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We report a case of severe central sleep apnea incidentally diagnosed during polysomnography for suspected obstructive sleep apnea. Characteristic clinical features included episodic hyperventilation followed by apnea from hypocapnia, which did not follow a Cheyne-Stokes pattern. Combined with the identification of cerebellar and brainstem malformations known as the "molar tooth sign" on a brain magnetic resonance imaging, developmental delay, and motor coordination problems, Joubert syndrome (a congenital disease) was first diagnosed at the age of 50 years. Central apneas were also observed during wakefulness, although not continuously. During sleep, continuous positive airway pressure and adaptive servo-ventilation were ineffective at the referring clinic and at our hospital. Supplemental oxygen decreased the frequency of central apneas and significantly shortened the duration of each central sleep apnea compared with room air. In contrast, the opposite response was observed with acetazolamide administration., Citation: Murashima R, Shiota S, Sugiyama A, et al. A case of middle-aged central sleep apnea due to Joubert syndrome with different treatment effects of oxygen and acetazolamide. J Clin Sleep Med . 2024;20(10):1705-1710., (© 2024 American Academy of Sleep Medicine.)

Hypoglossal nerve stimulation is indicated for obstructive sleep apnea but is ineffective in treating central sleep apnea. We describe 2 patients implanted with hypoglossal nerve stimulation after being diagnosed with obstructive sleep apnea at outside sleep laboratories and failing a trial of continuous positive airway pressure therapy. Despite successful hypoglossal nerve stimulation implantation, the patients continued to have persistent symptoms with residual apnea-hypopnea indices above 25 events/h. Although obstructive sleep apnea was the presenting diagnosis, we discovered a significant central sleep apnea component in the original diagnostic sleep data upon careful review. One patient was confirmed to have a central sleep apnea-predominant sleep disorder and improved with adaptive servo-ventilation therapy. The other was diagnosed with central sleep apnea and severe periodic limb movement disorder, and improved with medication. Based on these sleep apnea cases, we propose guidelines emphasizing the importance of reviewing basic clinical information upon treatment failure and initiating multidisciplinary collaboration early in the treatment course., Citation: Banerjee D, Lee C-H, Im K. Case report of hypoglossal nerve stimulation therapy failure due to significant underlying central sleep apnea. J Clin Sleep Med . 2024;20(6):1003-1007., (© 2024 American Academy of Sleep Medicine.)

Congenital central hypoventilation syndrome (CCHS), a rare disease caused by paired-like homeobox 2B variants, affects control of breathing. We report on a 21-month-old boy with CCHS caused by a novel nonpolyalanine repeat mutation, neuroblastoma, severe obstructive and central sleep apnea, and sleep-related hypoxemia without hypoventilation. At 10 months, due to persistent central sleep apnea during serial polysomnography, bilevel positive airway pressure therapy was initiated despite the absence of hypoventilation. Nonpolyalanine repeat mutations are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and neural crest tumors; however, our patient had a relatively milder respiratory phenotype requiring sleep-only assisted ventilation without tracheostomy. Although alveolar hypoventilation is the hallmark of CCHS, our patient lacked hypoventilation. Bilevel positive airway pressure could be considered in some infants with CCHS requiring sleep-only assisted ventilation for tracheostomy avoidance. Our case demonstrates the expanding phenotypic spectrum in CCHS and the importance of formulating an individualized care plan., Citation: Fain ME, Raghunandan S, Pencheva B, Leu RM, Kasi AS. Images: atypical presentation of congenital central hypoventilation syndrome in an infant with central and obstructive sleep apnea. J Clin Sleep Med . 2024;20(3):478-481., (© 2024 American Academy of Sleep Medicine.)

Study Objectives: Treatment-emergent central sleep apnea (TECSA) describes the appearance or persistence of central sleep apnea while undergoing treatment for obstructive sleep apnea. TECSA is well studied in continuous positive airway pressure therapy with an estimated prevalence of 8%. Based on a few case reports, mandibular advancement devices (MAD) may also provoke TECSA. This study aims to gain insight into the prevalence of TECSA with MAD therapy., Methods: This retrospective study includes a total of 129 patients with moderate to severe obstructive sleep apnea who were treated with a custom-made titratable MAD. Baseline and follow-up sleep studies were compared to identify patients with TECSA. Since different diagnostic criteria to define TECSA are used in literature, prevalence was calculated according to three definitions (TECSA-1, -2, and -3). Demographics, MAD treatment variables, and findings of the diagnostic polysomnography were compared between TECSA and non-TECSA patients to identify possible predictors., Results: Depending on the definition used, TECSA was found in 3.1%-7.8% of patients undergoing MAD therapy. TECSA patients had a higher apnea index (9.2 vs 2.0 events/h, P = .042), central apnea-hypopnea index (4.1 vs 0.2 events/h, P = .045) and oxygen desaturation index (23.9 vs 16.3 events/h, P = .018) at baseline compared to non-TECSA patients. No differences were found in demographics and treatment variables., Conclusions: These findings demonstrate that TECSA also occurs in patients starting MAD treatment. Patients with TECSA had a higher apnea index, central apnea-hypopnea index, and oxygen desaturation index at baseline compared to non-TECSA patients., Citation: Hellemans S, Van de Perck E, Braem MJ, Verbraecken J, Dieltjens M, Vanderveken OM. The prevalence of treatment-emergent central sleep apnea with mandibular advancement device therapy. J Clin Sleep Med . 2023;19(12):2035-2041., (© 2023 American Academy of Sleep Medicine.)

Study Objectives: To describe the outcomes of central sleep apnea requiring home supplemental oxygen therapy in otherwise healthy term infants., Methods: All children < 1 year of age undergoing polysomnography between 2015 and 2020 at the Queensland Children's Hospital were retrospectively studied. Children with gestational age < 37 weeks, underlying syndrome, cleft palate, those with obstructive apnea-hypopnea index > 50% of total apnea-hypopnea index, or with underlying cardiac or pulmonary parenchymal pathology were excluded. Polysomnography parameters were extracted for periods both on and off supplemental oxygenation., Results: Fifty-two (mean [standard deviation] age at polysomnography 32.6 [34.7] days; 21 females) term infants were included. There was a statistically significant improvement in apnea-hypopnea index on supplemental oxygen (mean [standard deviation] in room air 50.2 [36.3] vs 11.6 [9], P < .001 on supplemental oxygen), in both rapid eye movement and nonrapid eye movement sleep, as well as in mean oxygen saturations (96.6% in room air to 98.9% on oxygen; P < .001). There was no statistically significant change in transcutaneous carbon dioxide levels or sleep duration. Oxygenation was prescribed for a median (interquartile range) age of 197 (127) days., Conclusions: Central sleep apnea in term infants who are otherwise healthy generally has a good prognosis, with oxygen therapy prescribed for around 6 months. Oxygen therapy was associated with improved saturations and decrease in apnea-hypopnea index when assessed with polysomnography., Citation: Hayashi A, Suresh S, Kevat A, Robinson J, Kapur N. Central sleep apnea in otherwise healthy term infants. J Clin Sleep Med . 2022; 18(12):2813-2817., (© 2022 American Academy of Sleep Medicine.)

Study Objectives: Cheyne-Stokes respiration (CSR), a kind of central sleep apnea, is referred to as a poor prognostic factor in heart failure patients with reduced ejection fraction (HFrEF). Matrix metalloproteinase (MMP) and B-type natriuretic peptide (BNP) play important roles in HFrEF patients and are markers of poor prognosis. However, there is no literature mentioning the changes in MMP and BNP in HFrEF patients with CSR., Methods: From June 2018 to June 2019, 41 adult patients with stable heart failure and left ventricular ejection fraction < 50% were enrolled from the cardiology clinic. After history-taking and medication review to exclude possible central nervous system- or medication-related central sleep apnea, an overnight polysomnography study was performed, and CSR was identified. The morning serum MMP-2, MMP-9, and BNP levels were determined using enzyme-linked immunosorbent assay and fluorescence immunoassay techniques. A positive airway pressure device was applied to 7 patients for 3 months., Results: The serum MMP-2 and BNP levels were significantly higher in HFrEF patients with CSR than in patients without CSR. In addition, elevated serum MMP-2 levels correlated well with the severity of sleep apnea and intermittent hypoxia, which were represented as the apnea-hypopnea index and the oxygen desaturation index. No positive correlation was found between those markers and left ventricular ejection fraction. Finally, the treatment of sleep apnea with continuous positive airway pressure for 3 months tended to reduce the elevated serum MMP-2 levels., Conclusions: Higher serum MMP-2 and BNP levels were found in HFrEF patients with CSR. Elevated MMP-2 levels were correlated with the severity of sleep apnea and intermittent hypoxia., Citation: Chuang L-P, Pang J-HS, Lin S-W, et al. Elevated serum matrix metalloproteinase-2 levels in heart failure patients with reduced ejection fraction and Cheyne-Stokes respiration. J Clin Sleep Med . 2022;18(5):1365-1373., (© 2022 American Academy of Sleep Medicine.)

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare and potentially lethal disorder of respiratory control, autonomic, and hypothalamic dysfunction of unknown etiology. We report a 15-year-old girl with ROHHAD who developed hyperphagia and rapid weight gain of 16 kg between 2.5 and 4 years of age and cardiorespiratory arrest at 4 years. Initial polysomnography showed central sleep apnea and severe oxygen desaturations without hypoventilation. Mild obstructive sleep apnea and intermittent hypoxemia were identified at 4.5 years, following which nocturnal bilevel positive airway pressure therapy was initiated. At 6 years, she developed sleep-related hypoventilation, and subsequent polysomnograms continued to show obstructive sleep apnea and hypoventilation requiring bilevel positive airway pressure. Clinicians interpreting polysomnograms should become familiar with the evolution of sleep-disordered breathing in ROHHAD and that hypoventilation may develop over time. Our case highlights the importance of serial polysomnography in patients with ROHHAD and optimal ventilatory management., Citation: Ghosh R, Malik M, Daley TC, Kasi AS. Images: Sleep-disordered breathing and hypoventilation in a child with obesity and hypothalamic dysfunction. J Clin Sleep Med . 2022;18(1):339-342., (© 2022 American Academy of Sleep Medicine.)

None: Diaphragm pacing (DP), a modality of ventilatory support in children with congenital central hypoventilation syndrome, generates respiration using the patient's own diaphragm as the respiratory pump. We report a 14-year-old boy with congenital central hypoventilation syndrome who uses DP with an uncapped tracheostomy during sleep. Polysomnography to titrate DP settings identified artifacts occurring in regular intervals coinciding with the onset of inspiration during all sleep stages in several channels including legs, snore, and electrocardiogram. Clinicians interpreting polysomnograms performed during DP should become familiar with the multichannel artifacts due to DP impulses. We also identified that our patient was hyperventilated on home DP settings that led to adjustment of DP settings during the polysomnogram to achieve optimal oxygenation and ventilation. Our case also highlights the utility of polysomnography to ensure optimal gas exchange during sleep in children with congenital central hypoventilation syndrome using DP., (© 2020 American Academy of Sleep Medicine.)

Study Objectives: Idiopathic central sleep apnea (ICSA) is a rare disorder diagnosed when known causes of central sleep apnea are excluded. No established treatments exist for ICSA, and long-term studies are lacking. We assessed the long-term effectiveness and safety of transvenous phrenic nerve stimulation in patients with ICSA., Methods: In the remedē System Pivotal Trial, 16/151 (11%) participants with central sleep apnea were diagnosed as having ICSA. Patients were implanted and followed through 18 months of active therapy. Polysomnograms obtained at baseline and at 6, 12, and 18 months were scored by a central laboratory. Sleep metrics and patient-reported quality of life outcomes were assessed., Results: Patients experienced moderate-severe central sleep apnea. The baseline AHI, central apnea index, and arousal index were 40, 25, and 32 events/h of sleep, respectively. These metrics improved at 6, 12, and 18 months of therapy: the AHI decreased by 25, 25, and 23 events/h (P < .001 at each visit), the central apnea index by 22, 23, and 22 events/h (P < .001 at each visit), and the arousal index by 12 (P = .005), 11 (P = .035), and 13 events/h (P < .001). Quality of life instruments showed clinically meaningful improvements in daytime somnolence, fatigue, general and mental health, and social functioning. The only related serious adverse event was lead component failure in 1 patient., Conclusions: This is the longest prospective study for the treatment of ICSA. Transvenous phrenic nerve stimulation significantly decreased sleep-disordered breathing metrics with consequent improvement in quality of life at 6 months, and all benefits were sustained through 18 months., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: Respicardia, Inc. Pivotal Trial of the remedē System; URL: https://clinicaltrials.gov/ct2/show/NCT01816776; Identifier: NCT01816776., (© 2020 American Academy of Sleep Medicine.)

Study Objectives: Congenital central hypoventilation syndrome (CCHS) is caused by the paired-like homeobox 2B (PHOX2B) mutation and predominantly diagnosed during the neonatal period. Although late-onset CCHS and PHOX2B mutation carriers have been reported, the features of these disease states in adults remain uncertain. This study aimed to identify the characteristics of adult-onset CCHS and PHOX2B-mutation carriers in adult., Methods: We mainly searched the PubMed/Medline and Cochrane Databases and classified our target patients into 2 groups: group A, symptomatically diagnosed with late-onset CCHS in adulthood; group B, adult PHOX2B-mutation carriers. Then, clinical characteristics, including the onset, treatment, long-term course, and pattern of the PHOX2B mutation in both groups were analyzed. Additionally, a new adult-case of late-onset CCHS was added to the analysis., Results: Group A was comprised of 12 patients. The onset triggers of illness included a history of respiratory compromise following general anesthesia and respiratory tract infections. All patients in group A had 20/25 polyalanine repeat mutations and required some chronic ventilatory support at least during sleep, including portable positive pressure ventilator via tracheostomy or noninvasive positive pressure ventilation. In these patients with ventilatory support during sleep, sudden death or poor prognosis was not reported. Group B was comprised of 33 adults from 24 families with PHOX2B mutations. Nine patients in group B were confirmed with the diagnosis of CCHS. Although polyalanine repeat mutations 20/25 represented the most common gene mutation, diverse mutations, including mosaicism, were observed. Hypoventilation of several cases in group B were underdiagnosed by overnight polysomnography without monitoring for CO₂., Conclusion: Alveolar hypoventilation with unknown origin can be caused by the PHOX2B mutation even in adult cases. Both the identification of the PHOX2B mutation and the incorporation of capnography in polysomnography are important for adult cases with unexplained alveolar hypoventilation or asymptomatic mutation carriers., (© 2020 American Academy of Sleep Medicine.)

Study Objectives: Patients who have experienced heart failure with central sleep apnea/Cheyne-Stokes respiration (CSA/CSR) have an impaired prognosis. Continuous positive airway pressure (CPAP) and adaptive servoventilation (ASV) as well as nocturnal oxygen (O₂) are proposed treatment modalities of CSA/CSR. The goal of the study is to assess whether and how different treatments of CSA/CSR affect cardiac function., Methods: Databases were searched up to December 2017 for randomized controlled trials (RCTs) comparing the effect of any combination of CPAP, ASV, O₂ or an inactive control on left ventricular ejection fraction (LVEF) in patients with heart failure and CSA/CSR. A systematic review and network meta-analysis using multivariate random-effects meta-regression were performed., Results: Twenty-four RCTs (1,289 patients) were included in the systematic review and data of 16 RCTs (951 patients; apnea-hypopnea-index 38 ± 3/h, LVEF 29 ± 3%) could be pooled in a network meta-analysis. Compared to an inactive control, both CPAP and ASV significantly improved LVEF by 4.4% (95% confidence interval 0.3-8.5%, P = 0.036) and 3.8% (95% confidence interval 0.6-7.0%, P = 0.025), respectively, whereas O₂ had no effect on LVEF (P = 0.35). There was no difference in treatment effects on LVEF between CPAP and ASV (P = 0.76). The treatment effect of positive pressure ventilation was larger when baseline LVEF was lower in systolic heart failure., Conclusions: CPAP and ASV are effective in improving LVEF in patients with heart failure and CSA/CSR to a clinically relevant amount, whereas nocturnal O₂ is not. There is no difference between CPAP and ASV in the comparative beneficial effect on cardiac function., (© 2019 American Academy of Sleep Medicine.)

Study Objectives: Early evidence with transvenous phrenic nerve stimulation (PNS) demonstrates improved disease severity and quality of life (QOL) in patients with central sleep apnea (CSA). The goal of this analysis is to evaluate the complete prospective experience with PNS in order to better characterize its efficacy and safety, including in patients with concomitant heart failure (HF)., Methods: Using pooled individual data from the pilot (n = 57) and pivotal (n = 151) studies of the remedē System in patients with predominant moderate to severe CSA, we evaluated 12-month safety and 6- and 12-month effectiveness based on polysomnography data, QOL, and cardiac function., Results: Among 208 combined patients (June 2010 to May 2015), a remedē device implant was successful in 197 patients (95%), 50/57 pilot study patients (88%) and 147/151 pivotal trial patients (97%). The pooled cohort included patients with CSA of various etiologies, and 141 (68%) had concomitant HF. PNS reduced apnea-hypopnea index (AHI) at 6 months by a median of -22.6 episodes/h (25th and 75th percentile; -38.6 and -8.4, respectively) (median 58% reduction from baseline, P < .001). Improvement in sleep variables was maintained through 12 months of follow-up. In patients with HF and ejection fraction ≤ 45%, PNS was associated with improvement in systolic function from 27.0% (23.3, 36.0) to 31.1% (24.0, 41.5) at 12 months (P = .003). In the entire cohort, improvement in QOL was concordant with amelioration of sleep measures., Conclusions: Transvenous PNS significantly improves CSA severity, sleep quality, ventricular function, and QOL regardless of HF status. Improvements, which are independent of patient compliance, are sustained at 1 year and are associated with acceptable safety., (© 2019 American Academy of Sleep Medicine.)

Study Objectives: A strong association between sleep-disordered breathing (SDB) and atrial fibrillation and/or atrial flutter (AF) has consistently been observed in epidemiologic and interventional studies. The effect of positive airway pressure (PAP) on AF recurrence is inconclusive. This study sought to evaluate the effectiveness of PAP therapy for SDB on AF recurrence., Methods: This was a single-center, retrospective study conducted at a tertiary referral center. All adult patients who had SDB on polysomnography and underwent AF intervention (ablation or cardioversion) following polysomnography from January 1992-December 2014 were analyzed. Primary outcome was time to first-documented recurrence of AF after AF intervention by Kaplan-Meier estimates., Results: Among 30,188 patients with obstructive and central SDB, 429 had this diagnosis before AF intervention; 269 were "PAP-adherent users," the remaining 160 were "PAP-nonusers." Patients in both groups had similar age, sex, body mass index (BMI), ejection fraction, left atrial volume index (LAVI), antiarrhythmic medications, diabetes mellitus, systemic hypertension, and heart failure diagnoses. Time to recurrence of AF postintervention was no different in PAP-adherent users and nonusers (4.8 and 4.1 months respectively, P = .7). Cardioversion (compared to catheter ablation) was the strongest independent predictor of recurrent AF (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.39-2.94, P < .001). BMI and LAVI were also significant predictors of recurrence in adjusted analyses (HR 1.01, 95% CI 1.003-1.023, P = .10 and HR 1.01, 95% CI 1.001-1.019, P = .024 respectively)., Conclusions: Our study found no effect of PAP treatment of SDB on time to recurrence of AF post-AF intervention. Increased risk of recurrent AF was associated with high BMI and LAVI. These findings may affect the clinical management of AF., (© 2019 American Academy of Sleep Medicine.)

Study Objectives: Adaptive servoventilation (ASV) is the suggested treatment for many forms of central sleep apnea (CSA). We aimed to evaluate the impact of treating CSA with ASV on health care utilization., Methods: In this population-based study using the Rochester Epidemiology Project database, we identified patients over a 9-year period who were diagnosed with CSA (n = 1,237), commenced ASV therapy, and had ≥ 1 month of clinical data before and after ASV initiation. The rates of hospitalizations, emergency department visits (EDV), outpatient visits (OPV) and medications prescribed per year (mean ± standard deviation) in the 2 years pre-ASV and post-ASV initiation were compared., Results: We found 309 patients (68.0 ± 14.6 years, 80.3% male, apnea-hypopnea index 41.6 ± 26.5 events/h, 78% with cardiovascular comorbidities, 34% with heart failure) who met inclusion criteria; 65% used ASV ≥ 4 h/night on ≥ 70% nights in their first month. The overall 2-year mortality rate was 9.4% and CSA secondary to cardiac cause was a significant risk factor for mortality (hazard ratio 1.81, 95% CI 1.09-3.01, P = .02). Comparing pre-ASV and post-ASV initiation, there was no change in the rate of hospitalization (0.72 ± 1.63 versus 0.79 ± 1.44, P = .46), EDV (1.19 ± 2.18 versus 1.26 ± 2.08, P = .54), OPV (31.59 ± 112.42 versus 13.60 ± 17.36, P = .22), or number of prescribed medications (6.68 ± 2.0 versus 5.31 ± 5.86, P = .06). No differences in these outcomes emerged after accounting for adherence to ASV, CSA subtype and comorbidities via multiple regression analysis (all P > .05)., Conclusions: Our cohort of patients with CSA was quite ill and the use of ASV was not associated with a change in health care utilization., (© 2019 American Academy of Sleep Medicine.)

Abstract: PHOX2B 20/27 polyalanine repeat mutation (PARM) in patients with congenital central hypoventilation syndrome (CCHS) is generally associated with full-time ventilator dependence, Hirschsprung disease, and increased risk for cardiac asystole. We follow a 14-year-old boy with CCHS PHOX2B 20/27 PARM who is full-time ventilator dependent via tracheostomy and has Hirschsprung disease. His mother, age 52 years, has a history of prolonged recovery from anesthesia and an elevated serum bicarbonate level of 45 mEq/L discovered on routine blood chemistry. PHOX2B gene mutation analysis was performed and showed an identical 20/27 PARM, diagnostic of CCHS. Late-onset CCHS has been reported in those with 20/24, 20/25 PHOX2B PARM, and in nonpolyalanine repeat mutations. This is the first report of a patient with PHOX2B 20/27 PARM with a mild phenotype diagnosed during adulthood. This unusual presentation supports the screening for PHOX2B mutations in parents of children with CCHS., (© 2018 American Academy of Sleep Medicine.)

Abstract: There have been no published reports of central respiratory control abnormalities in pediatric patients with UNC80 or KCNJ11 mutations which cause neurologic channelopathies. We describe an 8-year-old male with a pathogenic UNC80 mutation, intellectual disability, hypotonia and epilepsy with severe central sleep apnea (213.5 events/h) on polysomnography (PSG). We also describe a 20-month-old female with a KCNJ11 mutation, neonatal diabetes and developmental delay who had severe central sleep apnea (131.1 events/h). Both patients had irregular respiratory patterns during sleep and wakefulness and were placed on empiric bilevel positive airway pressure therapy, which was well tolerated with resolution of abnormal respiratory control and hypercapnia. Patients with UNC80 and KCNJ11 gene mutations may have abnormal respiratory rhythm during sleep and wakefulness, mirroring animal models. We recommend routine PSG tests and further investigation into the respiratory control of patients with pediatric channelopathies involved in chemoreceptor function or central integration of respiratory control., (© 2018 American Academy of Sleep Medicine.)

Abstract: A medullary tumor is a relatively rare disease that causes severe and complicated respiratory disorders, including sleep-related breathing disorders, due to dysregulation of respiratory control. A severely obese 12-year-old male was admitted to our hospital for worsening dyspnea and received a diagnosis of type II respiratory failure. Although obstructive sleep apnea (OSA) and/or obesity hypoventilation syndrome were suspected, a polysomnogram obtained during a nap (nap study) revealed central sleep apnea (CSA) and sleep-related hypoventilation disorder (SRHD) in addition to OSA. Brain magnetic resonance imaging showed a mass in the medulla oblongata. The patient received a diagnosis of CSA/SRHD caused by a medullary tumor, and with OSA. A partial brainstem tumor resection was performed. Noninvasive positive airway pressure therapy was initiated, and was continued after surgery. However, the patient died unexpectedly, 20 months after surgery. When children with sleep problems caused by OSA present with atypical symptoms of OSA, a neurological examination and polysomnography should be conducted to detect CSA and SRHD., (© 2018 American Academy of Sleep Medicine.)

Abstract: Treatment-emergent central sleep apnea has recently been noted after various treatment modalities for obstructive sleep apnea. It often remits spontaneously or can be treated with continuous positive airway pressure. However, we encountered a pediatric patient with obstructive sleep apnea who presented with severe complications, including growth failure, attention-deficit hyperactivity disorder, poor school performance, daytime sleepiness, and urinary difficulty that required permanent cystostomy. His obstructive sleep apnea resolved after adenotonsillectomy. However, treatment-emergent central sleep apnea developed after adenotonsillectomy and was further aggravated after continuous positive airway pressure and bilevel positive airway pressure without a backup respiratory rate use. After bilevel positive airway pressure with a backup respiratory rate treatment for 3 months initially, all his symptoms improved, except growth failure. Later, after adaptive servoventilation was used for 10 months, the patient's growth began to improve., (© 2018 American Academy of Sleep Medicine.)

Study Objectives: There is a lack of data regarding adherence trajectories when switching from continuous positive airway pressure (CPAP) to adaptive servoventilation (ASV) in the context of persistent or treatment-emergent central sleep apnea (CSA). This study investigated 90-day adherence rates in patients with sleep apnea based on the type of positive airway pressure (PAP) device used and any switching of PAP modality over time., Methods: Telemonitoring data were obtained from a United States PAP database. Eligible patients were a 30% random sample who started PAP, plus all who started ASV, from January 1, 2015 to October 2, 2015. All received PAP and had at least one session with usage of 1 hour or more. Adherence and device usage were determined in three groups: started on CPAP and stayed on CPAP (CPAP only); started on ASV and stayed on ASV (ASV only); started on CPAP, switched to ASV (Switch). The United States Medicare definition of adherence was used., Results: The study included 198,890 patients; 189,724 (CPAP only), 8,957 (ASV only) and 209 (Switch). In the Switch group, average apnea-hypopnea index decreased significantly on ASV versus CPAP. At 90 days, adherence rates were 73.8% and 73.2% in the CPAP only and ASV only groups. In the Switch group, CPAP adherence was 62.7%, improving to 76.6% after the switch to ASV. Mean device usage at 90 days was 5.27, 5.31, and 5.73 h/d in the CPAP only, ASV only, and Switch groups, respectively., Conclusions: Treatment-emergent or persistent CSA during CPAP reduced therapy adherence, but adherence improved early after switching from CPAP to ASV., (© 2018 American Academy of Sleep Medicine)

Abstract: PHOX2B non-polyalanine repeat mutation (NPARM) in patients with congenital central hypoventilation syndrome (CCHS) is generally considered to be associated with full-time ventilator dependence and severe autonomic nervous system dysfunction. We report a three-generation family with four individuals possessing a novel PHOX2B NPARM (c.245C > T) with variable phenotypes. This mutation was inherited in an autosomal dominant pattern with variable penetrance. The affected family members with CCHS have a milder phenotype than is typically expected with a NPARM. Two family members are ventilator dependent only during sleep and do not have Hirschsprung disease or neural crest tumors. One family member was asymptomatic until systemic hypertension developed during adulthood and another family member remains asymptomatic as an adult. Our findings emphasize the importance of monitoring adults with a PHOX2B NPARM who are considered asymptomatic in childhood., (© 2017 American Academy of Sleep Medicine)

Abstract: Central sleep apnea (CSA) and continuous positive airway pressure (CPAP) emergent CSA are common in patients for whom opioids have been prescribed for chronic pain management. It is not known if opioids are the potential cause of CSA. We report the case of a patient who underwent multiple full nights of polysomnography testing while on opioids, off opioids, and with various positive airway pressure devices. While on opioids, the patient had severe CSA that persisted during both CPAP and bilevel titration but was eliminated with adaptive servoventilation therapy. Some time later, opioid use was discontinued by the patient. Repeat polysomnography showed resolution of the sleep-disordered breathing. Later-while the patient was still off opioids-she had gained weight and become symptomatic; polysomnography showed obstructive sleep apnea without CSA. This time, therapy with CPAP showed elimination of sleep apnea without emergent CSA. These data collectively indicate that opioids were the cause of CSA as well as emergent CSA., (© 2017 American Academy of Sleep Medicine)

Abstract: An update of the 2012 systematic review and meta-analyses were performed and a modified-GRADE approach was used to update the recommendation for the use of adaptive servo-ventilation (ASV) for the treatment of central sleep apnea syndrome (CSAS) related to congestive heart failure (CHF). Meta-analyses demonstrated an improvement in LVEF and a normalization of AHI in all patients. Analyses also demonstrated an increased risk of cardiac mortality in patients with an LVEF of ≤ 45% and moderate or severe CSA predominant sleep-disordered breathing. These data support a Standard level recommendation against the use of ASV to treat CHF-associated CSAS in patients with an LVEF of ≤ 45% and moderate or severe CSAS, and an Option level recommendation for the use of ASV in the treatment CHF-associated CSAS in patients with an LVEF > 45% or mild CHF-related CSAS. The application of these recommendations is limited to the target patient populations; the ultimate judgment regarding propriety of any specific care must be made by the clinician., (© 2016 American Academy of Sleep Medicine.)

Study Objectives: This study challenged on a bench-test the efficacy of auto-titrating positive airway pressure (APAP) devices for obstructive sleep disordered breathing treatment and evaluated the accuracy of the device reports., Methods: Our bench consisted of an active lung simulator and a Starling resistor. Eleven commercially available APAP devices were evaluated on their reactions to single-type SDB sequences (obstructive apnea and hypopnea, central apnea, and snoring), and to a long general breathing scenario (5.75 h) simulating various SDB during four sleep cycles and to a short scenario (95 min) simulating one sleep cycle., Results: In the single-type sequence of 30-minute repetitive obstructive apneas, only 5 devices normalized the airflow (> 70% of baseline breathing amplitude). Similarly, normalized breathing was recorded with 8 devices only for a 20-min obstructive hypopnea sequence. Five devices increased the pressure in response to snoring. Only 4 devices maintained a constant minimum pressure when subjected to repeated central apneas with an open upper airway. In the long general breathing scenario, the pressure responses and the treatment efficacy differed among devices: only 5 devices obtained a residual obstructive AHI < 5/h. During the short general breathing scenario, only 2 devices reached the same treatment efficacy (p < 0.001), and 3 devices underestimated the AHI by > 10% (p < 0.001). The long scenario led to more consistent device reports., Conclusion: Large differences between APAP devices in the treatment efficacy and the accuracy of report were evidenced in the current study., (© 2015 American Academy of Sleep Medicine.)

Study Objectives: To compare the efficacy and patient comfort of a new mode of minute ventilation-targeted adaptive servoventilation (ASVAuto) with auto-titrating expiratory positive airway pressure (EPAP) versus bilevel with back-up respiratory rate (bilevel-ST) in patients with central sleep apnea (CSA) associated with chronic use of opioid medications., Methods: Prospective, randomized, crossover polysomnography (PSG) study. Eighteen consecutive patients (age ≥ 18 years) who had been receiving opioid therapy (≥ 6 months), and had sleep disordered breathing with CSA (central apnea index [CAI] ≥ 5) diagnosed during an overnight sleep study or positive airway pressure (PAP) titration were enrolled to undergo 2 PSG studies-one with ASVAuto and one with bilevel-ST. Patients completed 2 questionnaires after each PSG; Morning After Patient Satisfaction Questionnaire and PAP Comfort Questionnaire., Results: Patients had a mean age of 52.9 ± 15.3 years. PSG prior to randomization showed an apnea hypopnea index (AHI) of 50.3 ± 22.2 and CAI of 13.0 ± 18.7. Titration with ASVAuto versus bilevel-ST showed that there were significant differences with respect to AHI and CAI. The AHI and CAI were significantly lower on ASVAuto than bilevel-ST (2.5 ± 3.5 versus 16.3 ± 20.9 [p = 0.0005], and 0.4 ± 0.8 versus 9.4 ± 18.8 [p = 0.0002], respectively). Respiratory parameters were normalized in 83.3% of patients on ASVAuto versus 33.3% on bilevel-ST. Patients felt more awake and alert on ASVAuto than bilevel-ST based on scores from Morning After Patient Satisfaction Questionnaire (p = 0.0337)., Conclusions: The ASVAuto was significantly more effective than bilevel-ST for the treatment of CSA associated with chronic opioid use.

Rationale: Opioids have become part of contemporary treatment in the management of chronic pain. Although severe daytime ventilatory depression is uncommon, chronic use of opioids could be associated with severe central and obstructive sleep apnea., Objectives: To determine the acute efficacy, and prolonged use of adaptive servoventilation (ASV) to treat central sleep apnea in patients on chronic opioids., Methods: Twenty patients on opioid therapy referred for evaluation of obstructive sleep apnea (OSA) were found to have central sleep apnea (CSA). The first 16 patients underwent continuous positive airway pressure (CPAP) titration, which showed persistent CSA. With the notion that CSA will be eliminated with continued use of CPAP, 4 weeks later, 9 of the 16 patients underwent a second CPAP titration which proved equally ineffective. Therefore, therapy with CPAP was abandoned. All patients underwent ASV titration., Main Results: Diagnostic polysomnography showed an average apnea-hypopnea index (AHI) of 61/h and a central-apnea index (CAI) of 32/h. On CPAP 1, AHI was 34/h and CAI was 20/h. Respective indices on CPAP 2 were AHI 33/h and CAI 19/h. During titration with ASV, CAI was 0/h and the average HI was 11/h on final pressures. With a reduction in AHI, oxyhemoglobin saturation nadir increased from 83% to 90%, and arousal index decreased from 29/h of sleep to 12/h on final ASV pressures. Seventeen patients were followed for a minimum of 9 months and up to 6 years. The mean long-term adherence was 5.1 ± 2.5 hours., Conclusions: Chronic use of opioids could be associated with severe CSA which remains resistant to CPAP therapy. ASV device is effective in the treatment of CSA and over the long run, most patients remain compliant with the device. Randomized long-term studies are necessary to determine if treatment of sleep apnea with ASV improves quality of life and the known mortality associated with opioids.

Rationale: Adaptive servoventilation devices are marketed to overcome sleep disordered breathing with apneas and hypopneas of both central and obstructive mechanisms often experienced by patients with chronic heart failure. The clinical efficacy of these devices is still questioned., Study Objectives: This study challenged the detection and treatment capabilities of the three commercially available adaptive servoventilation devices in response to sleep disordered breathing events reproduced on an innovative bench test., Methods: The bench test consisted of a computer-controlled piston and a Starling resistor. The three devices were subjected to a flow sequence composed of central and obstructive apneas and hypopneas including Cheyne-Stokes respiration derived from a patient. The responses of the devices were separately evaluated with the maximum and the clinical settings (titrated expiratory positive airway pressure), and the detected events were compared to the bench-scored values., Results: The three devices responded similarly to central events, by increasing pressure support to raise airflow. All central apneas were eliminated, whereas hypopneas remained. The three devices responded differently to the obstructive events with the maximum settings. These obstructive events could be normalized with clinical settings. The residual events of all the devices were scored lower than bench test values with the maximum settings, but were in agreement with the clinical settings. However, their mechanisms were misclassified., Conclusion: The tested devices reacted as expected to the disordered breathing events, but not sufficiently to normalize the breathing flow. The device-scored results should be used with caution to judge efficacy, as their validity depends upon the initial settings.

Obstructive sleep apnea results from structural compromise of the upper airway and decreased muscle tone during sleep. Central sleep apnea is usually due to instability of the feedback mechanism of the body that controls respiration. While positional changes commonly affect the severity of obstructive sleep apnea, the effect of positional changes on the severity of central sleep apnea is less well known.

Background: There are no standard therapies for the management of central sleep apnea (CSA). Either positive pressure therapy (PAP) or supplemental oxygen (O(2)) may stabilize respiration in CSA by reducing ventilatory chemoresponsiveness. Additionally, increasing opioid use and the presence of comorbid conditions in US veterans necessitates investigations into alternative titration protocols to treat CSA. The goal was to report on the effectiveness of titration with PAP, used alone or in conjunction with O(2), for the management of CSA associated with varying comorbidities and opioid use., Methods: This was a retrospective chart review over 3 years, performed at a VA sleep disorders center. The effects of CPAP, CPAP+O(2), and BPAP+O(2), used in a step-wise titration protocol, on consecutive patients diagnosed with CSA were studied., Results: CSA was diagnosed in 162 patients. The protocol was effective in eliminating CSA (CAI ≤ 5/h) in 84% of patients. CPAP was effective in 48%, while CPAP+O(2) combination was effective in an additional 25%, and BPAP+O(2) in 11%. The remaining 16% were non-responders. Forty-seven patients (29%) were on prescribed opioid therapy for chronic pain, in whom CPAP, CPAP+O(2), or BPAP+O(2) eliminated CSA in 54%, 28%, and 10% cases, respectively. CPAP, CPAP+O(2), and BPAP+O(2) each produced significant declines in the AHI, CAI, and arousal index, and an increase in the SpO(2)., Conclusion: The data demonstrate that using a titration protocol with CPAP and then PAP with O(2) effectively eliminates CSA in individuals with underlying comorbid conditions and prescription opioid use. Comparative studies with other therapeutic modalities are required.

Study Objectives: Adaptive servoventilation (ASV) is often used to treat central sleep apnea (CSA) and complex sleep apnea syndrome (CompSAS). Both CompSAS and CSA may occur in the setting of CHF and with the use of chronic opioids. We hypothesized that ASV would be less successful in treatment of CSA and CompSAS secondary to opioid use than in CHF patients., Methods: Consecutive patients were studied between January and December 2009 who underwent ASV titration for CSA or CompSAS due to CHF (defined as EF < 45%, or > 50% with evidence for diastolic dysfunction on echocardiogram) and chronic opioid users (defined by the use of opioids > 6 months)., Results: Study included one hundred and eight patients with 77 males (71.3%) and 31 females (28.7%). Subjects had severe sleep apnea at baseline (AHI 45.6 ± 27.4) and inadequate control of sleep disordered breathing on CPAP (AHI 50.0 ± 32.2, CAI 36.6 ± 32). No significant differences were found between the groups in overall ASV success, defined as AHI < 10/h (p = 0.236). ASV was successful in 28 (59.6%) of those in the opioid group, compared to 43 (70.5%) of those in the CHF group. When ASV success was defined as AHI < 5/h at optimum EEP, there was again no significant difference between the groups (p-value = 0.812). Logistic regression showed unit increases in BMI, unit increases in HCO(3), and presence of CSR were each associated with decreased likelihood of ASV success., Conclusion: We did not find a statistically significant difference in the effectiveness of ASV between CHF patients and chronic opioid users, with the overall success rate approaching 70%, as defined by an AHI < 10/h., Commentary: A commentary on this article appears in this issue on page 577.

An 80-year-old man with severe central sleep apnea due to Cheyne-Stokes breathing (AHI 41.2) caused by severe cardiac failure underwent a trial of adaptive servo-ventilation (ASV) by full face mask after failure of a fixed CPAP trial. Recommended procedure was closely followed and the ASV device activated normally during central apneas. Initial settings were EEP 5, PSmin 3, PSmax 15 on room air. The device did not capture the thorax or abdomen, as shown by lack of change in respiratory inductive plethysmography, despite expected mask pressure waveforms. Snoring was also detected during apneas with device activation. Desaturation continued, followed by arousals during hyperpnea. On the device, the patient clearly slept for 1-3 epochs during the central apneas only to awaken during hyperpnea. We hypothesize that the failure to capture may have resulted from "reverse" obstructive apnea, possibly due to glottic closure during ASV activation. We suggest that earlier manual adjustments to ASV in cases such as ours, prior to waiting for the recommended 20 to 40 min of sleep, may be appropriate in selected patients. We also consider additional interventions that may increase the likelihood of a successful trial.

Study Objectives: This study documents both the incidence and effects of central apnea on diagnosis and treatment of OSA at different altitudes in the Mountain West and substantiates the clinical impression that individuals living at altitude with moderate to severe OSA are significantly more difficult to treat with PAP., Methods: Split-night polysomnography was compared between sites for patients with a diagnostic AHI > 15 living at 1421 meters (Site 1; N = 150), at 1808 m (Site 2; N = 150) and at 2165 m (Site 3; N = 142). The quality of PAP titration obtained was rated, based on AASM clinical guidelines, from 1 = optimal to 4 = unacceptable. Patients developing central apneas during PAP therapy (CAI > 5.0) were titrated with an alternative O(2) > CPAP/Bilevel PAP protocol., Results: The mean number of central apneas in the diagnostic portion of studies was significantly higher (p < 0.01) at Sites 2 (19.26) and 3 (12.36) than at Site 1 (3.11). Mean numbers of central apneas/h developing on treatment with PAP varied from 4.8/h at Site 1, to 9.79/h at Site 2, to 19.25/h at Site 3 (p < 0.001). At Site 1, 10.6% had a central apnea index (CAI) > 5.0, while 22% met this criterion at Site 2 and 38.7% at Site 3 (Site 3 vs Site 1, p = 0.01; Site 2 vs Site 1, p = 0.02). Rated titration quality varied significantly between sites. At Site 1, mean titration quality was 1.437 (SD 0.821); for Site 2, 1.569 (SD 0.96), and for Site 3, 1.772 (SD 1.025). Titration quality at Site 3 was significantly worse than at Site 1 (t = 3.22, p < 0.01) and at Site 2 (t = 2.55, p < 0.02). Repeat titration requirement differed significantly (p = 0.025). Analysis of covariance comparing titration across 3 altitude levels, controlling for age, was significant for the effect of altitude (p = 0.017). Utilizing the alternative O(2) > C-PAP/Bi-PAP protocol in patients with CAI > 5.0 developing on PAP treatment, an overall optimal or good titration (AASM criteria) was attained in 75/79 (95%) of titrated patients., Conclusions: This study demonstrates that central apnea becomes significantly more common at increasing altitude in both diagnostic and treatment portions of split-night polysomnography in patients with significant OSA. An apparent exponential increase in the percentage of OSA patients with a CAI > 5.0 occurs with increasing altitude. Altitude associated central apnea has a significant negative effect on the quality of OSA treatment obtained during PAP titration for patients living at the altitudes addressed in this study.

Study Objectives: Central sleep apnea can be refractory to traditional positive airway pressure (PAP) therapy (CPAP or bilevel PAP), whether appearing first as a feature of baseline polysomnography or only later once PAP is applied in what is termed "complex sleep apnea" (CompSA). This retrospective study examined the efficacy of adaptive servoventilation (ASV) in 25 consecutive patients with PAP-refractory central sleep apnea, most exhibiting predominantly obstructive apnea during baseline polysomnography., Methods: Patient characteristics were: age = 59.8 ± 16.5 yr; BMI = 30.4 ± 6.1 kg/m(2); apnea/hypopnea index (AHI) = 48.5 ± 30.2/h; and central apnea index (CAI) = 10.8 ± 16.0/h. Following unsuccessful PAP titrations, patients underwent ASV titration. Eighteen met established criteria for CompSA., Results: On traditional PAP, AHI did not improve significantly compared to baseline, whether based on the entire titration (38.5 ± 23.4/h, p = 0.10) or the final PAP pressure(s) (44.4 ± 25.9/h, p = 0.54); CAI tripled across the titration (27.4 ± 23.5/h, p = 0.001) and at the final pressure(s) (34.8 ± 24.2/h, p < 0.001). On ASV, AHI fell to 11.4 ± 8.2/h across the titration (p < 0.001) and decreased further to 3.6 ± 4.2/h at the optimal end expiratory pressure (p < 0.001). AHI was ≤ 5/h in 80% of patients and < 10/h in 92%. ASV virtually eliminated central apneas at optimal end expiratory pressure (0.7 ± 2.2/h, p < 0.001). Respiratory arousals showed parallel improvements on ASV but not PAP., Conclusions: ASV proved superior to traditional PAP in reducing the AHI, CAI, and respiratory arousals in a heterogeneous patient group with sleep disordered breathing in whom central apneas emerged or persisted on PAP.

Congenital central hypoventilation syndrome (CCHS) is an uncommon disorder characterized by the absence of adequate autonomic control of respiration, which results in alveolar hypoventilation and decreased sensitivity to hypercarbia and hypoxemia, especially during sleep. Patients with CCHS need lifelong ventilatory support. The treatment options for CCHS include intermittent positive pressure ventilation administered via tracheostomy, noninvasive positive pressure ventilation, negative-pressure ventilation by body chamber or cuirass, and phrenic nerve pacing. However, it may be necessary to alter the mode of ventilation according to age, psychosocial reasons, complications of therapy, and emergence of new modes of ventilation. We present a case of a 16-year-old girl with CCHS who was mechanically ventilated via tracheostomy for 16 years and was successfully transitioned to a new modality of noninvasive ventilation (average volume-assured pressure support [AVAPS]) that automatically adjusts the pressure support level in order to provide a consistent tidal volume.

Noninvasive positive pressure ventilation (NPPV) devices are used during sleep to treat patients with diurnal chronic alveolar hypoventilation (CAH). Bilevel positive airway pressure (BPAP) using a mask interface is the most commonly used method to provide ventilatory support in these patients. BPAP devices deliver separately adjustable inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP). The IPAP and EPAP levels are adjusted to maintain upper airway patency, and the pressure support (PS = IPAP-EPAP) augments ventilation. NPPV devices can be used in the spontaneous mode (the patient cycles the device from EPAP to IPAP), the spontaneous timed (ST) mode (a backup rate is available to deliver IPAP for the set inspiratory time if the patient does not trigger an IPAP/EPAP cycle within a set time window), and the timed (T) mode (inspiratory time and respiratory rate are fxed). During NPPV titration with polysomnography (PSG), the pressure settings, backup rate, and inspiratory time (if applicable) are adjusted to maintain upper airway patency and support ventilation. However, there are no widely available guidelines for the titration of NPPV in the sleep center. A NPPV Titration Task Force of the American Academy of Sleep Medicine reviewed the available literature and developed recommendations based on consensus and published evidence when available. The major recommendations derived by this consensus process are as follows: General Recommendations: 1. The indications, goals of treatment, and side effects of NPPV treatment should be discussed in detail with the patient prior to the NPPV titration study. 2. Careful mask fitting and a period of acclimatization to low pressure prior to the titration should be included as part of the NPPV protocol. 3. NPPV titration with PSG is the recommended method to determine an effective level of nocturnal ventilatory support in patients with CAH. In circumstances in which NPPV treatment is initiated and adjusted empirically in the outpatient setting based on clinical judgment, a PSG should be utilized if possible to confirm that the final NPPV settings are effective or to make adjustments as necessary. 4. NPPV treatment goals should be individualized but typically include prevention of worsening of hypoventilation during sleep, improvement in sleep quality, relief of nocturnal dyspnea, and providing respiratory muscle rest. 5. When OSA coexists with CAH, pressure settings for treatment of OSA may be determined during attended NPPV titration PSG following AASM Clinical Guidelines for the Manual Titration of Positive Airway Pressure in Patients with Obstructive Sleep Apnea. 6. Attended NPPV titration with PSG is the recommended method to identify optimal treatment pressure settings for patients with the obesity hypoventilation syndrome (OHS), CAH due to restrictive chest wall disease (RTCD), and acquired or central CAH syndromes in whom NPPV treatment is indicated. 7. Attended NPPV titration with PSG allows definitive identification of an adequate level of ventilatory support for patients with neuromuscular disease (NMD) in whom NPPV treatment is planned. Recommendations for NPPV Titration Equipment: 1. The NPPV device used for titration should have the capability of operating in the spontaneous, spontaneous timed, and timed mode. 2. The airflow, tidal volume, leak, and delivered pressure signals from the NPPV device should be monitored and recorded if possible. The airflow signal should be used to detect apnea and hypopnea, while the tidal volume signal and respiratory rate are used to assess ventilation. 3. Transcutaneous or end-tidal PCO2 may be used to adjust NPPV settings if adequately calibrated and ideally validated with arterial blood gas testing. 4. An adequate assortment of masks (nasal, oral, and oronasal) in both adult and pediatric sizes (if children are being titrated), a source of supplemental oxygen, and heated humidification should be available. Recommendations for Limits of IPAP, EPAP, and PS Settings: 1. The recommended minimum starting IPAP and EPAP should be 8 cm H2O and 4 cm H2O, respectively. 2. The recommended maximum IPAP should be 30 cm H2O for patients > or = 12 years and 20 cm H2O for patients < 12 years. 3. The recommended minimum and maximum levels of PS are 4 cm H2O and 20 cm H2O, respectively. 4. The minimum and maximum incremental changes in PS should be 1 and 2 cm H2O, respectively. Recommendations for Adjustment of IPAP, EPAP, and PS: 1. IPAP and/or EPAP should be increased as described in AASM Clinical Guidelines for the Manual Titration of Positive Airway Pressure in Patients with Obstructive Sleep Apnea until the following obstructive respiratory events are eliminated (no specific order): apneas, hypopneas, respiratory effort-related arousals, and snoring. 2. The pressure support (PS) should be increased every 5 minutes if the tidal volume is low (< 6 to 8 mL/kg) 3. The PS should be increased if the arterial PCO2 remains 10 mm Hg or more above the PCO, goal at the current settings for 10 minutes or more. An acceptable goal for PCO, is a value less than or equal to the awake PCO2. 4. The PS may be increased if respiratory muscle rest has not been achieved by NPPV treatment at the current settings for 10 minutes of more. 5. The PS may be increased if the SpO, remains below 90% for 5 minutes or more and tidal volume is low (< 6 to 8 mL/kg). Recommendations for Use and Adjustment of the Backup Rate/ Respiratory Rate: 1. A backup rate (i.e., ST mode) should be used in all patients with central hypoventilation, those with a significant number of central apneas or an inappropriately low respiratory rate, and those who unreliably trigger IPAP/EPAP cycles due to muscle weakness. 2. The ST mode may be used if adequate ventilation or adequate respiratory muscle rest is not achieved with the maximum (or maximum tolerated) PS in the spontaneous mode. 3. The starting backup rate should be equal to or slightly less than the spontaneous sleeping respiratory rate (minimum of 10 bpm). 4. The backup rate should be increased in 1 to 2 bpm increments every 10 minutes if the desired goal of the backup rate has not been attained. 5. The IPAP time (inspiratory time) should be set based on the respiratory rate to provide an inspiratory time (IPAP time) between 30% and 40% of the cycle time (60/respiratory rate in breaths per minute). 6. If the spontaneous timed mode is not successful at meeting titration goals then the timed mode can be tried. Recommendations Concerning Supplemental Oxygen: 1. Supplemental oxygen may be added in patients with an awake SpO2 < 88% or when the PS and respiratory rate have been optimized but the SpO2 remains < 90% for 5 minutes or more. 2. The minimum starting supplemental oxygen rate should be 1 L/minute and increased in increments of 1 L/minute about every 5 minutes until an adequate SpO2 is attained (> 90%). Recommendations to Improve Patient Comfort and Patient-NPPV Device Synchrony: 1. If the patient awakens and complains that the IPAP and/or EPAP is too high, pressure should be lowered to a level comfortable enough to allow return to sleep. 2. NPPV device parameters (when available) such as pressure relief, rise time, maximum and minimum IPAP durations should be adjusted for patient comfort and to optimize synchrony between the patient and the NPPV device. 3. During the NPPV titration mask refit, adjustment, or change in mask type should be performed whenever any significant unintentional leak is observed or the patient complains of mask discomfort. If mouth leak is present and is causing significant symptoms (e.g., arousals) use of an oronasal mask or chin strap may be tried. Heated humidification should be added if the patient complains of dryness or significant nasal congestion. Recommendations for Follow-Up: 1. Close follow-up after initiation of NPPV by appropriately trained health care providers is indicated to establish effective utilization patterns, remediate side effects, and assess measures of ventilation and oxygenation to determine if adjustment to NPPV is indicated.

Sleep disordered breathing (SDB) including obstructive sleep apnea (OSA), central sleep apnea (CSA), and Cheyne-Stokes breathing is common in patients with congestive heart failure (CHF). In a study of 81 males with an ejection fraction (EF) < 45%, 51% of patients had documented SDB with the majority of cases representing CSA. Studies suggest that SDB is an independent risk factor for increased morbidity and mortality in the setting of CHF. Like OSA, CSA frequently presents with nighttime awakenings, nocturnal hypoxia, and daytime somnolence, but only OSA has been reported to present with delirium. We present a patient with clear manifestations of CSA with frank delirium that improved only after BPAP therapy.