Clinical effects of N-acetylcysteine in ICU patients with respiratory disease: a systematic review and meta-analysis

Objective: Critically ill patients with respiratory disease often experience impaired airway clearance, which contributes to adverse clinical outcomes. N-acetylcysteine (NAC) has mucolytic and antioxidant properties, and may have therapeutic potential in this setting. This study evaluated the impact of NAC on clinical outcomes in ICU patients with underlying respiratory disease. Methods: A systematic literature search was conducted in PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from January of 2000 to July of 2025 in order to identify randomized controlled trials evaluating NAC in ICU patients with respiratory conditions. Primary outcomes included hospital mortality, duration of mechanical ventilation, ICU length of stay (LOS), and hospital LOS. Data were synthesized using fixed- or randomeffects models based on heterogeneity. Subgroup analyses were performed based on the route of NAC administration. Results: Five randomized controlled trials comprising 340 patients were included. Hospital mortality was 44.76% in the NAC group and 47.61% in the control group (OR = 0.87; 95% CI: 0.49-1.53). No significant differences were observed in ventilation duration (mean difference [MD] = 0.79 days; 95% CI: −2.87 to 4.44) or ICU LOS (MD = 0.21 days; 95% CI: −3.75 to 4.17). However, NAC was associated with a shorter hospital stay (MD = −3.84 days; 95% CI: −7.44 to −0.24). Subgroup analysis suggested variability in mortality outcomes based on administration route. Conclusions: NAC may reduce hospital LOS in critically ill patients with respiratory disease, although its effects on mortality and ventilation duration remain inconclusive. These findings may inform future research, particularly in patients with post-infectious lung damage such as that seen in COVID-19 or tuberculosis.