High-Altitude Illnesses: Physiology, Risk Factors, Prevention, and Treatment

Abstract

High-altitude illnesses encompass the pulmonary and cerebral syndromes that occur in non-acclimatized individuals after rapid ascent to high altitude. The most common syndrome is acute mountain sickness (AMS) which usually begins within a few hours of ascent and typically consists of headache variably accompanied by loss of appetite, nausea, vomiting, disturbed sleep, fatigue, and dizziness. With millions of travelers journeying to high altitudes every year and sleeping above 2,500 m, acute mountain sickness is a wide-spread clinical condition. Risk factors include home elevation, maximum altitude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-acclimatization, genetic make-up, and pre-existing diseases. At higher altitudes, sleep disturbances may become more profound, mental performance is impaired, and weight loss may occur. If ascent is rapid, acetazolamide can reduce the risk of developing AMS, although a number of high-altitude travelers taking acetazolamide will still develop symptoms. Ibuprofen can be effective for headache. Symptoms can be rapidly relieved by descent, and descent is mandatory, if at all possible, for the management of the potentially fatal syndromes of high-altitude pulmonary and cerebral edema. The purpose of this review is to combine a discussion of specific risk factors, prevention, and treatment options with a summary of the basic physiologic responses to the hypoxia of altitude to provide a context for managing high-altitude illnesses and advising the non-acclimatized high-altitude traveler.

Full text

Open Access Rambam Maimonides Medical Journal
RAMBAM GRAND ROUNDS
High-Altitude Illnesses: Physiology,
Risk Factors, Prevention, and
Treatment
Andrew T. Taylor, M.D.*
Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA
ABSTRACT
High-altitude illnesses encompass the pulmonary and cerebral syndromes that occur in non-
acclimatized individuals after rapid ascent to high altitude. The most common syndrome is acute moun-
tain sickness (AMS) which usually begins within a few hours of ascent and typically consists of headache
variably accompanied by loss of appetite, nausea, vomiting, disturbed sleep, fatigue, and dizziness. With
millions of travelers journeying to high altitudes every year and sleeping above 2,500 m, acute moun-
tain sickness is a wide-spread clinical condition. Risk factors include home elevation, maximum alti-
tude, sleeping altitude, rate of ascent, latitude, age, gender, physical condition, intensity of exercise, pre-
acclimatization, genetic make-up, and pre-existing diseases. At higher altitudes, sleep disturbances may
become more profound, mental performance is impaired, and weight loss may occur. If ascent is rapid,
acetazolamide can reduce the risk of developing AMS, although a number of high-altitude travelers tak-
ing acetazolamide will still develop symptoms. Ibuprofen can be effective for headache. Symptoms can
be rapidly relieved by descent, and descent is mandatory, if at all possible, for the management of the
potentially fatal syndromes of high-altitude pulmonary and cerebral edema. The purpose of this review
is to combine a discussion of specific risk factors, prevention, and treatment options with a summary of
the basic physiologic responses to the hypoxia of altitude to provide a context for managing high-
altitude illnesses and advising the non-acclimatized high-altitude traveler.
KEY WORDS: Acute mountain sickness, high-altitude pulmonary edema, high-altitude cerebral edema,
acetazolamide
Abbreviations: AMS, acute mountain sickness; CSF, cerebral spinal fluid; CT, computed tomography; H+, hydrogen ion;
H2CO3, carbonic acid; HACE, high-altitude cerebral edema; HAPE, high-altitude pulmonary edema; HCO3-, bicarbonate; Hg, mer-
cury; HVR, hypoxic ventilatory response; m, meters; mL, milliliters; mm, millimeters; MRI, magnetic resonance imaging; O2,
oxygen; PaCO2, partial pressure of arterial carbon dioxide; PAO2, partial pressure of oxygen in the alveoli; PCO2, partial pressure
of carbon dioxide; PDE, phosphodiesterase; PiO2, partial pressure of inspired oxygen; PO2, partial pressure of oxygen; RQ, respir-
atory quotient; SaO2, arterial oxygen saturation of hemoglobin.
Citation: Taylor AT. High-altitude illnesses: Physiology, risk factors, prevention, and treatment. RMMJ 2011;2(1):e0022.
doi:10.5041/RMMJ.10022
Copyright: © 2011 Andrew T. Taylor. This is an open-access article. All its content, except where otherwise noted, is distributed
under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Conflict of interest: No potential conflict of interest relevant to this article was reported.
* E-mail: ataylor@emory.edu
RMMJ|www.rmmj.org.il 1 January 2011  Volume 2  Issue 1  e0022

High-Altitude Illnesses
High-altitude illnesses encompass the pulmonary
and cerebral syndromes that occur in non-
acclimatized individuals shortly after rapid ascent
to high altitude. The most common of these syn-
dromes is acute mountain sickness (AMS) which is
described in the editorial, “See Nuptse and Die”,
as “vile at best, fatal at worst and an entity to be
avoided”.1 Nuptse, meaning west peak, rises next
to Mount Everest and is commonly viewed from
elevations ranging from 3,000–5,000 meters
(Figure 1). Excluding Antarctica, only 2.5% of the
world’s land mass lies above 3,000 m, yet these
heights attract the tourist, hiker, skier, and moun-
taineer, many of whom dwell near sea-level.1 Mil-
lions of visitors travel to high altitudes every year,
and, with the growth of ecotourism and global ad-
venture travel, ever-increasing numbers of people
of all ages are hiking and climbing to very high
and even extreme altitudes (Table 1). At 3,000 m,
an altitude commonly encountered in ski resorts,
the partial pressure of oxygen (PO2) is only about
70% of the value at sea-level; at 5,000 m, this val-
ue falls to 50% (Table 2). Many high-altitude trav-
elers will be poorly prepared for their trip and na-
ive about the associated risks. This review has two
purposes: the first is to highlight the basic
physiologic responses to high-altitude hypoxia to
provide a context for understanding high-altitude
illnesses; the second is to discuss specific risk fac-
tors, prevention, and treatment options for acute
mountain sickness (AMS) and the potentially fatal
syndromes of high altitude pulmonary and cere-
bral edema so that physicians and health care pro-
fessionals can appropriately advise travelers as-
cending to high altitude. The review is organized
by specific topics to allow the reader to quickly
identify areas of interest.
Figure 1. Nuptse on the right, Lhotse in the center, and Mount Everest to the left rear with the Khumbu ice-fall
and glacier in the foreground.
Table 1.
Definitions of high, very high, and extreme
altitude.
Altitude Meters Feet
High altitude 1,500-3,500 5,000-11,500
Very high altitude 3,500-5,500 11,500-18,000
Extreme altitude above 5,500 above 18,000
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High-Altitude Illnesses
ACUTE MOUNTAIN SICKNESS (AMS)
Acute mountain sickness has been recognized for
centuries. As early as two thousand years ago, a
Chinese official warned of the dangers of crossing
from China into what is now probably Afghani-
stan. Travelers, he said, would have to cross the
“Little Headache Mountain” and the “Great Head-
ache Mountain” where “men’s bodies become fe-
verish, they lose color and are attacked with head-
ache and vomiting”.2 Although high altitude is de-
fined as beginning at an elevation of 1,500 m
(5,000 feet), symptoms are rarely present at 1,500
m but become increasingly common with rapid
ascent to higher elevations. Studies conducted in
Nepal, Colorado, Kilimanjaro, and the Alps show a
prevalence of AMS ranging from 9% to 58%, with
a higher prevalence at higher altitudes (Table 3).3–
7 AMS is typically associated with headache varia-
bly accompanied by loss of appetite, disturbed
sleep, nausea, fatigue, and dizziness beginning
within 12 hours of ascent in two-thirds of suscep-
tible subjects and within 36 hours in the remain-
ing third.3 Although more advanced forms of AMS
may be accompanied by peripheral edema, perior-
bital edema, a change in mental status, ataxia, or
rales, the initial absence of any definitive signs
usually requires clinicians and researchers to rely
on subjective symptoms for the diagnosis.
Symptom rating is reasonably reliable for in-
tra-subject evaluation where a person compares
his or her current symptoms to a base-line status,
but symptom rating becomes much more prob-
lematic for inter-subject comparisons since there
is no standard of discomfort giving the same score
for all subjects. The subjective nature of AMS has
resulted in the development of several self-scoring
grading systems to determine the presence of AMS
and to quantitate its severity.
A very straightforward and common grading
system for diagnosing AMS is the Lake Louise self-
assessment questionnaire (Table 4), with head-
ache and a score ≥ 3 representing AMS, but other
cut-off points and other scoring systems are in
common use.8–12 These scoring systems are not
linearly correlated and do not give equivalent re-
Table 2.
Changes in barometric pressure and inspired PO2 with altitude.*
Meters
Feet
Barometric pressure
mmHg
Inspired PO2
(% of sea-level)
0 0 149 100%
1,000 3,281 132 89%
2,000 6,562 117 79%
3,000 9,843 103 69%
4,000 13,123 90 60%
5,000 16,404 78 52%
6,000 19,685 67 45%
7,000 22,966 58 39%
8,000 26,247 51 34%
9,000 29,528 42 28%
* Adapted from West JB. J Appl Physiol 1996;81:1850-4.
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High-Altitude Illnesses
sults; for this reason, study results are often de-
pendent on the scoring system and cut-off points
used to determine the presence or absence of
AMS. The literature is further complicated by the
fact that many studies are observational investiga-
tions, where the many confounding variables
(home elevation, rate of ascent, etc.) cannot be
taken into account. To avoid the difficulty of con-
trolled and randomized studies in the field, a large
number of studies have also been carried out in
decompression (hypobaric) chambers.
BAROMETRIC PRESSURE, WATER
VAPOR, AND CARBON DIOXIDE
Barometric or atmospheric pressure is usually ex-
pressed in mmHg (mercury) although it is occa-
sionally expressed in torr in honor of Evangelista
Torricelli (1608–1647) who was the first person to
demonstrate that the atmosphere exerts a pres-
sure and can support a column of mercury. One
mmHg is essentially equivalent to one torr. At sea-
level, the barometric pressure is 760 mmHg. The
Table 3.
Prevalence of acute mountain sickness (AMS).
Author
Location
Altitude (m)
AMS
Maggiorini
5
Alps
2,85o
9%
3,050
13%
3,650 34%
4,559 53%
Dean 7 Colorado 2,987 42%
Honigman 3 Colorado 2,000–3,000 25%
Vardy
4
Nepal
3,000–4,000
10%
4,000–4,500 15%
4,500–5,000
51%
0ver 5,000 34%
Karinen
6
Kilimanjaro
2,743
9%
3,760 44%
4,730 58%
Table 4. Lake Louise self-assessment AMS scoring system.*
1. Headache:
None (0) to incapacitating (3)
2. Gastrointestinal symptoms:
None (0), poor appetite or nausea (1), moderate nausea or vomiting
(2), incapacitating severe nausea or vomiting
(3)
3. Fatigue/weakness:
None (0) to severe or
incapacitating (3)
4. Dizziness/lightheadedness:
None (0) to incapacitating (3)
5. Difficulty sleeping (last night):
None or slept as well as usual (0) to could not sleep at all (3)
* Each symptom is graded on a scale of 0–3; the presence of headache plus a score greater than or equal to 3 is
usually considered positive for AMS.8
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High-Altitude Illnesses
percentage of oxygen (O2) in dry air is 20.94%;
consequently, the partial pressure of O2 at sea-
level is 159 mmHg (0.2094 × 760). When air is
inhaled, it is warmed and saturated with water
vapor. At 37°C, the saturated vapor pressure in the
lungs is 47 mmHg regardless of altitude; because
water vapor displaces oxygen and nitrogen, the
partial pressure of inspired oxygen is 149 mmHg
(0.2094 × (760 – 47)). The partial pressure of wa-
ter vapor in the lungs at sea-level accounts for only
6% of the total barometric pressure, but water va-
por becomes increasingly important at high alti-
tudes. On the summit of Mount Everest, where the
barometric pressure is only 250 mmHg, water va-
por accounts for nearly 19% of the total barometric
pressure, further diminishing the oxygen availabil-
ity.13
At rest, the partial pressure of carbon dioxide
(PCO2) in the lungs is 40 mmHg, which further
displaces oxygen. Although the partial pressure of
inspired oxygen at sea-level is 159 mmHg, the
combined effects of CO2, water vapor, and dead
space reduce the partial pressure of oxygen (PO2)
in the lungs to approximately 100 mmHg. Hyper-
ventilation can reduce the partial pressure of CO2
in the lungs below 40 mmHg, thereby allowing the
partial pressure of O2 to rise. This effect is exag-
gerated at altitude. On the summit of Mount Ever-
est where the inspired PO2 is only 29% of its value
at sea-level, alveolar ventilation is increased by a
factor of 5. This extreme hyperventilation reduces
the alveolar PCO2 to 7–8 mmHg, about one-fifth
of its normal value. Because of the reduction of
PCO2, the alveolar PO2 can rise and be maintained
near 35 mmHg, enough to keep the climber
alive.14,15
THE HYPOXIC VENTILATORY RESPONSE
AND CONTROL OF RESPIRATION
At higher altitudes, the rate and depth of ventila-
tion increase to compensate for the reduced par-
tial pressure of oxygen (PO2). This increase in ven-
tilation is termed the hypoxic ventilatory response
(HVR) and is partially mediated by the carotid
body which is located at the bifurcation of the
common carotid artery and is sensitive to dis-
solved oxygen in the blood. The primary stimulus
to breath, however, is not hypoxia; it is hypercap-
nia, an increase in the level of carbon dioxide in
the blood. This stimulus is mediated by potent
chemoreceptors located in the medulla. Although
the blood–brain barrier separates these medullary
chemoreceptors from the arterial blood, the
blood–brain barrier is permeable to CO2. Increas-
es in the arterial pressure of CO2 (PaCO2) and hy-
drogen ion concentration (acidemia) stimulate
respiration, and decreases in PaCO2 and hydrogen
ion concentration (alkalemia) depress respiration.
Through the action of carbonic anhydrase, the
CO2 generated in peripheral tissues combines with
water to form carbonic acid (H2CO3) where it rap-
idly dissociates into hydrogen and bicarbonate
ions as shown below:
H2O + CO2 ()
󰇎
󰇏
H2CO3 ()
󰇎
󰇏
H+ + HCO3-
The reaction rate of carbonic anhydrase (1) is
one of the fastest of all enzymes, and its rate is
typically limited by the diffusion rate of the sub-
strates; ionic dissociation (2) is not subject to en-
zymatic acceleration and is virtually instantan-
eous. In tissues where there is a high CO2 concen-
tration, the reaction proceeds to the right resulting
in increased bicarbonate and hydrogen ion pro-
duction. The hydrogen ions are buffered by deoxy-
genated hemoglobin which binds the hydrogen
ions and delivers them to the lungs. In the lungs
where CO2 is being removed, the binding of oxy-
gen by hemoglobin forces the hydrogen ions off
the hemoglobin, and the reaction is reversed.
The serum pH is proportional to the bicar-
bonate/PaCO2 ratio. Although the PaCO2 depends
on the balance between CO2 production and CO2
elimination, it is highly dependent on the rate of
CO2 elimination.16
PaCO2 ~    
   
Hyperventilation accelerates CO2 elimination
and produces a respiratory alkalosis by lowering
the PaCO2 and raising the pH of the blood. The
decrease in PaCO2 and the resulting alkalosis
combine to act on the medullary chemoreceptor to
decrease ventilation. Consequently, the ventilatory
response to hypoxia, the HVR, becomes especially
important in maintaining oxygen saturation, since
the normal CO2-mediated ventilatory drive is di-
minished by the hypocapnia. The magnitude and
rapidity of onset of the HVR on arrival at altitude
varies considerably from individual to individual,
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High-Altitude Illnesses
and a failure to increase the HVR contributes to
hypoxemia and the development of AMS.17
RENAL ADAPTATIONS TO HIGH-
ALTITUDE HYPOXIA
As described in the preceding section, the initial
response to high-altitude hypoxia is a respiratory
alkalosis produced by hyperventilation. Within
minutes, the kidneys respond to the alkalosis with
an increased excretion of bicarbonate ions; this
renal effect can continue for hours or days and
functions to correct the alkalosis and return the
pH of the serum toward a normal value.
The kidneys also respond to hypoxia by the
secretion of erythropoietin. Erythropoietin leads
to an increase in red cell mass and the oxygen-
carrying capacity of the blood (dissolved oxygen
accounts for only about 2% of the oxygen-carrying
capacity); however, it takes several days before an
increased rate of erythrocyte production can be
measured, and the process is not complete for
weeks or months.14,18 For short-term ascents, the
erythropoietin-mediated increase in red cell mass
is of minor importance, although it is important
for extended expeditions. The hematocrit, not the
total hemoglobin, is increased during short-term
ascents by a reduction in plasma volume caused
by a hypoxia-mediated diuresis; the elevation in
hematocrit increases the oxygen-carrying capacity
per 100 mL of blood.17–20
THE HEMOGLOBIN SATURATION CURVE
AT ALTITUDE
When blood is exposed to a high oxygen pressure
in the lungs, oxygen rapidly and reversibly com-
bines with hemoglobin to form oxyhemoglobin. At
sea-level where the PO2 is approximately 100
mmHg, the arterial oxygen saturation of hemoglo-
bin (SaO2) is 95%–98%. The oxygen–hemoglobin
dissociation curve (Figure 2) shows the changes in
hemoglobin saturation as the partial pressure of
O2 decreases.21 Its sigmoidal shape arises from the
fact that the hemoglobin molecule contains four
heme groups which each react with a molecule of
O2; oxygenation of the first heme group increases
the affinity of O2 for the remaining groups. This
characteristic shape facilitates oxygen loading in
the lungs and oxygen release in the tissues. With
increasing altitude, the SaO2 is initially well main-
tained compared to the PO2 due to the relatively
flat component of the upper portion of the oxy-
gen–hemoglobin dissociation curve. As altitude
increases, the steeper section of the oxyhemoglo-
bin dissociation curve assumes a greater im-
portance, resulting in a more rapid decrease in
SaO2. At 8,400 m on Mount Everest where the
partial pressure of arterial oxygen (PaO2) drops to
25 mmHg, hemoglobin saturation is only 50%.22
The increased oxygen demands of actively me-
tabolizing tissues lead to an increased production
of CO2 and hydrogen ion concentration accompa-
nied by an increase in local temperature and in-
creased levels of 2,3-diphosphoglycerate, all of
which shift the oxygen–hemoglobin dissociation
curve to the right and facilitate oxygen release in
the tissues, while shifts to the left occur under the
reverse conditions. At high altitude, the acute res-
piratory alkalosis arising from hyperventilation
causes a leftward shift in the oxygen–hemoglobin
dissociation curve, increasing arterial saturation
for any given PaO2. This leftward shift improves
oxygen uptake in the lungs more than it impairs
off-loading in the tissues. Under conditions of ex-
treme hypoxia when pulmonary loading is at a
premium, the left-shifted increase in hemoglobin
oxygen affinity helps maximize the level of tissue
oxygenation for a given difference in oxygen ten-
sion between the sites of oxygen loading in the
pulmonary capillaries and sites of oxygen unload-
ing in the tissue capillaries.23
Figure 2. Oxygen-hemoglobin dissociation curve
(adapted from reference 21 and used with permission).
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High-Altitude Illnesses
AMS: CLINICAL FEATURES
The hypoxia of high altitude can lead to sleep dis-
turbances, impaired mental performance, weight
loss, and reduced exercise capacity.
SLEEP
Humans rapidly ascending from sea-level to sleep
at altitudes above 2,500 m often experience dis-
turbances in sleep quantity and quality caused by
a combination of low arterial oxygen levels and
periodic breathing. Periodic breathing, oscillations
in respiratory frequency and/or tidal volume, is a
well documented phenomenon in normal healthy
adults.24 Following rapid ascent to high altitude,
periodic breathing during sleep is almost universal
and contributes to the disturbing dreams, frequent
arousals, awakenings, and subjective sense of
poor-quality sleep often experienced at alti-
tude.25,26 The underlying pattern of periodic
breathing is exacerbated by hypoxia and amplified
by an increased hypoxic ventilatory response. The
resulting hyperventilation leads to a hypocapnic
alkalosis which can depress ventilation even to the
point of apnea. Hypoventilation leads to hypoxia
and a further reduction in oxygen saturation
which, in turn, stimulates hyperventilation and
generates a self-sustaining cycle.26 Via its effect on
the carotid body, acetazolamide leads to a signifi-
cant reduction in periodic breathing, improves
arterial saturation during sleep at high altitude,
and helps to prevent or diminish the symptoms of
AMS.26 Because of the risk of respiratory depres-
sion, sedative hypnotic drugs should be avoided.
MENTAL PERFORMANCE AND CEREBRAL
ATROPHY
The brain normally accounts for 20% of total oxy-
gen consumption. Under the high-altitude condi-
tions of moderate to severe hypoxia, mental per-
formance is impaired.14 Impairment in codifica-
tion and short-term memory is especially noticea-
ble above 6,000 m, and alterations in accuracy
and motor speed occur at lower altitudes.27 Of
greater concern are studies that indicate both am-
ateur and professional climbers ascending to very
high and extreme altitudes are at risk for subcorti-
cal lesions and cortical atrophy.28,29
WEIGHT LOSS AT ALTITUDE
Altitude exposure may lead to considerable weight
loss, which appears to be a function of both abso-
lute altitude and the duration of exposure. Physi-
cal activity, nausea due to AMS, and lack of palat-
able food all contribute to weight loss at altitude,
and this weight loss can be further exacerbated by
gastro-enteritis, upper respiratory infections, and
low temperatures. Initial weight losses of approx-
imately 3% occur at elevations below 4,000 m,
and weight losses up to 15% may occur during ex-
tended stays from 5,000 to 8,000 m.30 The initial
weight loss likely reflects a diuresis and loss of
water. Beyond this initial diuresis, weight loss ap-
pears to be preventable by maintaining physical
activity and an adequate dietary intake; unfortu-
nately, some trekking companies skimp on the
quality and variety of food and contribute to
weight loss by failing to provide an adequate diet.
Above 5,000 m weight loss is probably unavoida-
ble and is mainly a result of muscle fiber atrophy
independent of activity level, possibly related to
the direct effects of hypoxia on protein metab-
olism.30,31
PHYSICAL CONDITION AND EXERCISE
Exercise capacity diminishes with altitude. The
alveolar partial pressure of oxygen is slightly high-
er than the partial pressure of oxygen in the arte-
rial blood, and this alveolar–arterial pressure dif-
ference widens progressively during exercise in
conjunction with an increased cardiac output,
shortened capillary transit time, and greater ven-
ous oxygen desideration. At sea-level, this exer-
cise-induced pressure differential is accompanied
by a ventilatory response that rises out of propor-
tion to increasing oxygen demands; this height-
ened ventilatory response is usually sufficient to
maintain the arterial PO2 and prevent the devel-
opment of hypoxemia.32 Under the hypoxic condi-
tions of high altitude, however, the ventilatory
response is no longer sufficient to prevent arterial
oxygen desaturation with exercise; and even mild
arterial desaturation (< 94% SaO2) is associated
with a significant reduction in maximum oxygen
consumption and endurance performance.33 Max-
imum oxygen consumption is reduced to about
85% of its value at sea-level at 3,000 m, and it falls
to 60% at 5,000 m.14
When combined with rapid ascent, strenuous
exercise and over-exertion are risk factors for
AMS. In a controlled study of subjects experienc-
ing a simulated altitude gain of 3,000 m in a de-
compression chamber, exercise significantly re-
duced arterial saturation (SaO2) and increased the
AMS symptom scores.34 The effect of physical
conditioning in preventing AMS is more difficult
to evaluate since those in good physical condition
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High-Altitude Illnesses
are apt to engage in more strenuous exercise and
undertake more rapid ascent, both risk factors for
AMS. Data suggest, however, that subjects in ex-
cellent physical condition probably have a risk of
AMS similar to that in less highly trained individ-
uals.3,35,36
AMS: RISK FACTORS
AMS is associated with a number of potential risk
factors including home elevation, maximum sleep-
ing altitude, rate of ascent, latitude, age, gender,
physical condition, intensity of exercise, hemoglo-
bin saturation, pre-acclimatization, prior experi-
ence at altitude, genetic make-up, and pre-existing
diseases.
HOME ELEVATION AND MAXIMUM SLEEPING
ALTITUDE
Travelers ascending from sea-level are at higher
risk for AMS than those living at higher elevations.
This difference is illustrated by a study at a Colo-
rado ski resort showing that the risk of developing
AMS was 27% for residents arriving from sea-level
compared to 8.4% for those residing above 1,000
m.3 The risk of AMS increases with sleeping alti-
tude; among mountaineers staying at huts in the
Swiss Alps, the prevalence of AMS ranged from
9% at 2,850 m to 53% at 4,559 m (Table 2).5 These
results are comparable to the prevalence of AMS
among trekkers staying at tea houses in Nepal
which ranged from 10% at 3,000–4,000 m to 51%
at 4,500–5,000 m (Table 2).4 Interestingly, in this
study, the prevalence of AMS decreased from 51%
at 4,500–5,000 m to 34% above 5,000 m (Table
2) and was likely due to self-selection or prior ex-
perience at altitude among those ascending above
5,000 m.
RATE OF ASCENT AND KILIMANJARO
A rapid rate of ascent is an important contributor
to the development of AMS.3 Trekkers in the Ever-
est region of Nepal appear to have a slower rate of
ascent and a lower prevalence of AMS compared
to those climbing Kilimanjaro where the rate of
ascent is more rapid.4,6,37,38 In climbers ascending
to very high altitudes, differences of a few days in
acclimatization can have a significant impact on
the prevalence of AMS, symptom severity, and
mountaineering success.36
At 5,895 m, Kilimanjaro is the world’s highest
free-standing mountain measured from base to
summit. It is popular, easily accessible, and its
location near the equator offers the option of
combining a summit attempt with a safari to
neighboring game preserves. Every year 20,000
climbers try to reach the summit.6 The standard
routes to the summit, with the possible exception
of the Western Breech which requires some
scrambling, are not technical and can potentially
be hiked by anyone in good physical condition. In
spite of the non-technical nature of the climb,
there have been numerous fatalities on this moun-
tain.6 To cut costs and compete effectively, trek-
king companies often schedule relatively rapid
climbs leaving limited time for acclimatization. Of
particular concern is the observation that some
hikers continue to ascend in spite of developing
life-threatening signs of high-altitude pulmonary
or cerebral edema.6 Although not always practical,
current recommendations are to limit the increase
in sleeping altitude to 600 m in a 24-hour period
once above 2,500 m and to add an extra day of
acclimatization for every 600–1,200 m gain in
elevation.
LATITUDE
Latitude affects oxygen availability, hemoglobin
saturation, and the risk of developing AMS. Due to
its rotation, the Earth bulges at the equator; con-
sequently, both barometric pressure and PO2 are
higher at the equator than at the poles. On the
6,194 m summit of Denali in central Alaska, the
barometric pressure is equivalent to barometric
pressure on the summit of a 6,900-m peak in the
Himalayas.39 Because of this effect, at an equiva-
lent elevation climbers will be less hypoxic on Kil-
imanjaro (3°S) or even Everest (23°N) than on
Denali (63°N). If Everest had been situated at the
same latitude as Denali, it could not have been
climbed without supplemental oxygen.
GENDER AND AGE
Men and women appear to be equally at risk for
AMS,4,5,39 although some observational studies
suggest a slightly higher risk for women.3 Older
individuals do not appear to have an increased
risk of AMS;4,36 in fact, one study suggests that
younger individuals may be at higher risk. Eight-
een-to-nineteen-year-olds had a 45% incidence of
AMS at Colorado ski resorts compared to only 16%
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High-Altitude Illnesses
for those between 60 and 87 years of age.3 This
study was uncontrolled, and the results are proba-
bly affected by a greater exercise intensity in the
younger age group. There are no controlled trials
of AMS in children, but the attack rate appears
similar to that in adults.40
INTENSITY OF EXERCISE
As described above, the alveolar–arterial pressure
difference widens progressively with increasing
exercise, leading to reduced hemoglobin satura-
tion at altitude with an increase in the risk and
severity of AMS. 32,34 To decrease the risk of AMS,
strenuous exercise and over-exertion should be
avoided immediately after rapid ascent to high
altitude.
ARTERIAL OXYHEMOGLOBIN SATURATION
Early hypoxemia, a decrease in the SaO2 greater
than that expected for a given altitude, is a risk
factor for developing AMS.41–43 Early hypoxemia
appears to be the result of a diffusion impairment
or venous admixture and can be monitored with a
pulse oximeter (Figure 3).41–43 Individuals with
early hypoxemia should be advised to avoid stren-
uous exercise and, if continuing to ascend, to as-
cend slowly. Pulse oximeters are relatively inex-
pensive and are commonly carried by trekking
companies to monitor SaO2 in individuals with
worsening symptoms of AMS; however, if they are
to be used at very high or extreme altitudes, it is
important to check the calibration. SaO2 meas-
urements below 83% may not have the same de-
gree of accuracy and precision as measurements
with higher saturations.44
Pulse oximeters have a pair of small diodes
that emit light of different wavelengths through a
translucent part of the patient’s body such as the
finger-tip or ear-lobe; based on differences in ab-
sorption of the two wavelengths, the instrument
can distinguish between deoxyhemoglobin and
oxyhemoglobin. To function properly, the pulse
oximeter must detect a pulse since it is calibrated
to detect the pulsatile expansion and contraction
of the arterial blood vessels with the heart-beat.
Inaccurate readings may occur in subjects with
frost-bite, cold digits, or hypovolemia.
PRIOR AMS AND PREVIOUS EXPOSURE TO
ALTITUDE
A prior history of AMS is an important predictor
for developing AMS on subsequent exposures to
comparable altitudes.45 Conversely, a history of
recent or extreme altitude exposure is associated
with a lower risk of AMS (6,962 m).45,46 Self-
selection is likely an important factor; those who
tolerate and enjoy the high mountains without
developing AMS are more likely to repeat the ex-
perience.
GENETIC ADAPTATIONS
Humans have lived and worked at high altitudes
for thousands of years. Perhaps the best known
high-altitude populations are the Sherpas and Ti-
betans in the Himalaya and the Quecha and Aya-
mara in the Andes. Hemoglobin concentration is
higher in the Andean populations than in Hima-
layan highlanders, whereas Himalayans respond
to their hypoxic environment with a higher venti-
latory response.47 These differences are likely to
have a genetic component, although no specific
genetic differences have yet been identified.
Many cellular functions such as protein syn-
thesis are down-regulated by hypoxia, but select
subsets are up-regulated. Prominent among the
up-regulated subsets is the family of genes gov-
erned by hypoxia-inducible factor 1.48 Hypoxia-
inducible factor 1 functions as a global regulator of
oxygen homeostasis facilitating both O2 delivery
and adaptation to O2 deprivation. The first-
discovered example of hypoxia-dependent gene
expression was erythropoietin which leads to an
increased hematocrit and O2-carrying capacity.
Another genetic factor which may contribute to
high-altitude performance is a polymorphism in
the angiotensin-converting enzyme gene that ap-
pears to be more prevalent in elite mountaineers
Figure 3. Pulse oximeter.
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High-Altitude Illnesses
and in endurance athletes than in the general
population.49 Individuals differ widely in their
susceptibility to high-altitude disorders; some suf-
fer the life-threatening complications of high-
altitude cerebral or pulmonary edema at altitudes
as low as 3,000 m, whereas others can climb to
8,000 m without supplemental oxygen. Genetic
influences remain an active area of investigation.50
PRE-EXISTING DISEASES
Recreational travelers, hikers, and skiers with un-
derlying cardiac or pulmonary diseases often seek
advice regarding high-altitude travel. Asymptom-
atic patients with coronary disease generally do
well, although it is probably prudent to avoid
highly strenuous exercise; patients with heart fail-
ure should avoid the hypoxia of high altitude.51
Severe anemia and sickle cell disease are also con-
tra-indications to high-altitude travel.51 The advice
for patients with lung disease depends on the un-
derlying disease, its severity, and the anticipated
altitude and activity level; specific recommenda
tions are contained in an extensive review of the
subject.52
HIGH-ALTITUDE CEREBRAL EDEMA
High-altitude cerebral edema (HACE) is likely a
continuum of AMS. AMS is generally self-limiting,
whereas HACE can be fatal. Individuals with high
Lake Louise scores should be carefully monitored
for the signs of ataxia, confusion, and hallucina-
tions which may mark the onset of HACE. HACE
is a clinical diagnosis and consists of ataxia and
altered consciousness in someone with AMS or
high-altitude pulmonary edema. Individuals with
AMS should not ascend until symptoms have re-
solved; if symptoms fail to resolve, they should
descend. Individuals with HACE should descend
immediately if at all possible and should never
descend unaccompanied.
The exact processes leading to high-altitude
cerebral edema are unknown although the edema
is probably extracellular, due to blood–brain bar-
rier leakage (vasogenic edema), rather than intra-
cellular, due to cellular swelling (cytotoxic ede
Figure 4. Portable hyperbaric chamber.
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High-Altitude Illnesses
ma).53 Vasogenic edema preferentially spreads
along white matter tracts, whereas cytotoxic ede-
ma affects both gray and white matter. MRI stud-
ies of patients with HACE showed that the majori-
ty had intense T2 signal in white matter areas,
particularly the splenium of the corpus callosum,
but no gray matter abnormalities.53 The predilec-
tion for the splenium and corpus callosum is puz-
zling. Possibly the splenium has more easily per-
turbed cellular fluid mechanics than surrounding
tissues. Splenium MRI abnormalities are not lim-
ited to patients with HACE and occur in settings
that include alcohol use, infections, hypoglycemia,
and electrolyte abnormalities;54 in these cases,
abnormalities in the splenium were also associat-
ed with confusion and ataxia, and this set of symp-
toms may be characteristic for edema involving
the splenium. The cause of death in HACE is brain
herniation.
Dexamethasone (see below) can be used to
treat AMS and HACE, but, unlike acetazolamide,
dexamethasone does not facilitate acclimatization
and may give a false sense of security. It is an ex-
cellent rescue drug to assist in descent.55,56 If de-
scent is not possible, both oxygen and portable
inflatable hyperbaric chambers (Figure 4) improve
oxygen saturation and can be effective treatments
for subjects with HACE or high-altitude pulmo-
nary edema.57,58
Inflatable hyperbaric chambers are often car-
ried by trekking companies taking clients to alti-
tude; the bags weigh about 6.5 kg and, when ex-
panded, are cylindrical in shape and large enough
to accommodate a person (Figure 4). By inflating
the bag with a foot pump, the effective altitude can
be decreased as much as 1,500 meters (5,000
feet). The foot pump has to be used continuously
while the person is in the bag to supply fresh oxy-
gen and to flush out carbon dioxide.
HIGH-ALTITUDE PULMONARY EDEMA
High-altitude pulmonary edema (HAPE) is a po-
tentially fatal consequence of rapid ascent to high
altitude. Early diagnosis may be difficult since
many of the early symptoms (shortness of breath,
tachypnea, tachycardia, reduced arterial satura-
tion, fatigue, and cough) are often present in unaf-
fected climbers at higher altitudes, particularly in
cold, dry, or dusty environments. Distinguishing
features of high-altitude pulmonary edema in-
clude incapacitating fatigue, dyspnea with min-
imal effort that advances to dyspnea at rest, or-
thopnea, and a dry non-productive cough pro-
gressing to a productive cough with pink frothy
sputum due to hemoptysis. Fever may also ac-
company HAPE, and its presence does not imply
infection; prompt administration of antibiotics is
not required unless other symptoms or a chest
radiograph indicate pneumonia.59
The onset of HAPE is usually delayed and typi-
cally occurs 2–4 days after arrival at altitude; it is
not uniformly preceded by AMS.14 HAPE is most
common at altitudes greater than 3,000 m,52 but
HAPE can and does occur at lower altitudes. Over
a 7-year period, 47 cases of HAPE were reported at
a single Colorado ski resort with an elevation of
2,500 m.60
The pathogenesis of high-altitude pulmonary
edema is still a subject for investigation; however,
it is probably triggered by an increase in pulmo-
nary artery pressure due to the normal pulmonary
vasoconstriction induced by hypoxia. Patients
with HAPE have an enhanced pulmonary reactivi-
ty to hypoxia, an exaggerated increase in pulmo-
nary artery pressures, and are improved by phar-
macological interventions that decrease pulmo-
nary artery pressure.61–63 In a subset of individ-
uals, moderate to intense exercise may play a con-
tributory role since exercise independently leads
to an increase in pulmonary artery pressures and
this effect may be additive to the increased pres-
sures resulting from hypoxia.
Compelling evidence indicates that HAPE is a
hydrostatic-induced permeability leak with mild
alveolar hemorrhage.62,64,65 Two explanations have
been suggested. The first is that that hypoxic pul-
monary vasoconstriction is not homogeneous;
consequently, pulmonary capillaries supplied by
dilated arterioles are exposed to high pressures
which cause damage to the capillary walls (stress
failure) and leads to a leak of high-protein edema
fluid with erythrocytes.4 The second explanation
hypothesizes an increase in pulmonary capillary
pressures due to hypoxic pulmonary venous con-
striction.62,65 Regardless of the mechanisms, suc-
cessful prophylaxis and treatment of high-altitude
pulmonary edema using nifedipine, a pulmonary
vasodilator, indicates that pulmonary hyperten-
sion is crucial for the development of high-altitude
pulmonary edema.63,66
There are no randomized controlled trials
evaluating treatment strategies. Oxygen, rest, and
descent are commonly agreed upon.59,66 When
patients fail to respond to conservative measures
or develop HAPE in remote settings, nifedipine is
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High-Altitude Illnesses
recommended, 10 mg orally initially and then 30
mg of the extended release formulation orally eve-
ry 12–24 hours.66 Phosphodiesterase inhibitors
such as tadalafil have been shown to prevent
HAPE in susceptible individuals67 and may also be
effective in patient management. Some physicians
are now employing combination therapy with ni-
fedipine and phosphodiesterase inhibitors,68 alt-
hough these are off-label uses. If descent is not
possible, use of a portable hyperbaric chamber is
recommended.
AMS: PREVENTION AND TREATMENT
Drugs used in the prevention and management of
AMS include acetazolamide, dexamethasone,
phosphodiesterase inhibitors, and analgesics.
Strategies to prevent AMS include preacclimat-
ization, copious water consumption, and a high-
carbohydrate diet.
ACETAZOLAMIDE
Acetazolamide is a potent carbonic anhydrase in-
hibitor; its efficacy in preventing and ameliorating
AMS has been well demonstrated although there
is still debate regarding the optimal dose.69–71 A
recent double-blind, randomized, placebo-
controlled study in the Everest region of Nepal
showed that 125 mg twice a day was just as effect-
ive in preventing AMS as 375 mg twice a day.69 In
this study, the incidence of AMS among subjects
taking acetazolamide averaged about 22% com-
pared to 51% for those taking a placebo. Acetazo-
lamide is not a panacea; a substantial percentage
of subjects taking acetazolamide still develop
AMS. In fact, on Kilimanjaro, where the rate of
ascent tends to be faster than in Nepal, the inci-
dence of AMS in those taking acetazolamide (250
mg twice a day) was 55% versus 84% for a com-
parison/placebo group.72 Although the precise
dose and recommended duration of treatment
have never been established,56 a reasonable ap-
proach for prevention is 125 mg twice a day begin-
ning 1 day prior to ascent and continuing for 2
days after reaching maximal altitude or until de-
scent is initiated; if ascent is rapid, 250 mg twice a
day may be more efficacious but carries a greater
risk of side-effects. In children, the recommended
dose of acetazolamide is 2.5 mg/kg orally given
every 12 hours with a maximum dose of 250 mg;73
treatment for 48 hours is usually sufficient for
resolution of symptoms.40
The actual mechanisms by which acetazola-
mide increases minute ventilation, leads to im-
provements in arterial blood gases, and reduces
the symptoms of AMS remain poorly under-
stood.71 The efficacy of acetazolamide has been
attributed to inhibition of carbonic anhydrase in
the kidneys resulting in bicarbonaturia and meta-
bolic acidosis, which offsets the respiratory-
induced alkalosis and allows chemoreceptors to
respond more fully to hypoxia stimuli at altitude.
Other mechanisms, however, are likely involved:
the bicarbonaturia ultimately lowers the cerebral
spinal fluid (CSF) bicarbonate concentration,
thereby lowering the CSF pH and stimulating ven-
tilation.71 Membrane-bound carbonic anhydrase
isoenzymes are present on the luminal side of al-
most all capillary beds including the brain and can
be inhibited by low doses of acetazolamide leading
to a local tissue retention of CO2 in the order of 1–
2 mmHg.71,74 This slight increase in partial pres-
sure of CO2 in the brain may stimulate profound
changes in ventilation given the high CO2 ventila-
tory responsiveness of central chemoreceptors.74
In fact, inhibition of red blood cell and vascular
endothelial carbonic anhydrase has been shown to
cause an almost immediate retention of CO2 in all
tissues as the normal mechanisms for exchange
and transport are attenuated. The resulting tissue
acidosis is postulated to be an important stimulus
to the hyperventilation associated with carbonic
anhydrase inhibition.71,74 In addition to improve-
ments in ventilation from tissue acidosis, other
operative mechanisms likely include improve-
ments in sleep quality from carotid body carbonic
anhydrase inhibition and the effects of diuresis.71
Acetazolamide is a sulfonamide drug; patients
with an allergic reaction to sulfonamide antibiotics
are more likely to have a subsequent allergic reac-
tion to a non-antibiotic sulfonamide drug, but this
association appears to be due to a predisposition
to allergic reactions rather than to a specific cross-
reactivity with sulfonamide-based antibiotics.75
Nevertheless, the general recommendation is that
patients with known allergies to sulfa drugs
should avoid acetazolamide.56 The most common
side-effects of acetazolamide are peripheral and
circumoral paresthesias, but loss of appetite and
nausea have been reported. The effect of carbonic
anhydrase inhibition in the mouth can also affect
the taste of carbonated beverages. Higher doses
(250 mg twice or three times a day) are associated
with greater side-effects. Finally, the safety of ac-
etazolamide in pregnancy has not been estab-
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High-Altitude Illnesses
lished, and it should be used in pregnancy only if
the benefits clearly outweigh the risks.66
DEXAMETHASONE
Dexamethasone is probably less effective than ac-
etazolamide in preventing AMS,70 but it is effective
as an emergency treatment of AMS in a dosage of
4–10 mg initially, followed by 4 mg every 6
hours.55,56,76,77 Dexamethasone reduces AMS
symptomatology but does not improve objective
physiologic abnormalities related to exposure to
high altitudes; a subject with severe AMS may
have a dramatic response in symptomatology after
treatment with dexamethasone but still show cer-
ebral edema on a CT scan.77 At present, dexame-
thasone is recommended only when descent is
impossible or to facilitate co-operation in evacua-
tion efforts.76,77
PHOSPHODIESTERASE INHIBITORS
Decreased nitric oxide synthesis may be a contrib-
utory factor in HAPE. Nitric oxide, a vasodilator
produced in the pulmonary vascular endothelium,
has a short half-life as a result of local phos-
phodiesterase (PDE) activity; consequently, PDE
inhibitors enhance the effect of nitric oxide. The 5-
PDE inhibitor sildenafil (Viagra) diminishes the
pulmonary hypertension induced by acute expos-
ure to hypobaric hypoxia at rest and after exer-
cise,78 protects against the development of alti-
tude-induced pulmonary hypertension, and im-
proves gas exchange, limiting the altitude-induced
hypoxemia and decrease in exercise perform-
ance.79 Tadalafil has been shown to prevent HAPE
in susceptible individuals,67 and this class of drugs
shows promise in the management of patients
with HAPE.
ACETAMINOPHEN AND IBUPROFEN
Acetaminophen and non-steroidal anti-inflamma-
tory drugs such as ibuprofen and aspirin are often
effective in relieving the headache associated with
AMS.80,81
HYDRATION
Avoiding dehydration is important, especially
since considerable moisture can be lost through
respiration at high altitude. Although hypo-
hydration degrades aerobic performance at alti-
tude, it does not appear to increase the prevalence
or severity of AMS.82 Nevertheless, a belief has
developed that hypo-hydration increases the risk
of AMS and that excessive hydration can prevent
or treat the disorder.83 Some trek leaders even
urge clients to consume excess quantities of water
to avoid or ameliorate AMS, but there is no scien-
tific basis for this advice.66,84 The belief may have
originated from observations on the Jungfraujoch
(3,471 m) where it was noted that new arrivals
passing the greatest quantity of urine tolerated
altitude better than those passing the least amount
of urine.83 This observation may have led to the
assumption that consuming large quantities of
water would lead to a diuresis and prevent AMS.
The early diuresis that occurs at altitude, however,
is a response to hypoxia not excess fluid consump-
tion; the development of AMS is associated with a
rise in the plasma concentrations of antidiuretic
hormone and fluid retention.19
PRE-ACCLIMATIZATION AND ALTITUDE
SIMULATION
Pre-acclimatization, spending time at altitude pri-
or to undertaking a higher ascent, reduces the
likelihood of developing AMS.46 Living at high ele-
vation and training at low elevation improves per-
formance in athletes of all abilities; the primary
mechanism is an increase in erythropoietin which
leads directly to an increase in red cell mass. The
increase in red cell mass allows greater oxygen
delivery to the tissues, an increase in maximum
oxygen consumption, and an improvement in ex-
ercise capacity.85,86 Pre-acclimatization is usually
impractical for the high-altitude traveler or recrea-
tional climber, and the “live high, train low” ap-
proach is not an option for most athletes. Inter-
mittent hypoxic training has been introduced us-
ing normobaric or hypobaric hypoxia in an at-
tempt to reproduce some of the key features of
altitude acclimatization and enhance perfor-
mance.85,87,88 Hypoxia at rest has the primary goal
of stimulating acclimatization, while hypoxia dur-
ing exercise has the goal of enhancing perfor-
mance.
The simplest intermittent hypoxic training
strategy is breathing air with a reduced partial
pressure of oxygen under resting conditions; this
strategy is straightforward, but unresolved varia-
bles are the optimum number of sessions, opti-
mum length of each session, and timing of the ses-
sions prior to ascent. At present, no set of resting,
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High-Altitude Illnesses
normobaric, hypoxic training parameters have
been defined that will reproducibly reduce the
likelihood of AMS. A much more sophisticated
approach is the use of an altitude simulation sys-
tem which can safely reduce the oxygen content in
a room or tent. This system creates a hypoxic envi-
ronment that is portable, ideally suited for a “liv-
ing high, training low” environment and is now
used in Olympic training centers around the
world.86 Red cell transfusions as well as exogenous
erythropoietin have been used to increase red cell
mass, but neither approach is legal in athletic
competition.
CARBOHYDRATES
Ingestion of pure carbohydrates 40 min prior to
acute hypoxic exposure has been shown to im-
prove hemoglobin saturation by as much as 4%;
the effect, however, wears off by 150 min, and any
advantage of carbohydrate consumption in im-
proving oxygenation is only applicable during the
period the carbohydrates are being digested.89
This effect depends on the respiratory quotient
(RQ) which represents the ratio of carbon dioxide
excreted to the amount of oxygen utilized; the val-
ue of this ratio depends on the carbon content of
food and is typically around 0.85, but it ranges
from 0.7 (pure fat) to 1.0 (pure carbohydrates). As
shown in the following equation, metabolism of
carbohydrates produces a higher PAO2 than the
metabolism of fat:
PAO2 = PiO2 – PaCO2/RQ
where PAO2 is the partial pressure of oxygen in the
alveoli, PiO2 is the partial pressure of inspired ox-
ygen, and PaCO2 is the partial pressure of carbon
dioxide. A higher PAO2 will result in a higher he-
moglobin oxygen saturation. Effectively, the me-
tabolism of carbohydrates produces a larger quan-
tity of CO2 than the metabolism of proteins or li-
pids;90 the increased CO2 production provides an
added stimulus to the respiratory centers.
SUMMARY
The typical symptoms of AMS include headache,
loss of appetite, disturbed sleep, nausea, fatigue,
and dizziness, beginning shortly after rapid ascent
to high altitude. The hypoxia of high altitude can
lead to sleep disturbances, impaired mental per-
formance, weight loss, and reduced exercise ca-
pacity. Factors impacting the risk of AMS include
home elevation, maximum altitude, sleeping alti-
tude, rate of ascent, latitude, intensity of exercise,
pre-acclimatization, prior experience at altitude,
and genetic make-up. Symptoms can usually be
relieved by rest and by delaying further ascent un-
til symptoms have resolved; if symptoms are se-
vere, they can be rapidly relieved by descent to a
lower elevation. Acetazolamide in doses of 125 mg
twice a day reduces the incidence and severity of
AMS in areas of relatively slow ascent such as the
Everest region of Nepal; under these conditions,
higher doses do not appear to be more effective
but may be advantageous during the more rapid
ascent that occurs on mountains such as Kiliman-
jaro. AMS may progress to high-altitude cerebral
edema (HACE), and high-altitude pulmonary
edema (HAPE) may occur in the absence of AMS.
Both of these conditions are medical emergencies;
if possible, initial management should include de-
scent, supplemental oxygen, and, in the case of
HACE, dexamethasone. Nifedipine and phos-
phodiesterase may be effective in the management
of HAPE. A person suspected of either of these
conditions should never descend alone. Portable
hyperbaric chambers should be considered if de-
scent is not an option.
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