Introduction
Hypobaric hypoxia plays a vital role in acute mountain sickness (AMS). However, partial pressure of oxygen (PaO2) values – sometimes estimated through peripheral oxygen saturation (SpO2) measurements – do not necessarily correlate with susceptibility or clinical symptoms, leading to the hypothesis that cerebral hypoxia may be more relevant. Reference Imray, Barnett and Walsh1 Brain oxygenation has been deemed critical in determining performance and illness at high altitude. This is also partly due to the close relation of cerebral oxygenation with cerebral carbon dioxide levels, vasodilation, and constriction, and resulting cerebral hemodynamics. Reference Imray, Brearey and Clarke2 Regional cerebral oxygen saturation (rSO2) measured non-invasively through near-infrared spectroscopy (NIRS) is an emerging tool in modern clinical medicine. Especially in acute settings, rSO2 can give an insight towards cerebral oxygenation. Reference Murkin and Arango3–Reference Schnaubelt, Sulzgruber, Menger, Skhirtladze-Dworschak, Sterz and Dworschak5 It is important to observe dynamics over a period of time rather than single measurements. Also, a high inter-subject variability makes individual rather than general baselines and normal ranges necessary. Reference Ito, Kanno and Fukuda6–Reference Ohmae, Ouchi and Oda8 Near-infrared spectroscopy has been described to be suitable for use in the high-altitude field in both patients and healthy volunteers. Reference Imray, Barnett and Walsh1,Reference Imray, Brearey and Clarke2,Reference Ulrich, Nussbaumer-Ochsner and Vasic9
Due to a constant increase in mountain leisure time activity and a considerable amount of tourists with comorbid conditions, Mountain Rescue Services (MRS) continuously gain in importance. Reference Martínez-Caballero and Sierra Quintana10–Reference Ströhle, Vögele, Neuhauser, Rauch, Brugger and Paal12 Helicopter Emergency Medical Service (HEMS) can improve the speed of response for injured or acutely-ill mountaineers until adverse weather conditions or difficult terrain make a conventional ascent of MRS necessary, inducing considerable physical strain. Reference Egger, Niederer and Tscherny13 Either way, rescuers are usually exposed to high altitudes and most often also hypobaric hypoxic environments. Therefore, this study aimed at assessing the influence of an active on-foot ascent of MRS to a high altitude on their cerebral oxygenation.
Methods
Experienced members of the Austrian MRS over 18 years of age were included, who took part in this proof-of-concept study voluntarily. The Austrian MRS is an emergency response force with a nation-wide 24-hour stand-by service. In alpine areas, the MRS is in charge of tending to and rescuing individuals in need. This encompasses tasks like locating missing individuals, performing avalanche rescues, and extracting injured and ill patients in rough terrain.
The study measurements took place both at a low altitude (Lienz, East Tyrol, Austria; 673m above sea level) and after an ascent by foot from a mid-height base camp (at 2,240m; >1,213m difference in altitude for the ascent) to a mountain shelter at 3,454m (Erzherzog Johann Hütte; Großglockner Mountain, Austria). The ascent was carried out with a backpack to mimic standard mountain rescue gear. Study logistics were conducted in cooperation with the Austrian Armed Forces, and this study reproduced a previously-described setup. Reference Egger, Niederer and Tscherny13 All data were collected prospectively. In brief, NIRS was measured at the low (673m) and high (3,454m) altitudes using NONIN SenSmart X-100 (Nonin Medical Inc.; Plymouth, Minnesota USA) devices, which are portable, lightweight, and highly-reliable under bright ambient light conditions. 14 One optode was placed on the right and one on the left forehead of each study subject, and measurements of five minutes with data points every four seconds were conducted. The acquisition of subjects’ demographic data including smoking status, fitness assessment, and SpO2 has been described in a previous publication. Reference Egger, Niederer and Tscherny13
Continuous data are presented as absolute differences and medians, with the respective 95% confidence intervals (CI) and interquartile ranges (IQR), and were compared among subgroups using Mann-Whitney-U tests. Categorical data are presented as counts and percentages and were compared using χ²-square tests. Statistical significance was defined by two-tailed P values of <.05. Data analysis was performed using SPSS 22.0 (IBM; Armonk, New York USA).
Ethical approval for this study (N° 1291/2018) was acquired from the Ethical Committee of the Medical University of Vienna, Austria, and all participants provided informed consent. The study protocol complies with the Declaration of Helsinki.
Results
Twenty active members of the Austrian MRS were included. High fitness levels were determined via a standardized fitness questionnaire (FFB mot [Funktionsfragebogen Motorik; motor functions]), as reported previously. Reference Egger, Niederer and Tscherny13 The active on-foot ascent was achieved in 178 (SD = 40) minutes, with a median backpack weight of 10 (8-14) kg. The weather conditions were as follows - Lienz: Sunny, 18°C, 11km/h wind from the south direction, 75% humidity; Großglockner: Sunny, 0.4°C, 25km/h wind from the southwest direction, 70% humidity.
Basic demographics of the study subjects as well as respective NIRS values are summarized in Table 1. The rSo2 values were significantly higher when measured at baseline altitude than at high working altitude (69.9 [SD = 0.6] versus 59.5 [SD = 1.0]; absolute difference 10.4 (95% CI, 6.3-14.5); P <.001), and this was also seen in the subgroups of smokers, non-smokers, men, and women (Table 1 and Table 2). When assessing the single dynamics of each mountain rescuer, there was a wide variability in delta rSO2, ranging from a minimum of 0% to a maximum of 32.1% (Table 3; mean 10.4 [SD = 8.4]%). No symptoms of any kind were reported by the participants.
Table 1. Cerebral Oxygenation (rSO2) Measured via Near-Infrared Spectroscopy (NIRS) in the Valley at 673m Above Sea Level and on the Mountain at 3,454m

Note: Overall study population and subgroups. All of the differences were statistically significant.
Abbreviations: rSO2, regional cerebral oxygen saturation; SD, standard deviation.
Table 2. Differences in Cerebral Oxygenation (rSO2) Measured via Near-Infrared Spectroscopy (NIRS) between Men and Women as well as Smokers and Non-Smokers

Note: None of the differences were statistically significant.
Abbreviations: rSO2, regional cerebral oxygen saturation; SD, standard deviation.
Table 3. Single Cerebral Oxygenation (rSO2) Values of the Mountain Rescuers Measured via Near-Infrared Spectroscopy (NIRS), as well as Individual Differences between Values in the Valley at 673m Above Sea Level and on the Mountain at 3,454m

Note: Age 28 (SD = 12) years, BMI 23 (SD = 2).
Abbreviations: rSO2, regional cerebral oxygen saturation; BMI, body mass index; SD, standard deviation.
Discussion
A depletion of cerebral oxygenation in high altitudes is well-known, with a potential adaptation in long-term residents of high-altitude areas. Reference Ze, Liu and Yang Jin15–Reference Furian, Latshang and Aeschbacher17 However, to the authors’ knowledge, this was the first study assessing cerebral oxygenation (and confirming depleted values) at a high altitude in mountain rescuers after a steep active ascent towards a potential patient, and therefore serving as proof-of-concept. The measured rSO2 values roughly reflect known ranges from other high-altitude populations. Reference Furian, Latshang and Aeschbacher17,Reference Hadolt and Litscher18 A high inter-variability of delta rSO2 could be observed when looking at the mountain rescuers’ values individually. This was not directly reflected by the degree of hypoxemia measured by SpO2 (%) which were at levels that are comparable to previous literature. Reference Egger, Niederer and Tscherny13,Reference Wang, Tsai and Chen19,Reference Narahara, Kimura and Suto20 Many confounders that could not be assessed may have played a role. However, it must be remembered that the participants were all relatively young, very fit, and generally healthy. This, and the low degree of subjective and objective physical exhaustion in the study subjects, Reference Egger, Niederer and Tscherny13 make the results even more interesting and lead to additional questions: (1) Are there factors influencing cerebral oxygenation that are independent of physical fitness and mountain experience? And (2) Is individual adaptation of cerebral oxygenation at high altitudes maybe the more promising method of assessing and determining task performance in mountainous settings? These questions are in line with previous findings. For instance, Hadolt, et al also found a more pronounced depletion in cerebral than in peripheral oxygenation in Himalayan trekkers, Reference Hadolt and Litscher18 whereas Manferdelli, et al reported individuals being more prone to AMS when they showed low cerebral oxygenation values both at rest and during exercise. It was suggested that those individuals were unable to increase microvascular blood volume and therefore maintain oxygenation in hypoxic surroundings. Reference Manferdelli, Marzorati, Easton and Porcelli21
The theory of decreased cognitive function in hypobaric hypoxic conditions is well-established. Reference Furian, Latshang and Aeschbacher17,Reference Wang, Sang and Cui22,Reference Kammerer, Faihs and Hulde23 High-altitude ascents undoubtedly pose a (patho-)physiological cerebrovascular challenge, Reference Lafave, Zouboules and James24 and a reduction of cerebral oxygenation is thought to be the primary cause of AMS. Reference Hadolt and Litscher18,Reference Kammerer, Faihs and Hulde23 It has previously been shown that the physical strain of an alpine ascent potentially leads to a reduction in performance quality performed of mountain rescuers, and that respective guidelines (for instance on cardiopulmonary resuscitation) are thus potentially not a good fit to alpine surroundings. Reference Egger, Niederer and Tscherny13 Performing an active on-foot ascent to get to a patient or victim in alpine surroundings is regularly necessary, as the use of HEMS is not always possible. Reference Egger, Niederer and Tscherny13 Also, individuals transported to high altitudes with a helicopter have previously shown unfavorable neurocognitive Reference Davranche, Casini, Arnal, Rupp, Perrey and Verges25 and practical Reference Wang, Tsai and Chen19 performance, probably due to changes in cerebrovascular reactivity. Reference Liu, Zhang, Luo, Hu, Ma and Wu26 Vuyk, et al reported that Acetazolamide may dampen the exercise-induced depletory effect of high altitudes on cerebral oxygenation. Reference Vuyk, Van Den Bos and Terhell27 Accordingly, Sildenafil is thought to improve rSO2 at altitude. Reference Chan, Hoar and Pattinson28 Whether such pharmacological interventions could be an option to improve performance of mountain rescuers after they had to perform strenuous ascents remains unknown and could be the goal of future research.
Other supportive tools of MRS such as mechanical chest compression devices have already been tested in alpine settings Reference Alexander, Katharina and Verena29 and may be worthwhile to use when optimal human performance cannot be guaranteed because rescuers are simply not oxygenated enough.
Due to rising numbers of complex medical cases in mountainous regions, Reference Martínez-Caballero and Sierra Quintana10–Reference Ströhle, Vögele, Neuhauser, Rauch, Brugger and Paal12 the performance of rescue teams should indeed be moved more into the spotlight of research – cerebral oxygenation and its modulation could play a vital role.
Limitations
This study was merely a pilot trial to show proof-of-concept and to develop suggestions about potential applications and future research possibilities. The small sample size as well as the lack of a complete picture of potential confounders for rSO2 in individual mountain rescuers could have impacted on the results substantially. These data showed a wide variability in outcome measurements among the study subjects. There was no information about the exact permanent residence altitude of the participants (however, all of them lived in the general mountainous vicinity of the study area). Subject number four (Table 3) did not show any difference in NIRS values. As more information on the subject was not available, it can only be speculated about the reasons for this: they could have been especially adapted to high altitudes due to more or very intense training than the others.
Conclusion
Cerebral oxygenation (rSO2) was depleted in healthy and fit mountain rescuers at high altitude after a steep ascent and was significantly lower than in the valley. There were considerable inter-individual differences concerning delta rSO2, the origins of which remain unexplained. Since cognitive impairment in hypobaric hypoxic conditions is known, using rSO2 to assess performance-readiness in mountain rescuers and individual proneness to cognitive dysfunction or AMS could be further research goals.
Conflicts of interest
The authors declare to have no potential conflict of interest in relation to this study.
Acknowledgements
The authors thank all personnel involved in acquiring the study data, especially the members of the Austrian Mountain Rescue Service and the Austrian Army (High Mountain Infantry Battalion 24).
Author Contributions
AE, VF, KT, MN, WS, HH, and DR contributed to data acquisition and study design. SS crafted the manuscript and executed data analyses. TU, WS, HH, and DR supervised the study process and amended the manuscript. SS, AE, VF, KT, MN, TU, WS, HH, and DR critically revised and approved the final version of the manuscript.