Feasibility of oropharyngeal and respiratory muscle training in individuals with OSA and spinal cord injury or disease: A pilot study.

OBJECTIVES: To examine the feasibility of individuals with spinal cord injury or disease (SCI/D) to perform combined oropharyngeal and respiratory muscle training (RMT) and determine its impact on their respiratory function. METHODS: A prospective study at a single Veterans Affairs (VA) Medical Center. Inclusion criteria included: 1) Veterans with chronic SCI/D (>6 months postinjury and American Spinal Injury Association (ASIA) classification A-D) and 2) evidence of OSA by apnea-hypopnea index (AHI ≥5 events/h). Eligible participants were randomly assigned to either an experimental (exercise) group that involved performing daily inspiratory, expiratory (using POWERbreathe and Expiratory Muscle Strength Trainer 150 devices, respectively), and tongue strengthening exercises or a control (sham) group that involved using a sham device, for a 3-month period. Spirometry, maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP), polysomnography, and sleep questionnaires were assessed at baseline and at 3 months. RESULTS: Twenty-four individuals were randomized (12 participants in each arm). A total of eight (67%) participants completed the exercise arm, and ten (83%) participants completed the sham arm. MIP was significantly increased (p < 0.05) in the exercise group compared with the baseline. CONCLUSIONS: Combined oropharyngeal and RMT are feasible for individuals with SCI/D. Future studies are needed to determine the clinical efficacy of these respiratory muscle exercises.

Mirtazapine reduces susceptibility to hypocapnic central sleep apnea in males with sleep-disordered breathing: a pilot study.

Studies in humans and animal models with spinal cord injury (SCI) have demonstrated that medications targeting serotonin receptors may decrease the susceptibility to central sleep-disordered breathing (SDB). We hypothesized that mirtazapine would decrease the propensity to develop hypocapnic central sleep apnea (CSA) during sleep. We performed a single-blind pilot study on a total of 10 men with SDB (7 with chronic SCI and 3 noninjured) aged 52.0 ± 11.2 yr. Participants were randomly assigned to either mirtazapine (15 mg at bedtime) or a placebo for at least 1 wk, followed by a 7-day washout period before crossing over to the other intervention. Split-night studies included polysomnography and induction of hypocapnic CSA using a noninvasive ventilation (NIV) protocol. The primary outcome was CO2 reserve, defined as the difference between eupneic and end of NIV end-tidal CO2 ([Formula: see text]) preceding induced hypocapneic CSA. Secondary outcomes included controller gain (CG), other ventilatory parameters, and SDB severity. CG was defined as the ratio of change in minute ventilation (V̇e) between control and hypopnea to the change in CO2 during sleep. CO2 reserve was significantly widened on mirtazapine than placebo (-3.8 ± 1.2 vs. -2.0 ± 1.5 mmHg; P = 0.015). CG was significantly decreased on mirtazapine compared with placebo [2.2 ± 0.7 vs. 3.5 ± 1.9 L/(mmHg × min); P = 0.023]. There were no significant differences for other ventilatory parameters assessed or SDB severity between mirtazapine and placebo trials. These findings suggest that the administration of mirtazapine can decrease the susceptibility to central apnea by reducing chemosensitivity and increasing CO2 reserve; however, considering the lack of changes in apnea-hypopnea index (AHI), further research is required to understand the significance of this finding.NEW & NOTEWORTHY To our knowledge, this research study is novel as it is the first study in humans assessing the effect of mirtazapine on CO2 reserve and chemosensitivity in individuals with severe sleep-disordered breathing. This is also the first study to determine the potential therapeutic effects of mirtazapine on sleep parameters in individuals with a spinal cord injury.

Buspirone decreases susceptibility to hypocapnic central sleep apnea in chronic SCI patients.

Spinal cord injury (SCI) is a risk factor for central sleep apnea (CSA). Previous studies in animal models with SCI have demonstrated a promising recovery in respiratory and phrenic nerve activity post-injury induced by the systemic and local administration of serotonin receptor agonists such as Buspirone and Trazodone. Human trials must be performed to determine whether individuals with SCI respond similarly. We hypothesized that Buspirone and Trazodone would decrease the propensity to hypocapnic CSA during sleep. We studied eight males with chronic SCI and sleep-disordered breathing (SDB) [age: 48.8 ± 14.2 yr; apnea-hypopnea index (AHI): 44.9 ± 23.1] in a single-blind crossover design. For 13 days, participants were randomly assigned either Buspirone (7.5-15 mg twice daily), Trazodone (100 mg), or a placebo followed by a 14-day washout period before crossing over to the other interventions. Study nights included polysomnography and induction of CSA using a noninvasive ventilation protocol. We assessed indexes of SDB, CO2 reserve, apneic threshold (AT), controller gain (CG), plant gain (PG), and ventilatory parameters. CO2 reserve was significantly widened on Buspirone (-3.6 ± 0.9 mmHg) compared with both Trazodone (-2.5 ± 1.0 mmHg, P = 0.009) and placebo (-1.8 ± 1.5 mmHg, P < 0.001) but not on Trazodone vs. placebo (P = 0.061). CG was significantly decreased on Buspirone compared with placebo (1.8 ± 0.4 vs. 4.0 ± 2.0 L/(mmHg·min), P = 0.025) but not on Trazodone compared with placebo (2.5 ± 1.1 vs. 4.0 ± 2.0 L/(mmHg·min); P = 0.065). There were no significant differences for PG, AT, or any SDB indexes (AHI, obstructive apnea index, central apnea index, oxygen desaturation index). The administration of Buspirone decreased the susceptibility to induced hypocapnic central apnea by reducing chemosensitivity and increasing CO2 reserve in chronic SCI patients.NEW & NOTEWORTHY This research study is novel as it is the first study in a humans that we are aware of that demonstrates the ability of Buspirone to increase CO2 reserve and hence decrease susceptibility to hypocapnic central apnea in patients with spinal cord injury.

Longitudinal effect of nocturnal R-R intervals changes on cardiovascular outcome in a community-based cohort.

RATIONALE: Sleep-disordered breathing (SDB) is strongly linked to adverse cardiovascular outcomes (cardiovascular diseases (CVD)). Whether heart rate changes measured by nocturnal R-R interval (RRI) dips (RRI dip index (RRDI)) adversely affect the CVD outcomes is unknown. OBJECTIVES: To test whether nocturnal RRDI predicts CVD incidence and mortality in the Wisconsin Sleep Cohort study (WSCS), independent of the known effects of SDB on beat-to-beat variability. METHODS: The study analysed electrocardiograph obtained from polysomnography study to assess the nocturnal total RRDI (the number of RRI dips divided by the total recording time) and sleep RRDI (the number of RRI dips divided by total sleep time). A composite CVD risk as a function of total and sleep RRDI was estimated by Cox proportional hazards in the WSCS. RESULTS: The study sample consisted of 569 participants from the WSCS with no prior CVD at baseline were followed up for up to 15 years. Nocturnal total RRDI (10-unit change) was associated with composite CVD event(s) (HR, 1.24 per 10-unit increment in RRDI (95% CI 1.10 to 1.39), p<0.001). After adjusting for demographic factors (age 58±8 years old; 53% male; and body mass index 31±7 kg/m2), and apnoea-hypopnoea index (AHI 4%), individuals with highest total nocturnal RRDI category (≥28 vs<15 dips/hour) had a significant HR for increased incidence of CVD and mortality of 7.4(95% CI 1.97 to 27.7), p=0.003). Sleep RRDI was significantly associated with new-onset CVD event(s) (HR, 1.21 per 10-unit increment in RRDI (95% CI 1.09 to 1.35), p<0.001) which remained significant after adjusting for demographic factors, AHI 4%, hypoxemia and other comorbidities. CONCLUSION: Increased nocturnal RRDI predicts cardiovascular mortality and morbidity, independent of the known effects of SDB on beat-to-beat variability. The frequency of RRDI is higher in men than in women, and is significantly associated with new-onset CVD event(s) in men but not in women.

Characteristics and Consequences of Non-apneic Respiratory Events During Sleep.

Rationale: Current scoring criteria of non-apneic events (ie, hypopnea) require the presence of oxyhemoglobin desaturation and/or arousal. However, other sleep study parameters may help to identify abnormal respiratory events (REs) and assist in making more accurate diagnosis. Objectives: To investigate whether non-apneic REs without desaturation or cortical arousal are associated with respiratory and cardiac consequences. Methods: Thirteen participants with sleep disturbances (snoring and/or excessive day time sleepiness), were screened using attended in laboratory polysomnography (PSG) while monitoring pressure and airflow via a nasal mask with an attached pneumotach. To separate the contribution of the upper airway resistance (RUA) and total pulmonary resistance (RL), supraglottic and esophageal pressures were measured using Millar pressure catheters. RL and RUA were calculated during baseline and hypopneas. RL was defined as the resistive pressure divided by the maximal flow during inspiration and expiration. Hypopnea was defined 30% decrease in flow with 3% desaturation and/or cortical arousal. REs was defined as 30% decrease in the flow without desaturation and/or cortical arousal. In eight subjects continuous positive airway pressure (CPAP) was titrated to optimal pressure. R-R interval (RRI) was defined as consecutive beat-to-beat intervals on single lead electrocardiograph (ECG) during baseline, RE/hypopnea and on optimal CPAP. Results: REs associated with increased expiratory RUA (14.6 ± 11.3 vs. 7.5 ± 4.5 cmH2O L-1 s-1; p < .05), and increased expiratory RL relative to baseline (29.2 ± 14.6 vs. 20.9 ± 11.0 and 23.7 ± 12.1 vs. 14.3 ± 5.6 cmH2O L-1 s-1 during inspiration and expiration, respectively; p < .05). RRI decreased significantly following RE and hypopnea relative to baseline (804.8 ± 33.1 vs. 806.4 ± 36.3 vs. 934.3 ± 45.8 ms; p < .05). Optimal CPAP decreased expiratory RUA (4.0 ± 2.5 vs. 7.5 ± 4.5 cmH2O L-1 s-1; p < .05), decreased inspiratory RL (12.6 ± 14.1 vs. 7.5 ± 4.5 cmH2O L-1 s-1; p < .05), and allowed RRI to return to baseline (p < .05). RRI dips index was an independent predictor of sleep-disordered breathing (SDB) when non-apneic REs were accounted for in symptomatic patients (p < .05). Conclusions: Non-apneic REs without cortical arousal or desaturation are associated with significant respiratory and heart rate changes. Optimal CPAP and the reduction of resistive load are associated with the normalization of heart rate indicating potential clinical benefit.