Drug Therapy For High Altitude Pulmonary Edema (HAPE)
A 25 year old male (165 cm, 55 kg) student by profession was referred to our institute with history of breathlessness for 1 day after a trip from a hill station. He complained of difficulty in breathing and slurring of speech with generalised weakness, after which he was admitted to a local hospital where decision for tracheal intubation was taken in view of decreasing oxygen saturation and referred to higher centre for further management as they were ill equiped. Breathlessness was acute in onset and not associated with pedal edema or fever. He was received in the emergency department of our institute with 8.0 mm endotracheal tube in situ and oxygen saturation (Sp02) of 91%. The condition of the patient was assessed and the decision to shift the patient to our intensive care unit (ICU) was taken. On admission to ICU of our institute, he had a blood pressure of 100/50 mm Hg and heart rate of 125 per minute. History of frothy secretions was documented. General physical examination was normal. On auscultation of chest, patient had bilateral crepts and decreased air entry in both the bases. Rest of the systemic examination was normal. Chest x ray reported bilateral homogeneous opacities, mostly in the middle zone and lower zone. As the trachea was already intubated, he was then put on ventilatory support on spontaneous intermittent mechanical ventilation with pressure control ( SIMV PC ) mode with with tidal volume of 500 ml, respiratory rate of 12 per minute, positive end expiratory pressure (PEEP) of 7 cm H20, pressure support of 10 cm H20, fraction of inspired oxygen ( FiO2) of 100% . Gradually the Sp02 improved to 94 % , after which FiO2 was decreased to 50 % and maintained . He was sedated with infusion of injection (inj.) midazolam @ 2ml/hr inj. morphine 2mg/hr. IV inj. methylprednisolone 15 mg was given stat followed by 15 mg infusion over 24 hrs. IV inj. dexamethasone 4 mg tds was also advised.
All blood investigations were within normal limits. Initially the arterial blood gases revealed hypoxemia (Pa O2 of 57 mm Hg) and compensated respiratory alkalosis. After mechanical ventilation, hypoxemia and respiratory alkasosis were resolved , Serial chest x rays showed improvement corresponding with clinical condition.
Patient was gradually weaned off from ventilatory support and after adequate criteria of weaning were met, spontaneous breath trial was given which was successful after which the trachea was extubated and put on non invasive ventilation for one day . Next day patient was mainatined on Venturi mask on oxygen at 6 l/min. After two days of monitoring, he was shifted to ward on nasal prongs in stable condition.
Discussion
Pulmonary edema is a common complication seen in the ICU setting. It may be cardiogenic which results from increased pulmonary capillary pressure (due to left heart failure) or non cardiogenic which is due to endothelial injury which results in increased permeability.
Pulmonary edema resulting from high altitude is commonly seen in individuals ascending to altitude of more than 2500 m from the sea level . High altitude sickness may involve lungs ( high altitude pulmonary edema -HAPE) or the central nervous system (high altitude cerebral edema-HACE). The most common cause of mortality from high altitude sickness is due to HAPE. Individuals with previous history of similar events are predisposed to the condition as it has a recurrence rate of 60%. Other risk factors which increase the incidence of HAPE are fast ascent , altitudes of > 2500 m from sea level, pre existing lung infections, sickle cell disease, pulmonary hypertension, atrial septal defect and patent foramen ovale.
Various theories have been postulated which show a genetic predisposition to HAPE. At the molecular level, various pathways are involved in the pathogenesis which include renin-angiotensin-aldosterone system (RAAS), nitric oxide pathway, and hypoxia-inducible factor pathway. Localized areas of pulmonary capillaries stress failure is characteristic of HAPE. High altitudes leads to physiological response in the body which is characterized by increase in respiratory rate, increase in heart rate but with a lower stroke volume. Longer exposure leads to polycythemia, increase in myoglobin and hypoxic pulmonary vasoconstriction.
Kurtzman etal. advocates pretreatment with a carbonic anhydrase inhibitor, oxygen inhalation and proper hydration to reduce the risk. Initial presentation of HAPE includes breathlessness, dysnea on exertion headache , chest congestion. As the disease advances bilateral coarse crepts and pink frothy sputum is seen. Arterial blood gas analysis show hypoxemia and respiratory alkasosis as was seen in our case.
To prevent HAPE, the major predictor is the rate of ascent which should be gradually over few days. It should not exceed 350 m per day as it will provide ample time for the body to acclimatize to the new altitude. But once an individual starts to show the spectrum of HAPE , patient should be brought to 1000m as soon as possible and oxygen therapy started with an aim to maintain SpO2 of greater than 90%.
Few drugs have been found to play a role in reversing the effect. These include phosphodiesterase inhibitors, such as tadalafil or sildenafil, which cause pulmonary vasodilation and decrease pulmonary artery pressure thus providing relief. Another physiological challenge is to maintain normothermia as it will reduce the sympathomimetic effects of hypothermia.
Steroid cover will lead to decrease in pulmonary artery pressure. The recommended dose of dexamethasone is 8 mg initially followed by 4 mg every 6 hours. Nitric oxide inhalation and portable hyperbaric bags like Gamow bag both have shown improvement in the clinical picture.
Conclusion
HAPE is a life threatening disease which is preventable by gradual ascent but once it manifests, the aim should be to maintain arterial saturation of >90%. Drug therapy may be helpful to alleviate the symptoms and may fasten the recovery process.
