Assessment of hypoxia tolerance to high-altitude exposure following sleep deprivation

INTRODUCTION

Hypoxia is an important aviation stressor in high-altitude flying operations. This is especially the case in helicopter crew who fly maintenance sorties in unpressurized helicopters for transport of men and materials between forwarding posts for replenishment, removal, and evacuation.^[1] Psychological functions such as mental, psychomotor, and cognitive performances are impaired on exposure to reduced oxygen tension at altitude and are of great operational and practical significance in the aviation environment.

Performance of well-learned and practiced tasks is generally preserved adequately up to an altitude of at least 10,000 ft, but when alveolar oxygen tension falls to below 38–40 mmHg (i.e., above an altitude of 16,000–18,000 ft), psychomotor and cognitive functions get impaired significantly. Simple reaction time, pursuit tasks, choice reaction time, tasks involving complex eye-hand coordination, muscular coordination, conceptual reasoning, and short- and long-term memory have been found to get impaired under hypoxia.^[1,2]

Sleep is a basic physiological requirement for optimum cognitive and psychomotor functioning of individuals. Sleep deprivation (SD) has been found to cause impairment in alertness, attention, vigilance, and performance of tasks.^[3] Taking this into consideration, we can logically assume that SD would have a compounding influence on the effects of hypoxia, causing greater concern for aerospace safety. Although these two issues have been studied separately,^[2-4] there is little if any, literature available regarding the interplay between both the factors. This is relevant in the scenario of operations in the Armed Forces, as the aircrew is likely to be exposed to both hypoxia and short spells of SD. It, thus, appears that hypoxia tolerance may well be affected by lack of sleep. Keeping this as a background, a need was felt to study the combined effects of hypoxia and short spells of SD to see if they have any additive effect on performance, compromising aerospace safety.

The study aimed to assess hypoxia tolerance to high-altitude exposure following SD. The objectives of the study were to determine SD in individuals based on sleep-wake data through actigraphy and sleep diary, monitor and compare various physiological parameters such as heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO₂) recorded before and after the exposure to simulated hypobaric hypoxia, assess the symptoms of hypoxia by employing Lake Louise AMS Score, determine the time-lapse for achieving SpO₂ of 75%, and objectively assess the cognitive performance impairment in the hypobaric hypoxic condition among the sleep-deprived personnel using a cognitive testing tool Psychometric Evaluation Designed for Aviators (pSuMEDhA).

MATERIAL AND METHODS

RESULTS

Time to arterial desaturation to 75% SpO₂

On exposure to the altitude of 17,000 ft, a gradual fall of SpO₂ was observed on all 4 days. The values of time to desaturation to 75% SpO₂ are displayed in [Table 2]. ANOVA revealed that the time to 75% SpO₂ was lesser on day 2 (13.24 min) and day 3 (12.14 min) in comparison to a baseline value of day 1 (13.45 min) which again showed a rising trend on day 4 (12.71 s) [Figure 1]. However, these changes in the means were not statistically significant (F = 0.587, P = 0.625).

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Figure 1:

The levels of mean time to 75% SpO2 on exposure to simulated hypobaric hypoxia on days 1–4 in EDC (n=15).

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Dual task test

When compared with baseline ground level, the DTT reaction time showed an increase on exposure to a simulated altitude of 17,000 ft, as shown in [Figure 2]. The “Main Effects (MEs)” of altitude and day were not significant (F = 2.92, P =0.09 with observed power = 0.395 for altitude and F = 1.256, P =0.293 with observed power = 0.328 for day). The “Interaction Effect” of “Altitude_Day” on DTT reaction time was also not significant (P = 0.927).

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Figure 2:

Means of DTT time on ground and at 17,000 ft altitude on day 1, day 2, day 3, and day 4.

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Stroop test

The difference between the Stroop response time of the two phases is a sensitive measure of the response inhibition in the executive functioning cognitive ability. This difference is called Stroop time (ST). When compared with the baseline value, the ST showed an increase on exposure to a simulated altitude of 17,000 ft, as shown in [Figure 3]. The “Main Effects (MEs)” of altitude were significant (F = 6.538, P = 0.012 with observed power = 0.717). However, it was not significant for day (F = 1.064, P = 0.368 with observed power = 0.282). Similarly, the “Interaction Effect” of “Altitude_Day” for ST was also not significant (P = 0.501).

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Figure 3:

Means of Stroop time on ground and at 17,000 ft altitude on day 1, day 2, day 3, and day 4 (n = 15).

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Digit symbol substitution test

When compared with the baseline value at ground level, the DSST response time revealed an increase in exposure to a simulated altitude of 17,000 ft, as shown in [Figure 4]. The “MEs” of altitude were significant (F = 7.455, P = 0.007 with power = 0.772). However, it was not significant for day (F = 1.306, P = 0.276 with power = 0.341). Similarly, the “Interaction Effect” of “Altitude_Day” for DSST time was also not significant (P = 0.552).

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Figure 4:

Means of DSST time on ground and at 17,000 ft altitude on day 1, day 2, day 3, and day 4 (n=15).

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The above results confirmed that there were statistically significant changes in the Stroop and DSST time on exposure to altitude. However, there were no statistically significant changes in the ST and DSST time on the sleep-deprived days (day 2 and day 3) in comparison to the normal sleep days (day 1 and day 4). The result also indicated that there is no accentuation of the effect of hypoxia on DTT, ST, and DSST due to 2 h of SD.

The results of MANOVA with altitude (ground level vs. 17,000 feet) and day (with day 1 and day 4 following normal sleep and day 2 and day 3 following 2 h of SD) and the reaction time in the three tests (DTT, ST, and DSST) are depicted in [Table 3].

Table 3: The results of multifactor ANOVA were computed for three cognitive tests carried out at a simulated altitude of 17,000 ft on 4 days (n=15).

	Main effects				Interaction effects (Altitude_Day) Power		Validity
	Day		Altitude
	F	P	F	P	F	P	R2
DTT	1.256	0.293	2.92	0.09	0.154	0.927	0.060
ST	1.064	0.368	6.538	0.012*	0.792	0.501	0.098
DSST	1.306	0.276	7.455	0.007*	0.754	0.522	0.109

ANOVA: Analysis of variance, DTT: Dual task test, DSST: Digit symbol substitution test, ST: Stroop test

DISCUSSION

In isolation, both the stressors, hypoxia, and SD are known to affect mental performance. In a repeated measure design, the present study intended to evaluate the combined effects of these two stressors across 4 days with 2 consecutive days of 2 h of SD and one night of recovery sleep following that. The functional neuroimaging techniques (fMRI) have shown that the regional, but not global, reduction of the cerebral blood flow, especially in frontal areas of the brain on hypoxia exposure.^[4-6] Similarly, fMRI signals in the dorsolateral prefrontal cortex and intraparietal sulcus while performing attentional tasks were reduced and seen to be a reliable consequence of SD.^[7-9] The literature available on the combined effect of hypoxia and SD^[10,11] is scanty and gives little information on their effect on hypoxia tolerance of an individual. The present study was undertaken to see if the stress of partial SD contributes further in impairing cognition due to hypoxic hypoxia and if it has any bearing on an individual’s overall ability to tolerate hypoxia exposure. This study is thus more relevant in the setting of the Indian Armed Forces, especially during operational requirements, wherein aircrew may suffer short-term SD^[12] and maybe exposed to hypoxic conditions. In the study, 2 h of SD was considered as the average sleep time of aircrew was seen to be about 6 h against a total sleep requirement of 8 h.^[12-14] The present study aimed to find if tolerance to hypoxia of a subject was affected by acute partial SD of 2 h for 2 consecutive days. The effect of recovery of sleep following short spells of SD was also studied. The hypoxia tolerance on exposure to 17,000 ft simulated altitude was assessed by evaluating the scores of subjective symptoms of hypoxia, comparison of physiological parameters (HR and RR), rate of desaturation of arterial blood, and cognitive performance scores on 4 days.

The mean LLAMS score (subjective symptoms of hypoxia) was highest on day 3 (2.13 ± 1.6) and it was below the cutoff criteria of 3.^[15] A comparison of the scores between the baseline day and SD days showed an increasing trend; however, the same was not statistically significant. The scores provided an objective measurement of the severity of hypoxic exposure. However, the usage of the scores itself for quantifying short-duration exposures to hypoxia may not be a suitable option. Although symptoms of hypoxia may be seen on sudden exposure to high altitude, the LLAMS scores should be more appropriately used in a setting of longer exposure to altitudes since the questionnaire has been validated for assessing symptoms following 6 h of exposure to altitude.^[15]

The means of time to 75% SpO₂ (TTSPS), which was representing the hypoxia tolerance at that altitude^[16] are given in [Table 2]. A comparison of time to 75% SpO₂ across 4 days did not show any significant difference, thereby eliminating any influence of 2 h SD on the rate of desaturation of arterial blood. A study by Yoneda et al. used this parameter of arterial desaturation of oxygen to compare hypoxia tolerance in two age groups (those above and below 40 years of age) and found that the lower age group had longer times for fall in oxygen saturation.^[17] In the present study, all participants were below the age of 40 years with a mean age of 33.53 ± 3.6 years which may explain the insignificant reduction in the time to 75% SpO₂.

The HR and RR showed an increase in their means following acute exposure to altitude. This indicates the cardiovascular and respiratory response to the stress of hypoxia.^[1] The difference in the means of HR on ground and altitude of 17,000 ft compared over 4 days showed no significant change. The effect of fatigue due to sleep loss did not show a quantifiable worsening in physiological parameters when exposed to hypoxic conditions.

The effect of SD on cerebral function is similar to that of hypoxia itself, with sleeplessness shown to decrease hypoxic and hypercapnic ventilatory responsiveness.^[18,19] This is suggested by the decreased alpha activity,^[7,8,18,20] the electroencephalographic wave of wakefulness seen during SD. Hypoxia tolerance is a known physiological balance between the cardiorespiratory compensation and the hypoxic insult. SD could be an influencing factor for hypoxia tolerance. However, 2 h of SD did not cause any significant effects on hypoxia tolerance. The duration of SD was probably not enough to bring such overwhelming effects of altered ventilatory responses. The absence of sleep could stress a person, thereby producing endogenous opiates, endorphins, in which animals have shown to decrease ventilatory responses.^[21] However, endorphins have not shown to have such profound effects on adult human respiration, making this explanation unlikely. In a study by White et al., decrease in hypoxic ventilatory responses was seen with SD with measures of resting ventilation and arterial oxygen saturations remaining unchanged.^[19] It is possible that the chemical control of breathing may be important in the maintenance of adequate ventilation and satisfactory arterial gas concentrations in these patients. The adverse effects of SD on these drives could have implications concerning the pathogenesis of acute-on-chronic episodes of hypoventilation and did not show any decrement in the oxygen saturations of healthy adult individuals exposed to short spells of reduced sleep in the present study.

A statistically significant increase in reaction times was noted for ST and DSST on exposure to altitude on all 4 days. However, a comparison of reaction times in all the tests did not show any significant difference across the 4 days indicating that the effect of “2 h SD” on cognitive performance under hypoxia condition could not be established. The effect of SD as a stressor sufficient enough to produce cognitive decrements was seen to be weaker than expected. A study by Dinges et al.^[22] showed a significant cumulative increase in reaction time over 7 days when exposed to 5 h SD. A study by Elmenhorst et al.^[10] showed a cumulative effect of SD on altitude exposure and similarities with cognitive impairments on blood alcohol concentration of 0.4–0.6%. Reduced duration of sleeping may still have some bearing on the performance abilities of an individual who is exposed to hypoxia since altitude has shown a definite decline whereas added SD was seen to be a weaker stressor. In safety-sensitive operational roles, the two stressors acting in conjunction may still show less than an optimum performance by aircrew. However, our study could not establish this fact, probably attributed to the absence of a sufficient level of cumulative sleep loss following 2 h of SD only for 2 days.

Although statistically not significant, an improvement in cognitive performance was seen when comparing the means of cognitive test responses on the day following recovery of sleep. This improvement could reflect that the sleep debt might have been partially recovered which needs further evaluation with larger sample size and longer duration of sleep loss.

Our study had few limitations. The Lake Louise Acute Mountain Sickness scores were used as a measure of the severity of symptoms of hypoxia exposure. The scale is ideally used in studies of altitude of longer duration. Furthermore, time to SpO₂ of 75% was considered as hypoxia tolerance in this study. The reliability of finger pulse oximeters at oxygen saturations below 65–70% is questionable, and thus, the duration of exposure to hypoxia in subjects was restricted. A longer duration of hypoxia exposure may show more pronounced effects since the TUC at a chosen altitude of 17,000 ft is between 20 and 30 min.

CONCLUSION

The results of the study revealed that 2 h of SD on 2 consecutive nights did not alter the physiological parameters of HR, RR, and time to arterial desaturation to 75% SpO₂ on exposure to 17,000 ft. Such exposure to 17,000 ft showed a significant slowing of responses in two cognitive tests (ST and DSST) on all days of study; however, the study could not elicit a statistically significant effect of 2 h of SD across 2 consecutive nights on the cognitive performance measures on exposure to hypoxia.