Salmeterol for the Prevention of High-Altitude Pulmonary Edema

doi:10.1056/NEJMoa013183

Volume 346:1631-1636		May 23, 2002		Number 21

Salmeterol for the Prevention of High-Altitude Pulmonary Edema

Claudio Sartori, M.D., Yves Allemann, M.D., Hervé Duplain, M.D., Mattia Lepori, M.D., Marc Egli, M.D., Ernst Lipp, M.D., Damian Hutter, M.D., Pierre Turini, M.D., Olivier Hugli, M.D., Stéphane Cook, M.D., Pascal Nicod, M.D., and Urs Scherrer, M.D.

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ABSTRACT

Background Pulmonary edema results from a persistent imbalancebetween forces that drive water into the air space and the physiologicmechanisms that remove it. Among the latter, the absorptionof liquid driven by active alveolar transepithelial sodium transporthas an important role; a defect of this mechanism may predisposepatients to pulmonary edema. Beta-adrenergic agonists up-regulatethe clearance of alveolar fluid and attenuate pulmonary edemain animal models.

Methods In a double-blind, randomized, placebo-controlled study,we assessed the effects of prophylactic inhalation of the beta-adrenergicagonist salmeterol on the incidence of pulmonary edema duringexposure to high altitudes (4559 m, reached in less than 22hours) in 37 subjects who were susceptible to high-altitudepulmonary edema. We also measured the nasal transepithelialpotential difference, a marker of the transepithelial sodiumand water transport in the distal airways, in 33 mountaineerswho were prone to high-altitude pulmonary edema and 33 mountaineerswho were resistant to this condition.

Results Prophylactic inhalation of salmeterol decreased theincidence of high-altitude pulmonary edema in susceptible subjectsby more than 50 percent, from 74 percent with placebo to 33percent (P=0.02). The nasal potential-difference value underlow-altitude conditions was more than 30 percent lower in thesubjects who were susceptible to high-altitude pulmonary edemathan in those who were not susceptible (P<0.001).

Conclusions Prophylactic inhalation of a beta-adrenergic agonistreduces the risk of high-altitude pulmonary edema. Sodium-dependentabsorption of liquid from the airways may be defective in patientswho are susceptible to high-altitude pulmonary edema. Thesefindings support the concept that sodium-driven clearance ofalveolar fluid may have a pathogenic role in pulmonary edemain humans and therefore represent an appropriate target fortherapy.

Source Information

From the Department of Internal Medicine (C.S., H.D., M.L., M.E., P.T., O.H., S.C., P.N., U.S.) and the Botnar Center for Clinical Research (C.S., H.D., M.L., M.E., P.T., O.H., S.C., U.S.), Centre Hospitalier Universitaire Vaudois, Lausanne; and the Swiss Cardiovascular Center, University Hospital, Bern (Y.A., E.L., D.H.) — both in Switzerland.

Address reprint requests to Dr. Scherrer at the Department of Internal Medicine, BH 10.642, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland, or at urs.scherrer{at}chuv.hospvd.ch.

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Salmeterol for the Prevention of High-Altitude Pulmonary Edema
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N Engl J Med 2002; 347:1282-1285, Oct 17, 2002. Correspondence

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