What are the typical symptoms of acute mountain sickness (AMS) and the recommended treatment and prophylaxis, including medication choices, dosing regimens, and contraindications?

Altitude Sickness: Symptoms and Treatment

Symptoms of Acute Mountain Sickness (AMS)

The hallmark symptoms of AMS include headache, nausea, dizziness, fatigue, and insomnia, typically beginning within hours of ascent above 2,500 m. 1

Mild to Moderate AMS

• Headache (the cardinal symptom, rated 0-3 in severity) 2
• Loss of appetite and nausea (may progress to vomiting in severe cases) 3, 4
• Dizziness and lightheadedness 5
• Fatigue and weakness 3
• Disturbed sleep and insomnia 3

Severe AMS/High-Altitude Cerebral Edema (HACE)

• Severe headache unrelieved by acetaminophen 4
• Vomiting (signals potential progression to HACE) 4
• Ataxia and loss of coordination 4
• Mental deterioration progressing to coma 4
• Altered mental status 2

High-Altitude Pulmonary Edema (HAPE)

• Incapacitating fatigue and dyspnea at minimal effort progressing to dyspnea at rest 4
• Chest tightness 4
• Dry cough progressing to pink frothy sputum (hemoptysis) 4
• Orthopnea 4

Treatment Medications

First-Line Pharmacological Treatment

Acetazolamide 250 mg twice daily or 500 mg once daily is the first-line medication for both prophylaxis and treatment of AMS. 1

Acetazolamide Dosing

• Standard prophylactic dose: 250 mg twice daily or 500 mg once daily, started 1-2 days before ascent and continued 2-3 days after reaching terminal altitude 1
• For rapid ascent above 3,500 m: 500-750 mg/day appears most effective for military/emergency personnel 5
• Lower dose option: 125 mg twice daily or once at bedtime for those concerned about side effects 6, 5
• Mechanism: Carbonic anhydrase inhibitor causing mild diuresis and metabolic acidosis, which stimulates ventilation and improves oxygenation 1

Common Side Effects of Acetazolamide

• Paresthesias (tingling in fingers/toes) 1
• Vertigo 1
• Unpleasant taste 1
• Risk of dehydration when combined with other diuretics 2

Alternative and Adjunctive Medications

Dexamethasone

• Dose: 4 mg every 6 hours for prevention 7
• Use when acetazolamide is contraindicated or as adjunctive therapy in high-risk individuals 1
• Effective for cerebral symptoms but not routinely recommended as sole prophylactic agent 6
• Can be combined with other agents for enhanced prophylaxis in high-risk patients 1

Nifedipine (for HAPE Prevention/Treatment)

• Extended-release nifedipine 20 mg every 8 hours for HAPE-susceptible individuals 1
• Start with ascent and continue 3-4 days after reaching terminal altitude 1
• Reduces HAPE incidence from 64% to 10% in susceptible climbers 1
• Mechanism: Pulmonary vasodilator that counteracts exaggerated hypoxic pulmonary vasoconstriction 4

Ibuprofen

• Effective for headache treatment in AMS 3
• Can be used as adjunctive analgesic therapy 1

PDE5 Inhibitors (Sildenafil/Tadalafil)

• Second-line agents for HAPE prophylaxis 1
• Caution: Tadalafil has been associated with severe AMS in some subjects 1

Non-Pharmacological Treatment

Immediate descent to lower altitude is the primary and most effective therapy for all forms of altitude illness. 1, 4

Essential Management Steps

• Halt further ascent if symptoms develop 1
• Descend immediately for severe symptoms, HACE, or HAPE 1, 4
• Supplemental oxygen improves hypoxemia and symptoms 4
• Rest and avoid vigorous exertion until acclimatized 1

Prevention Strategies

Gradual Ascent Protocol

• Ascend 300-600 m/day above 2,500 m 1, 4
• Include rest day every 600-1,200 m of elevation gain 1
• Slow ascent (<400 m/day) further reduces AMS risk 2

Pre-Acclimatization

• Long pre-acclimatization (2 weeks, >8 hours/day) at progressively increasing altitudes is preferable 8
• Hypoxic facility training may benefit those with access 2

Special Populations and Considerations

Women

• Women may have statistically higher AMS risk and require closer monitoring 8, 2
• Systematic screening using Lake Louise Score is recommended 8
• Iron supplementation (210 mg daily) should be considered, as women are at higher risk of iron deficiency affecting acclimatization 8

Cardiovascular Patients

• Continue pre-existing cardiac medications at altitude 1
• Acetazolamide may reduce subendocardial ischemia risk in these patients 1, 2
• Hypertensive patients may benefit from acetazolamide's blood pressure-lowering effects 8

Pediatric Patients

• No randomized trials exist for children; recommendations extrapolated from adult data 1
• Same principles apply: gradual ascent, acetazolamide dosing adjusted for weight 1

Critical Pitfalls to Avoid

• Never continue ascent with symptoms present—this markedly increases risk of severe illness 1
• Avoid combining acetazolamide with other diuretics without careful monitoring due to dehydration/electrolyte risk 2
• Do not underestimate importance of gradual ascent—pharmacological prophylaxis does not replace proper acclimatization 1
• Prolonged acetazolamide use beyond 2-3 days at terminal altitude is unnecessary and increases side effects 1
• Inadequate hydration worsens symptoms—maintain aggressive fluid intake 1