TY -的T1 -吗啡改变呼吸控制but not other key OSA phenotypes: A randomised trial JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.01344-2019 SP - 1901344 AU - Martins, Rodrigo T. AU - Carberry, Jayne C. AU - Wang, David AU - Rowsell, Luke AU - Grunstein, Ronald R. AU - Eckert, Danny J. Y1 - 2020/01/01 UR - //www.qdcxjkg.com/content/early/2020/03/04/13993003.01344-2019.abstract N2 - Accidental opioid-related deaths are increasing. These often occur during sleep. Opioids such as morphine may worsen obstructive sleep apnoea (OSA). Thus, people with OSA may be at greater risk of harm from morphine. Possible mechanisms include respiratory depression and reductions in drive to the pharyngeal muscles to increase upper airway collapsibility. However, the effects of morphine on the 4-key phenotypic causes of OSA (upper airway collapsibility [Pcrit], pharyngeal muscle responsiveness, respiratory arousal threshold and ventilatory control [loop gain] during sleep) are unknown.Twenty one men with OSA (AHI range=7–67 events·h−1) were studied on 2 nights (1-week wash-out) according to a double-blind, randomised, cross-over design (ACTRN12613000858796). Participants received 40 mg of MS-Contin on one visit and placebo on the other. Brief reductions in continuous positive airway pressure (CPAP) from the therapeutic level were delivered to induce airflow limitation during non-REM sleep to quantify the 4 phenotypic traits. CO2 was also delivered via nasal mask on therapeutic CPAP to quantify hypercapnic ventilatory responses during non-REM sleep.Compared to placebo, 40 mg of morphine did not change Pcrit (−0.1±2.4 versus −0.4±2.2 cmH2O, p=0.58), genioglossus muscle responsiveness (−2.2[−0.87 to −5.4] versus −1.2[−0.3 to −3.5]microV/cmH2O, p=0.22), or arousal threshold (−16.7±6.8 versus −15.4±6.0 cmH2O, p=0.41), but did reduce loop gain (−10.1±2.6 versus −4.4±2.1 dimensionless, p=0.04) and hypercapnic ventilatory responses (7.3±1.2 versus 6.1±1.5 L·min−1, p=0.006).Concordant with recent clinical findings, 40 mg of MS-Contin does not systematically impair airway collapsibility, pharyngeal muscle responsiveness or the arousal threshold in moderately severe OSA patients. However, consistent with blunted chemosensitivity, ventilatory control is altered.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Tomazini Martins reports grants from NHMRC, during the conduct of the study.Conflict of interest: Dr. Carberry reports grants from National Health and Medical Research Council (NHMRC) of Australia, NeuroSleep-Centre for Research Excellence, grants from NHMRC, during the conduct of the study.Conflict of interest: Dr. Wang reports grants from National Health and Medical Research Council of Australia (NHMRC), during the conduct of the study.Conflict of interest: Dr. Rowsell reports grants from National Health and Medical Research Council of Australia (NHMRC), during the conduct of the study.Conflict of interest: Dr. Grunstein reports grants from National Health and Medical Research Council of Australia (NHMRC), during the conduct of the study; grants from Collaborative Research Centre (CRC) Consortium Grant between the Australian Government, Academia and Industry, other from Teva, other from Merck, outside the submitted work.Conflict of interest: Dr. Eckert reports grants from National Health and Medical Research Council of Australia (NHMRC), during the conduct of the study; grants and personal fees from Bayer, grants and personal fees from Apnimed, grants from Collaborative Research Centre (CRC-P) Consortium Grant between the Australian Government, Academia and Industry, outside the submitted work. ER -