Kathleen J. Maddison

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.

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.

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.

Hypoglossal nerve stimulation improves obstructive sleep apnea: 12-month outcomes

Reduced upper airway muscle activity during sleep is a key contributor to obstructive sleep apnea pathogenesis. Hypoglossal nerve stimulation activates upper airway dilator muscles, including the genioglossus, and has the potential to reduce obstructive sleep apnea severity. The objective of this study was to examine the safety, feasibility and efficacy of a novel hypoglossal nerve stimulation system (HGNS®; Apnex Medical, St Paul, MN, USA) in treating obstructive sleep apnea at 12 months following implantation. Thirty‐one subjects (35% female, age 52.4 ± 9.4 years) with moderate to severe obstructive sleep apnea and unable to tolerate positive airway pressure underwent surgical implantation and activation of the hypoglossal nerve stimulation system in a prospective single‐arm interventional trial. Primary outcomes were changes in obstructive sleep apnea severity (apnea–hypopnea index, from in‐laboratory polysomnogram) and sleep‐related quality of life [Functional Outcomes of Sleep Questionnaire (FOSQ)]. Hypoglossal nerve stimulation was used on 86 ± 16% of nights for 5.4 ± 1.4 h per night. There was a significant improvement (P < 0.001) from baseline to 12 months in apnea–hypopnea index (45.4 ± 17.5 to 25.3 ± 20.6 events h−1) and Functional Outcomes of Sleep Questionnaire score (14.2 ± 2.0 to 17.0 ± 2.4), as well as other polysomnogram and symptom measures. Outcomes were stable compared with 6 months following implantation. Three serious device‐related adverse events occurred: an infection requiring device removal; and two stimulation lead cuff dislodgements requiring replacement. There were no significant adverse events with onset later than 6 months following implantation. Hypoglossal nerve stimulation demonstrated favourable safety, feasibility and efficacy.

Feasibility of Applying Real-time Optical Imaging During Bronchoscopic Interventions for Central Airway Obstruction

BackgroundInterventional bronchoscopists manage central airway obstruction (CAO) through dilation, tumor ablation, and/or stent insertion. Anatomical optical coherence tomography (aOCT), a validated light-based imaging technique, has the unique capacity of providing bronchoscopists with intraprocedural central airway measurements. This study aims to describe the potential role of real-time aOCT in guiding interventions during CAO procedures. MethodsProspective case series were recruited from patients referred for bronchoscopic management of symptomatic CAO. Preprocedure chest computed tomography (CT) scans were analyzed for relevant airway dimensions, such as stenosis caliber and length, and aided procedure planning. During bronchoscopy, an aOCT fiberoptic probe was inserted through the working channel of the bronchoscope to image the airway stenosis. From these aOCT images, stenosis dimensions were measured and compared with the preprocedure CT measurements. Preprocedure and postprocedure spirometry, Medical Research Council dyspnea score, and Eastern Cooperative Oncology Group performance status were collected to assess intervention efficacy. ResultsFourteen patients were studied. CT and aOCT-based measurements of airway caliber and length correlated closely (r2=0.87, P<0.001). Bland-Altman analysis showed strong agreement between measurements (mean difference 0.4±8.6 mm). The real-time nature of aOCT imaging provided the advantage of more up-to-date measurements where a delay occurred between CT and bronchoscopy or where the quality of the CT image was suboptimal. After bronchoscopy, the predicted forced expiratory flow in 1 second increased from 67±26% to 78±19% (P=0.04). Eastern Cooperative Oncology Group and dyspnea scores improved in 83% and 75% of the patients, respectively. ConclusionsaOCT provides real-time measurements of obstructing central airway lesions that can assist therapeutic interventions such as selection of endobronchial stents and airway dilatation procedures.

Effects on upper airway collapsibility of presence of a pharyngeal catheter

Catheters that traverse the pharynx are often in place during clinical or research evaluations of upper airway function. The purpose of this study was to determine whether the presence of such catheters affects measures of upper airway collapsibility itself. To do so, pharyngeal critical closing pressure (Pcrit) and resistance upstream of the site of collapse Rus) were assessed in 24 propofol‐anaesthetized subjects (14 men) with and without a multi‐sensor oesophageal catheter (external diameter 2.7 mm) in place. Anaesthetic depth and posture were maintained constant throughout each study. Six subjects had polysomnography(PSG)‐defined obstructive sleep apnea (OSA) and 18 either did not have or were at low risk of OSA. Airway patency was maintained with positive airway pressure. At intervals, pressure was reduced by varying amounts to induce varying degrees of inspiratory flow limitation. The slope of the pressure flow relationship for flow‐limited breaths defined Rus. Pcrit was similar with the catheter in and out (−1.5 ± 5.4 cmH2O and −2.1 ± 5.6 cmH2O, respectively, P = 0.14, n = 24). This remained the case both for those with PSG‐defined OSA (3.9 ± 2.2 cmH2O and 2.6 ± 1.4 cmH2O, n = 6) and those at low risk/without OSA (−3.3 ± 4.9 cmH2O and ‐3.7 ± 5.6 cmH2O, respectively, n = 18). Rus was similar with the catheter in and out (20.0 ± 12.3 cmH2O mL−1 s−1 and 16.8 ± 10.1 cmH2O mL−1 s−1, P = 0.22, n = 24). In conclusion, the presence of a small catheter traversing the pharynx had no significant effect on upper airway collapsibility in these anaesthestized subjects, providing reassurance that such measures can be made reliably in their presence.

The effect of diaphragm contraction on upper airway collapsibility

Increasing lung volume increases upper airway patency and decreases airway resistance and collapsibility. The role of diaphragm contraction in producing these changes remains unclear. This study was undertaken to determine the effect of selective diaphragm contraction, induced by phrenic nerve stimulation, on upper airway collapsibility and the extent to which any observed change was attributable to lung volume-related changes in pressure gradients or to diaphragm descent-related mediastinal traction. Continuous bilateral transcutaneous cervical phrenic nerve stimulation (30 Hz) was applied to nine supine, anesthetized human subjects during transient decreases in airway pressure to levels sufficient to produce flow limitation when unstimulated. Stimulation was applied at two intensities (low and high) and its effects on lung volume and airflow quantified relative to unstimulated conditions. Lung volume increased by 386 ± 269 ml (means ± SD) and 761 ± 556 ml during low and high stimulation, respectively (P < 0.05 for the difference between these values), which was associated with peak inspiratory flow increases of 69 ± 57 and 137 ± 108 ml/s, respectively (P < 0.05 for the difference). Stimulation-induced change in lung volume correlated with change in peak flow (r = 0.65, P < 0.01). Diaphragm descent-related outward displacement of the abdominal wall produced no change in airflow unless accompanied by lung volume change. We conclude that phrenic nerve stimulation-induced diaphragm contraction increases lung volume and reduces airway collapsibility in a dose-dependent manner. The effect appears primarily mediated by changes in lung volume rather than mediastinal traction from diaphragm descent. The study provides a rationale for use of continuous phrenic stimulation to treat obstructive sleep apnea.

Treating Chronic Hypoventilation With Automatic Adjustable Versus Fixed EPAP Intelligent Volume-Assured Positive Airway Pressure Support (iVAPS): A Randomized Controlled Trial

Objectives New noninvasive ventilation (NIV) modes can automatically adjust pressure support settings to deliver effective ventilation in response to varying ventilation demands. It is recommended that fixed expiratory positive airway pressure (FixedEPAP) is determined by attended laboratory polysomnographic (PSG) titration. This study investigated whether automatically determined EPAP (AutoEPAP) was noninferior to FixedEPAP for the control of obstructive sleep apnea (OSA) during intelligent volume-assured pressure support (iVAPS) treatment of chronic hypoventilation. Methods In this randomized, double-blind, crossover study, patients with chronic hypoventilation and OSA used iVAPS with AutoEPAP or FixedEPAP over two separate nights of attended PSG. PSG recordings were scored by an independent scorer using American Academy of Sleep Medicine 2012 criteria. Results Twenty-five adults (14 male) with chronic hypoventilation secondary to obesity hypoventilation syndrome (n = 11), chronic obstructive pulmonary disease (n = 9), or neuromuscular disease (n = 5), all of whom were on established home NIV therapy, were included (age 57 ± 7 years, NIV for ≥3 months, apnea-hypopnea index [AHI] >5/hour). AutoEPAP was noninferior to FixedEPAP for the primary outcome measure (median [interquartile range] AHI 2.70 [1.70-6.05]/hour vs. 2.40 [0.25-5.95]/hour; p = .86). There were no significant between-mode differences in PSG sleep breathing and sleep quality, or self-reported sleep quality, device comfort, and patient preference. Mean EPAP with the Auto and Fixed modes was 10.8 ± 2.0 and 11.8 ± 3.9 cmH2O, respectively (p = .15). Conclusions In patients with chronic hypoventilation using iVAPS, the AutoEPAP algorithm was noninferior to FixedEPAP over a single nights therapy.

Airway Collapse or Closure via the Soft Palate as Mechanism of Obstruction in Sedated Patients

To the Editor: The article by Hillman et al., demonstrating airway collapsibility during incrementally increasing propofol sedation-anesthesia as an inferred mechanism of respiratory impairment (measured via a nasal mask) relied heavily on a technique using nonphysiologic negative airway pressure to induce “collapse.” This method of collapse was strangely documented also in awake patients subjected to sudden high negative pressures (undisclosed) and also occurring abruptly at lower negative pressures just before unconsciousness. Genioglossus electromyogram activity was recorded as a benchmark for muscular activity combating airway collapse and was yet found to increase significantly in a number of patients before collapse at lower pressures under these conditions. Nine subjects were recruited irrespective of “vulnerability to upper airway collapse,” and all mouths were taped shut, with pressure measurements only in esophagus and external airway. Negative airway pressures were induced as expiration started and returned to continuous positive airway pressure on a “posttest” inspiratory effort, with airflow cessation deemed the determinant of “airway collapse.” I would suggest that soft palate obstruction be considered as impairing expiration (and airflow measurements) here for the following reasons: