ArticlePDF Available

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


Abstract and Figures

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.
Content may be subject to copyright.
Open Access Rambam Maimonides Medical Journal
High-Altitude Illnesses: Physiology,
Risk Factors, Prevention, and
Andrew T. Taylor, M.D.*
Department of Radiology, Emory University School of Medicine, Atlanta, GA, USA
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,
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.
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 (, 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:
RMMJ| 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 3,0005,000 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 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
Rambam Maimonides Medical Journal 2 January 2011 Volume 2 Issue 1 e0022
High-Altitude Illnesses
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.*
Barometric pressure
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.
Rambam Maimonides Medical Journal 3 January 2011 Volume 2 Issue 1 e0022
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 or atmospheric pressure is usually ex-
pressed in mmHg (mercury) although it is occa-
sionally expressed in torr in honor of Evangelista
Torricelli (16081647) 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
Prevalence of acute mountain sickness (AMS).
Altitude (m)
3,650 34%
4,559 53%
Dean 7 Colorado 2,987 42%
Honigman 3 Colorado 2,000–3,000 25%
4,000–4,500 15%
0ver 5,000 34%
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. 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 03; the presence of headache plus a score greater than or equal to 3 is
usually considered positive for AMS.8
Rambam Maimonides Medical Journal 4 January 2011 Volume 2 Issue 1 e0022
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-
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 78 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
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 bloodbrain barrier separates these medullary
chemoreceptors from the arterial blood, the
bloodbrain 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,
Rambam Maimonides Medical Journal 5 January 2011 Volume 2 Issue 1 e0022
High-Altitude Illnesses
and a failure to increase the HVR contributes to
hypoxemia and the development of AMS.17
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.1720
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 oxygenhemoglobin
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-
genhemoglobin 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 oxygenhemoglobin 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 oxygenhemoglobin
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).
Rambam Maimonides Medical Journal 6 January 2011 Volume 2 Issue 1 e0022
High-Altitude Illnesses
The hypoxia of high altitude can lead to sleep dis-
turbances, impaired mental performance, weight
loss, and reduced exercise capacity.
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.
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
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-
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
Rambam Maimonides Medical Journal 7 January 2011 Volume 2 Issue 1 e0022
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-
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
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 3,0004,000 m to 51%
at 4,5005,000 m (Table 2).4 Interestingly, in this
study, the prevalence of AMS decreased from 51%
at 4,5005,000 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.
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 6001,200 m gain in
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.
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%
Rambam Maimonides Medical Journal 8 January 2011 Volume 2 Issue 1 e0022
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
As described above, the alveolararterial 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
Early hypoxemia, a decrease in the SaO2 greater
than that expected for a given altitude, is a risk
factor for developing AMS.4143 Early hypoxemia
appears to be the result of a diffusion impairment
or venous admixture and can be monitored with a
pulse oximeter (Figure 3).4143 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.
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-
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.
Rambam Maimonides Medical Journal 9 January 2011 Volume 2 Issue 1 e0022
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
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
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 bloodbrain bar-
rier leakage (vasogenic edema), rather than intra-
cellular, due to cellular swelling (cytotoxic ede
Figure 4. Portable hyperbaric chamber.
Rambam Maimonides Medical Journal 10 January 2011 Volume 2 Issue 1 e0022
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
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 (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 24 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.6163 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
Rambam Maimonides Medical Journal 11 January 2011 Volume 2 Issue 1 e0022
High-Altitude Illnesses
recommended, 10 mg orally initially and then 30
mg of the extended release formulation orally eve-
ry 1224 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
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 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.6971 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-
Rambam Maimonides Medical Journal 12 January 2011 Volume 2 Issue 1 e0022
High-Altitude Illnesses
lished, and it should be used in pregnancy only if
the benefits clearly outweigh the risks.66
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
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 non-steroidal anti-inflamma-
tory drugs such as ibuprofen and aspirin are often
effective in relieving the headache associated with
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, 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-
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,
Rambam Maimonides Medical Journal 13 January 2011 Volume 2 Issue 1 e0022
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
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:
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.
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.
1. Rennie D. See Nuptse and die. Lancet 1976;2:
2. Rennie D. The great breathlessness mountains.
JAMA 1986;256:812.
3. Honigman B, Theis MK, Koziol-McLain J, et al.
Acute mountain sickness in a general tourist popu-
lation at moderate altitude. Ann Intern Med
4. Vardy J, Vardy J, Judge K. Acute mountain sick-
ness and ascent rates in trekkers above 2500 m in
the Nepali Himalaya. Aviat Space Environ Med
5. Maggiorini M, Buhler B, Walter M, Oelz O. Preva-
lence of acute mountain sickness in the Swiss Alps.
BMJ 1990;301:8535.
6. Karinen H, Peltonen J, Tikkanen H. Prevalence of
acute mountain sickness among Finnish trekkers
on Mount Kilimanjaro, Tanzania: an observational
study. High Alt Med Biol 2008;8:3016.
Rambam Maimonides Medical Journal 14 January 2011 Volume 2 Issue 1 e0022
High-Altitude Illnesses
doi:10.1089/ham. 2008.1008
7. Dean AG, Yip R, Hoffmann RE. High incidence of
acute mountain sickness in conference attendees
at 10,000 foot altitude. J Wilderness Med 1990;
8. Roach RC, Bärtsch P, Oelz O, Hackett PH. The
Lake Louise Acute Mountain Sickness Scoring Sys-
tem. In: Sutton JR, Houston CS, Coates G, eds.
Hypoxia and Molecular Medicine. Burlington, VT:
Queen City Press; 1993:2724.
9. Sampson JB, Cymerman A, Burse RL, Maher JT,
Rock PB. Procedures for the measureement of
acute mountain sickness. Aviat Space Environ Med
10. Wagner DR, Tatsugawa K, Parker D, Young TA.
Reliability and utility of a visual analog scale for
the assessment of acute mountain sickness. High
Alt Med Biol 2007;8:2731. doi:10.1089/ham.
11. Dellasanta P, Gaillard S, Loutan L, Kayser B.
Comparing questionnaires for the assessment of
acute mountain sickness. High Alt Med Biol
2007;8:18491. doi:10.1089/ham. 2007.8305
12. Kayser B, Alverti A, Pellegrino R, et al. Compari-
son of a visual analogue scale and Lake Louise
symptom scores for acute mountain sickness. High
Alt Med Biol 2010;11:6972.
13. West JB, Schoene RB, Milledge JS. High Altitude
Medicine and Physiology. 4th ed. London, Great
Britain: Hodder Arnold; 2007: 23.
14. West JB. The physiologic basis of high-altitude
diseases. Ann Intern Med 2004;141:780–800.
15. West JB, Hackett PH, Maret KH, et al. Pulmonary
gas exchange on the summit of Mount Everest. J
Appl Physiol 1983;55:67887.
16. Laffey JG, Kavanagh BP. Hypocapnia. N Engl Med
2002;347:4352. doi:10.1056/NEJM ra012457
17. Bärtsch P, Swenson ER, Paul A, Julg B, Hohen-
hause E. Hypoxic ventilatory response, ventilation,
gas exchange and fluid balance in acute mountain
sickness. High Alt Med Biol 2002;3:36176.
18. Pugh LG. Blood volume and haemoglobin concen-
tration at altitudes above 18,000 ft (5500 m). J
Physiol (London) 1964;170:34453.
19. Loeppky JA, Icenogle MV, Maes D, Riboni K,
Hinghofer-Szalkay H, Roach RC. Early fluid re-
tention and severe acute mountain sickness. J
Appl Physiol 2005;98:5917. doi:10. 1152/jappl
20. Swenson ER. High-Altitude Diuresis: Fact or Fan-
cy. In: Houston CS, Coates G, eds. Hypoxia: Wom-
en at Altitude. Burlington, VT: Queen City Print-
ers; 2006: 27283.
21. Oxyhaemoglobin dissociation curve.png. Available
at: Oxyhaemo-
globin_dissociation_curve.png#globalusage (ac-
cessed November 7, 2010).
22. Grocott MPW, Martin DS, Levett DZH, McMorrow
R, Windsor J, Montgomery H; for the Caudwell
Xtreme Everest Research Group. Arterial blood
gases and oxygen content in climbers on Mount
Everest. N Eng J Med 2009;360:14098. doi:10.
1056/NEJM oa0801581
23. Storz JF, Moriyama H. Mechanisms of hemoglobin
adaptation to high altitude hypoxia. High Alt Med
Biol 2008;9:14857. doi:10.1089/ham.2007.1079
24. Phillipson EA. Control of breathing during sleep.
Am Rev Respir Dis 1978;90939.
25. Zielinski J, Koziej M, Mankowski M, et al. The
quality of sleep and periodic breathing in healthy
subjects at an altitude of 3,200 m. High Alt Med
Biol 2000;1:3316. doi:10.1089/15270290050502
26. Weil JV. Sleep at high altitude. High Alt Med Biol
2004;5:1809. doi:10.1089/1527029041 352162
27. Virués-Ortega J, Buela-Casal B, Garrido E, Alcazár
B. Neuropsychological functioning associated with
high-altitude exposure. Neuropsychol Rev 2004;
14:197224. doi:10. 1007/s11065-004-8159-4
28. Paola MD, Bozzali M, Fadda L, Musicco M, Saba-
tini U, Caltagirone C. Reduced oxygen due to high-
altitude exposure relates to atrophy in motor-
function brain areas. Eur J Neurol 2008;15:1050
7. doi:10.1111/j.1468-1331.2008.02243.x
29. Fayed N, Modergo PJ, Morales H. Evidence of
brain damage after high-altitude climbing by
means of magnetic resonance imaging. Am J Med
30. Kayser B. Nutrition and energetics of exercise at
altitude. Theory and possible practical impli-
cations. Sports Med 2004;17:30923. doi:10.2165/
31. Mizuno M, Savard GK, Areskog N, Lundby C,
Saltin B. Skeletal muscle adaptations to prolonged
exposure to extreme altitude: a role for physical
activity. High Alt Med Biol 2008;9:3117. doi:10.
32. Dempsey JA, Wagner PD. Exercise-induced arteri-
al hypoxemia. J Appl Physiol 1999;87:1997–2006.
33. Dempsey JA, McKenzie DC, Haverkamp HC,
Eldridge MW. Update in the understanding to ex-
ercise performance in fit, active adults. Chest
2008;134:61322. doi:10.1378/chest. 07-2730
Rambam Maimonides Medical Journal 15 January 2011 Volume 2 Issue 1 e0022
High-Altitude Illnesses
34. Roach RC, Maes D, Sandoval D, et al. Exercise
exacerbates acute mountain sickness at simulated
high altitude. J Appl Physiol 2000;88:5815.
35. Honigman B, Read M, Lezotte D, Roach RC. Sea-
level physical activity and acute mountain sickness
at moderate altitude. West J Med 1995;163:11721.
36. Bloch KE, Turk AJ, Maggiorini M, et al. Effect of
ascent protocol on acute mountain sickness and
success at Muztagh Ata, 7546 m. High Alt Med Bi-
ol 2009:10:2532. doi:10. 1089/ham.2008.1043
37. Basnyat B, Gertsch JH, Johnson EW, Castro-
Marin F, Inoue Y, Yeh C. Efficacy of low-dose acet-
azolamide (125 mg BID) for the prophylaxis of
acute mountain sickness: A prospective, double-
blind, randomized, placebo-controlled trial. High
Alt Med Biol 2003;4:4552. doi:10.1089/152
38. Davies AJ, Kalson NS, Stokes S, et al. Determi-
nants of summiting success and acute mountain
sickness on Mt. Kilimanjaro (5895 m). Wilderness
Environ Med 2009;4:3117. doi:10.1580/1080-
6032-020. 004.0311
39. McIntosh SD, Campbell AD, Dow J, Grisson CK.
Mountaineering fatalities on Denali. High Alt Med
Biol 2008;9:8995. doi:10.1089/ham.2008.1047
40. Yaron M, Niermeyer S. Travel to high altitude with
young children: an approach for clinicians. High
Alt Med Biol 2008;9:2659. doi:10.1089/ham.
41. Burtscher M, Flatz M, Faulhaber M. Prediction of
susceptibility to acute mountain sickness by
Sa(O2) values during short-term exposure to hy-
poxia. High Alt Med Biol 2004;5:33540.
42. Loeppky JA, Icenogle MV, Charlton GA, et al. Hy-
poxemia and acute mountain sickness: which
comes first? High Alt Med Biol 2008;9:2719.
43. Karinen HM, Peltonen JE, Kähönen M, Heikki
Tikkanen HO. Prediction of acute mountain sick-
ness by monitoring arterial oxygen saturation dur-
ing ascent. High Alt Med Biol 2010;11:32532.
doi:10.1089/ham. 2009.1060
44. Hannhart B, Habberer J-P, Saunier C, Laxenaire
MC. Accuracy and precision of fourteen pulse oxi-
meters. Eur Respir J 1991;4:1159.
45. Pesce C, Leal C, Pinto H, et al. Determinants of
acute mountain sickness and success on Mount
Aconcagua (6962 m). High Alt Med Biol
2005;6:15866. doi:10.1089/ham.2005 .6.158
46. Schneider M, Bernasch D, Weymann J, Holle R.
Acute mountain sickness: influence of susceptibil-
ity, pre-exposure, and ascent rate. Med Sci Sports
Exerc 2002;34:188691. doi:10.1097/00005768-
47. Stobdan T, Karar J, Pasha MAQ. High altitude
adaptation: genetic perspectives. High Alt Med Bi-
ol 2008;9:1407. doi:10. 1089/ham.2007.1076
48. Breen E, Tang K, Olfert M, Knapp A, Wagner P.
Skeletal muscle capillarity during hypoxia: VEGF
and its activation. High Alt Med Biol 2008;9:158–
66. doi:10.1089/ham.2008.1010
49. Thompson J, Raitt J, Hutchings L, et al. Angioten-
sin-converting enzyme genotype and successful
ascent to extreme high altitude. High Alt Med Biol
2007;8:27885. doi:10.1089/ ham.2007.1044
50. Rupert J. Will blood tell? Three recent articles
demonstrate genetic selection in Tibetans. High
Alt Med Biol 2010;11:3078. doi:10.1089/ham.
51. West JB. Who should not go high. High Alt Med
Biol 2009;10:12. doi:10.1089/ham. 2009.10101
52. Luks AM, Swenson ER. Travel to high altitude
with pre-existing lung disease. Eur Respir J
2007;29:77092. doi:10.1183/09031936.00052
53. Hackett PH, Yarnell PR, Hill R, Reynard K, Heit J,
McCormick J. High-altitude cerebral edema evalu-
ated with magnetic resonance imaging. JAMA
54. Dohery MJ, Jayadev S, Watson NF, Konchada RS,
Hallam DK. Clinical implications of splenium
magnetic resonance imaging signal changes. Arch
Neurol 2005;62:4337. doi:10.1001/archneur.62.
55. Schoene RB. Dexamethasone: by safe means, by
fair means. High Alt Med Biol 2005;6:2735. doi:
56. Schoene RB. Illnesses at high altitude. Chest
2008;134:402–16. doi:10.1378/chest.07-0561
57. Kasic JF, Yaron M, Nicholas RA, Lichteig JA,
Roach R. Treatment of acute mountain sickness:
hyperbaric versus oxygen therapy. Ann Emerg
Med 1991;20:110912. doi:10.1016/S0196-0644
58. Freeman K, Shalit M, Stroh G. Use of the Gamow
Bag by EMT-basic park rangers for treatment of
high-altitude pulmonary edema and high-altitude
cerebral edema. Wilderness Environ Med 2004;
59. Luks AM. Do we have a “best practice” for treating
high altitude pulmonary edema? High Alt Med Bi-
ol 2008;9:1114. doi:10.1089/ham.2008.1017
60. Sophocles AM. High altitude pulmonary edema in
Vail, Colorado, 19751982. West J Med 1986;144:
Rambam Maimonides Medical Journal 16 January 2011 Volume 2 Issue 1 e0022
High-Altitude Illnesses
61. Hultgren HN, Lopez CE, Lundberg E, Miller H.
Physiologic studies of pulmonary edema at high al-
titude. Circulation 1964;29:393408.
62. Maggiorini M, Melot C, Pierre S, et al. High alti-
tude pulmonary edema is initially a hydrostatic,
not a permeability edema. Circulation
63. rtsch P, Maggiorini M, Ritter M, Noti C, Vock P,
Oelz O. Prevention of high-altitude pulmonary
edema by nifedipine. N Eng J Med 1991;325:
12849. doi:10.1056/NEJM 199110313251805
64. Swenson ER, Maggiorini M, Mongovin S, et al.
Pathogenesis of high-altitude pulmonary edema:
inflammation is not an etiologic factor. JAMA
65. Hackett P, Rennie D. High-altitude pulmonary
edema. JAMA 2002;287:22758.
66. Hackett PH, Roach RC. High-altitude illness. New
Engl J Med 2001;345:10714. doi:10.1056/NEJM
67. Maggiorini M, Brunner-La Rocca HP, Fischler PS,
et al. Both tadalafil and dexamethasone may re-
duce the incidence of high-altitude pulmonary
edema: a randomized trial. Ann Intern Med 2006;
68. Fagenholz PJ, Gutman JA, Murray AF, Harris NS.
Treatment of high altitude pulmonary edema at
4240 m in Nepal. High Alt Med Biol 2007;8:139
46. doi:10.1089/ham.2007.3055
69. Basnyat B, Gertsch JF, Holck PS, et al. Acetazola-
mide 125 mg BD is not significantly different from
375 mg BD in the prevention of acute mountain
sickness: the prophylactic acetazolamide dosage
comparison for efficacy (PACE) trial. High Alt Med
Biol 2006;7:1727. doi: 10.1089/ham.2006.7.17
70. Ried LD, Carter KA, Ellsworth A. Acetazolamide or
dexamethasone for prevention of acute mountain
sickness: a meta-analysis. J Wilderness Med 1994;
71. Leaf DE, Goldfarb DS. Mechanisms of action of
acetazolamide in the prophylaxis and treatment of
acute mountain sickness. J Appl Physiol
2007;102:131322. doi:10.1152/japplphysiol. 0157
72. Kayser B, Hulsebosch R, Bosch F. Low-dose ace-
tylsalicylic acid analog and acetazolamide for pre-
vention of acute mountain sickness. High Alt Med
Biol 2008;9:1523. doi:10. 1089/ham.2007. 1037
73. Pollard AJ, Niermeyer S, Barry P, et al. Children at
high altitude: an international consensus state-
ment by an ad hoc committee of the International
Society for Mountain Medicine, March 12, 2001.
High Alt Med Biol 2001;2:389403. doi:10.1089/
15270290152 608561
74. Swenson ER. Carbonic anhydrase inhibitors and
ventilation: a complex interplay of stimulation and
suppression. Eur Respir J 1998;12:12427. doi:10.
1183/09031936.98.12061 242
75. Strom BL, Schinnar R, Apter AJ, et al. Absence of
cross-reactivity between sulfonamide antibiotics
and sulfonamide nonantibiotics. N Eng J Med
2003;349:162835. doi:10.1056/ NEJMoa022963
76. Ferrazini G, Maggiorini M, Kreimler S, Bärtsch P,
Oelz O. Successful treatment of acute mountain
sickness with dexamethasone. BMJ 1987;294:
77. Levine BD, Yoshimura K, Kobayashi T, Fukashima
M, Toshishige S, Udea G. Dexamethasone in the
treatment of acute mountain sickness. N Engl J
Med 1989;321:170713. doi:10.1056/NEJM198912
78. Ricart A, Maristany J, Fort N, Leal C, Pagés T, Vis-
cor G. Effects of sildenafil on the human response
to acute hypoxia and exercise. High Alt Med Biol
2008;6:439. doi:10.1089/ham. 2005.6.43
79. Richalet J, Gratadour P, Robach P, et al. Sildenafil
inhibits altitude-induced hypoxemia and pulmo-
nary hypertension. Am J Respir Crit Care Med
2005;171:27581. doi:10.1164/rccm.200406-804OC
80. Broome JR, Stoneham MD, Beeley JM, Milledge
JS Huges AS. High altitude headache: treatment
with ibuprofen. Aviat Space Environ Med 1994;65:
81. Burtschler M, Likar R, Nachbauer W, Schaffert W,
Philadelphy M. Ibuprofen versus sumatriptan for
high-altitude headache. Lancet 1994;346:2545.
doi:10.1016/S0140-6736 (95)91303-3
82. Castellani JW, Muza SR, Cheuvront SN, et al. Ef-
fect of hypohydration and altitude exposure on
aerobic exercise performance and acute mountain
sickness. J Appl Physiol 2010;6:1792–800. doi:10.
1152/japplphysiol .00517.2010
83. Houston C. Going Higher: Oxygen, Man and
Mountains. 4th ed. Seattle, WA: The Mountain-
eers; 1998: 185.
84. West JB, Schoene RB, Milledge JS. High Altitude
Medicine and Physiology. 4th ed. London, Great
Britain: Hodder Arnold; 2007: 264.
85. Levine BD. Intermittent hypoxic training: fact or
fancy. High Alt Med Biol 2002;3:17793. doi:10.
86. Kutt LM. Should altitude simulation be legal for
athletics training [letter to the editor]. High Alt
Med Biol 2005;6:18990. doi:10.1089/ham. 2005
Rambam Maimonides Medical Journal 17 January 2011 Volume 2 Issue 1 e0022
High-Altitude Illnesses
87. Schommer K, Wiesegart N, Menold E, et al. Train-
ing in normobaric hypoxia and its effects on acute
mountain sickness after rapid ascent to 4559 m.
High Alt Med Biol 2010;11:1925. doi:10.1089/
Jones J E, Muza SR, Fulco CS, Beidleman BA,
Tapia ML, Cymerman A. Intermittent hypoxic ex-
posure does not improve sleep at 4300 m. High
Alt Med Biol 2008;9:2818. doi:10.1089/ham.
2008. 1039
88. Askew EW. Food for high-altitude expeditions:
Pugh got it right in 1954. Wilderness Environ Med
89. Golja P, Flandere P, Klemenc M, Maver J, Princi T.
Carbohydrate ingestion improves oxygen delivery
in acute hypoxia. High Alt Med Biol 2008;9:53–
62. doi:10.1089/ham. 2008.1021
Rambam Maimonides Medical Journal 18 January 2011 Volume 2 Issue 1 e0022
... [Grimminger i in., 2017] Dzieje się tak, ponieważ wraz ze wzrostem wysokości (i idącą za tym zmianą ciśnienia atmosferycznego) w pęcherzykach płucnych zwiększa się ilość pary wodnej i dwutlenku węgla, które "zajmują miejsce" tlenu. [Taylor, 2011] Warunki takie opisuje się jako warunki hipoksji hipobarycznej, ponieważ dostępność tlenu jest zmniejszona z powodu niskiego ciśnienia atmosferycznego. Przebywanie w takim środowisku powoduje, że dostępność O 2 dla organizmu jest zmniejszona, co jest wspólną podstawą dla jednostek chorobowych wchodzących w spektrum choroby wysokościowej. ...
... Dzięki nim organizm jest w stanie sam doprowadzić do powrotu prawidłowego pH krwi w przeciągu 24-48 godzin. [Taylor, 2011] Stosowanie acetazolamidu przyspiesza ten proces. ...
... An additional possibility is that, given the increased biomechanical difficulty of bearing a heavy load (Attwells et al. 2006), frontal cortex motor activity and metabolic demand were increased relative to unloaded exercise thereby enhancing the distribution of cerebral blood flow to that region (Delp et al. 2001), without substantially altering overall cerebral blood flow. Whatever the case may be, our finding has potentially important health implications as cerebral pressure/perfusion has been implicated in the pathophysiology of acute mountain sickness and high-altitude cerebral edema (Hackett 1999;Taylor 2011). Thus, the present study indicates that load carriage exercise may exacerbate the risks for these conditions; although, more study is needed to confirm this. ...
Full-text available
Purpose To determine the effects of load carriage in normoxia and normobaric hypoxia on ventilatory responses, hemodynamics, tissue oxygenation, and metabolism. Methods Healthy males (n = 12) completed 3 randomly ordered baseline graded exercise tests in the following conditions: (1) unloaded normoxic (U: FIO2 = 20.93%), (2) loaded (~ 30 kg) normoxic (LN), and (3) loaded hypoxic simulating ~ 3650 m (LH: FIO2 = ~ 13%). Thereafter, experimental exercise trials were completed in quasi-randomized order (i.e., U completed first) consisting of 3 × 10 min of walking (separated by 5 min seated rest) with stages matched with the U condition (in ascending order) for relative intensity, absolute oxygen consumption ([VO2]; 1.7 L min⁻¹), and walking speed (1.45 ± 0.15 m s⁻¹). Results Load carriage increased perceived exertion and reduced VO2max (LN: − 7%; LH: − 32%; p < 0.05). At matched VO2, stroke volume and tidal volume were reduced and maintained with LN and LH vs. U, respectively (p < 0.05). Increases in cardiac output and minute ventilation at matched VO2 (with LH) and speed (with LN and LH), were primarily accomplished via increases in heart rate and breathing frequency (p < 0.05). Cerebral oxygenated hemoglobin (O2HHb) was increased at all intensities with LN, but deoxygenated hemoglobin and total hemoglobin were increased with LH (p < 0.05). Muscle oxygen kinetics and substrate utilization were similar between LN and U, but LH increased CHO dependence and reduced muscle O2HHb at matched speed (p < 0.05). Conclusion Load carriage reduces cardiorespiratory efficiency and increases physiological strain, particularly in hypoxic environments. Potential load carriage-induced alterations in cerebral blood flow may increase the risk for altitude illnesses and requires further study.
... Compared to living in lower altitude areas, high-altitude places may induce breathing instability because the oxygen content of blood is reduced, probably leading to sleep disturbances due to a lack of air when sleeping [57]. In addition, during sleep at a high altitude, the hypoxic drive or the response to carbon dioxide (CO 2 ) may increase the instability of the control system, thus resulting in periodic breathing, which is considered the main causative factor of sleep problems in people who live at high altitudes above 4,000 m [58]. Furthermore, a large number of psychiatric disorders, such as anxious mood, are associated with long-term accumulated damage to the nervous system due to lack of sleep and high arousal [59]. ...
Full-text available
Background Anxiety and sleep problems are common comorbidities among outpatients living in high-altitude areas. Network analysis is a novel method to investigate the interaction and the association between symptoms across diverse disorders. This study used network analysis to investigate the network structure symptoms of anxiety and sleep problems among outpatients in high-altitude areas, and to explore the differences in symptom associations in various sex, age, educational levels and employment groups. Methods The data was collected from the Sleep Medicine Center of The First People’s Hospital of Yunnan Province from November 2017 to January 2021 with consecutive recruitment (N = 11,194). Anxiety and sleep problems were measured by the Chinese version of the seven-item Generalized Anxiety Disorder Scale (GAD-7) and the Pittsburgh Sleep Quality Index (PSQI) respectively. Central symptoms were identified based on centrality indices and bridge symptoms were identified with bridge indices. The difference of network structures in various sex, age, educational levels and employment groups were also explored. Results Among all the cases, 6,534 (58.37%; 95% CI: 57.45-59.29%) reported experiencing anxiety (GAD-7 total scores ≥ 5), and 7,718 (68.94%; 95% CI: 68.08-69.80%) reported experiencing sleep problems (PSQI total scores ≥ 10). Based on the results of network analysis, among participants, “Nervousness”, “Trouble relaxing”, “Uncontrollable worry” were the most critical central symptoms and bridge symptoms within the anxiety and sleep problems network structure. The adjusted network model after controlling for covariates was significantly correlated with the original (r = 0.75, P = 0.46). Additionally, there were significant differences in edge weights in the comparisons between sex, age and educational levels groups (P < 0.001), while the employed and unemployed groups did not show significant differences in edge weights (P > 0.05). Conclusions In the anxiety and sleep problems network model, among outpatients living in high-altitude areas, nervousness, uncontrollable worry, and trouble relaxing were the most central symptoms and bridge symptoms. Moreover, there were significant differences between various sex, age and educational levels. These findings can be used to provide clinical suggestions for psychological interventions and measures targeting to reduce symptoms that exacerbate mental health.
... [1] Long-term residents may have higher haematocrit and pulmonary hypertension, lower partial pressure of carbon dioxide, and bicarbonate concentrations. [2] Because of the reduced PaO 2 , the risk of perioperative hypoxia is likely to be increased, particularly in persons who have recently ascended to such an altitude. Nevertheless, delayed awakening, bladder and bowel distension, and postanaesthetic headache with nausea have been reported after GA due to perioperative hypoxia at high altitude. ...
Full-text available
Approximately 140 million people worldwide live permanently at altitudes greater than 9,000 feet and many of them might require surgical care. We describe a case of an emergency open appendectomy in a high-altitude environment in an underground dug-in forward surgical centre in an austere environment
While the literature regarding return to play and recovery protocols from mild traumatic brain injury (mTBI) and sports-related concussions (SRC) is growing, there continues to be a paucity of data regarding when air travel is safe for athletes after sustaining certain brain injuries, such as mTBI and SRC. Although it is known hypoxia can negatively affect severe TBI patients, it is unclear whether mild hypoxia, which may be experienced during commercial air travel, is clinically significant for athletes who have recently sustained mTBI injuries. Further research is required to provide more standardized recommendations on when air travel is safe. With the current available literature, clinicians still need to weigh the evidence, consider how it applies to each individual patient, and engage in shared decision making to ultimately decide what is best for the patient.
Full-text available
Penyakit Creutzfeldt-Jakob merupakan salah satu penyakit prion pada manusia yang fatal, ditandai oleh demensia yang cepat dan progresif disertai mioklonus. Insidensi penyakit yang sangat rendah dan banyaknya gejala atipikal pada stadium awal penyakit menyulitkan penegakkan diagnosis. Belum ada laporan kasus penyakit Creutzfeldt-Jakob di Indonesia. Laki-laki berusia 56 tahun dirujuk dengan keluhan penurunan kesadaran disertai kejang. Pasien mengalami penurunan daya ingat progresif, diawali oleh perubahan perilaku, antara lain tampak bingung, iritabilitas, agresi dan insomnia.
Exposure to high altitude severely impacts performance of unacclimatized individuals and contraindications associated with synthetic drugs ascertain the need for development of herbal drugs. Thus, the present study investigated the adaptogenic potential of Ophiocordyceps sinensis aqueous extract (CSAQ) using simulated altitude stress models such as severe hypoxia (SH) in hermetic vessel, cold restraint (CR) at 4°C, and hypobaric hypoxia (HBH) at 7,620 meter, ~ 282 mm Hg. To further address safety limits of extract, subacute toxicity studies were conducted in rats orally administered with CSAQ (0, 100, 500 and 1000 mg/kg) in a single dose/day for 28 days. Results revealed that animals administered with CSAQ increased convulsion time and core body temperature during SH and CR stress. CSAQ modulated thermogenic response by upregulating uncoupling protein 1 and maintaining metabolic homeostasis. Further, CSAQ improved antioxidant status (glutathione and 2,3-diposhphoglycerate), attenuated pro-inflammatory cytokine NF-κB, and augmented hypoxia inducible factor and nuclear erythroid 2 related factor 2 in HBH exposed animals. Toxicity studies revealed no observed adverse effect level with 1000 mg/kg extract in body weight gain, organ/body weight ratio, hematological variables, biochemical parameters and histoarchitecture of vital organs. In conclusion, CSAQ initiated dose dependent adaptive response and exhibited high safety margins, which strongly suggests the therapeutic potential of CSAQ in mitigating high altitude maladies.
Full-text available
We agree with Dr. Basnyat that dehydration in the mountains is a concern, but no compelling data confirm that dehydration has a role in acute mountain sickness. The report he cites demonstrated a correlation between lower water intake and acute mountain sickness, but causality could not be established; persons with acute mountain sickness are often nauseated and therefore have reduced fluid intake. The only well-controlled investigation found no effect of hydration status on the development of acute mountain sickness.1 As for the rate of ascent, 600 m per day may indeed be too rapid for some, whereas for others, 400 m per day is agonizingly slow. Such is the problem with offering general guidelines. We cited the article by Dumont et al. only to acknowledge the uncertainty regarding the lowest effective dose of acetazolamide. Unlike Dr. Ogilvie, we consider the conclusion by Dumont et al. invalid, for reasons that have already been described elsewhere.2,3 In fact, 500 mg of acetazolamide per day is helpful during rapid ascent.2,3 Only studies directly comparing different doses of acetazolamide will be able to establish the optimal dose; the meta-analysis of Dumont et al. does not. Dr. White highlights the risk of dexamethasone abuse. Dexamethasone should not be used for routine prophylaxis, since it does not enhance acclimatization, as acetazolamide does. However, it is useful for those who have an intolerance to acetazolamide, preferably in the setting of rapid ascent to a high altitude with no further ascent until acclimatization has occurred. We agree that its use as a performance-enhancing agent at high altitude is dangerous. In addition, dexamethasone does not prevent high-altitude pulmonary edema, a deadly risk for those who push their limit of acclimatization. In response to Dr. O’Brien: we did not mention nitric oxide as a therapeutic agent for high-altitude pulmonary edema because no clinical advantage over oxygen has yet been demonstrated, and its use is impractical in the field.Oxygen is remarkably effective for the rapid resolution of high-altitude pulmonary edema. Whether the finding of Anand et al.4 that oxygen combined with nitric oxide is more effective than either alone for decreasing pulmonary vascular resistance will translate into a clinical benefit remains unknown. Perhaps the combination will prove useful for the occasional victim who does not have a prompt response to oxygen. Only a clinical trial can answer this question.
Full-text available
Acute mountain sickness (AMS) describes a constellation of symptoms that is usually self-limited and benign. However, it may impair judgement and physical abilities at high altitudes and interfere with the pleasure of recreational activities. Severe cases may be fatal. Acclimatization is an effective prevention, but is not always practical or possible. Therefore, pharmacologic prophylaxis of AMS is an active area of research.This study used meta-analytic techniques to evaluate the published literature regarding pharmacologic prophylaxis of AMS with acetazolamide and dexamethasone. Twenty eligible reports were located via a computer-assisted search, reference lists and review articles. Dependent measures for this study were the percentage of patients with AMS and the percentage of patients with specific symptoms associated with AMS.An effect size (ES) is the standardized mean difference between experimental and control groups or the conversion from the point-biserial correlation between treatment and effect and allows integration of the results of independent studies. In this study, a negative ES indicates that the prophylaxis regimen exerted a protective effect; the greater the magnitude of the ES the greater its effect. The overall average weighted ES was −0.59 (95% confidence interval (CI) = −0.41 to −0.77) when both drugs’ results were pooled. The average weighted ES for studies comparing acetazolamide to placebo was −0.61 and it was −0.32 for studies comparing dexamethasone to placebo. The average ES was −0.38 when all of the reported symptoms were pooled together.This report confirms the effectiveness of pharmacologic prophylaxis against AMS with acetazolamide or dexamethasone. Acetazolamide appears to be more effective, but inconsistencies in dexamethasone dosing, environmental conditions, and rate of ascent confound interpretation. This meta-analysis points out areas for future research.
Full-text available
Background: The level of environmental hypobaric hypoxia that affects climbers at the summit of Mount Everest (8848 m [29,029 ft]) is close to the limit of tolerance by humans. We performed direct field measurements of arterial blood gases in climbers breathing ambient air on Mount Everest. Methods: We obtained samples of arterial blood from 10 climbers during their ascent to and descent from the summit of Mount Everest. The partial pressures of arterial oxygen (PaO(2)) and carbon dioxide (PaCO(2)), pH, and hemoglobin and lactate concentrations were measured. The arterial oxygen saturation (SaO(2)), bicarbonate concentration, base excess, and alveolar-arterial oxygen difference were calculated. Results: PaO(2) fell with increasing altitude, whereas SaO(2) was relatively stable. The hemoglobin concentration increased such that the oxygen content of arterial blood was maintained at or above sea-level values until the climbers reached an elevation of 7100 m (23,294 ft). In four samples taken at 8400 m (27,559 ft)--at which altitude the barometric pressure was 272 mm Hg (36.3 kPa)--the mean PaO(2) in subjects breathing ambient air was 24.6 mm Hg (3.28 kPa), with a range of 19.1 to 29.5 mm Hg (2.55 to 3.93 kPa). The mean PaCO(2) was 13.3 mm Hg (1.77 kPa), with a range of 10.3 to 15.7 mm Hg (1.37 to 2.09 kPa). At 8400 m, the mean arterial oxygen content was 26% lower than it was at 7100 m (145.8 ml per liter as compared with 197.1 ml per liter). The mean calculated alveolar-arterial oxygen difference was 5.4 mm Hg (0.72 kPa). Conclusions: The elevated alveolar-arterial oxygen difference that is seen in subjects who are in conditions of extreme hypoxia may represent a degree of subclinical high-altitude pulmonary edema or a functional limitation in pulmonary diffusion.
Burtscher, Martin, Markus Flatz, and Martin Faulhaber. Prediction of susceptibility to acute mountain sickness by SaO(2) values during short-term exposure to hypoxia. High Alt. Med. Biol. 5:335-340, 2004 - Prediction of the development of acute mountain sickness (AMS) in individuals going to high altitudes is still a matter of debate. Whereas some studies found that subjects with a blunted hypoxic ventilatory response (HVR) are predisposed to AMS, others did not. However, the HVR has often been determined under very acute (5 to 10 min) isocapnic hypoxia without consideration of the subsequent hypoxic ventilatory decline (HVD), and the assessment of AMS susceptibility was based on a single altitude exposure. Therefore, the aim of the present study was to evaluate the relationship between the individual arterial oxygen saturation (SaO(2)) after a 20- to 30-min exposure to poikilocapnic hypoxia and the AMS susceptibility based on repeated observations. A total of 150 healthy male and female mountaineers (ages: 42 +/- 13 yr), 63 of whom had known susceptibility to AMS and 87 of whom never suffered from AMS, were exposed to various degrees of normobaric and hypobaric hypoxia. SaO(2) values were taken by finger pulseoximetry after 20 to 30 min of hypoxic exposure. SaO(2) values after 20 to 30 min of hypoxia were on average 4.9% lower in subjects susceptible to AMS than in those who were not. Logistic regression analysis revealed altitude-dependent SaO(2) values to be predictive for AMS susceptibility. Based on the derived model, AMS susceptibility was correctly predicted in 86% of the selected individuals exposed to short-term hypoxia. In conclusion, SaO(2) values after 20 to 30 min of exposure to normobaric or hypobaric hypoxia represent a useful tool to detect subjects highly susceptible to AMS.
Context.—Because of its onset in generally remote environments, high-altitude cerebral edema (HACE) has received little scientific attention. Understanding the pathophysiology might have implications for prevention and treatment of both this disorder and the much more common acute mountain sickness. Objectives.—To identify a clinical imaging correlate for HACE and determine whether the edema is primarily vasogenic or cytotoxic. Design.—Case-comparison study. Setting.—Community hospitals accessed by helicopter from mountains in Colo-rado and Alaska. Patients.—A consecutive sample of 9 men with HACE, between 18 and 35 years old, 8 of whom also had pulmonary edema, were studied after evacuation from high-altitude locations; 5 were mountain climbers and 4 were skiers. The control group, matched for age, sex, and altitude exposure, consisted of 3 subjects with high-altitude pulmonary edema only and 3 who had been entirely well at altitude. Four patients with HACE were available for follow-up imaging after complete recovery. Main Outcome Measures.—Magnetic resonance imaging (MRI) of the brain during acute, convalescent, and recovered phases of HACE, and once in controls, immediately after altitude exposure. Results.—Seven of the 9 patients with HACE showed intense T 2 signal in white matter areas, especially the splenium of the corpus callosum, and no gray matter abnormalities. Control subjects demonstrated no such abnormalities. All patients completely recovered; in the 4 available for follow-up MRI, the changes had resolved entirely. Conclusions.—We conclude that HACE is characterized on MRI by reversible white matter edema, with a predilection for the splenium of the corpus callosum. This finding provides a clinical imaging correlate useful for diagnosis. It also suggests that the predominant mechanism is vasogenic (movement of fluid and protein out of the vascular compartment) and, thus, that the blood-brain barrier may be important in HACE.
An epidemic of mild acute mountain sickness (AMS) occurred at a 4-day meeting of epidemiologists held at an altitude of 3000 m (9800 ft) in the Rocky Mountains of Colorado, USA. Questionnaires from 96% of the 105 attendees documented the following symptom frequencies: headache, 59%; shortness of breath, 59%; difficulty in sleeping, 45%; weakness or dizziness, 40%; and nausea, 12%. AMS, defined as three or more symptoms, occurred in 42% of the respondents, and 90% had at least one symptom. One third felt the illness interfered with their concentration at the meeting, and 31% would not plan another meeting at this altitude, although only one person missed meeting sessions as a result of the AMS. AMS should be anticipated by those planning meetings of short duration at high altitude, and by physicians advising travelers to altitudes over 2000 m.
The pathophysiology of high-altitude illnesses has been well studied in normal individuals, but little is known about the risks of high-altitude travel in patients with pre-existing lung disease. Although it would seem self-evident that any patient with lung disease might not do well at high altitude, the type and severity of disease will determine the likelihood of difficulty in a high-altitude environment. The present review examines whether these individuals are at risk of developing one of the main forms of acute or chronic high-altitude illness and whether the underlying lung disease itself will get worse at high elevations. Several groups of pulmonary disorders are considered, including obstructive, restrictive, vascular, control of ventilation, pleural and neuromuscular diseases. Attempts will be made to classify the risks faced by each of these groups at high altitude and to provide recommendations regarding evaluation prior to high-altitude travel, advice for or against taking such excursions, and effective prophylactic measures.
Acute mountain sickness (AMS) is a common condition that affects people that ascend too rapidly to high altitude. It is typically assessed with the Lake Louise AMS Self-report Score (LLSelf) that uses a categorical numeric rating scale to answer five questions addressing AMS-related symptoms, such as headache. A 100-mm visual analog scale (VAS) is commonly used to assess subjective phenomena such as pain, but this scale has never been used for the self-assessment of AMS. The purpose of this study was to compare a VAS score to the total LLSelf and to evaluate the test-retest and interrater reliability of the VAS when used as an assessment of AMS. Participants (N = 356) completed both the LLSelf and the VAS on the summit of Mt. Whitney (4419 m). There was a significant relationship (r = 0.65, p < 0.01) between the LLSelf (2.8 +/- 2.0, mean +/- SD) and the VAS (14.4 +/- 14.1 mm). Fifty-seven participants were randomly selected for reliability testing of the VAS. Both test-retest reliability (ICC = 0.996, 95% CI = 0.992 to 0.998) and interrater reliability (ICC = 1.000, 95% CI = 0.999 to 1.000) were high. The mean difference in the VAS score between tests was <1 mm, as was the difference between raters. These results demonstrate excellent reliability for the VAS as an assessment of AMS.