High-altitude illness includes acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema. Acute mountain sickness is the least severe along the spectrum, but it can progress to high-altitude cerebral edema and high-altitude pulmonary edema, which are potentially deadly forms of high-altitude illness.
High-altitude illness occurs in those who are not acclimated to high altitude, usually within six to 10 hours of ascent. Severity of illness is a complex function related to the rate of ascent, final altitude, sleeping altitude, and individual physiology. (N Engl J Med 2001;345:107.)
Acute mountain sickness is completely preventable. It cannot occur without ascent, and its incidence can be significantly reduced if ascent occurs slowly, allowing appropriate time for acclimatization. Its prevention and treatment remain challenging, however. Slow ascent is not always feasible, as in many recreational, rescue, or military operations, and descent, one of the cardinal principles of high-altitude illness treatment, is not always immediately possible because of rescue access, inclement weather, or injury.
Options for pharmacological prophylaxis are limited. A recent, comprehensive review of the literature found only seven high-quality randomized-controlled trials on prevention. (Ann Emerg Med 2012;59:307.) This review concluded that only acetazolamide — not antioxidants, magnesium, sumatriptan, gabapentin, or Ginkgo biloba — was clearly effective as prophylaxis. A new study brings a fresh focus and potential new indication for an unfashionable medication long past its prime.
Ibuprofen Prevents Altitude Illness: A Randomized Controlled Trial for Prevention of Altitude Illness with Nonsteroidal Anti-inflammatories
Lipman GS, Kanaan NC, et al
Ann Emerg Med
2012 Mar 21. [Epub ahead of print]
The exact pathophysiology of acute mountain sickness remains uncertain. Vasodilation and altered blood-brain permeability have been implicated along with inflammatory mediators, which are the potential target of NSAIDs.
Healthy volunteers capable of hiking at high altitude were recruited for this study. Participants were excluded if younger than 18, older than 65, pregnant, or on certain medications (diuretics, steroids, acetazolamide, or NSAIDs) within the previous week. Other notable exclusions were baseline symptoms of acute mountain sickness, a history of high-altitude cerebral and pulmonary edema, a history of cerebral edema or brain tumor, and contraindications to NSAIDs.
Participants were randomly assigned to receive ibuprofen 600 mg three times a day or an identical-looking placebo. Treatment was initiated on the morning of ascent. Symptoms of acute mountain sickness were self-reported using the validated Lake Louise Questionnaire developed by an expert committee at the International Hypoxia Symposia. (Hypoxia and Molecular Medicine. Burlington, VT: Charles S. Houston; 1993, p. 272.) Using this instrument, symptoms were graded on a scale of 0 to 3 and included headache, GI symptoms, weakness, dizziness, and sleeplessness. Patients met criteria for acute mountain sickness if they reported headache and had an LLQ score higher than 3.
Acute mountain sickness occurred in 69 percent (29/42) of those who received placebo but in only 43 percent (19/44) of those who received ibuprofen (OR 0.3, 95% CI [0.1–0.8]). A decrease in its severity was reported in the ibuprofen group, but the difference did not meet predetermined statistical significance.
This study has a few notable limitations. Although randomized and blinded to intervention, participants were self-selected, recruited volunteers, all of whom participated on the same hike in one small area of central California over the same period of time, and they all reached the same endpoint elevation. Although some control of the protocol is necessary to reduce confounding variables, it may be that these same restrictions make the results inapplicable to other populations with different baseline characteristics, in different climates, with different rates of ascent, or different final elevations.
Ibuprofen has many advantages over acetazolamide. Acetazolamide can cause nausea, dizziness, and fatigue, which are usually mild but can be debilitating, but more importantly, these symptoms can complicate the diagnosis of acute mountain sickness. Acetazolamide used for prophylaxis has been associated with paresthesias in 76 percent to 91 percent of patients. (High Alt Med Biol 2006;7:17.) Acetazolamide, to be effective, must be taken 24 hours prior to ascent, which may make it a useless prophylaxis agent in time-sensitive operations. (N Engl J Med 2001;345:107.) Ibuprofen is also inexpensive, familiar, and safe, especially in short courses. Its wide availability without a prescription makes it much more likely to be used.
The next time your patient decides to head for the hills, be certain he takes ibuprofen with him. Its minimal cost and minimal risk are likely to make his ascent much less symptomatic and much more pleasurable. And it could save his life.
* Read an abstract of the Annals of Emergency Medicine article, “Ibuprofen Prevents Altitude Illness: A Randomized Controlled Trial for Prevention of Altitude Illness with Nonsteroidal Anti-inflammatories,” at http://bit.ly/AMSibuprofen.
* Read all of Dr. Lovato's past columns in the EM-News.com archive.
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