Medication Summary
Drugs are not as effective as descent from altitude and oxygen in the treatment of high-altitude pulmonary edema (HAPE). Nifedipine, by reducing pulmonary arterial pressure, may be effective in treating HAPE. [29] However, in two separate studies, nifedipine did not outperform placebo or oxygen alone. [33, 34]
Prevention
In general, acetazolamide facilitates acclimatization, but this agent should not be relied on as the sole preventive agent in individuals with known HAPE susceptibility. [2, 3]
The Centers for Disease Control and Prevention (CDC) strongly recommends acetazolamide prophylaxis in all individuals with a prior history of HAPE or HACE, as well as with the following [4] :
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History of acute mountain sickness and ascending more than 2,800 m in 1 day
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All people ascending to more than 3,500 m in 1 day
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All people ascending more than 500 m per day (increase in sleeping elevation) above 3,000 m, without extra days for acclimatization
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Very rapid ascents
The CDC recommends the following pharmacologic agents and regimens for HAPE prophylaxis [4] :
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Oral nifedipine (generally reserved for HAPE-susceptible individuals) - 30 mg sustained-release formulation every 12 hours (same regimen for HAPE treatment)
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Oral tadalafil - 10 mg twice daily
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Oral sildenafil - 50 mg every 8 hours
Treatment
Further research is needed before tadalafil or dexamethasone can be recommended over nifedipine for prophylaxis. The Wilderness Medical Society (WMS) advises that diuretics or acetazolamide should not be used for treatment of HAPE, and it makes no recommendation regarding beta-agonists or dexamethasone for HAPE treatment due to insufficient/lack of data. [2, 3] Furthermore, WMS indicates there is no established role for acetazolamide, beta-agonists, diuretics, or dexamethasone in the treatment of HAPE, although dexamethasone should be considered where there is concern for concomitant high-altitude cerebral edema (HACE)
In the setting of concomitant HAPE and HACE, WMS recommends adding dexamethasone to the treatment regimen for patients with HAPE and neurologic dysfunction that does not resolve rapidly with administration of supplemental oxygen and improvement in the patient’s oxygen saturation. [2, 3] If supplemental oxygen is not available, initiate dexamethasone in addition to medications for HAPE in those with mental status changes and/or suspected concurrent HACE. Note the following:
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Dexamethasone should be administered at the doses recommended for the treatment of HACE.
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Nifedipine or other pulmonary vasodilators may be used to treat concurrent HAPE and HACE, but avoid lowering mean arterial pressure, as this may decrease cerebral perfusion pressure and thereby increase the risk for cerebral ischemia.
Calcium channel blockers
Class Summary
Nifedipine is used for its pulmonary vasodilating effects.
Nifedipine (Procardia, Adalat)
Nifedipine is used in HAPE for pulmonary vasodilation. It often improves SaO2 modestly within a few minutes.
Carbonic anhydrase inhibitors
Class Summary
These agents are helpful in the prevention of HAPE.
Acetazolamide (Diamox)
Acetazolamide is used in the prevention of HAPE. It is not used in the treatment of this condition. Acetazolamide promotes renal excretion of bicarbonate, which stimulates respiration. For the prophylaxis of altitude illness, start 24-48 hours before ascent and continue for 48 hours after arrival at high altitude.
Corticosteroids
Class Summary
These agents have profound and varied metabolic effects. They suppress inflammation and the immune response.
Dexamethasone (Decadron)
Dexamethasone alleviates vasogenic cerebral edema and improves endothelial integrity.
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High-altitude pulmonary edema (HAPE). Plain chest x-ray (radiograph) of a patient diagnosed with HAPE. There are patchy infiltrates throughout the lung tissue, with predominant changes in the right middle lobe/right central hemithorax. Courtesy of Wikipedia (https://en.wikipedia.org/wiki/File:Chest_XR_of_HAPE.png).
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High-altitude pulmonary edema (HAPE). Medical students demonstrate the use of a portable hyperbaric chamber. Courtesy of Wikipedia (https://en.wikipedia.org/wiki/File:Portable_hyperbaric_chamber.jpg).
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High-altitude pulmonary edema (HAPE). Initial chest x-ray showing pulmonary infiltrates in the right lung especially in the right mid and lower lung zones indicative of pulmonary edema. The patient was a middle-aged woman trekker who was emergency air-lifted from an altitude of 4410 m in the Nepal Himalayas to 1300 m in Kathamandu. She had continued ascending despite experiencing mild altitude symptoms at Namche (3440 m), with considerably worsened symptoms at Tengboche (3860 m). Courtesy of Extreme Physiology & Medicine (PMID: 24636661, online at https://extremephysiolmed.biomedcentral.com/track/pdf/10.1186/2046-7648-3-6).
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High-altitude pulmonary edema (HAPE). Repeat chest x-ray after 2 days showing rapid resolution of the pulmonary edema in the same Himalayan trekker discussed in the previous image. The patient received bed rest, supplemental oxygen, and oral sustained-release nifedipine 20 mg twice daily. Courtesy of Extreme Physiology & Medicine (PMID: 24636661, online at https://extremephysiolmed.biomedcentral.com/track/pdf/10.1186/2046-7648-3-6).
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High-altitude pulmonary edema (HAPE). Pulmonary embolism masquerading as HAPE. Axial computed tomography (CT) pulmonary angiogram showing thrombi as filling defects in the right main pulmonary artery (right arrow) extending into its branch and in the distal left pulmonary artery (left arrow) with extension into its superior branch. Courtesy of High Altitude Medicine & Biology (PMID: 27768392, online at https://www.liebertpub.com/doi/full/10.1089/ham.2016.0008).
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- HAPE Prevention and Treatment Guidelines (WMS, CDC)
- FDA Policy for Face Masks, Face Shields, and Respirators in COVID-19 (2020)
- COVID-19–Related Airway Management Clinical Practice Guidelines (SIAARTI/EAMS, 2020)
- COVID-19 Ventilation Clinical Practice Guidelines (ESICM, 2020)
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