What is the recommended dose of acetyl cysteine (N-acetylcysteine) for dengue hepatitis?

N-acetylcysteine (NAC) for Dengue Hepatitis

N-acetylcysteine should be administered intravenously at a dose of 100 mg/hour for 3-5 days in patients with severe dengue hepatitis, particularly those with significantly elevated liver enzymes (AST/ALT >500 U/L) and/or coagulopathy (PT/INR >1.5). 1

Mechanism of Action and Rationale

• NAC serves as a precursor to glutathione and provides antioxidant effects that help protect hepatocytes from damage in viral hepatitis, including dengue-related liver injury 2
• NAC has demonstrated efficacy in non-acetaminophen-related acute liver failure, with improvements in overall survival (76% vs 59%) and transplant-free survival (64% vs 26%) 2

Dosing Protocol for Dengue Hepatitis

• Intravenous administration at 100 mg/hour for 3-5 days has shown efficacy in case series of severe dengue hepatitis 1
• Treatment should be initiated early in the disease course for maximum benefit, particularly in patients with early-stage disease (grades I-II hepatic encephalopathy) 2
• Mean duration of treatment in successful case series was 3.61 ± 0.75 days 1

Clinical Evidence in Dengue Hepatitis

• A retrospective analysis of 30 adults with severe dengue fever and severe hepatitis (AST/ALT >500 U/L and/or PT/INR >1.5) treated with NAC infusion at 100 mg/hour for 3-5 days showed:
  • Statistically significant reduction in both ALT (p=0.034) and AST (p=0.049) from day 1 to day 4 after NAC infusion 1
  • Significant rise in platelet count between day 1 and day 4 (p=0.011) 1
  • Low mortality rate of 3.3% (only one patient died) 1
  • No reported adverse drug reactions due to NAC 1

Patient Selection and Monitoring

• NAC should be considered for dengue patients with:
  • AST/ALT >500 U/L 1
  • PT/INR >1.5 1
  • Signs of hepatic encephalopathy 2
• Monitor liver enzymes, coagulation parameters, and platelet counts daily during treatment 1
• Consider higher packed cell volume (PCV) targets during treatment to maintain adequate tissue perfusion, even in the absence of bleeding or dropping PCV 3

Adjunctive Management

• Fresh frozen plasma may be required in cases with significant coagulopathy 4
• In cases of massive bleeding, activated recombinant factor VII has been used successfully alongside NAC 5
• Early consultation with a liver transplantation center is recommended for patients with acute liver failure regardless of etiology 2

Safety Profile

• Common adverse effects include nausea, vomiting, and gastrointestinal disturbances 2
• Less common side effects include skin rash (<5%) and transient bronchospasm (1-2%) 2
• NAC has shown a favorable safety profile in dengue hepatitis case series with no reported adverse reactions 1

Limitations and Considerations

• While case series show promising results, large randomized controlled trials are needed to definitively establish efficacy 3, 6
• Treatment should be part of comprehensive management of dengue fever, including appropriate fluid management and supportive care 1