Lipman, Grant S., Nicholas C. Kanaan, Caleb Phillips, Dave Pomeranz, Patrick Cain, Kristin Fontes, Becky Higbee, Carolyn Meyer, Michael Shaheen, Sean Wentworth, and Diane Walsh. Study Looking at End Expiratory Pressure for Altitude Illness Decrease (SLEEP-AID). High Alt Med Biol 16:154–161, 2015.—Acute mountain sickness (AMS) affects 25%–70% of the tens of millions of high altitude travelers annually, with hypoxia and nocturnal desaturations as major contributing factors. This is the first double blind randomized placebo controlled trial to assess expiratory positive airway pressure (EPAP) for AMS prevention and nocturnal hypoxic events. Healthy adult participants trekking in the Khumbu region of the Himalayas were randomized to a single-use EPAP nasal strip, or a visually identical sham device (placebo) prior to first night sleeping between 4371–4530 m (14,340–14,800 ft). The primary outcome was AMS incidence, measured by Lake Louise Questionnaire (LLQ), with secondary outcomes of AMS severity (by LLQ) and physiologic sleep indices measured by continuous sleep monitor. Intent-to-treat analysis included 219 participants with comparable demographic characteristics, of which 115 received EPAP and 104 placebo. There was no decrease in AMS with EPAP intervention (14% EPAP vs. 17% placebo; p=0.65; risk difference -3.15%, 95% CI -12.85%–6.56%). While overall AMS severity was not different between groups, EPAP reported decreased incidence of headache (64% vs. 76%; p<0.05, OR 0.51, 95% CI 0.27–0.95) and dizziness (81% vs. 98%; p<0.03, OR 0.29, 95% CI 0.09–0.78). During sleep, EPAP resulted in significant improvements in average peripheral oxygenation (Spo2) (80% versus 78%; p<0.01, mean difference=2, 95% CI 0.58–3.63) and a reduced percentage of time below 80% Spo2 (31% vs. 46%; p<0.03, median difference=16, 95% CI 2.22–28.18). This lightweight and inexpensive EPAP device did not prevent acute mountain sickness, but did reduce the subgroup incidence of headache and dizziness while improving average nighttime peripheral oxygenation.
Get full access to this article
View all access options for this article.
References
1.
AnholmJD, PowlesAC, DowneyR3rd, HoustonCS, SuttonJR, BonnetMH, and CymermanA. (1992). Operation Everest II: Arterial oxygen saturation and sleep at extreme simulated altitude. Am Rev Respir Dis, 145:817–826.
2.
BarashIA, BeattyC, PowellFL, PriskGK, and WestJB. (2001). Nocturnal oxygen enrichment of room air at 3800 meter altitude improves sleep architecture. High Alt Med Biol, 2:525–533.
3.
BartschP, BaumgartnerRW, WaberU, MaggioriniM, and OelzO. (1990). Comparison of carbon-dioxide-enriched, oxygen-enriched, and normal air in treatment of acute mountain sickness. Lancet, 336:772–775.
4.
BreslerM, SheffyK, PillarG, PreiszlerM, and HerscoviciS. (2008). Differentiating between light and deep sleep stages using an ambulatory device based on peripheral arterial tonometry. Physiol Meas, 29:571–584.
5.
BurgessKR, JohnsonP, EdwardsN, and CooperJ. (2004). Acute mountain sickness is associated with sleep desaturation at high altitude. Respirology, 9:485–492.
6.
BurtscherM, LikarR, NachbauerW, and PhiladelphyM. (1998). Aspirin for prophylaxis against headache at high altitudes: Randomised, double blind, placebo controlled trial. BMJ, 316:1057–1058.
7.
BurtscherM, MairerK, WilleM, and BroessnerG. (2011). Risk factors for high-altitude headache in mountaineers. Cephalalgia, 31:706–711.
8.
CushingT, PatersonR, HaukoosJ, and HarrisNS. (2013). Intraocular pressure is not associated with acute mountain sickness. High Alt Med Biol, 14:342–345.
9.
Di GiulioC, and WestJB. (2013). Angelo Mosso's experiments at very low barometric pressures. High Alt Med Biol, 14:78–79.
10.
DoshiR, and WestbrookP. (2012). A novel non-prescription nasal EPAP device (theravent) to treat snoring. Sleep Diagn Ther, 7:1–5.
11.
DuncanAW, OhTE, and HillmanDR. (1986). PEEP and CPAP. Anaesth Intensive Care, 14:236–250.
12.
DvirI, AdlerY, FreimarkD, and LavieP. (2002). Evidence for fractal correlation properties in variations of peripheral arterial tone during REM sleep. Am J Physiol Heart Circ Physiol, 283:H434–439.
13.
EichenbergerU, WeissE, RiemannD, OelzO, and BartschP. (1996). Nocturnal periodic breathing and the development of acute high altitude illness. Am J Respir Crit Care Med, 154:1748–1754.
14.
ErbaP, AnastasiS, SennO, MaggiorirniM, and BlochKE. (2004). Acute mountain sickness is related to nocturnal hypoxemia but not to hypoventilation. Eur Respir J, 24:303–308.
15.
FagenholzPJ, GutmanJA, MurrayAF, NobleVE, CamargoAJr, and HarrisNS. (2009). Optic nerve sheath diameter correlates with the presence and severity of acute mountain sickness: Evidence for increased intracranial pressure. J Appl Physiol, 106:1207–1211.
16.
FergussonD, AaronSD, GuyattG, and HebertP. (2002). Post-randomisation exclusions: The intention to treat principle and excluding patients from analysis. BMJ, 325:652–654.
17.
GoldenbergF, RichaletJP, JouhandinM, GisquetA, KeromesA, and LarmignatP. (1988). [Periodic respiration during sleep at high altitude. Effects of a hypnotic benzodiazepine, loprazolam]. Presse Med, 17:471–474.
18.
HackettPH, and RoachRC. (2001). High-altitude Illness. N Engl J Med, 345:107–114.
19.
HeinzerRC, StanchinaML, MalhotraA, FogelRB, PatelSR, JordanAS, and WhiteDP. (2005). Lung volume and continuous positive airway pressure requirements in obstructive sleep apnea. Am J Respir Crit Care Med, 172:114–117.
20.
HeinzerRC, StanchinaML, MalhotraA, JordanAS, PatelSR, LoYL, and WhiteDP. (2006). Effect of increased lung volume on sleep disordered breathing in patients with sleep apnoea. Thorax, 61:435–439.
21.
HerscoviciS, Pe'erA, PapyanS, and LavieP. (2007). Detecting REM sleep from the finger: An automatic REM sleep algorithm based on peripheral arterial tone (PAT) and actigraphy. Physiol Meas, 28:129–140.
22.
HonigmanB, TheisMK, Koziol-McLainJ, RoachR, YipR, HoustonC, and PearceP. (1993). Acute mountain sickness in a general tourist population at moderate altitudes. Ann Intern Med, 118:587–592.
23.
HultgrenHN. (1997). High Altitude Medicine. Stanford, CA: Herb Hultgren.
24.
JacksonSJ, VarleyJ, SellersC, JosephsK, CodringtonL, DukeG, and BaillieJK. (2010). Incidence and predictors of acute mountain sickness among trekkers on Mount Kilimanjaro. High Alt Med Biol, 11:217–222.
25.
JafarianS, GorouhiF, TaghvaA, and LotfiJ. (2008). High-altitude sleep disturbance: Results of the Groningen Sleep Quality Questionnaire survey. Sleep Med, 9:446–449.
26.
JohnsonPL, JohnsonCC, PoudyalP, RegmiN, WalmsleyMA, and BasnyatB. (2013). Continuous positive airway pressure treatment for acute mountain sickness at 4240 m in the Nepal Himalaya. High Alt Med Biol, 14:230–233.
27.
JohnsonPL, PopaDA, PriskGK, EdwardsN, and SullivanCE. (2010). Non-invasive positive pressure ventilation during sleep at 3800 m: Relationship to acute mountain sickness and sleeping oxyhaemoglobin saturation. Respirology, 15:277–282.
28.
KochR, PunterE, GattererH, FlatzM, FaulhaberM, and BurtscherM. (2008). [Application of CPAP improves oxygenation during normobaric and hypobaric hypoxia]. Wien Med Wochenschr, 158:156–159.
29.
LarsonEB, RoachRC, SchoeneRB, and HornbeinTF. (1982). Acute mountain sickness and acetazolamide. Clinical efficacy and effect on ventilation. JAMA, 248:328–332.
30.
LaunayJC, NespoulosO, Guinet-LebretonA, BesnardY, and SavoureyG. (2004). Prevention of acute mountain sickness by low positive end-expiratory pressure in field conditions. Scand J Work Environ Health, 30:322–326.
31.
LavieP, SchnallRP, SheffyJ, and ShlitnerA. (2000). Peripheral vasoconstriction during REM sleep detected by a new plethysmographic method. Nat Med, 6:606.
32.
LavieP, ShlitnerA, SheffyJ, and SchnallRP. (2000). Peripheral arterial tonometry: A novel and sensitive non-invasive monitor of brief arousals during sleep. Isr Med Assoc J, 2:246–247.
33.
LipmanGS, KanaanNC, HolckPS, ConstanceBB, and GertschJH. (2012). Ibuprofen prevents altitude illness: A randomized controlled trial for prevention of altitude illness with nonsteroidal anti-inflammatories. Ann Emerg Med, 59:484–490.
34.
LuksAM, van MelickH, BatarseRR, PowellFL, GrantI, and WestJB. (1998). Room oxygen enrichment improves sleep and subsequent day-time performance at high altitude. Respir Physiol, 113:247–258.
35.
MacinnisMJ, LantingSC, RupertJL, and KoehleMS. (2013). Is poor sleep quality at high altitude separate from acute mountain sickness? Factor structure and internal consistency of the Lake Louise Score Questionnaire. High Alt Med Biol, 14:334–337.
36.
MahadeviaAK, OnalE, and LopataM. (1983). Effects of expiratory positive airway pressure on sleep-induced respiratory abnormalities in patients with hypersomnia-sleep apnea syndrome. Am Rev Respir Dis, 128:708–711.
37.
MandolesiG, AvanciniG, BartesaghiM, BernardiE, PomidoriL, and CogoA. (2014). Long-term monitoring of oxygen saturation at altitude can be useful in predicting the subsequent development of moderate-to-severe acute mountain sickness. Wilderness Environ Med, 25:384–391.
38.
McDevittM, McIntoshSE, RodwayG, PeelayJ, AdamsDL, and KayserB. (2014). Risk determinants of acute mountain sickness in trekkers in the Nepali Himalaya: A 24-year follow-up. Wilderness Environ Med, 25:152–159.
39.
MizunoK, AsanoK, and OkudairaN. (1993). Sleep and respiration under acute hypobaric hypoxia. Jpn J Physiol, 43:161–175.
40.
PatzDS, PatzMD, and HackettPH. (2013). Dead space mask eliminates central apnea at altitude. High Alt Med Biol, 14:168–174.
41.
PenzelT, KesperK, PinnowI, BeckerHF, and VogelmeierC. (2004). Peripheral arterial tonometry, oximetry and actigraphy for ambulatory recording of sleep apnea. Physiol Meas, 25:1025–1036.
42.
PillarG, BarA, ShlitnerA, SchnallR, ShefyJ, and LavieP. (2002). Autonomic arousal index: An automated detection based on peripheral arterial tonometry. Sleep, 25:543–549.
43.
RiegAD, StoppeC, RossaintR, CoburnM, HeinM, and SchalteG. (2012). [EzPAP(R) therapy of postoperative hypoxemia in the recovery room: Experiences with the new compact system of end-expiratory positive airway pressure]. Anaesthesist, 61:867–874.
44.
RoachRC, GreeneER, SchoeneRB, and HackettPH. (1998). Arterial oxygen saturation for prediction of acute mountain sickness. Aviat Space Environ Med, 69:1182–1185.
45.
RoachRC, BartschP, OelzO, and HackettPH. (1993). Lake Louise AMS Scoring Consensus Committee. The Lake Louise acute mountain sickness scoring system. Hypoxia and Molecular Medicine. pp. 272–274. Burlington, VT.: Queens City Printers.
46.
SavoureyG, CateriniR, LaunayJC, GuinetA, BesnardY, HanniquetAM, and BittelJ. (1998). Positive end expiratory pressure as a method for preventing acute mountain sickness. Eur J Appl Physiol Occup Physiol, 77:32–36.
47.
SchnallRP, ShlitnerA, SheffyJ, KedarR, and LavieP. (1999). Periodic, profound peripheral vasoconstriction—A new marker of obstructive sleep apnea. Sleep, 22:939–946.
48.
SchoeneRB, RoachRC, HackettPH, HarrisonG, and MillsWJJr. (1985). High altitude pulmonary edema and exercise at 4,400 meters on Mount McKinley. Effect of expiratory positive airway pressure. Chest, 87:330–333.
SuttonJR, HoustonCS, MansellAL, McFaddenMD, HackettPM, RiggJR, and PowlesAC. (1979). Effect of acetazolamide on hypoxemia during sleep at high altitude. N Engl J Med, 301:1329–1331.
51.
WagnerDR, D'ZatkoK, TatsugawaK, MurrayK, ParkerD, StreeperT, and WillardK. (2008). Mt. Whitney: Determinants of summit success and acute mountain sickness. Med Sci Sports Exerc, 40:1820–1827.
52.
WayneKS. (1976). Positive end-expiratory pressure (PEEP) ventilation. A review of mechanisms and actions. JAMA, 236:1394–1396.
53.
WestJB. (2003). Improving oxygenation at high altitude: Acclimatization and O2 enrichment. High Alt Med Biol, 4:389–398.
54.
WhiteDP, GleesonK, PickettCK, RannelsAM, CymermanA, and WeilJV. (1987). Altitude acclimatization: Influence on periodic breathing and chemoresponsiveness during sleep. J Appl Physiol, 63:401–412.
55.
WickramasingheH, and AnholmJD. (1999). Sleep and breathing at high altitude. Sleep Breath, 3:89–102.
