Efficacy of acetazolamide for the prophylaxis of acute mountain sickness: A systematic review, meta-analysis, and trial sequential analysis of randomized clinical trials.

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Date: Oct-Dec 2021
From: Annals of Thoracic Medicine(Vol. 16, Issue 4)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Article
Length: 4,675 words
Lexile Measure: 1540L

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Byline: Daiquan. Gao, Yuan. Wang, Rujiang. Zhang, Yunzhou. Zhang

BACKGROUND: Acute mountain sickness (AMS) is a benign and self-limiting syndrome, but can progress to life-threatening conditions if leave untreated. This study aimed to assess the efficacy of acetazolamide for the prophylaxis of AMS, and disclose factors that affect the treatment effect of acetazolamide. METHODS: Randomized controlled trials comparing the use of acetazolamide versus placebo for the prevention of AMS were included. The incidence of AMS was our primary endpoint. Meta-regression analysis was conducted to explore factors that associated with acetazolamide efficacy. Trial sequential analyses were conducted to estimate the statistical power of the available data. RESULTS: A total of 22 trials were included. Acetazolamide at 125, 250, and 375 mg/bid significantly reduced incidence of AMS compared to placebo. TAS indicated that the current evidence was adequate confirming the efficacy of acetazolamide at 125, 250, and 375 mg/bid in lowering incidence of AMS. There was no evidence of an association between efficacy and dose of acetazolamide, timing at start of acetazolamide treatment, mode of ascent, AMS assessment score, timing of AMS assessment, baseline altitude, and endpoint altitude. CONCLUSION: Acetazolamide is effective prophylaxis for the prevention of AMS at 125, 250, and 375 mg/bid. Future investigation should focus on personal characteristics, disclosing the correlation between acetazolamide efficacy and body mass, height, degree of prior acclimatization, individual inborn susceptibility, and history of AMS.

Acute mountain sickness (AMS) is a syndrome of headache, nausea, light-headedness, fatigue, and dyspnea that affects approximately 10%-25% of unacclimatized individuals ascending above 2,500 m to up to more than 80% above 4500 m.[1],[2],[3],[4] Although AMS is usually a benign and self-limiting condition, if leave untreated, it can progress to life-threatening high altitude cerebral edema (HACE) or high altitude pulmonary edema (HAPE). A gradual ascent to permit acclimatization remains to be the most effective strategy to prevent AMS.[5] However, it is often logistically infeasible in AMS-susceptible population, recreational and tactical situations. Therefore, the search for effective, reliable, and readily available prophylactic agents with a low adverse effect profile become important.

For the chemoprophylactic prevention of AMS, acetazolamide is the drug of choice. Acetazolamide is proposed to prevent AMS through the inhibition of renal carbonic anhydrase that induces urinary bicarbonate wasting diuresis, resultant metabolic acidosis, cerebrospinal fluid bicarbonate decrease and ensuing fall in fluid pH that stimulates the central chemoreceptors to respond more fully to hypoxic stimuli.[6],[7] Acetazolamide has been proven to be effective in preventing AMS with dosage range from 125 mg twice daily (bid) to 375 mg bid.[8],[9] However, the debate on the optimal dosage is still ongoing. There have been successive recommendations to decrease acetazolamide dosage for AMS prevention in the past several decades, usually to minimize side effects including headache, nausea, polyuria, and dysgeusia.[9],[10] These adverse effects are similar to AMS symptoms, which can result in misdiagnoses and underestimation of the treatment effect. Yet, others suggested that a low dosage (125 mg bid) could not fully prevent AMS.[11]

Several attempts have been made to disclose the prophylactic...

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Gale Document Number: GALE|A680637883