HIGH ALTITUDE PULMONARY EDEMA (HAPE)

GENERAL APPROACH TO HAPE

During the mission planning phase, prioritize risk mitigation strategies and identify individuals who are at high risk of HAPE. Identify HAPE early in the disease process, as early administration of oxygen and descent of 1000m can potentially resolve symptoms. Once diagnosed, evacuation to lower altitude should be the top priority. Use pharmaceuticals and adjuncts listed above to temporize HAPE pathophysiology while coordinating evacuation. Do not delay evacuation for the aforementioned therapies.

Once diagnosed with HAPE, the roles of acetazolamide and dexamethasone have not been shown to be beneficial in the treatment of HAPE. Treatment and evacuation efforts should be aggressive.

#### Diagnostic Criteria for HAPE

2 Signs from:

- Tachycardia
- Tachypnea
- Crackles or wheezing in at least 1 lung field
- Central Cyanosis

2 Symptoms from:

- Dyspnea at rest
- Cough
- Decreased exercise tolerance or weakness
- Chest tightness or congestion

HAPE EVALUATION

HAPE is life threatening and early diagnosis is critical. The international diagnostic criteria for HAPE are a combination of two signs and two symptoms. The symptoms are dyspnea at rest, cough, decreased exercise tolerance or weakness, and chest tightness or congestion. The earliest symptoms are commonly decreased exercise tolerance and dyspnea at rest. Signs include crackles or wheezing in at least one field. Central cyanosis, tachycardia, and tachypnea.

Risk factors for HAPE include pulmonary arterial hypertension, previous history of HAPE (50-60% risk of recurrence after a first HAPE episode), pulmonary infection, PFO, and use of respiratory depressants. HAPE presents in isolation from AMS/HACE in 50% of cases and will often present on the second night of higher sleeping altitude exposure.3 Development of disease after 4 days of stable altitude exposure is unusual. Disease progression can present as fever, increasing tachycardia, tachypnea, fatigue, productive cough, hypoxia/cyanosis, and hypoxic encephalopathy. Physical exam findings can include rales, particularly in the right mid-lung fields. SpO2 readings will be lower than expected for a given elevation. Differential diagnoses to consider include asthma, chronic obstructive pulmonary disease, heart failure, bronchitis, myocardial infarction, pneumonia, pulmonary embolism, pneumothorax, and trauma.3,17

HAPE PREVENTION

Mission planning, pre-acclimatization strategy, nutrition, and hydration are discussed above for all HAI and will mitigate incidence and severity of HAPE. Identify those at high risk of developing HAPE, particularly those with risk factors for HAPE participating in aggressive ascent profiles with limited pre-acclimatization.

Slow ascent rate is more critical for those at high risk of HAPE. These individuals should ascend no faster than 350M sleeping elevation per night.

Nifedipine: For individuals at high risk of HAPE, prophylaxis with nifedipine extended- release formulation 30mg orally every 12 hours or immediate-release formulation 20mg orally every 8 hours, beginning on the day of ascent is recommended. Prophylaxis should be continued for 7 days at maximum altitude and can be discontinued upon descent.3,17

Phosphodiesterase inhibitors: For individuals at high risk of HAPE who are not candidates for nifedipine, prophylaxis with tadalafil 10mg orally every 12 hours or sildenafil 50mg orally every 8 hours, beginning on day of ascent is recommended. Do not use phosphodiesterase inhibitors in combination with nifedipine due to risk of hypotension. Prophylaxis should be continued for 7 days at maximum altitude and can be discontinued upon descent.3,17,38

Dexamethasone: There is weak evidence showing benefit of dexamethasone in preventing HAPE and the mechanism is poorly understood. Thus, if patients are at high risk of HAPE and are not candidates for nifedipine or a phosphodiesterase inhibitor, consider prophylaxes with dexamethasone 8mg orally every 12 hours, beginning on day of ascent. Prophylaxis should continue until at a stable altitude for two days.3,17,38

Acetazolamide: No robust data exists supporting the use of acetazolamide in HAPE prevention; however, the physiologic response to acetazolamide and acclimatization likely leads to a benefit in reducing severity of HAPE.17,39 Patients at risk of HAPE are probably also at risk of severe AMS/HACE. Thus, patients at high risk for HAPE should be on prophylactic acetazolamide. See AMS prevention recommendation.

Salmeterol: Inhaled salmeterol has been shown to decrease HAPE risk up to 50% in susceptible individuals. The studies utilized 250mcg doses which are not standard. Inhaled salmeterol should not be used for HAPE prevention.

HAPE TREATMENT

Descent: HAPE leads to high mortality and morbidity; thus, descent to lowest possible altitude in the most expeditious manner should be of the highest priority until symptoms fully resolve. Individuals suffering from HAPE should descend using as little exertion to themselves as possible, ideally via vehicle. If they must walk themselves, then remove any burdening load.4,17

Oxygen: If available, oxygen should be given continuously, titrating to an SpO2>90%. Rapid evacuation should not be delayed for oxygen therapy.

Portable hyperbaric chambers: See PHC recommendation for HACE.4,17,40

Nifedipine: In cases when evacuation to lower altitude is prolonged or unavailable, patients should be treated with nifedipine. Treatment dose of nifedipine is identical to prophylactic dose. If immediate evacuation is available, then nifedipine is not indicated.3,17,41

Phosphodiesterase inhibitors: In cases where the patient is not a candidate for nifedipine, consider treating with tadalafil or sildenafil at the prophylactic dose. See phosphodiesterase inhibitor recommendation for HAPE prevention.

ADDITIONAL CONSIDERATIONS

For air evacuation of HAI casualties, pilots should fly at the lowest allowable elevation possible. All efforts should be made to avoid flying at higher elevations than the point of injury unless the cabin is pressurized to an altitude lower than point of injury.

Individuals who conduct dive operations should refrain from flying and ascending to high altitudes for at least 12 to 24 hours after the last dive due to increased risk of decompression sickness.42

Underwater diving operations at altitude compound the inherent risks of diving operations at sea-level. These risks are beyond the scope of this guideline. Consult your Dive Medical Officer or Master Diver to discuss alternative decompression tables and considerations when executing dive missions at altitude.43

Physiologic changes that take place at altitude can unmask previously subclinical conditions, such as seizure disorders, brain masses, and vascular malformations. New onset focal neurologic deficits at altitude should be evaluated by a qualified medical provider for consideration of evacuation with further neurologic workup once at higher level of care.3-4

Sickle cell disease and sickle cell trait have not been described as risk factors for HAI; however, these individuals are at increased risk of vaso-occlusive crisis and splenic infarction at altitude.3-4

Pregnant women should not participate in non-routine high altitude military operations without first talking to a medical officer about the risks.