Increased cortical arousal propensity in opiate users with complex sleep apnea syndrome

Abstract

Complex sleep apnea syndrome (CompSAS) presumably involves unstable ventilatory control mechanisms, possibly including cortical brain arousal indexed by NREM cyclic alternating pattern (CAP) sleep microarchitecture. CompSAS has been associated with opiate use, but may also be idiopathic or associated with underlying cardiac disease. We aimed to determine whether cortical arousal propensity indexed by NREM CAP differed between CompSAS opiate users (OU) and non-opiate users (NOU), and OSA controls. A retrospective analysis of clinical and diagnostic polysomnographic data of 39 consecutive CompSAS patients (18 OU, 21 NOU) and 18 OSA controls without CompSAS matched for age, gender, body mass index, and polysomnographic apnea-hypopnea index (AHI) was performed. Polysomnograms were manually analyzed for CAP and log transformed CAP A Ratio Index (ARI, with higher values indicating higher sleep-preservation propensity) according to standard methods using Hypnolab scoring software (ATES Medica Labs, Verona, Italy). Groups were compared utilizing Wilcoxon Rank Sum tests, and multivariable regression was performed to determine associations between predictor variables and CompSAS. AHI ( p = 0.66) and arousal indices ( p = 0.42) were similar between OU, NOU, and OSA controls. CAP rate was lower in OU than NOU or OSA controls (66 vs. 77 vs. 77, p = 0.13). OU had lower CAP A1 and higher A2 indices (A1: 52 vs. 94 vs. 88, p = 0.096; A2: 39.7 vs. 24.0 vs. 21.1, p = 0.068), resulting in a signifi cantly lower ARI in OU ( p = 0.02) with ARI below 0.55 associated with CompSAS ( p = 0.0026). CompSAS OU demonstrated a higher cortical arousal propensity when compared to CompSAS NOU and OSA controls, resulting from reduced A1 (slow, sleep promoting) and higher A2 (fast, sleep fragmenting) CAP rhythms. Our fi ndings suggest that opiates alter cortical arousal mechanisms that could induce central apnea, possibly causing postarousal/sleep-onset central apneas during positive airway pressure treatment.