Pulmonary Edema, High-Altitude
High-altitude illness may result from short-term exposures to altitudes in excess of 2000 m (6560 ft). This illness comprises a spectrum of clinical entities that are probably the manifestations of the same disease process. High-altitude pulmonary edema (HAPE) and cerebral edema are the most ominous of these symptoms, while acute mountain sickness, retinal hemorrhages, and peripheral edema are the milder forms of the disease. The rate of ascent, the altitude attained, the amount of physical activity at high altitude, and individual susceptibility are contributing factors to the incidence and severity of high-altitude illness.
The pathophysiology is not well understood. HAPE is a noncardiogenic form of pulmonary edema resulting from a leak in the alveolar capillary membrane. The various mechanisms believed to be responsible are pulmonary arterial vasoconstriction resulting in circulatory shear forces and a consequent permeability leak and antidiuresis possibly mediated by increased antidiuretic hormones, which contribute to fluid retention. The inciting factor appears to be excessive hypoxia.
A number of compensatory mechanisms improve oxygen delivery when its inspired concentration is reduced. The first adaptation to high altitude is an increase in minute ventilation. The ventilatory response to a relatively hypoxic stimulus can be divided into 4 phases: (1) initial increase on ascent, (2) subsequent course over hours and weeks, (3) deacclimatization on descent, and (4) long-term response of high-altitude natives.
The barometric pressure decreases with distance above the Earth’s surface in an approximately exponential manner. The pressure at 5500 m (18,000 ft) is only half the normal 760 mm Hg, so that the partial pressure of oxygen (PO2) of moist inspired gas is (380-47) X 0.2093 = 70 (47 mm Hg is the partial pressure of water vapor at body temperature [ie, 37ºC]). At the summit of Mount Everest (altitude 8848 m or 29,028 ft), the inspired PO2 is only 43. In spite of hypoxia associated with high altitude, approximately 15 million people live at elevations over 3050 m, and some permanent residents live higher than 4900 m in the Andes. A remarkable degree of acclimatization occurs when humans ascend to these altitudes. Climbers have lived for several days at altitudes that would cause unconsciousness within a few seconds in the absence of acclimatization.
Spirometric studies have shown that with increasing altitude, both forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) are reduced by up to 25% (74.8% / 74.6% of baseline). In the same study, peak expiratory flow (PEF) initially increased up to 4451 m and returned to baseline values above 5000 m. After descent below 2000 m, all values normalized within one day. These findings were consistent with increasing pulmonary restriction at high altitudes (without a marked reduction of PEF). Portable spirometry may provide clinically relevant information (impending pulmonary edema) in high-altitude travelers.1
Bronchoalveolar lavage fluid (BALF) studies have shown that after heavy exercise, under all conditions, athletes develop a permeability edema with high BALF RBC and protein concentrations in the absence of inflammation. Exercise at altitude (3810 m) caused significantly greater leakage of RBCs (92,000 [SD 3.1] cells/mL) into the alveolar space than that seen with normoxic exercise (54,000 [SD 1.2] cells/mL). At altitude, the 26-hour postexercise BALF had significantly higher RBC and protein concentrations, suggesting an ongoing capillary leak. These findings suggest that pulmonary capillary disruption occurs with intense exercise in healthy humans and that hypoxia augments the mechanical stresses on the pulmonary microcirculation.2
Autopsy studies performed on patients who died of HAPE have shown a proteinaceous exudate with hyaline membranes. The studies have shown areas of pneumonitis with neutrophil accumulation, although none was noted to contain bacteria. Pulmonary veins were not dilated. Most reports mention capillary and arteriolar thrombi with deposits of fibrin, hemorrhage, and infarcts. The findings suggest a protein-rich edema with a possibility that clotting abnormalities may be partially responsible for this illness.
Bronchoalveolar lavages performed on patients with HAPE have also shown the fluid to have a high protein content, higher than in patients with adult respiratory distress syndrome (ARDS). The fluid was also highly cellular. Unlike ARDS, which primarily has neutrophils in the lavage fluid, HAPE fluid contains a higher percentage of alveolar macrophages. Additionally, chemotactic (leukotriene B4) and vasoactive (thromboxane B2) mediators were present in the lavage.
In one study on Colorado skiers, incidence of acute mountain sickness was as high as 15-40%. Incidence of HAPE is much lower, at about 0.1-1%.
In a study on Mount Everest trekkers, incidence of HAPE was about 1.6%. Incidence of mountain sickness appears to be unusually high in trekkers on Mount Rainier; however, the incidence of pulmonary edema is the same as in other places.
HAPE may be fatal within a few hours if left untreated. Patients who recover from HAPE have rapid clearing of edema fluid and do not develop long-term complications.
Men and women are equally susceptible to acute mountain sickness, but women may be less likely to develop HAPE. In addition to individual differences in susceptibility, other factors, such as alcohol, respiratory depressants, and respiratory infections, may enhance vulnerability to altitude illness.
The typical patient with HAPE is a young person who is otherwise physically fit. HAPE is rare in infants and small children.
HAPE generally occurs 1-4 days after rapid ascent to altitudes in excess of 2500 m (8000 ft). Young people and previously acclimatized people reascending to a high altitude following a short stay at low altitude seem more predisposed to HAPE. Cold weather and physical exertion at high altitude are other predisposing factors.
The earliest indications are decreased exercise tolerance and slow recovery from exercise.
The person usually notices fatigue, weakness, and dyspnea on exertion.
The condition typically worsens at night, and tachycardia and tachypnea occur at rest. Periodic breathing during sleep is almost universal in sojourners at high altitude.
Cough, frothy sputum, cyanosis, rales, and dyspnea progressing to severe respiratory distress are symptoms of the disease.
A low-grade fever, respiratory alkalosis, and leukocytosis are other common features.
In severe cases, an altered mental status, hypotension, and death may result.
In addition to the symptoms discussed, HAPE is diagnosed by the presence of at least 2 of the following signs:
Crackles on auscultation
Disproportionately low oxygen saturation relative to altitude
Physical exertion at high altitude
Exposure to cold