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

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.

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.

Randomised sham-controlled trial of transcutaneous electrical stimulation in obstructive sleep apnoea.

INTRODUCTION: Obstructive sleep apnoea (OSA) is characterised by a loss of neuromuscular tone of the upper airway dilator muscles while asleep. This study investigated the effectiveness of transcutaneous electrical stimulation in patients with OSA. PATIENTS AND METHODS: This was a randomised, sham-controlled crossover trial using transcutaneous electrical stimulation of the upper airway dilator muscles in patients with confirmed OSA. Patients were randomly assigned to one night of sham stimulation and one night of active treatment. The primary outcome was the 4% oxygen desaturation index, responders were defined as patients with a reduction >25% in the oxygen desaturation index when compared with sham stimulation and/or with an index <5/hour in the active treatment night. RESULTS: In 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/m(2), 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) the primary outcome measure improved when comparing sham stimulation (median 26.9 (17.5-39.5)/hour) with active treatment (median 19.5 (11.6-40.0)/hour; p=0.026), a modest reduction of the mean by 4.1 (95% CI -0.6 to 8.9)/hour. Secondary outcome parameters of patients' perception indicated that stimulation was well tolerated. Responders (47.2%) were predominantly from the mild-to-moderate OSA category. In this subgroup, the oxygen desaturation index was reduced by 10.0 (95% CI 3.9 to 16.0)/hour (p<0.001) and the apnoea-hypopnoea index was reduced by 9.1 (95% CI 2.0 to 16.2)/hour (p=0.004). CONCLUSION: Transcutaneous electrical stimulation of the pharyngeal dilators during a single night in patients with OSA improves upper airway obstruction and is well tolerated. TRIAL REGISTRATION NUMBER: NCT01661712.

Comparison of manual versus automatic continuous positive airway pressure titration and the development of a predictive equation for therapeutic continuous positive airway pressure in Chinese patients with obstructive sleep apnoea.

BACKGROUND AND OBJECTIVE: Whether the therapeutic nasal continuous positive airway pressure (CPAP) derived from manual titration is the same as derived from automatic titration is controversial. The purpose of this study was to compare the therapeutic pressure derived from manual titration with automatic titration. METHODS: Fifty-one patients with obstructive sleep apnoea (OSA) (mean apnoea/hypopnoea index (AHI) = 50.6 ± 18.6 events/h) who were newly diagnosed after an overnight full polysomnography and who were willing to accept CPAP as a long-term treatment were recruited for the study. Manual titration during full polysomnography monitoring and unattended automatic titration with an automatic CPAP device (REMstar Auto) were performed. A separate cohort study of one hundred patients with OSA (AHI = 54.3 ± 18.9 events/h) was also performed by observing the efficacy of CPAP derived from manual titration. RESULTS: The treatment pressure derived from automatic titration (9.8 ± 2.2 cmH(2)O) was significantly higher than that derived from manual titration (7.3 ± 1.5 cmH(2)O; P < 0.001) in 51 patients. The cohort study of 100 patients showed that AHI was satisfactorily decreased after CPAP treatment using a pressure derived from manual titration (54.3 ± 18.9 events/h before treatment and 3.3 ± 1.7 events/h after treatment; P < 0.001). CONCLUSIONS: The results suggest that automatic titration pressure derived from REMstar Auto is usually higher than the pressure derived from manual titration.

[Neural respiratory drive and nocturnal hypoventilation in patients with chronic obstructive pulmonary disease].

OBJECTIVE: To explore the effects of neural respiratory drive on ventilation in patients with chronic obstructive pulmonary disease (COPD) during sleep. METHODS: Diaphragm electromyogram (EMG) from a multipair esophageal electrodes and airflow derived from pneumotachography were recorded during overnight polysomnography in 13 patients with stable COPD recruited from outpatient clinic of First Affiliated Hospital of Guangzhou Medical College from May 2010 to May 2011. Changes in diaphragm EMG and ventilation during wakefulness and different sleep stages were observed. RESULTS: Diaphragm EMG decreased by 26% in non-rapid eye movement sleep (NREM) stage and 39% in rapid eye movement (REM) as compared with wakefulness. Coinciding with change in diaphragm EMG, ventilation (VE) (ml×min(-1)×kg(-1)) significantly decreased from wakefulness (156 ± 53) ml×min(-1)×kg(-1) to steady NREM stage (112 ± 35) ml×min(-1)×kg(-1) (P < 0.05) and further decreased from NREM stage to REM stage (95 ± 27) ml×min(-1)×kg(-1) (P < 0.05). Oxygen saturation also decreased significantly from 97.1% ± 1.8% in wakefulness to REM stage (94.0% ± 3.9%) (P < 0.01). CONCLUSION: Reduced neural respiratory drive contributes to nocturnal hypoventilation in COPD patients.

[Assessment of neural respiratory drive in humans].

OBJECTIVE: Assessment of neural respiratory drive is useful for diagnosis of dyspnea and respiratory failure with unknown causes. The purpose of the study was to compare the sensitivity of trandiaphragmatic pressure (Pdi) and diaphragm electromyogram (EMGdi) in assessment of neural respiratory drive. METHODS: A combined catheter with 10 electrodes and 2 balloons was used to record EMGdi and Pdi during CO2 rebreathing. Three different inspiratory maneuvers-inspiration from functional residual capacity to total lung capacity (TLC), deep inspiration from functional residual capacity against closed airway (MIP), and short sharp inspiration through the nose (Sniff) were performed. Ten healthy subjects [male 4 and female 6; age (26 ± 4) years] were studied. RESULTS: Linear relationship between EMGdi and end-tidal CO2 (r = 0.83-0.98, all P < 0.01) was better than that between Pdi and end-tidal CO2 (r = 0.48-0.96, all P < 0.01) during CO2 rebreathing, Z = -2.731, P < 0.05. The slope of linear relation between EMGdi and end-tidal CO2 (16.3-32.5) was significantly higher than that between Pdi and end-tidal CO2 (0.4-11.1), Z = -3.780, P < 0.01. The maximal EMGdi derived from TLC maneuver (211 ± 48) µV was larger than those from the MIP maneuver (161 ± 48) µV and the Sniff maneuver (145 ± 37) µV, F = 5.931, P < 0.05, whereas the maximal Pdi derived from TLC maneuver (58 ± 27) cm H2O (1 cm H2O = 0.098 kPa) was significantly lower than those from the MIP maneuver (92 ± 32) cm H2O and the Sniff maneuver (95 ± 27) cm H2O, F = 5.155, P < 0.05. CONCLUSION: EMGdi is more sensitive than Pdi in the assessment of neural respiratory drive.

Absence of dynamic hyperinflation during exhaustive exercise in severe COPD reflects submaximal IC maneuvers rather than a nonhyperinflator phenotype.

Approximately 20% of chronic obstructive pulmonary disease (COPD) patients have been considered to have a "nonhyperinflator phenotype." However, this judgment depends on patients making a fully maximal inspiratory capacity (IC) maneuver at rest, since the IC during exercise is compared with this baseline measurement. We hypothesized that IC maneuvers at rest are sometimes submaximal and tested this hypothesis by measuring IC and associated neural respiratory drive at rest and during inhalation of CO2 and exercise in patients with COPD. Twenty-six COPD patients [age 66 ± 6 yr, mean forced expiratory volume in 1 s (FEV1) 40 ± 11% predicted] and 39 healthy subjects (age 39 ± 14 yr, FEV1 98 ± 12% predicted) were studied. IC and the diaphragm electromyogram (EMGdi) associated with it (EMGdi-IC) and forced inspiratory vital capacity (FIVC) and its corresponding EMGdi (EMGdi-FIVC) were measured during inhalation of 8% CO2 (8% CO2-92% O2) and room air. Incremental exhaustive cycle ergometer exercise was also performed in both patients with COPD and healthy subjects. IC, EMGdi-IC, FIVC, and EMGdi-FIVC during breathing 8% CO2 were significantly greater than those during breathing room air in both patients with COPD and healthy subjects (all P < 0.001). EMGdi-IC in patients with COPD constantly increased during exercise from 145 ± 40 µV at rest to 185 ± 52 µV at the end of exercise but change in IC was variable. Neural respiratory drive and its relevant IC increased during hypercapnia. Exercise-related hypercapnia in patients with COPD raises neural respiratory drives, which compensate for IC reduction, leading to underestimation of dynamic hyperinflation measured by IC at rest breathing room air.NEW & NOTEWORTHY Inspiratory capacity measured during hypercapnia is higher than that during eucapnia. Thus total lung capacity is not always be achieved by a standard inspiratory capacity maneuver, leading to risk of underestimation of dynamic hyperinflation in patients with severe chronic obstructive pulmonary disease after exhaustive exercise.

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.

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.

Effect of expiratory load on neural inspiratory drive.

BACKGROUND: Neural respiratory drive is usually measured during inspiration, even in patients with chronic obstructive pulmonary disease (COPD) in whom the primary physiological deficit is expiratory flow limitation. The purpose of the study was to test the hypothesis that inspiratory muscle neural respiratory drive could be used to assess expiratory load. METHODS: Ten healthy young men, (26 ± 4) years old, were asked to expire through a tube immersed in water where an expiratory load was required. The load was judged by the depth of the tube in water and the different loads (0 cmH2O, 10 cmH2O, 20 cmH2O and 30 cmH2O) were randomly introduced. Each expiratory load lasted for 3 - 5 minutes and inspiration was unimpeded throughout. Diaphragm electromyogram (EMG) and transdiaphragmatic pressure were recorded by a catheter with 10 metal coils and two balloons. Incremental cycle exercise with and without an expiratory load at 30 cmH2O was also performed. RESULTS: Neural drive during expiratory loaded breathing was larger than during unloaded breathing but neural drive did not increase proportionally with increasing expiratory load; neural drive during expiratory loading at 0, 10, 20 and 30 cmH2O was (10.1 ± 3.1) µV, (16.7 ± 7.3) µV, (18.4 ± 10.7) µV and (22.9 ± 13.2) µV, respectively. Neural drive as a percentage of maximum at the end of exercise with or without load was similar ((57.4 ± 11.0)% max vs. (62.7 ± 16.4)% max, P > 0.05). CONCLUSION: Neural respiratory drive measured at inspiration does not accurately quantify expiratory load either at rest or during exercise.