High Altitude Medical Advice for Travelers

Treatment of Altitude Illness

Pressurization and Oxygen

It was once written that altitude illness had three treatments: descent, descent, and descent. Descent remains the critical treatment of all altitude syndromes, but the availability of bottled oxygen, the invention of pressurization bags, and the recognition of the value of three medications—acetazolamide, nifedipine, and dexamethasone--have expanded the choices when confronted with altitude illness.

Descent invariably improves altitude illness. However, in severe cases, descent must continue either until clear signs of improvement are recognized, or the person is below the altitude at which his symptoms have started. As mentioned above, it is not necessary to descend until all symptoms are gone, as this can take up to 48-72 hours to take place. Any sign of improvement usually heralds the crossing of the acclimatization line, and further improvement can be expected.

Pressurization in a commercial pressurization bag effectively mimics descent. The first commercial pressurization bag was created by Igor Gamow in the late 1980’s. Approximately 24" by 80" in size, with an airtight zipper, the bags are inflated by a rafting foot pump. An automatic blow-off valve limits the inside pressure to 2 pounds per square inch, and the steady leaking of air through the valve requires continuous pumping, which assures a steady flow of fresh air inside (usually about 10-15 pumps per minute). The amount of descent achieved within the bag depends on the height at which the descent began, but the amount of descent is usually about 1/3 the current height (that is, the bag lowers someone from 14,000 to about 9000 feet). People generally tolerate being placed in the bag, but people with severe HAPE have difficulty lying flat, which is required in order to fit in the bag.

A treatment of one hour is usually enough to dramatically improve mild to moderate AMS. Relapse occasionally occurs, but often does not. In more severe cases, several hours in the bag may be necessary, and repeat treatments may also be necessary if symptoms relapse. However, treatment in the bag can effectively mimic descent, and a person can be maintained at altitude if descent is problematic due to darkness, cold, storm, or difficult terrain. There are now at least two other commercially available versions of the pressurization bag. Groups contemplating long and committing Himalayan treks or climbs should consider carrying a pressurization bag.

Bottled oxygen is heavy to carry, and there is usually not enough oxygen available to use freely. A highly compressed expedition oxygen bottle at a flow of 2 liters/minute will last for 6 hours. The bottle and regulator can cost over $1000. At 4 liters/minute, which is more likely to be therapeutic for altitude illness, one gains only 3 hours of therapy. The effect of bottled oxygen versus pressurization has been compared and appear to be equal. However, the pressurization bag has the advantage of being able to be used for an indefinite period or to treat multiple patients. In less remote areas, where oxygen supply is not limited, it can be a valuable adjunct to treatment of altitude illness, particularly HAPE.

Acetazolamide (Diamox ®)

Acetazolamide is the medication with the longest history of use for preventing and treating AMS. Initially it was given for three days before ascent, but it is now thought that starting the day before is adequate. Acetazolamide is labeled in the PDR for use in prevention of AMS because adequate placebo-controlled studies have been done. There are only a few small studies supporting the effectiveness of acetazolamide in the treatment of AMS, but plenty of anecdotal experience that it is helpful. The recommended dose in the PDR is 250mg three times per day. This later evolved into 250mg twice a day for both the prevention and treatment of AMS. Recently, experience has been gained in using 125 mg BID to prevent AMS. The advantage of the lower dose is fewer side-effects.

Acetazolamide is a carbonic anhydrase inhibitor and its mechanism of action is thought to be to acidify the blood, causing an increase in respiration centrally. It may also improve symptoms by decreasing the production of cerebral spinal fluid. It works as a diuretic, but this appears to be a side-effect at present, rather than a benefit. People taking acetazolamide invariably notice an increase in urination, and the presence of paresthesias in their fingers and toes (occasionally peri-orally as well). The paresthesias feel as if the digits have been "asleep" and are waking up. When one prescribes acetazolamide, it is important to mention these consistent side-effects, otherwise the person may suspect that they are having an allergic reaction, and needlessly stop the medication.

Acetazolamide is distantly related to sulfa drugs, and people with a known sulfa allergy should not take acetazolamide. However, allergic reactions to acetazolamide are extremely rare. If a person is not sure whether they are allergic to sulfa, and are concerned about whether they can take acetazolamide or not, the drug could be administered in a controlled environment before the trip to see if an allergy exists.

Acetazolamide is also a very effective tool for treating the periodic breathing and sleep apnea that occurs at altitude. Controlled studies showed a marked decrease in both periodic breathing and a concomitant drop in arterial oxygen saturation when acetazolamide was taken prior to bedtime. If a person sleeping at altitude is troubled by awakening with a profound sense of breathlessness, acetazolamide 125 mg at bedtime will effectively eliminate this problem. However, it should be pointed out that there are many reasons that people don’t sleep well at high altitude, including crowded lodges, lumpy ground, going to bed at 7:00 p.m., and so forth. Therefore, a careful history should be taken as to why sleep is difficult at altitude before routinely recommending acetazolamide.

Dexamethasone (Decadron ®)

When HACE was thought to be due to diffuse hypoxic cerebral edema, dexamethasone was often tried to treat severely ill patients. The effects of treatment on comatose patients was not very dramatic, and dexamethasone did not appear to have a very strong role to play in the treatment of altitude illness. Then, a pressure chamber study demonstrated that dexamethasone given prophylactically was effective at preventing AMS. This led to field studies that demonstrated that dexamethasone was also effective at treating mild to moderate AMS, and even improving HACE prior to the onset of coma.

Since then, people have used dexamethasone prophylactically and therapeutically in the field. A comprehensive hypobaric pressure chamber study by Levine re-confirmed the efficacy of dexamethasone in preventing AMS, but failed to show any physiologic improvement within the subjects who were being treated with dexamethasone. In other words, the subjects felt better, but were not better acclimatized in any demonstrable way. This study is an additional source for caution in attempting to use dexamethasone to facilitate ascent.

Currently, it is felt that dexamethasone can be safely used to facilitate the evacuation of someone with relatively severe AMS or HACE. Once dexamethasone is given, the person should not move up to sleep at a higher elevation until dexamethasone has been discontinued for 24 hours or more.

Nifedipine

Nifedipine is a calcium channel blocker that effectively lowers pressure in the pulmonary artery. Initial studies in Italy showed a dramatic improvement of HAPE in a group of people who get HAPE easily and volunteered to climb rapidly to over 15,000 feet. The following year, the same cohort were able to demonstrate that nifedipine was effective at preventing HAPE if taken prior to ascent. Thus, nifedipine has been added to the list of drugs known to be effective in treating altitude illness. However, anecdotal reports from the Himalayan Rescue Association aid post in Pheriche, Nepal, located at 14,000 feet, suggest that the effect of nifedipine on HAPE is not dramatic in that setting, and should not be relied upon to be life-saving, in the absence of other therapy.

Other Treatments

No physician who has ever treated congestive heart failure can resist the urge to give furosemide to someone in severe HAPE. The effectiveness of furosemide in HAPE has never been demonstrated in controlled studies, but the earliest use of this drug in HAPE, by Singh et al in India suggested a beneficial effect. Although not confirmed as effective in HAPE, it has been my experience that no doctor can resist giving it if it is available. Physicians opting to give furosemide for HAPE should bear in mind that all persons at high altitude tend to be dehydrated from the insensible fluid loss, and could be come orthostatic or collapse from a strong dose of furosemide. Therefore, furosemide is most safely used after an intravenous line has been established, and fluid is available.

Morphine has been used gingerly at altitude as an adjunct to treatment for HAPE. Physicians should be aware of the potential for respiratory suppression and worsening of the patients condition. However, Singh noted that the use of morphine during the treatment of HAPE at altitude was safe, and made the patients feel better more rapidly than oxygen therapy alone. Positive end expiratory pressure (PEEP) has been used during HAPE at altitude, and was associated with a beneficial response. However, it requires a special mask to be carried, and there are not enough case reports to comment on its use in the field.

Effect of High Altitude on Pre-Existing Medical Conditions

Very few studies have been carried out to measure the direct effect of altitude on various medical conditions. The following advice is based on the few existing studies and anecdotal observations. In general, the more severely limited a person’s exercise is limited at sea level, the less well they are going to do at altitude. If traveling to altitude is important to the patient—for example to visit relatives, work, or because of a love of the mountains—the patient should initially go to high altitude areas that have excellent medical care available. An intermediate altitude should be tried first to see if the exposure to altitude can be tolerated.

Some high altitude areas, such as trekking regions in Nepal, add a significant factor of remoteness. Patients who may be nervous about pre-existing conditions may not do well, knowing that if they have a problem they are 24-48 hours or more from medical help. Individual counseling, describing the potential exposure and remoteness and the patient’s motivation for going are the best way to resolve these issues. If the medical practitioner does not have the expertise or experience to counsel a patient regarding a remote high altitude exposure, try to identify someone in the community or on the internet who could help give some advice in individual cases.

Cardiovascular System

Because high altitude is an inherently hypoxic environment, most physicians are concerned about the effect of high altitude on various cardiac conditions. Some have even urged that older travelers undergo a stress ECG prior to being approved for a high altitude trek. We can divide our concerns into two categories: those persons who have no known heart disease, but who might be at risk due to age; and those persons with documented cardiac disease.

People with no known cardiac disease have not been shown to be at increased risk of new symptoms when traveling to high altitude. A study of trekking deaths in Nepal from 1984-1987 found very few deaths from apparent coronary disease. An accompanying editorial cited other evidence from the European Alps, and factoring in the lack of sensitivity and specificity of the stress ECG test, concluded that the predictive value of a stress ECG in preventing a new ischemic coronary event at altitude would be about 1/1,000,000. Researchers have noted that there is an initial increase in catecholamines in the first few days at a new altitude, which decreases after 3-4 days. This could be associated with increased coronary risk, but it is counterbalanced somewhat by a limited maximal heart rate due to the hypoxia. Thus, the heart appears to be somewhat protected from a maximal exertion and therefore maximal risk by a decreased chance of reaching maximal work at high altitude. However, in recent years, documented first myocardial infarctions have occurred in the Khumbu icefall on Mt. Everest, at altitudes of approximately 19,000 feet in extremely fit and previously healthy climbers.

It seems, though, that the risk of new ischemic cardiac events at altitude is extremely low, and there is no evidence that the rate is higher than the background rate of ischemic events in similarly aged persons at low altitude. It further seems that requiring a stress ECG prior to being approved for a high altitude journey does not make sense based on a one in a million chance of accomplishing its goal. A common sense approach to older travelers concerned about performance at altitude would be to investigate their current level of physical activity. If hiking and/or climbing are routine activities for the person involved and their exercise is not limited by any symptoms, there is no reason to be especially concerned about a decision to go trekking to high altitude. If the proposed traveler has a sedentary lifestyle and does not have a feel for maximal exercise, it can be more difficult to predict how that person will react to altitude. Trekking at high altitude involves quite a lot of exertion and some would-be trekkers are simply not fit enough to complete the journey, or to enjoy it even if they can complete it. Encourage people who are contemplating a high altitude journey to undergo a graded training program to prepare for a trek. If the person has no symptoms during this training period, they should be reassured that they should be able to trek safely. The ability to hike steadily for at least 4 hours over steep terrain should be a minimum requirement for trekking in high mountains.

Persons with known cardiac disease should approach high altitude much more cautiously. People with stable angina, controlled by medication, could theoretically visit high altitude, but will feel much more comfortable staying near appropriate medical care. Trying to determine whether one is having angina, breathlessness at high altitude, or HAPE can be extremely difficult at high altitude, and if the person subsequently had a prolonged episode of chest pain, help would be days away. People with angina should not be encouraged to trek.

Persons with a history of successful revascularization of coronary arteries, who are currently exercising without symptoms, have done well at high altitude if they are sufficiently prepared to deal with the psychological burden of remoteness. In other words, they should not have an increased risk of having problems at altitude, but they may feel too nervous to enjoy themselves in a remote third world country.

People with congestive heart failure can experience difficulties at high altitude, since it takes much less stress on their heart to tip the scales adversely. If they wish to visit the mountains, they should be moderate and stay in areas that have medical care readily available.

Blood pressure is increased somewhat as one ascends to high altitude. Systolic pressure is increased more than diastolic. People who are hypertensive and take blood pressure medication should be urged to stay on their medication throughout their stay at altitude.

Pulmonary System

People who have chronic obstructive pulmonary disease (COPD) will have increased difficulties in a hypoxic environment. Although theoretically at increased risk for developing HAPE, they may also be partially acclimatized to hypoxia. People with any significant degree of COPD will not do well at high altitude.

Since HAPE is associated with hypertension, people with primary pulmonary hypertension may not do well at altitude. A rare sub-group of persons who have the congenital absence of a pulmonary artery all got HAPE at relatively low altitude.

People with asthma have been thought to be at theoretically increased risk at altitude due to the possible adverse effects of cold and exercise. However, asthmatics have generally done very well at altitude, possibly due to the greatly decreased presence of allergens at high altitude. However, people with asthma should be cautioned to carry their medications with them at all times.

Neurologic System

There are enough anecdotal reports to suggest that altitude may serve to lower the threshold for having a seizure. Epileptic patients who have been stable for years and eventually gone off their medications have had seizures within a short time of traveling to high altitude. People with no known seizure disorder have had their first ever seizure at high altitude, usually within a few days of arrival. A few of these people have been shown to have a previously unrecognized seizure disorder, and some have had completely normal work-ups after returning home. Although it is impossible to screen people who have never had a seizure, one should make sure that people with a history of seizure disorder are aware that altitude could possibly be a factor in inducing a seizure.

Shlim and Meijer documented three people who had previously unsuspected brain tumors who all became severely symptomatic within 24 hours of exposure to altitude ranging from 9,000 to 13,000 feet. All of the patients had severe symptoms at altitude that persisted after they returned to low altitude. Any severe neurologic deficit that persists after descent should be investigated promptly with a brain scan.

A few people have had subarachnoid hemorrhages at high altitude. Whether these were due to exposure to high altitude, or merely occurred at high altitude is not clearly defined. However, intracerebral blood flow is increased at altitude, and could be a factor in causing a leak in an aneurysm or arterio-venous malformation. One case, in a woman who had just flown into 9,000 feet, presented as confusion leading to headache and then coma, which was then complicated by pulmonary edema. She was felt to have had high altitude illness, but her symptoms persisted after evacuation, and an arteriogram eventually confirmed the correct diagnosis. History of a subarachnoid hemorrhage or an AVM should be a contraindication to traveling to high altitude.

Hematological System

Even moderate altitudes, such as those encountered in airplane travel, can trigger a sickle cell crisis in a person will sickle cell anemia. High altitude is clearly contraindicated in this population. People with low red cell counts could experience difficulty adjusting to high altitude, as their oxygen-carrying capacity would already be low. They would need to proceed with caution. Patients with polycythemia could experience problems at altitude with sludging and a risk of blood clots and embolism.

Endocrine System

Stable diabetics can travel safely to high altitude if they are comfortable with self-monitoring and are willing to pay closer attention than usual to their glucose balance. High altitude can be associated with severe ketoacidosis for reasons that are not yet clear. However, Shlim reported 5 cases of ketoacidosis associated with high altitude (above 16,000 feet), and 3 of these people died⁴. Risk factors for developing ketoacidosis at altitude include intercurrent illness (gastroenteritis, respiratory infection, and altitude illness), and the possible adverse interplay of respiratory alkalosis which could mask a deepening metabolic acidosis. Acetazolamide was used in at least two of these cases, and may have further blocked the body’s attempt to correct the acidosis. A further practical problem for diabetics is the need to keep their insulin supplies at close hand and unfrozen during a long, cold backcountry journey.

Pregnancy

When pregnant women inquire about the risks of altitude on the fetus, there is no data to turn to. However, pregnancy is an emotional issue, and the question needs to be carefully addressed. There are no reported cases of high altitude exerting a negative outcome on pregnancy in a trekker or climber. Oxygen saturation is fairly well maintained up to an altitude of 10,000-12,000 feet. After that, the person approaches the steep portion of the oxy-hemoglobin dissociation curve, and blood oxygen levels drop precipitously. A well acclimatized person at 14,000 feet altitude has a pO₂ of 55 mm hg. A pregnant woman who presented to an emergency room at sea level with a pO₂ of 55 would be immediately placed on oxygen! Because of the rapid drop-off in oxygenation above 12,000 feet or so, we generally recommend that pregnant women avoid exposures above that height. However, there are numerous anecdotal stories of women who have traveled higher while pregnant and gave birth to normal children.

Practitioners who counsel pregnant women regarding high altitude exposure should take into account the following: the outcome of pregnancy is always somewhat uncertain. An adverse outcome could be due to any number of causes, but if the woman chooses to go to high altitude during the pregnancy, she may feel that the high altitude exposure was the cause. Therefore, the woman should carefully weigh the need to go on this particular high altitude trip at this time versus the potential for having regret should there be an adverse outcome of the pregnancy.

If the high altitude exposure is also coupled with traveling in a third world country, the woman should be further counseled regarding the risks of diarrhea and other infectious diseases, as well as the potential for trauma in third world conveyances. Remoteness from medical care could also be a problem if a miscarriage or early labor should occur.

Summary

Clients planning to travel to high altitude can be re-assured that a slow itinerary and awareness of the symptoms of altitude illness can prevent any likelihood of dying of altitude illness. The acclimatization line concept is useful in presenting a more graphical illustration of planning itineraries and evaluating symptoms after they have occurred. Treatment options have expanded in recent years, but none of these options are superior to descent, which should always be the first choice in severe cases, if physically possible.