ENDOGENOUS OPIATES MODULATE THE POSTAPNEA VENTILATORY RESPONSE IN THE OBSTRUCTIVE SLEEP-APNEA SYNDROME

Defense of ventilatory homeostasis against recurrent hypercapnia, hypoxia, and acidosis resulting from apnea in obstructive sleep apnea syndrome (OSAS) is dependent on compensatory mechanisms operative between episodes of airway obstruction (2, 3). This investigation was designed to examine whether endogenous opiate activity modulates the compensatory ventilatory response to apnea in OSAS. Polysomnography and quantitative measurement of tidal volume was performed in 12 patients with moderate to severe OSAS during a morning nap study before and after intravenous administration of 10 mg of naloxone. Apnea index was not significantly altered. There was a small but significant shortening of apneas (postnaloxone apnea duration, 91.2% of prenaloxone; p = 0.002 by ANOVA). Tidal volume of the first postapnea breath and minute ventilation extrapolated from the first two postapnea breaths, but not frequency, increased significantly after naloxone (postnaloxone first breath volume, 112.7% of prenaloxone value [p = 0.03], with a similar increase for minute ventilation, 115.1% [p = 0.007]). The volume of the first postapnea breath was correlated with the duration of the previous apnea, both before (r = 0.59, p = 0.0001) and after naloxone. Despite this, analysis of covariance with apnea duration as the covariate confirmed a significant independent increase in postapnea breath volume after naloxone (p = 0.001). Naloxone also altered sleep architecture, increasing percent time awake during the study period (prenaloxone, 36.3 +/- 15.6%; postnaloxone, 56.7 +/- 22.4%; p = 0.0003) and decreasing total sleep time and percent time in Stage 1. Furthermore, naloxone increased continuity of awake periods (mean length of awake periods increased from 27.0 +/- 8.4 to 66.0 +/- 66.6 s after naloxone, p = 0.05). A close correlate of this interapnea arousal period, the interval between apneas, also increased after naloxone (postnaloxone interapnea interval, 136.9% of prenaloxone value; p = 0.0002), suggesting that naloxone increased the degree of postapnea wakefulness. Despite this, an analysis of covariance with interapnea duration as the covariate also demonstrated augmentation of postapnea tidal volume after naloxone (p = 0.04), suggesting that prolongation of wakefulness was not the sole mechanism for the change in postapnea ventilation. These data suggest that endogenous opiate activity influences the magnitude of postapnea ventilatory events in OSAS by directly modulating ventilatory control and indirectly by altering level of postapnea wakefulness. Because postapnea ventilation contributes to the preservation of ventilatory homeostasis, we propose that enhanced endogenous opiate activity in OSAS modifies compensatory mechanisms defending ventilatory homeostasis and could contribute to the development of chronic hypercapnia in this syndrome.