Effects of Pentobarbital on Genioglossus Muscle Activity and Upper Airway Collapsibility during Sleep.

Background Reversal of residual neuromuscular blockade by acetylcholinesterase inhibitors (e.g., neostigmine) improves respiratory function. However, neostigmine may also impair muscle strength. We hypothesized that neostigmine administered after recovery of the train-of-four (TOF) ratio impairs upper airway integrity and genioglossus muscle function. Methods We measured, in 10 healthy male volunteers, epiglottic and nasal mask pressures, genioglossus electromyogram, air flow, respiratory timing, and changes in lung volume before, during (TOF ratio: 0.5), and after recovery of the TOF ratio to unity, and after administration of neostigmine 0.03 mg/kg IV (with glycopyrrolate 0.0075 mg/kg). Upper airway critical closing pressure (Pcrit) was calculated from flow-limited breaths during random pharyngeal negative pressure challenges. Results Pcrit increased significantly after administration of neostigmine/glycopyrrolate compared with both TOF recovery (mean ± SD, by 27 ± 21%; P = 0.02) and baseline (by 38 ± 17%; P = 0.002). In parallel, phasic genioglossus activity evoked by negative pharyngeal pressure decreased (by 37 ± 29%, P = 0.005) compared with recovery, almost to a level observed at a TOF ratio of 0.5. Lung volume, respiratory timing, tidal volume, and minute ventilation remained unchanged after neostigmine/glycopyrrolate injection. Conclusion Neostigmine/glycopyrrolate, when administered after recovery from neuromuscular block, increases upper airway collapsibility and impairs genioglossus muscle activation in response to negative pharyngeal pressure. Reversal with acetylcholinesterase inhibitors may be undesirable in the absence of neuromuscular blockade.

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Collapsibility of the Upper Airway at Different Concentrations of Propofol Anesthesia

Anesthesiology ◽

10.1097/00000542-200509000-00007 ◽

2005 ◽

Vol 103 (3) ◽

pp. 470-477 ◽

Cited By ~ 179

Author(s):

Peter R. Eastwood ◽

Peter R. Platt ◽

Kelly Shepherd ◽

Kathy Maddison ◽

David R. Hillman

Keyword(s):

Upper Airway ◽

Inspiratory Flow ◽

Electromyographic Activity ◽

Flow Limitation ◽

Genioglossus Muscle ◽

Airway Collapsibility ◽

Effect Site Concentration ◽

Intramuscular Electrodes ◽

Upper Airway Collapsibility ◽

Spontaneously Breathing

Background This study investigated the effect of varying concentrations of propofol on upper airway collapsibility and the mechanisms responsible for it. Methods Upper airway collapsibility was determined from pressure-flow relations at three concentrations of propofol anesthesia (effect site concentration = 2.5, 4.0, and 6.0 mug/ml) in 12 subjects spontaneously breathing on continuous positive airway pressure. At each level of anesthesia, mask pressure was transiently reduced from a pressure sufficient to abolish inspiratory flow limitation (maintenance pressure = 12 +/- 1 cm H2O) to pressures resulting in variable degrees of flow limitation. The relation between mask pressure and maximal inspiratory flow was determined, and the critical pressure at which the airway occluded was recorded. Electromyographic activity of the genioglossus muscle (EMGgg) was obtained via intramuscular electrodes in 8 subjects. Results With increasing depth of anesthesia, (1) critical closing pressure progressively increased (-0.3 +/- 3.5, 0.5 +/- 3.7, and 1.4 +/- 3.5 cm H2O at propofol concentrations of 2.5, 4.0, and 6.0 microg/ml respectively; P < 0.05 between each level), indicating a more collapsible upper airway; (2) inspiratory flow at the maintenance pressure significantly decreased; and (3) respiration-related phasic changes in EMGgg at the maintenance pressure decreased from 7.3 +/- 9.9% of maximum at 2.5 microg/ml to 0.8 +/- 0.5% of maximum at 6.0 microg/ml, whereas tonic EMGgg was unchanged. Relative to the levels of phasic and tonic EMGgg at the maintenance pressure immediately before a decrease in mask pressure, tonic activity tended to increase over the course of five flow-limited breaths at a propofol concentration of 2.5 microg/ml but not at propofol concentrations of 4.0 and 6.0 microg/ml, whereas phasic EMGgg was unchanged. Conclusions Increasing depth of propofol anesthesia is associated with increased collapsibility of the upper airway. This was associated with profound inhibition of genioglossus muscle activity. This dose-related inhibition seems to be the combined result of depression of central respiratory output to upper airway dilator muscles and of upper airway reflexes.

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

European Respiratory Journal ◽

10.1183/13993003.01344-2017 ◽

2017 ◽

Vol 50 (6) ◽

pp. 1701344 ◽

Cited By ~ 17

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.

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Upper Airway Collapsibility (Pcrit) and Pharyngeal Dilator Muscle Activity are Sleep Stage Dependent

SLEEP ◽

10.5665/sleep.5516 ◽

2016 ◽

Vol 39 (3) ◽

pp. 511-521 ◽

Cited By ~ 61

Author(s):

Jayne C. Carberry ◽

Amy S. Jordan ◽

David P. White ◽

Andrew Wellman ◽

Danny J. Eckert

Keyword(s):

Muscle Activity ◽

Sleep Stage ◽

Upper Airway ◽

Dilator Muscle ◽

Airway Collapsibility ◽

Upper Airway Collapsibility

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Supplemental Carbon Dioxide Stabilizes the Upper Airway in Volunteers Anesthetized with Propofol

Anesthesiology ◽

10.1097/aln.0000000000002239 ◽

2018 ◽

Vol 129 (1) ◽

pp. 37-46 ◽

Cited By ~ 2

Author(s):

Katarina Jennifer Ruscic ◽

Janne Bøgh Stokholm ◽

Johann Patlak ◽

Hao Deng ◽

Jeroen Cedric Peter Simons ◽

...

Keyword(s):

Carbon Dioxide ◽

Deep Level ◽

Muscle Tone ◽

Secondary Analysis ◽

Upper Airway ◽

Dependent Manner ◽

Genioglossus Muscle ◽

Airway Collapsibility ◽

Upper Airway Collapsibility ◽

Closing Pressure

Abstract Background Propofol impairs upper airway dilator muscle tone and increases upper airway collapsibility. Preclinical studies show that carbon dioxide decreases propofol-mediated respiratory depression. We studied whether elevation of end-tidal carbon dioxide (Petco2) via carbon dioxide insufflation reverses the airway collapsibility (primary hypothesis) and impaired genioglossus muscle electromyogram that accompany propofol anesthesia. Methods We present a prespecified, secondary analysis of previously published experiments in 12 volunteers breathing via a high-flow respiratory circuit used to control upper airway pressure under propofol anesthesia at two levels, with the deep level titrated to suppression of motor response. Ventilation, mask pressure, negative pharyngeal pressure, upper airway closing pressure, genioglossus electromyogram, bispectral index, and change in end-expiratory lung volume were measured as a function of elevation of Petco2 above baseline and depth of propofol anesthesia. Results Petco2 augmentation dose-dependently lowered upper airway closing pressure with a decrease of 3.1 cm H2O (95% CI, 2.2 to 3.9; P < 0.001) under deep anesthesia, indicating improved upper airway stability. In parallel, the phasic genioglossus electromyogram increased by 28% (23 to 34; P < 0.001). We found that genioglossus electromyogram activity was a significant modifier of the effect of Petco2 elevation on closing pressure (P = 0.005 for interaction term). Conclusions Upper airway collapsibility induced by propofol anesthesia can be reversed in a dose-dependent manner by insufflation of supplemental carbon dioxide. This effect is at least partly mediated by increased genioglossus muscle activity.

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Faculty Opinions recommendation of The effect of diaphragm contraction on upper airway collapsibility.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718112874.793483877 ◽

2013 ◽

Author(s):

William Sheel

Keyword(s):

Upper Airway ◽

Airway Collapsibility ◽

Upper Airway Collapsibility

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Effect of Head Elevation on Passive Upper Airway Collapsibility in Normal Subjects during Propofol Anesthesia

Anesthesiology ◽

10.1097/aln.0b013e318223ba6d ◽

2011 ◽

Vol 115 (2) ◽

pp. 273-281 ◽

Cited By ~ 16

Author(s):

Masato Kobayashi ◽

Takao Ayuse ◽

Yuko Hoshino ◽

Shinji Kurata ◽

Shunji Moromugi ◽

...

Keyword(s):

Upper Airway ◽

Normal Subjects ◽

Target Concentration ◽

Airway Patency ◽

Head Elevation ◽

Jaw Opening ◽

Airway Collapsibility ◽

Upper Airway Collapsibility ◽

Head Flexion ◽

Male Subjects

Background Head elevation can restore airway patency during anesthesia, although its effect may be offset by concomitant bite opening or accidental neck flexion. The aim of this study is to examine the effect of head elevation on the passive upper airway collapsibility during propofol anesthesia. Method Twenty male subjects were studied, randomized to one of two experimental groups: fixed-jaw or free-jaw. Propofol infusion was used for induction and to maintain blood at a constant target concentration between 1.5 and 2.0 μg/ml. Nasal mask pressure (PN) was intermittently reduced to evaluate the upper airway collapsibility (passive PCRIT) and upstream resistance (RUS) at each level of head elevation (0, 3, 6, and 9 cm). The authors measured the Frankfort plane (head flexion) and the mandible plane (jaw opening) angles at each level of head elevation. Analysis of variance was used to determine the effect of head elevation on PCRIT, head flexion, and jaw opening within each group. Results In both groups the Frankfort plane and mandible plane angles increased with head elevation (P < 0.05), although the mandible plane angle was smaller in the free-jaw group (i.e., increased jaw opening). In the fixed-jaw group, head elevation decreased upper airway collapsibility (PCRIT ~ -7 cm H₂O at greater than 6 cm elevation) compared with the baseline position (PCRIT ~ -3 cm H₂O at 0 cm elevation; P < 0.05). Conclusion : Elevating the head position by 6 cm while ensuring mouth closure (centric occlusion) produces substantial decreases in upper airway collapsibility and maintains upper airway patency during anesthesia.

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