High Altitude Pulmonary Edema (HAPE)


Article Author:
Jacob Jensen


Article Editor:
Andrew Vincent


Editors In Chief:
Mitchell Farrell
Brian Froelke


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Steve Bhimji
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Nazia Sadiq
Hajira Basit
Phillip Hynes
Tehmina Warsi


Updated:
12/24/2018 12:07:07 PM

Introduction

High Altitude Pulmonary Edema (HAPE) is a fatal form of severe high-altitude illness. HAPE is a form of noncardiogenic pulmonary edema that occurs secondary to hypoxia. It is a clinical diagnosis characterized by fatigue, dyspnea, and dry cough with exertion. If left untreated, it can progress to dyspnea at rest, rales, cyanosis, and a mortality rate of up to 50%.[1][2][3]

Etiology

Along with other illnesses related to altitude, HAPE occurs above 2500 meters but can occur at altitudes as low as 2000 meters. Risk factors include individual susceptibility due to low hypoxic ventilatory response (HVR), the altitude attained, a rapid rate of ascent, male sex, use of sleep medication, excessive salt ingestion, ambient cold temperature, and heavy physical exertion. Preexisting conditions such as those leading to increased pulmonary blood flow, pulmonary hypertension, increased pulmonary vascular reactivity, or patent foramen ovale may have a higher predisposition towards the development of HAPE.   [4][5][6]

Epidemiology

The severity of HAPE will depend on multiple factors including altitude, initial recognition and management, and access to medical care. At 4500 meters the incidence is 0.6% to 6%, and at 5500 meters the incidence is 2% to 15%, with faster ascent time correlating to a higher incidence. Those with a prior incidence of HAPE have a recurrence rate as high as a 60%. One’s level of fitness is not proven to be a protective factor. Mortality rate, when treated, can be as high as 11% and as high as 50% when untreated. Up to 50% of cases may have concomitant acute mountain sickness (AMS), and up to 14% will have concomitant high altitude cerebral edema (HACE).  

Pathophysiology

The development of HAPE occurs as a response of the pulmonary vasculature to hypoxia. At altitude, the body responds to hypoxia by hyperventilation. This is known as the hypoxic ventilatory response (HVR). This response varies between individuals and has a genetic component. High altitude adaptation is an interesting phenomenon that regularly applies to individuals living at altitude for long periods of time but is not usual for those visiting altitude. Understanding the principles of tissue oxygen delivery, however, is useful when considering the effects and adaptations of those coming from higher barometric pressures to the lower pressures of high elevation. The concentration of oxygen in 1 liter of air at sea level is 21%. This concentration is the same at 4000 meters (~13,200 feet), but due to the decreased barometric pressure at this altitude, only 63% of the number of available oxygen molecules remain as compared to sea level. Thus, to adequately deliver oxygen to the tissues, particularly those that are most in need of oxygen for aerobic metabolism (brain, heart, lungs, kidneys), certain adaptations must occur. 

There are four potential adaptations to overcome the constraints of high altitude hypoxia: (1) resting ventilation, (2) hypoxic ventilatory response, (3) oxygen saturation of arterial hemoglobin, and (4) hemoglobin concentration. Studies of populations in the Andes and Tibetian ranges and ranges have shown different adaptive changes between groups despite being at the same altitude. Those from Tibet had mean 0.5 standard deviations above that of the Aymara people of the Andes for the first two traits and a full standard deviation below for the latter two traits. This research suggests a genetic predisposition to how different groups of people at the same altitude may adapt to high altitude stress. For those traveling to a high altitude for a short period, minute-ventilation tends to be the mechanism by which trekkers from low altitude will acclimate. In general, it takes as much as 1 to 2 weeks for erythropoietin levels to increase enough to cause hematopoiesis and increased circulating hemoglobin. As one enters higher elevations, minute-ventilation increases almost immediately and respiratory alkalosis ensues. This causes a shift in the oxygen-dissociation curve to the left (increased affinity of oxygen by hemoglobin). In response to this mechanism, the kidneys begin increasing proton reabsorption which stabilizes the blood pH. RBC 2,3-DPG levels which begin to increase on days 2 and 3. Then, the Hgb-O2 dissociation curve shifts to the right (decreased affinity for O2 by hemoglobin). This allows for a more adequate delivery of oxygen to the tissues, particularly muscle tissues that may be under greater levels of stress due to exertion with climbing and/or trekking. If the HVR is blunted, due to genetic predisposition or sedatives, it will lead to further hypoxia causing a non-uniform, exaggerated hypoxemic pulmonary vasoconstriction (HPV). This pulmonary vasoconstriction then results in increased perfusion to affected alveoli, causing increased hydrostatic stress/pressure and thus increased mechanical stress on the blood-gas barrier. Damage to the blood-gas barrier results in increased capillary permeability and subsequent non-uniform pulmonary edema. This edema formation impedes oxygen transport, resulting in more widespread and worsening HPV. Sympathetic stimulation and circulating vasoconstrictors from the HPV response result in vasoconstriction, worsening pulmonary hypertension, and increasing capillary pressures. If an individual lacks innate adaptation to these organ level changes or the condition is not recognized and treated, the disease condition will persist and continue to worsen.

History and Physical

HAPE typically occurs 2 to 5 days after arrival at altitude. It has an insidious onset with a non-productive cough, decreased exercise tolerance, chest pain, and exertional dyspnea. Without treatment, it can progress to dyspnea at rest and severe exertional dyspnea. A cough may become productive of pink and frothy sputum or frank blood. The patient also may have rales or wheezes, central cyanosis, tachypnea, and/or tachycardia. SpO2 is often 10% less than expected for altitude, and the patient often will appear better than expected given their level of hypoxemia and SpO2 value, which typically resides around 40% to 70%. 

Evaluation

HAPE's clinical diagnosis would include at least two of the following symptoms or complaints: chest tightness or pain, cough, dyspnea at rest, and decreased exercise tolerance. It also would have two of the following exam findings: central cyanosis, rales/wheezes, tachycardia, and tachypnea.  If available, CXR may show patchy alveolar infiltrates with normal-sized mediastinum/heart, and ultrasound may show B-lines consistent with pulmonary edema. ECG may show signs of right axis deviation and/or ischemia. In a patient with infiltrates on CXR, rapid correction of clinical status and SpO2 with supplemental oxygen is pathognomonic of HAPE. Even if available, labs are of limited utility, and the clinician should always consider concomitant AMS and/or HACE.

Treatment / Management

The mainstay of treatment is to descend 1000 meters or until there is a resolution of symptoms with the descent. During the descent, it is important to minimize exertion as exertion may increase hypoxemia from metabolic demands of the body and worsen an individual’s condition. If available, a trial of oxygen therapy may ameliorate symptoms and help temporize the patient if the descent is technically difficult or delayed. That said, the mainstay of treatment remains descent, regardless of oxygen availability. Supplemental oxygen via a high-flow nasal cannula and facemask titrated to Sp02 greater than 90% is a reasonable alternative when available. Portable hyperbaric chambers also may be used when descent is not possible, but these typically require constant care and may be difficult for individuals experiencing nausea or vomiting, claustrophobia, or altered mental status from concomitant AMS/HACE. There also exists the risk of recurrence of symptoms after exiting from the chamber. Nifedipine improves symptoms as an adjunct by decreasing pulmonary vasoconstriction but should not be used as the sole therapy if oxygen or descent are options. Phosphodiesterase inhibitors may be used to help to decrease pulmonary artery and capillary pressure through vasodilation if nifedipine is unavailable. There is no clinically proven role for acetazolamide, B-agonist, or diuretics.[7][8]

Enhancing Healthcare Team Outcomes

High Altitude Pulmonary Edema (HAPE) is a fatal form of severe high-altitude illness. HAPE is a form of noncardiogenic pulmonary edema that occurs secondary to hypoxia. It is a clinical diagnosis characterized by fatigue, dyspnea, and dry cough with exertion. If left untreated, it can progress to dyspnea at rest, rales, cyanosis, and a mortality rate of up to 50%. The condition is best managed by a multidisciplinary team that consists of an internist, sports physician, neurologist and cardiologist. The key to prevention is education of the patient. Individuals may consider resuming ascent at an appropriate rate once symptoms resolve and they no longer require oxygen or vasodilator therapy and have an increased exercise tolerance compared to symptom onset. Clinicians also should consider nifedipine, PDE inhibitors, or salmeterol as prophylaxis for those with a prior incidence of HAPE.


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High Altitude Pulmonary Edema (HAPE) - Questions

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Which diuretic is used in the treatment of acute mountain sickness?



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A patient was been staying in a cabin at an altitude of 5,000 feet. After 5 days his respiratory rate is elevated and his arterial PCO2 is decreased. What other changes would be present?



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A healthy young person is mountain climbing and develops severe shortness of breath. The patient has diffuse inspiratory crackles. Which of the following is the most likely diagnosis?



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Which of the following is not a treatment for acute high-altitude pulmonary edema?



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Which of the following are features of high-altitude pulmonary edema (HAPE)?



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A 30-year-old woman moves to Colorado from Texas and experiences dizziness and shortness of breath on arrival in her new city. She eventually acclimates to the altitude change and her symptoms disappear. Which of the following substances has likely increased in her blood and helped to reduce her symptoms?



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A patient on a mountain climbing expedition experiences the sudden onset of headache, nausea, vomiting, and exertional dyspnea. What is the most likely diagnosis?



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A patient from Miami, Florida presents for care regarding bilateral fingertip tingling to a physician in Denver, Colorado, elevation 5280 feet. The patient has no past medical history, takes no medication, and is a vegetarian. She denies nausea, vomiting, chest discomfort or shortness of breath. Neurologic exam shows intact sensation to pin-prick, temperature, 2-point discrimination, position sense, and vibratory sense. Gait, deep tendon reflexes, finger-to-nose, tandem gait, and heal-to-toe walking are all within normal limits. Select the appropriate next step.



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Which is not suggestive of high-altitude pulmonary edema?



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A 43-year-old male is planning a backcountry fishing trip in Colorado this coming June. He is a resident of Illinois and has been to Colorado only once, 12 years ago. On the first day of the trip, he drives from Illinois (600 feet) and parks his truck at 7,000 feet. He then begins trekking and gains 1,000 vertical feet before making camp. What changes would you anticipate to have occurred at the conclusion of day 1?



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High Altitude Pulmonary Edema (HAPE) - References

References

Gonzalez Garay A,Molano Franco D,Nieto Estrada VH,Martí-Carvajal AJ,Arevalo-Rodriguez I, Interventions for preventing high altitude illness: Part 2. Less commonly-used drugs. The Cochrane database of systematic reviews. 2018 Mar 12;     [PubMed]
Nieto Estrada VH,Molano Franco D,Medina RD,Gonzalez Garay AG,Martí-Carvajal AJ,Arevalo-Rodriguez I, Interventions for preventing high altitude illness: Part 1. Commonly-used classes of drugs. The Cochrane database of systematic reviews. 2017 Jun 27;     [PubMed]
Khodaee M,Grothe HL,Seyfert JH,VanBaak K, Athletes at High Altitude. Sports health. 2016 Mar-Apr;     [PubMed]
Derby R,deWeber K, The athlete and high altitude. Current sports medicine reports. 2010 Mar-Apr;     [PubMed]
Gallagher SA,Hackett PH, High-altitude illness. Emergency medicine clinics of North America. 2004 May;     [PubMed]
Basnyat B,Murdoch DR, High-altitude illness. Lancet (London, England). 2003 Jun 7;     [PubMed]
Murdoch DR, Prevention and Treatment of High-altitude Illness in Travelers. Current infectious disease reports. 2004 Feb;     [PubMed]
Li Y,Zhang Y,Zhang Y, Research advances in pathogenesis and prophylactic measures of acute high altitude illness. Respiratory medicine. 2018 Dec;     [PubMed]

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