Effects of pentobarbital on upper airway patency during sleep

Abstract

We hypothesised that pentobarbital would improve upper airway mechanics based on an increase in latency to arousal and amplitude of the phasic genioglossus electromyogram (EMG), and a decrease in the active upper airway critical closing pressure (P(crit)). 12 healthy subjects received pentobarbital (100 mg) or placebo in a double-blind, crossover protocol. During wakefulness, we measured the genioglossus reflex response to negative pressure pulses. During sleep, carbon dioxide was insufflated into the inspired air. Airway pressure was then decreased in a stepwise fashion until arousal from sleep. With basal breathing during sleep: flow rate was lower in volunteers given pentobarbital; end-tidal CO(2) concentration and upper airway resistance were greater; and P(crit) was unaffected (pentobarbital mean ± SD -11.7 ± 4.5 versus placebo -10.25 ± 3.6 cmH(2)O; p = 0.11). Pentobarbital increased the time to arousal (297 ± 63s versus 232 ± 67 s; p<0.05), at which time phasic genioglossus EMG was higher (6.2 ± 4.8% maximal versus 3.1 ± 3%; p<0.05) as were CO(2) levels. The increase in genioglossus EMG after CO(2) administration was greater after pentobarbital versus placebo. Pentobarbital did not affect the genioglossus negative-pressure reflex. Pentobarbital increases the time to arousal and stimulates genioglossus muscle activity, but it also increases upper airway resistance during sleep.

Figures

FIGURE 1

Study protocol. Subjects were studied twice: during placebo and during pentobarbital treatment. Each study day, measurements were performed during wakefulness (before and after test-drug application) and sleep. During sleep, subjects were studied at atmospheric pressure first, to measure normal breathing and the respiratory response to inspiratory carbon dioxide insufflation. Subjects were then put on continuous positive airway pressure (CPAP) (3 mmHg) to avoid flow limitation, and negative-pressure ramps were performed until arousal. GG-EMG: genioglossus electromyography; Pcrit: critical closing pressure.

FIGURE 2

Method of calculation of upper airway critical closing pressure (Pcrit) during stage II sleep by linear regression in one volunteer. Peak air flow during flow-limited breathing is plotted as a function of mask pressure. Throughout the study night, 12 negative-pressure ramps were performed, while flow limitation was observed. Values derived from 31 flow-limited breaths were used for analysis and extrapolated to Pcrit (mask pressure at zero flow) by linear regression. Note that, at a given mask pressure, peak flow during flow-limited breathing varied throughout the overnight study, suggesting that the balance between the collapsing and dilating forces acting at the upper airway varied throughout the night.

FIGURE 3

Effect of pentobarbital () and placebo () on genioglossus activity during negative pharyngeal pressure challenges. Average values of genioglossus (GG) electromyogram (EMG) just prior to arousal are shown. Phasic genioglossus activity was significantly higher after pentobarbital (100 mg) compared with the control night, and tonic genioglossus activity tended to be higher. % max: % maximal. *: p<0.05 versus placebo; #: p<0.1 versus placebo.

FIGURE 4

Effect of pentobarbital on active upper airway critical closing pressure (Pcrit) during sleep. The figure shows the average Pcrit values in 11 subjects during the pentobarbital night compared with the placebo night. Vertical bars represent mean±sd. Note that Pcrit tended to be more negative during the pentobarbital night compared with the placebo night. #: p=0.11 versus placebo.

FIGURE 5

Difference in active upper airway critical closing pressure (Pcrit) during the pentobarbital night and control night versus the difference in tonic genioglossus activity (as % of maximum (max) value). Measurements during negative pharyngeal pressure challenges during sleep. Average values from all pressure drops. r= -0.66, p=0.03.