'Air hunger' arising from increased PCO2 in mechanically ventilated quadriplegics

A number of investigators have proposed that the sense of respiratory discomfort accompanying hypercapnia depends on respiratory mechanoreceptors which inform the sensory cortex of reflex increases in breathing. To test this hypothesis, we studied subjects whose respiratory muscles were paralyzed, and who were thus unable to increase breathing in response to hypercapnia. We gradually elevated inspired PCO2 in four tracheostomized quadriplegic subjects supported by constant mechanical ventilation. These subjects reported sensations of 'air hunger' (e.g., "short of breath", "air-starved") when end-tidal PCO2 increased 10 Torr (mean) above their resting levels. In a second experiment we used the forced-choice technique to determine the ability of three of these subjects to detect repeated changes of end-tidal PCO2. Two detected 7 Torr changes, the third detected 11 Torr changes. These data suggest that changes in breathing are not necessary to evoke the sense of 'air hunger'. We conclude that the likely mechanisms are (1) projection of chemoreceptor afferent traffic to the sensory cortex, and (2) projection of corollary discharge from brainstem respiratory centers to the sensory cortex.