ImportanceEmergency medical services (EMS) providers transiently ascend to high altitude for primary missions and secondary transports in mountainous areas in helicopters that are unpressurised and do not have facilities for oxygen supplementation. The decrease in cerebral oxygen saturation can lead to impairment in attention and reaction time as well as in quality of care during acute exposure to altitude.ObjectiveThe primary aim of the current study was to investigate the effect of oxygen supplementation on cognitive performance in Helicopter EMS (HEMS) providers during acute exposure to altitude.Design, setting, and participantsThis interventional, randomized, controlled, double-blind, cross-over clinical trial was conducted in October 2021. Each trial used a simulated altitude scenario equivalent to 4000 m, in which volunteers were exposed to hypobaric hypoxia with a constant rate of ascent of 4 m/s in an environmental chamber under controlled, replicable, and safe conditions. Trials could be voluntarily terminated at any time. Inclusion criteria were being members of emergency medical services and search and rescue services with an age between 18 and 60 years and an American Society of Anesthesiologists physical status class I.ExposuresEach participant conducted 2 trials, one in which they were exposed to altitude with oxygen supplementation (intervention trial) and the other in which they were exposed to altitude with ambient air supplementation (control trial).Main outcomes and measuresMeasurements included peripheral oxygen saturation (SpO2), cerebral oxygenation (ScO2), breathing and heart rates, Psychomotor Vigilance Test (PVT), Digit-Symbol Substitution Test (DSST), n-Back test (2-BACK), the Grooved Pegboard test, and questionnaires on subjective performance, stress, workload, and positive and negative affect. Paired t-tests were used to compare conditions (intervention vs. control). Data were further analyzed using generalized estimating equations (GEE).ResultsA total of 36 volunteers (30 men; mean [SD] age, 36 [9] years; mean [SD] education, 17 [4] years) were exposed to the intervention and control trials. The intervention trials, compared with the control trials, had higher values of SpO2 (mean [SD], 97.9 [1.6] % vs. 86 [2.3] %, t-test, p = 0.004) and ScO2 (mean [SD], 69.9 [5.8] % vs. 62.1 [5.2] %, paired t-test, p = 0.004). The intervention trials compared with the control trials had a shorter reaction time (RT) on the PVT after 5 min (mean [SD], 277.8 [16.7] ms vs. 282.5 [15.3] ms, paired t-test, p = 0.006) and after 30 min (mean [SD], 276.9 [17.7] ms vs. 280.7 [15.0] ms, paired t-test, p = 0.054) at altitude. While controlling for other variables, there was a RT increase of 0.37 ms for each % of SpO2 decrease. The intervention trials showed significantly higher values for DSST number of correct responses (with a difference of mean [SD], 1.2 [3.2], paired t-test, p = 0.035). Variables in the intervention trials were otherwise similar to those in the control trials for DSST number of incorrect responses, 2-BACK, and the Grooved Pegboard test.Conclusions and relevanceThis randomized clinical trial found that oxygen supplementation improves cognitive performance among HEMS providers during acute exposure to 4000 m altitude. The use of oxygen supplementation may allow to maintain attention and timely reaction in HEMS providers. The impact of repeated altitude ascents on the same day, sleep-deprivation, and additional stressors should be investigated.Trial registration NCT05073406, ClinicalTrials.gov trial registration.