Ibuprofen for Acute Mountain Sickness?

The Background

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.

Lake Louise

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

The landmark study comparing motrin and acetazolamide was a randomized, controlled trial on 343 patients who were given either ibuprofen, acetazolamide, or placebo prior to trekking from 4300 m to 4928 m camps in the Himalayas. Patients were excluded if they were already symptomatic or acclimatized or already taking either of the study drugs. The primary outcome was headache “as calculated on the Lake Louise Questionnaire.” Secondary outcomes were headache as calculated on a visual analog scale and development of AMS by the LLQ. Both ibuprofen and acetazolamide were found to reduce the primary outcome and incidence of AMS compared to placebo, without significant difference between the two treatments. Acetazolamide was found to be slightly better at preventing headache by the visual analog scale. No adverse effects were reported, and no episodes of HAPE or HACE were reported.

The caveat

While this study suggests that ibuprofen may be as effective as acetazolamide at prevention of AMS, it is already well established that the former treats headache. The LLQ uses headache as a primary diagnostic symptom and may therefore incorrectly overestimate the effectiveness of ibuprofen for prevention of AMS. Furthermore, this study was insufficient in its evaluation of prevention of the progression of HAPE or HACE as no cases of either were identified. It’s therefore impossible to draw any conclusions regarding the effect that ibuprofen may have at preventing progression to either of these two deadly entities.

The Take-Away

The HEAT study suggests that, at the very least, ibuprofen is effective at preventing headache associated with ascension to high altitude. However, it’s true effect on preventing AMS as an entity that goes beyond headache remains to be seen. While ibuprofen may have a more favorable side effect profile, it shouldn’t be relied upon for prophylaxis of AMS.

References

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.