Hypnotics on Obstructive Sleep Apnea Severity and Endotypes: A Systematic Review and Meta-Analysis.

RATIONALE: Low arousal threshold and poor muscle responsiveness are common determinants of obstructive sleep apnea (OSA). Hypnotics were hypothesized as an alternative OSA treatment via raising the arousal threshold and possibly genioglossus responsiveness. OBJECTIVES: Effect of common hypnotics on arousal threshold, OSA severity and genioglossus responsiveness. METHODS: We searched MEDLINE, EMBASE, CENTRAL and ClinicalTrials.gov for randomized clinical trials, and ran meta-analyses to determine the effect of oral hypnotics on arousal threshold, OSA severity and genioglossus responsiveness. GRADE was used to rate the quality of evidence (QoE). The association between post-treatment AHI and arousal threshold percent reductions was explored in individual patient data (IPD) metanalyses (overall sample and low arousal threshold subgroups). MEASUREMENTS AND MAIN RESULTS: Based on our analysis (27 studies; 25 for AHI, 11 for arousal threshold, 4 for genioglossus responsiveness), hypnotics minimally raised arousal threshold (mean difference [95% CI]: 2.7 [1.5, 3.8] cmH2O epiglottic pressure swings; moderate QoE), but did not change OSA severity (1.4 [3.5, 0.7] events/h; moderate QoE). IPD meta-analysis (N=114) showed no association between changes in arousal threshold and AHI, independent of low arousal threshold subgrouping. However, people with very-low arousal threshold or those who exhibited 0-25% arousal threshold increase from placebo experienced the greatest-yet still modest-post-treatment AHI reductions (10%). Hypnotics did not affect genioglossus responsiveness (high QoE). CONCLUSIONS: Further research testing or clinical use of hypnotics as OSA alternative treatments should be discouraged, unless in the presence of comorbid insomnia or as part of combination therapy in individuals with very-low arousal threshold.

Circuit-dependent carbon dioxide rebreathing during continuous positive airway pressure.

BACKGROUND: The current standard treatment for obstructive sleep apnea (OSA), continuous positive airway pressure (CPAP), is characterized by a low adherence rate due to various factors including circuit-dependent carbon dioxide (CO2) rebreathing, which can exacerbated by disparate factors, such as low PAP, use of auto-titrating PAP or ramps. However, risk factors for rebreathing are often overlooked or poorly understood in clinical practice. Therefore, our objective was to evaluate the extent of rebreathing occurring with commonly used CPAP masks across varying PAPs, tidal volumes, and respiratory rates. METHODS: In a bench study, we assessed the rebreathing rate of nine masks interfacing a CPAP with a lung simulator providing different breathing respiratory rates (15 or 20 breaths/min) and tidal volumes (400, 500, 600, 700 and 750 mL). Additionally, a theoretical model was developed to describe the likelihood of CO2 rebreathing from four different masks at various breathing settings. RESULTS: Overall, all masks performed worse in situations characterized by low PAPs, high tidal volumes, and high respiratory rates. However, Dreamwear, Nuance, Siesta, Vitera, and particularly V2 masks exhibited greater susceptibility to rebreathing compared to F20, P10, Brevida, and Rio masks for the same variations of PAPs or ventilatory parameters. The mathematical model suggested that the risk of rebreathing for Rio, P10 and Nuance mask is negligible for respiratory rates of 10 breaths/min or below. CONCLUSIONS: Circuit-dependent CO2 rebreathing can be a common occurrence and warrants careful mask selection upon CPAP therapy initiation for optimal clinical outcomes.

Treatment of Sleep Apnea and Reduction in Blood Pressure: The Role of Heart Rate Response and Hypoxic Burden.

BACKGROUND: Obstructive sleep apnea is associated with increased blood pressure (BP). Obstructive sleep apnea treatment reduces BP with substantial variability, not explained by the apnea-hypopnea index, partly due to inadequate characterization of obstructive sleep apnea's physiological consequences, such as oxygen desaturation, cardiac autonomic response, and suboptimal treatment efficacy. We sought to examine whether a high baseline heart rate response (ΔHR), a marker of high cardiovascular risk in obstructive sleep apnea, predicts a larger reduction in post-treatment systolic BP (SBP). Furthermore, we aimed to assess the extent to which a reduction in SBP is explained by a treatment-related reduction in hypoxic burden (HB). METHODS: ΔHR and HB were measured from pretreatment and posttreatment polygraphy, followed by a 24-hour BP assessment in 168 participants treated with continuous positive airway pressure or nocturnal supplemental oxygen from the HeartBEAT study (Heart Biomarker Evaluation in Apnea Treatment). Multiple linear regression models assessed whether high versus mid (reference) ΔHR predicted a larger reduction in SBP (primary outcome) and whether there was an association between treatment-related reductions in SBP and HB. RESULTS: A high versus mid ΔHR predicted improvement in SBP (adjusted estimate, 5.8 [95% CI, 1.0-10.5] mm Hg). Independently, a greater treatment-related reduction in HB was significantly associated with larger reductions in SBP (4.2 [95% CI, 0.9-7.5] mm Hg per 2 SD treatment-related reduction in HB). Participants with substantial versus minimal treatment-related reductions in HB had a 6.5 (95% CI, 2.5-10.4) mm Hg drop in SBP. CONCLUSIONS: A high ΔHR predicted a more favorable BP response to therapy. Furthermore, the magnitude of the reduction in BP was partly explained by a greater reduction in HB.