LAUSR

Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, placebo-controlled, double-blind study. Thirteen healthy, non-acclimatized lowlanders with a history of HAPE ascended (<22h) from 1,130 to 4,559m with one overnight stay at 3,611m. Medications started 48h before ascent (acetazolamide: n=7, 250mg 3x/d; placebo: n=6, 3x/d). HAPE was diagnosed by chest radiography, and pulmonary artery pressure by measurement of right ventricular to atrial pressure gradient (RVPG) by transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and AMS-C Score. Incidence of HAPE was 43% vs. 67% (acetazolamide vs. placebo, p=0.39). Ascent to altitude increased RVPG from 20±5 to 43±10mmHg (p<0.001) without a group difference (p=0.68). Arterial PO2 fell to 36±9mmHg (p<0.001) and was 8.5mmHg higher with acetazolamide at high altitude (p=0.025). At high altitude, the LLS and AMS-C score remained lower in those taking acetazolamide (both p<0.05). Although acetazolamide reduced HAPE incidence by 35%, this effect was not statistically significant, and considerably less than reductions of about 70-100% with prophylactic dexamethasone, tadalafil, and nifedipine performed with the same ascent profile at the same location. We could not demonstrate a reduction in RVPG compared to placebo treatment despite reductions in AMS severity and better arterial oxygenation. Limited by a small sample size, our data do not support recommending acetazolamide for prevention of HAPE in mountaineers ascending rapidly to over 4,500m.