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High Altitude Medical Problems (Medi- Medical Progress Cal Progress)

High Altitude Medical Problems (Medi- Medical Progress Cal Progress)

Refer to: Hultgren HN: High medical problems (Medi- Medical Progress cal Progress). West J Med 131:8-23, Jul 1979

High Altitude Medical Problems HERBERT N. HULTGREN, MD, Palo Alto, California

Increased travel to high altitude areas by mountaineers and nonclimbing tour- ists has emphasized the clinical problems associated with rapid ascent. Acute mountain sickness affects most sojourners at elevations above 10,000 feet. Symptoms are usually worse on the second or third day after arrival. Gradual ascent, spending one to three days at an intermediate altitude, and the use of (Diamox) will prevent or ameliorate symptoms in most instances. Serious and potentially fatal problems, such as high altitude pulmonary or , occur in approximately 0.5 percent to 1.0 percent of visitors to elevations above 10,000 feet-especially with heavy physical exertion on arrival, such as climbing or skiing. Early recognition, high flow and prompt descent are crucially important in management. Our knowledge of the causes of these and other high altitude problems, such as retinal hemor- rhage, systemic edema and pulmonary , is still incomplete. Even less is known of the effect of high on medical conditions common at sea level or on the action of commonly used .

EXPOSURE TO HIGH ALTITUDE of people of all hiked up to Pheriche (14,000 feet) en route to the ages and degrees of health has enormously in- Everest base camp. In the Mount Kenya area 3,- creased in the last ten years. Modern travel facili- 500 climbers and trekkers climb above 13,000 ties and the advent of mountain tours and trek- feet each year. Skiers in the Rocky Mountains are king safaris now permit access to high mountain not immune to high altitude illness; many ski re- regions previously visited only rarely by hardy sorts are located at 8,000 feet or higher, with ski climbers. In 1976 there were 671 climbers on runs starting at 11,000 and 12,000 feet. Such re- Mount McKinley (20,320 feet) and each year sorts can be easily reached in one day from any more than 5,000 people climb Mount Rainier part of the . High altitude pulmonary (14,408 feet). In the Himalayas during one four- edema has been observed in hikers and skiers in week period in 1975 there was 522 trekkers who the Sierra Nevadas, and helicopters now carry skiers to 12,500 feet from the eastern side of the Dr. Hultgren is Chief, Service, Veterans Administra- tion Medical Center, Palo Alto, California; Professor of Medicine, Sierras. In South America large permanent popu- Stanford University School of Medicine, and Chairman, Medical Committee, American Alpine Club, New York City. lations live and work at altitudes as high as 16,- This work was supported by research funds from the Veterans Administration Medical Center, Palo Alto, California. 500 feet. should be aware of common Reprint requests to: Herbert N. Hultgren, MD, Veterans Ad- medical problems of acute and chronic high alti- ministration Medical Center, 3801 Miranda Avenue, Palo Alto, CA 94304. tude exposure. For these reasons this review of

8 JULY 1979 * 131 * 1 HIGH ALTITUDE MEDICAL PROBLEMS

10r ABBREVIATIONS USED IN TEXT a AMS=acute mountain sickness HAPE=high altitude z 90F- 0 current concepts of high altitude illness has been D 80 prepared. : cn Definition of High Altitude Z 70 0crui For the purpose of this review high altitude will w o Rest 0L refer to elevations of 8,000 to 15,000 feet above 60_ * Exercise 300 kg-m/min. sea level. It is rare for symptoms of altitude ill- * 900 kg-m/min. ness to occur below 8,000 feet and few mountain ft tours or permanent human habitations extend Sea level 5,400 10,150 14,900 19,000 above 15,000 feet. ALTITUDE (Ft.) Figure 1.-Arterial oxygen saturation in normal man at Role of sea level and various altitudes at rest and during It is apparent that the most moderate exercise. (Reprinted with permission from important effect Banchero et of high altitude exposure is hypoxia. At 12,000 al.1) feet the normal resting arterial oxygen saturation AMS is the most common high altitude illness. is 85 percent. At 15,000 feet the saturation falls Excellent descriptions of AMS have been pub- to 78 percent. At 19,000 feet the arterial satura- lished by Acosta5 and Barcroft.6 Acosta's descrip- tion is 69 percent. During exercise at sea level tion is one of the earliest published records of arterial oxygen saturation does not fall. However, AMS (1589). Barcroft's report describes symp- during exercise at high altitude oxygen saturation toms affecting passengers on a train trip from falls due to limitations in maximal pulmonary Lima to Cerro de Pasco, (14,200 feet). The diffusing capacity (Figure 1). At 15,000 feet the most common initial symptom consists of head- saturation may fall to 69 percent and at 19,000 ache, which may vary in severity from a mild feet heavy exercise may decrease arterial satura- feeling of or to severe, tion to levels as low as 40 percent to 50 per- prolonged, incapacitating pain. Lassitude, ano- cent.'-3 This is one factor that limits climbing rexia, drowsiness, a general feeling of , performance at very high altitudes. In addition, weakness and dyspnea on exertion are common. during sleep at high altitude the drop in arterial During ascent, , chilliness with pallor saturation is considerably more than the slight of the face, and of the lips and nailbeds decrease observed at sea level. Persons at 17,200 are frequently noted. and may feet with an arterial oxygen saturation of 74 occur, especially in children. percent when awake have a mean saturation of After arrival, a feeling of warmth and flushing 64 percent during sleep. With irregular respiration of the face may be noted for the first 24 to 48 during sleep, saturations below 40 percent have hours. The above symptoms may persist for sev- been observed.4 eral days, although in most instances they disap- While arterial tension (Pco2) pear within 24 to 48 hours. Sleep, especially for falls during high altitude exposure it is unlikely the first few nights, is difficult, with frequent that is responsible for symptoms of periods of wakefulness and often strange dreams. altitude exposure. Even slight physical effort may produce trouble- some dyspnea, often requiring considerable rest Acute Mountain Sickness until the respiratory distress has ceased. Weakness Rapid exposure to high altitude of unacclima- and palpitation on effort may be noted; tachy- tized persons commonly results in a group of cardia may be present. A common complaint is symptoms generally known as acute mountain dull pain and discomfort in the the muscles of the sickness (AMS). Severe symptoms rarely occur posterolateral chest wall. Cheyne-Stokes respira- below 8,000 feet and in most persons some symp- tion may be experienced above 8,000 feet and it toms will be present from 10,000 to 12,000 feet. occurs in nearly all persons at altitudes above

THE WESTERN JOURNAL OF MEDICINE 9 HIGH ALTITUDE MEDICAL PROBLEMS 13,000 feet. It appears most frequently during in the relief of symptoms but in facilitating restful the night and is a major factor in preventing sleep. Lightweight oxygen tankws are now available sound, restful sleep. If present during the day, that provide 247 liters of oxygen with a variable it does not appear to be related to activity or flow regulator with a carrying weight of only meals. It is rarely continuous, but appears and 6h pounds (Erie Manufacturing Co., 4000 S. disappears, lasting for minutes to hours. 13th St., Milwaukee, Wisconsin 53221). Neurologic and cerebral symptoms may be Prevention experienced, including a reduced capacity for The most effective method of preventing AMs sustained mental work, memory defects, auditory is by acclimatization. This can be achieved by a. and visual disturbances, vertigo and tinnitus. Ir- sojourn at an intermediate altitude (6,000 to ritability may be noted. may remain 8,000 feet) for two to four days before going to poor; a weight loss of from 5 to 10 pounds may a higher altitude. Another effective measure is occur in adults. In some persons symptoms may gradual ascent by climbing 1,000 feet per day persist throughout their stay at high altitudes and interrupted by an occasional day of rest. In trek- may result in their inability to work efficiently king parties to the Everest base camp AMS was or, in some cases, may necessitate a return to seen far more frequently in those who flew from sea level. Katmandu to Lukla (9,240 feet) than in those is the most severe and disabling who walked this distance over 13 days.' For those symptom of AMS. It has been suggested that head- persons susceptible to AMS the administration of ache is due to cerebral edema; however, cerebral acetaxolamide (Diamox) may be helpful.74- Ace- edema in other clinical conditions is not regu- tazolamide may be given in a of 250 mg once larly assocated with headache. A more plausible or twice a day beginning on the day of ascent cause is spasm or dilatation of cerebral and continued for two to five days after arrival. vessels related to hypocapnia (which causes cere- Side effects such as tingling of the lips and finger bral vasoconstriction) or hypoxia (which causes tips, alteration in the taste of beer and myopia cerebral vasodilatation). usually occur only if acetazolamide administra- AMS may not be evident during the first 24 tion is continued for more than five days.7'8 Field hours of altitude exposure and the symptoms are studies of troops have shown that AMS at 14,200 usually most severe on the second and third day. feet can be ameliorated by staging for four days Sleep at high altitude is more conducive to AMS at 5,300 feet and administering acetazolamide and reinforces the wisdom of the climbers' stra- (500 mg twice a day) for the last two days of tegy of "sleep low and climb high." On Mount staging and the first two days at high altitude. Whitney (14,495 feet), for example, AMS occurs Treated persons at high altitude had a higher less frequently in climbers who make the ascent arterial oxygen tension, a lower arterial carbon in one day from Owens Valley than in those who dioxide tension and a lower pH than control spend the night at Mirror Lake (10,640. feet). subjects.8 The dosage of acetazolamide in these Treatment studies was high, usually 250 mg twice a day. A higher staging altitude of 6,000 to 7,000 feet Mild or moderately severe AMS is best treated may be preferable. by rest, light diet, increased fluid intake and symp- Furosemide (Lasix) is of no value in prevent- tomatic measures to relieve headache (, does codeine). Smoking and the use of should ing AMS. Physical conditioning before ascent be avoided. Voluntary every 10 not appear to reduce the incidence or severity of to 15 minutes may be helpful. Excessive hyper- AMS but it will permit more effective climbing. ventilation may result in symptoms of acapnea Alkalinization of the blood by the use of including dizziness and tingling or numbness of is of no value. Even the ingestion of 50 grams of the hands and lips. Barbituates may make rest sodium bicarbonate per day for three days re- and sleep possible, but may be associated with an sulted in no major effect upon the respiratory intensification of symptoms upon awakening. For response to hypoxia.10 severe episodes descent or administration of oxy- Subacute Mountain Sickness gen are indicated. Continuous oxygen administra- Symptoms of AMS disappear in two to six days. tion (1 to 2 liters per minute) with a plastic face In rare instances symptoms may persist for weeks mask during sleep may be very helpful, not only or months. Major problems may consist of ano-

10 JULY 1979 * 131 * 1 HIGH ALTITUDE MEDICAL PROBLEMS rexia with weight loss, , and mental and tricular failure are absent. Pulmonary artery pres- physical . Symptoms will disappear upon sures will return to normal upon return to sea descent to a lower altitude. level."'18 This condition appears to be benign with an excellent . Continued residence Chronic Mountain Sicknes at high altitudes does not appear to be harmful. Chronic mountain sickness is a rare condition Increased pulmonary vasoconstriction due to hy- seen only in people who have lived for months poxia (pulmonary vascular hyperreactivity?) is the or years at high altitudes. Weakness, fatigue, som- probable cause. The condition should not be con- nolence and mental confusion are common symp- fused with the sea level disorder of primary pul- toms. Physical findings consist of pronounced monary hypertension, which has a poor prognosis. cyanosis and plethora with, occasionally, clubbing of the fingers and toes. Signs of pulmonary hy- Hlgh Altitude Pulmonary Edema pertension are present. Arterial oxygen saturation General is low and notable ' is present with High altitude pulmonary edema (HAPE) occurs hematocrit readings as high as 80 percent being in unacclimatized persons who are rapidly ex- occasionally observed. Right ventricular failure posed to altitudes greater than 8,000 feet. It is may occur and cause . Symptoms and signs most frequently seen in climbers who ascend to disappear upon return to a lower altitude. Alve- high altitudes without previous acclimatization and olar due to a diminished respira- who engage in heavy physical exertion on arrival. tory response to hypoxia is the probable cause.1"'19 Initial symptoms of dyspnea, , fatigue and occasionally appear, usually within Chronic Mountain Polycythemia two to seven days after arrival. Common physical In persons living permanently at high altitudes, signs are , tachycardia, rales, cyanosis hematocrit readings may occasionally be high and hypotension. In severe episodes there may be without symptoms or signs of chronic mountain disturbances of consciousness or coma. Descent sickness. At 12,000 feet the normal hematocrit to a lower altitude, bed rest and oxygen adminis- reading is 54 percent and at 14,900 feet it is 58 tration result in rapid clinical improvement. Fatal percent. However, occasionally values of 60 per- episodes continue to occur in many parts of the percent to 70 percent may occur in evidently world as access to high altitudes by unacclima- healthy persons living at high altitudes. The ex- tized visitors is facilitated by modern means of cessive polycythemia that occurs is probably due travel. Most occur when a prompt diag- to decreases in arterial oxygen saturation during nosis is not made, when the victim is not moved sleep, which is more severe in polycythemic per- to a lower altitude or when oxygen is unavailable. sons than in normal persons. All night mean Preexisting cardiac or pulmonary has not arterial saturation in five polycythemic subjects been shown to be a factor in the development of was 79 percent compared with 88 percent for HAPE. Physiologic studies during the acute stage five normal subjects studied by Kryger and his in have shown normal pulmonary artery associates at 10,152 feet in Leadville, Colorado.18 wedge pressure, pronounced elevation of pulmo- nary artery pressure, severe arterial unsaturation of High Altitude and usually low cardiac output. Pulmonary arteri- A moderate increase in pulmonary artery pres- olar (precapillary) resistance is elevated. The in- sure and pulmonary arteriolar (precapillary) re- cidence is higher in adolescents but may occur at sistance is present in people living at high alti- any age. HAPE represents one of several varieties tudes. At 12,000 feet and 14,900 feet the normal of acute pulmonary edema in which left ventricu- mean pulmonary artery pressure is 22 mm and 30 lar filling pressure is normal. mm, respectively (compared with the normal sea level value of 14 mm of ). In occasional Clinical Presentation instances, particularly in children, high pulmo- The first symptoms of HAPE usually begin 24 to nary artery pressures may be encountered without 96 hours after arrival at high altitude and are symptoms. Signs of pulmonary hypertension may commonly preceded by heavy physical exertion be shown on physical examination, x-ray studies such as climbing, skiing or carrying heavy loads. of the chest and electrocardiograms. The subjects Dyspnea, a persistent nonproductive cough, and are usually asymptomatic and signs of right ven- notable weakness and fatigue are the most com-

THE WESTERN JOURNAL OF MEDICINE 11 HIGH ALTITUDE MEDICAL PROBLEMS mon early symptoms. Headache, nausea, vomit- nervous system dysfunction and altered con- ing or somnolence is often seen in children. As sciousness are probably related to hypoxia or the severity of the pulmonary edema increases, cerebral edema, which may be profound in severe usually during the night, dyspnea at rest becomes HAPE."' severe and the cough becomes productive of clear, Common clinical signs include cyanosis, hy- copious watery . Rhonchi and gurgling perpnea, crepitant rales and rhonchi. The blood sounds can be heard without a . He- pressure is low. In a study of 21 patients in Peru, moptysis, sometimes involving fairly large quanti- the mean arterial pressure was 106/69 mm of ties of blood, can be seen in about 20 percent of mercury. Tachycardia due to severe hypoxia is severe episodes. A typical becomes appre- present, withi heart rates up to 160 per minute hensive, fears death, and may become incoherent in severe episodes. The mean heart rate in 34 or irrational or experience hallucinations. Coma Peruvian episodes was 122 per minute. The res- may follow and precedes death by 6 to 12 hours piratory rate is increased and a mean value of if oxygen is not administered or the patient is not 32 per minute was observed in Peruvian studies.18 carried to a lower altitude. In rare instances, stupor progressing to coma may occur, with mini- Laboratory Studies mal symptoms or signs of respiratory distress, Laboratory studies in persons with high alti- and the clinical features may resemble those of tude pulmonary edema show elevated hematocrit encephalitis or intracranial disease.'6 17 Central reading and acid urine with high specific gravity

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FiC I 1:A D Figure 2.-A, Mild high altitude pulmonary edema (HAPE) occurring in a hiker in the Sierra Nevadas. B, HAPE of moderate severity in a 14-year-old boy at 14,200 feet. C, Severe HAPE in a young boy at 12,500 feet. D, Cardiac pulmonary edema due to acute chordal rupture with mitral regurgitation.

12 JULY 1979 * 131 * 1 HIGH ALTITUDE MEDICAL PROBLEMS compatible with hemoconcentration. Signs of in- from HAPE show clearing of infiltrates and de- fection are absent, with only minor temperature crease in prominence of the pulmonary arteries, elevation, a normal or molerately raised leuko- but no consistent change in heart size.18 The cyte count and a normal sedimentation rate. radiologic features of HAPE are illustrated in Electrocardiograms during acute HAPE show Figure 2. tachycardia and signs of acute right ventricular In persons with severe HAPE, especially when overload, including right axis deviation, P-wave treatment has been delayed or recovery is slow, abnormalities compatible with right atrial strain, infiltrates persisting for many days, or even up prominent R waves in the right precordial leads, to two weeks after clinical recovery, may be noted and S waves in leads V5 and V6. In one instance on x-ray films of the chest.19 For this reason it is transient atrial flutter has been noted. The changes advisable that such studies be done on any per- are similar to those occurring during pulmonary son who may have had an episode of HAPE, even embolism and acute cardiac pulmonary edema though clinical recovery has occurred. Films and subside during treatment. The electrocardio- showing a slowly clearing residual pulmonary graphic abnormalities are probably due to acute infiltrate may confirm, therefore, the diagnosis of pulmonary hypertension. suspected HAPE even after return to sea level. Radiologic Features Severity Radiologic studies have been done in many In evaluating treatment and prognosis, objec- instances of HAPE and the extent of the edema tive assessment of the severity of HAPE iS im- shown on films of the chest roughly parallels the portant. In an evaluating therapy for HAPE in clinical severity. In mild episodes, single or sev- Peru,20 a simple method of grading severity has eral small patchy infiltrates are present. In severe been used based on clinical features, echocardi- forms the infiltrates may nearly fill both lung ographic findings and x-ray films of the chest fields. The infiltrates are rarely confluent and (see Table 1). General experience indicates that clear spaces of aerated lung are usually present patients with grade 4 severity usually die unless especially at the lung bases. The edema is more prompt therapy can be instituted. severe and common in the right mid-lung field. The mortality of HAPE is variable and depends The usual symmetrical, bat-wing, distribution of on many factors. Studies of large population edema commonly seen in cardiac pulmonary groups at indicate a mortality of 0.5 percent edema or uremia is rare. The central branches of to 12.7 percent.21'22 the pulmonary artery are prominent but the overall heart size is not increased. Left atrial Incidence and Age enlargement and pulmonary venous congestion A study of the incidence of HAPE has been car- are absent. Kerley lines of pulmonary venous ried out in the mining town of La Oroya (altitude hypertension are absent. Pleural effusion is rare. 12,300 feet) in the central Peruvian Andes.23 Serial x-ray films of the chest during recovery Many permanent residents live in this community

TABLE 1.-Classification of the Severity of HAPE Grade* Clinical Electrocardiogram X-ray Film of the Chest I Mild ...... Minor symptoms with dyspnea Tachycardia only; heart rate at Minor exudate involving less only on heavy exertion rest <110 than a fourth of one lung field 2 Moderate ... Symptoms of dyspnea, weak- Tachycardia with resting heart Exudate involving at least half ness, fatigue on ordinary effort; rate 110-120; P wave changes of one lung field headache, dry cough only 3 Serious ..... Symptoms of dyspnea, head- Tachycardia with heart rate Bilateral exudates involving at ache, weakness, nausea at rest; 120-140; P wave and minor least half of each lung field loose recurrent productive cough QRS-T wave changes 4 Severe ...... Stupor or coma; inability to Tachycardia with heart rate Bilateral exudates involving stand or walk; severe cyanosis; >140; right axis deviation, more than half of each lung bubbling rales present with co- QRS, T wave and P wave field pious sputum, usually bloody changes HAPE = high altitude pulmonary edema *Grades 1 and 2 can usually be treated with bed rest alone without descent. Grade 4 is usually fatal unless immediate descent and oxygen treatment can be carried out.

THE WESTERN JOURNAL OF MEDICINE 13 HIGH ALTITUDE MEDICAL PROBLEMS and make frequent trips to sea level for vacations clinical pulmonary edema, therefore, can be esti- or business purposes. Questionnaires were sent mated to occur at least three times as frequently to families living in the area asking for details as the more severe form. about altitude exposure, trips to sea level and occurrence of HAPE in their families during the Altitude of Occurrence and Acclimatization preceding year. A total of 860 exposures to high High altitude pulmonary edema rarely occurs altitude in 95 persons was reported. An exposure below 8,000 feet and the incidence increases with was defined as a rapid ascent to 12,300 feet or altitude. Episodes occurring between 8,000 and higher from sea level either for the first time or 10,000 feet are usually related to heavy physical after a sea level visit of greater than two weeks. exertion, but at higher altitudes pulmonary edema The overall incidence of HAPE during 860 ex- occurs with only light activity or even at rest. HAPE posures to high altitude was 3.4 percent. It oc- rarely develops in persons who are acclimatized curred in two of 50 adults (4 percent) and in 17 for one to two weeks except at very high altitudes. of 45 subjects younger than 21 (38 percent). At the base camp in 1963, several No cases affecting children less than 2 years old thoroughly acclimatized members of the party had occurred. Three of the younger group had a total clinical signs of mild pulmonary edema after of nine repeat episodes of HAPE. For a single strenuous climbing during the day. These signs ascent, the estimated chance of HAPE is 6 percent disappeared after bed rest and low-flow oxygen for persons less than 21 years old and 0.4 percent administration during the night. HAPE is rare in for persons older than 21. fully acclimatized residents of high altitude regions The incidence in Indian troops transported by unless there is rapid ascent to a higher altitude. air to altitudes above 11,500 feet was 5.7 per- cent in another study. If travel was by automo- HAPE During Reascent bile, the incidence was 0.3 percent. About half In fully acclimatized persons who descend to the patients were between 20 and 29 years old.22 sea level and then return to high altitude, HAPE Singh has reported an incidence of 13 percent to may develop on reascent. HAPE during reascent 15 percent in troops moved rapidly to altitudes is rare when the sea-level sojourn is less than 10 of 11,000 to 18,000 feet.2' The incidence was to 14 days,'8'2'22 Pulmonary edema during re- similar for men going to high altitudes for the ascent may occur more frequently than pulmo- first time and those who were returning from a nary edema during initial ascent to high alti- furlough at lower altitudes. tudes,20 but further data are needed to settle Previous studies from Peru have also shown a this point. high incidence of HAPE in children and adoles- cents compared with adults."8 The characteristics Susceptible Persons of HAPE occurring in children have been de- Some persons seem to be susceptible to HAPE scribed.24,2' The incidence of HAPE in women is and may have recurrent episodes when again low, but for children there is no sex dominance."8 ascending to high altitude.'8 28 In the study in La Studies in Leadville, Colorado, (10,150 feet) Oroya, Peru, 20 percent of patients with HAPE have also shown a higher incidence of HAPE in had experienced at least one previous episode.28 children.26 Physiologic studies have indicated that in persons Subclinical HAPE with a history of HAPE there are an abnormal rise in The data described refer only to obvious HAPE pulmonary arteriolar resistance and an impaired severe enough to require medical attention. If oxygen exchange during acute altitude exposure one includes subclinical HAPE, the true incidence that are not observed in normal subjects.'" In will be substantially higher than indicated. Hous- susceptible persons there is also a more pro- ton has made observations of climbers before and nounced rise in pulmonary artery pressure and after an ascent to Mount Rainier, Washington arteriolar resistance than in normal persons dur- (14,408 feet). Of 140 subjects, 15 percent had ing low oxygen .27-29 pulmonary rales after descent, suggesting the presence of mild pulmonary edema.'8 Singh noted Treatment that about a third of patients with severe acute Prompt recognition of the syndrome, bed rest, mountain sickness had pulmonary rales." Sub- descent to a lower altitude and oxygen adminis-

14 JULY 1979 * 131 * I HIGH ALTITUDE MEDICAL PROBLEMS tration are the most effective methods of therapy H. R. for HAPE.20'80 160 o Cedilanid IV. Recognition 1Contlnuous 02 Severe HAPE and many fatalities among moun- 120. tain climbers have occurred because initial symp- toms have been ignored or concealed, or because 100- pneumonia has been incorrectly diagnosed. Rec- 80 \\ ognizing early symptoms permits prompt initia- tion of therapy and may prevent progression to 60 a more serious stage. 1 I} 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 12 Bed Rest (PM) (AM) Absolute bed rest is important in therapy be- Figure 3.-Effect of digitalis and oxygen upon the heart rate in acute severe high altitude pulmonary edema cause physical exercise will aggravate HAPE by studied at 12,500 feet. Cedilanid, 0.3 mg given intra- increasing pulmonary artery pressure and reduc- venously, was administered in doses two hours apart arterial oxygen saturation. Results of studies as shown by the arrows. There were no changes in ing physical signs and dyspnea became worse. Prompt re- in Peru have shown that HAPE can be treated with lief of symptoms and clinical improvement occurred bed rest alone at high altitude, without oxygen with 100 percent oxygen (third arrow). (Reprinted from administration or descent.20 In severe cases, re- Hultgren,38 p 477, by permission of Marcel Dekker, Inc.) covery is slower with bed rest than when oxygen is used. Mild cases of HAPE can be treated at high increase arterial oxygen saturation, lower pulmo- altitudes without descent by one to two days of nary artery pressure, reduce heart rate and respir- bed rest. Serial examinations of the chest and atory rate, and relieve symptoms. In field con- measurement of heart rate and respiratory rate, ditions oxygen can be effectively administered as well as evaluation of symptoms, are necessary; with a plastic face mask.30 High flow rates of 6 if deterioration occurs, there should be prompt to 8 liters per minute should be used for the first assistance to a lower altitude. 15 to 30 minutes because of the rapid respiratory rate. To conserve oxygen, rates of 2 to 4 liters Descent to a Lower Altitude per minute can be used for 12 to 48 hours until There are many reports of persons with HAPE recovery or evacuation to a lower altitude. Rescue whose conditions have improved on descent to a teams or helicopters should carry oxygen to the lower altitude. A descent of even 2,000 or 3,000 victim so that therapy can be begun immediately. feet may result in improvement because at high Treatment by descent and administration of oxy- altitude oxygen saturation lies on the steep part of gen has been described vividly in a severe case of the oxygen-dissociation curve and small changes HAPE occurring during the 1969 American Dha- in altitude and resultant pressure of inspired oxy- ulagiri expedition.3' New lightweight portable gen (Pio2) will be accompanied by major changes oxygen tanks are available (see Acute Mountain in arterial oxygen saturation. For climbing par- Sickness section). ties at high altitude, descent to a lower altitude may be the only method of treatment available. Therapy Early recognition of mild symptoms will permit Evaluating the effect of drug intervention in the victim to be helped to a lower altitude before cases of HAPE is difficult for several reasons: serious HAPE occurs and the victim is unable to (1) HAPE usually occurs in the mountains, where walk. If symptoms are severe, evacuation by a facilities for systematic studies are not available. litter will be necessary because the effort of climb- (2) Treatment by bed rest, removal to a lower ing down may increase the severity of HAPE. altitude or oxygen administration may be done at the same time; consequently, the effect of drug Oxygen intervention alone cannot be evaluated. (3) No The administration of 100 percent oxygen is animal model of HAPE is available that would the most effective and rapid method of treating permit proper investigation of drug intervention. HAPE (Figure 3). Results of studies in Peru have (4) Anecdotal reports of alleged successful use shown that oxygen administration will rapidly of drugs are common and tend to be repeated in

THE WESTERN JOURNAL OF MEDICINE 15 HIGH ALTITUDE MEDICAL PROBLEMS the literature, whereas failure of drug therapy is tude pulmonary edema is being reported with rarely reported. increasing frequency in places where unacclima- such as furosemide have been used tized persons travel rapidly to high altitudes. in patients with HAPE, and workers in India have These places include Colorado ski areas, Khli- recommended furosemide for prevention and manjaro and Mount Kenya in Africa, the Mount treatment of HAPE. There are several physiologic Everest base camp in India, and the Argentinian features that suggest that a would be of and Peruvian Andes. Houston recommends one limited value in treatment: (1) Blood volume is day per 500 feet of ascent from 9,000 feet and low due to fluid loss into the lungs, fluid loss by above, interrupted by a day of partial rest at the respiratory tract and inadequate fluid intake. 14,000 and 18,000 feet.16 This pace may be too (2) Cardiac output and systemic blood pressure slow. Experienced Himalayan trekkers advise are low. (3) Left ventricular failure is not pres- two rest days during an ascent from 11,000 to ent. In these circumstances, a further decrease in 15,000 feet. plasma volume by diuresis may lower blood pres- Heavy physical activity on arrival at high alti- sure, cardiac output and perfusion of vital organs. tude should be avoided during the first two to In the mountains this may result in a patient's in- five days, especially if ascent has been rapid. Mild ability to walk; consequently, there may be diffi- cases of HAPE may be treated at high altitude by culty evacuating the patient.'7 Furosemide therapy one to two days of bed rest provided that de- has been shown to be of no value in preventing terioration does not occur. acute mountain sickness, and it results in a high in- In well controlled studies,36 it has been shown cidence of postural hypotension and syncope.32'33 that use of acetazolamide reduces the incidence The degree of body hydration has shown no re- and severity of acute mountain sickness. Side lation to the incidence of severity of acute moun- effects are minimal and disappear when adminis- tain sickness.34 Proponents of diuretic therapy tration of the drug is stopped. Results of pre- argue that furosemide has a dilating effect in the liminary studies have suggested that acetazola- veins and may also reduce cerebral edema. These mide may be of value in preventing recurrent effects have not been shown in patients with HAPE. HAPE in susceptible persons, but other workers With no clear evidence of benefit and with the have noted failure with this .33 Aceta- potential of harmful side effects, it is prudent not zolamide, in a dose of 250 mg, is administered to use diuretics for preventing or treating HAPE once or twice a day beginning on the day of until further data are available. ascent and continuing for three to five days after has also been used in treating HAPE, arrival at high altitude. Administration of the probably because of its traditional use in cases of drug should not be continued for more than seven cardiac pulmonary edema.21'22'35 The use of mor- days. One 250 mg dose of acetazolamide at night phine in HAPE has not been subjected to ade- may promote more restful sleep. quately controlled studies and, until beneficial Furosemide and other diuretic agents have not effects have clearly been shown, its use should been shown to be valuable in preventing HAPE. be avoided. Unfavorable effects have been re- ported. The depressant effect of morphine on Physiologic Features ventilation could increase the severity of hypoxia, . Pulmonary hypertension due an important cause of HAPE. to an increased pulmonary vascular resistance is Other drugs such as digoxin, isoproterenol pre- consistently found in patients with HAPE. Pulmo- parations and have no proven value in nary artery wedge and left atrial pressures are the treatment of HAPE. normal or low.'3'37 Cardiac output is decreased and systemic blood pressure is low. Right atrial Prevention pressure is normal or occasionally raised. Blood Because the occurrence of HAPE is related to pressure response to the Valsalva maneuver is the speed of ascent, the altitude reached and the normal.'4 amount of physical exertion at high altitude, the Hemodynamic studies of persons who have most effective means of prevention is acclimatiza- recovered from HAPE have shown normal values tion-either by slow ascent or a sojourn of sev- and normal responses to exercise. Data from a eral days at an intermediate altitude. High alti- few patients suggest that a rise in pulmonary

16 JULY 1979 * 131 * 1 HIGH ALTITUDE MEDICAL PROBLEMS artery pressure during exercise and during acute Cerebral edema related to severe hypoxia may hypoxia may be greater than that in normal occur.16"17,2 persons. Blood Gases. Arterial oxygen saturation is de- Causes creased with HAPE, often to very low levels. The The causes of HAPE must be considered within carbon dioxide pressure is decreased or normal the framework of the following well-established and the pH is increased.37-39 Exercise or induced features of this unusual form of pulmonary hypoxia results in an increase in pulmonary artery edema: (1) a rapid rise in pulmonary artery pressure and a fall in arterial oxygen saturation. pressure due to high altitude ascent, with a low Administration of 100 percent oxygen is ac- pulmonary artery wedge and left atrial pressure; companied by a prompt rise in arterial oxygen (2) acute hypoxic pulmonary arteriolar vasocon- saturation but normal values are usually not at- striction, which is reversed on breathing oxygen; tained; this suggests that there is intrapulmonary (3) absence of left ventricular failure or pneu- shunting. Oxygen administration will rapidly lower monia; (4) pronounced pulmonary capillary con- pulmonary artery pressure, but normal levels are -gestion and presence of capillary and arterial not usually attained. thromboses in many fatal cases; (5) harmful effect of heavy exercise, but improvement with bed rest. Pathologic Conditions In 1966 the author proposed the following Autopsy findings in fatal cases of HAPE have concept of the etiologic factors in HAPE.88'42 It been reported by several workers.24404' Severe, was proposed that the primary cause of HAPE confluent pulmonary edema is present, with a was nonhomogeneous obstruction of the pulmo- -rich exudate filling the alveoli. In some nary vascular bed by hypoxic vasoconstriction cases fibrinous intraalveolar exudates or hyaline and possibly intravascular thromboses. During membranes are present that are like those seen periods of exercise and increased pulmonary in influenzal pneumonia in patients with mitral blood flow, unobstructed areas of the pulmonary stenosis, or in the respiratory distress syndrome circulation would be subjected to high pressure of infants. Such deposits are usually found when and flow; the precapillary arterioles would be- very high capillary pressures occur or when capil- come dilated, permitting the high pulmonary larly injury is present with increased permeabil- artery pressure to be transmitted directly to the to capillary bed, with resulting interstitial and alve- ity protein. Hemorrhage into alveoli may olar of occur. Pronounced capillary congestion and dis- edema. With dilation arterioles and cap- illaries, pulmonary veins may then become the tension of capillaries by erythrocytes is commonly which found. Obstruction of capillaries and arterioles site of resistance to flow, would also result by thrombi consisting of platelet aggregates, leu- in a high capillary pressure. Therefore, an im- kocytes, red cells and fibrin strands or clumps portant mechanism of HAPE is failure of hypoxic have been described. Numerous megakaryocytes vasoconstriction and dilatation of nonconstricted vessels in local areas of the lung. A similar con- may be present in such aggregates.24 Notable dila- has been for the mechanism of tation of preterminal arterioles, capillaries and cept proposed small veins hypertensive encephalopathy in systemic hyper- pulmonary has also been observed.40 tension. It is proposed that in this condition cere- Pneumonitis is rare. In one patient with pneu- bral edema is due to failure of cerebral vasocon- monitis the clinical history suggested that a viral striction, permitting a high arterial pressure to be respiratory existed before HAPE OC- transmitted to the capillary bed with resultant curred.24 Pneumonitis may have facilitated HAPE; edema. Failure of vasoconstriction seems to occur pneumonia in experimental animals increases cap- when a very high arterial pressure is present. The illary permeability and susceptibility to pulmo- degree of pressure elevation is thought to be the nary edema. cause. Clinical and experimental evidence sup- The right atrium, right ventricle and large pul- porting this concept is available.4345 monary arteries are usually distended and hepatic congestion may be present. Signs of left ventricle Reports of Cases failure are absent. The left ventricle, left atrium CASE 1. An example of severe, nonfatal pul- and pulmonary veins are not distended. Under- monary edema in a skier is illustrated by the fol- lying cardiac or pulmonary disease is absent. lowing report. A 41-year-old man skied at Mam-

THE WESTERN JOURNAL OF MEDICINE 17 HIGH ALTITUDE MEDICAL PROBLEMS moth, California, during the Christmas holidays. The patient nearly died; previous experience On both December 23 and 24 he skied at altitudes indicates that when mental dysfunction or coma between 8,500 and 10,000 feet. On the afternoon occurs as a result of severe hypoxia, death will of the second day he noted unusual fatigue and occur within a few hours unless descent or oxygen dyspnea, and felt "feverish." On the third day he therapy is initiated. An incorrect diagnosis of felt no better and saw a local . An x-ray pneumonitis complicated the situation. Descent to film of the chest showed "pulmonary infiltrate" a lower elevation when the pulmonary infiltrate and he was given 1.2 million units of penicillin was detected probably would have resulted in intramuscularly. On the fourth day he still felt ill, complete recovery. Atrial flutter is rare in HAPE, a second injection of penicillin was given. He con- but acute right ventricle strain due to acute pul- tinued to ski and on the sixth day he had extreme monary hypertension is common. Right atrial dis- difficulty breathing and was weak. He retired to tention probably contributed to the onset of atrial his room and was found soon thereafter in a flutter. semicomatose state. HAPE in skiers is more common in the Rocky He was taken to a in Bishop, Califor- Mountains, but a previous episode has been re- nia, (altitude 4,100 feet) by ambulance. On ar- ported from the Mammoth Lake area in Cali- rival he was able to respond only to his name. fornia. The altitude of overnight accommodations Pronounced cyanosis was present. Blood pressure there is 8,500 feet and skiers can ascend to was 105/60 mm of mercury, pulse rate was 160, 10,000 feet. No known cases have been observed respirations were 30 per minute and temperature in the Lake Tahoe area where most overnight was 38.4°C (101.2°F). Bilateral, moist, bub- accommodations are at 6,200 feet. HAPE usually bling rales were present in both lung fields. No occurs when skiers sleep above 7,000 feet. other abnormalities were noted. Hematocrit was CASE 2. A 38-year-old healthy man, an ex- 52 percent; leukocyte count was 21,000 per cu perienced mountaineer, was climbing in the Cor- mm, with 80 percent polymorphonuclear neutro- dillera Blanca in Peru. In three days he climbed phils. Arterial blood gas values were oxygen with a heavy pack from 9,000 to 14,000 feet over pressure, 32 mm of mercury; carbon dioxide pres- a series of ridges, one of which was 16,000 feet. sure, 32 mm of mercury; pH, 7.46. Serum en- On the evening of the third day he was more zymes were normal. An electrocardiogram showed tired than other members of the party and had atrial flutter (2: 1 atrioventricular block) and Cheyne-Stokes respirations. The following day he signs of moderate acute right heart strain. Ad- engaged in light activity only, but on the fifth ministration of 100 percent oxygen by face mask day he climbed steep slopes with a heavy pack increased arterial oxygen pressure to 52 mm of to a higher camp. He was far more short of breath mercury. An x-ray film of the chest showed a than other members of the party, and upon ar- normal heart. Numerous fluffy infiltrates were rival at the 16,000 foot camp was tired and list- present in all lung fields especially in the right less and could not eat. He began to cough and mid-lung field where a confluent infiltrate was one of his companions said that he "obviously present. There was no history of cardiac or pul- had fluid in his lungs." He was comfortable only monary disease, or altitude intolerance. in a seated position. Because he was thought to Treatment with bed rest and administration of have pneumonia, he was given penicillin. His 100 percent oxygen and digoxin resulted in rapid breathing rapidly became more labored, and his improvement. On the second hospital day sinus cough became more severe and frequent. His rhythm returned, aterial oxygen pressure was 99 companion, who was not a physician, wrote in his mm of mercury with the patient breathing 100 diary "the next few hours his breathing became percent oxygen, and his mental state was normal. progressively more congested and labored. He On the third hospital day nearly complete clearing sounded as though he were literally in of the infiltrate was noted. The leukocye count his own fluid with an almost continuous loud was 11,000 per cu mm with 60 percent poly- bubbling sound as if breathing through liquid." morphonuclear. During the night his breathing became far worse On the fifth day recovery was complete and the and he lost consciousness. He died at dawn on patient was referred to a medical center in the the second day of illness. His companion stated San Francisco Bay area for further studies. No in his diary "a couple of hours after his death, cardiac or pulmonary abnormalities were noted. when we got up to carry on the day's activities,

18 JULY 1979 * 131 * 1 HIGH ALTITUDE MEDICAL PROBLEMS I noticed that white froth resembling cotton candy Subsequently, many instances of high altitude had appeared to well up out of his mouth." An illness characterized by cerebral and neurologic autopsy done five days after death disclosed find- symptoms and signs associated with mental dys- ings compatible with severe pulmonary edema. At function, confusion, stupor or coma have been the time of this incident high altitude pulmonary observed at high altitudes."1'17'21 Findings from edema had not been recognized, so there was no autopies have shown cerebral edema. Because the prompt evacuation to a lower altitude-which syndrome has sometimes occurred without symp- might have been lifesaving. toms and signs of HAPE, it is likely that cerebral An analysis of 33 instances of HAPE occurring edema represents another manifestation of high in mountain climbers is shown in Table 2. altitude exposure. Data from a small number of cases have shown that , retinal hemor- Cerebral Edema of Hlgh Altitude rhage and increased cerebrospinal fluid pressure In 1959 Chiodi described a patient who had are present. In one instance the symptoms were predominantly neurological symptoms and signs so suggestive of a subdural hematoma or neo- during exposure to high altitude in the Andes.-' plasm that a craniotomy was done. Cerebral Occipital were intense and associated edema was noted and a biopsy of the brain ap- with cervical pain. Tinnitus was troublesome. peared to confirm the gross diagnosis.'7 A pos- Areas of anesthesia and , particularly sible mechanism is the effect-of severe hypoxia on in the arms and legs, were present. Paralysis of the brain with inhibition of the sodium pump and the arms and legs, as well as hemiplegia, occurred. intracellular edema. Cerebral edema has been There was severe pain in the limbs, joints and observed in monkeys subjected to an altitude of lumbar regions. Examination showed cervical 18,000 feet in a low pressure chamber.'8 It has rigidity, ankle clonus, an abnormal Babinski sign, been proved that hypoxia results in cerebral localized areas of cutaneous anesthesia and dila- edema in humans.-' Prompt removal to a low tation of retinal veins. On lumbar puncture, the altitude and use of will result in spinal fluid was bloody but dynamics were nor- recovery. Late neurologic complications are rare mal. Symptoms and signs disappeared promptly and mental processes appear to recover com- on return to sea level. There was no evidence of pletely. unusual polycythemia or alveolar hypoventilation. A cerebral arteriogram and cerebral blood flow Retinal Hemorrhage studies were normal. The usual increase in cere- A study carried out at Mount Logan (17,- bral blood flow in response to low-oxygen breath- 500 feet) in the Yukon Territory in 1968 led to ing was absent and Chiodi suggests that this may the discovery that retinal hemorrhage may occur be a factor in the development of the clinical above 10,000 feet. In most instances symptoms features. are absent, but in some persons there is visual

TABLE 2.-Analysis of 33 Instances of HAPE In Cllmbers Mean Ranre Age ...... 30 years 20 to 43 years Altitude of occurrence ...... 13,670 feet 8,600 to 24,000 feet Duration of ascent ...... 3.9 days I to 11 days Interval before onset of symptoms ...... 3 days 1 to 11 days Most common features ...... Cough (24) (20) Fatigue (16) Confusion, mental changes (16) Gurgling in chest (14) Pulse rate ...... 115 per minute 96 to 170 per minute Duration of edema ...... 5.2 days 2 to 10 days Previous episodes of HAPE . 4 (12 percent) Deaths ...... ,.9 (27 percent) HAPE - high altitude pulmonary edema THE WESTERN JOURNAL OF MEDICINE 19 HIGH ALTITUDE MEDICAL PROBLEMS disturbance (clouding of vision). Ophthalmos- was healthy and there was no history of cardiopul- copy shows retinal hemorrhage which may be monary or renal disease, or unusual edema during multiple, bilateral and occasionally severe enough pregnancies. Her mother and maternal grand- to obscure the macula. Pronounced hyperemia mother both had had periodic edema of the ankle. near the optic disk, tortuousness and increased Within 24 hours of arrival at high altitudes, head- diameter of veins and arteries are present. These ache, nausea, and fatigue appear and changes may occur without hemorrhage. Descent continue for four to six days. On the third to to sea level results in recovery in two to six weeks. fourth day, edema of the face and eyelids usually Permanent visual impairment is rarely observed. appears followed by edema of the feet, ankles and The mechanism is not clear. Afflicted persons may lower legs ("Legs feel heavy"). have no other symptoms and papilledema is not No abnormalities were found on physical ex- always present. Studies done at Mount Logan amination, electrocardiogram, x-ray studies of the have shown that retinal blood flow increases at chest or routine laboratory studies. Serum al- high altitude.50'51 Increased flow and pressure, bumin values were normal. combined with hypoxic injury to the retinal vas- The patient was advised to use acetazolamide, cular bed, are probable causes. Intraocular pres- 250 mg once a day, on the day of ascent and for sures are normal.52 Retinal hemorrhage has been three days after arrival. Acetylsalicylic acid and observed in hypoxic states in persons at sea level. a compound of acetylsalicylic acid, phenacetin Carbon monoxide poisoning is frequently ac- and (Empirin Compound) were pre- companied by retinal hemorrhage. scribed for headache. Furosemide, 40 mg, was suggested for use if edema appeared. Systemic Edema at High Altitudes The following summer the patient reported the Asymptomatic edema of the face, hands and results of a two-week return trip to the High feet, associated with a weight gain of 4 to 12 Sierras. The patient was in a premenstrual period pounds for four to ten days at high altitudes, is and menstrual flow began eight days after arrival most common in women. Puffiness of the face at high altitude. She took 250 mg of acetazola- and eyelids in the morning after sleep may be mide on the day of ascent and once a day for troublesome and unsightly. Edema may occur in four days after arrival. A minor headache was the absence of other symptoms of altitude illness. noted on the fourth and fifth days, as well as In susceptible persons repeated episodes during slight numbness and tingling of the finger tips. On each exposure to altitude are common. Upon the sixth and seventh days moderate edema of return to sea level, diuresis with weight loss oc- the face, eyelids and lower legs appeared. Furo- curs. Edema may persist for one to three days semide, 40 mg, was taken once a day for two after return to a lower altitude. The cause is not days and resulted in diuresis and complete relief clear. There appears to be no relation to the of edema. Five days later edema returned; the menstrual cycle or the use of birth control pills. patient descended to sea level and spontaneous It is possible that sodium and water retention is diuresis occurred with loss of edema. The patient stimulated by the decrease in plasma volume that said that this was her "first fully enjoyable trip occurs during high altitude exposure.53-55 Pub- to the mountains in many years." Numbness and lished data regarding this syndrome are minimal tingling of the fingers are common side effects of and studies of etiologic mechanisms are clearly acetazolamide therapy. The second episode of indicated.56'57 edema should have been treated with furosemide. Prevention and treatment by the use of furo- semide or other diuretic agents is usually effec- Thrombotic Disease of High Altitude tive. Salt intake should be reduced. Exposure to very high altitudes may be ac- The following illustrates the prob- companied by or cerebral lem of systemic edema at high altitude associated . During the first attempt by Houston's with AMS. Relief was obtained by the use of group to climb in Kashmir, pulmonary em- acetazolamide and furosemide. bolism developed in one of the climbers and he CASE 3. A 48-year-old housewife has had "al- died during descent. At 22,000 feet on Makalu, titude sickness" for several years during annual Hillary sustained a transient and had to two-week backpacking trips to the Sierra Nevadas descend. Other episodes have been described by at altitudes between 8,000 and 10,000 feet. She Ward.58 Such complications are rare but are most

20 JULY 1979 * 131 * 1 HIGH ALTITUDE MEDICAL PROBLEMS likely to occur at very high altitudes, especially tion may ascend to moderate altitudes without in bad weather when prolonged stay in a tent serious symptoms or deterioration in pulmonary with no activity and inadequate fluid intake are function. If arterial unsaturation is present at sea common. level, it will increase at high altitude. Houston Thrombotic obstruction of the pulmonary vas- studied eight cases of mild to moderate chronic cular bed may play a role in causing HAPE. Studies obstructive disease at sea level and at 6,340 feet. of changes in clotting factors in persons ascend- Arterial Pao2 at sea level was 66 mm of mercury. ing to high altitudes have indicated that there This dropped to 52 mm at high altitude, and dur- may be evidence of increased coagulability or ing exercise a Pao2 of 47 mm was noted.63 It is thrombosis.59-6' possible that some patients with obstructive air- way disease may do better at high altitude be- Effect of High Altitudes on Sea Level cause of the reduced air density. Medical Problems Airline travel may have the same effect as acute Several medical conditions clearly are ad- high altitude exposure with equivalent altitudes versely affected by high altitudes: (1) primary of between 1,000 and 8,000 feet. Cabin altitudes pulmonary hypertension, (2) cyanotic congenital rarely exceed an equivalent elevation of 8,000 feet, heart disease, (3) chronic pulmonary disease with but at this altitude the arterial Po, is 55 mm of arterial unsaturation, (4) coronary artery disease mercury. A patient with pulmonary disease should with severe angina or cardiac failure, (5) con- not undertake long airline flights unless the arterial gestive failure with arterial unsaturation. Po2 and Pco2 are at reasonable levels at sea Patients with primary pulmonary hypertension level. In doubtful cases, oxygen must be available who have decreased arterial oxygen saturation, or during the journey. Recommendations to airlines in whom there is a rise in pulmonary vascular and patients should be specific. High concentra- resistance with hypoxia, should not be exposed to tions of oxygen should not be used because of the even moderate altitudes. Symptoms of patients danger of carbon dioxide retention. A Venturi living at high altitudes will usually improve when mask which delivers from 25 percent to 30 per- they move to sea level.62 cent oxygen is recommended.64 In patients with even modest degrees of arterial Patients with pneumothorax should not fly or unsaturation, pronounced decreases in oxygen sat- ascend to high altitudes. Hazards of high altitudes uration may occur with exposure to only moder- were more common in earlier years when thera- ate altitudes. This is due to the fact that they are peutic pneumothorax or pneumoperitoneum was on the steep part of the oxygen dissociation curve used in treating tuberculosis, and cabin altitudes where a modest change in inspired Po2 will cause in aircraft were higher. greater changes in arterial saturation than occurs Chronic high altitude exposure does not have in normal persons. an in persons with essential hyper- In patients with coronary disease or cardiac tension. Several studies have shown that systolic failure, hypoxia will not only decrease oxygen blood pressure is lower in normal residents at supply to the myocardium but will increase car- high altitude than in a similar population at sea diac work by an increase in heart rate and an level." 62'65 Systolic pressure is decreased more increase in the work of breathing. than diastolic pressure. Cardiac output is normal.' When patients with one of the conditions men- Results of studies in persons who have moved tioned above must travel to high altitudes for a from sea level to the Peruvian Andes have shown short time, or must travel long distances by air, that after five to ten years of living at high alti- oxygen should be provided to relieve symptoms tudes the expected rise in blood pressure with in- if necessary. If the disease is mild, patients may creasing age does not occur. Instead there is a be permitted to travel to high altitudes for a short major fall in systolic pressure and a lesser de- time. They should be cautioned to avoid physical crease in diastolic pressure.66'67 Results of one activity for the first two to three days, to use study have shown no adverse effect of high alti- oxygen if necessary and to descend if symptoms tude exposure in patients with essential hyper- persist. High altitudes can be tolerated by many tension. patients after an initial rest of a few days. In patients with sickle cell disease or sickle cell Patients with chronic obstructive pulmonary trait an increase in sickling or splenic infarction disease who do not have notable arterial unsatura- may develop at high altitude. Although elevations

THE WESTERN JOURNAL OF MEDICINE 21 HIGH ALTITUDE MEDICAL PROBLEMS of 15,000 feet must be attained to reduce the ing area of research. Our knowledge of most alti- capillary oxygen tension to a level where sickling tude problems is still in the stage of infancy. For will occur (Po2, 10 to 15 mm) episodes of sickle readers interested in other sources several refer- cell crises have been observed in Peru at eleva- ences can be highly recommended. In Barometric tions between 3,500 and 4,500 meters (11,483 Pressure by Bert, some of the earliest experiments and 14,764 feet).68 relating to hypoxia and altitude exposure are Despite the large number of patients with mild recorded.72 In Life of Man on the High Alps by or moderate chronic disease, as well as the elderly Mosso, the earliest experiments done in the moun- persons who travel to high altitude regions, our tains of Europe are recorded.73 Barcroft's Lessons knowledge of the effect of high altitudes in such from High Altitude describes the first scientific situations is woefully inadequate. Further re- studies done on the effects of high altitudes on search in this area is clearly needed. persons in the Andes." Mountain Medicine by Ward and Effects at Man at High Altitude by Heath and Drug High Altitudes Williams are recent publications that summarize Another area in which our knowledge is defici- much of our current knowledge about high alti- ent is the effect of high altitudes in persons using tude exposure.58'74 common . Barbiturates, for example, REFERENCES may have a greater soporific effect at high alti- 1. Banchero N, Sime F, Pefialoza D, et al: Pulmonary pressure, cardiac output, and arterial oxygen saturation during exercise at tudes than at sea level and should be used with high altitude and at sea level. Circulation 33:249-262, Feb 1966 2. West H, Lahiri S, Gill M, et al: Arterial oxygen saturation caution. The depressant effect of such drugs on during exercise at high altitude. J Appl Physiol 17:617-621, Jul 1962 respiration during sleep may accentuate 3. Vogel J, Weaver W, Rose R, et al: Pulmonary hypertension hypoxia on exertion in normal man living at 10,150 ft. (Leadville, Colo- and result in increasing the severity of AMS. rado). Med Thorac 19:461-477, 1962 4. Powles A, Sutton J, Gray G, et al: Ventilatory responsive- It is well known that a person's tolerance to ness at sea level and sleep at altitude (abstract). Clin alcohol is diminished at altitude. Part of Res 25:672A, Dec 1977 high this 5. Jarcho S: Mountain sickness as described by Fray Joseph effect may be due to diminished by De Acosta, 1589. Am J Cardiol 2:246-247, 1958 6. Barcroft J: Respiratory functions of the blood, In Lessons the . from High Altitudes, Vol I. London, Cambridge University Press, Problems of anesthesia at 1925 high altitude have 7. Hackett P, Rennle D: The incidence, Importance and pro- phylaxis of acute mountain sickness. Lancet 2:1149-1154, Nov been reviewed by Safar and Tenicela.09 Prolonged 27, 1976 effects from hypnotic agents, opiates and bar- 8. Evans WO, Robinson SM, Horstman DH, et al: Ameliora- tion of the symptoms of acute mountain sickness by staging and biturates may occur and may be partly corrected acetazolamide. Aviat Space Environ Med 47:512-516, May 1976 use 9. Carson RP, Evans WO, Shields JL, et al: Symptomatology, by the of oxygen. Many and medi- pathophysiology and treatment of acute mountain sickness. Fed cal facilities are located at high altitudes, such as Proc 28:1085-1091, May-Jun 1969 10. Falchuk K, Lamb T, Tenney S: Ventilatory response to at , (12,000 feet) and Cerro de hypoxia and C02 following C02 exposure and NaHCOa ingestion. J Appl Physiol 21:393-398, Mar 1966 Pasco, Peru (14,200 feet). 11. Pefialoza D, Sime F: Chronic cor pulmonale due to loss of altitude acclimatization (chronic mountain sickness). Am J Med Patients who are receiving oral 50:728-743, Jun 1971 agents should check their prothrombin levels fre- 12. Arias-Stella J, KrUger H, Recavarren S: of chronic mountain sickness. 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22 JULY 1979 * 131 * 1 HIGH ALTITUDE MEDICAL PROBLEMS

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