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Inhaled salmeterol prevents high-altitude pulmonary edema
ABSTRACT
BACKGROUND: High-altitude pulmonary edema (HAPE) is a life-threatening manifestation of high-altitude illness. Although conventional medications such as acetazolamide and dexamethasone can prevent acute mountain sickness (a more common and less severe stage of high-altitude illness). Dexamethasone is known to be ineffective and acetazolamide has not been studied specifically for HAPE.1 Beta-agonists may decrease HAPE by promoting the clearance of alveolar fluid and thus relieving pulmonary edema and alveolar hypoxia. This study investigated the use of salmeterol to prevent HAPE in climbers at high risk for this condition.
POPULATION STUDIED: The investigators studied 37 mountaineers who had a history of HAPE (average of 2 previous episodes per subject). Most subjects were men, and the average age was 48 years. Baseline demographics were similar between groups. The population was appropriate for the condition being studied, although these men were at much higher risk for HAPE than the average recreational mountain climber.
STUDY DESIGN AND VALIDITY: This study was double-blind, randomized, and placebo controlled. Starting the day before ascent, the climbers inhaled either salmeterol 125 μg (about 3 times the normal asthma dosage) or placebo every 12 hours via metered-dose inhaler with spacer. They ascended (via cable car and mountaineering) from 1130 m to a high-altitude (4559 m) research laboratory in Italy over a period of 22 hours. Investigators then observed the subjects over a period of 2 days and nights for clinical and laboratory signs of HAPE and acute mountain sickness. Participants who developed symptoms of HAPE were evacuated to low altitude.
OUTCOMES MEASURED: The major patient-oriented end point was clinical and radiographic evidence of pulmonary edema. Investigators recorded Lake Louise Acute Mountain Sickness scores, arterial oxygen saturations, and carbon dioxide and oxygen arterial partial pressures. They also compared chest radiographs obtained at the high-altitude laboratory.
RESULTS: The incidence of pulmonary edema was less in the salmeterol group than with placebo (74% vs 33%; P=.02; numbers needed to treat=2.5). Lake Louise Acute Mountain Sickness scores were significantly better in the salmeterol group than in the placebo group (5.8 vs 11.5 out of a possible 24; P < .001). Chest radiographs, arterial oxygen saturations, and oxygen arterial partial pressures were also significantly improved with salmeterol.
Inhaled salmeterol decreases the incidence of HAPE in climbers with previous episodes of this condition. Nifedipine is the only other drug specifically shown to prevent HAPE2; although both the nifedipine study and the current salmeterol study were small, the 2 drugs appear roughly comparable in efficacy. It is unclear whether salmeterol would be effective for preventing more common and less severe stages of high-altitude illness (eg, acute mountain sickness), or whether the drug would be worthwhile in persons without a history of HAPE. Because of established efficacy in preventing acute mountain sickness, acetazolamide or dexamethasone should remain first-line agents for prevention of high-altitude illness in most climbers, with salmeterol or nifedipine added for individuals at high risk of HAPE.
ABSTRACT
BACKGROUND: High-altitude pulmonary edema (HAPE) is a life-threatening manifestation of high-altitude illness. Although conventional medications such as acetazolamide and dexamethasone can prevent acute mountain sickness (a more common and less severe stage of high-altitude illness). Dexamethasone is known to be ineffective and acetazolamide has not been studied specifically for HAPE.1 Beta-agonists may decrease HAPE by promoting the clearance of alveolar fluid and thus relieving pulmonary edema and alveolar hypoxia. This study investigated the use of salmeterol to prevent HAPE in climbers at high risk for this condition.
POPULATION STUDIED: The investigators studied 37 mountaineers who had a history of HAPE (average of 2 previous episodes per subject). Most subjects were men, and the average age was 48 years. Baseline demographics were similar between groups. The population was appropriate for the condition being studied, although these men were at much higher risk for HAPE than the average recreational mountain climber.
STUDY DESIGN AND VALIDITY: This study was double-blind, randomized, and placebo controlled. Starting the day before ascent, the climbers inhaled either salmeterol 125 μg (about 3 times the normal asthma dosage) or placebo every 12 hours via metered-dose inhaler with spacer. They ascended (via cable car and mountaineering) from 1130 m to a high-altitude (4559 m) research laboratory in Italy over a period of 22 hours. Investigators then observed the subjects over a period of 2 days and nights for clinical and laboratory signs of HAPE and acute mountain sickness. Participants who developed symptoms of HAPE were evacuated to low altitude.
OUTCOMES MEASURED: The major patient-oriented end point was clinical and radiographic evidence of pulmonary edema. Investigators recorded Lake Louise Acute Mountain Sickness scores, arterial oxygen saturations, and carbon dioxide and oxygen arterial partial pressures. They also compared chest radiographs obtained at the high-altitude laboratory.
RESULTS: The incidence of pulmonary edema was less in the salmeterol group than with placebo (74% vs 33%; P=.02; numbers needed to treat=2.5). Lake Louise Acute Mountain Sickness scores were significantly better in the salmeterol group than in the placebo group (5.8 vs 11.5 out of a possible 24; P < .001). Chest radiographs, arterial oxygen saturations, and oxygen arterial partial pressures were also significantly improved with salmeterol.
Inhaled salmeterol decreases the incidence of HAPE in climbers with previous episodes of this condition. Nifedipine is the only other drug specifically shown to prevent HAPE2; although both the nifedipine study and the current salmeterol study were small, the 2 drugs appear roughly comparable in efficacy. It is unclear whether salmeterol would be effective for preventing more common and less severe stages of high-altitude illness (eg, acute mountain sickness), or whether the drug would be worthwhile in persons without a history of HAPE. Because of established efficacy in preventing acute mountain sickness, acetazolamide or dexamethasone should remain first-line agents for prevention of high-altitude illness in most climbers, with salmeterol or nifedipine added for individuals at high risk of HAPE.
ABSTRACT
BACKGROUND: High-altitude pulmonary edema (HAPE) is a life-threatening manifestation of high-altitude illness. Although conventional medications such as acetazolamide and dexamethasone can prevent acute mountain sickness (a more common and less severe stage of high-altitude illness). Dexamethasone is known to be ineffective and acetazolamide has not been studied specifically for HAPE.1 Beta-agonists may decrease HAPE by promoting the clearance of alveolar fluid and thus relieving pulmonary edema and alveolar hypoxia. This study investigated the use of salmeterol to prevent HAPE in climbers at high risk for this condition.
POPULATION STUDIED: The investigators studied 37 mountaineers who had a history of HAPE (average of 2 previous episodes per subject). Most subjects were men, and the average age was 48 years. Baseline demographics were similar between groups. The population was appropriate for the condition being studied, although these men were at much higher risk for HAPE than the average recreational mountain climber.
STUDY DESIGN AND VALIDITY: This study was double-blind, randomized, and placebo controlled. Starting the day before ascent, the climbers inhaled either salmeterol 125 μg (about 3 times the normal asthma dosage) or placebo every 12 hours via metered-dose inhaler with spacer. They ascended (via cable car and mountaineering) from 1130 m to a high-altitude (4559 m) research laboratory in Italy over a period of 22 hours. Investigators then observed the subjects over a period of 2 days and nights for clinical and laboratory signs of HAPE and acute mountain sickness. Participants who developed symptoms of HAPE were evacuated to low altitude.
OUTCOMES MEASURED: The major patient-oriented end point was clinical and radiographic evidence of pulmonary edema. Investigators recorded Lake Louise Acute Mountain Sickness scores, arterial oxygen saturations, and carbon dioxide and oxygen arterial partial pressures. They also compared chest radiographs obtained at the high-altitude laboratory.
RESULTS: The incidence of pulmonary edema was less in the salmeterol group than with placebo (74% vs 33%; P=.02; numbers needed to treat=2.5). Lake Louise Acute Mountain Sickness scores were significantly better in the salmeterol group than in the placebo group (5.8 vs 11.5 out of a possible 24; P < .001). Chest radiographs, arterial oxygen saturations, and oxygen arterial partial pressures were also significantly improved with salmeterol.
Inhaled salmeterol decreases the incidence of HAPE in climbers with previous episodes of this condition. Nifedipine is the only other drug specifically shown to prevent HAPE2; although both the nifedipine study and the current salmeterol study were small, the 2 drugs appear roughly comparable in efficacy. It is unclear whether salmeterol would be effective for preventing more common and less severe stages of high-altitude illness (eg, acute mountain sickness), or whether the drug would be worthwhile in persons without a history of HAPE. Because of established efficacy in preventing acute mountain sickness, acetazolamide or dexamethasone should remain first-line agents for prevention of high-altitude illness in most climbers, with salmeterol or nifedipine added for individuals at high risk of HAPE.