Sichang Xiao

Neural Respiratory Drive and Arousal in Patients with Obstructive Sleep Apnea Hypopnea

STUDY OBJECTIVES It has been hypothesized that arousals after apnea and hypopnea events in patients with obstructive sleep apnea are triggered when neural respiratory drive exceeds a certain level, but this hypothesis is based on esophageal pressure data, which are dependent on flow and lung volume. We aimed to determine whether a fixed threshold of respiratory drive is responsible for arousal at the termination of apnea and hypopnea using a flow independent technique (esophageal diaphragm electromyography, EMGdi) in patients with obstructive sleep apnea. SETTING Sleep center of state Key Laboratory of Respiratory Disease. PATIENTS Seventeen subjects (two women, mean age 53 ± 11 years) with obstructive sleep apnea/hypopnea syndrome were studied. METHODS We recorded esophageal pressure and EMGdi simultaneously during overnight full polysomnography in all the subjects. MEASUREMENTS AND RESULTS A total of 709 hypopnea events and 986 apnea events were analyzed. There was wide variation in both esophageal pressure and EMGdi at the end of both apnea and hypopnea events within a subject and stage 2 sleep. The EMGdi at the end of events that terminated with arousal was similar to those which terminated without arousal for both hypopnea events (27.6% ± 13.9%max vs 29.9% ± 15.9%max, P = ns) and apnea events (22.9% ± 11.5%max vs 22.1% ± 12.6%max, P = ns). The Pes at the end of respiratory events terminated with arousal was also similar to those terminated without arousal. There was a small but significant difference in EMGdi at the end of respiratory events between hypopnea and apnea (25.3% ± 14.2%max vs 21.7% ± 13.2%max, P < 0.05]. CONCLUSIONS Our data do not support the concept that there is threshold of neural respiratory drive that is responsible for arousal in patients with obstructive sleep apnea.

Coexistence of OSA may compensate for sleep related reduction in neural respiratory drive in patients with COPD

Background The mechanisms underlying sleep-related hypoventilation in patients with coexisting COPD and obstructive sleep apnoea (OSA), an overlap syndrome, are incompletely understood. We compared neural respiratory drive expressed as diaphragm electromyogram (EMGdi) and ventilation during stage 2 sleep in patients with COPD alone and patients with overlap syndrome. Methods EMGdi and airflow were recorded during full polysomnography in 14 healthy subjects, 14 patients with OSA and 39 consecutive patients with COPD. The ratio of tidal volume to EMGdi was measured to indirectly assess upper airway resistance. Results Thirty-five patients with COPD, 12 healthy subjects and 14 patients with OSA completed the study. Of 35 patients with COPD, 19 had COPD alone (FEV1 38.5%±16.3%) whereas 16 had an overlap syndrome (FEV1 47.5±16.2%, AHI 20.5±14.1 events/hour). Ventilation (VE) was lower during stage 2 sleep than wakefulness in both patients with COPD alone (8.6±2.0 to 6.5±1.5 L/min, p<0.001) and those with overlap syndrome (8.3±2.0 to 6.1±1.8 L/min). Neural respiratory drive from wakefulness to sleep decreased significantly for patients with COPD alone (29.5±13.3% to 23.0±8.9% of maximal, p<0.01) but it changed little in those with overlap syndrome. The ratio of tidal volume to EMGdi was unchanged from wakefulness to sleep in patients with COPD alone and healthy subjects but was significantly reduced in patients with OSA or overlap syndrome (p<0.05). Conclusions Stage 2 sleep-related hypoventilation in COPD alone is due to reduction of neural respiratory drive, but in overlap syndrome it is due to increased upper airway resistance.

Continuous Positive Airway Pressure and Breathlessness in Obese Patients with Obstructive Sleep Apnea: A Pilot Study.

STUDY OBJECTIVES Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnea (OSA). However, long-term compliance with CPAP is limited. We tested the hypothesis that CPAP levels routinely used during sleep increase neural respiratory drive (NRD) and breathlessness, which may discourage compliance. METHODS This was an observational physiological cohort study in a respiratory physiology and sleep unit, University Hospital. Patients with a body mass index (BMI) > 25 kg/m(2) and confirmed OSA were studied supine and awake on CPAP (4-20 cm H2O, increments of 2 cm H2O/3 min). We measured NRD during awake CPAP titration in obese subjects to quantify the response to the load of the respiratory system and compared it to the CPAP used for nocturnal treatment, with the modified Borg Scale (mBorg) for dyspnea recorded (from 0 to 10 points, with higher numbers indicating more breathlessness). RESULTS Fifteen patients (age 48 ± 10 years, 12 male, BMI 38.9 ± 5.8 kg/m(2)) with OSA (AHI 32.2 ± 21.1/h, 95(th) percentile of CPAP 14.1 ± 3.8 cm H2O) were studied and NRD (electromyogram of the parasternal intercostals, EMGpara; EMG of the external oblique, EMGabdomen) was recorded (awake, supine). Awake, EMGpara declined from baseline to 70.2% ± 17.1% when CPAP of 10.7 ± 3.4 cm H2O (P = 0.026) was applied. Further increase in CPAP led to a rise in EMGpara and increased breathlessness (P = 0.02). CPAP compliance (nights used) correlated negatively with mBorg scores (r = -0.738, P = 0.006). CONCLUSIONS Awake, the respiratory system is maximally offloaded with lower than therapeutic CPAP levels in obese patients with OSA. Levels of NRD observed at effective CPAP levels while asleep are associated with breathlessness which may limit long-term CPAP compliance.

The acute effect of continuous positive airway pressure titration on blood pressure in awake overweight/obese patients with obstructive sleep apnoea

Abstract Objectives: Continuous positive airway pressure (CPAP) improves upper airway obstruction in patients with obstructive sleep apnoea (OSA), who often are overweight-obese. Although it is thought that CPAP improves long-term blood pressure control (BP), the impact of acute and short-term CPAP use on the cardiovascular system in obese patients has not been described in detail. Methods: Obese patients (body mass index, BMI > 25 kg/m2) with OSA were studied awake, supine during incremental CPAP titration (4–20 cmH2O, +2 cmH2O/3 mins). BP was measured continuously with a beat-to-beat BP monitor (Ohmeda 2300, Finapres Medical Systems, Amsterdam/NL), BP variability (BPV) was calculated as the standard deviation of BP at each CPAP level, the 95% confidence interval (95%CI) was calculated and changes in BP and BPV were reported. Results: 15 patients (12 male, 48 ± 10) years, BMI 38.9 ± 5.8 kg/m2) were studied; the baseline BP was 131.0 ± 10.2/85.1 ± 9.1 mmHg. BP and BPV increased linearly with CPAP titration (systolic BP r = 0.960, p < .001; diastolic BP r = 0.961, p < .001; systolic BPV r = 0.662, p = .026; diastolic BPV r = 0.886, p < .001). The systolic BP increased by +17% (+23.15 (7.9, 38.4) mmHg; p = .011) and the diastolic BP by +23% (+18.27 (2.33, 34.21) mmHg; p = .009), when titrating CPAP to 20 cmH2O. Systolic BPV increased by +96% (+5.10 (0.67, 9.53) mmHg; p < .001) and was maximal at 14 cmH2O, and diastolic BPV by +97% (+3.02 (0.26, 5.78) mmHg; p < .001) at 16 cmH2O. Conclusion: Short-term incremental CPAP leads to significant increases in BP and BPV in obese patients with OSA while awake. Careful titration of pressures is required to minimise the risk of nocturnal awakenings while improving BP control.

FEASIBILITY AND PATIENT TOLERABILITY OF TRANSCUTANEOUS ELECTRICAL STIMULATION IN OBSTRUCTIVE SLEEP APNOEA

Introduction Transcutaneous electrical stimulation (TES) provides neuromuscular tone to the pharyngeal dilator muscles of the upper airway (UA) while asleep, but feasibility of this method to treat obstructive sleep apnoea (OSA) throughout the whole night has not been tested. Patients and methods We conducted a phase two double-blind, sham-controlled, randomised controlled trial using TES of the UA muscles in 36 patients with confirmed OSA to assess patients’ device acceptance and the side effect profile. Patients were studied using polysomnography during randomly assigned nights of sham-stimulation and active treatment following titration of the current while awake. Assessment of patients’ device acceptance and experience of side effects was measured using a visual analogue scale (0–10 points) where high scores indicated better outcomes. Results We included 36 patients (age mean 50.8 (SD 11.2) years, male/female 30/6, body mass index median 29.6 (IQR 26.9–34.9) kg/m2, Epworth Sleepiness Scale 10.5 (4.6) points, oxygen desaturation index median 25.7 (16.0–49.1)/hour, apnoea-hypopnoea index median 28.1 (19.0–57.0)/hour). None of the patients reported skin discomfort, unpleasant tongue sensations or morning headache. There was no difference in patients’ perceived sleep quality. There was a 59% reduction in mouth dryness after active treatment compared to sham-stimulation. There were no severe adverse events (Table). Conclusion TES of the UA dilator muscles in OSA can be delivered throughout the night with few side effects and does not lead to arousal from sleep, if appropriately titrated. Abstract S26 Table 1 Device acceptance and side effect profile of TES and polysomnography data. Variables presented as median and interquartilerange. p-value derived from the Wilcoxon test. Parameters Sham- Stimulation Active treatment p-value Feeling refreshed 5.7 (2.7–7.2) 6.6 (2.2–8.5) 0.40 Skin discomfort 9.9 (9.5–10.0) 9.9 (9.7–10.0) 0.95 Tongue unpleasant sensation 9.9 (9.4–10.0) 9.9 (9.4–10.0) 0.63 Sleep quality 5.6 (2.9–7.1) 6.4 (2.4–8.0) 0.28 Morning headache 9.4 (6.3–10.0) 9.9 (8.1–10.0) 0.27 Mouth dryness 4.4 (2.2–8.5) 7.4 (4.9–9.7) 0.007

S48 Continuous positive airway pressure titration in awake obese subjects with obstructive sleep apnoea and its impact on neural respiratory drive and breathlessness

Background Continuous positive airway pressure (CPAP) is an effective treatment for obstructive sleep apnoea (OSA). We assessed neural respiratory drive (NRD), as measured by the surface electromyogram of the parasternal intercostals (sEMGpara), during awake CPAP titration to quantify the effect of chest inflation on the load of the respiratory system. Patients and methods Obese patients (body-mass-index, BMI >30) with confirmed obstructive sleep apnoea (OSA) were studied and NRD (sEMGpara) and the surface EMG of the external oblique (sEMGabd) were recorded and normalised to baseline activity (awake, supine). The apnoea-hypopnoea index (AHI) and 95th percentile of CPAP were determined in sleep studies. The patients were then studied whilst awake and breathing on CPAP (4–20 cmH2O, increments of 2 cmH2O/3 mins), with the modified Borg score (mBorg) recorded. Results 15 patients (age 48 ± 10 years, 12 male, BMI 38.9 ± 5.8) suffering with moderate-severe OSA (AHI 32.2 ± 21.1/h, 95th percentile nocturnal CPAP 14.1 ± 3.8 cmH2O) were studied. Awake, sEMGpara declined by 15.1 ± 1.5% from baseline when CPAP was applied, with the nadir at a CPAP of 10.6 ± 3.4 cmH2O (p = 0.026). Further increase in CPAP levels led to a rise in sEMGpara and breathlessness (mBorg at lowest sEMGpara 0.9 ± 0.8 points, at CPAP of 20 cmH2O 2.7 ± 2.7 points, p = 0.02). Conclusion The respiratory system is maximally offloaded with subtherapeutic CPAP levels in OSA. Levels of NRD observed at effective CPAP levels are associated with breathlessness which can impact on CPAP compliance.