Increased episodes and duration of
apnea during sleep associated with arterial
oxygen desaturation have been reported after administration of
flurazepam. We postulated that an alteration in respiratory control during sleep might be the underlying mechanism of this observation. Accordingly, we measured isocapnic hypoxic and hyperoxic hypercapnic ventilatory and arousal responses during natural (NS) and during
flurazepam-induced (FS) sleep. We found no significant difference in the ventilatory response to
hypoxia during FS compared with that during NS in 8 normal subjects. Similarly, although the ventilatory response to
hypercapnia was performed in only 4 of the 8 subjects during FS, no significant difference from that during NS was noted in these subjects. There was, however, a significant decrease in the number of hypercapnic response tests in which arousal occurred after
flurazepam administration (85% in NS versus 54% in FS; p less than 0.005). Additionally, an increase was seen in the mean PACO2 level at which arousal occurred during FS (51 +/- 1.6, means +/- SEM) as compared with that during
NS (49 +/- 0.9; p less than 0.07). A similar but not significant decrease was noted in the number of hypoxic response tests in which arousal occurred (28% during NS versus 17% during FS). We conclude that while ventilatory responses to
hypoxia and
hypercapnia are normal during sleep after
flurazepam administration, a decrease in arousal response is seen after administration of this
drug in normal subjects. This alteration in arousal response may be the pathogenic mechanism of the increased duration of
apnea reported in association with
flurazepam.