• Kannan Sridharan and Gowri Sivaramakrishnan.
• a Department of Pharmacology and Therapeutics, College of Medicine and Medical Sciences , Arabian Gulf University , Manama , Bahrain.
• Ann. Med. 2018 Mar 1; 50 (2): 147-155.

BackgroundIndividuals ascending to high altitude are at a risk of getting acute mountain sickness (AMS). The present study is a network meta-analysis comparing all the interventions available to prevent AMS.MethodsElectronic databases were searched for randomized clinical trials evaluating the use of drugs to prevent AMS. Incidence of AMS was the primary outcome and incidence of severe AMS, paraesthesia (as side effect of acetazolamide use), headache and severe headache, and oxygen saturation were the secondary outcomes. Odds ratio [95% confidence interval] was the effect estimate for categorical outcomes and weighted mean difference for oxygen saturation. Random effects model was used to derive the direct and mixed treatment comparison pooled estimates. Trial sequential analysis and grading of the evidence for key comparisons were carried out.ResultsA total of 24 studies were included. Acetazolamide at 125, 250 and 375 mg twice daily, dexamethasone and ibuprofen had statistically significant lower incidence of AMS compared to placebo. All the above agents except ibuprofen were also observed to significantly reduce the incidence of severe AMS. Acetazolamide alone or in combination with Ginkgo biloba were associated with lower incidence of headache, but higher risk of paraesthesia. Acetazolamide at 125 mg and 375 mg twice daily significantly reduce the incidence of severe headache as like ibuprofen. Trial sequential analysis indicates that the current evidence is adequate for the incidence of AMS only for acetazolamide 125 and 250 mg twice daily. Similarly, the strength of evidence for acetazolamide 125 and 250 mg twice daily was moderate while it was either low or very low for all other comparisons.ConclusionsAcetazolamide at 125, 250 and 375 mg twice daily, ibuprofen and dexamethasone significantly reduce the incidence of AMS of which adequate evidence exists only for acetazolamide 125 and 250 mg twice daily therapy. Acetazolamide 125 mg twice daily could be the best in the pool considering the presence of enough evidence for preventing AMS and associated with lower incidence of paraesthesia. Key messages Acetazolamide 125, 250 and 375 mg twice daily, dexamethasone and ibuprofen reduce the incidence of AMS in high altitudes. Adequate evidence exists supporting the use of acetazolamide 125 mg and 250 mg twice daily for preventing AMS of which acetazolamide 125 mg twice daily could be the best.

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