Termination of respiratory events with and without cortical arousal in obstructive sleep apnea

Abstract

Rationale: A total of 20-30% of respiratory events in obstructive sleep apnea are terminated without clear arousal. Arousals are thought to predispose to further events by promoting hyperventilation, hypocapnia, and upper-airway dilator muscle hypotonia. Therefore, events terminated without arousal may promote stable breathing.

Objectives: To compare physiologic changes at respiratory event termination with American Sleep Disorders Association (ASDA) Arousal to No Arousal, and determine whether secondary respiratory events are less common and have higher dilator muscle activity after No Arousal compared with ASDA Arousal.

Methods: Patients with obstructive sleep apnea wore sleep staging, genioglossus (EMG(GG)), and tensor palatini (EMG(TP)) electrodes plus a nasal mask and pneumotachograph. During stable sleep, continuous positive airway pressure (CPAP) was lowered for 3-minute periods to induce respiratory events. Physiologic variables were compared between events terminated with (1) ASDA Arousal, (2) No Arousal, or (3) sudden CPAP increase (CPAPinc, control).

Measurements and main results: Sixteen subjects had adequate data. EMG(GG), EMG(TP), and heart rate increased after ASDA Arousal (340 ± 57%, 215 ± 28%, and 110.7 ± 2.3%) and No Arousal (185 ± 32%, 167 ± 15%, and 108.5 ± 1.6%) but not CPAPinc (90 ± 10%, 94 ± 11%, and 102.1 ± 1%). Ventilation increased more after ASDA Arousal than No Arousal and CPAPinc, but not after accounting for the severity of respiratory event. Fewer No Arousals were followed by secondary events than ASDA Arousals. However, low dilator muscle activity did not occur after ASDA Arousal or No Arousal (EMG(GG) rose from 75 ± 5 to 125 ± 7%) and secondary events were less severe than initial events (ventilation rose 4 ± 0.4 to 5.5 ± 0.51 L/min).

Conclusions: Respiratory events that were terminated with ASDA Arousal were more severely flow-limited, had enhanced hyperventilation after event termination, and were more often followed by secondary events than No arousal. However, secondary events were not associated with low dilator muscle activity and airflow was improved after both No Arousal and ASDA Arousal.

Figure 1.

Examples of the three respiratory event termination types in one subject. Airflow, mask pressure (P_MASK), epiglottic pressure (P_EPI), central EEG, the raw and moving time averages (MTA) genioglossus (EMG_GG), and tensor palatini (EMG_TP) muscle activities are shown after sudden termination of respiratory events in three conditions: in association with an American Sleep Disorders Association arousal (A), without American Sleep Disorders Association arousal (B), and at the time of sudden continuous positive airway pressure increase (C). The arrows on each panel indicate the breath on which the respiratory event was considered to end.

Figure 2.

(A–F) Physiologic changes after respiratory event termination with and without American Sleep Disorders Association (ASDA) arousal from sleep or by sudden continuous positive airway pressure (CPAP) increase. Peak inspiratory flow (PIF), inspired minute ventilation (V_I), epiglottic pressure (P_EPI), peak inspiratory and tonic genioglossus muscle (GG) activity, and tensor palatini muscle (TP) activity for five breaths before and after respiratory event termination by sudden CPAP increase, or with (ASDA Arousal) or without (No ASDA Arousal) arousal. Analysis of variance results are reported in the text, but post hoc differences are indicated for CPAP increase versus No Arousal by gray bars, differences between No Arousal versus ASDA Arousal by the checked bars, and differences between CPAP increases and ASDA Arousal in the black bars.

Figure 3.

Heart rate changes after respiratory event termination with and without American Sleep Disorders Association (ASDA) arousal from sleep. The heart rate (expressed as a percentage of each subject's mean heart rate across the whole recording period) is shown for 20 beats before and after the termination of respiratory events by sudden continuous positive airway pressure (CPAP) increase, or with (ASDA Arousal) or without (No ASDA Arousal) arousal. Analysis of variance results are reported in the text, but post hoc differences are indicated for CPAP increase versus No Arousal by gray bars, differences between No Arousal versus ASDA Arousal by the checked bars, and differences between CPAP increases and ASDA Arousal in the black bars.

Figure 4.

Physiologic changes after respiratory event termination with and without American Sleep Disorders Association (ASDA) arousal from sleep in events matched for severity and duration of hypoventilation. Ventilatory (V_I) (A) and peak inspiratory genioglossus activity (Peak GG) (B) did not differ between ASDA Arousal and No ASDA Arousal events when the severity and duration of hypopneas were matched between arousal types. See results for details regarding matching and online supplement for results of other physiologic variables.

Figure 5.

Physiologic variables during initial and secondary respiratory events that were terminated with or without American Sleep Disorders Association (ASDA) Arousal. The top panel shows an example of the breaths analyzed (dashed boxes) for initial and secondary respiratory events. Airflow (Flow), mask pressure (P_MASK), epiglottic pressure (P_EPI), raw and moving time averaged (MTA) genioglossus (EMG_GG), and tensor palatini (EMG_TP) muscle activity during the first two respiratory events after sudden continuous positive airway pressure (CPAP) drop. The large black and gray arrows indicate the breaths on which the initial and secondary respiratory events are terminated, respectively. (A–F) Peak inspiratory flow (PIF), inspired minute ventilation (V_I), epiglottic pressure (P_EPI), peak inspiratory and tonic genioglossus muscle (GG) activity, and tensor palatini muscle (TP) activity on initial and secondary events that were terminated either with or without ASDA arousal (white squares and gray triangles, respectively). * Significantly different to initial event. $ Indicates a significant analysis of variance main effect for arousal type.