR, creatinine, and acetaminophen levels throughout treatment 1, 3