Low-Dose CO₂ Inhalation to Improve Oxygenation and Exercise Capacity at High Altitude: A Double-Blind Pilot Study

Inhalation of CO₂ 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 CO₂ at precise concentrations at high altitude.

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% CO₂ 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.

Both PaCO₂ and PaO₂ during CO₂ inhalation were significantly higher than during ambient air breathing (PaCO₂: 33.5 ± 4.0 vs. 31.4 ± 3.5 mmHg; PaO₂: 42.3 ± 5.8 vs. 34.9 ± 5.1 mmHg; all p < 0.001) at high altitude. Compared with ambient air, CO₂ inhalation was also associated with a lower heart rate. There was no difference in pH and respiratory rate during inhalation of 2.5% CO₂ and ambient air. ESWT distance during inhaling 2.5% CO₂ 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).

Our results suggest that inhalation of 2.5% CO₂ increases both PaO₂ and exercise performance at 4505 m.

ClinicalTrials. gov identifier: NCT05798416.