Effects of controlled carbon dioxide delivery by a novel device on sleep in healthy subjects.

Low-dose carbon dioxide (CO2) can stabilize ventilatory drive, reduce sleep-disordered breathing, and improve sleep quality. However, the existing delivery systems introduce dead space and resistance that limit tolerability. We developed a novel mask with low resistance and minimal dead space to deliver CO2 and evaluated its overnight effects on neural respiratory drive, sleep architecture, and potential CO2 accumulation in healthy individuals. Sixteen healthy volunteers [age 42 ± 15 yr; body mass index (BMI) 22.0 ± 2.3 kg/m2] first underwent polysomnography with diaphragmatic electromyography (EMG) recorded via esophageal electrodes under inhalation of different concentrations of CO2. Participants then completed four consecutive overnight polysomnography sessions, with each night involving inhalation of a different CO2 concentration (0.0%, 2.5%, 3.5%, or 5.0%) in randomized order. Arterial blood gases were sampled in the evening before inhalation and the following morning during CO2 exposure. Overnight urinary catecholamines were also measured. Neural respiratory drive increased dose-dependently. Sleep efficiency was highest at 2.5% CO2 (91.7 ± 5.7%) and lowest at 5.0% (78.5 ± 10.1%, P < 0.001); 3.5% CO2 showed sleep efficiency similar to room air, whereas 5.0% reduced rapid eye movement (REM) sleep and increased arousals. Blood gases, blood pressure, heart rate, and catecholamines remained normal at ≤3.5%. Baseline blood gases remained normal after multiple consecutive nights of CO2 inhalation. Overnight inhalation of 2.5% CO2 delivered via the special mask enhances sleep efficiency without adverse physiological effects. Concentrations ≤3.5% appear safe, and no cumulative effect was observed after multiple consecutive nights of CO2 inhalation in healthy subjects.NEW & NOTEWORTHY A novel low-resistance open-mask system enables safe delivery of low-dose CO2 during sleep. Inhaling 2.5% CO2 improves sleep efficiency and increases N3 sleep in healthy adults, without CO2 retention or physiological stress. CO2 up to 3.5% was safe and well tolerated and showed no cumulative effects. These findings demonstrate the physiological safety of low-dose CO2 during sleep and support its potential for treating hypocapnia-related central sleep apnea.