Treatment and Prevention of High Altitude Pulmonary Edema

Herbert N. Hultgren*

High altitude pulmonary edema is a serious illness which may occur in persons who rapidly go to altitudes over 9000 feet without adequate prior acclimatization. It may also occur in acclimatized individuals who perform heavy work at high altitude. The first symptoms consist of unusual shortness of breath and weakness during slight effort. A dry persistent cough appears which later may be associated with gurgling sounds in the chest and the coughing up of foamy liquid or blood. The heart rate is usually over 120 per minute, the pulse may be very weak and the lips and fingernail beds may be blue (cyanosis). If prompt treatment is not employed the patient may become unconscious and death may occur within 6 to 48 hours. In previous years many attacks of pulmonary edema were erroneously diagnosed as pneumonia.

The cause of the condition is the leakage of fluid and blood from small blood vessels (capillaries) of the lung into the air sacs (alveoli). The filling of the air sacs of the lung with fluid prevents oxygen from reaching the blood, resulting in a low oxygen content of arterial blood and interruption of vital functions especially of the brain and the heart by oxygen lack.

High altitude pulmonary edema is a frequent cause of disability and, occasionally, death of mountaineers, skiers and travellers to high altitudes. During the past ten years at least seven mountaineers have died from pulmonary edema.1,2 Three non-fatal cases reported in the United States have involved skiers.3,4 Approximately 12 cases a year are seen at the Chulec General Hospital in La Oroya, Peru (elevation 12,300 feet) and fatal cases have been reported from that area.5 The military implications are apparent from the high incidence of pulmonary edema among Indian soldiers brought quickly from the plains of India to the Himalayas during the Sino-Indian border dispute. Many fatal cases were observed.6

This paper will discuss the treatment and prevention of high altitude pulmonary edema in relation to mountaineering. The importance of prompt recognition and proper management is illustrated by the following episode: A 34-year-old climber from Estes Park, Colorado (7800 feet) flew to Lima, Peru. One week after leaving home he reached base camp (14,000 feet) in the Peruvian Andes. The next day he climbed easily to 15,000 feet and returned to camp. The following morning he had a headache, was nauseated and weak with occasional spells of coughing. Nevertheless he climbed again to 15,000 feet. The next morning he was very weak, confused, and had a persistent dry cough. His breathing sounded clear but his oral temperature was 101.6°. Penicillin was started. By noon he was unable to walk and was completely disoriented. By 7:00 p.m. his temperature was 102° and his heart rate was 120/min. His breathing was now associated with sounds of gurgling liquid in the chest heard easily with a stethoscope or by the ear placed to the back of the chest. Oxygen was administered using a face mask and some improvement was noted within 30 minutes. The oxygen was stopped at 10:30 p.m. when the first tank ran out. By 11:00 p.m. his breathing rate had increased to 60/min. and his heart rate was 100/min. Audible gurgling sounds with each breath were again present over both lungs. Oxygen, given from 2:30 to 3:30 a.m. and from 6:00 to 7:00 A.M., caused slight improvement. At 8:30 A.M. he was put on a horse with a man behind for support and started down to a lower altitude. At 9:30 a.m. he received more oxygen with some relief. He reached Vicos (altitude 10,000 feet) at 6:30 p.m. greatly improved. He was aware of his surroundings and able to breathe easily and quietly. His temperature was 99.5°, breathing rate 28/min. and heart rate 80/min. After resting at Vicos, he descended to Lima, rested there several days more and then visited Cuzco at 11,250 feet without difficulty. A medical examination before going to Peru and upon his return to the U. S. showed no abnormalities. The physician on the expedition who treated the patient commented … “there was a definite decrease in respiratory rate after about 30 minutes of oxygen therapy each time it was used. During more prolonged oxygen administration mental confusion and restlessness definitely decreased. Following the administration of digitalis, there was no improvement and I feel it had no helpful effect.” Comment: The patient had severe pulmonary edema with evidence of oxygen lack to the brain. The effort of climbing to 15,000 feet when he was not feeling well probably made his edema more severe. Prompt administration of oxygen and evacuation to a lower altitude saved his life. Two deaths due to pulmonary edema have occurred in the same area in previous years. In neither of these instances was oxygen available, 1

1. Rest. A day or two of rest may be sufficient to permit recovery from mild or suspected pulmonary edema. This is particularly true of episodes that may occur following heavy exertion such as climbing or skiing even by persons who have been at high altitude for a week or more. Occasionally pulmonary edema afflicts even thoroughly acclimatized subjects doing very heavy work at high altitude.10,11 Since more severe cases have generally been treated with oxygen the value of rest alone has not been determined. Rest is probably sufficient treatment, however, for mild or suspected cases.

2. Oxygen therapy. Oxygen remains the most important single therapeutic agent in high altitude pulmonary edema. Within a few minutes after the use of oxygen there will be a decrease in breathing rate and heart rate and improvement in the individual’s state of consciousness (Figure 1). Blueness of the lips and nail beds will disappear. Headache,

nausea and vomiting will cease.1 Gurgling breath sounds and cough will gradually subside over six hours. Cough and fever persisting after 48 hours of treatment suggest the possibility of pneumonia. Oxygen can be efficiently delivered from a small cylinder through a pressure-reducing valve and flow meter to a properly fitting face mask. Standard oxygen tanks are heavy and cumbersome and therefore climbing parties rarely carry oxygen except where it is necessary for high altitude climbing. Though light alloy tanks manufactured abroad were employed by the 1963 American Mount Everest expedition, such tanks are not readily available in the United States.8 A reasonable compromise may be achieved by the use of standard anesthesia gas bottles (Size “E” cylinders) containing approximately 640 liters of oxygen at 2000 pounds per square inch pressure. Such bottles weighing 14 to 16 pounds should provide over 5 hours of oxygen at a flow rate of 2 liters per minute. A compact reducing valve with pressure indicator and flow meter indicating flows of 1 to 10 liters per minute is necessary. Such units can be obtained from companies dealing in medical oxygen equipment. The apparatus illustrated in Figure 2 was supplied by The National Welding Equipment Co., Richmond, California. (Single stage flow meter regulator, pressure compensated for small size D and E cylinder — reference number 59 25-Y.) It weighs 3.1 pounds. The flow meter illustrated in Figure 2 works only in an upright position. Flow meters using a dial indicator may be used in any position and may be more convenient for this reason. Light, disposable oxygen masks weighing 1½ ounces each as illustrated in Figure 2 can be obtained from the Hudson Oxygen Therapy Sales Co., Los Angeles, California. Not less than 4 feet of rubber or plastic tubing (internal diameter 5 mm.) are needed to make the connection to the face mask.

Since commercial flow meters may be inaccurate at flows below 4 liters per minute, it is important to calibrate the meter before departure at flow rates of 1, 2 and 4 liters per minute. Flow rates in the field can also be roughly estimated by putting one’s thumb over the opening between the plastic reservoir bag and the face piece while oxygen is running and noting the time required to fill the plastic bag. At sea level, flow rates of 1, 2 and 4 liters per minute filled the bag to tenseness in 30, 20 and 12 seconds respectively. At the lower atmospheric pressure of altitudes between 16,000 and 20,000 feet, the above times are approximately halved with even shorter filling times over 20,000 feet for equivalent flows.

A conservative estimate of medical oxygen requirements for a 5 to 15- man expedition would consist of 9 cylinders with 3 masks and tubes and 3 sets of reducing valves with flow meters. Three tanks with 2 masks, 2 reducing valves and 2 flow meters should be transported to the first base camp during the initial acclimatization period. The total weight would be about 60 pounds. Three tanks should be cached between the roadhead and Base Camp to be available during evacuation. Three tanks with one reducing valve, flow meter and mask should be left at the roadhead as either a reserve to be moved up if needed, or to be used during evacuation to sea level. All tanks should be checked for leaks by submerging the heads in a bucket of water after tightening the main valve. Bubbles will indicate improper valve closure.

Oxygen can be conserved by using a flow rate of 2 liters per minute after an initial flow rate of 4 liters per minute for 15 minutes as a priming dose. If the patient’s condition at a low flow rate is not improved as evidenced by a decrease in breathing rate, heart rate and cough, or by an improvement in the level of consciousness, a higher flow rate must be used. A flow rate of 2 liters per minute using this apparatus in a normal subject at sea level will provide a partial pressure of oxygen in the arterial blood of approximately 240 mm.Hg. or about 3 times normal (Figure 3).

If it is necessary to conserve a small oxygen supply, occasionally a flow of 1 liter per minute may be adequate if higher flows have been previously used for 15 or 30 minutes with improvement. A flow rate of 1 liter per minute will increase the partial pressure of oxygen in the lungs by almost 100% and would be roughly equivalent to the benefits obtained by descending from an altitude of 15,000 to 10,000 feet elevation.

In June 1964 the equipment described above was employed in the treatment of the following instance of acute pulmonary edema:

J. O., a 17-year-old student, returned to his home in La Oroya, Peru (altitude 12,300 feet) after attending college in Arkansas for the previous nine months. Two days later he developed headache, cough, shortness of breath and weakness. He was admitted to the Chulec General Hospital. He was drowsy with blueness of his lips and skin indicating a lack of oxygen in arterial blood. His rate of breathing was 26/min. (normal 8 to 12) and his heart rate was 116/min. (normal 70 to 80). With a stethoscope fine moist crackling sounds were heard in his lungs with each breath indicating the presence of fluid. X-rays of his chest showed patchy areas of fluid throughout both lungs. After six hours of complete bed rest he had not improved. Blood samples removed from an artery revealed an oxygen saturation of 55% (the normal value at this altitude is 88%). Oxygen was then given at a flow of 2 liters per minute, (equivalent to approximately 1½ liters per minute at sea level). In 10 minutes his arterial blood was 95% saturated with oxygen (equivalent to a normal sea level value). After 20 minutes his breathing rate and heart rate had decreased to 16/min. and 96/min. respectively. He was comfortable and alert. Continued treatment resulted in complete recovery in 24 hours.

3. Evacuation to a lower altitude. When oxygen is not available prompt descent to a lower altitude may be life-saving. At high altitude a descent of even 3000 feet will result in a significant increase in the partial pressure of oxygen. The higher the initial altitude the greater will be the benefit obtained from a given distance of descent. If at all possible the patient should be taken to below 10,000 feet for the most beneficial effect. In severe cases, careful planning of the evacuation is necessary. Prior to moving, the patient’s condition should be improved as much as possible by rest and oxygen. He should be transported by car, horse, or litter if possible. Oxygen should be given during the descent either continuously or intermittently (15 minutes of every hour at 4 liters per minute), depending on the patient’s condition.

In mild cases a week at a lower altitude may allow recovery but severe cases often require several days hospitalization followed by two to three weeks of gradually increasing activity. After recovery a return to high altitude can be made but usual precautions should be observed to avoid recurrence.

Because of the importance of prompt evacuation to a lower altitude in the event of an episode of pulmonary edema, initial base camps for acclimatization should be located, if possible, in an area where rapid transport to low altitude can be accomplished, either by air or surface transport. Three to six days spent at such a camp should allow sufficient acclimatization to avoid pulmonary edema at higher more inaccessible camps.

An example of improvement of pulmonary edema by descent is described below :

In 1960 a 35-year-old climber was flown from 350 feet above sea level to Base Camp (7000 feet) on Mount McKinley. The next five days were spent in heavy climbing up to 12,000 feet. On the morning of the sixth day at 12,000 feet he noted a hacking cough and a gurgling sound in his chest with each deep breath. He was weak and tired, without appetite. He rested all that day. The next day, despite persisting symptoms, he climbed with great difficulty to 13,000 feet. His shortness of breath and gurgling breathing persisted and he became partly unconscious. The following day he was able to make his way down to a camp at 10,000 feet with great difficulty. Here … “there was a remarkable change. Breathing and cough improved almost immediately and only physical weakness remained.” Four days later he returned to Talkeetna by plane.

In 1963 the same person experienced a similar attack of high altitude pulmonary edema while climbing at an altitude of 18,000 feet in the Peruvian Andes six days after leaving Lima. Removal to an elevation of 14,000 feet by a rescue team was accomplished with great difficulty but at this elevation marked improvement again occurred. Oxygen was administered at 10,000 feet and the patient was taken to Lima for recuperation.

Comment: Pulmonary edema occurred on two occasions at altitudes of 12,000 and 18,000 feet five and six days after leaving low altitude. The edema was probably made worse by exertion when symptoms were present. A descent of 3000 and 4000 feet resulted in marked improvement. Oxygen was not available during the acute stage of either episode. Evacuation was delayed during the second episode because of the inaccessibility of the higher camp. Similar prompt relief of symptoms of pulmonary edema have occurred with descents of 10,000, 5600 and 4000 feet by another climber. 1

4. Drugs. Many drugs have been employed in the treatment of acute pulmonary edema without any evidence of beneficial effect.1 The most frequently employed preparations have been penicillin, digitalis and morphine. Penicillin should be used if there is any suspicion of pneumonia: 600,000 units of Procaine Penicillin G (aqueous) given deep in the buttocks daily for one week is adequate. Digitalis has been given with the assumption that high altitude pulmonary edema is due to heart failure and digitalis may improve the function of the heart and thereby relieve the edema. Recent studies, however, have demonstrated that heart failure is not present and therefore digitalis would not be expected to be beneficial. 7 A review of cases in which digitalis preparations have been used reveal no consistent benefit, although occasionally patients may experience transient improvement. One controlled laboratory study revealed no beneficial effect.9 While morphine is an effective sedative and may allay apprehension, it also will depress respiration largely by slowing the rate of breathing. This will result in a further decrease in the oxygen content of the blood and worsen the situation. For this reason morphine and large doses of other sedatives which also may depress respiration should be avoided. Drugs which increase urine production and thus loss of body water (diuretics such as Diuril) are not helpful and may do harm by causing further water loss in a patient already dehydrated by failure to drink and increased water loss via the lungs. Because the small blood vessels of the lungs (pulmonary arterioles) are markedly narrowed (constricted) due to oxygen lack in high altitude pulmonary edema, it would seem that drugs which would dilate these vessels would be useful in treatment. Tolazoline (Priscoline), isoproterenol (Isuprel), and ami- nophylline would seem most suited for this purpose. These preparations may be given orally but are more effective when given as a slow continuous infusion into a vein after appropriate dilution in a larger volume of glucose or saline solution (500 ml. of 5% dextrose in water or physiological saline). At present their value in the treatment of high altitude pulmonary edema is unknown. Such therapy must be given only by a physician.

Prevention of Pulmonary Edema

Persons going above 9000 feet from sea level in one or two days may develop pulmonary edema. Acclimatized individuals living at high altitude are susceptible to pulmonary edema when they return to high altitude after being at sea level for two weeks or more. Youngsters aged 5 to 18 years, especially boys, seem quite prone to develop pulmonary edema during re-ascent. Those individuals who have previously experienced high altitude pulmonary edema are especially likely to develop repeat attacks upon return to high altitude. Some subjects living in the Peruvian Andes have had 10 separate hospital admissions for attacks occurring upon returning to the mountains from sea level vacations.

Prevention can be achieved by gradual acclimatization, rest and oxygen. Spending a few days at an intermediate altitude, i.e. from 5000 to 7000 feet with a moderate amount of physical exercise may help. In susceptible persons a period of 24 to 48 hours of complete bed rest is desirable upon arrival at high altitude, but this does not guarantee protection. In spite of such precautions some individuals in the Peruvian Andes still have developed pulmonary edema. In these subjects bed rest for 24 to 48 hours after arrival and oxygen at low flow rates (1 to 2 liters per minute) by mask will prevent pulmonary edema. This is the method used at the Chulec General Hospital in Peru.

It is not known if any drugs will prevent pulmonary edema. A logical choice would seem to be the use of Isuprel glossets, 10 mg. four times daily during ascent and for the first 48 hours after arrival. During the past two years steroids have been employed in an attempt to prevent attacks in susceptible individuals. Prednisone 40 mg. twice daily beginning two days before ascent and continued until 48 hours after arrival is the usual regimen. There is some evidence that this may be beneficial but current studies of drug prophylaxis are not complete. No side effects have been observed, although the danger of reducing one’s resistance to infection, especially bronchopneumonia and tuberculosis by steroids should be emphasized. In the absence of a history of previous episodes of pulmonary edema, the use of steroids as a preventive measure is not warranted.

At high altitude prevention of attacks is most efficient if one can detect early signs or symptoms of pulmonary edema. Undue fatigue, severe breathlessness on slight effort, cough and a rapid heart rate at rest are useful clues of early or mild pulmonary edema. Treatment consists of bed rest and oxygen at a low flow rate for 12 to 24 hours.

In planning the location of base camps, climbers should consider the problem of rapid evacuation to lower altitude of an ill person, either by aircraft or trail and road. The rate of ascent to higher elevations should be conservatively governed by the climber’s subjective feeling of strength and fitness. Even mild symptoms of altitude sickness should dictate a suitable period of rest until symptoms subside.

Acknowledgment: The author wishes to acknowledge the valuable assistance of the following individuals in preparing this report: Harry Miller, Kent Heathershaw, William Greig, James Petroske, M.D., Richard Irvin, Thomas Hornbein, M.D., Thomas Nevison, M.D.

Bibliography

1. Hultgren H. N., Spickard, W., Hellriegel, K. and Houston, C.: High altitude pulmonary edema, Medicine 40:289-313, 1961.

2. Hultgren, H. N., Spickard, W. and Lopez, C.: Further studies of high altitude pulmonary oedema, British Heart Journal 24:95-102, 1962.

3. Houston, C.: Acute pulmonary edema of high altitude, New England Journal of Medicine 263:478-480, 1960.

4.Fred H.,Schmidt, A., Bates, T. and Hecht, H.: Acute pulmonary edema of altitude. Clinical and physiologic observations, Circulation 25:929-937, 1962.

5. Arias-Stella, J. and Kruger, H.: Pathology of high altitude pulmonary edema, Archives of Pathology 76:147-157, 1963.

6. Nayak N., Roy, S. and Narayanan, T.: Pathologic features of altitude sickness, American Journal of Pathology 45:381-391, 1964.

7. Hultgren, H. N., Lopez, C., Lundberg, E. and Miller H.: Physiologic studies of pulmonary edema at high altitude. Circulation 29:393-408, 1964.

8. Ullman, J.: Americans on Everest, J. B. Lippincott Co., Philadelphia and New York, 1964.

9. Hultgren, H.: Unpublished observations.

10. Roberts, Gil, M.D.: Personal communication.

11. Nevison, T.: Progress in research in emphysema and chronic bronchitis. Normal and abnormal pulmonary circulation. Fifth Annual Conference on Research in Emphysema, Aspen, Colorado, June 13-16, 1962, S. Karger, New York, 1963.

*Associate Professor of Medicine, Stanford University School of Medicine, Palo Alto, California.