Peter R. Eastwood

Collapsibility of the Upper Airway at Different Concentrations of Propofol Anesthesia

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 &mgr;g/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 &mgr;g/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 &mgr;g/ml to 0.8 ± 0.5% of maximum at 6.0 &mgr;g/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 &mgr;g/ml but not at propofol concentrations of 4.0 and 6.0 &mgr;g/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.

Treating obstructive sleep apnea with hypoglossal nerve stimulation.

BACKGROUND Reduced upper airway muscle activity during sleep is fundamental to obstructive sleep apnea (OSA) pathogenesis. Hypoglossal nerve stimulation (HGNS) counteracts this problem, with potential to reduce OSA severity. STUDY OBJECTIVES To examine safety and efficacy of a novel HGNS system (HGNS, Apnex Medical, Inc.) in treating OSA. PARTICIPANTS Twenty-one patients, 67% male, age (mean ± SD) 53.6 ± 9.2 years, with moderate to severe OSA and unable to tolerate continuous positive airway pressure (CPAP). DESIGN Each participant underwent surgical implantation of the HGNS system in a prospective single-arm interventional trial. OSA severity was defined by apnea-hypopnea index (AHI) during in-laboratory polysomnography (PSG) at baseline and 3 and 6 months post-implant. Therapy compliance was assessed by nightly hours of use. Symptoms were assessed using the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep Questionnaire (FOSQ), Calgary Sleep Apnea Quality of Life Index (SAQLI), and the Beck Depression Inventory (BDI). RESULTS HGNS was used on 89% ± 15% of nights (n = 21). On these nights, it was used for 5.8 ± 1.6 h per night. Nineteen of 21 participants had baseline and 6-month PSGs. There was a significant improvement (all P < 0.05) from baseline to 6 months in: AHI (43.1 ± 17.5 to 19.5 ± 16.7), ESS (12.1 ± 4.7 to 8.1 ± 4.4), FOSQ (14.4 ± 2.0 to 16.7 ± 2.2), SAQLI (3.2 ± 1.0 to 4.9 ± 1.3), and BDI (15.8 ± 9.0 to 9.7 ± 7.6). Two serious device-related adverse events occurred: an infection requiring device removal and a stimulation lead cuff dislodgement requiring replacement. CONCLUSIONS HGNS demonstrated favorable safety, efficacy, and compliance. Participants experienced a significant decrease in OSA severity and OSA-associated symptoms. CLINICAL TRIAL INFORMATION NAME: Australian Clinical Study of the Apnex Medical HGNS System to Treat Obstructive Sleep Apnea. REGISTRATION NUMBER NCT01186926. URL: http://clinicaltrials.gov/ct2/show/NCT01186926.

Comparison of upper airway collapse during general anaesthesia and sleep.

Measurement of the collapsibility of the upper airway while a patient is awake is not a good guide to such collapsibility during sleep, presumably because of differences in respiratory drive, muscle tone, and sensitivity of reflexes. To assess whether a relation existed between general anaesthesia and sleep, we measured collapsibility of the upper airway during general anaesthesia and severity of sleep-disordered breathing in 25 people who were having minor surgery on their limbs. Anaesthetised patients who needed positive pressure to maintain airway patency had more severe sleep-disordered breathing than did those whose airways remained patent at or below atmospheric pressure. Such an association was strongest during rapid-eye-movement (REM) sleep. Our findings suggest that sleep-disordered breathing should be considered in all patients with a pronounced tendency for upper airway obstruction during anaesthesia or during recovery from it.

Neurocognitive function in obstructive sleep apnoea: A meta-review

Adult obstructive sleep apnoea (OSA) is associated with cognitive dysfunction. While many review articles have attempted to summarize the evidence for this association, it remains difficult to determine which domains of cognition are affected by OSA. This is because of marked differences in the nature of these reviews (e.g. many are unsystematic) and the many different tasks and domains assessed. This paper addresses this issue by comparing the results of only systematic reviews or meta‐analyses assessing the effects of OSA on cognition, the relationship between OSA severity and cognition, and/or the effects of treatment on cognition in OSA. Electronic databases and hand‐searching were undertaken to select reviews that reported on these areas. We found 33 reviews; five reviews met predetermined, stringent selection criteria. The majority of reviews supported deficits in attention/vigilance, delayed long‐term visual and verbal memory, visuospatial/constructional abilities, and executive function in individuals with OSA. There is also general agreement that language ability and psychomotor function are unaffected by OSA. Data are equivocal for the effects of OSA on working memory, short‐term memory and global cognitive functioning. Attention/vigilance dysfunction appears to be associated with sleep fragmentation and global cognitive function with hypoxaemia. Continuous positive airway pressure treatment of OSA appears to improve executive dysfunction, delayed long‐term verbal and visual memory, attention/vigilance and global cognitive functioning. In order to improve our understanding of cognitive dysfunction in OSA, future research should pay particular attention to participant characteristics, measures of disease severity and choice of neuropsychological tests.

Collapsibility of the upper airway during anesthesia with isoflurane.

Background The unprotected upper airway tends to obstruct during general anesthesia, yet its mechanical properties have not been studied in detail during this condition. Methods To study its collapsibility, pressure–flow relationships of the upper airway were obtained at three levels of anesthesia (end-tidal isoflurane = 1.2%, 0.8%, and 0.4%) in 16 subjects while supine and spontaneously breathing on nasal continuous positive airway pressure. At each level of anesthesia, mask pressure was transiently reduced from a pressure sufficient to abolish inspiratory flow limitation (11.8 ± 2.7 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. The site of collapse was determined from simultaneous measurements of nasopharyngeal, oropharyngeal, and hypopharyngeal and esophageal pressures. Results The airway remained hypotonic (minimal or absent intramuscular genioglossus electromyogram activity) throughout each study. During flow-limited breaths, inspiratory flow decreased linearly with decreasing mask pressure (r2 = 0.86 ± 0.17), consistent with Starling resistor behavior. At end-tidal isoflurane of 1.2%, critical pressure was 1.1 ± 3.5 cm H2O; at 0.4% it decreased to −0.2 ± 3.6 cm H2O (P < 0.05), indicating decreased airway collapsibility. This decrease was associated with a decrease in end-expiratory esophageal pressure of 0.6 ± 0.9 cm H2O (P < 0.05), suggesting an increased lung volume. Collapse occurred in the retropalatal region in 14 subjects and in the retrolingual region in 2 subjects, and did not change with anesthetic depth. Conclusions Isoflurane anesthesia is associated with decreased muscle activity and increased collapsibility of the upper airway. In this state it adopts the behavior of a Starling resistor. The decreased collapsibility observed with decreasing anesthetic depth was not a consequence of neuromuscular activity, which was unchanged. Rather, it may be related to increased lung volume and its effect on airway wall longitudinal tension. The predominant site of collapse is the soft palate.

Evolution of changes in upper airway collapsibility during slow induction of anesthesia with propofol.

Background:Upper airway collapsibility is known to increase under anesthesia. This study assessed how this increase in collapsibility evolves during slow Propofol induction and how it relates to anesthesia-induced changes in upper airway muscle activity and conscious state. Methods:Nine healthy volunteers were studied. Anesthesia was induced with Propofol in a step-wise manner (effect-site concentration steps of 0.5 &mgr;g · ml−1 from 0 to 3 &mgr;g · ml−1 and thereafter to 4 &mgr;g · ml−1 and 6 &mgr;g · ml−1 [target-controlled infusion]). Airway patency was maintained with continuous positive airway pressure. Pharyngeal collapsibility was assessed at each concentration by measuring critical pressure. Intramuscular genioglossus electromyogram and anesthetic depth (bispectral index score) were monitored throughout. Loss of consciousness was defined as failure to respond to loud verbal command. Results:Loss of consciousness occurred at varying Propofol effect-site concentrations between 1.5 and 4.0 &mgr;g · ml−1. Initially genioglossus electromyographic activity was sustained with increases in Propofol concentration, increasing in some individuals. At or approaching loss of consciousness, it decreased, often abruptly, to minimal values with an accompanying increase in critical pressure. In most subjects, bispectral index score decreased alinearly with increasing Propofol concentration with greatest rate of change coinciding with loss of consciousness. Conclusions:Slow stepwise induction of Propofol anesthesia is associated with an alinear increase in upper airway collapsibility. Disproportionate decreases in genioglossus electromyogram activity and increases in pharyngeal critical closing pressure were observed proximate to loss of consciousness, suggesting that particular vulnerability exists after transition from conscious to unconscious sedation. Such changes may have parallels with upper airway behavior at sleep onset.

High-intensity inspiratory muscle training in COPD

The aim of the present study was to investigate the effects of an interval-based high-intensity inspiratory muscle training (H-IMT) programme on inspiratory muscle function, exercise capacity, dyspnoea and health-related quality of life (QoL) in subjects with chronic obstructive pulmonary disease. A double-blind randomised controlled trial was performed. Sixteen subjects (11 males, mean forced expiratory volume in one second (FEV1) 37.4±12.5%) underwent H-IMT performed at the highest tolerable inspiratory threshold load (increasing to 101% of baseline maximum inspiratory pressure). Seventeen subjects (11 males, mean FEV1 36.5±11.5%) underwent sham inspiratory muscle training (S-IMT) at 10% of maximum inspiratory pressure. Training took place three times a week for 8 weeks and was fully supervised. Pre- and post-training measurements of lung function, maximum inspiratory pressure, maximum threshold pressure, exercise capacity, dyspnoea and QoL (Chronic Respiratory Disease Questionnaire; CRDQ) were obtained. H-IMT increased maximum inspiratory pressure by 29%, maximum threshold pressure by 56%, 6-min walk distance by 27 m, and improved dyspnoea and fatigue (CRDQ) by 1.4 and 0.9 points per item, respectively. These changes were significantly greater than any seen following S-IMT. In conclusion, high-intensity inspiratory muscle training improves inspiratory muscle function in subjects with moderate-to-severe chronic obstructive pulmonary disease, yielding meaningful reductions in dyspnoea and fatigue.

In vivo size and shape measurement of the human upper airway using endoscopic long-range optical coherence tomography

We describe a long-range optical coherence tomography system for size and shape measurement of large hollow organs in the human body. The system employs a frequency-domain optical delay line of a configuration that enables the combination of high-speed operation with long scan range. We compare the achievable maximum delay of several delay line configurations, and identify the configurations with the greatest delay range. We demonstrate the use of one such long-range delay line in a catheter-based optical coherence tomography system and present profiles of the human upper airway and esophagus in vivo with a radial scan range of 26 millimeters. Such quantitative upper airway profiling should prove valuable in investigating the pathophysiology of airway collapse during sleep (obstructive sleep apnea).

Improvements in Symptoms and Quality of Life following Exercise Training in Older Adults with Moderate/Severe Persistent Asthma

Background: Some individuals with moderate/severe persistent asthma develop irreversible airway obstruction. These individuals present with dyspnoea, exercise intolerance and impaired quality of life (QOL), all of which could potentially be alleviated with exercise training. Objective: To investigate whether exercise training improves functional exercise capacity and QOL in middle-aged and older adults with fixed airway obstruction asthma (FAOA). Methods: 35 subjects aged 67.8 ± 10.6 years, with FEV1 59 ± 16% of predicted, were randomised to a 6-week ‘intervention’ period of supervised exercise training (n = 20) or usual care (n = 15). This period was preceded by a 3-week run-in period during which asthma control was assessed weekly. Functional exercise capacity (6-min walk distance, 6MWD) and QOL (Asthma QOL Questionnaire, AQLQ) were measured before, immediately following and 3 months after the intervention period. Results: 34 subjects (exercise group, n = 19, and control group, n = 15) completed the intervention period. Relative to the control group, the exercise group had greater improvements immediately following and 3 months after the intervention in the AQLQ symptom domain (0.61, p = 0.001, and 0.57 points per item, p = 0.005) and AQLQ activity limitation domain (0.43, p = 0.04, and 0.55 points per item, p = 0.04). 6MWD increased (36 ± 37 m, p < 0.01) in the exercise group immediately following training and remained elevated (34 ± 45 m, p < 0.01) at the 3-month follow-up. The magnitude of change in 6MWD between groups was not significant, despite no change in the control group. Conclusions: Supervised exercise training improves symptoms and QOL in adults with FAOA.

Evaluation of pharyngeal shape and size using anatomical optical coherence tomography in individuals with and without obstructive sleep apnoea

This study compared shape, size and length of the pharyngeal airway in individuals with and without obstructive sleep apnoea (OSA) using a novel endoscopic imaging technique, anatomical optical coherence tomography (aOCT). The study population comprised a preliminary study group of 20 OSA patients and a subsequent controlled study group of 10 OSA patients and 10 body mass index (BMI)‐, gender‐ and age‐matched control subjects without OSA. All subjects were scanned using aOCT while awake, supine and breathing quietly. Measurements of airway cross‐sectional area (CSA) and anteroposterior (A‐P) and lateral diameters were obtained from the hypo‐, oro‐ and velopharyngeal regions. A‐P : lateral diameter ratios were calculated to provide an index of regional airway shape. In all subjects, pharyngeal CSA was lowest in the velopharynx. Patients with OSA had a smaller velopharyngeal CSA than controls (maximum CSA 91 ± 40 versus 153 ± 84 mm2; P < 0.05) but comparable oro‐ (318 ± 80 versus 279 ± 129 mm2; P = 0.48) and hypopharyngeal CSA (250 ± 105 versus 303 ± 112 mm2; P = 0.36). In each pharyngeal region, the long axis of the airway was oriented in the lateral diameter. Airway shape was not different between the groups. Pharyngeal airway length was similar in both groups, although the OSA group had longer uvulae than the control group (16.8 ± 6.2 versus 11.2 ± 5.2 mm; P < 0.05). This study has shown that individuals with OSA have a smaller velopharyngeal CSA than BMI‐, gender‐ and age‐matched control volunteers, but comparable shape: a laterally oriented ellipse. These findings suggest that it is an abnormality in size rather than shape that is the more important anatomical predictor of OSA.