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Nasal high flow (NHF) is an emerging therapy for respiratory support, but knowledge of the mechanisms and applications is limited. It was previously observed that NHF reduces the tidal volume but does not affect the respiratory rate during sleep. The authors hypothesized that the decrease in tidal volume during NHF is due to a reduction in carbon dioxide (CO 2 ) rebreathing from dead space. In nine healthy males, ventilation was measured during sleep using calibrated respiratory inductance plethysmography (RIP). Carbogen gas mixture was entrained into 30 l/min of NHF to obtain three levels of inspired CO 2 : 0.04% (room air), 1%, and 3%. NHF with room air reduced tidal volume by 81 ml, SD 25 ( P &lt; 0.0001) from a baseline of 415 ml, SD 114, but did not change respiratory rate; tissue CO 2  and O 2  remained stable, indicating that gas exchange had been maintained. CO 2  entrainment increased tidal volume close to baseline with 1% CO 2  and greater than baseline with 3% CO 2  by 155 ml, SD 79 ( P = 0.0004), without affecting the respiratory rate. It was calculated that 30 l/min of NHF reduced the rebreathing of CO 2  from anatomical dead space by 45%, which is equivalent to the 20% reduction in tidal volume that was observed. The study proves that the reduction in tidal volume in response to NHF during sleep is due to the reduced rebreathing of CO 2 . Entrainment of CO 2  into the NHF can be used to control ventilation during sleep.    NEW &amp; NOTEWORTHY The findings in healthy volunteers during sleep show that nasal high flow (NHF) with a rate of 30 l/min reduces the rebreathing of CO 2  from anatomical dead space by 45%, resulting in a reduced minute ventilation, while gas exchange is maintained. Entrainment of CO 2  into the NHF can be used to control ventilation during sleep.

Nasal high flow reduces minute ventilation during sleep through a decrease of carbon dioxide rebreathing