Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

High altitude pulmonary edema

Scott A Gallagher, MD
Peter Hackett, MD
Section Editor
Daniel F Danzl, MD
Deputy Editor
Jonathan Grayzel, MD, FAAEM


Anyone who travels to high altitude, whether a recreational hiker, skier, mountain climber, soldier, or rescue worker, is at risk of developing high altitude illness. High altitude pulmonary edema (HAPE) is a life-threatening form of such illness that involves abnormal accumulation of fluid in the lungs, and in fact is the most common fatal manifestation of severe high altitude illness.

The pathophysiology, clinical presentation, treatment, and prevention of HAPE are reviewed here. Other forms of high altitude illness are discussed separately. (See "Acute mountain sickness and high altitude cerebral edema" and "High altitude illness: Physiology, risk factors, and general prevention" and "High altitude disease: Unique pediatric considerations".)


High altitude pulmonary edema (HAPE) is the abnormal accumulation of plasma and some red cells in the lung due to a breakdown in the pulmonary blood-gas barrier, triggered by hypobaric hypoxia. This breakdown develops from a number of maladaptive responses to the hypoxia encountered at higher altitudes, including poor ventilatory response, increased sympathetic tone, exaggerated and uneven pulmonary vasoconstriction (pulmonary hypertension), inadequate production of endothelial nitric oxide, and overproduction of endothelin, many of which are genetically determined [1-3]. The end result is a patchy accumulation of extravascular fluid in the alveolar spaces that impairs respiration and can, in severe cases, prove fatal.

Genetics clearly play an important role in the risk of HAPE, as suggested by the marked variability in individual susceptibility, the higher rates of recurrence among some individuals, and the pathophysiological factors mentioned above. However, HAPE genetic studies are conflicting and clear conclusions are elusive. Genes associated with HAPE have included those in the pathways for nitric oxide, renin-angiotensin-aldosterone, hypoxia-inducible factor (HIF), heat shock protein (HSP 70), pulmonary surfactant proteins A1 and A2, and aquaporin-5 [4].  

High mean pulmonary artery (PA) pressure, in excess of 35 to 40 mmHg, appears to be the initiating event. Specific segmental and subsegmental capillary beds with relatively less vasoconstriction are disproportionately exposed to elevated microvascular pressures (>20 mmHg) that arise from the elevated mean PA pressure. This uneven vasoconstriction and regional overperfusion result in failure of the alveolar-capillary barrier and patchy pulmonary edema.

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Oct 2017. | This topic last updated: Dec 12, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Stream JO, Grissom CK. Update on high-altitude pulmonary edema: pathogenesis, prevention, and treatment. Wilderness Environ Med 2008; 19:293.
  2. Bärtsch P, Mairbäurl H, Maggiorini M, Swenson ER. Physiological aspects of high-altitude pulmonary edema. J Appl Physiol (1985) 2005; 98:1101.
  3. Scherrer U, Allemann Y, Rexhaj E, et al. Mechanisms and drug therapy of pulmonary hypertension at high altitude. High Alt Med Biol 2013; 14:126.
  4. Hackett PH, Luks, AM, et al. High altitude medicine and pathophysiology. In: Wilderness Medicine, 7th ed, Auerbach PS (Ed), Elsevier, Philadelphia 2016. p.8.
  5. Hackett PH, Rennie D, Levine HD. The incidence, importance, and prophylaxis of acute mountain sickness. Lancet 1976; 2:1149.
  6. Singh I, Roy SB. High altitude pulmonary edema: Clinical hemodynamic and pathologic studies. In: Biomedical Problems of High Terrestrial Elevations, Hegnauer A (Ed), Federal Scientific Technical Informatino Service, Springfield 1962. p.108.
  7. Hultgren HN, Honigman B, Theis K, Nicholas D. High-altitude pulmonary edema at a ski resort. West J Med 1996; 164:222.
  8. Jones BE, Stokes S, McKenzie S, et al. Management of high altitude pulmonary edema in the Himalaya: a review of 56 cases presenting at Pheriche medical aid post (4240 m). Wilderness Environ Med 2013; 24:32.
  9. Hackett PH, Roach RC. High-altitude illness. N Engl J Med 2001; 345:107.
  10. Schoene RB. Illnesses at high altitude. Chest 2008; 134:402.
  11. Duster MC, Derlet MN. High-altitude illness in children. Pediatr Ann 2009; 38:218.
  12. Yaron M, Niermeyer S, Lindgren KN, Honigman B. Evaluation of diagnostic criteria and incidence of acute mountain sickness in preverbal children. Wilderness Environ Med 2002; 13:21.
  13. Yaron M, Waldman N, Niermeyer S, et al. The diagnosis of acute mountain sickness in preverbal children. Arch Pediatr Adolesc Med 1998; 152:683.
  14. Pollard AJ, Niermeyer S, Barry P, et al. Children at high altitude: an international consensus statement by an ad hoc committee of the International Society for Mountain Medicine, March 12, 2001. High Alt Med Biol 2001; 2:389.
  15. Vock P, Brutsche MH, Nanzer A, Bärtsch P. Variable radiomorphologic data of high altitude pulmonary edema. Features from 60 patients. Chest 1991; 100:1306.
  16. Pratali L, Cavana M, Sicari R, Picano E. Frequent subclinical high-altitude pulmonary edema detected by chest sonography as ultrasound lung comets in recreational climbers. Crit Care Med 2010; 38:1818.
  17. Bouzat P, Walther G, Rupp T, et al. Time course of asymptomatic interstitial pulmonary oedema at high altitude. Respir Physiol Neurobiol 2013; 186:16.
  18. Garbella E, Catapano G, Pratali L, Pingitore A. Pulmonary edema in healthy subjects in extreme conditions. Pulm Med 2011; 2011:275857.
  19. Fagenholz PJ, Gutman JA, Murray AF, et al. Chest ultrasonography for the diagnosis and monitoring of high-altitude pulmonary edema. Chest 2007; 131:1013.
  20. Picano E, Frassi F, Agricola E, et al. Ultrasound lung comets: a clinically useful sign of extravascular lung water. J Am Soc Echocardiogr 2006; 19:356.
  21. Wimalasena Y, Windsor J, Edsell M. Using ultrasound lung comets in the diagnosis of high altitude pulmonary edema: fact or fiction? Wilderness Environ Med 2013; 24:159.
  22. Hackett PH, Roach RC. High-Altitude Medicine. In: Wilderness Medicine, 6th ed, Auerbach PS (Ed), Mosby, Philadelphia 2012. p.2.
  23. Luks AM, McIntosh SE, Grissom CK, et al. Wilderness Medical Society consensus guidelines for the prevention and treatment of acute altitude illness. Wilderness Environ Med 2010; 21:146.
  24. Oelz O, Maggiorini M, Ritter M, et al. Nifedipine for high altitude pulmonary oedema. Lancet 1989; 2:1241.
  25. Deshwal R, Iqbal M, Basnet S. Nifedipine for the treatment of high altitude pulmonary edema. Wilderness Environ Med 2012; 23:7.
  26. Marticorena E, Hultgren HN. Evaluation of therapeutic methods in high altitude pulmonary edema. Am J Cardiol 1979; 43:307.
  27. Zafren K, Reeves JT, Schoene R. Treatment of high-altitude pulmonary edema by bed rest and supplemental oxygen. Wilderness Environ Med 1996; 7:127.
  28. Hackett PH, Roach RC, Hartig GS, et al. The effect of vasodilators on pulmonary hemodynamics in high altitude pulmonary edema: a comparison. Int J Sports Med 1992; 13 Suppl 1:S68.
  29. Anand IS, Prasad BA, Chugh SS, et al. Effects of inhaled nitric oxide and oxygen in high-altitude pulmonary edema. Circulation 1998; 98:2441.
  30. Luks AM. Do we have a "best practice" for treating high altitude pulmonary edema? High Alt Med Biol 2008; 9:111.
  31. Freeman K, Shalit M, Stroh G. Use of the Gamow Bag by EMT-basic park rangers for treatment of high-altitude pulmonary edema and high-altitude cerebral edema. Wilderness Environ Med 2004; 15:198.
  32. Schoene RB, Roach RC, Hackett PH, et al. High altitude pulmonary edema and exercise at 4,400 meters on Mount McKinley. Effect of expiratory positive airway pressure. Chest 1985; 87:330.
  33. Koch RO, Hinterhuber L, Faulhaber M, et al. A successful therapy of high-altitude pulmonary edema with a CPAP helmet on Lenin Peak. Clin J Sport Med 2009; 19:72.
  34. Oelz O, Maggiorini M, Ritter M, et al. Prevention and treatment of high altitude pulmonary edema by a calcium channel blocker. Int J Sports Med 1992; 13 Suppl 1:S65.
  35. Maggiorini M, Brunner-La Rocca HP, Peth S, et al. Both tadalafil and dexamethasone may reduce the incidence of high-altitude pulmonary edema: a randomized trial. Ann Intern Med 2006; 145:497.
  36. Bates MG, Thompson AA, Baillie JK. Phosphodiesterase type 5 inhibitors in the treatment and prevention of high altitude pulmonary edema. Curr Opin Investig Drugs 2007; 8:226.
  37. Bärtsch P, Swenson ER, Maggiorini M. Update: High altitude pulmonary edema. Adv Exp Med Biol 2001; 502:89.
  38. Bärtsch P, Maggiorini M, Ritter M, et al. Prevention of high-altitude pulmonary edema by nifedipine. N Engl J Med 1991; 325:1284.
  39. Swenson ER. Hypoxic lung whiteout: further clearing but more questions from on high. Ann Intern Med 2006; 145:550.
  40. Richalet JP, Gratadour P, Robach P, et al. Sildenafil inhibits altitude-induced hypoxemia and pulmonary hypertension. Am J Respir Crit Care Med 2005; 171:275.
  41. Ghofrani HA, Reichenberger F, Kohstall MG, et al. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. Ann Intern Med 2004; 141:169.
  42. Humpl T, Reyes JT, Holtby H, et al. Beneficial effect of oral sildenafil therapy on childhood pulmonary arterial hypertension: twelve-month clinical trial of a single-drug, open-label, pilot study. Circulation 2005; 111:3274.
  43. Baquero H, Soliz A, Neira F, et al. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics 2006; 117:1077.
  44. Sartori C, Allemann Y, Duplain H, et al. Salmeterol for the prevention of high-altitude pulmonary edema. N Engl J Med 2002; 346:1631.