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					The Air is Rare

Darlene Smallman, MD
USAFA Cadet Clinic
Colorado Springs, CA
darschultz@gmail.com

         I was sitting at poolside during a USAFA water polo game and wondering what I
should write about for this article. Then I saw the sign above the pool, no doubt painted
to intimidate the opposition. The sign reads United States Air Force Academy, 7250 ft
(2210 m) above sea level. “The air is rare.”
         Although much of the US Military operational focus is in Iraq, we now have
increasing numbers of troops deployed to Afghanistan. The Northeast area of
Afghanistan includes part of the Himalayan Range. Over 64% of the country is
mountainous. The highest elevations include peaks over 6400 m (21,000 ft). Troops
deployed in this area may be exposed to high altitudes with “rare air.” Therefore
knowledge of high altitude medicine is essential for medics deploying to this area.
          This article includes a synopsis on altitude medicine as expertly outlined by Drs
Hackett and Roach in Dr. Auerbach’s Wilderness Medicine. The article will define acute
mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude
cerebral edema (HACE) and other manifestations of altitude sickness. It will look at
diagnosis and treatment of these high altitude ailments. The article will then look at
proven and experimental ways to prevent altitude illness and finally it will briefly
comment on some future research topics that are currently being explored at USAFA by
our human performance lab.
         High altitude is defined by the experts as 1500-3500 m (4921-11,483 ft). At this
altitude you may see mild decrease in exercise performance and increased ventilation.
We see this in USAFA Basic Cadet physical fitness test (PFT) performance at USAFA.
Basics who previously resided at sea level have a difficult time with the initial PFT done
1-2 days after arrival at altitude (7250 ft) and show marked improvement after 6 weeks of
basic training at altitude. This improvement of performance continues for six months to a
year until they seem to become completely acclimated. Very high altitude is 3500-5500
m (11,483-18,045 ft). At this altitude, subjects become markedly hypoxic and
hypocapnic. This is the most common altitude range for severe altitude sickness. People
climbing 14ers (a popular sport in Colorado) attain this altitude. Extreme altitude is over
5500 m (18,045 ft). Ascent to this height without acclimatization will most certainly
result in severe altitude sickness. There is no permanent human habitation above 18,045
ft (2).
         As altitude increases, the barometric pressure decreases. This results in low
partial pressures (not change in concentrations which is a common misconception) of
inspired oxygen and can result in hypoxia. At 5800 m (19,030 ft) the barometric pressure
is one half that at sea level and therefore the inspired pressure of oxygen is ½ the sea
level value (2,6). The USAF requires oxygen for jumping operations at 11,000 ft mean
sea level (MSL). The USAF has determined that flying above this level with no
supplemental oxygen can result in hypoxia and possible poor decision
making/performance.
         Upon becoming exposed to high altitudes, one’s body then acclimatizes to the
situation. One of the first physiologic changes is an increase in ventilation. By
increasing ventilation, the body reduces alveolar carbon dioxide and raises alveolar
oxygen resulting in increased oxygen delivery to tissues. The carotid body, then sensing
a decrease in arterial PO2, signals the medulla to increase ventilation. This carotid body
function is termed hypoxic ventilatory response (HVR). Current medical research on
high altitude climbers reveals subjects with a moderate (not too brisk) HVR and higher
ventilatory reserve resulting in maximum ventilatory efficiency have the greatest ability
to adapt to altitude changes. These subjects were able to summit K2 and Everest without
oxygen (1).
         Factors adversely affecting the ventilatory response and HVR include alcohol,
older sleeping agents, (zolpidem/Ambien is thought to be safe for use at higher altitudes
and its use is even encouraged in AMS patients with fragmented sleep) and fragmented
sleep. Caffeine and coco increase HVR. Physical conditioning has no real effect on
HVR. Acetazolamide (Diamox) increases ventilation and helps prevent altitude sickness
by acting on the central respiratory center and not the peripheral carotid body. Diamox
should not be used in patients with known sulfa allergy as there is cross reactivity (2).
         Hypoxemia can induce an increase in erythropoietin production and therefore a
slow increase in RBC mass. This change will be seen over weeks to months. An
overshoot of this response can cause polycythemia. This increase in RBC mass is
augmented by iron supplementation. This supplementation at altitude may be especially
important in females. In an older study, women supplemented with iron achieved
hematocrit values of men at altitude. Iron supplementation and physical performance of
both men and women at high altitude is currently being studied by the human
performance lab (HPL) at USAFA.
                 Sleep at altitude is often disturbed. Sleep architecture may be disrupted by
hypoxia. Subjects show a decrease in deep sleep or stage 3 and 4 sleep. They have an
increase in stage 1 and no change in stage 2. Treatment with acetazolamide can diminish
periodic breathing and help prevent AMS/HAPE. It acts on the central respiratory center
and diminishes periodic breathing. Zolpidem is a safe sleep adjunct that does not
adversely affect HVR and will help restore fragmented sleep. It can be added to
acetazolamide treatment (2).
         Aerobic exercise capacity at altitude is greatly diminished. Maximal oxygen
uptake (VO2 max) falls approximately 10% for every 1000m (3281 ft) above 1500m
(4921ft) and overall performance at high altitude can’t be predicted by sea level VO2
max. In fact at altitude those with the highest sea level VO2 max have the greatest
decrement in function. Elite mountaineers have normal VO2 max at sea level and
therefore physical performance at altitude is not related to VO2 max. At this time, it is
not known what variables determineVO2 max at altitude, but it is thought that genetics
may play a role. Recently sildenafil (Viagra) has also been shown to improve athletic
performance in some cyclists (with variable response) at altitude. Sildenafil works by
causing lung vasodilation., This drug shows promise not only for increased aerobic
performance at altitude but also for the treatment of HAPE (7). Further studies are
needed to determine which subjects are better able to have maximal aerobic performance
at altitude.
         Since we know aerobic performance is impaired at altitude, how then can athletes
and soldiers prepare themselves for physical rigors at high altitudes? It is currently
recommended that if performing aerobic events (ones lasting greater than 3-4 minutes) at
altitudes greater then 2000 m, that athletes should arrive and train in the area 10-20 days
prior to their event. A recent presentation by the USAFA HPL suggests that one needs an
even longer time period to fully adjust for aerobic competition. Therefore in order to
minimize altitude sickness in soldiers, it would make sense to allow soldiers deployed to
high altitude areas 3-4 weeks to acclimatize before they perform any rigorous physical
missions. Anaerobic events need no time period for acclimatization, but competitors risk
symptoms from AMS if they are only onsite a few days prior to the competition. Other
elite athletes (including some from the Olympic Training Center in Colorado Springs)
subscribe to the “Live high, train low” theory. In this situation, the athletes take
advantage of the physiologic effects hypoxia (some Olympians live in Woodland Park,
CO cabins at 8,500+ ft MSL and train in Colorado Springs at 6000 ft MSL) while resting,
but then take full advantage of the lower altitude environment to maximize their
workouts. Current estimates reveal that training at greater than 2400 m (7878 ft) does not
result in an improvement in sea level performance (2).
         Although exposure to high altitudes can result in increased performance, it can
also lead to illness. Acute, abrupt exposure to high altitude hypoxic environment can
result in acute cerebral hypoxia, loss of consciousness and death. This loss of
consciousness occurs at saturation of oxyhemoglobin from 40-60% (2). The time of
useful consciousness (a term also used by the military aviators referring to G-induced
LOC) with the onset of hypoxia is determined by the severity of the hypoxia (amount of
altitude and current barometric pressure) and the rapidity of onset.
         Most exposures to high altitude, however, do not lead to death. One of the
mildest forms of altitude sickness is a high altitude headache (HAH). The headache is
characterized by bilateral temporal aching headache. It usually occurs 24 hours after a
sudden ascent to altitude greater than 3000 m (9842 ft). The etiology is multi-factoral.
The HAH can be prevented or treated with NSAIDs or acetaminophen. According to the
Auerbach text it appears ibuprofen and aspirin work better than naproxen. Oxygen
therapy is also effect for controlling HAH. Sumitriptan has variable efficacy.
Acetazolamide and dexamethasone can also be used as treatment (2,6).
         High altitude headache may also be the start of acute mountain sickness (AMS).
This illness is characterized by headache, nausea/vomiting, fatigue/lassitude, dizziness
and difficulty sleeping. Symptoms closely mimic those of a hangover. A key feature to
distinguish AMS from dehydration is a trial of hydration. Hydration will not improve
AMS symptoms. Severe extremes of AMS include high altitude pulmonary edema
(HAPE) and high altitude cerebral edema (HACE). It is important to remember that
dyspnea at rest is never normal and is HAPE until proven otherwise. Likewise ataxia is
the one consistent finding in all HACE victims and AMS patients with ataxia should be
treated for HACE (2,6).
         The biochemical mechanisms for these illnesses are not completely understood
and a complete review is beyond the scope of this article. Suffice it to say that subjects
experiencing AMS, HAPE and HACE seem to have changes in their rennin-angiotensin-
aldosterone system. HACE victims experience vasogenic edema which may in part be
mediated by vascular endothelial growth factor (VEGF). These are clearly areas for more
study (2).
        AMS is scored using the Lake Louise system (see attached handout below) (5).
Subjects are more susceptible to AMS when they ascend quickly, attain high altitudes and
sleep at high altitudes, stay at high altitudes for prolonged time periods and exert
themselves at high altitude. Those subjects who ascend slowly, sleep at lower altitudes
than which they climb, minimize their time at very high altitudes and minimize exertion
at high altitudes seem to have the fewest symptoms. Recent altitude exposure (even for a
few days within the last few months) will diminish AMS symptoms. Finally most
experts agree that some subjects have a genetic susceptibility to developing AMS, but
currently we are unable to determine exactly how to test for such a defect (2).
        The most important factors for developing AMS are genetic predisposition,
altitude of residence, rate of ascent, and prior recent altitude exposure (2). To troops
deploying and working in mountainous regions, this information is invaluable. These
troops could be allowed to live in a mountainous area in the US before deploying or at
least upon arrival in a mountainous area, they could be allowed to live there for at least 3-
4 weeks prior to carrying out strenuous missions in the mountains, thus minimizing their
risk for developing AMS. If the troops were forced to ascend to altitude, they could do it
slowly over days and not abruptly in order to minimize AMS casualties. Finally troops
that experience repeated AMS symptoms are probably not suited for duty in high altitude
regions and should consider reassignment of duties. Per the Auerbach text, there does not
appear to be a relationship to fitness with AMS. So increasing fitness standards prior or
during deployment will not help prevent AMS. Smoking also does not increase AMS
risk and while there are hundreds of other reasons to quit smoking, AMS is not one of
them. Oral contraceptives also do not increase AMS risk, so there is no need to change a
female soldier’s contraception prior to her high altitude deployment.
        About 3% of patients who develop AMS may also develop high altitude cerebral
edema (HACE). As previously mentioned, this disorder is thought to be due to vasogenic
edema which may be mediated by vascular endothelial growth factor. The symptoms of
HACE include mental status changes, mental lassitude and ataxia. The treatment
includes descent, O2 2-4 l nasal canula(NC), dexamethasone 6-8 mg IM, po or IV initial
dose then 4 mg q 6 hours, and hyperbaric treatment (with portal hyperbaric bag such as a
Gamow bag). Failure to treat this illness properly can result in death (2,4,6).
        Patient’s with HACE often simultaneously develop high altitude pulmonary
edema (HAPE). HAPE often develops on days 2-4 on ascent to altitudes greater than
2500 m. The patients first notice decreased exercise performance, fatigue and weakness.
This can progress to dyspnea at rest and rales found on physical exam. Patients also
often have other signs and symptoms of AMS. HAPE is treated by minimizing exertion,
heat loss and descent to a lower altitude (or portable hyperbaric therapy if descent is not
possible). O2 4-6 l NC with a taper to 2-4 l NC is used. Medications that can help
symptoms include the following: Nifedipine 10 mg po once then titrate to effect (may
also use long acting 30 mg Nifedipine dose), sildenafil (Viagra) 50 mg po q 8 hours and
inhaled beta agaonist (albuterol). Both HACE and HAPE can also be prevented and
treatment augmented with acetazolamide (Diamox) 125-250 mg po BID (2,6).
        Current research on high altitude medicine includes predictive models to access
individual susceptibility to AMS/HAPE/HACE prior to ascent to altitude. A reservist
medical technician who recently rotated at USAFA is using PJ subjects and monitoring
physiologic parameters during Mt Rainer ascent. He is hoping to develop a simple tool
for determining which troops are more susceptible to AMS/HAPE/HACE. The USAFA
HPL is currently studying the results of fitness test scores of a select group of cadets from
both sea level and high altitude throughout their four year stay at USAFA. The HPL data
suggests that it may take 6 months to a year to develop complete acclimatization to
altitude. The HPL is also researching athletic performance at altitude and ferritin
supplementation. Perhaps we will see future recommendations to test high altitude
deploying soldiers’ ferritin and iron levels and supplement those with low levels one-two
months prior to high altitude deployment. The variable response of cyclists exposed to
simulated high altitude environment and treated with sildenafil also may pave the way for
further studies revealing which patients are more susceptible to AMS/HAPE/HACE (7).
Finally, Stephen Muza, an Army researcher, has published an interesting review paper on
intermittent hypoxic exposure (IHE). He is hopeful that IHE prior to deployment may
provide soldiers deploying to high altitude environments with a competitive edge (3).

Bottomline: When deploying to a high altitude environment make sure that you carry the
following: oxygen, dexamethasone, nifedipine, acetazolamide, albuterol, and sildenafil.
If doing prolonged military operations at high altitudes consider asking for the purchase
of a portable hyperbaric bag such as a Gamow bag. Remember that ataxia and dyspnea at
rest at altitude are never normal and HACE and HAPE need to be ruled out.


References:

1. Bernadi L, Schneider A, Pomidori L, Paolucci E and Cogo A. Hypoxic ventilatory
response in successful altitude climbers. Eur Resir J 27:165-171, 2006.

2. Hackett PH and Roach RC: Altitude Medicine in Auerbach PS editor: Wilderness
Medicine, Philadelphia, PA, 2007, Mosby.

3. Muza S. Military Applications of Hypoxic Training for High Altitude Operations.
Medicine and Science in Sports and Exercise 39(9) 1625-1631, 2007.

4. The Nepal International Clinic, Travel and Mountain Medicine Center website:
http://www.nepalinternationalclinic.com/altitudesicknesstreatment.html

5. On line Altitude Illness Clinical Guide for Physicians:
http://www.high-altitude-medicine.com/AMS-worksheet.html

6. Rigsby, Larry, MD. Website:
http://www.everestnews.com/stories2005/illness01112005.htm

7. Science daily Website:
http://www.sciencedaily.com/releases/2006/06/060624120556.htm
                          AMS Worksheet (5)
                  Based on the Lake Louise AMS Questionnaire

Name______________________________       Age ____    Sex____   Date
_____________

Prev Hx AMS/HAPE/HACE?
Meds:

Ascent Profile:
Treatment:


                                      Time    ____   ____   ____   ____   ____
                                   Altitude   ____   ____   ____   ____   ____
Symptoms:
1.Headache:
                            No headache 0     ____   ____   ____   ____   ____
                            Mild headache 1   ____   ____   ____   ____   ____
                        Moderate headache 2   ____   ____   ____   ____   ____
                   Severe, incapacitating 3   ____   ____   ____   ____   ____
2.GI:
                         No GI symptoms   0   ____   ____   ____   ____   ____
                Poor appetite or nausea   1   ____   ____   ____   ____   ____
           Moderate nausea or vomiting    2   ____   ____   ____   ____   ____
            Severe N&V, incapacitating    3   ____   ____   ____   ____   ____
3.Fatigue/weak:
                      Not tired or weak   0   ____   ____   ____   ____   ____
                  Mild fatigue/weakness   1   ____   ____   ____   ____   ____
             Moderate fatigue/weakness    2   ____   ____   ____   ____   ____
            Severe F/W, incapacitating    3   ____   ____   ____   ____   ____
4.Dizzy/lightheaded:
                              Not dizzy   0   ____   ____   ____   ____   ____
                         Mild dizziness   1   ____   ____   ____   ____   ____
                     Moderate dizziness   2   ____   ____   ____   ____   ____
                 Severe, incapacitating   3   ____   ____   ____   ____   ____
5.Difficulty sleeping:
                    Slept well as usual   0   ____   ____   ____   ____   ____
        Did not sleep as well as usual    1   ____   ____   ____   ____   ____
   Woke many times, poor night's sleep    2   ____   ____   ____   ____   ____
                 Could not sleep at all   3   ____   ____   ____   ____   ____
Symptom Score:
                                              ____   ____   ____   ____   ____

Clinical Assessment:
6.Change in mental status:
                             No change    0   ____   ____   ____   ____   ____
                    Lethargy/lassitude    1   ____   ____   ____   ____   ____
                  Disoriented/confused    2   ____   ____   ____   ____   ____
              Stupor/semiconsciousness    3   ____   ____   ____   ____   ____
7.Ataxia(heel to toe walking):
                              No ataxia   0   ____   ____   ____   ____   ____
         Maneuvers to maintain balance    1   ____   ____   ____   ____   ____
                        Steps off line    2   ____   ____   ____   ____   ____
                             Falls down   3   ____   ____   ____   ____   ____
                            Can't stand   4   ____   ____   ____   ____   ____
8.Peripheral edema:
                               No edema   0   ____   ____   ____   ____   ____
                           One location   1   ____   ____   ____   ____   ____
                 Two or more locations    2   ____   ____   ____   ____   ____
Clinical Assessment Score:
                                              ____   ____   ____   ____   ____
Total Score:
                                              ____   ____   ____   ____   ____

				
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