New Insights into the Timing and Potential Mechanisms of Respiratory-Induced Cortical Arousals in Obstructive Sleep Apnea.

Abstract

A negative intrathoracic pressure threshold is one commonly proposed mechanism for triggering respiratory-induced arousals in obstructive sleep apnea (OSA). If so, they should occur during inspiration, shortly after maximal negative pressure swings. Alternatively, respiratory-induced arousals may occur throughout the respiratory cycle if other mechanisms also contribute. However, arousal timing has been minimally investigated. This study aimed to: 1) determine the temporal relationship between respiratory-induced arousals and breathing phase and 2) characterize neuromuscular and load compensation responses prior to arousal. 51 CPAP-treated OSA patients underwent a sleep physiology study with genioglossus and tensor palatini EMG, nasal mask/pneumotachograph and epiglottic pressure. Transient CPAP reductions were delivered to induce respiratory-related arousals. Of 354 arousals, 65(60-70)%[mean(CI)] occurred during inspiration, 35(30-40)% during expiration. Nadir epiglottic pressure occurred 68(66-69)% into inspiration, while inspiratory arousals had a uniform distribution throughout inspiration. Expiratory arousals occurred predominantly in early expiration. CPAP reductions initially reduced minute ventilation by ~2.5L/min, which was restored immediately prior to expiratory but not inspiratory arousals. Duty cycle just prior to arousal was greater for inspiratory versus expiratory arousals [0.20(0.18-0.21) vs. 0.13(0.11-0.15)Δbaseline, P=0.001]. Peak tensor palatini EMG was higher for expiratory versus inspiratory arousals during pre-arousal breaths [7.6(5.8-9.6) vs. 3.7(3.0-4.5)%Δbaseline, P=0.001], while genioglossus and tonic tensor palatini EMG were similar between arousal types. Over one third of respiratory-induced arousals occur during expiration. These findings highlight the importance of non-pressure threshold mechanisms of respiratory-induced arousals in OSA and suggest expiratory arousals may be a novel marker of enhanced tensor palatini neuromuscular compensation.