Abstract / Summary
Abstract Background Acute respiratory distress syndrome (ARDS) is often life-threatening, associated with high morbidity and mortality. N-acetylcysteine(NAC), a precursor to Glutathione(GSH), has been proposed as an adjuvant to counteract oxidative stress, inflammation, and endothelial damage in ARDS. Objective To systematically review the effectiveness of GSH and NAC in ARDS and high-risk patients in randomized controlled trials(RCTs). Methods Systematic search of PubMed, Scopus, and Web of Science for RCTs evaluating GSH and NAC in patients with or at risk of ARDS was conducted. Eligible trials compared GSH and or NAC (any regimen, route, or dose) with placebo or usual care and reported clinical outcomes. The Cochrane RoB 2.0 was used to evaluate the risk of bias. Data were qualitatively synthesized and pooled where feasible according to random-effects models. Results NAC therapy did not show any significant difference in mortality rate after 28 days (relative risk, RR = 0.83; 95% CI: 0.58–1.18). There was a small reduction in length of stay (standardized mean difference, SMD = –0.30; 95% CI: –0.50 to –0.10; p = 0.004), but this result needs to be interpreted carefully given the clinical heterogeneity across the included studies and the absence of significant changes in other important clinical outcomes. Conclusions Biological and physiological changes were observed in some studies, but NAC did not demonstrate consistent improvements in key clinical outcomes. The small reduction in length of hospital stay is unlikely to represent a clinically meaningful benefit and should be considered hypothesis-generating. Overall, current randomized evidence does not support a consistent clinical benefit of NAC in ARDS or patients at risk of developing ARDS. Trial registration ProsperoCRD420251155902 .