High-altitude
illnesses
FIGURE 1
Chest film in a
patient with
high-altitude
pulmonary edema
H
igh-altitude illness includes the pulmonary and
cerebral syndromes that can develop in unaccli-
mated persons after an ascent to high altitude.
The three major types of high-altitude illness are acute
mountain sickness (AMS), high-altitude pulmonary
edema (HAPE), and high-altitude cerebral edema
(HACE). Individual susceptibility to altitude illness
varies considerably, and there are no screening tests to
predict risk for altitude illness. Susceptibility appears
to be inherent in some way and is not affected by train-
ing or physical fitness. How a traveler has responded in
the past to exposure to high altitude is the most reliable
guide for future trips, but even this is not infallible. PAs
should be familiar with these illnesses, as they may be
called upon to treat the acutely ill or may be asked to
consult with patients before high-altitude travel.
ACUTE MOUNTAIN SICKNESS
AMS is the most common form of altitude illness.
Among lowland-living people visiting high altitudes, the
prevalence of AMS has been reported at 25% to 75%.1-4
The author works in emergency medicine at the Eden Medical
Center, Castro Valley, Calif. He has indicated no relationships to
disclose relating to the content of this article.
From the limited
to the potentially
lethal
If you have skiers or other high-altitude
travelers in your practice, awareness of
high-altitude illnesses is a must. Acute
mountain sickness is the most common
and most benign form.
D. Cristopher Benner, PA-C, MMSc
Onset of symptoms typically occurs 8 to 96 hours after
arrival at altitudes greater than 8,000 feet, although
symptoms of AMS can also occur at lower altitudes. In
one study of more than 3,000 tourists visiting moderate
altitude (6,300-9,700 feet) ski resorts in Colorado, 25%
CME Earn Category I CME credit by reading this
article and the article beginning on page 16
and successfully completing the posttest on
page 45. Successful completion is defined as a
cumulative score of at least 70% correct.
This material has been reviewed and is approved for
1 hour of clinical Category I (Preapproved) CME credit by the AAPA.
The term of approval is for 1 year from the publication date of
January 2007.
Learning objectives
• Understand the pathophysiology of high-altitude
sickness
• Describe the signs and symptoms of the three
main types of altitude sickness
• Outline strategies and medications used to prevent
high-altitude sickness
• Discuss treatment choices for the more serious
consequences of high-altitude sickness
www.jaapa.com VOL. 20, NO. 1 JANUARY 2007 JAAPA 37
High-altitude illness
IN THIS ARTICLE
Key Points
➤ Acute mountain sickness is the most common
form of altitude illness, causing shortness of breath
on exertion, headache, nausea, anorexia, insom-
nia, and fatigue.
➤ High-altitude pulmonary edema is a potentially
lethal illness with typical symptoms of productive
cough and shortness of breath at rest. Treatment
with nifedipine or sildenafil shows promise.
➤ High-altitude cerebral edema is another potentially
lethal illness with symptoms of headache and glob-
ally diminished neurologic function, decreased men-
tal status, and confusion. Symptoms typically re-
spond well to dexamethasone and descent to
lower altitudes.
➤ PAs should encourage patients to acclimate
appropriately, ascend slowly, recognize symptoms
of altitude illness early, stop ascent at the first signs
of altitude illness, and be prepared to descend at
the first indication of more serious illness.
Competencies
Medical knowledge
Interpersonal & communication skills
Patient care
Professionalism
Practice-based learning and improvement
Systems-based practice
For an explanation of competencies ratings, see the table of contents.
experienced manifestations of AMS, including at least
three or more of the following: loss of appetite, vomit-
ing, shortness of breath, dizziness or lightheadedness,
unusual fatigue, sleep disturbance, and headache.1 The
majority of these symptoms occurred within the first 12
hours after arrival.
Clinical manifestations
The most common symptoms of AMS are a mild head-
ache, anorexia, insomnia, fatigue, nausea, shortness of
breath with exertion, and sensation of an alcohol hang-
over5 (see Table 1). The headache of AMS is typically
described as throbbing, bitemporal or occipital, and
worse with Valsalva’s maneuver or stooping over.5 There
is no neurologic dysfunction or deficit. Differentiating
AMS from other conditions is important. AMS is com-
monly misdiagnosed as a viral illness, but AMS does not
cause fever or myalgia. An alcohol hangover can typical-
ly be excluded by the history.
38 JAAPA VOL. 20, NO. 1 JANUARY 2007
Diagnosis
The diagnosis of AMS is based on setting, symptoms,
physical findings, and exclusion of other illnesses.5 In
1991, the Lake Louise scoring system was developed. It
serves primarily as a tool for research and academic
purposes, although recent studies have cast doubt on its
sensitivity.6 The most sensitive test for AMS is a de-
crease in activity level and a subjective sensation of
feeling ill.7 Physical examination findings may be quite
unremarkable. Increased respiratory and pulse rates
may be observed, but the remainder of the physical
examination is usually normal.8 Laboratory tests and
radiographs are of little value when the history and
examination are normal aside from findings suggesting
AMS and when other illnesses have been excluded.
Prevention and treatment
Acclimation at altitude may take 12 hours to 4 days.5
Recognizing AMS early is crucial if prevention of fur-
ther, more critical illness is to be avoided. Upon first rec-
ognizing symptoms, the person should stop any further
ascent and should rest and acclimate until symptoms
improve. Ideally, the person should receive supplemen-
◆◆◆◆◆ tal oxygen and prepare for descent to a symptom-free
altitude (typically, descending 1,500-3,000 feet provides
◆◆◆◆
relief).7 Descent is not always possible, however, in
◆◆◆◆ which case medical therapy is crucial.
For relief of mild symptoms, including nausea and
◆
headache without neurologic dysfunction, antiemetics,
◆ supplemental oxygen, and analgesics usually suffice. In
◆
addition, use of a portable hyperbaric chamber—now
common on expeditions to popular high-altitude destina-
tions in remote locations—may provide relief. Inflating
the chamber to a pressure of 2 pounds per square inch
provides an altitude equivalent that is roughly 6,000 feet
lower than the actual surrounding altitude.9 For people
requiring treatment, the safest agent is acetazolamide,
which reduces periodic breathing and improves noctur-
nal oxygenation.9 Zolpidem does not depress ventilation
at high altitude and may therefore be a safe treatment
for insomnia in persons with AMS.10 After the AMS has
resolved, any further ascent should be made with cau-
tion, perhaps with acetazolamide prophylaxis.9
Acetazolamide Mountaineers and other high-altitude
travelers have used acetazolamide for prophylaxis and
acute treatment of AMS for several years. A carbonic
anhydrase inhibitor and mild diuretic, it forces bicarbon-
ate excretion from the kidneys, which reacidifies the
blood, balancing the effects of the expected hyperventi-
lation that occurs at altitude in an attempt to get oxy-
gen. This reacidification acts as a respiratory stimulant,
particularly at night, reducing or eliminating the period-
ic breathing pattern common at altitude. The net effect
is to accelerate acclimation.11 Acetazolamide is not a
www.jaapa.com
magic bullet, and cure of AMS is not immediate. The
effect of acetazolamide is to accelerate a process that
would normally take 24 to 72 hours to a period of 12 to 24
hours. The most common adverse effect associated with
acetazolamide is extremity paresthesias, which usually
stop once the medication is ceased.
The ideal dosing of acetazolamide has been the subject
of much research. Studies have shown excellent results in
the prevention and treatment of AMS with daily dosages
from as low as 250 mg to as high as 750 mg.7,12 The optimal
dosage is uncertain; more comparisons of dosing regimens
are necessary. The 750-mg dosage clearly works, but
patients may complain of unbearable paresthesias.7 Until
further studies are performed, current recommendations
of acetazolamide for otherwise healthy adults are 250 mg
daily in two divided doses for acute treatment or started
3 to 4 days before ascent for prophylaxis.11-12 Persons with
a hypersensitivity to sulfonamides should avoid acetazo-
lamide. Concomitant use of salicylates and acetazolamide
should be avoided because it may cause CNS depression
and metabolic acidosis.
Ginkgo biloba While some studies have found pre-
treatment with Ginkgo biloba to be effective,13 other
research has not.14 Studies are inconclusive, in part be-
cause ginkgo is a complicated plant extract and prep-
arations vary considerably. In addition, dosing, timing,
and ascent profiles have differed.7 Although ginkgo is
relatively safe, further studies are needed.
HIGH-ALTITUDE PULMONARY EDEMA
HAPE is potentially fatal and causes most of the deaths
due to high-altitude illness.15 HAPE is a noncardiogenic
pulmonary edema associated with pulmonary hyperten-
sion and elevated capillary pressure.16
Clinical manifestations
The symptoms of HAPE may appear insidiously over
the course of several hours or days but can also mani-
fest explosively and occur without preceding AMS.
HAPE generally affects healthy young persons, and
children appear to be more susceptible than adults.17 In
addition, those who have experienced HAPE in the past
are at increased risk for recurrence.17
Early symptoms of HAPE include dry cough and
dyspnea with exertion and at rest. These symptoms
often progress to subjective and objective findings of

TA B L E 1
High-altitude illnesses

Manifestations Treatment Prevention

Acute mountain sickness (AMS)

Headache with nausea, dizziness,
and fatigue during first 12 h
after ascent to high altitude; no
neurologic dysfunction
Stop; rest; acclimate; treat symptoms
with analgesics, antiemetics; increase
fluid intake; consider acetazolamide,
250 mg bid; do not ascend higher until
symptoms resolve
Ascend at slow rate; avoid
overexertion; consider prophylaxis
with acetazolamide, 250 mg bid,
started 3-4 d before ascent

High-altitude pulmonary edema (HAPE)

Shortness of breath at rest;
tachypnea; productive, often
rust-colored sputum; rales;
weakness; tachycardia
Initiate plan for immediate descent; if
immediate descent not possible,
administer supplemental oxygen, place
patient in portable hyperbaric chamber,
administer 10 mg nifedipine sublingually;
add dexamethasone if neurologic
function deteriorates
Ascend at slow rate; avoid
overexertion; if previous history
of HAPE, consider prophylaxis
with nifedipine, 20 mg q8h,
and/or inhaled beta-agonist
(eg, salmeterol)

High-altitude cerebral edema (HACE)

Globally diminished neurologic
function, papilledema, loss of
cerebellar control, confusion,
decreased mental status, coma
Initiate plan for immediate descent; if
immediate descent not possible,
administer supplemental oxygen; place
patient in portable hyperbaric chamber;
administer dexamethasone, 8 mg PO,
then 4 mg q6h PO
Ascend at slow rate; avoid
overexertion; consider prophylaxis
with acetazolamide, 250 mg bid,
started 3-4 d before ascent;
treat AMS early

Data from Hackett PH and Roach RC.9

www.jaapa.com VOL. 20, NO. 1 JANUARY 2007 JAAPA 39

High-altitude illness
elevated jugular venous pressure, diffuse crackles on
lung auscultation, and development of frothy sputum,
tachypnea, and cyanosis.9 Chest radiography typically
reveals a normal-sized heart, full pulmonary arteries,
and patchy infiltrates, which are generally confined to
the right middle and lower lobes in mild cases and are
found in both lungs in more severe cases9 (see Figure 1,
page 37). ECG usually demonstrates sinus tachycardia
and often shows right ventricular strain, right axis devi-
ation, right bundle branch block, and P-wave abnormal-
ities.9 Arterial blood gas measurements typically reveal
severe hypoxemia and respiratory alkalosis but not res-
piratory acidosis.9
PAs should encourage appropriate
acclimation, slow ascension,
and early recognition of symptoms.
Prevention and treatment
Ascending slowly is the most effective means of pre-
venting HAPE. People who have previously experi-
enced HAPE may want to consider prophylaxis with
nifedipine. In a study of mountaineers with a history of
radiographically documented HAPE, 20 mg of nifedi-
pine was given by mouth every 8 hours while subjects
ascended from a low altitude and during the following
3 days at altitude. Compared to a placebo group, those
taking nifedipine had a significantly decreased inci-
dence of HAPE (10% in the nifedipine group versus
70% in the placebo group).18
Prophylactic inhalation of high doses of a beta-agonist
is another way to decrease the risk of developing HAPE.
In a double-blind, randomized controlled trial of inhaled
salmeterol, a dosage of 125 mcg every 12 hours was asso-
ciated with a 50% decrease in the incidence of HAPE.19
Oxygen The highest priority in patients with HAPE is
to increase alveolar and arterial oxygenation. Breathing
supplemental oxygen reduces pulmonary artery pressure
30% to 50%, which is sufficient to reverse the effects of
HAPE early.20-22 Portable hyperbaric oxygen therapy
units, which are becoming increasingly popular on moun-
taineering expeditions, may provide dramatic temporary
relief until a patient can be moved to a lower altitude.
Hyperbaric oxygen units effectively “lower” a patient
several thousand feet in a matter of minutes.
Nifedipine Well-controlled studies have been per-
formed examining nifedipine use for HAPE prophylax-
is. Nifedipine in the acute treatment of HAPE contin-
ues to be studied, but preliminary data support this
use.20,23 In patients experiencing HAPE, the sublingual
40 JAAPA VOL. 20, NO. 1 JANUARY 2007 www.jaapa.com
administration of 10 mg of nifedipine resulted in clinical
improvement, better oxygenation, reduction of pulmo-
nary artery pressure, and progressive clearing of alve-
olar edema.23 Since hypotension is the most worrisome
side effect of nifedipine, BP monitoring is important;
however, nifedipine offers a potential emergency treat-
ment for HAPE when descent or evacuation is impossi-
ble and oxygen is not available.
Sildenafil Preliminary research on the use of silden-
afil for acute treatment of HAPE has shown promising
results. In one study of healthy mountaineers, 50 mg of
sildenafil taken orally reduced pulmonary artery pres-
sure at rest and with exercise, allowing increased exer-
cise capacity at high elevation.24 Other studies have also
shown sildenafil to significantly decrease pulmonary hy-
pertension.25-28 These investigations used varying dos-
ages, and although results are promising, further re-
search is needed.
HIGH-ALTITUDE CEREBRAL EDEMA
HACE is another potentially life-threatening condition.
The current hypothesis is that HACE involves de-
creased integrity in the blood-brain barrier coupled
with an increase in cerebral blood flow induced by
hypoxia.9,29,30 MRI studies of people with HACE have
shown reversible white-matter edema, most promi-
nently in the splenium of the corpus callosum.31
Clinical manifestations
Symptoms of HACE may appear within hours or days
of arrival at high altitude. Signs and symptoms include
papilledema, loss of cerebellar control, confusion, de-
creased mental status, and coma.5 Typically, globally
diminished neurologic function is observed, rather than
focal neurologic deficits. A headache, commonly seen in
AMS, typically precedes HACE symptoms. However,
headaches seen in AMS lack any accompanying neuro-
logic dysfunction.
Prevention and treatment
Slow ascent is the best way to prevent HACE, a po-
tentially life-threatening emergency that requires
immediate management. Upon recognizing HACE in
an individual, make plans for immediate descent and
administer supplemental oxygen and dexamethasone.
The suggested dose of dexamethasone is 8 mg by mouth
initially, followed by 4 mg by mouth every 6 hours.32 If
descent to a lower altitude is not immediately possible,
the patient may be placed in a portable hyperbaric
chamber as a temporary measure.
Conclusion
Whether skiing the slopes of Colorado’s high country or
wandering the streets of La Paz, Bolivia, travelers at
high altitude find both exciting opportunities and the
potential for serious illness. Those who do not live at
high altitudes rarely want to spend 2 to 3 days of a 7-day
vacation resting and acclimating. Whether treating
patients in a high-altitude ski town or consulting with
them before a high-altitude trip, PAs should encourage
appropriate acclimation, slow ascension, and early
recognition of symptoms. ■

REFERENCES
1. Honigman B, Theis MK, Koziol-McLain J, et al. Acute mountain sickness in a gener-
al tourist population at moderate altitudes. Ann Intern Med. 1993;118(8):587-592.
2. Hackett PH, Rennie D. Rales, peripheral edema, retinal hemorrhage and acute
mountain sickness. Am J Med. 1979;67(2):214-218.
3. Maggiorini M, Buhler B, Walter M, Oelz O. Prevalence of acute mountain sickness in
the Swiss Alps. BMJ. 1990;301:853-855.
4. Johnson TS, Rock PB. Current concepts. Acute mountain sickness. N Engl J Med.
1988;319(13):841-845.
5. Hackett PH, Roach RC. High-altitude medicine. In: Auerbach PS, ed. Wilderness
Medicine. 3rd ed. St Louis, Mo: Mosby; 2001:1.
6. Southard AG, Roosa JR, Skurky-Thomas MA, et al. Lake Louise scoring system
underestimates symptoms of acute mountain sickness in 4-11-year-old children.
Acad Emerg Med. 2005;12(5 suppl 1):168.
7. Hackett PH. Proceedings of the Wilderness Medical Society Summer Conference,
Snowmass, Colorado, 2005. Lawrence, Kan: Wilderness Medical Society; 2005.
Available at: http://www.wms.org. Accessed December 8, 2006.
8. O’Connor T, Dubowitz G, Bickler PE. Pulse oximetry in the diagnosis of acute moun-
tain sickness. High Alt Med Biol. 2004;5(3):341-348.
9. Hackett PH, Roach RC. High altitude illness. N Engl J Med. 2001;345(2):107-114.
10. Beaumont M, Goldenberg F, Lejeune D, et al. Effect of zolpidem on sleep and venti-
latory patterns at simulated altitude of 4,000 meters. Am J Respir Crit Care Med.
1996;153(6 pt 1):1864-1869.
11. Dietz TE. ISMM: International Society for Mountain Medicine. Draft 5a: An altitude
tutorial. Available at: http://www.ismmed.org/np_altitude_tutorial.htm. Accessed
December 8, 2006.
12. Basnyat B, Gertsch JH, Johnson EW, et al. Efficacy of low-dose acetazolamide (125
mg bid) for the prophylaxis of acute mountain sickness: a prospective, double-blind,
randomized, placebo-controlled trial. High Alt Med Biol. 2003;4(1):45-52.
13. Gertsch JH, Seto TB, Mor J, Onopa J. Ginkgo biloba for the prevention of severe
acute mountain sickness (AMS) starting one day before rapid ascent. High Alt Med
Biol. 2002;3(1):29-37.
14. Chow T, Browne V, Heileson HL, et al. Ginkgo biloba and acetazolamide prophylaxis
for acute mountain sickness: a randomized, placebo-controlled trial. Arch Intern
Med. 2005;165(3):296-301.
15. Hackett PH, Roach RC. High-altitude medicine. In: Auerbach PS (ed). Wilderness
Medicine. 3rd ed. St Louis, Mo: Mosby: 2001:2.
16. Maggiorini M, Melot C, Pierre S, et al. High altitude pulmonary edema is initially
caused by an increase in capillary pressure. Circulation. 2001;103(16):2078-2083.
17. Scoggin CH, Hyers TM, Reeves JT, Grover RF. High altitude pulmonary edema in the
children and young adults of Leadville, Colorado. N Engl J Med. 1977;297(23):1269-
1272.
18. Bartsch P, Maggiorini M, Ritter M, et al. Prevention of high-altitude pulmonary edema
by nifedipine. N Engl J Med. 1991;325(18):1284-1289.
19. Sartori C, Allemann Y, Duplain H, et al. Salmeterol for the prevention of high-altitude
pulmonary edema. N Engl J Med. 2002;346(21):1631-1636.
20. Oelz O, Maggiorini M, Ritter M, et al. Nifedipine for high altitude pulmonary oedema.
Lancet. 1991;2:556.
21. Hackett PH, Roach RC, Hartig GS, et al. The effect of vasodilators on pulmonary
hemodynamics in high altitude pulmonary edema: a comparison. Int J Sports Med.
1992;13(suppl 1):S68-S71.
22. Hultgren HN, Lopez CE, Lundberg E, Miller H. Physiologic studies of pulmonary
edema at high altitude. Circulation. 1964;29:393-408.
23. Mong CC, Whittembury J. Chronic mountain sickness. Johns Hopkins Med J. 1976;
139(suppl):87-89.
24. Ghofrani HA, Reichenberger F, Kohstall MG, et al. Sildenafil increased exercise capac-
ity during hypoxia at low altitude and at Mount Everest base camp: a randomized, dou-
ble-blind, placebo-controlled crossover trial. Ann Intern Med. 2004;141(3):169-177.
25. Aldashev AA, Kojonazarov BK, Amatov TA, et al. Phosphodiesterase type 5 and high
altitude pulmonary hypertension. Thorax. 2005;60(8):683-687.
26. Ricart A, Maristany J, Fort N, et al. Effects of sildenafil on the human response to
acute hypoxia and exercise. High Alt Med Biol. 2005;6(1):43-49.
27. Perimenis P. Sildenafil for the treatment of altitude-induced hypoxaemia. Expert Opin
Pharmacother. 2005;6(5):835-837.
28. Richalet JP, Gratadour P, Robach P, et al. Sildenafil inhibits altitude-induced hypox-
emia and pulmonary hypertension. Am J Respir Crit Care Med. 2005;171(3):275-281.
29. Severinghause JW, Chiodi H, Eger EI 2nd, et al. Cerebral blood flow in man at high
altitude: role of cerebrospinal fluid pH in normalization of flow in chronic hypocapnia.
Circ Res. 1966;19(2):274-282.
30. Huang SY, Tawney KW, Bender PR, et al. Internal carotid flow velocity with exercise
before and after acclimatization to 4,300 m. J Appl Physiol. 1991;71(4):1469-1476.
31. Hackett PH, Yarnell PR, Hill R, et al. High altitude cerebral edema evaluated with
magnetic resonance imaging: clinical correlation and pathophysiology. JAMA. 1998;
280(22):1920-1925.
32. West JB; American College of Physicians; American Physiological Society. The phys-
iologic basis of high altitude diseases. Ann Intern Med. 2004;141(10):789-800.