How should acute mountain sickness be prevented and managed in a healthy adult with no prior high‑altitude exposure, no severe cardiopulmonary disease, and no contraindications to acetazolamide?

Acute Mountain Sickness Prevention and Management

Primary Recommendation

For a healthy adult with no prior high-altitude exposure and no contraindications, acetazolamide 250 mg twice daily (or 500 mg once daily) should be initiated 1 day before ascent above 2500 m and continued for 2-3 days after reaching terminal altitude, combined with gradual ascent at 300-600 m/day. 1

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Prevention Strategy: Non-Pharmacological Foundation

The most effective prevention is controlled ascent rate, which forms the foundation of all altitude illness prevention:

• Ascend at 300-600 m per day once above 2500 m to allow physiological acclimatization 1
• Include a rest day for every 600-1200 m of cumulative elevation gain to consolidate acclimatization 1
• Avoid vigorous physical exertion before adequate acclimatization as exercise worsens hypoxemia at altitude 1, 2
• Stop ascent immediately if early symptoms appear (headache, nausea, dizziness) as continuing ascent markedly increases risk of severe illness 1, 3

More than 50% of unacclimatized individuals develop AMS above 4500 m with rapid ascent, making gradual ascent critical 1. The risk rises steeply with increasing altitude 4.

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Pharmacological Prophylaxis: Acetazolamide

Acetazolamide is the first-line prophylactic medication recommended by the American Heart Association 1:

Dosing

• Standard dose: 250 mg twice daily or 500 mg once daily 1
• Start 1 day before ascent above 3000 m 5
• Continue for 2-3 days after arrival at terminal altitude 1
• Prolonged use beyond 2-3 days at terminal altitude is unnecessary and increases cumulative side effects 1

Mechanism and Efficacy

• Acts as a carbonic anhydrase inhibitor causing mild metabolic acidosis, which stimulates ventilation and improves oxygenation 1
• Produces a 48% relative-risk reduction in AMS incidence compared to placebo 6
• Increases minute ventilation significantly at altitude (24.9 L/min vs 16.9 L/min in placebo) 7
• 250 mg/day has similar efficacy to higher doses with a more favorable side-effect profile 6

Clinical Trial Evidence

In a randomized trial on Mount Rainier (4394 m), 93.6% of climbers taking acetazolamide reached the summit versus 75.8% on placebo, with significantly less headache, nausea, drowsiness, and dizziness 7. Another Kilimanjaro study (5895 m) demonstrated that 500 mg daily starting one day before 3000 m resulted in higher altitudes reached and lower symptom scores 5.

Side Effects

• Common adverse effects include paresthesias (tingling), vertigo, and unpleasant taste, which are generally mild but dose-related 1
• Some climbers experience nausea and tiredness at low elevations (1300-1600 m), which may obscure prophylactic benefits 8
• Avoid combining with other diuretics due to increased risk of dehydration and electrolyte imbalances 1, 3

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Alternative Prophylactic Agents

Dexamethasone

• Use when acetazolamide is contraindicated 1
• Dose: 4 mg every 8 hours 8
• In head-to-head trials, dexamethasone reduced headache, tiredness, dizziness, and nausea more than placebo, with some euphoric effects 8
• May be combined with acetazolamide in high-risk individuals to enhance prophylaxis 1

Nifedipine

• Specifically indicated for prevention of high-altitude pulmonary edema (HAPE), not AMS 1
• Reserved for individuals with prior HAPE episode (recurrence rate 62% with rapid ascent) 1, 2
• Dose: Extended-release 20 mg every 8 hours, started with ascent and continued 3-4 days after arrival 1, 2
• Reduces HAPE incidence from 64% to 10% in susceptible climbers 1

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Acute Management of Established AMS

If symptoms develop despite prophylaxis:

1. Stop ascent immediately and rest at current altitude 1, 3
2. Assess severity using Lake Louise Scoring (rates headache, nausea, dizziness, fatigue on 0-3 scale) 3
3. Initiate descent if symptoms worsen or do not improve within 24 hours - descent is the primary therapy 1, 2
4. Administer supplemental oxygen if available to maintain saturation >91% 2
5. Consider acetazolamide for treatment if not already taking prophylactically 3

Light exercise equivalent to slow walking can worsen hypoxemia, so absolute rest is fundamental while organizing descent 2.

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Critical Pitfalls to Avoid

• Underestimating the importance of gradual ascent - pharmacological prophylaxis does not replace proper acclimatization 1
• Continuing ascent with early symptoms - this markedly increases risk of progression to life-threatening HACE (50% mortality if untreated) 4, 1
• Inadequate hydration - dehydration worsens symptoms 1
• Using rapid-release nifedipine - only extended-release formulations should be used due to hypotension risk 2
• Assuming acetazolamide side effects at low altitude indicate drug failure - separate analysis shows prophylactic benefit persists in those without early side effects 8

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Special Populations

Women

• May have statistically higher risk of developing AMS and should be monitored more closely 3
• Sex hormones influence hypoxia responses, though this is insufficiently understood 4
• Adequate acclimatization, slow ascent, and prophylactic acetazolamide remain the solutions 1

Individuals with Prior AMS

• Prophylactic acetazolamide should be strongly considered before future ascents 3
• Susceptibility to altitude illness is generally reproducible in individuals 9