Altitude illness affects 25–50% of travelers to 2,500–3,500m (8,200–11,500 feet) and up to 75% of unacclimatized individuals ascending rapidly to 4,500m+. The spectrum ranges from the headache and fatigue of mild acute mountain sickness (AMS) to the life-threatening brain swelling (high altitude cerebral edema, HACE) and pulmonary edema (high altitude pulmonary edema, HAPE) that kill climbers on Kilimanjaro, in the Himalayas, and at high-altitude ski resorts. Evidence-based prevention is highly effective but requires planning before departure.
Pathophysiology and Risk Factors
Altitude illness is driven by hypobaric hypoxia — reduced partial pressure of oxygen triggers: carotid body chemoreceptor activation → hyperventilation; relative sympathetic dominance → peripheral vasoconstriction; blood-brain barrier disruption → vasogenic cerebral edema (HACE); pulmonary vasoconstriction with fluid leakage → HAPE. Individual susceptibility is largely genetic — prior AMS is the strongest predictor of future AMS (positive predictive value 75%). Fitness level is NOT protective — elite athletes at sea level are equally susceptible to AMS as sedentary individuals at altitude. Rate of ascent is the primary modifiable risk factor: the Wilderness Medical Society recommends sleeping altitude increase of ≤500m/day above 2500m, with a rest day every 3rd day.
Pharmacological Prevention and Treatment
Acetazolamide (Diamox): inhibits carbonic anhydrase → increased ventilatory response to hypoxia → better oxygenation. Dose: 125mg twice daily starting 24–48 hours before ascent, continuing until descent. Reduces AMS incidence by 48% in meta-analysis (Cochrane 2012, 8 RCTs). Side effects: paresthesias (extremely common but benign), diuresis, nausea — rare serious: sulfa allergy cross-reactivity (contraindicated in sulfa allergy). Dexamethasone: 8mg load, then 4mg every 6 hours — highly effective for treatment and prevention, but doesn't facilitate acclimatization (masks rather than prevents). Reserved for rescue descent situations or individuals with absolute contraindications to acetazolamide. For travel medicine clinics and wilderness medicine programs, our first aid supplies include emergency medication management supplies, and our diagnostic equipment section includes portable pulse oximeters essential for altitude illness monitoring.
