The impact of cardiac resynchronization therapy on obstructive sleep apnea in heart failure patients: a pilot study.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to improve cardiac function and reduce Cheyne-Stokes respiration but has not been evaluated in patients with obstructive sleep apnea (OSA). In this pilot study, we investigated the impact of both CRT and CRT plus increased rate pacing in heart failure (ie, congestive heart failure [CHF]) patients with OSA. We hypothesized that through increased cardiac output CRT/pacing would reduce obstructive events and daytime symptoms of sleepiness. METHODS: Full polysomnograms were performed on CHF patients who were scheduled for CRT, and those patients with an apnea-hypopnea index (AHI) of > 5 events per hour were approached about study enrollment. Patients had a pre-CRT implant baseline echocardiogram and an echocardiogram a mean (+/- SEM) duration of 6.6 +/- 1.4 months post-CRT implant; polysomnography; and responded to the Minnesota Living with Heart Failure questionnaire, the Epworth sleepiness scale, and the Functional Outcomes of Sleep Questionnaire. An additional third polysomnography was performed combining CRT with a pacing rate of 15 beats/min above the baseline sleeping heart rate within 1 week of the second polysomnography. Assessments for the change in cardiac output during the polysomnography were performed using circulation time to pulse oximeter as a surrogate. RESULTS: Twenty-four patients were screened, and 13 patients (mean age, 68.6 years; body mass index, 28.7 kg/m(2)) had evidence of OSA. The mean AHI decreased from 40.9 +/- 6.4 to 29.5 +/- 5.9 events per hour with CRT (p = 0.04). The mean baseline ejection fraction was 22 +/- 1.7% and increased post-CRT to 33.6 +/- 2.0% (p < 0.05). The reduction in AHI with CRT closely correlated with a decrease in circulation time (r = 0.89; p < 0.001) with CRT. Increased rate pacing made no additional impact on the AHI or circulation time. CRT had a limited impact on sleep architecture or daytime symptom scores. CONCLUSIONS: CRT improved cardiac function and reduced the AHI. Reduced circulatory delay likely stabilized ventilatory control systems and may represent a new therapeutic target in OSA.

The influence of white noise on sleep in subjects exposed to ICU noise.

BACKGROUND AND PURPOSE: There is disagreement in the literature about the importance of sleep disruption from intensive care unit (ICU) environmental noise. Previous reports have assumed that sleep disruption is produced by high-peak noise. This study aimed to determine whether peak noise or the change in noise level from baseline is more important in inducing sleep disruption. We hypothesized that white noise added to the environment would reduce arousals by reducing the magnitude of changing noise levels. PATIENTS AND METHODS: Four subjects underwent polysomnography under three conditions: (1) baseline, (2) exposure to recorded ICU noise and (3) exposure to ICU noise and mixed-frequency white noise, while one additional subject completed the first two conditions. Baseline and peak noise levels were recorded for each arousal from sleep. RESULTS: A total of 1178 arousals were recorded during these studies. Compared to the baseline night (13.3+/-1.8 arousals/h) the arousal index increased during the noise (48.4+/-7.6) but not the white noise/ICU noise night (15.7+/-4.5) (P<0.004). The change in sound from baseline to peak, rather than the peak sound level, determined whether an arousal occurred and was the same for the ICU noise and white noise/ICU noise condition (17.7+/-0.4 versus 17.5+/-0.3 DB, P=0.65). CONCLUSIONS: Peak noise was not the main determinant of sleep disruption from ICU noise. Mixed frequency white noise increases arousal thresholds in normal individuals exposed to recorded ICU noise by reducing the difference between background noise and peak noise.

Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis.

BACKGROUND: Although continuous positive airway pressure (CPAP) has become the standard of care in the treatment of obstructive sleep apnea (OSA), 2 systematic reviews have questioned its utility. Since the publication of these reviews, several randomized controlled trials have been reported. We, therefore, performed a meta-analysis to assess the effect of CPAP on subjective and objective sleepiness. METHODS: We conducted a thorough literature search to identify all published randomized controlled trials of CPAP in patients with OSA. Meta-analyses were performed using a random-effects model. Statistical heterogeneity was assessed using the Q statistic. RESULTS: Twelve trials of CPAP in patients with OSA meeting our inclusion criteria were found. The Epworth Sleepiness Scale score was reported in 11 studies (706 patients). A meta-analysis found that CPAP reduced the Epworth Sleepiness Scale score an average of 2.94 points more than placebo (P<.001). The heterogeneity (Q10 = 57.7, P<.001) between studies could not be explained by differences in sex composition, mean age, mean body mass index, or country of study. Trials recruiting subjects with severe OSA plus sleepiness (mean apnea-hypopnea index, > or =30 events per hour; and mean Epworth Sleepiness Scale score, > or =11) had a greater decrease in the Epworth Sleepiness Scale score than the other studies (4.75 vs 1.10; P<.001). Objective measures of sleepiness were reported in 8 trials (482 subjects). Continuous positive airway pressure increased sleep onset latency by 0.93 minute (P =.04) more than placebo. CONCLUSIONS: Continuous positive airway pressure therapy significantly improves subjective and objective measures of sleepiness in patients with OSA across a diverse range of populations. Patients with more severe apnea and sleepiness seem to benefit the most.

The influence of lung volume on pharyngeal mechanics, collapsibility, and genioglossus muscle activation during sleep.

STUDY OBJECTIVES: Previous studies in both awake and sleeping humans have demonstrated that lung-volume changes substantially affect upper-airway size and pharyngeal resistance and, thus, may influence pharyngeal patency. We sought to systematically investigate the isolated effects of lung-volume changes on pharyngeal collapsibility and mechanics and genioglossus muscle activation during stable non-rapid eye movement sleep. We hypothesized that lower lung volumes would lead to increased pharyngeal collapsibility, airflow resistance, and, in compensation, augmented genioglossus muscle activation. DESIGN: Nineteen normal individuals (age, 30.4 +/- 0.5 years; body mass index: 24.5 +/- 0.4 kg/m2) were studied during stable non-rapid eye movement sleep in a rigid head-out shell equipped with a variable positive/negative pressure attachment for manipulations of extrathoracic pressure and, thus, lung volume. SETTING: Sleep physiology laboratory. PARTICIPANTS: Normal healthy volunteers. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: We measured change in end-expiratory lung volume (EELV) (magnetometers), genioglossus electromyogram (GGEMG) (intramuscular electrodes), pharyngeal pressure, and collapsibility of the pharynx in response to a brief pulse of negative pressure (-8 to -15 cm H2O) under the following conditions: (1) baseline, (2) increased EELV (+1 liter), and (3) decreased EELV (-0.6 liter). Reduced lung volumes led to increased inspiratory airflow resistance (7.54 +/- 2.80 cm H2O x L(-1) x s(-1) vs 4.53 +/- 1.05 cm H2O x L(-1) x s(-1), mean +/- SEM, P = 0.02) and increased genioglossus muscle activation (GGEMG peak 14.6% +/- 1.5% of maximum vs 8.6% +/- 1.5% of maximum, maximum P = 0.001) compared to baseline. The pharynx was also more collapsible at low lung volumes (4.3 +/- 0.5 cm H2O vs 5.4 +/- 0.6 cm H2O, P = 0.04). CONCLUSIONS: We conclude that upper-airway muscles respond to changes in lung volumes but not adequately to prevent increased collapsibility. These results suggest that lung volume has an important influence on pharyngeal patency during non-rapid eye movement sleep in normal individuals.

Association of lung perfusion disparity and mortality in patients with cystic fibrosis awaiting lung transplantation.

BACKGROUND: The risk of death for patients with end-stage cystic fibrosis awaiting lung transplantation remains high and most patients succumb to respiratory failure. This study was conducted to evaluate the usefulness of ventilation-perfusion scintillation scans, obtained during the pre-transplant period, to identify patterns that predict prognosis while on the waiting list. These patterns were compared with other pulmonary physiologic markers of ventilation and perfusion obtained from pulmonary function and cardiopulmonary exercise tests. METHODS: From November 1990 to January 1999, 46 patients with cystic fibrosis were listed for bilateral lung transplantation. Fourteen (30.4%) died while waiting for a transplant (Group 1), whereas 32 were transplanted successfully or remain alive and waiting (Group 2). Mean arterial blood gas values, Brasfield radiograph scores, cardiopulmonary exercise data and the degree of scintillation scan abnormalities between lungs were compared for each group. RESULTS: Mean survival for Group 1 was 10.2 +/- 1.7 months, and for Group 2 was 23.5 +/- 3.0 months (p < 0.001). The right upper lung zone was the most severely affected segment. The Cox proportional hazards model revealed an increased perfusion disparity and resting hypercapnia as the main predictors of death while on the transplant list. The Kaplan-Meier analysis indicated greater survival for the groups with <30% disparity between lungs on the pre-transplant scintillation scans. CONCLUSIONS: The results suggest that severe, unilateral perfusion abnormalities seen on scintillation scans in patients with cystic fibrosis are associated with an increased risk of dying while on the lung transplant waiting list and may be helpful in identifying patients who should be considered for early or living-donor transplantation.

Impact of CPAP use and age on mortality in patients with combined COPD and obstructive sleep apnea: the overlap syndrome.

BACKGROUND: The overlap syndrome, defined by concurrent existence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), is associated with poor outcomes. From a large outpatient cohort we aimed to define better the risk factors for increased mortality in the overlap syndrome and hypothesized that CPAP adherence would be associated with improved survival in patients with overlap syndrome. METHODS: A post hoc analysis from an outpatient database of 10,272 patients from 2007-2010, identified 3,396 patients which were classified in 6 groups; patients both alive or deceased, with the known diagnosis of COPD, OSA, and the overlap of COPD plus OSA. Information regarding their gender, age, pulmonary function, obstructive sleep apnea parameters, and CPAP compliance was collected. A multivariate Cox proportional hazards model was generated for the determinants of mortality. RESULTS: 1,112 COPD patients and 2,284 OSA patients were identified by diagnostic coding and then comprehensive chart review. Of these, 227 patients were identified with the overlap syndrome. From this group, 17 patients (7.4%) died. Multivariate analysis revealed hours of CPAP use and age as independent predictors of mortality (HR 0.71 and 1.14, p < 0.001, 0.002). Greater time on CPAP was associated with reduced mortality; although age did not correlate with CPAP use (p = 0.2), mean age of those with CPAP use < 2 hours per night was significantly higher than those using CPAP > 2 hours per night. CONCLUSIONS: From this observational cohort, mortality in the overlap syndrome is impacted by CPAP use. Age is also an independent factor which has a negative association with survival and CPAP usage.

Lung volume and continuous positive airway pressure requirements in obstructive sleep apnea.

Previous studies have demonstrated that lung volume during wakefulness influences upper airway size and resistance, particularly in patients with sleep apnea. We sought to determine the influence of lung volume on the level of continuous positive airway pressure (CPAP) required to prevent flow limitation during non-REM sleep in subjects with sleep apnea. Seventeen subjects (apnea-hypopnea index, 42.6 +/- 6.2 [SEM]) were studied during stable non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. An epiglottic pressure catheter plus a mask/pneumotachometer were used to assess flow limitation. When lung volume was increased by 1,035 +/- 22 ml, the CPAP level could be decreased from 11.9 +/- 0.7 to 4.8 +/- 0.7 cm H(2)O (p < 0.001) without flow limitation. The decreased CPAP at the same negative extrathoracic pressure yielded a final lung volume increase of 421 +/- 36 ml above the initial value. Conversely, when lung volume was reduced by 732 +/- 74 ml (n = 8), the CPAP level had to be increased from 11.9 +/- 0.7 to 17.1 +/- 1.0 cm H(2)O (p < 0.001) to prevent flow limitation, with a final lung volume decrease of 567 +/- 78 ml. These results demonstrate that relatively small changes in lung volume have an important effect on the upper airway in subjects with sleep apnea during non-REM sleep.

Vasoactive drug use in septic shock.

Sepsis accounts for more than 210,000 deaths per year. Despite adequate fluid resuscitation the associated maldistribution of blood flow may cause an imbalance between oxygen delivery and demand, leading to global tissue hypoxia, shock, and, if not reversed, death. Vasoactive therapies including catecholamine and noncatecholamine vasopressors, ionotropes, and vasodilating agents aimed at restoring perfusion and normalizing oxygen consumption have improved outcomes in patients with persistent shock despite crystalloid resuscitation. In this review we discuss the mechanisms, clinical use, and commonly observed pitfalls of the most common and a few uncommon vasodilator agents used in the management of sepsis and septic shock.

Genioglossus muscle responsiveness to chemical and mechanical stimuli during non-rapid eye movement sleep.

Previous studies have suggested that during non-rapid eye movement (NREM) sleep, neither large short-duration resistive loads nor sustained normoxic hypercapnia alone leads to increased genioglossus muscle activation. However, in normal individuals during stable NREM sleep, genioglossus activity rises above baseline as PCO2 rises and airway resistance increases. We therefore hypothesized that combinations of chemical (PCO2, PO2) and mechanical stimuli during NREM sleep would lead to increased genioglossal activation. We studied 15 normal subjects (9 males, 6 females) during stable NREM sleep, measuring genioglossus electromyogram, epiglottic/choanal pressure, and airflow under six conditions: (1) baseline, (2) inspiratory resistive loading (-5 to -15 cm H2O/ L/second), (3) increased PCO2 (5-10 mm Hg above baseline), (4) combined resistive loading and increased PCO2, (5 ) hypoxia (SaO2 80-85%), and (6 ) combined hypoxia/inspiratory resistive loading. Only the combined condition of hypercapnia and resistive loading led to significantly increased genioglossal activation, 3.91 +/- 0.77% to 9.64 +/- 1.96% of maximum. These data suggest that the genioglossus muscle is less responsive to either chemical stimuli (hypercapnia, hypoxia) or inspiratory resistive loading alone during NREM sleep at the degrees tested. When hypercapnia is combined with resistive loading, the muscle does respond. However, the possibility that higher levels of PCO2 or greater resistive loading alone could activate the muscle cannot be excluded.