By Marcello Cherchi, MD PhD
For patients
Going to high altitudes (such as mountains), and getting there quickly, increase the risk of getting altitude sickness. The best treatment is prevention, but some studies suggest that medication (acetazolamide) or a natural remedy (gingko biloba) can be helpful.
For clinicians
Overview
“Altitude sickness,” also called “acute mountain sickness,” is a colloquial term for a non-life-threatening type of high altitude illness. More severe forms of high altitude illness include pulmonary edema and cerebral edema. Higher altitudes and more rapid ascent are the main risk factors for altitude sickness. Acetazolamide and gingko biloba appear superior to placebo for treating altitude sickness.
Introduction
At higher altitudes there is lower barometric pressure and lower oxygen concentration, resulting in hypobaric hypoxia. Such conditions can cause several types of high altitude illness (HAI), including acute mountain sickness, high altitude pulmonary edema and high altitude cerebral edema. The risk of HAI is greater at higher altitudes and with more rapid ascents. Younger people are more vulnerable to HAI. Some studies suggest that women are more vulnerable than men. The best treatment is prevention. Some studies suggest that acetazolamide or gingko biloba are superior to placebo. Some genes appear to confer greater resilience against high altitude illness.
Epidemiology
Maggiorini and colleagues (Maggiorini et al. 1990) studied 466 recreational climbers in the Swiss Alps and found a very clear correlation between increasing altitude and increasing risk of acute mountain sickness (AMS), specifically, “The prevalence of acute mountain sickness correlated with altitude: it was 9% at 2850 m, 13% at 3050 m, 34% at 3650 m, and 53% at 4559 m.”
Burtscher and colleagues (Burtscher et al. 2023) reviewed 21 studies (total 11,021 patients) who ascended to altitudes of 2200 – 4559 meters. They found that air travel (rapid ascent) was associated with a 4.5-fold steeper increase in acute mountain sickness (AMS), compared to more gradual ascent.
Most studies report that report that younger age is associated with a higher risk of AMS (Burtscher et al. 2023).
Some (Burtscher et al. 2023), though not all (Hackett et al. 1976) studies report that women are more vulnerable to AMS than men.
Genetics
Some human populations (e.g., inhabitants of the Tibetan Plateau or the Andes) appear better adapted to altitude (West 2012), and the study of such populations has revealed that specific genes confer more rapid acclimatization to hypobaric hypoxia (Mallet et al. 2023).
Pathophysiological mechanism of disease
West comments that, “The deleterious effects of high altitude are primarily caused by the low inspired PO2” (West 2012). The main mechanism for this is that at high altitudes there is lower barometric pressure and lower oxygen concentration, leading to hypobaric hypoxia (Mallet et al. 2023).
Several physiologic mechanisms can enable a person to acclimatize to hypobaric hypoxia, and different mechanisms act in different time frames when adapting to such conditions acutely (minutes, days) and chronically (months) (Mallet et al. 2023). These mechanisms include hyperventilation, polycythemia, hypoxic pulmonary vasoconstriction, changes in oxygen affinity of hemoglobin, increases in oxidative enzymes, and increased concentration of capillaries in peripheral muscle (West 2012).
Clinical presentation
Potential manifestations of “high altitude illness” (HAI) include (Mallet et al. 2023):
- Acute mountain sickness (AMS), the most common type, usually occurs at altitudes of greater than 2500 meters. Symptoms manifest within hours or days, and consist of some combination of headache, weakness, fatigue, listlessness, nausea and anorexia (Mallet et al. 2023).
- High altitude pulmonary edema (HAPE) is characterized by symptoms such as shortness of breath, coughing and frothy or blood-stained sputum (Mallet et al. 2023).
- High altitude cerebral edema (HACE) is characterized by confusion, ataxia and decreasing level of consciousness (Mallet et al. 2023).
Imaging
In a patient with the most severe manifestation of high altitude illness, brain imaging may demonstrate cerebral edema.
Treatment
The most effective management strategy is prevention. Hackett and colleagues (Hackett et al. 1976) state that, “Prevention consists in slow ascent, rapid recognition of warning signs, and prompt descent to avoid progression.”
A systematic review (Murdoch 2010) concluded there is moderate quality evidence that that acetazolamide (250 – 700 mg) is superior to placebo at “reducing the proportion of people who develop altitude sickness.” The same review concluded that acetazolamide is more effective than gingko biloba, but acetazolamide is also associated with a higher risk of adverse effects (paresthesias).
Prognosis
A systematic review (Murdoch 2010) found “no reliable data on prognosis. It is widely held that if no further ascent is attempted, then the symptoms of acute mountain sickness tend to resolve over a few days. We found no reliable data about long-term sequelae in people whose symptoms have completely resolved.”
References
Burtscher J, Swenson ER, Hackett PH, Millet GP, Burtscher M (2023) Flying to high-altitude destinations: Is the risk of acute mountain sickness greater? J Travel Med 30. doi: 10.1093/jtm/taad011
Hackett PH, Rennie D, Levine HD (1976) The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 2: 1149-55. doi: 10.1016/s0140-6736(76)91677-9
Maggiorini M, Buhler B, Walter M, Oelz O (1990) Prevalence of acute mountain sickness in the Swiss Alps. BMJ 301: 853-5. doi: 10.1136/bmj.301.6756.853
Mallet RT, Burtscher J, Pialoux V, Pasha Q, Ahmad Y, Millet GP, Burtscher M (2023) Molecular Mechanisms of High-Altitude Acclimatization. Int J Mol Sci 24. doi: 10.3390/ijms24021698
Murdoch D (2010) Altitude sickness. BMJ Clin Evid 2010.
West JB (2012) High-altitude medicine. Am J Respir Crit Care Med 186: 1229-37. doi: 10.1164/rccm.201207-1323CI
