Abstract Rationale High-Altitude Pulmonary Edema (HAPE) is a potentially fatal, non-cardiogenic pulmonary edema affecting individuals who rapidly ascend above 2,500-3,000 meters. It results from exaggerated hypoxic pulmonary vasoconstriction, leading to elevated pulmonary pressures and alveolar capillary leakage. Several pharmacologic agents such as nifedipine, tadalafil, salmeterol, and dexamethasone have been proposed for prophylaxis, but comparative evidence remains limited. This systematic review and network meta-analysis aimed to evaluate the efficacy and safety of these agents in preventing HAPE. Methods A systematic search of PubMed, Scopus, Web of Science, Embase, and Cochrane Library was conducted following PRISMA 2020 guidelines. for studies evaluating the effectiveness of pharmacological prophylaxis for preventing HAPE. Only randomized controlled trials (RCTs) assessing pharmacological prevention of HAPE in adults ascending ≥2,500m were included. The primary outcome was incidence of HAPE. Risk ratios were pooled using a random-effects model with continuity correction. Heterogeneity and inconsistency were assessed, and risk of bias was evaluated using the ROB-2 tool. Results A total of five studies (n = 223) met inclusion criteria. Both nifedipine and tadalafil significantly reduced the incidence of HAPE compared with placebo across all model specifications (RR = 0.20; 95% CI, 0.05-0.77 and RR = 0.20; 95% CI, 0.05-0.76, respectively). Dexamethasone also appeared protective (RR = 0.06; 95% CI, 0.004-0.93), though estimates were imprecise due to limited sample size. Acetazolamide and salmeterol did not demonstrate statistically significant benefit, with wide confidence intervals indicating uncertainty. Heterogeneity was minimal (I² = 0%), and no inconsistency was detected across the network. Discussion Among available pharmacologic strategies, nifedipine and tadalafil show the most consistent and robust evidence for preventing HAPE, with protective effects persisting under multiple modeling assumptions. Dexamethasone may confer additional benefit, but evidence remains fragile. Acetazolamide and salmeterol appear less effective in current data. Conclusion Our findings support nifedipine and tadalafil as the most effective pharmacologic options for HAPE prevention in high-risk individuals. Future RCTs with standardized diagnostic criteria and safety reporting are warranted to confirm these findings and optimize prophylactic strategies for ascent-related hypoxemic injury. Abbreviations: HAPE - High-Altitude Pulmonary Edema, RR - Risk Ratio This abstract is funded by: None
Franco et al. (Fri,) studied this question.
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