Hypercapnia can induce arousal from sleep in the absence of altered respiratory mechanoreception

Possible mechanisms of arousal from respiratory stimuli include changes in PO₂, PCO₂, central respiratory drive, or respiratory mechanoreceptor activity. We sought to determine whether hypercapnia alone could induce arousal from sleep in four subjects with high (≥ C3) neurologically complete spinal cord injuries while on constant positive pressure mechanical ventilation (hence, respiratory mechanoreceptor activity remained constant). Subjects were chronically hypocapnic (mean baseline PET(CO₂) = 21 mm Hg; range, 13-30 mm Hg). On the first night, the baseline rate of spontaneous awakenings was determined by polysomnography. On night two, FI(CO₂) was increased rapidly in stable NREM sleep. Awakenings occurred in 19 of 19 trials within 5 min, with each subject waking and complaining of shortness of breath (mean time to arousal, 115 s; range, 26-264 s). It is unlikely that these were spontaneous, as the times to awakening during hypercapnia were much higher than during baseline conditions (p < 0.05). During rapidly induced hypercapnia, PET(CO₂) overestimates the PCO₂ at the central chemoreceptors. To determine more precisely the PET(CO₂) arousal threshold, PET(CO₂) was increased slowly (approximately 2 mm Hg/min); arousal occurred at a mean PET(CO₂) of 37 mm Hg (range, 23-45 mm Hg; mean change from baseline, 15.8 mm Hg, range, 10-20 mm Hg). Hence, both rapid and slow increases in PET(CO₂) can induce arousal in humans in the absence of changes in respiratory mechanoreceptor activity.