Comparative effects of pharmacological interventions for the prevention of acute mountain sickness: A systematic...

Acute Mountain Sickness (AMS), the most prevalent high-altitude illness, necessitates effective preventive measures due to rising sudden high-altitude exposure from tourism and occupational activities. Current Pharmacological prophylaxis lack robust comparisons, dose optimization, and confounder-adjusted analysis.

This network meta-analysis (NMA) included 28 randomized controlled trials (RCTs), evaluated healthy individuals with a rapid ascent to >2500 m, compared 13 drugs for AMS incidence, severe AMS (SAMS) incidence, Lake Louise Score (LLS), peripheral oxygen saturation (SpO2), and pulmonary artery pressure (PAP). Quality was evaluated using Cochrane Risk of Bias tools and CINeMA (Confidence in Network Meta-Analysis) for evidence grading. Network meta-regression adjusted for ascent altitude and exposure duration to identify "time" windows or "height" windows.

250 mg BID acetazolamide (OR = 0.31, 95 %CI: 0.20-0.47) demonstrated a 5-day preventive efficacy window, while 375 mg BID acetazolamide (OR = 0.31, 95 %CI: 0.18-0.54) showed a shorter 3-day window. 4 mg BID dexamethasone (OR = 0.29, 95 %CI: 0.16-0.54) and 600 mg TID ibuprofen (OR = 0.44, 95 %CI: 0.3-0.64) also significantly reduced AMS incidence. No pharmacological interventions reduced SAMS incidence. After altitude adjustment, sildenafil (40 mg TID; MD = -1.11, 95 %CI: 2.01-0.25) attenuated altitude-induced PAP elevation.

Moderate-dose acetazolamide (125-250 mg BID) effectively prevents AMS with a longer prophylactic window compared to high-dose regimens (375 mg BID). There is no pharmacological intervention to prevent SAMS and no high-quality evidence to prevent high-altitude-induced PAP elevation. Our findings delineate the efficacy duration of acetazolamide across doses, while underscoring the imperative for robust clinical trials to advance the evidence base.