Key messages

• We are uncertain whether treatment with acetazolamide decreases the symptoms of acute mountain sickness or if it increases the risk of adverse effects as the certainty of the evidence has been assessed as very low.
• The outcomes mortality and acute mountain sickness symptoms resolution were not reported.

What is the evidence.
See evidence matrix  in Epistemonikos later

We found one systematic review [1], which included two primary studies [2], [3], both corresponding to randomized trials.

What types of patients were included*

Both trials included patients with acute mountain sickness, that is, subjects acutely exposed to high-altitude, presenting symptoms of headache, fatigue, dizziness, nausea, vomiting, sleep disturbances and anorexia.
The patients included were adult mountaineers. In one trial [2] 91% of the participants were male, while in the other sex was not reported [3].
One trial [2] defined the syndrome according to the AMS (Acute Mountain Sickness) Symptom Questionnaire, with a score greater than or equal to two (with onset of symptoms over 4,200 masl and maximum 24 hours before inclusion) and excluded patients with previous use of acetazolamide, confirmed diagnosis of high-altitude pulmonary or cerebral edema, or with severe comorbidity.
The other trial [3] included patients with a score greater than or equal to three in a self-administered acute mountain sickness questionnaire (18 questions and a maximum score of 180) and excluded patients with severe comorbidity, obese and previous acclimatation.

What types of interventions were included*

Both trials evaluated the use of acetazolamide orally. One trial [2] administered 250 mg at 0 and 8 hours and the other [3] 20 mg/kg at baseline and then 500 mg daily for 5 days.
Both trials compared against placebo.

What types of outcomes
were measured

To whom this evidence does and does not apply

• The evidence presented in this summary applies to adult patients with acute mountain sickness.
  The patients included in the trials were male adults, however, it is reasonable to extrapolate these results to female patients.
• The evidence presented in this summary should not be extrapolated to the pediatric population or pregnant women, due to the different requirements and risks of these groups that were not evaluated in the included trials.

• The selected outcomes are those considered critical for decision-making according to the opinion of the authors of this summary, coinciding with the identified systematic review.

• There is no clarity regarding the effectiveness or safety of acetazolamide as a treatment for acute mountain disease because the certainty of the evidence is very low. Additionally, there is no evidence on the benefit of treatment in mortality and resolution of symptoms of patients with acute mountain sickness, since these were not evaluated.
• In consideration of the above, the balance between benefits and risks should be assessed individually, taking into account additional factors associated with the experience and preferences of both patients and physicians regarding the use of acetazolamide.

• There are no studies evaluating the cost-effectiveness of acetazolamide as a treatment for acute mountain disease. However, even if the economic value of acetazolamide is not high, it is not possible to make an adequate cost/effectiveness balance because the certainty of the evidence is very low.

• Travelers and mountaineers who are exposed to high-altitude are the main ones affected by acute mountain sickness, whose symptoms constitute an important impediment to the realization of their recreational and/or sports activities.
• In this scenario, given the uncertainty about the benefits and risks, patients and physicians could both lean in favor of its use and against it. The final decision should be individualized considering the values and preferences of the patients and explaining the existing uncertainty.

Differences between this summary and other sources

• The conclusions of this summary are consistent with those of the systematic review identified [1].
• The results of this summary partially coincide with those of the guidelines of the International Society of Travel Medicine [4] and Wilderness Medical Society [5] in which the use of acetazolamide is recommended as an alternative treatment for acute mountain sickness, despite the uncertain evidence and its very low level of certainty of the evidence.

• It is very likely that future research will modify the conclusions of this summary, mainly due to the very low certainty of the evidence available and the low number of randomized trials and patients evaluated.
• No ongoing trials or systematic reviews of acetazolamide were found as a treatment for acute mountain disease in PROSPERO database or in the International Clinical Trials Registry Platform of the World Health Organization.