Obstructive Sleep Apnea, Obesity Hypoventilation Syndrome, and Pulmonary Hypertension: A State-of-the-Art Review.

The pathophysiological interplay between sleep-disordered breathing (SDB) and pulmonary hypertension (PH) is complex and can involve a variety of mechanisms by which SDB can worsen PH. These mechanistic pathways include wide swings in intrathoracic pressure while breathing against an occluded upper airway, intermittent and/or sustained hypoxemia, acute and/or chronic hypercapnia, and obesity. In this review, we discuss how the downstream consequences of SDB can adversely impact PH, the challenges in accurately diagnosing and classifying PH in the severely obese, and review the limited literature assessing the effect of treating obesity, obstructive sleep apnea, and obesity hypoventilation syndrome on PH.

The assessment and management of obstructive sleep apnoea-hypopnoea syndrome and obesity hypoventilation syndrome in obesity.

Obesity is associated with respiratory dysfunction. It is a key risk and contributory factor in the sleep related breathing disorders, obstructive sleep apnoea/hypopnoea syndrome (OSAHS) and obesity hypoventilation syndrome (OHS). Weight management is an integral part of the management of these disorders, in addition to continuous positive airways pressure (CPAP) and non-invasive ventilation (NIV). Untreated, these conditions are associated with a high disease burden and as treatment is effective, early recognition and referral is critical. Best practice in on-going care is multidisciplinary.

A Novel Nomogram and Online Calculator for Predicting the Risk of Obesity Hypoventilation Syndrome in Bariatric Surgery Candidates.

BACKGROUND: Obesity hypoventilation syndrome (OHS) is frequently misdiagnosed and undertreated, increasing the risk of perioperative complications. We aimed to determine the predictors of OHS and to develop and validate a novel nomogram and online calculator for identifying patients at risk of OHS in bariatric surgery candidates. METHODS: We retrospectively analyzed the data of patients undergoing bariatric surgery between March 2017 and June 2020. Predictors were identified using univariate and multivariate analyses to establish the nomogram. The discriminative ability, calibration, and clinical value of the nomograms were tested using C-statistics, calibration plots, and decision curve analysis. The nomogram was internally validated using bootstrap resampling. RESULTS: A total of 577 patients were enrolled, and OHS was presented in 17.9% (103/577). Body mass index (BMI) (odds ratio [OR], 1.11; 95% confidence interval (CI), 1.04-1.18; p = 0.001), neck circumference (OR, 1.09; 95% CI, 1.01-1.18; p = 0.035), type 2 diabetes (T2D) (OR, 2.02; 95% CI, 1.17-3.45; p = 0.011), serum bicarbonate (OR, 1.47; 95% CI, 1.30-1.67; p < 0.001), and C-reactive protein (CRP) (OR, 1.03; 95% CI, 1.01-1.06; p = 0.017) were independent risk factors for OHS and incorporated to develop the nomogram. The nomogram revealed good discrimination, with a C-index of 0.830 (95% CI: 0.784-0.876) (0.8227 through internal validation), and good calibration. Decision curve analysis further confirmed the nomogram's clinical usefulness. CONCLUSIONS: The novel nomogram and online calculator provided an excellent preoperative individualized prediction of OHS in patients undergoing bariatric surgery, hereby potentially assisting clinicians and surgeons in the early detection and intensive monitoring of OHS.

Obesity hypoventilation syndrome in bariatric surgery patients: an underestimated disease.

BACKGROUND: Obesity is a known risk factor for obesity hypoventilation syndrome (OHS). However, study on the prevalence and clinical characteristics of OHS among bariatric surgery patients is scarce. OBJECTIVES: To investigate the prevalence of OHS in bariatric surgery patients and to identify its related predictors. SETTING: The study was conducted at a bariatric surgery center in a tertiary university hospital. METHODS: A cross sectional analysis was performed in the patients undergoing bariatric surgery between March 2017 and January 2020. Anthropometric, laboratory, pulmonary function, blood gas analysis, and polysomnographic data was collected and analyzed. RESULTS: Of 522 patients, the overall prevalence of OHS was 15.1%, with men (22.8 %) having a greater frequency than women (9.4%) (P < .001). The prevalence increases with obesity severity, from 4.1% in those with body mass index (BMI) <35 kg/m2 to 39.1% in those with BMI ≥50 kg/m2. Of 404 patients with obstructive sleep apnea (OSA), OHS was present in 17.3%, with 9.8% in mild OSA, 10.0% in moderate OSA, and 27.3%in severe OSA. Only 11.4% of patients diagnosed with OHS had no OSA. On logistic regression, BMI (odds ratio [OR]: 1.10; 95% confidence interval [CI], 1.01-1.21; P = .033), neck circumference (OR: 1.15; 95% CI, 1.03-1.28; P = .014), serum bicarbonate (OR: 1.39; 95% CI, 1.20-1.61; P = .000), C-reactive protein (CRP) (OR: 1.04; 95% CI, 1.00-1.07; P = .034) were independently associated with OHS. CONCLUSION: In bariatric surgery patients, OHS presented a high prevalence, especially in men. Higher levels of BMI, neck circumference, serum bicarbonate, and CRP indicated higher risk of OHS.

A novel case of central hypoventilation syndrome or just heavy breathing?

With the growing prevalence of obesity in the pediatric population, reports of its severe complications are increasing. Obesity hypoventilation syndrome is an uncommon disorder in children with altered respiratory mechanics, sleep-disordered breathing, and impaired ventilatory responses leading to persistent hypercapnia. Presentation is varied, and children may remain relatively asymptomatic until challenged with a respiratory infection, when they may present with acute respiratory failure. With increasing use of genetic testing in pediatric patients, our knowledge of potential contributors to hypoventilation syndromes is growing. Although mutations in the paired-like homeobox 2B gene are known to be causative of congenital central hypoventilation syndrome, other genes may also contribute to hypoventilation phenotypes. We report one of the youngest reported patients with obesity hypoventilation syndrome in pediatrics, with a proposed congenital predisposition for central hypoventilation derived from a deletion in the brain-derived neurotrophic factor gene. CITATION: McCoy J, Karp N, Brar J, Amin R, St-Laurent A. A novel case of central hypoventilation syndrome or just heavy breathing? J Clin Sleep Med. 2022;18(9):2321-2325.

Severity stages of obesity-related breathing disorders - a cross-sectional cohort study.

INTRODUCTION: There is a general underappreciation of the spectrum of obesity-related breathing disorders and their consequences. We therefore compared characteristics of obese patients with eucapnic obstructive sleep apnea (OSA), OSA with obesity-related sleep hypoventilation (ORSH) or obesity hypoventilation syndrome (OHS) to identify the major determinants of hypoventilation. PATIENTS AND METHODS: In this prospective, diagnostic study (NCT04570540), obese patients with OSA, ORSH or OHS were characterized applying polysomnography with transcutaneous capnometry, blood gas analyses, bodyplethysmography and measurement of hypercapnic ventilatory response (HCVR). Pathophysiological variables known to contribute to hypoventilation and differing significantly between the groups were specified as potential independent variables in a multivariable logistic regression to identify major determinants of hypoventilation. RESULTS: Twenty, 43 and 19 patients were in the OSA, ORSH and OHS group, respectively. BMI was significantly lower in OSA as compared to OHS. The extent of SRBD was significantly higher in OHS as compared to OSA or ORSH. Patients with ORSH or OHS showed a significantly decreased forced expiratory volume in 1 s and forced vital capacity compared to OSA. HCVR was significantly lower in OHS and identified as the major determinant of hypoventilation in a multivariable logistic regression (Nagelkerke R2 = 0.346, p = 0.050, odds ratio (95%-confidence interval) 0.129 (0.017-1.004)). CONCLUSION: Although there were differences in BMI, respiratory mechanics and severity of upper airway obstruction between groups, our data support HCVR as the major determinant of obesity-associated hypoventilation.

Obesity and Obesity Hypoventilation, Sleep Hypoventilation, and Postoperative Respiratory Failure.

Obesity hypoventilation syndrome (OHS) is considered as a diagnosis in obese patients (body mass index [BMI] ≥30 kg/m2) who also have sleep-disordered breathing and awake diurnal hypercapnia in the absence of other causes of hypoventilation. Patients with OHS have a higher burden of medical comorbidities as compared to those with obstructive sleep apnea (OSA). This places patients with OHS at higher risk for adverse postoperative events. Obese patients and those with OSA undergoing elective noncardiac surgery are not routinely screened for OHS. Screening for OHS would require additional preoperative evaluation of morbidly obese patients with severe OSA and suspicion of hypoventilation or resting hypoxemia. Cautious selection of the type of anesthesia, use of apneic oxygenation with high-flow nasal cannula during laryngoscopy, better monitoring in the postanesthesia care unit (PACU) can help minimize adverse perioperative events. Among other risk-reduction strategies are proper patient positioning, especially during intubation and extubation, multimodal analgesia, and cautious use of postoperative supplemental oxygen.

Diagnostic approach to sleep disordered-breathing among patients with grade III obesity.

Sleep apnea test (SAT) is a cost-effective approach to evaluate subjects without associated comorbidities suspected for obstructive sleep apnea (OSA), a disorder particularly common in obese subjects. The association of obesity with awake hypercapnia (carbon dioxide arterial pressure, PaCO2 ≥45 mmHg) defines the obesity-hypoventilation syndrome (OHS), which in turn results in increased morbidity and mortality compared to simple OSA. Isolated hypoventilation during sleep in obese patients (obesity-related sleep hypoventilation, ORSH) is now considered as an early stage of OHS. The aim of this study was to assess the performance of SAT in diagnosing OSA and predicting the presence of ORHS among patients with grade III obesity without awake hypercapnia. METHODS: Over a 14-months period, patients with grade III obesity (body mass index≥40 kg/m2) presenting moderate-to-severe OSA (apnea-hypopnea index [AHI]≥15) upon SAT and normal awake PaCO2 at arterial blood gas analysis, systematically underwent in-lab nocturnal polysomnography combined with transcutaneous carbon dioxide pressure (PtcCO2) monitoring. RESULTS: Among 48 patients included in the study, 16 (33%) presented an AHI<15 upon polysomnography and 14 (29%) had ORSH. The test revealed no difference in ORSH prevalence between patients with AHI <15 or ≥15 (31% vs. 25%). No SAT variables were independently associated with increased PtCO2. CONCLUSIONS: This study shows that SAT overestimates OSA severity and ORSH affects one third of patients with grade III obesity without awake hypercapnia and with moderate-to-severe OSA at SAT, suggesting how polysomnography combined with PtCO2 monitoring is the most appropriate diagnostic approach for OSA and ORSH in this population.

Obesity Hypoventilation: Traditional Versus Nontraditional Populations.

Obesity hypoventilation syndrome is the most frequent cause of chronic hypoventilation and is increasingly more common with rising obesity rates. It leads to considerable morbidity and mortality, particularly when not recognized and treated adequately. Long-term nocturnal noninvasive ventilation is the mainstay of treatment but evidence suggests that CPAP may be effective in stable patients. Specific perioperative management is required to reduce complications. Some unique syndromes associated with obesity and hypoventilation include rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation (ROHHAD), and Prader-Willi syndrome. Congenital central hypoventilation syndrome (early or late-onset) is a genetic disorder resulting in hypoventilation. Several acquired causes of chronic central hypoventilation also exist. A high level of clinical suspicion is required to appropriately diagnose and manage affected patients.

Extubating to Noninvasive Ventilation: Noninvasive Ventilation from Intensive Care Unit to Home.

Weaning to noninvasive ventilation in intensive care unit and bridging the patients to home with respiratory support is evolving as the technology of noninvasive ventilation is improving. In patients with chronic obstructive pulmonary disease exacerbation, timing of initiation of noninvasive ventilation is the key, as persistently hypercapnic patients show benefits. High-intensity pressure support seems to do better in comparison to low-intensity pressure support. In patients with obesity and hypercapnia, obesity hypoventilation cannot be ruled out especially in an inpatient setting, and it is crucial that these patients are discharged with noninvasive ventilation.

Pulmonary embolism in obesity-hypoventilation syndrome.

INTRODUCTION: Obesity-hypoventilation syndrome occurs with alveolar hypoventilation during sleeping and daytime. Obesity may be a risk factor for venous thromboembolism. However, the venous thromboembolism in the obesity-hypoventilation syndrome is not well characterized. OBJECTIVE: This case series aimed to investigate the presence and clinical features of venous thromboembolism in patients with the obesity-hypoventilation syndrome. METHODS: Data of eight case reports were collected. Ages ranged from 36 to 73 years. RESULTS: All patients had mosaic perfusion and enlarged main pulmonary artery, two had signs of infarction and mostly segmental and subsegmental filling defects. On the basis of this information some conclusions can be drawn carefully. CONCLUSION: Present cases indicate that pulmonary embolism are also very common in patients with obesity-hypoventilation syndrome, anticoagulant therapy is at least as important as the treatment of the current disease. Clinicians will frequently be faced with patients with obesity-hypoventilation syndrome suspected of PE.

Long-term outcome with focus on pulmonary hypertension in Obesity Hypoventilation Syndrome.

INTRODUCTION: Pulmonary Hypertension (PH) is a frequent comorbidity in Obesity Hypoventilation Syndrome (OHS). OBJECTIVE: We investigated long-term outcome of OHS with a particular emphasis on PH. METHODS: In a prospective design, 64 patients with OHS and established noninvasive positive pressure ventilation (NPPV), were assessed by serum biomarkers, right heart catheterization, blood gases analysis, lung function, Epworth-Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), World Health Organization-functional class (WHO-FC) and health-related quality of life (HRQL) via the Severe Respiratory Insufficiency (SRI) questionnaire. After a planned follow-up of 5 years patients were reassessed regarding vital status, WHO-FC, ESS, SRI, PSQI, body mass index (BMI) and NPPV use. Prognostic markers were explored using univariate and multivariate Cox regression analyses. RESULTS: At the 5-year follow-up, BMI tended to decrease (P = 0.05), while WHO-FC, ESS and PSQI remained unchanged. HRQL deteriorated in terms of SRI summary score and most subdomains (P < .05 each). NPPV adherence still was high (89%), while daily NPPV use increased from 6.7 (5.1; 8.0) h/d to 8.2 (7.4; 9.0) h/d (P < .05). After a 5-year follow-up, mortality was 25.8%. In univariate regression analyses only age > 69.5 years (HR = 4.145, 95%-CI = 1.180-14.565, P = 0.016), NT-proBNP > 1256 pg/mL (HR = 5.162, 95%-CI = 1.136-23.467, P = 0.018), diffusion capacity for carbon monoxide (DLCO, %pred) (HR = 0.341, 95%-CI = 0.114-1.019, P = 0.043) and higher oxygen use during daytime (HR = 5.236, 95%-CI = 1.489-18.406, P = 0.004) predicted mortality. No independent factor predicting mortality was detected in multivariate analysis. CONCLUSION: Despite a high long-term NPPV use HRQL worsened. Age, oxygen use at baseline, DLCO (%pred) and NT-proBNP, as a surrogate parameter for PH, were related to long-term survival.

Effectiveness of different treatments in obesity hypoventilation syndrome.

Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity, defined as daytime hypoventilation, sleep disorder breathing and obesity; during the past few years the prevalence of extreme obesity has markedly increased worldwide consequently increasing the prevalence of OHS. Patients with OHS have a lower quality of life and a higher risk of unfavourable cardiometabolic consequences. Early diagnosis and effective treatment can lead to significant improvement in patient outcomes; therefore, such data has noticeably raised interest in the management and treatment of this sleep disorder. This paper will discuss the findings on the main current treatment modalities OHS will be discussed.

Diagnosing obstructive sleep apnea patients with isolated nocturnal hypoventilation and defining obesity hypoventilation syndrome using new European Respiratory Society classification criteria: an Indian perspective.

BACKGROUND: Recently, new classification criteria for obesity hypoventilation syndrome (OHS) have been described. OHS prevalence according to new criteria has not been reported in obstructive sleep apnea (OSA). Prevalence of OHS has not been previously reported from India. METHODS: Retrospective study was carried out in OSA patients for whom both arterial blood gases (ABG) and end-tidal CO2 (etCO2) records were available. OHS was defined according to old and new criteria. Analysis was carried out among various groups: patients without OHS (Group A), patients with sleep hypoventilation but without daytime hypercapnia (Group B) and patients with daytime hypercapnia (Group C). RESULTS: Out of 367 patients with OSA (body mass index, BMI) 31.9 ± 12.27 kg/m2), finally 128 obese OSA patients were included for analysis. Of those, 15 (5.9%, 95% confidence interval (CI) 3.5-9.4) and 45 patients (17.8%, 95% CI 13.4-22.9) fulfilled prevalence of OHS according to old and new criteria, respectively. Continuous positive airway pressure (CPAP) titration failed in 9.6%, 53.3% and 66.7% in Groups A, B, and C, respectively. For all parameters of OSA severity (apnea-hypopnea index (AHI), Nadir O2, T90) and positive airway pressure (PAP) requirements, patients in Group B were in between those in Groups A and C. Statistically significant difference was seen between Group A and Group B, and between Groups A and C, but not between Groups B and C. CONCLUSION: One in six OSA patients and one in three obese OSA patients (BMI >30 kg/m2) have OHS according to new criteria. Since patients with isolated nocturnal hypoventilation were as sick as patients with daytime hypercapnia, screening for sleep hypoventilation should be carried out in all obese OSA patients.

Perioperative considerations in the management of obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is characterised by repetitive compromise of the upper airway, causing impaired ventilation, sleep fragmentation, and daytime functional impairment. It is a heterogeneous condition encompassing different phenotypes. The prevalence of OSA among patients presenting for elective surgery is growing, largely attributable to an increase in age and obesity rates, and most patients remain undiagnosed and untreated at the time of surgery. This condition is an established risk factor for increased perioperative cardiopulmonary morbidity, heightened in the presence of concurrent medical comorbidities. Therefore, it is important to perform preoperative OSA screening and risk stratification - using the STOP-Bang screening questionnaire, nocturnal oximetry, and ambulatory and in-laboratory polysomnography, for example. Postoperative risk assessment is an evolving process that encompasses evaluation of upper airway compromise, ventilatory control instability, and pain-sedation mismatch. Optimal postoperative OSA management comprises continuation of regular positive airway pressure, a multimodal opioid-sparing analgesia strategy to limit respiratory depression, avoidance of supine position, and cautious intravenous fluid administration. Supplemental oxygen does not replace a patient's regular positive airway pressure therapy and should be administered cautiously to avoid risk of hypoventilation and worsening of hypercapnia. Continuous pulse oximetry monitoring with specified targets of peripheral oxygen saturation measured by pulse oximetry is encouraged.

Evaluation and Management of Obesity Hypoventilation Syndrome. An Official American Thoracic Society Clinical Practice Guideline.

Background: The purpose of this guideline is to optimize evaluation and management of patients with obesity hypoventilation syndrome (OHS).Methods: A multidisciplinary panel identified and prioritized five clinical questions. The panel performed systematic reviews of available studies (up to July 2018) and followed the Grading of Recommendations, Assessment, Development, and Evaluation evidence-to-decision framework to develop recommendations. All panel members discussed and approved the recommendations.Recommendations: After considering the overall very low quality of the evidence, the panel made five conditional recommendations. We suggest that: 1) clinicians use a serum bicarbonate level <27 mmol/L to exclude the diagnosis of OHS in obese patients with sleep-disordered breathing when suspicion for OHS is not very high (<20%) but to measure arterial blood gases in patients strongly suspected of having OHS, 2) stable ambulatory patients with OHS receive positive airway pressure (PAP), 3) continuous positive airway pressure (CPAP) rather than noninvasive ventilation be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea, 4) patients hospitalized with respiratory failure and suspected of having OHS be discharged with noninvasive ventilation until they undergo outpatient diagnostic procedures and PAP titration in the sleep laboratory (ideally within 2-3 mo), and 5) patients with OHS use weight-loss interventions that produce sustained weight loss of 25% to 30% of body weight to achieve resolution of OHS (which is more likely to be obtained with bariatric surgery).Conclusions: Clinicians may use these recommendations, on the basis of the best available evidence, to guide management and improve outcomes among patients with OHS.

The utility of STOP-BANG questionnaire in the sleep-lab setting.

Polysomnography (PSG) is considered the gold standard in obstructive sleep apnea-hypopnea syndrome (OSAS) diagnostics, but its availability is still limited. Thus, it seems useful to assess patients pre-diagnostic risk for OSAS to prioritize the use of this examination. The purpose of this study was to assess positive (PPV) and negative (NPV) predictive values of the STOP BANG questionnaire (SBQ) in patients with presumptive diagnosis of OSAS. From a database of 1,171 (880 men) patients of a university based sleep center, 1,123 (847 men) met eligibility criteria and their SBQ scores were subject to the Bayesian analysis. The analysis of PPV and NPV was conducted at all values of SBQ for all subjects, but also separately for males and females, and for total sleep time (TS) and for sleep in the lateral position (LP). The probability of OSAS (AHI ≥ 5) and at least moderate OSAS (AHI ≥ 15) for TS was 0.766 and 0.516, while for LP the values were 0.432 and 0.289, respectively. Overall, due to low specificity, SBQ had low PPV for TS and LP. Negative test result (SBQ < 3) revealed NPV of 0.620 at AHI < 5 and 0.859 at AHI < 15 for TS, while in LP NPV values were 0.935 at AHI < 5 and 1.0 at AHI < 15, (n = 31), while SBQ < 4 generated NPV of 0.943 in LP (n = 105). SBQ did not change probabilities of OSAS to confirm or rebut diagnosis for TS. However, it is highly probable that SQB can rule out OSAS diagnosis at AHI ≥ 15 for LP.

Automatic EPAP intelligent volume-assured pressure support is effective in patients with chronic respiratory failure: A randomized trial.

BACKGROUND AND OBJECTIVE: Patients with chronic respiratory failure are increasingly managed with domiciliary non-invasive ventilation (NIV). There may be limited ability to provide NIV titration for these complex patients, and ventilatory requirements and upper airway support needs may change over time. Therefore, an automatically adjusting expiratory positive airway pressure (AutoEPAP) algorithm may offer advantages over manually adjusted EPAP for treating these patients. This study compared 4% oxygen desaturation index (ODI4%) values during the use of an AutoEPAP algorithm versus manual EPAP titration with the intelligent volume-assured pressure support (iVAPS) algorithm. METHODS: This prospective, single-blind, randomized, crossover study was conducted at six US sites. Patients with chronic respiratory failure (neuromuscular disease, chronic obstructive pulmonary disease, obesity hypoventilation and other aetiologies) and an apnoea-hypopnoea index of >5/h who were already established NIV users underwent a single night of NIV with the iVAPS manual EPAP and iVAPS AutoEPAP in the sleep laboratory in random order. RESULTS: A total of 38 patients constituted the study population. Mean ODI4% was statistically non-inferior with AutoEPAP versus manual EPAP (P < 0.0001). There was no difference in the effect on ODI4% across respiratory failure subgroups. Ventilation parameters and gas exchange were similar with either NIV mode, indicating equally effective treatment of respiratory failure. Sleep parameters were improved during AutoEPAP versus manual EPAP. CONCLUSION: A single night of NIV using the iVAPS with AutoEPAP algorithm was non-inferior to a single night of iVAPS with manual EPAP titration in patients with respiratory failure. CLINICAL TRIAL REGISTRATION: NCT02683772 at clinicaltrials.gov.