scholarly journals Zolpidem increases sleep efficiency and the respiratory arousal threshold without changing sleep apnoea severity and pharyngeal muscle activity

2020 ◽  
Vol 598 (20) ◽  
pp. 4681-4692
Author(s):  
Ludovico Messineo ◽  
Danny J. Eckert ◽  
Richard Lim ◽  
Alan Chiang ◽  
Ali Azarbarzin ◽  
...  
Keyword(s):  
Muscle Activity ◽  
Sleep Apnoea ◽  
Sleep Efficiency ◽  
Pharyngeal Muscle ◽  
Arousal Threshold

scholarly journals Role of common hypnotics on the phenotypic causes of obstructive sleep apnoea: paradoxical effects of zolpidem

2017 ◽  
Vol 50 (6) ◽  
pp. 1701344 ◽  
Author(s):  
Jayne C. Carberry ◽  
Lauren P. Fisher ◽  
Ronald R. Grunstein ◽  
Simon C. Gandevia ◽  
David K. McKenzie ◽  
...  
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Muscle Activity ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Double Blind ◽  
Genioglossus Muscle ◽  
Airway Narrowing ◽  
Arousal Threshold ◽  
Obstructive Sleep ◽  
Airway Collapsibility

Hypnotics are contraindicated in obstructive sleep apnoea (OSA) because of concerns of pharyngeal muscle relaxation and delayed arousal worsening hypoxaemia. However, human data are lacking. This study aimed to determine the effects of three common hypnotics on the respiratory arousal threshold, genioglossus muscle responsiveness and upper airway collapsibility during sleep.21 individuals with and without OSA (18–65 years) completed 84 detailed sleep studies after receiving temazepam (10 mg), zolpidem (10 mg), zopiclone (7.5 mg) and placebo on four occasions in a randomised, double-blind, placebo-controlled, crossover trial (ACTRN12612001004853).The arousal threshold increased with zolpidem and zopicloneversusplacebo (mean±sd−18.3±10 and −19.1±9versus−14.6±7 cmH2O; p=0.02 and p<0.001) but not with temazepam (−16.8±9 cmH2O; p=0.17). Genioglossus muscle activity during stable non-REM sleep and responsiveness during airway narrowing was not different with temazepam and zopicloneversusplacebo but, paradoxically, zolpidem increased median muscle responsiveness three-fold during airway narrowing (median −0.15 (interquartile range −1.01 to −0.04)versus−0.05 (−0.29 to −0.03)% maximum EMG per cmH2O epiglottic pressure; p=0.03). The upper airway critical closing pressure did not change with any of the hypnotics.These doses of common hypnotics have differential effects on the respiratory arousal threshold but do not reduce upper airway muscle activity or alter airway collapsibility during sleep. Rather, muscle activity increases during airway narrowing with zolpidem.

Morphine alters respiratory control but not other key obstructive sleep apnoea phenotypes: a randomised trial

2020 ◽  
Vol 55 (6) ◽  
pp. 1901344
Author(s):  
Rodrigo T. Martins ◽  
Jayne C. Carberry ◽  
David Wang ◽  
Luke Rowsell ◽  
Ronald R. Grunstein ◽  
...  
Keyword(s):  
Upper Airway ◽  
Sleep Apnoea ◽  
Loop Gain ◽  
Ventilatory Control ◽  
Pharyngeal Muscle ◽  
Arousal Threshold ◽  
Ventilatory Responses ◽  
Obstructive Sleep ◽  
Airway Collapsibility ◽  
Upper Airway Collapsibility

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 four key phenotypic causes of OSA (upper airway collapsibility (pharyngeal critical closure pressure; Pcrit), pharyngeal muscle responsiveness, respiratory arousal threshold and ventilatory control (loop gain) during sleep) are unknown.21 males with OSA (apnoea–hypopnoea index range 7–67 events·h−1) were studied on two nights (1-week washout) 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-rapid eye movement (REM) sleep to quantify the four phenotypic traits. Carbon dioxide was 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) μV·cmH2O−1, 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, 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.

scholarly journals P019 Obstructive sleep apnoea endotypes in people with multiple sclerosis

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A27-A28
Author(s):  
S Carter ◽  
H Hensen ◽  
A Krishnan ◽  
A Chiang ◽  
J Carberry ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Obstructive Sleep Apnoea ◽  
Group Analysis ◽  
Respiratory Control ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Loop Gain ◽  
Male Predominance ◽  
Arousal Threshold ◽  
Obstructive Sleep

Abstract Purpose Obstructive sleep apnoea (OSA) is common in people with multiple sclerosis (MS) despite a lack of typical risk factors for OSA in people with MS such as obesity and male predominance. Therefore, underlying factors other than sex and obesity may be particularly important in the pathogenesis of OSA in people with MS. Thus, the primary aim of this study was to determine the relative contributions of OSA endotypes in people with MS and compare this to matched controls with OSA only. Methods Eleven people with MS and OSA (MS-OSA group) (apnoea-hypopnoea index [AHI]&gt;5events/h) and eleven controls matched for OSA severity, age and sex without MS (OSA group) were studied. Participants underwent a detailed overnight polysomnography with an epiglottic pressure catheter and genioglossus intramuscular electrodes to allow for quantification of pathophysiological contributors to OSA. This included the respiratory arousal threshold, genioglossus muscle responsiveness, respiratory loop gain and upper airway collapsibility. Results Measures of the four primary OSA endotypes were not different between the MS-OSA and OSA groups (e.g. NREM respiratory arousal threshold -27±15 vs. -23±8 cmH2O respectively, p=0.24). Within group analysis indicated higher loop gain in non-obese MS-OSA participants compared to obese MS-OSA participants (0.53±0.11 vs. 0.37±0.11, p=0.04). Conclusions Overall, OSA endotypes are similar between MS-OSA participants and matched OSA controls. However, within the MS-OSA group, non-obese participants have higher loop gain (unstable respiratory control) compared to obese participants. Thus, unstable respiratory control may play an important role in OSA pathogenesis in many people with MS.

scholarly journals Trazodone increases arousal threshold in obstructive sleep apnoea

2008 ◽  
Vol 31 (6) ◽  
pp. 1308-1312 ◽  
Author(s):  
R. C. Heinzer ◽  
D. P. White ◽  
A. S. Jordan ◽  
Y. L. Lo ◽  
L. Dover ◽  
...  
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Sleep Apnoea ◽  
Arousal Threshold ◽  
Obstructive Sleep

scholarly journals Targeting Endotypic Traits with Medications for the Pharmacological Treatment of Obstructive Sleep Apnea. A Review of the Current Literature

2019 ◽  
Vol 8 (11) ◽  
pp. 1846 ◽  
Author(s):  
Taranto-Montemurro ◽  
Messineo ◽  
Wellman
Keyword(s):  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Muscle Activity ◽  
Upper Airway ◽  
Loop Gain ◽  
Arousal Threshold ◽  
The Past ◽  
Obstructive Sleep ◽  
Near Future ◽  
Made In

Obstructive sleep apnea (OSA) is a highly prevalent condition with few therapeutic options. To date there is no approved pharmacotherapy for this disorder, but several attempts have been made in the past and are currently ongoing to find one. The recent identification of multiple endotypes underlying this disorder has oriented the pharmacological research towards tailored therapies targeting specific pathophysiological traits that contribute differently to cause OSA in each patient. In this review we retrospectively analyze the literature on OSA pharmacotherapy dividing the medications tested on the basis of the four main endotypes: anatomy, upper airway muscle activity, arousal threshold and ventilatory instability (loop gain). We show how recently introduced drugs for weight loss that modify upper airway anatomy may play an important role in the management of OSA in the near future, and promising results have been obtained with drugs that increase upper airway muscle activity during sleep and reduce loop gain. The lack of a medication that can effectively increase the arousal threshold makes this strategy less encouraging, although recent studies have shown that the use of certain sedatives do not worsen OSA severity and could actually improve patients’ sleep quality.

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