Low‐Dose CO 2 Inhalation to Improve Oxygenation and Exercise Capacity at High Altitude: A Double‐Blind Pilot Study

ABSTRACT Background and Objectives Inhalation of CO 2 might improve hypoxia and exercise performance at high altitude by increasing respiratory drive and offsetting hypocapnia. We developed a novel device with minimized dead space and respiratory resistance to deliver CO 2 at precise concentrations at high altitude. Methods Twenty‐eight healthy lowlanders (aged 38 ± 13 years, male/female: 13/15) were recruited and taken from an altitude lower than 500 m to 4505 m in Tibet by airplane. A randomized double‐blind study was performed to compare blood gases and endurance shuttle walk test (ESWT) during inhalation of ambient air and 2.5% CO 2 using the device. Arterial blood gases were measured within 4 h of arrival at high altitude, and the ESWT was performed on the morning of the second day after arrival. Results Both PaCO 2 and PaO 2 during CO 2 inhalation were significantly higher than during ambient air breathing (PaCO 2 : 33.5 ± 4.0 vs. 31.4 ± 3.5 mmHg; PaO 2 : 42.3 ± 5.8 vs. 34.9 ± 5.1 mmHg; all p < 0.001) at high altitude. Compared with ambient air, CO 2 inhalation was also associated with a lower heart rate. There was no difference in pH and respiratory rate during inhalation of 2.5% CO 2 and ambient air. ESWT distance during inhaling 2.5% CO 2 was significantly longer than that during inhalation of ambient air at high altitude (960.0 (713.2–1464.8) m vs. 677.0 (554.2–1026.9) m, p < 0.001). Conclusions Our results suggest that inhalation of 2.5% CO 2 increases both PaO 2 and exercise performance at 4505 m. Trial Registration ClinicalTrials. gov identifier: NCT05798416