How to Treat Patients with Obstructive Sleep Apnea
Syndrome during an Altitude Sojourn
Tsogyal D. Latshang and Konrad E. Bloch
Latshang, Tsogyal D. and Konrad E. Bloch. How to treat patients with obstructive sleep apnea syndrome during
an altitude sojourn. High Alt. Med. Biol. 12:303-307.—Considering the high prevalence of the obstructive sleep
apnea syndrome (OSA), it is expected that many patients with the disorder are traveling to altitude. However,
this may expose them to the risk of pronounced hypoxemia, exacerbation of nocturnal breathing disturbances by
frequent central apneas, impaired daytime performance, and high blood pressure. Recently, randomized studies
specifically investigated the effects of altitude (1630–2590m) in OSA patients and the optimal treatment in this
setting. The results indicate that patients should continue to use continuous positive airway pressure therapy
(CPAP) when sleeping at altitude. Since CPAP alone does not control central sleep apnea emerging at altitude,
combined treatment with acetazolamide and CPAP should be considered, in particular, in patients with severe
OSA and co-morbidities. Supplemental oxygen combined with CPAP might be advantageous in patients with
OSA and concomitant cardiopulmonary disease by preventing hypoxemia and central sleep apnea. In patients
unable to use CPAP or if electrical power is not available, an optimally fitted mandibular advancement device
might be an alternative treatment option that can be combined with acetazolamide during altitude sojourns.
Acetazolamide alone is also beneficial and better than no treatment at all, since it improves oxygen saturation,
breathing disturbances, and the excessive blood pressure elevation in OSA patients traveling to altitude.
Key Words: obstructive sleep apnea; continuous positive airway pressure; acetazolamide; treatment; hypoxia;
2%–5% in adult women, many patients are expected to travel
to the mountains. It is therefore surprising that relatively few
studies specifically addressing the health effects of altitude
onsidering the high prevalence of obstructive
sleep apnea (OSA) of at least 3%–7% in adult men and
exposure in OSA patients have been performed. After a brief
review of OSA in general, we will discuss the available sci-
entific data on OSA at altitude and give recommendations on
pre-travel evaluation and treatment at altitude.
The main manifestations of OSA comprise excessive
sleepiness, impaired concentration, unrefreshing sleep with
habitual snoring, and witnessed apneas (McNicholas, 2008).
Sleep Disorders Center, Pulmonary Division, University Hospital of Zurich and Center for Integrative Human Physiology, University of
Zurich, Zurich, Switzerland.
HIGH ALTITUDE MEDICINE & BIOLOGY
Volume 12, Number 4, 2011
ª Mary Ann Liebert, Inc.
OSA represents a risk factor for traffic accidents and cardio-
vascular disease (Bradley and Floras, 2009). The diagnosis is
suspected on clinical grounds and confirmed by a sleep study
(McNicholas, 2008). The main treatment is nocturnal contin-
uous positive pressure (CPAP) applied through a nasal or
oral-nasal mask (Gordon and Sanders, 2005). CPAP splints
the upper airway, thereby preventing airway occlusion with
apneas, oxygen desaturation, and sleep disruption. Daytime
CPAP include mandibular advancement devices (MAD) and
surgery in selected cases (Randerath et al., 2011). Weight loss
in obese patients and avoidance of alcohol and smoking are
important adjuncts (Ryan, 2005).
OSA Patients at Altitude
Prompted by the observation that occasional obstructive
apneas in healthy trekkers ascending to 5050m in Nepal
disappeared with increasing altitude while frequent central
apneas/hypopneas emerged, Burgess and colleagues studied
effects of altitude exposure in 5 men with OSA (Burgess et al.,
2004). During sleep studies in normobaric hypoxia simulating
an altitude of 2750m, obstructive apneas were replaced by
central sleep apneas (Burgess et al., 2006). Patz and colleagues
reported on 11 OSA patients living at >2400m evaluated by
polysomnography at home, in a sleep laboratory at 1370m,
and (in 5 of the 11 patients) near sea level (Patz et al., 2006).
Altitude descent resulted in a significant decrease in sleep-
related breathing disturbances due to a decrease in hy-
popneas and central apneas. In order to corroborate these
findings, we performed a randomized cross-over trial in
34 OSA patients studied during a few days off CPAP at
490m, 1860m, and 2590m, respectively, in the Swiss Alps
(Nussbaumer-Ochsner et al., 2010). Altitude exposure in-
duced pronounced hypoxemia and increased sleep-related
breathing disturbances due to frequent central apneas/
hypopneas (Fig. 1). Daytime evaluation at altitude revealed
that the patients performed poorly in driving simulator tests,
had increased blood pressure, cardiac arrhythmias, weight
gain, and leg edema suggesting water retention (Nussbau-
mer-Ochsner et al., 2010). These data suggested unfavorable
health effects of altitude in untreated OSA patients. Since
cardiovascular diseases and diabetes are common in OSA
patients and since altitude worsens intermittently and im-
poses sustained hypoxemia, the resulting excessive sympa-
thetic activation may expose patients to a high risk of adverse
cardiovascular events at altitude.
Treatment of OSA at altitude
We recently performed a randomized, placebo-controlled,
double-blind trial evaluating acetazolamide as a treatment for
OSA at altitude (Nussbaumer-Ochsner et al., 2011). The study
confirmed that acetazolamide (250mg twice a day) signifi-
cantly improved nocturnal oxygen saturation, reduced cen-
tral apneas/hypopneas and sleep disturbances at 1860m and
2590m, when compared to no treatment at all (Nussbaumer-
Ochsner et al., 2011). In addition, acetazolamide prevented
excessive blood pressure rise and weight gain. However, a
considerable amount of obstructive apneas/hypopneas per-
sisted. Thus, acetazolamide provides some benefit but is not
an optimal treatment for OSA at altitude. Nevertheless, it
might be a valuable option if CPAP therapy is not feasible.
In a subsequent randomized, placebo-controlled, double-
blind study we evaluated whether combined treatment with
acetazolamide and CPAP was superior to CPAP alone (Lat-
shang et al., 2010). Fifty-one OSA patients living below 800m
were studied during a sojourn of a few days in a Swiss alpine
village at 1630m and 2590m, respectively. On combined
treatment with CPAP (RemStar M-series, Philips Respironics,
500mg in the evening), the apnea/hypopnea index (AHI) was
normalized at both moderate altitudes. On CPAP alone, re-
applied pressure at 2590m exceeded values at 490m by 2cm
H2O if acetazolamide was not used; on combined autoCPAP
and acetazolamide treatment, no difference in mask pressure
between values at 2590m and 490m was noted. The data from
this study suggest that the combined treatment seems to be
appropriate for OSA patients at moderate altitude.
withdrawal, altitude exposure was associated with a significant increase in the total AHI (represented by the total length of
the horizontal bars). The increase was related to emergence of frequent central apneas/hypopneas (represented by bars to the
right) while obstructive apneas/hypopneas changed little (bars to the left). Bars and lines are medians and quartile ranges
from data in 34 patients reported by Nussbaumer-Ochsner et al. (2010).
In patients with OSA syndrome studied at 490 m, 1860 m, and 2590 m, respectively, during a few days of CPAP
304 LATSHANG AND BLOCH
Theophylline has been shown to improve high altitude
periodic breathing in healthy subjects (Fischer et al., 2004) but
it is not an effective therapy for OSA and has the drawback of
being arrhythmogenic and sleep disturbing. Modafinil is a
stimulant that improves reaction time and subjective sleepi-
ness in OSA patients during a few days of CPAP withdrawal
(Williams et al., 2010). It might be of some use in very special
circumstances when a patient is unable to use an effective
OSA therapy but needs to maintain a high level of alertness.
Since modafinil does not improve nocturnal breathing and
oxygenation and considering its potential to trigger cardio-
not in hypoxic conditions.
Custom-fitted mandibular advancement devices (MAD)
symptoms, and vigilance in OSA patients at low altitude (Fig.
have not been performed so far but MAD seem to be prom-
ising for persons traveling frequently to the mountains and
ready to make the effort of getting a custom-fitted appliance.
It usually takes several weeks to fabricate a MAD and become
accustomed to its use. Efficacy should be verified prior to
4 days. This treatment can therefore not be established within
short time before departing to high altitude. Prefabricated
devices can be purchased at a lower cost than custom-fitted
appliances, but they are less effective and therefore not re-
commended (Vanderveken et al., 2008).
A nasal expiratory pressure device (Provent) consisting of
valves inserted into the nares has been shown to improve OSA
in highly selected patients (Berry et al., 2011). Further studies
are required to evaluate whether Provent works at altitude.
Nasal obstruction due to dry air at altitude might be a problem
with this therapy. In OSA patients with coexistent chronic
rhinitis, nasal decongestants (during an altitude sojourn of a
few days) or topical steroids might be useful adjuncts that
contribute to a better sleep quality and might also slightly im-
prove OSA (Clarenbach et al., 2008; Kohler et al., 2009).
Surgical interventions have a limited role in the treatment
of OSA and cannot be recommended in general. In particular,
the effects of soft tissue surgery on snoring and OSA are un-
predictable and might not persistent (Ryan, 2005).
Recommendations for OSA Patients
Traveling to Altitude
Pre-travel considerations and preparation
Depending on the time until departure, the destination and
duration of the planned travel, the sleeping altitude, the
available infrastructure (electricity), co-morbidities, age, and
other individual factors, preparations may vary consider-
ably (Nussbaumer-Ochsner and Bloch, 2007; Nussbaumer-
Ochsner and Bloch, 2010). General recommendations include
sleeping pills, and smoking. Concomitant illness such as car-
diovascular disease, diabetes, and obstructive airway disease
should be controlled and stable. Specific recommendations re-
garding diseases other than OSA have been reported elsewhere
and are not further discussed (Dehnert and Bartsch, 2010; Luks
and Swenson, 2007; Nussbaumer-Ochsner and Bloch, 2010).
Patients should have sufficient supply of their regular medica-
tion and a reserve for emergencies. Counseling regarding sus-
related illnesses should also be provided (Bartsch et al., 2004;
used for OSA therapy. Snapped onto the teeth during the
night, this custom-fitted device holds the mandible in a
protruded position thereby preventing upper airway occlu-
sion with obstructive sleep apnea. A mandibular advance-
ment device may be an alternative to CPAP therapy in
frequent altitude travelers. Adapted from Bloch et al. (2000).
Mandibular advancement device. Monobloc device
Table 1. Recommendations to Patients
With Obstructive Sleep Apnea Syndrome
Traveling to Altitude
Pre-travel considerations and evaluation
? Consider available time until departure, duration of travel,
destination, sleeping altitude, available infrastructure.
? Evaluate proper control of OSA by assessing symptoms
and by analyzing CPAP device memory; perform sleep
study and autoCPAP titration if deemed appropriate.
? Check CPAP equipment, proper mask fit, get electrical
cable connections, supplementary batteries and humidifier
if desired; CPAP may be operated in auto-adjusting or in
fixed pressure mode at the level effective at low altitude.
? Inform patients about mandibular advancement devices, a
treatment not requiring electrical power. They should be
custom-fitted and optimally adjusted to control breathing
disturbances which may take several weeks.
? Assess concomitant diseases and associated risks at
altitude and assure proper treatment; sufficient medication
should be available during travel.
? Inform patients about high altitude related illnesses.
Measures during stay at altitude
? Encourage patients to follow general recommendations
regarding sleep hygiene and prevention of high altitude
? Encourage the use of CPAP or mandibular advancement
device at altitude.
? Consider prescribing acetazolamide (2–3·250mg per day)
to be used in combination with CPAP or a mandibular
advancement device, in particular in patients traveling to
high or very high altitude and in those with concomitant
? Prescribe acetazolamide (2–3·250mg per day) in patients
unable to use CPAP or a mandibular advancement device.
OBSTRUCTIVE SLEEP APNEA AT ALTITUDE305
previoususeofacetazolamide. Ashort trialof the drugat home
unpleasant effects (bad taste, paresthesias).
During the pre-travel consultation, effectiveness of OSA
be assessed. Patients should be asked about residual sleepi-
ness, unrefreshing sleep, and other symptoms suggesting in-
complete control of sleep apnea. Application of the CPAP
equipment in the office may identify an imperfect mask fit,
leaks, and skin lesions thatshould be taken care of. Patterns of
CPAP device during home therapy should be downloaded to
assess effectiveness of treatment (Ueno et al., 2010). Depend-
ing on the results, further evaluations including a sleep study
on CPAP should be considered. In patients on fixed pressure
CPAP, a 1–2 week autoCPAP titration period might help to
determine the current effective mask pressure. In the absence
of further scientific studies, it seems that autoCPAP works at
altitude (at least with the one device used in the cited study)
and might have the advantages over a fixed CPAP setting by
continuously adjusting mask pressure according to the actual
needs of the patient (Latshang et al., 2010). Virtually all
modern CPAP devices can be operated at altitude, but man-
ufacturer’s documentation should be studied (according to
the manufacturer’s specification verified at the time of man-
uscript preparation, the most recent CPAP devices from Re-
sMed, Philips Respironics, Breas, Weinmann, and Covidien
incorporate altitude adjustment). Patients planning to use
CPAP during travel should be made aware that an extension
cord and adapters to connect the device to the power outlet
might be required when traveling to foreign countries. CPAP
devices can also be operated from the 12 V electrical circuit of
a car or from portable 12 V batteries (which requires an in-
verter for some CPAP devices). However, the weight of bat-
teries and the need for recharging are drawbacks. The use
of a CPAP device with a humidifier should be considered to
enhance comfort in dry altitude environments, although this
increases power consumption and equipment weight. In pa-
tients with chronic rhinitis, nasal decongestants or topical
steroids might be prescribed (Kohler et al., 2009). In regular
altitude travelers with OSA, analysis of data stored in the
CPAP device during use at altitude with pulse oximetry in-
sleep apnea and requirements for treatment adjustments
during subsequent altitude sojourns.
For patients frequently traveling to altitude on treks away
from electricity and who have sufficient time to establish this
treatment, a custom-fitted MAD (Fig. 2) might be prescribed.
MAD treatment generally requires a minimum of 6–8 upper
and lower teeth (although cases of MAD therapy in edentu-
lous patients have been reported) and absence of periodontal
disease and temporomandibular joint pain. A pre-evaluation
expertise in thisfield is stronglyrecommended. MAD therapy
usually requires a preparation during several months and is
therefore not an option for patients immediately departing to
altitude (Bloch et al., 2003; Randerath et al., 2011).
In patients with severe OSA and cardiovascular or pul-
monary co-morbidity, supplemental oxygen applied into
the CPAP tubing might be advisable and will reverse the
adverse effects of being at altitude. The indication has to
be assessed individually according to recommendations for
the underlying disease (Luks and Swenson, 2007). Appro-
priate infrastructure has to be available and the oxygen
dose has to be titrated according to the individual needs.
Monitoring of pulse oximetry might be advisable. In patients
with COPD, restrictive chest-wall or lung disease, or with
neuromuscular disease, ventilatory stimulation by acet-
azolamide might impose an excessive load on respiratory
muscles. It is therefore not generally recommended in these
conditions at altitude.
Recommended OSA Treatment During
OSA patents living at lowlands and sleeping at an altitude
>1600m without treatment are likely to experience pro-
nounced hypoxemia, aggravated breathing disturbances, ele-
vated blood pressure, and vigilance impairment during
to continue using their CPAP therapy if feasible. Both auto-
humidifier might enhance comfort. As an alternative to CPAP,
patients might use a custom-fitted and optimally adjusted
altitude-related illnesses, including a moderate ascent rate,
avoidance of overexertion should be respected (Nussbaumer-
Ochsner and Bloch, 2007). Depending on the sleeping altitude,
severity of OSA, age, and co-morbidities, the use of acetazol-
amide might be advisable in combination with CPAP (Lat-
at a dose of 2·125mg per day is sufficient to prevent acute
mountainsickness. However,inOSA patients,a higher doseof
2·250mgor250mgin themorningand500mginthe evening
is recommended to treat sleep apnea at altitudes (Latshang
et al., 2010). In settings where CPAP therapy is not feasible,
OSA patients may benefit from acetazolamide alone since it is
better than no treatment at all and mitigates hypoxemia and
sleep-related breathing disturbances and improves subjective
well-being at altitude (Nussbaumer-Ochsner et al., 2011).
patients at altitude is provided in Table 1. The proposed
measures should allow patients to enjoy a refreshing sleep
and wonderful daytime experiences in the mountains despite
Author Disclosure Statement
The authors have no conflicts of interest or financial ties to
Bartsch P, Bailey DM, Berger MM, Knauth M, Baumgartner RW
(2004). Acute mountain sickness: Controversies and advances.
High Alt Med Biol 5:110–124.
Berry RB, Kryger MH, Massie CA (2011). A novel nasal expi-
ratory positive airway pressure (EPAP) device for the treat-
ment of obstructive sleep apnea: A randomized controlled
trial. Sleep 34:479–485.
Bloch KE, Iseli A, Zhang JN, Xie X, Stoeckli PW, Russi EW
(2000). Randomized, controlled trial of two oral appliances for
sleep apnea treatment. Am J Respir Crit Care Med 162:246–
Bloch KE, Senn O, Iseli A (2003). Oral appliances for treatment of
snoring and obstructive sleep apnea. In Surgery for sleep apnea,
306 LATSHANG AND BLOCH
eds. Fabiani M & Saponara M, Kugler Publications, The Ha-
gue, pp. 559–575.
Bradley TD, Floras JS (2009). Obstructive sleep apnoea and its
cardiovascular consequences. Lancet 373:82–93.
Burgess KR, Cooper J, Rice A, Wong K, Kinsman T, Hahn A
(2006). Effect of simulated altitude during sleep on moderate-
severity OSA. Respirology 11:62–69.
Burgess KR, Johnson PL, Edwards N (2004). Central and ob-
structive sleep apnoea during ascent to high altitude. Respir-
Clarenbach CF, Kohler M, Senn O, Thurnheer R, Bloch KE
(2008). Does nasal decongestion improve obstructive sleep
apnea? J Sleep Res 17:444–449.
Dehnert C, Bartsch P (2010). Can patients with coronary heart
disease go to high altitude? High Alt Med Biol 11:183–88.
Fischer R, Lang SM, Leitl M, Thiere M, Steiner U, Huber RM
(2004). Theophylline and acetazolamide reduce sleep-disor-
dered breathing at high altitude. Eur Respir J 23:47–52.
Gordon P, Sanders MH (2005). Sleep 7: Positive airway pressure
therapy for obstructive sleep apnoea/hypopnoea syndrome.
Kohler M, Bloch KE, Stradling JR (2009). The role of the nose in
the pathogenesis of obstructive sleep apnea. Curr Opin Oto-
laryngol Head Neck Surg 17:33–37.
Latshang TD, Nussbaumer-Ochsner Y, Ulrich-Somaini S, Kohler
M, Bloch KE. (2010). Combined autoCPAP and acetazolamide
treatment controls breathing disturbances in patients with
obstructive sleep apnea syndrome at altitude. Eur Respir J
Luks AM, Swenson ER (2007). Travel to high altitude with pre-
existing lung disease. Eur Respir J 29:770–792.
Maggiorini M (2010). Prevention and treatment of high-altitude
pulmonary edema. Prog Cardiovasc Dis 52:500–506.
McNicholas WT (2008). Diagnosis of obstructive sleep apnea in
adults. Proc Am Thorac Soc 5:154–160.
Nussbaumer-Ochsner Y, Bloch KE (2007). Lessons from high-
altitude physiology. Breathe 4:123–132.
Nussbaumer-Ochsner Y, Bloch KE (2010). Air travel and alti-
tude. In Environmental Medicine, eds. Ayres JG, Harrison RM,
Nichols GL, Maynard RL, Hodder Arnold, London; pp. 547–
Nussbaumer-Ochsner Y, Latshang TD, Ulrich S, Kohler M,
Thurnheer R, Bloch KE (2011). Patients with obstructive sleep
apnea syndrome benefit from acetazolamide during an alti-
tude sojourn: A randomized, placebo-controlled, double-blind
trial. Chest [June 9, 2011, epub ahead of print.]
Nussbaumer-Ochsner Y, Schuepfer N, Ulrich S, Bloch KE (2010).
Exacerbation of sleep apnoea by frequent central events in
patients with the obstructive sleep apnoea syndrome at alti-
tude: A randomised trial. Thorax 65:429–435.
Patz D, Spoon M, Corbin R, Patz M, Dover L, Swihart B, White
D (2006). The effect of altitude descent on obstructive sleep
apnea. Chest 130:1744–1750.
Punjabi NM (2008). The epidemiology of adult obstructive sleep
apnea. Proc Am Thorac Soc 5:136–143.
Randerath WJ, Verbraecken J, Andreas S, Bettega G, Boudewyns
A, Hamans E, Jalbert F, Paoli JR, Sanner B, Smith I, Stuck BA,
Lacassagne L, Marklund M, Maurer JT, Pepin JL, Valipour A,
Verse T, Fietze I (2011). Non-CPAP therapies in obstructive
sleep apnoea. Eur Respir J 37:1000–1028.
Ryan CF (2005). Sleep ·9: An approach to treatment of ob-
structive sleep apnoea/hypopnoea syndrome including upper
airway surgery. Thorax 60:595–604.
Ueno K, Kasai T, Brewer G, Takaya H, Maeno K, Kasagi S,
Kawana F, Ishiwata S, Narui K (2010). Evaluation of the
apnea-hypopnea index determined by the S8 auto-CPAP, a
continuous positive airway pressure device, in patients with
obstructive sleep apnea-hypopnea syndrome. J Clin Sleep
Vanderveken OM, Devolder A, Marklund M, Boudewyns AN,
Braem MJ, Okkerse W, Verbraecken JA, Franklin KA, De Backer
WA, Van de Heyning PH (2008). Comparison of a custom-
made and a thermoplastic oral appliance for the treatment of
mild sleep apnea. Am J Respir Crit Care Med 178:197–202.
Williams SC, Marshall NS, Kennerson M, Rogers NL, Liu PY,
Grunstein RR (2010). Modafinil effects during acute continu-
ous positive airway pressure withdrawal: A randomized
crossover double-blind placebo-controlled trial. Am J Respir
Crit Care Med 181:825–831.
Address correspondence to:
Konrad E. Bloch, MD
University Hospital of Zurich
Received July, 29, 2011;
accepted in final form September 15, 2011
OBSTRUCTIVE SLEEP APNEA AT ALTITUDE307
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