Is High Altitude Pulmonary Edema Relevant to Hawai‘i?

Abstract

High altitude clinical syndromes have been described in the medical literature but may be under recognized in the state of Hawai‘i. As tourism increases, high altitude injuries may follow given the easy access to high altitude attractions. Visitors and clinicians should be aware of the dangers associated with the rapid ascent to high altitudes in the perceived comfort of a vehicle. This paper will review the basic pathophysiology, prevention, and treatment of the most serious of the high altitude clinical syndromes, high altitude pulmonary edema.

Introduction

The physiologic effects of high altitude are complex and not simply limited to hypoxia.¹ This is reflected by the varying ability of individuals to acclimate to changes in altitude. High altitude clinical syndromes are diverse and can range from life threatening high altitude cerebral and pulmonary edema to less severe acute mountain sickness.² The rate of ascent is often directly related to the severity of the clinical syndrome.³ High altitude pulmonary edema (HAPE) is the most frequent cause of altitude related fatalities.⁴ Although the pathophysiology is not completely understood, HAPE is easily treatable; unrecognized, it may be fatal.⁵

Relevance to Hawai‘i and Pacific Region

Mauna Kea is the highest point in the Pacific Basin and if measured from base to summit, the tallest mountain in the world. From its origins deep within the Pacific Ocean, to its high altitude peak, this dormant volcano rises approximately 32,000 feet and stands at 13,796 feet above sea level. This sacred mountain, once regarded as “the abode of gods,” is now visited by several hundred visitors daily, usually by vehicle. Poli‘ahu, the ancient snow goddess of Mauna Kea and rival of Pele, now keeps watch over the world's largest collection of observatories, which occupy the summit of the hallowed peak.⁶ The Hawaiian Islands offer lowlanders the rare opportunity of ascending from near sea level to elevations in excess of two and a half miles. In fact, many of these volcanic peaks are readily accessible by automobile, allowing people of all backgrounds to rapidly visit areas previously limited to the determined mountaineer. Although easy access affords many the opportunity to experience the wonders of the volcanic goddess, Pele, it also exposes many tourists to the adverse effects of high altitude physiology.⁷

Case Report from the Medical Literature

One of the first reported cases of high altitude pulmonary edema appeared in a 1960 article by Dr. Charles S. Houston.⁸ Dr. Houston described a healthy 21 year old male who made a cross country ski trip from Aspen, Colorado (elevation 7,890ft) over a 12,000 foot mountain pass. On the third day of the expedition, the patient noted dyspnea, weakness, and cough that subsequently worsened over the fourth day. The patient was transported to the nearest hospital where he was found to have a temperature of 99.6F, a blood pressure of 120/80, a pulse of 96 and respirations of 30. His physical exam was remarkable for moderate cyanosis, with bilateral coarse pulmonary rales noted on auscultation. There was no cardiomegaly, peripheral edema, or jugular venous distention. The patient had a leukocytosis of 13,000 and a chest radiograph that revealed bilateral pulmonary edema. The patient experienced rapid resolution of his symptoms within 36 hours of admission. On further questioning, the patient described similar symptoms during a previous mountain expedition three years earlier with complete resolution of his dyspnea after descent from altitude.

Discussion

Hypoxia is the primary insult of high altitude exposure.⁹ Barometric pressure and the partial pressure of inspired oxygen (PIO₂) decreases in a logarithmic manner as altitude is increased.¹⁰ At altitudes below 10,000 feet, the changes in PIO₂ and resultant partial pressure of arterial oxygen (PaO₂) routinely have little effect on the arterial oxygen saturation (SaO₂). However, above 10,000 feet small decreases in PaO₂ can have significant effects on SaO₂.¹¹ Fortunately, the human body has innate physiologic mechanisms that allow for altitude acclimatization.

The process of acclimatization is complex and its success varies from individual to individual.¹² The rate of altitude gain directly correlates with the severity of high altitude pathology and therefore it is recommended that altitude gains be incremental, allowing time for physiologic adjustment. The recommended rate of ascent and time allowed for acclimatization is dynamic and based on an individual's overall risk for developing a high altitude illness.

Hyperventilation is an early response to low PaO₂ and works to enhance oxygen delivery to tissues. Hyperventilation causes a respiratory alkalosis which triggers renal excretion of bicarbonate as a compensatory mechanism to normalize serum pH. Maximum ventilation with renal adjustment is typically reached within one week at a given altitude. The degree of an individual's hyperventilatory response may correlate with overall acclimatization success and the prevention of high altitude illness.

Renal secretion of erythropoietin also occurs in response to hypoxia. Increased proliferation of red blood cells begins within four days, however, the complete effects of erythropoiesis may take several weeks. The success of acclimatization does not seem to correlate with the degree of erythropoiesis. Changes in mitochondrial architecture and quantity have also been proposed as another mechanism of altitude acclimatization.¹³

When acclimatization to altitude does not occur, several high- altitude syndromes may happen. The high-altitude syndromes (acute mountain sickness, high altitude cerebral edema, and high altitude pulmonary edema) likely represent a spectrum of pathophysiology. Symptoms often overlap making an accurate clinical distinction difficult.

HAPE is the leading cause of death related to high altitude syndromes. Symptom onset is often encountered within 2–4 days of arrival at high altitude (approximately 10,000 ft), however, incidents have occurred sooner and at lower altitudes. Affected individuals typically complain of malaise, cough, dyspnea, and fatigue. Physical examination may reveal a cyanotic appearance with vital signs demonstrating tachypnea and tachycardia, along with a possible fever. Predicting which individuals will be most susceptible to HAPE is difficult, though previous episodes seem to be the strongest predictor of future susceptibility. Certain underlying medical conditions such as lung disease, heart disease, diabetes, and pregnancy, may also put individuals at increased risk of developing HAPE.^14–17

The pathophysiology of HAPE is not completely understood, although increased pulmonary arterial pressure (PAP) seems to be uniformly present. Pulmonary vasoconstriction and resultant increased PAP is a known response to hypoxia. However, increased PAP alone cannot explain HAPE, as hypoxia and PAP are common findings among asymptomatic mountaineers at altitude.¹⁸ Increased capillary permeability, perhaps secondary to increased capillary stress from PAP, has been proposed as a possible mechanism in HAPE.¹⁹

Treatment in Resource-Constrained Environment

Simple awareness and education of HAPE often allows for appropriate preventive techniques to be used. All individuals should be encouraged to slow their rate of ascent once above 8,500 ft. For prolonged expeditions, most experts recommend no greater than an increase of 1,500 ft per day for sleeping elevations, with no elevation gain every third or fourth day. For individuals with a prior history of HAPE, pharmacologic prophylaxis should be considered. Numerous pharmacologic agents have been used to prevent HAPE (nifedipine, salmeterol, tadalafil, dexamethasone, acetazolamide), however, current guidelines only recommend the use of nifedipine.²⁰ Most experts recommend 30 mg of sustained release nifedipine every 12 hours which should be started on the day prior to ascent and continued until descent is initiated.

Prompt recognition of HAPE is essential, as most cases improve dramatically with descent from altitude. Emergent cases require rapid descent, whereas less severe symptoms may improve with a moderate decrease of 1,500ft to 3,000ft. Since patients frequently suffer from hypoxemia during HAPE, exertion during the descent should be minimized as much as possible and supplemental oxygen administered. Euthermia should also be maintained to lessen any increases in PAP, which may worsen the pulmonary edema. If attempts at re-ascent are made, additional time should be allowed for proper acclimatization.

Treatment in Non-Austere Environments

As most cases of HAPE resolve with descent from altitude, additional treatment is not typically required, however, severe cases of HAPE may require hospitalization with more intensive medical care. In addition to descending from altitude, supplemental oxygen is a mainstay of therapy. Hypoxia frequently resolves with low flow oxygen, though more severe cases may require high flow or even continuous positive airway pressure (CPAP). Portable hyperbaric chambers have also been used for HAPE treatment. Endotracheal intubation with mechanical ventilation is infrequently required but may be necessary.

There are several proposed medications often used in the adjunctive treatment of HAPE. Nifedipine, a dihydropyridine calcium channel blocker, is the most well studied of the treatment modalities and works through vasodilation which acts to lower PAP. Likewise, phosphodiesterase inhibitors such as sildenafil may blunt the hypoxic pulmonary vasoconstriction response, thus improving PAP. Other previously used adjuncts include diuretics, corticosteroids, carbonic anhydrase inhibitors, and inhaled beta-agonists, though current guidelines do not support their routine use in the treatment of HAPE.²⁰

Conclusion

High altitude pulmonary edema is an easily treatable, though potentially fatal, syndrome of the acute mountain illnesses. With education and implementation of proper preventive techniques, such as a judicious rate of ascent above 10,000ft and nifedipine when indicated, HAPE can often be avoided. Several of the volcanic peaks found among the Hawaiian Islands rise well above 10,000ft and many are directly accessible by vehicle and overly rapid ascent. Proper education and recognition of HAPE is paramount in decreasing its incidence and reducing its morbidity.

Disclosures

The author reported no conflicts of interest.

Disclaimer

The views expressed in this manuscript are those of the author and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government.