The diagnosis and treatment of high-altitude illness (HAI) require an understanding of the interplay between physics and physiology. As altitude increases, pressure decreases, affecting the partial pressure of oxygen and thus decreasing the amount of oxygen diffusing into the tissues. This hypobaric hypoxia results in a cascade of events known as HAI. In an effort to acclimate, the respiratory rate increases, leading to respiratory alkalosis with metabolic compensation. This also causes an overall left shift of the oxygen-hemoglobin dissociation curve, increasing oxygen uptake in the lungs. Hypoxemia causes increased release of erythropoietin, leading to an increase in red blood cell production and overall better oxygen-carrying capacity to the tissues.

The most important syndromes that make up the spectrum of HAI are high-altitude pulmonary edema (HAPE) and acute mountain sickness (AMS), which can progress to high-altitude cerebral edema (HACE). Younger athletes and males are at greater risk of HAI since they are more likely to engage in vigorous activity prior to acclimatization or continue ascent despite symptoms. Other risk factors include chronic obstructive pulmonary disease, restrictive lung disease, cystic fibrosis, pulmonary hypertension, congestive heart failure, and sickle cell disease. Contrary to popular belief, neither well-controlled asthma nor pregnancy (up to 3,000 meters) increase the risk of HAI.

High-Altitude Pulmonary Edema

There are two types of HAPE: classic, which occurs in low-altitude residents who rapidly ascend, and reentry, which occurs in high-altitude residents re-ascending after being at low altitudes. The pathophysiology of HAPE consists of breakdown of the pulmonary blood-gas barrier secondary to increased pulmonary artery pressure and uneven pulmonary vasoconstriction resulting in fluid accumulation within the alveoli. This typically occurs around 3,000 meters. Patients present with a dry cough that progresses to a productive cough with frothy pink sputum and increased dyspnea within four to six days of arrival at altitude. Patients demonstrate tachycardia, tachypnea, inspiratory crackles, and low pulse oximetry on physical exam. Chest X-ray reveals patchy infiltrates, but it is not required to make a diagnosis.¹

The treatment of stable patients with HAPE involves simply giving oxygen via high-flow nasal cannula and decreasing cold exposure to resolve the elevation in pulmonary artery pressure. Unstable patients should descend as soon as possible, and if that is not possible, use hyperbaric therapy as indicated.1 Medications can be used for treatment. However, they are more effective as preventative measures. Nifedipine can reduce pulmonary vascular resistance and decrease pulmonary artery pressure, and phosphodiesterase 5 inhibitors can increase cyclic guanosine 3’,5’-monophosphate (cGMP) to augment the pulmonary vasodilatory effects of nitric oxide. Nitric oxide is a potent pulmonary vasodilator, released from endothelial cells, that decreases hypoxic pulmonary vasoconstriction and the pulmonary hypertension associated with HAPE. Inhaled beta-agonists can be used as an adjunct, but they have limited effectiveness as a sole treatment option.^2–4