Is Nifedipine An Effective Treatment For Patients with High Altitude Pulmonary Edema?

Is Nifedipine An Effective Treatment For Patients with High Altitude Pulmonary Edema?

Tiffany Dawson
University of San Francisco, California
Aidan McGuinness
CETH, California Academy of Sciences, San Francisco
Matthew R. Lewin
Director, Center for Exploration and Travel Health, California Academy of Sciences, San Francisco


Introduction:


High Altitude Pulmonary Edema (HAPE) is a form of rapid-onset noncardiogenic pulmonary edema that can develop in those susceptible as well as those not susceptible[SUP]2[/SUP] within the first days of rapid ascent to high elevations (typically above 3000 m). Nifedipine has been used in wilderness medicine prophylactically to prevent the onset of HAPE and in many cases as a method of treatment after onset of the symptoms. In one study of vasodilators on pulmonary hemodynamics in HAPE, all vasodilators were found to improve gas exchange, suggesting a link between edema formation and pulmonary vasoconstriction.[SUP]3 [/SUP]Although Nifedipine is currently the only well-studied drug in the treatment of HAPE, studies involving a large series of HAPE patients are limited[SUP]1[/SUP], and thus, its effectiveness has yet to be conclusively determined.

In one single randomized, placebo-controlled study, 60 mg of sustained release Nifedipine administered daily was found to be effective in the prevention of HAPE, and the American College of Chest Physicians awarded it a grade of 1A[SUP]4[/SUP], implying that the medicine is strongly recommended based on quality evidence and that its “benefits clearly outweigh risks and burdens.”[SUP]2 [/SUP]However, the study at hand aimed to evaluate the efficacy of this drug as a treatment rather than a prophylactic, and did so by designing a prospective trial in which 110 patients diagnosed with HAPE were admitted and treated over a period of three years in a hospital in India.


Methods:


The primary risk factor for the development of HAPE was identified as improper acclimatization, but other risk factors included cold exposure, severe exercise, and respiratory infection. In all 110 subjects, researchers observed and documented the following variables: dyspnea, cough, chest pain, cyanosis, pulse rate, blood pressure, respiratory rate, crepitation, radiographic evidence, electrocardiogram, SpO[SUB]2[/SUB] at hospital admission, SpO[SUB]2[/SUB] normalization time, total leukocyte count, and total hospital stay. All patients were treated with reduction of altitude, supplemental oxygen, bed rest, and either oral Nifedipine (30 mg sustained release tablet twice daily) or placebo was administered to alternating patients.


Results:


All patients recovered fully within an average of 4.01 days after admission. No difference in rate of recovery was observed between patients who received the drug and patients who received the placebo. However, the question of whether or not administration of Nifedipine expedites the resolution of HAPE when used concurrently with oxygen support and descent remains unclear. Future research should involve comparing the effectiveness of oxygen and Nifedipine individually[SUP]1[/SUP].


Emergency Medicine Perspective:


Nifedipine has proved to be effective in the prevention of HAPE and remains a viable treatment option in the case that descent is not feasible and supplemental oxygen is unavailable. In the study of six patients with HAPE, not treated with descent, supplemental oxygen, or bed rest, Nifedipine was administered and resulted in clinical improvement, better oxygenation, reduction of alveolar arterial oxygen gradient and pulmonary artery pressure, and progressive clearing of alveolar edema[SUP]5[/SUP]. However, Nifedipine proved no more efficacious when used in conjunction with descent, bed rest, and supplemental oxygen, in the resolution of HAPE. Nifedipine offers a potential emergency treatment for HAPE when descent is impossible and oxygen is unavailable.



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[TD="class: contentReference"] References[/TD]
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[TD="class: contentBody"]1. Deshwal R, Iqbal M, Basnet S. Nifedipine for the Treatment of High Altitude Pulmonary Edema. Wilderness and Environmental Medicine. 2012;23:7-10. [PMID: 22441082][/TD]
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[TD="class: contentBody"]2. Bartsch P, Maggiorini M, Ritter M, et al. Prevention of High-Altitude Pulmonary Edema by Nifedipine. N Engl J Med. 1991;325:1284-1289. [PMID: 1922223][/TD]
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[TD="class: contentBody"]3. 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-S71. [PMID: 1483798][/TD]
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[TD="class: contentBody"]4. Luks A, McIntosh S, Grissom C, et al. Wilderness Medical Society Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness. Wilderness and Environmental Medicine. 2010;21:146-155. [PMID: 20591379][/TD]
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[TD="class: contentBody"]5. Oelz O, Maggiorini M, Ritter M, et al. Nifedipine for High Altitude Pulmonary Edema. Lancet. 1989 Nov 25;2(8674 1241-4. [PMID: 1671918][/TD]
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