Critique #279 – Effects of moderate alcohol consumption and hypobaric hypoxia: implications for passengers’ sleep, oxygen saturation and heart rate on long-haul flights 

Authors

Trammer RA; Rooney D; Benderoth S; Wittkowski M; Wenzel J; Elmenhorst E-M

Citation

Thorax 2024;0:1–9. https:/doi.org/10.1136/thorax-2023-220998. Epub ahead of print: [please include Day Month Year]

Author’s Abstract

Objective Passengers on long-haul flights frequently consume alcohol. Inflight sleep exacerbates the fall in blood oxygen saturation (SpO2) caused by the decreased oxygen partial pressure in the cabin. We investigated the combined influence of alcohol and hypobaric hypoxia on sleep, SpO2 and heart rate.

Methods Two groups of healthy individuals spent either two nights with a 4-hour

sleep opportunity (00:00–04:00 hours) in the sleep laboratory (n=23; 53 m above sea level) or in the altitude chamber (n=17; 753 hPa corresponding to 2438 m above sea level, hypobaric condition). Participants consumed alcohol before one of the nights (mean±SE blood alcohol concentration

0.043±0.003%). The order of the nights was counterbalanced. Two 8-hour recovery nights (23:00– 07:00 hours) were scheduled between conditions. Polysomnography, SpO2 and heart rate were recorded.

Results The combined exposure to alcohol and hypobaric condition decreased SpO2 to a median (25th/75th percentile) of 85.32% (82.86/85.93) and increased heart rate to a median (25th/75^th percentile) of 87.73 bpm (85.89/93.86) during sleep compared with 88.07% (86.50/88.49) and 72.90 bpm (70.90/78.17), respectively, in the non-alcohol hypobaric condition, 94.97% (94.59/95.33) and 76.97 bpm (65.17/79.52), respectively, in the alcohol condition and 95.88% (95.72/96.36) and 63.74 bpm (55.55/70.98), respectively, in the non-alcohol condition of the sleep laboratory group (all p<0.0001). Under the combined exposure SpO2 was 201.18 min (188.08/214.42) below the clinical hypoxia threshold of 90% SpO2 compared with 173.28 min (133.25/199.03) in the hypobaric condition and 0 min (0/0) in both sleep laboratory conditions. Deep sleep (N3) was reduced to 46.50 min (39.00/57.00) under the combined exposure compared with both sleep laboratory conditions (alcohol: 84.00 min (62.25/92.75); non-alcohol: 67.50 min (58.50/87.75); both p<0.003).

Conclusions The combination of alcohol and inflight hypobaric hypoxia reduced sleep quality, challenged the cardiovascular system and led to extended duration of hypoxaemia (SpO2 <90%).

Forum Summary

A simulation of inflight conditions was used to investigate the combined effect of moderate alcohol consumption and hypobaric hypoxia experienced during long-haul flights, on sleep, oxygen saturation and heart rate. Although high moderate alcohol consumption in these very specific conditions did influence oxygen saturation and heart rate, the results are less representative of the general airplane experience and passengers and do not suffice to suggest that the inflight consumption of alcoholic beverages should be restricted.

Forum Comments

Background

Sleep is a complex physiological and highly regulated process. Sleep is essential for many vital functions including development, energy conservation, brain waste clearance, modulation of immune responses, cognition, performance, vigilance, disease, and psychological state (Zielinski et al., 2016; Jung et al., 2011; Mantantzis et al., 2022; Xie et al., 2013). Both long and short sleep duration are associated with increased risk for all-cause mortality (Cappuccio et al., 2010). Long sleep duration, for example, is associated with increased cardiovascular mortality (da Silva et al., 2016). Sleep also has a demonstrated impact on cognitive function, with sleep disturbances linked to cognitive dysfunction. In addition, sleep has been shown to play a role in emotional processing and different sleep stages influence emotional reactions (Alhola & Polo-Kantola, 2007).

Throughout your time asleep, your brain will cycle repeatedly through two different types of sleep: REM (rapid-eye movement) sleep; and non-REM sleep. The first part of the cycle is non-REM sleep, which is composed of four stages (N1-3 and REM). The first stage (N1) comes between awake and falling asleep, lasting only several minutes. The second stage (N2) comprises the largest percentage of total sleep time and is considered a lighter stage of sleep from which you can be awakened easily. Also, heart rate and breathing slow, and body temperature drops. The third and fourth stages (N3 and REM) are deep sleep. In N3, your body performs a variety of important health-promoting tasks. In REM sleep, brain activity is markedly increased and was previously believed to be the most important sleep phase for learning and memory. Newer data suggests that non-REM sleep is more important for these tasks, as well as being the more restful and restorative phase of sleep (Benington & Heller, 1994; Siegel, 2022). The cycle repeats itself, but with each cycle, you spend less time in the deeper stages three and four of sleep and more time in REM sleep. On a typical night, you will cycle through four or five times[1].

Alcohol use and sleep have a complex relationship. At all dosages, acute alcohol consumption causes a reduction in sleep onset latency, a more consolidated first half of sleep, and an increase in sleep disruption in the second half of sleep. While acute alcohol consumption may induce drowsiness, it can disrupt sleep quality and exacerbate sleep disorders in the long run. During abstinence, sleep disruption is one of the greatest predictors of relapse (Feige et al., 2007). Further studies are needed to assess the impact of repeated nightly alcohol consumption on sleep and the immediate and delayed effects of afternoon alcohol intake on sleep parameters (Ebrahim et al., 2013).

Sleep-promoting effects of alcohol may be mediated via alcohol’s action on adenosine and the wake-promoting cholinergic neurons of the basal forebrain. Alcohol increases extracellular adenosine, resulting in the inhibition of wake-promoting neurons in the basal forebrain. Lesions of the basal forebrain cholinergic neurons or blockade of adenosine receptors results in attenuation of alcohol-induced sleep promotion, suggesting that adenosine and basal forebrain cholinergic neurons are critical for sleep-promoting effects of alcohol (Thakkar et al., 2015).

This study by Trammer et al. (2024) investigated the combined effect of moderate alcohol consumption and hypobaric hypoxia, a condition experienced during long-haul flights, on sleep, oxygen saturation, and heart rate. The authors concluded that the effects of both conditions were supra-additive oxygen saturation and heart rate, and that these young healthy individuals experienced prolonged and clinically relevant oxygen desaturations. The authors suggest restricting access to alcoholic beverages on board airplanes.

Critique

The design of the study is somewhat suboptimal. Two separate settings test for the effect of alcohol consumption. The first setting is a control consisting of a sleep laboratory in which 24 participants were monitored during their sleep having been previously exposed to alcohol or not in a cross-over design. The second setting is an inflight setting consisting of an altitude chamber mimicking flight conditions – hypobaric hypoxia. Similar to the first setting, 24 participants were monitored during a 4-hour sleep being previously exposed to alcohol or not in a cross-over design. Consequently, the effects of alcohol consumption on the physiological parameters measured are best compared within the hypobaric hypoxia condition rather than with normal sleep conditions.

Settings did not only differ in the hypobaric hypoxic condition; they also differed in noise level mimicking realistic flight conditions with 70 dB noise. Furthermore, participants in the hypobaric hypoxic condition were situated in a crew-rest compartment in a supine position. Participants in the control setting also appear to rest in a supine position, which may or may not resemble crew-rest compartment conditions and does not resemble the position usual in economy class during long-haul flights.

Since the settings differ in more aspects than just the hypobaric hypoxic condition, we may not rule out that other variables like noise, compartment, and group composition confounded the differences observed between control and inflight settings.

Sleeping time was restricted to four hours in all conditions. The choice for just four hours was not motivated, but the protocol described in this paper was a segment of a larger research project. The project and the design chosen for this specific segment of the protocol may be aimed at crew conditions rather than at passengers on long-haul flights since sleeping time is unrestricted for passengers.

The amount of alcohol provided was 114.5 mL of vodka, which may translate into approximately 37 g alcohol. This amount may be higher than what is usually considered to be moderate alcohol consumption. It may also be high for participants who usually drink 20-40 g alcohol per week (Table 1) and such an alcohol dose is unacceptable for crew members.

When the effects of high to moderate alcohol consumption are compared within the two settings rather than with normal sleep conditions, the study shows in Figure 2 that high to moderate alcohol consumption affects the duration of only a few sleep stages. Stage N1 is decreased by alcohol in the control condition, but not in the inflight condition, N2 and N3 seem not to change with alcohol in both conditions, and REM sleep duration is decreased by alcohol in both settings. These changes indicate a limited effect on sleep duration, which are in themselves consistent with existing literature.

Similarly, oxygen saturation decreased by alcohol in both settings. Lowered oxygen saturation was compensated for by a higher heart rate in both conditions. A low oxygen saturation of about 87% under inflight conditions is further reduced by high moderate alcohol consumption to 84%. Heart rate increased from about 75 beats to approximately 90 beats per minute in this inflight condition. Although oxygen saturation was reduced, increased heart rate seemed to compensate for a possible oxygen deficit. Since the normal range for heart beats per minute at rest varies between 60 to 100 beats per minute[2], it seems that low oxygenation in these conditions is easily compensated for within the normal physiological ranges for heart rate.

The air we normally breathe is made up of approximately 21% oxygen. The amount of oxygen in the air decreases the higher we move upwards, for example, on a mountain or in an airplane. To ensure sufficient oxygen for airplane passengers, airplanes are designed to artificially maintain cabin oxygen levels at the right level (pressurised). Oxygen levels, however, are only kept at this level up to 8,000 ft in the air. Above this level, the amount of oxygen in the air decreases to about 15%. This leads to lower levels of oxygen in your blood[3]. During flights and flight simulations, oxygenation may drop below 90% without seriously affecting performance (Steinman et al., 2024) and without pilots to recognize low oxygenation (Leinonen et al., 2021).

Altogether, the study shows that high moderate alcohol consumption in an acute setting under inflight conditions does affect the duration of some sleep stages and lowers oxygen saturation, which most likely is compensated for by increasing heart rate. Since the study was performed under specific conditions, such as a supine position in a crew-rest compartment and a restricted sleeping time, using healthy volunteers, the results may be less representative of the general airplane passenger population and experience. Also, the significance of the findings may not suffice to suggest that the inflight consumption of alcoholic beverages should be restricted.

Specific Comments from Forum Members

Forum member Harding shares the reservations expressed in the critique of the study design. “This study concludes that the combination of moderate alcohol consumption and inflight hypobaric conditions results in a decrease in oxygen saturation, an increase in heart rate, and disturbed sleep.  All three effects are considered undesirable, and together ‘pose a considerable strain on the cardiac system’ (Discussion, second paragraph).  It is assumed that this combination of effects increases the risk of cardiac arrest.  However, moderate alcohol consumption has an anti-clotting effect (not mentioned at all in the paper), so without the data that shows that moderate consumers of alcohol on flights do have a higher risk of cardiac arrest, I cannot see how the final statement, ‘Our findings strongly suggest that the inflight consumption of alcoholic beverages should be restricted’ can be justified.

Further, it is well known that long-haul flights increase the risk of deep vein thrombosis (DVT), both during the flight and for days afterward.  It is equally well established that moderate alcohol consumption decreases the risk of DVT a lot (Pomp et al., 2008), so the effect of moderate alcohol consumption on flights is more complex than the authors suggest.  They have not made their case.”

Furthermore, Forum member Skovenborg considers that “this is a very specialized issue which is difficult to review for the benefit of the general public and relevance to people with some cardiovascular diseases and lung diseases.”

Concluding comments

As suggested by both Forum Member Ellison and Harding, the study design has severe weaknesses, and the implications of their small study are exaggerated by the authors.  There should be epidemiological studies that can ascertain what the risk of sudden death is following flights (as has been shown for venous thrombosis) and whether or not the subject had been consuming alcohol on the flight.  This may be a better way of evaluating the risk.

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Trammer, R. A., Rooney, D., Benderoth, S., Wittkowski, M., Wenzel, J., & Elmenhorst, E.-M. (2024). Effects of moderate alcohol consumption and hypobaric hypoxia: implications for passengers’ sleep, oxygen saturation and heart rate on long-haul flights. Thorax. https://doi.org/10.1136/thorax-2023-220998

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Comments on this critique by the International Scientific Forum on Alcohol Research were provided by the following members:

Henk Hendriks, PhD, Netherlands

Creina Stockley, PhD, MBA, Independent consultant and Adjunct Senior Lecturer in the School of Agriculture, Food and Wine at the University of Adelaide, Australia

Erik Skovenborg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark

Richard Harding, PhD, Formerly Head of Consumer Choice, Food Standards and Special Projects Division, Food Standards Agency, UK

R. Curtis Ellison, MD, Section of Preventive Medicine/Epidemiology, Boston University School of Medicine, Boston, MA, USA

Giovanni Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy

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[1] https://www.hopkinsmedicine.org/health/wellness-and-prevention/the-science-of-sleep-understanding-what-happens-when-you-sleep

[2] https://www.mayoclinic.org/healthy-lifestyle/fitness/expert-answers/heart-rate/faq-20057979#:~:text=A%20normal%20resting%20heart%20rate%20for%20adults%20ranges%20from%2060,to%2040%20beats%20per%20minute.

[3] https://europeanlung.org/en/information-hub/living-with-a-lung-condition/air-travel/are-you-fit-to-fly/