N-Acetylcysteine Infusion: Clinical Uses
N-acetylcysteine (NAC) infusion is definitively indicated for acetaminophen-associated acute liver failure, where it reduces mortality, and should be administered immediately in this setting. 1, 2
Primary Established Indication
Acetaminophen Overdose and Acute Liver Failure
The FDA-approved indication for intravenous NAC is to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen, including both acute ingestion and repeated supratherapeutic ingestion (RSI). 2
The American Gastroenterological Association strongly recommends NAC use in acetaminophen-associated acute liver failure, demonstrating improved mortality (relative risk 0.65,95% CI 0.43-0.99). 1
NAC should be initiated based on the Rumack-Matthew nomogram for acute ingestions occurring at a known time, with treatment started when acetaminophen levels fall above the treatment line. 1
For patients who cannot be risk-stratified by the nomogram (delayed presentation >24 hours, unknown time of ingestion, extended-release preparations, or repeated supratherapeutic ingestions), NAC should be administered if there is clinical or laboratory evidence of hepatotoxicity or if acetaminophen levels are detectable with any elevation in transaminases. 1
In acute liver failure of indeterminate cause, NAC can be considered since some cases may be unrecognized acetaminophen toxicity. 1
Non-Acetaminophen Acute Liver Failure
For non-acetaminophen-associated acute liver failure, the AGA recommends NAC be used only in the context of clinical trials, as overall mortality benefit has not been demonstrated. 1
Post hoc analysis suggests potential mortality benefit in patients with stage 1 or 2 hepatic encephalopathy, but this requires further validation. 1
Chronic Respiratory Conditions (Oral, Not Infusion)
COPD Exacerbation Prevention
For patients with moderate to severe COPD and history of two or more exacerbations in the previous 2 years, the American College of Chest Physicians and Canadian Thoracic Society suggest oral NAC 600 mg twice daily to prevent acute exacerbations (Grade 2B). 1
The largest trial (Zheng et al, 1,006 patients) demonstrated reduced exacerbation rates (1.16 vs 1.49, RR 0.78) with oral NAC 600 mg twice daily. 1
NAC appears more effective in GOLD II COPD compared to GOLD III disease, with longer time to first exacerbation in moderate disease. 1
This recommendation applies to oral NAC, not intravenous infusion, for chronic use. 3
Cystic Fibrosis
The Cystic Fibrosis Foundation concludes that evidence is insufficient to recommend for or against chronic use of inhaled or oral NAC in patients with CF aged 6 years and older (Grade I recommendation). 1
Studies showed no clinical benefit or improvement in lung function, with zero net benefit despite theoretical mucolytic properties. 1
Mucolytic Use
NAC has been used as a mucolytic agent for chronic bronchitis and pulmonary diseases with viscous mucus production, though this typically involves nebulized or oral administration rather than intravenous infusion. 4, 5
The European Respiratory Society suggests oral mucolytic therapy for patients with moderate or severe airflow obstruction and exacerbations despite optimal inhaled therapy. 3
Important Clinical Caveats
Intravenous NAC infusion is specifically indicated for acute acetaminophen toxicity, not for chronic respiratory conditions where oral formulations are used. 2
NAC is generally well-tolerated with rare adverse gastrointestinal effects and low toxicity even with prolonged use. 1, 3
While NAC reduces exacerbations in COPD, it has not been shown to significantly impact mortality, which should inform discussions about long-term use. 3
Charcoal administration may interfere with oral NAC absorption (up to 96% adsorption), which is relevant in overdose management. 4