A randomized, placebo-controlled trial using a novel PAP delivery platform to treat patients with OSA and comorbid PTSD.

PURPOSE: Positive airway pressure (PAP) adherence is poor in comorbid OSA/PTSD. SensAwake™ (SA) is a wake-sensing PAP algorithm that lowers pressure when wake is detected. We compared auto-PAP (aPAP) with and without SA for comorbid OSA/PTSD. METHODS: Prospective, randomized crossover study comparing aPAP to aPAP + SA. We enrolled patients with OSA/PTSD who were PAP naïve. Four weeks after randomization, the patients were crossed over to the alternate treatment group, with final follow-up at eight weeks. Sleep questionnaires (ESS, ISI, FSS, and FOSQ-10) were assessed at baseline and follow-up. RESULTS: We enrolled 85 patients with OSA/PTSD. aPAP reduced AHI to < 5/h in both groups. Our primary endpoint, average hours of aPAP adherence (total) after 4 weeks, was significantly increased in the SA group in our intention-to-treat (ITT) analysis (ß = 1.13 (95% CI 0.16-2.1); p = 0.02), after adjustment for ESS differences at baseline. After adjustment for ESS, SA (ITT analysis) also showed significant improvement in percentage of nights used for ≥ 4 h (ß = 14.9 (95% CI 1.02-28.9); p = 0.04). There were trends toward an increase in percentage nights used total (ß = 17.4 (95% CI - 0.1 to 34.9); p = 0.05), average hours of aPAP adherence (nights used) (ß = 1.04 (95% CI - 0.07 to 2.1); p = 0.07), and regular use (OR = 7.5 (95% CI 0.9-64.7); p = 0.07) after adjustment for ESS at baseline. After adjustment for ESS and days to cross over, SA by actual assignment did not show any effect on adherence variables. The ESS, ISI, FSS, and FOSQ-10 all showed significant improvements with PAP, but there were no differences in the magnitude of improvement in any score between groups. CONCLUSIONS: Adherence to aPAP may be improved with the addition of SA and deserves further study. SA is as effective as standard aPAP for normalizing the AHI and improving sleep-related symptoms. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02549508 https://clinicaltrials.gov/ct2/show/NCT02549508?term=NCT02549508&rank=1 "Comparison Study Using APAP With and Without SensAwake in Patients With OSA and PTSD".

Zolpidem and Eszopiclone Pre-medication for PSG: Effects on Staging, Titration, and Adherence.

Introduction: The non-benzodiazepine sedative hypnotic (NBSH) eszopiclone improves polysomnography (PSG) quality and continuous positive airway pressure (CPAP) adherence. It is unclear whether zolpidem has the same effect and neither NBSH has been studied in populations with milder forms of obstructive sleep apnea. Materials and Methods: We performed a retrospective analysis on patients undergoing level I PSG at our institution. Patients are pre-medicated with NBSHs at the discretion of the sleep physician. We compared PSG/CPAP titration quality and subsequent CPAP adherence for patients receiving NBSHs or no pre-study medication. We adjusted for obstructive sleep apnea pre-test probability (PTP), arousal threshold, and other factors showing differences at baseline. Results: Data on 560 patients were analyzed. Mean age and body mass index were 42.2 ± 10.1 and 28.8 ± 4.5, respectively. Median apnea hypopnea index was 12.9 (6.4-25.3), 100 (18.0%) patients had normal studies, 97 (17.3%) were split, and 457 (81.6%) had a respiratory low-arousal threshold. After adjusting for differences at baseline, neither NBSH was associated with sleep efficiency, wake after sleep onset, or total sleep time on PSG. After adjustment, patients receiving eszopiclone had a higher apnea hypopnea index at the final CPAP pressure (ß = 14.2; 95% confidence intervals (CI) 7.2-21.2; p < 0.001) and were more likely to have an unacceptable titration (odds ratio (OR) = 6.6; 95% CI 2.0-21.0; p = 0.002). When only split-night studies were examined, there were no differences in any adherence variables across or between categories. Conclusions: In a population with predominantly mild obstructive sleep apnea, NBSHs did not improve PSG or CPAP titration quality and did not increase CPAP adherence. There was no difference in effect between eszopiclone and zolpidem.

Using the STOPBANG questionnaire and other pre-test probability tools to predict OSA in younger, thinner patients referred to a sleep medicine clinic.

BACKGROUND: The STOPBANG questionnaire is used to predict the presence of obstructive sleep apnea (OSA). We sought to assess the performance of the STOPBANG questionnaire in younger, thinner patients referred to a sleep medicine clinic. METHODS: We applied the STOPBANG questionnaire to patients referred for level I polysomnography (PSG) at our sleep center. We calculated likelihood ratios and area under the receiver operator characteristic (AUROC) curve and performed sensitivity analyses. RESULTS: We performed our analysis on 338 patients referred for PSG. Only 17.2% (n = 58) were above age 50 years, and 30.5 and 6.8% had a BMI above 30 and 35 years, respectively. The mean apnea-hypopnea index (AHI) was 12.9 ± 16.4 and 63.9% had an AHI ≥5. The STOPBANG (threshold ≥3) identified 83.1% of patients as high risk for an AHI ≥5, and sensitivity, specificity, positive (PPV), and negative predictive values (NPV) were 83.8, 18.0, 64.4, and 38.0%, respectively. Positive and negative likelihood ratios were poor at 1.02-1.11 and 0.55-0.90, respectively, across AHI thresholds (AHI ≥5, AHI ≥15 and AHI ≥30), and AUROCs were 0.52 (AHI ≥5) and 0.56 (AHI ≥15). Sensitivity analyses adjusting for insomnia, combat deployment, traumatic brain injury, post-traumatic stress disorder, clinically significant OSA (ESS >10 and/or co-morbid disease), and obesity did not significantly alter STOPBANG performance. CONCLUSIONS: In a younger, thinner population with predominantly mild-to-moderate OSA, the STOPBANG Score does not accurately predict the presence of obstructive sleep apnea.

A mobile, web-based system can improve positive airway pressure adherence.

SleepMapper is a mobile, web-based system that allows patients to self-monitor their positive airway pressure therapy, and provides feedback and education in real time. In addition to the usual, comprehensive support provided at our clinic, we gave the SleepMapper to 30 patients initiating positive airway pressure. They were compared with patients initiating positive airway pressure at our clinic without SleepMapper (controls) to determine whether SleepMapper affected adherence. A total of 61 patients had polysomnographic and adherence data analysed, 30 were given SleepMapper and 31 received our standard of care. The two groups were well matched at baseline to include no significant differences in age, apnea-hypopnea index, percentage receiving split-night polysomnographs and starting pressures. Patients in the control group received significantly more non-benzodiazepine sedative hypnotics the night of their polysomnography and during positive airway pressure initiation. At 11 weeks, patients in the SleepMapper group had a greater percentage of nights with any use (78.0 ± 22.0 versus 55.5 ± 24.0%; P < 0.001) and >4 h positive airway pressure use (78.0 ± 22.0 versus 55.5 ± 24.0%; P = 0.02). There was a trend toward more patients in the SleepMapper group achieving >4 h of use for at least 70% of nights [9/30 (30%) versus 3/31 (9.7%); P = 0.06]. In multivariate linear regression, the SleepMapper remained significantly associated with percentage of nights >4 h positive airway pressure use (ß coefficient = 0.18; P = 0.02). Added to our usual, comprehensive programme to maximize positive airway pressure adherence in new users, the SleepMapper was independently associated with an 18% increase in nights >4 h of use.

Eszopiclone and Zolpidem Do Not Affect the Prevalence of the Low Arousal Threshold Phenotype.

STUDY OBJECTIVES: We sought to determine whether non benzodiazepine sedative hypnotics (NBSH) reduce the occurrence of the low arousal threshold (LAT) phenotype. METHODS: Consecutive patients with suspected obstructive sleep apnea (OSA) referred for polysomnography (PSG) had demographic and PSG data abstracted. LAT was estimated using PSG criteria. After adjusting for pretest probability (PTP) for OSA, we calculated the effect that premedication with NBSHs has on LAT prevalence. RESULTS: Five hundred seventy-nine patients with a mean age and body mass index of 42.2 ± 10.1 y and 28.9 ± 4.5 kg/m2, respectively, had data available for analysis. Most patients (444, or 80.9%) had a LAT, and administering a NBSH (zolpidem or eszopiclone) on the same night as the PSG did not change LAT prevalence (NBSH: 339 (83.3%) versus no drug: 100 (80.6%); p = 0.50). Adjusting for PTP, neither administration of eszopiclone (odds ratio 0.80 (95% confidence interval: 0.33-2.0); 0.69) nor zolpidem (odds ratio 1.65 (95% confidence interval: 0.8-3.5); p = 0.19) reduced the odds that a patient had a LAT. NBSHs did not change the mean SpO2 nadir, percentage hypopneas, or apnea-hypopnea index. There was no association between zolpidem or eszopiclone dosing and SpO2 nadir (zolpidem: ß = -0.69, p = 0.80; eszopiclone: ß = -1.53, p = 0.68), percentage hypopneas (zolpidem: ß = 2.2, p = 0.43; eszopiclone ß = -6.2, p = 0.46), or apnea-hypopnea index (zolpidem: ß = 3.1, p = 0.22; eszopiclone: ß = 2.6, p = 0.39). CONCLUSIONS: The LAT is common in our population and NBSH premedication does not alter its occurrence. Further studies are needed to determine how the LAT can be optimally managed to improve OSA treatment.

Utility of split-night polysomnography in the diagnosis of upper airway resistance syndrome.

PURPOSE: Split-night polysomnography can both establish the diagnosis and titrate continuous positive airway pressure (CPAP) during a single study in patients with sleep-disordered breathing. We sought to determine if split-night polysomnography could be effectively used in upper airway resistance syndrome (UARS) without diminishing diagnostic accuracy or success of CPAP titration. METHODS: Consecutive patients diagnosed with UARS were included. Split-night studies were performed in patients meeting predefined criteria. We compared data between those undergoing traditional and split-night polysomnography. RESULTS: We included 100 consecutive patients (41.2 +/- 7.4 years, 54% men). Forty-six underwent split-night polysomnography. Groups were similar at baseline. There were no differences in polysomnography or success rate of CPAP titration. Among those not undergoing split-night studies, the mean time between diagnostic polysomnography and CPAP titration was 71.9 +/- 49.0 days. CONCLUSIONS: Split-night polysomnography can be effectively utilized to diagnose UARS and initiate CPAP therapy. This practice can reduce the number of studies needed and obviate the inherent delay in initiating CPAP therapy.

Eszopiclone improves overnight polysomnography and continuous positive airway pressure titration: a prospective, randomized, placebo-controlled trial.

STUDY OBJECTIVES: To assess whether premedication with eszopiclone would improve sleep duration and continuity during polysomnography, thereby improving the quality of diagnostic and CPAP titration studies. DESIGN: Prospective, double-blinded, placebo-controlled trial SETTING: Academic, multidisciplinary sleep center. PATIENTS: 226 adult subjects undergoing polysomnography for suspected sleep disordered breathing; 113 received eszopiclone and 113 received placebo. INTERVENTIONS: Subjects received eszopiclone 3 mg or matching placebo before polysomnography. We compared sleep latency, efficiency, total sleep time, and apnea-hypopnea index between these groups. We also compared rates of inadequate studies, defined as insufficient sleep time (< 120 min or sleep efficiency < or = 70%) or incomplete CPAP titrations (> or = 5 events/h on the highest CPAP or complete intolerance). MEASUREMENTS AND RESULTS: Eszopiclone premedication significantly improved a number of measured variables. Eszopiclone reduced sleep latency (21.7 +/- 27.1 vs. 32.6 +/- 38.2 min, P = 0.014), improved sleep efficiency (87.6% +/- 10.8% vs. 78.1% +/- 15.6%, P < 0.001), reduced wake after sleep onset (39.2 +/- 31.9 vs. 64.5 +/- 45.4 min, P <0.001) and prolonged sleep time (346.5 +/- 53.1 vs. 312.2 +/- 64.2 min, P < 0.001). Sleep efficiencies < or = 70% were more common with placebo than medication (21.2% vs. 7.1%, P = 0.004). Eszopiclone facilitated improved CPAP titrations with fewer residual events (5.7 +/- 10.3 vs. 11.9 +/- 19.6, P = 0.02) and fewer incomplete titrations (31.1% vs. 48.0%, P = 0.04). Poor quality studies (46.0% vs. 26.5%, P = 0.004) were more common with placebo than with eszopiclone. There was a trend for more non-usable studies with placebo (7.1% vs. 2.7%, P = 0.22). Side effects were uncommon and did not differ between groups. CONCLUSION: Pretreatment with eszopiclone improves the quality of polysomnography and CPAP titration and decreases the need to repeat studies. Given the ever-growing demand for polysomnography and the need to improve efficiency, the routine use of nonbenzodiazepines as premedication for polysomnography should be considered.

The role of telemedicine in CPAP compliance for patients with obstructive sleep apnea syndrome.

The objective of this study was to compare continuous positive airway pressure (CPAP) use, functional status, and client satisfaction in obstructive sleep apnea syndrome (OSAS) patients randomized to either telemedicine support or traditional care. In our university-affiliated sleep disorders center, patients with OSAS who were initiating CPAP therapy were randomized to receive telemedicine support vs traditional follow-up care for 30 days. The telemedicine group received a "Health Buddy" computer that provided daily Internet-based informational support and feedback for problems experienced with CPAP use. At 30 days, there were no significant differences in the hours of CPAP use between groups receiving traditional care (M = 4.22, SD+/-2.05) and telemedicine support (M = 4.29, SD+/-2.15), p = 0.87, or in the proportion of nights with CPAP use between the traditional (M = 50%+/-33.8) and telemedicine groups (M = 47%+/-34.2), p=0.61. No significant differences were found between groups in functional status (M = 2.27+/-4.56 vs M = 2.03+/-3.88, respectively, p = 0.76) or client satisfaction (M = 28.0+/-3.51 vs M = 28.5+/-3.05, p = 0.43). Patients in the telemedicine and traditional groups had similar CPAP use, functional status, and client satisfaction. The data suggest that telemedicine support as provided by our model compares favorably with traditional care. As a provider-extender, telemedicine support for patients initiating use of CPAP may allow for greater practice efficiency while maintaining quality of care.

Silent upper airway resistance syndrome: prevalence in a mixed military population.

STUDY OBJECTIVES: The upper airway resistance syndrome (UARS) is a recently described form of sleep-disordered breathing in which transient increases in upper airway resistance result in repetitive EEG arousals. UARS is not associated with apnea or diminished airflow, although snoring and excessive daytime somnolence (EDS) are common. This report describes a subset of patients with UARS diagnosed by polysomnography who do not manifest snoring, which we define as silent upper airway resistance syndrome (SUARS). DESIGN: A retrospective review of all polysomnographies performed at our sleep disorders center during 2000. SETTING: Sleep disorders center of a large, academic, military hospital. PATIENTS: Our center serves military personnel, military retirees, and their dependent families. INTERVENTIONS: Esophageal manometry during polysomnography was routinely performed on patients with hypersomnolence (Epworth sleepiness scale > 10) who demonstrated a total arousal index >or= 10/h and a respiratory disturbance index of < 5/h on prior polysomnography. UARS was definitely diagnosed in patients who demonstrated repetitive increased upper airway resistance (IUAR) associated with brief EEG arousals followed by normalization of esophageal pressure (Pes). IUAR was defined by a pattern of crescendo negative inspiratory Pes of

Does zolpidem enhance the yield of polysomnography?

STUDY OBJECTIVES: An uncomfortable environment or continuous positive airway pressure (CPAP) intolerance may cause poor sleep efficiency during polysomnography and result in a poor-quality study. Unsatisfactory polysomnograms often must be repeated. Nonbenzodiazepine hypnotics may improve sleep efficiency without disruption of sleep architecture. We hypothesized that premedication with zolpidem improves polysomnogram quality and decreases the need to restudy. METHODS: We retrospectively reviewed 200 consecutive polysomnograms. Zolpidem premedication was not standardized and was prescribed at the discretion of consulting sleep physicians, who were unaware of this study. We compared the quality of polysomnograms between patients who received zolpidem 10 mg prior to polysomnography and those who did not. A poor-quality polysomnogram was defined as having insufficient sleep time to allow for diagnosis, incomplete CPAP titration with a resulting apnea-hypopnea index > 10 on the highest level of CPAP achieved, or complete CPAP intolerance. RESULTS: Of 200 records reviewed, 54 patients (27%) received zolpidem. Demographics did not differ between groups. Premedication with zolpidem resulted in improved sleep latency (11.8 +/- 9.5 minutes vs 26.0 +/- 19.9 minutes, p = .002) and sleep efficiency (89.5% +/- 5.6% vs 78.8 +/- 12.3, p < .0001). Zolpidem premedication resulted in significantly fewer studies meeting criteria for poor quality (7.4% vs 33.6%, p = .005). Of the 49 studies meeting criteria for poor quality, 21 were repeated using zolpidem, showing significant improvements in sleep latency (10.8 +/- 7.1 minutes vs 42.8 +/- 30.5 minutes, p = .0004) and sleep efficiency (89.5% +/- 4.9% vs 61.8% +/- 13.7%, p < .0001). No study repeated with zolpidem met criteria for poor quality. CONCLUSIONS: Pretreatment with zolpidem significantly improved polysomnographic quality and may decrease the need to repeat polysomnograms.

Obstructive sleep apnea syndrome: are we missing an at-risk population?

STUDY OBJECTIVES: While age and body-mass index (BMI) are well-established risk factors for obstructive sleep apnea syndrome (OSAS), this disorder occurs across a wide spectrum of ages and weights. Preconceptions regarding "classic" patients with OSAS may lead to underdiagnosis in at-risk populations, particularly younger nonoverweight individuals. We hypothesized that the severity of OSAS is independent of age and BMI in a younger less-obese population. METHODS: Prospective study of consecutive patients diagnosed with OSAS. Active-duty military, National Guardsmen, and civilians were compared to determine if age and BMI correlated with disease severity. RESULTS: Two hundred seventy subjects (120 active-duty, 80 National Guardsmen, 70 civilians) were included. Active-duty military members were significantly younger and less overweight than both National Guardsmen and civilians. Of the civilians, 64.3% and, of National Guardsmen, 48.8% were obese, whereas only 19.2% of active-duty had a BMI > or = 30 kg/m2 (p < .001). However, the prevalence of severe disease did not differ between groups. Disease severity showed no correlation with BMI among active-duty subjects (r = 0.09, p = .33). Of the active-duty subjects, 37.5% had severe disease, as compared with 42.5% of National Guard and 45.7% of civilian subjects (p = .18 and .09, respectively). BMI did not differ between active-duty subjects with severe disease and those with mild to moderate OSAS (26.7 kg/m2 versus 26.9 kg/m2, p = .40). There was a low but significant correlation between age and AHI (r = 0.21, p = .02) among all subjects. CONCLUSIONS: OSAS occurs in young nonobese individuals and should be considered in patients reporting excessive daytime sleepiness, regardless of age or BMI.

Persistence of Apnea in Wakefulness in a Patient with Postradiation Pharyngitis.

We report on a patient with the onset of recurrent nocturnal awakenings associated with postawakening stridor with onset a few weeks after receiving radiation therapy to the neck. The onset of nocturnal stridor was also accompanied by complaints of snoring and excessive daytime sleepiness. Stridor did not occur during daytime wakefulness. Nocturnal polysomnography (NPSG) recorded with a calibrated pneumotachometer demonstrated snoring and severe obstructive sleep apnea (OSA) with a apnea/hypopnea index of 51 events/hr. One apneic episode persisted for 17 sec after the onset of wakefulness as evidenced by standard NPSG scoring criteria for arousals. With this event, video monitoring revealed the patient abruptly sitting upright and clutching his throat and auditory recording demonstrated stridorous sounds. During wakefulness endoscopy revealed moderate edema and erythema of the supraglottic region, epiglottis, palatine tonsils, and false and true vocal cords. Vocal cord function appeared normal. This case report represents the observation of two rare findings in a single patient, persistence of apnea in wakefulness, and OSA onset following neck irradiation. We review the literature on the persistence of apnea in wakefulness and discuss possible mechanisms for its occurrence in this patient.