High-Altitude Pulmonary Oedema

Original Editor - Kapil Narale

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Introduction

Factors that can contribute to High-Altitude Pulmonary Oedema (HAPE) include altitude, speed and mode of ascent, and individual variability.

HAPE usually develops 2-5 days after a person ascends to altitudes above 2500-3000m. It hardly occurs at an altitude below 2500-3000m, and after 1 week of acclimatisation at a given altitude. As mentioned on the Acclimatisation page, this is considered 'moderate altitude', where mountain sickness can occur, and acclimatization would be essential for athletic performance.

There are two different scenarios in which HAPE can occur. The first involves individuals who live at high altitude, and are returning from a journey at low altitude, while the second scenario involves individuals who live at low elevation or sea level and are rapidly ascending altitude.

The first type can be elicited with returning to HAPE conditions, and indicated as pulmonary oedema with electrocardiographic (ECG) signs of right-ventricular overload. This was reported in Peru. The type with unacclimatised individuals was reported in the Rocky Mountains. It is seen that both types may share the same pathophysiology.

Epidemiology

HAPE can occur in healthy individuals. It most commonly occurs in mountain climbers and trekkers.

In this population, when the ascent to an altitude of 4559m, takes 3 or more days, the prevalence of HAPE is <0.2%. However, when an ascent to the same altitude is completed within 22 hours, the incidence increases to 7% in individuals without radiographically proven HAPE, and increases to 62% in individuals with radiographically proven HAPE.

The incidence of HAPE also increases from 2.5-15.5% when an altitude of 5500m is ascended by airlift, rather than trekking, and having gradual exposure to changing conditions over 4-6 days.

HAPE can also occur at lower elevations ranging from 2500-3000m, which can be found in the Japanese Alps and North America. There is an estimated incidence of 0.01-0.1% in visitors of the ski resorts in the Rocky Mountains of Colorado. Re-entry HAPE (the first scenario) is seen to occur in the Rocky Mountains, which is also seen to occur in the Andes. It is common in vulnerable families, and commonly affects children.

It is interesting to note that HAPE has been found to occur at Alpine resorts at elevations of 1400 to 2400m, which have areas for skiing up to 3200m. Individuals who my be more prone to HAPE at these elevations may have had previous or unknown underlying conditions. It is possible that affected individuals may have had diastolic heart failure rather than HAPE caused by hypertensive heart disease.

In addition, Women are seen to be more prone to HAPE than Men.

Exaggerated Pulmonary Pressure

Cardiac catheterisation of untreated cases of HAPE at high altitude displayed mean pulmonary artery pressures of 60 mmHg (with a range of 33–117 mmHg), as it is seen that wedge pressures are normal. Systolic pulmonary artery pressure, estimated via ECG, displayed results between 50 and 80 mmHg for subjects with HAPE, and 30–50 mm Hg for healthy controls.

A marked increase in pulmonary artery pressure is important for the onset of HAPE. This pressure increase leads to the development of HAPE.

An example at Capanna Margherita (4559m), right heart catheterisation showed that the abnormal rise in pulmonary artery pressure in individuals who are prone to developing HAPE occur with a capillary pressure that is increased to above 20mmHg in individuals that develop HAPE. This helps explain that Pulmonary capillary hypertension is critical in the pathophysiology of HAPE.

Mechanisms Accounting for Increased Capillary Pressure

It is possible that individuals who are at risk of HAPE have an increased pulmonary capillary hypertension. There are two possible explanations. One reason is through homogenous hypoxic vasoconstriction, which causes regional overperfusion of capillaries where there are areas of low arterial vasoconstriction. This results in scattered pulmonary oedema, containing large amounts protein and red blood cells. Another reason explains that hypoxic constriction can occur at the smallest leaky arterioles and/or venules.

In either case, an increase in pulmonary blood flow during exercise raises pulmonary capillary pressure, caused y venous resistance.

Inflammation

There is a higher level of red blood cell count, with serum-derived protein concentration in BAL fluid, in individuals who have HAPE and those who developed HAPE after 24 hours, when bronchoalveolar lavage (BAL) was performed within the same day. It is possible that here may be a possible inflammatory leak, there is no difference between individuals resistant to or prone to HAPE. Active salt and water reabsorption occur, while gathering the protein leaked in the initial stages of HAPE occurs, which is seen when alveolar protein concentration is greater than the plasma protein concentration in HAPE.

Due to these reasons, in more advanced cases of HAPE, inflammaiton may occur and contribute to increased pulmonary capillary permeability.

HAPE can be seen as a hydrostatic type of pulmonary oedema. The pathophysiology can be explained with increased hypoxic pulmonary vasoconstriction of small arteries and veins. This would lead to an overdistension of the vessel walls, which would open cellular junctions. This may cause stress failure of the alveolo-capillary membrane. With this, the secondary occurrence would be noted by the signs of inflammation found in the BAL fluid of patients with advanced HAPE.

It is seen that an increase in the permeability of the alveolar-capillary membrane decreases the pressure needed to result in oedema. Thus, with increased permeability, HAPE may occur in individuals with a normal hypoxic pulmonary vascular response.

Therefore, the development of HAPE can occur at distinctly low altitudes if an individual has an upper respiratory tract infection prior to a journey in the French Alps and vigorous exercise between 2000-3000m. Other reasons could include diastolic heart failure in hypertension, and/or an undiagnosed pathology as an underlying factor of HAPE, which can include silent pulmonary embolism, which can occur from prolonged travel.

Alveolar Fluid Clearance

It is possible that an improper clearing of fluid from the alveoli can lead to the pathophysiology of HAPE. It is seen that hypoxia decreases the transepithelial sodium transport. This accounts for the reduced fluid clearance from the alveoli of hypoxic rats at an FiO2 of 0.08. Mice that are somewhat lacking of apical (alveolar-facing) epithelial sodium channel display an increased accumulation of lung water in hypoxia.

Signs & Symptoms

In many cases, HAPE is preceded by symptoms of Acute Mountain Sickness (AMS). Feel free to read about AMS in the 'Risks' section of the Acclimatisation page.

Primary symptoms of HAPE include dyspnoea on exertion, cough, and reduced exercise performance. As the pulmonary oedema condition increases, the cough can worsen, as well as breathlessness at rest and orthopnoea may result. Further progression may be indicated by gurgling in the chest, and pink frothy sputum.

Clinical features can include cyanosis, tachypnoea, tachycardia, and an increased body temperature though below 38.5 degrees. Rales can be noticed, and would specifically be located over the middle lung fields.

The degree of pulmonary oedema seen on a chest x-ray may outweigh the findings that can be noticed on auscultation.

In serious and progressed cases, there may be signs of cerebral oedema associated with the pulmonary oedema, such as ataxia or reduced levels of consciousness.

Subclinical HAPE may occur, but cause none to minimal symptoms, which can be ignored. I tis possible that people may have subclinical pleural oedema in the lung, which can vaguely represent oedema, and resolve on its own, even with the individuals at high altitude.

There are demonstrated drastic Arterial Blood Gas (ABG) values of HAPE at 4559m of elevation. Mean arterial PO2 was 23 ± 3 (SD) mm Hg, with controls at 40 ± 5 mmHg, and arterial oxygen saturation was 48 ± 8%, with controls at 78 ± 7%. In early stages of HAPE at this altitude, 30 mmHg for PO2 and 70% for SaO2 can be observed.

Individuals at risk of HAPE can also have a marked increased pulmonary artery pressure when exercising in hypoxic conditions.

The risk of HAPE can be increased during or subsequent to infections.

Chest x-ray

In early conditions of HAPE, patchy peripheral distribution of oedema is seen radiographically. In more advanced cases, and during recovery, the radiographic image is more homogenous and diffuse. Differing radiographic imaging within two cases in the same person shows that structural abnormalities may not represent consistency in oedema location.

Surgical Findings

Autopsies did not reveal left ventricular failure, but did show that there are distended pulmonary arteries and diffuse pulmonary oedema with bloody foamy fluid which is present in the airways. In many cases, hyaline membranes can be found, as well as arteriolar thrombi, pulmonary haemorrhages, or infarcts.

Treatment & Prevention

When a person is at ascent, there may be limited medical facilities or supplies available. If there is access to a medical facility, supplemental oxygen would be the primary choice of treatment.

Without any medical facilities available, immediately descending to a lower elevation would be indicated.

However, if neither of these options are viable, and a slow ascent i snot possible, treatment with prophylaxis and nifidipine would be recommended until descent becomes an available option.

Due to the increased arterial pressure causing HAPE, pharmacological medications lowering pulmonary artery pressure can improve gas exchange in HAPE.

Prevention

Individuals who are susceptible to HAPE can avoid the risk of such a condition if ascent is gradual, with an average ascent of 300-350m per day when at an altitude greater than 2500m. This is especially important for individual at greater risk.

It was found that mountaineers who have developed HAPE more than once with rapid ascent in the Alps can have the condition prevented. Altitudes of up to 7000m can be reached by these individuals, without experiencing medical issues, if they ascend only 350-400m per day when they are above 2000m, or with a gradual ascent.

If mountaineers are experiencing altitude sickness, and want to prevent the occurrence of life-threatening illnesses, they would be advised to stop their ascent and monitor their symptoms for a day. If the symptoms do not improve, they should descend from tat elevation.

If an individual has a history of HAPE, vigorous exercise should be avoided during the initial days of exposure to altitude, since exercise induced circulatory changes can worsen or cause pulmonary oedema. This would especially include individuals who are experiencing symptoms of altitude sickness with rapid ascent to altitudes of 3500-400m.

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