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.

scholarly journals Desipramine improves upper airway collapsibility and reduces OSA severity in patients with minimal muscle compensation

2016 ◽  
Vol 48 (5) ◽  
pp. 1340-1350 ◽  
Author(s):  
Luigi Taranto-Montemurro ◽  
Scott A. Sands ◽  
Bradley A. Edwards ◽  
Ali Azarbarzin ◽  
Melania Marques ◽  
...  
Keyword(s):  
Crossover Trial ◽  
Positive Airway Pressure ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Double Blind ◽  
Healthy Humans ◽  
Dilator Muscle ◽  
Obstructive Sleep ◽  
Airway Collapsibility ◽  
Upper Airway Collapsibility

We recently demonstrated that desipramine reduces the sleep-related loss of upper airway dilator muscle activity and reduces pharyngeal collapsibility in healthy humans without obstructive sleep apnoea (OSA). The aim of the present physiological study was to determine the effects of desipramine on upper airway collapsibility and apnoea–hypopnea index (AHI) in OSA patients.A placebo-controlled, double-blind, randomised crossover trial in 14 OSA patients was performed. Participants received treatment or placebo in randomised order before sleep. Pharyngeal collapsibility (critical collapsing pressure of the upper airway (Pcrit)) and ventilation under both passive (V′0,passive) and active (V′0,active) upper airway muscle conditions were evaluated with continuous positive airway pressure (CPAP) manipulation. AHI was quantified off CPAP.Desipramine reduced activePcrit(median (interquartile range) −5.2 (4.3) cmH2O on desipramineversus−1.9 (2.7) cmH2O on placebo; p=0.049) but not passivePcrit(−2.2 (3.4)versus−0.7 (2.1) cmH2O; p=0.135). A greater reduction in AHI occurred in those with minimal muscle compensation (defined asV′0,active−V′0,passive) on placebo (r=0.71, p=0.009). The reduction in AHI was driven by the improvement in muscle compensation (r=0.72, p=0.009).In OSA patients, noradrenergic stimulation with desipramine improves pharyngeal collapsibility and may be an effective treatment in patients with minimal upper airway muscle compensation.

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 P001 Safety, tolerability, and efficacy of 1 month of atomoxetine plus oxybutynin in obstructive sleep apnoea

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A22-A22
Author(s):  
A Aishah ◽  
K Loffler ◽  
B Tonson ◽  
S Mukherjee ◽  
R Adams ◽  
...  
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Side Effect ◽  
Vital Signs ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Side Effect Profile ◽  
Double Blind ◽  
Phone Calls ◽  
Obstructive Sleep ◽  
Single Night

Abstract Introduction Single-night studies with noradrenergic and anti-muscarinics have recently been shown to improve upper-airway function and reduce obstructive sleep apnoea (OSA) severity. This study aimed to determine the safety, tolerability, and efficacy profile of longer-term use of different doses of the noradrenergic agent atomoxetine combined with the anti-muscarinic oxybutynin (ato-oxy) in people with OSA. Methods Thirty-nine people with predominantly severe OSA received either 80/5mg ato-oxy, 40/5mg ato-oxy, 40/2.5mg ato-oxy or placebo nightly for 30 days according to a double-blind, randomised, parallel design. Safety and tolerability were assessed via weekly phone calls for adverse events, vital signs and objective measures of alertness and memory. Participants completed 3 in-laboratory sleep studies (baseline, night 1 and night 30) to assess efficacy. Results Side effects were generally mild and consistent with the known side-effect profile of each drug alone (e.g. dose-dependent increases in dry mouth with oxybutynin). Heart rate increased by night 30 in two of the drug arms versus placebo (e.g. 80/5mg ~9 beats/min, p=0.01). Blood pressure and measures of alertness and memory did not change between conditions. AHI4 and hypoxic burden decreased by ~50% in the 80/5mg arm on night 1 with similar magnitude reductions at night 30. ~50% of participants indicated willingness to continue taking the medication post-study. Discussion 1 month of nightly noradrenergic and anti-muscarinic combination therapy is generally well-tolerated with a side effect profile consistent with each agent alone. These findings also further highlight the potential to target noradrenergic and anti-muscarinic mechanisms for OSA pharmacotherapy development.

scholarly journals Flextube reflectometry for determination of sites of upper airway narrowing in sleeping obstructive sleep apnoea patients

2001 ◽  
Vol 95 (8) ◽  
pp. 639-648 ◽  
Author(s):  
C.E. FABER ◽  
O. HILBERG ◽  
F.T. JENSEN ◽  
O. NORREGAARD ◽  
L. GRYMER
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Airway Narrowing ◽  
Obstructive Sleep

scholarly journals O023 Impact of weight loss of OSA pathophysiology

2021 ◽  
Vol 2 (Supplement_1) ◽  
pp. A10-A11
Author(s):  
A Wong ◽  
S Landry ◽  
K Yang ◽  
S Joosten ◽  
L Thomson ◽  
...  
Keyword(s):  
Weight Loss ◽  
Upper Airway ◽  
Sleep Apnoea ◽  
Loop Gain ◽  
Arousal Threshold ◽  
Post Surgery ◽  
Obstructive Sleep ◽  
Airway Collapsibility ◽  
Upper Airway Collapsibility ◽  
The Impact

Abstract Introduction Obesity is a major risk factor for developing obstructive sleep apnoea (OSA), however, the underlying mechanisms are not fully understood. We aimed to assess the impact of weight loss on all OSA endotypes (i.e. upper airway collapsibility, muscle compensation, respiratory arousal threshold, and loop gain). Methods We analysed data from 40 OSA patients (collated from 3 centres) who underwent bariatric surgery. Demographics and clinical polysomnograms (PSG) were performed at baseline and at between 6–18 months post-surgery. OSA endotypes were measured during sleep using non-invasive endotyping methods (derived from clinical PSG). Results Participants lost 28±14 kg and had a post-surgery reduction in the AHI of 19.6 (Interquartile range[IQR] -9.8 to -35.4) events/hr [from baseline 39.9 (24.3 to 65.6) events/hr to 17.0 (9.9 to 33.3) events/hr]. Following surgical weight loss, there was significant improvement in collapsibility (∆6.2 [IQR -1.4 to 13]%Veupnoea, p&lt;0.0001), as well as significant reduction in loop gain and arousal threshold (∆-0.06 [-0.17 to 0.009], p&lt;0.001 and ∆-13.7 [-24.8 to -1.8]%Veupnoea, p&lt;0.001 respectively). There was no significant change in muscle compensation. Conclusion Our findings suggest that weight loss improves upper airway collapsibility and reduces loop gain and the arousal threshold, providing novel insights about the mechanisms by which obesity causes OSA. Further analysis is underway to determine whether knowledge of the baseline OSA endotypes (in isolation and/or in combination) can predict which individuals will have a response to weight loss alone.

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.

Volume-pressure properties of the upper airway in normal subjects and patients with obstructive sleep apnoea

Respirology ◽  
1999 ◽  
Vol 4 (1) ◽  
pp. 69-75 ◽  
Author(s):  
Denan Wu ◽  
Wataru Hida ◽  
Yoshihiro Kikuchi ◽  
Shinichi Okabe ◽  
Hajime Kurosawa ◽  
...  
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Upper Airway ◽  
Normal Subjects ◽  
Sleep Apnoea ◽  
Obstructive Sleep
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