What is the recommended N‑acetylcysteine (NAC) intravenous dosing protocol for an adult with ischemic (shock) hepatitis, calculated on actual body weight?

NAC Dosing for Ischemic (Shock) Hepatitis in Adults

For adults with ischemic hepatitis, administer intravenous N-acetylcysteine using the standard acetaminophen overdose protocol calculated on actual body weight: 150 mg/kg loading dose over 1 hour, followed by 12.5 mg/kg/hour for 4 hours, then 6.25 mg/kg/hour for 67 hours (total 72 hours). 1

Rationale for NAC Use in Ischemic Hepatitis

While NAC is most established for acetaminophen toxicity, guidelines now recommend NAC therapy for acute liver failure of any etiology to improve morbidity and mortality (GRADE 2+ recommendation with strong agreement). 2 This extends to ischemic hepatitis, which represents acute liver injury from hypoperfusion rather than direct toxicity.

Evidence Supporting NAC in Non-Acetaminophen Liver Injury

The strongest evidence comes from:

• Meta-analysis data showing NAC improves overall survival in non-acetaminophen acute liver failure (76% versus 59%, OR = 2.30,95% CI 1.54–3.45) 3
• Transplant-free survival increases substantially (64% versus 26%, OR = 4.81,95% CI 3.22–7.18) 3
• A randomized controlled trial in cirrhotic patients with variceal bleeding (a common cause of ischemic hepatitis) demonstrated NAC reduced ischemic hepatitis incidence (14% versus 23%) and deaths from liver failure (OR 0.33,95% CI 0.11-0.97) 1

Specific Dosing Protocol

The intravenous regimen based on actual body weight is:

• Loading dose: 150 mg/kg over 1 hour 1
• Second phase: 12.5 mg/kg/hour for 4 hours 1
• Maintenance phase: 6.25 mg/kg/hour for 67 hours 1

This totals 72 hours of continuous infusion. 1

Extended Duration Considerations

Recent evidence suggests extending NAC beyond 72 hours may improve outcomes in non-acetaminophen acute liver failure. 4 In a retrospective cohort study:

• Transplant-free survival was significantly higher with extended duration (76.9% versus 41.4%) 4
• All-cause mortality at 3 weeks trended lower (0% versus 24.1%) 4

Consider continuing NAC beyond 72 hours until INR normalizes to <1.3-1.5, particularly in patients with severe hepatic encephalopathy or those not showing clinical improvement. 4

Mechanism and Timing

NAC works in ischemic hepatitis by improving tissue oxygen delivery, reducing hepatic hypoxia, and providing antioxidant effects that protect hepatocytes during reperfusion injury. 3, 1

Initiate NAC as early as possible in the disease course—the interval between disease onset and treatment initiation directly correlates with outcomes. 3 The beneficial effects are most pronounced in patients with early-stage disease (grades I-II hepatic encephalopathy). 3

Safety Profile

NAC is well-tolerated with minimal adverse effects:

• Skin rash occurs in <5% of patients 5, 3
• Transient bronchospasm in 1-2% 5, 3
• Common GI effects include nausea, vomiting, diarrhea or constipation 3

For patients with asthma or atopic histories, IV NAC remains appropriate but monitor closely for bronchospasm. 5

Critical Pitfalls to Avoid

Do not delay NAC initiation while awaiting confirmatory testing or determining the exact etiology of liver failure. 2 In ischemic hepatitis, the diagnosis is often clinical (marked transaminase elevation with AST>ALT, history of hypotension/shock, rapid improvement with supportive care). 2

Do not routinely correct coagulopathy with clotting factors unless active bleeding is present—this can obscure prognostic markers. 2

Recognize that ischemic hepatitis carries high mortality (development of ischemic hepatitis increases death from liver failure with subdistribution hazard ratio of 21.6), making early NAC administration particularly important. 1

Additional Supportive Measures

Perform abdominal Doppler ultrasound to verify vascular patency and exclude chronic liver disease. 2 Obtain echocardiography when ischemic injury is suspected, particularly in critically ill patients with primary cardiac/circulatory failure, elderly patients, or those with acute renal failure. 2

NAC also reduces the incidence of acute kidney injury (OR 0.34,95% CI 0.15-0.75) in this population, providing additional organ protection beyond hepatic effects. 1