‘Air hunger’ from increased PCO2 persists after complete neuromuscular block in humans

Abstract The tolerance of totally curarized subjects for prolonged breath hold is viewed by many as evidence that respiratory muscle contraction is essential to generate the sensation of breathlessness. Although conflicting evidence exists, none of it was obtained during total neuromuscular block. We completely paralyzed four normal, unsedated subjects with vecuronium (a non-depolarizing neuromuscular blocker). Subjects were mechanically ventilated with hyperoxic gas mixtures at fixed rate and tidal volume. End-expiratory P CO 2 ( Pet CO 2 ) was varied surreptitiously by changing inspired P CO 2 . Subjects rated their respiratory discomfort or ‘air hunger’ every 45 sec. At low Pet CO 2 (median 35 Torr) they felt little or no air hunger. When Pet CO 2 was raised (median 44 Torr) all subjects reported severe air hunger. They had reported the same degree of air hunger at essentially the same Pet CO 2 before paralysis. When questioned afterwards all subjects said the sensation could be described by the terms ‘air hunger’, ‘urge to breathe’, and ‘shortness of breath’, and that is was like breath holding. They reported no fundamental difference in the sensation before and after paralysis. We conclude that respiratory muscle contraction is not important in the genesis of air hunger evoked by hypercapnia.