Photo by Kerem Titiz http://www.flickr.com/photos/keremtitiz/
Photo by Kerem Titiz
http://www.flickr.com/photos/keremtitiz/

Acute Mountain Sickness (AMS) is a condition that affects many outdoor enthusiasts and tourists every year.

Diagnosis of AMS is based on:
1. A rise in altitude within the last 4 days
2. Presence of a headache
PLUS
3. Presence of at least one other symptom
4.  A total score of 3 or more from the questions below.
0-3 scale of symptoms related to: 1) Headache 2) Gastrointestinal symptoms 3) Severe nausea &/or vomiting 4) Fatigue &/or weakness 5) Dizziness/lightheadedness 6) Difficulty sleeping

See: Lake Louise Score for the diagnosis of AMS.

Study objective: Compare ibuprofen versus placebo in the prevention of acute mountain sickness incidence and severity on ascent from low to high altitude.

Methods: Healthy adult volunteers living at low altitude were randomized to ibuprofen 600 mg or placebo 3 times daily, starting 6 hours before ascent from 1,240 m (4,100 ft) to 3,810 m (12,570 ft) during July and August 2010 in the White Mountains of California. The main outcome measures were acute mountain sickness incidence and severity, measured by the Lake Louise Questionnaire acute mountain sickness score with a diagnosis of ≥ 3 with headache and 1 other symptom.

Authors conclusions: Compared with placebo, ibuprofen was effective in reducing the incidence of acute mountain sickness.

My conclusions: This small double blinded placebo controlled RCT was well designed and relevant to those who plan to travel from low to high altitude. Currently the only medications with indications for prevention of AMS are Acetazolamide and Dexamethasone both of which can be associated with potentially serious side effects and safety concerns.

The authors main conclusion supporting the use of Ibuprofen is based on Table 2.

Variables: Placebo, N42; Ibuprofen, N44

Difference in Estimates Between Treatment Groups, OR (95% CI)

AMS incidence (%)  Placebo 29 (69) Ibuprofen 19 (43)  OR 0.3 (0.1–0.8)
AMS severity: peak LLQ score, mean (SD) Placebo 4.4 (2.6) Ibuprofen 3.2 (2.4) OR 0.9 (0.3–3.0)*

LLQ = Lake Louise Questionnaire. *Reported as the mean difference in percentage.

My main concern is the relatively small overall sample size and wide confidence intervals for the difference in AMS severity and potential for overlap (meaning no true difference) between AMS severity in the placebo and ibuprofen groups. One surprising finding for me was that the Ibuprofen group had a similar incidence of headache (0.6 (0.2–1.6)) compared to the control group, but decreased incidence of GI complaints (OR 0.3 (0.1–0.8)) which is the opposite of what I would have expected. That said the difference in headache finding was not statistically significant.

My bottom line is that until I see further studies supporting the efficacy of Ibuprofen for the prevention of AMS, I will not be endorsing this prevention strategy. While the risk of adverse events is quite low, as would be the cost of treatment, I still remain skeptical.  What I would like to see in future research is further validation of this finding in a larger study. I would also like to see a well designed head-to-head non-inferiority double blinded RCT comparing Acetazolamide, Dexamethasone and Ibuprofen, although given the difficulties of recruiting adequate numbers of participants for altitude related research, I won’t be holding my breath.

Reference: Lipman et al. Ibuprofen prevents altitude illness: A randomized controlled trial for prevention of altitude illness with nonsteroidal anti-inflammatories. Ann Emerg Med. 2012;59:484-490 2011;39(7):1607-1612.

Simple ideas for preventing Acute Mountain Sickness: 1) Follow a strategy of staged ascent (Category 1A) 2) High carbohydrate diet (Category 2) 3) Until acclimatized moderate physical activity 4) Maintain adequate hydration.  (Wilderness Medical Society Practice Guidelines  5th Edition – High Altitude Illness)

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