At elevation, the body needs to adapt to the decreased partial pressure of oxygen. In the short term adaptations include tachycardia, hypertension and hyperventilation. These physiologic alterations are usually enough to prevent serious physiological distress. However, if ascent occurs rapidly, individuals can become acutely ill, displaying a typical constellation of symptoms known as Acute Mountain Sickness (AMS). This disease typically manifests as headache, nausea, anorexia, insomnia and fatigue. While unpleasant, these symptoms alone are not dangerous, although AMS can progress to High Altitude Pulmonary Edema (HAPE) or High Altitude Cerebral Edema (HACE). HAPE and HACE both come with high mortality unless the afflicted individual can immediately descend. For this reason, researchers, mountain guides and experienced trekkers utilize the Lake Louise Questionnaire (LLQ) to assess the degree of AMS. The LLQ numerically grades the subject’s headache, GI symptoms, weakness, dizziness/lightheadedness, and insomnia. A high enough score correlates with severe AMS and should prompt the halt of further ascent.
Given the unpleasantness of AMS and its possibly fatal progression, there is a strong interest in prevention of AMS, HAPE and HACE. Traditional prophylaxis of this illness is accomplished with the carbonic anhydrase inhibitor, acetazolamide, which increases bicarbonate excretion in the kidneys, resulting in a metabolic acidosis to theoretically offset the hyperventilation-induced respiratory alkalosis. However, acetazolamide has many wide-ranging effects on the body, and its preventive mechanism is likely multifactorial. Unfortunately, acetazolamide also has many unpleasant side effects, including parasthesias, dysgeusia, polyuria (especially irritating if you’re in bulky clothing), and rash. Contrast this with recent data on ibuprofen, which is reasoned to prevent AMS by its anti-inflammatory effects and is unlikely to have the same rate of adverse reaction.
The HEAT study
Derry S, Wiffen PJ, Moore RA, Bendtsen L. Ibuprofen for acute treatment of episodic tension-type headache in adults. Cochrane Database of Systematic Reviews 2015
Estrada V, Franco DM, Medina RD, Garay AGG, Martí-Carvajal AJ, Arevalo-Rodriguez I. Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs. Cochrane Database of Systematic Reviews 2017
Gertsch JH, Lipman GS, Holck PS, et al. Prospective, Double-Blind, Randomized, Placebo-Controlled Comparison of Acetazolamide Versus Ibuprofen for Prophylaxis Against High Altitude Headache: The Headache Evaluation at Altitude Trial (HEAT). Wilderness & Environmental Medicine 2010;21(3):236–43.
Leaf DE, Goldfarb DS. Mechanisms of action of acetazolamide in the prophylaxis and treatment of acute mountain sickness. Journal of Applied Physiology 2006;102(4):1313–22.
Roach RC, Bartsch PH, Oelz O. The Lake Louise Acute Mountain Sickness Scoring System. Hypoxia and Molecular Medicine 1993:272–4.
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