Haematocrit level in obesity hypoventilation syndrome: a predictor of mortality?

BACKGROUND: The connection between obstructive sleep apnea and secondary erythrocytosis is controversial. We hypothesised that there may be a higher prevalence of erythrocytosis in patients with obesity hypoventilation syndrome (OHS) due to persistent hypoxemia. METHODS: The study was a retrospective, cross-sectional review of patients with OHS derived from an established cohort of "non-invasive ventilation" patients at the Department of Sleep Medicine at the Royal Infirmary Medical Centre, Edinburgh (2004-2017). Relevant clinical data were obtained from patient records. RESULTS: The cohort comprised 74 patients with OHS, 44 men (60%), mean age at diagnosis 54 ± 10 years. The mean haematocrit level for the group overall was 0.44, in men 0.45, and in women 0.41. Of 11 patients with erythrocytosis (15%), 7 were men. Thirteen patients (18%) died during follow-up (2004-2017). There was a statistically significant increase in risk of death in patients with higher and lower haematocrit levels compared to that in patients with OHS who had normal haematocrits. CONCLUSIONS: This is the first study showing increased prevalence of erythrocytosis in OHS patients. There was a "U"-shaped correlation with mortality according to haematocrit levels.

Acute Respiratory Failure in Obesity-Hypoventilation Syndrome Managed in the ICU.

BACKGROUND: Obesity-hypoventilation syndrome (OHS) is defined as the combination of obesity (body mass index ≥ 30 kg/m2) and daytime arterial hypercapnia (PaCO2 > 45 mm Hg) in the absence of other causes of hypoventilation, and can lead to acute hypercapnic respiratory failure in the ICU. Our objective was to describe the ventilatory management and outcomes of subjects with OHS who were admitted to the ICU for acute hypercapnic respiratory failure. METHODS: We retrospectively built a cohort of subjects with OHS who were admitted for acute hypercapnic respiratory failure in 4 ICUs of the university teaching hospital in Lyon, France, between 2013 and 2017. The main end point was the rate of success of noninvasive ventilation (NIV). Secondary end points were survival from OHS diagnosis to the last follow-up and risk factors for ICU admission and long-term survival. RESULTS: One hundred fifteen subjects with OHS were included. Thirty-seven subjects (32.1%) were admitted to the ICU for acute hypercapnic respiratory failure. Congestive heart failure was the leading cause of acute hypercapnic respiratory failure (54%). At ICU admission, pH before NIV use was median (range) 7.26 (7.22-7.31) and PaCO2 was 70 (61-76) mm Hg. NIV was used as first-line ventilatory support in 36 subjects (97.2%) and was successful in 33 subjects (91.7%). ICU mortality was low (2.7%). The subjects admitted to the ICU were significantly older and had a lower FEV1 and vital capacity at the time of an OHS diagnosis. The difference in the restricted mean survival time was 663 d in favor of subjects not admitted to the ICU. Multivariate analysis showed that lower vital capacity at an OHS diagnosis was significantly associated with a higher risk of ICU admission. No factor was independently associated with long-term overall mortality in multivariate analysis. CONCLUSIONS: Acute hypercapnic respiratory failure in subjects with OHS was generally responsive to NIV and was frequently associated with congestive heart failure.

Long-term clinical effectiveness of continuous positive airway pressure therapy versus non-invasive ventilation therapy in patients with obesity hypoventilation syndrome: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Obesity hypoventilation syndrome is commonly treated with continuous positive airway pressure or non-invasive ventilation during sleep. Non-invasive ventilation is more complex and costly than continuous positive airway pressure but might be advantageous because it provides ventilatory support. To date there have been no long-term trials comparing these treatment modalities. We therefore aimed to determine the long-term comparative effectiveness of both treatment modalities. METHODS: We did a multicentre, open-label, randomised controlled trial at 16 clinical sites in Spain. We included patients aged 15-80 years with untreated obesity hypoventilation syndrome and an apnoea-hypopnoea index of 30 or more events per h. We randomly assigned patients, using simple randomisation through an electronic database, to receive treatment with either non-invasive ventilation or continuous positive airway pressure. Both investigators and patients were aware of the treatment allocation. The research team was not involved in deciding hospital treatment, duration of treatment in the hospital, and adjustment of medications, as well as adjudicating cardiovascular events or cause of mortality. Treating clinicians from the routine care team were not aware of the treatment allocation. The primary outcome was the number of hospitalisation days per year. The analysis was done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, number NCT01405976. FINDINGS: From May 4, 2009, to March 25, 2013, 100 patients were randomly assigned to the non-invasive ventilation group and 115 to the continuous positive airway pressure group, of which 97 patients in the non-invasive ventilation group and 107 in the continuous positive airway pressure group were included in the analysis. The median follow-up was 5·44 years (IQR 4·45-6·37) for all patients, 5·37 years (4·36-6·32) in the continuous positive airway pressure group, and 5·55 years (4·53-6·50) in the non-invasive ventilation group. The mean hospitalisation days per patient-year were 1·63 (SD 3·74) in the continuous positive airway pressure group and 1·44 (3·07) in the non-invasive ventilation group (adjusted rate ratio 0·78, 95% CI 0·34-1·77; p=0·561). Adverse events were similar between both groups. INTERPRETATION: In stable patients with obesity hypoventilation syndrome and severe obstructive sleep apnoea, non-invasive ventilation and continuous positive airway pressure have similar long-term effectiveness. Given that continuous positive airway pressure has lower complexity and cost, continuous positive airway pressure might be the preferred first-line positive airway pressure treatment modality until more studies become available. FUNDING: Instituto de Salud Carlos III, Spanish Respiratory Foundation, and Air Liquide Spain.

Efficacy of bilevel positive airway pressure and continuous positive airway pressure therapy in patients with obesity hypoventilation syndrome: protocol for systematic review and meta-analysis.

INTRODUCTION: Obesity hypoventilation syndrome (OHS) is a major respiratory complication caused by severe obesity, being associated with significant morbidity, negative impacts on quality of life and reduced survival if not treated appropriately. Positive airway pressure therapy is the first-line treatment for OHS although the optimal modality remains unclear. The goal of this study is to identify the efficacy of home bilevel positive airway pressure therapy by comparison to continuous positive airway pressure therapy and determine the best strategy for patients with OHS. METHODS AND ANALYSIS: This study will be conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement. We will search the following databases: PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL. Ongoing studies will be identified through the ClinicalTrials.gov and WHO International Clinical Trials Registry Platform Search Portal. Grey literature will be recognised through Google Scholar and other search engines. Only randomised controlled trials meeting the eligibility criteria will be included. The risk of bias of the included studies will be evaluated through the Cochrane Collaboration's tool. RevMan V.5.3.5 software will be used for data analysis. The Q statistic and I2 index will be used for investigating heterogeneity, and subgroup analysis or sensitivity analysis will be used to explore the source of heterogeneity. In addition, the Grading of Recommendations Assessment, Development and Evaluation system will be used to inspect the quality of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required because this study contains no primary data collected from humans. This systematic review and meta-analysis will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42017078369.

Home Mechanical Ventilation: An Overview.

Prevalence studies have shown heterogeneous use of home mechanical ventilation in different conditions, with a marked increase in uptake especially in users of noninvasive ventilation. Although randomized controlled trials have examined noninvasive ventilation in acute exacerbations of chronic obstructive pulmonary disease, for weaning from invasive ventilation and for postextubation respiratory failure, the evidence base for long-term noninvasive ventilation and comparisons with invasive ventilation are less well developed. The combination of noninvasive ventilation and cough-assist devices has reduced the indications for tracheotomy ventilation in some situations (e.g., Duchenne muscular dystrophy, spinal muscular atrophy, myopathies, and amyotrophic lateral sclerosis) and has also prolonged survival. Several excellent overviews have been written on the history of home mechanical ventilation and its evolution from negative pressure to positive pressure techniques, including a systematic review of outcomes. This review, instead, will cover recent trials, trends in the field, outcomes, and safety. Because the greatest growth has been in home noninvasive ventilation, this will be the main focus of this article.

Mortalidad en el síndrome de obesidad-hipoventilación y factores de riesgo pronóstico / Mortality in obesity-hypoventilation syndrome and prognostic risk factors

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Obesity-hypoventilation syndrome: increased risk of death over sleep apnea syndrome.

AIM: To study whether mortality and cardiovascular morbidity differ in non-invasive ventilation (NIV)-treated patients with severe obesity-hypoventilation syndrome (OHS) as compared with CPAP-treated patients with obstructive sleep apnea syndrome (OSAS), and to identify independent predictors of mortality in OHS. MATERIAL AND METHODS: Two retrospective cohorts of OHS and OSAS were matched 1:2 according to sex, age (± 10 year) and length of time since initiation of CPAP/NIV therapy (± 6 months). RESULTS: Three hundred and thirty subjects (110 patients with OHS and 220 patients with OSAS) were studied. Mean follow-up time was 7 ± 4 years. The five year mortality rates were 15.5% in OHS cohort and 4.5% in OSAS cohort (p< 0.05). Patients with OHS had a 2-fold increase (OR 2; 95% CI: 1.11-3.60) in the risk of mortality and 1.86 fold (OR 1.86; 95% CI: 1.14-3.04) increased risk of having a cardiovascular event. Diabetes, baseline diurnal SaO2 < 83%, EPAP < 7 cmH2O after titration and adherence to NIV < 4 hours independently predicted mortality in OHS. CONCLUSION: Mortality of severe OHS is high and substantially worse than that of OSAS. Severe OHS should be considered a systemic disease that encompasses respiratory, metabolic and cardiovascular components that require a multimodal therapeutic approach.

Noninvasive mechanical ventilation in patients with obesity hypoventilation syndrome. Long-term outcome and prognostic factors.

INTRODUCTION: Obesity is associated with 2 closely related respiratory diseases: obesity hypoventilation syndrome (OHS) and obstructive sleep apnea-hypopnea syndrome (OSAHS). It has been shown that noninvasive ventilation during sleep produces clinical and functional improvement in these patients. The long-term survival rate with this treatment, and the difference in clinical progress in OHS patients with and without OSAHS are analyzed. METHODOLOGY: Longitudinal, observational study with a cohort of patients diagnosed with OHS, included in a home ventilation program over a period of 12 years, divided into 2 groups: pure OHS and OSAHS-associated OHS. Bi-level positive airway pressure ventilation was administered. During the follow-up period, symptoms, exacerbations and hospitalizations, blood gas tests and pulmonary function tests, and survival rates were monitored and compared. RESULTS: Eighty-three patients were eligible for analysis, 60 women (72.3%) and 23 men (27.7%), with a mean survival time of 8.47 years. Fifty patients (60.2%) were included in the group without OSAHS (OHS) and 33 (39.8%) in the OSAHS-associated OHS group (OHS-OSAHS). PaCO2 in the OHS group was significantly higher than in the OHS-OSAHS group (P<.01). OHS patients also had a higher hospitalization rate (P<.05). There was a significant improvement in both groups in FEV1 and FVC, and no differences between groups in PaCO2 and PaO2 values. There were no differences in mortality between the 2 groups, but low FVC values were predictive of mortality. CONCLUSIONS: The use of mechanical ventilation in patients with OHS, with or without OSAHS, is an effective treatment for the correction of blood gases and functional alterations and can achieve prolonged survival rates.

Obesity hypoventilation syndrome: from sleep-disordered breathing to systemic comorbidities and the need to offer combined treatment strategies.

Obesity hypoventilation syndrome (OHS) is defined as a combination of obesity (body mass index ≥ 30 kg/m(2)), daytime hypercapnia (partial arterial carbon dioxide concentration ≥45 mm Hg) and sleep-disordered breathing after ruling out other disorders that may cause alveolar hypoventilation. Through the prism of the International Classification of Functioning, OHS is a chronic condition associated with respiratory, metabolic, hormonal and cardiovascular impairments, leading to a decrease in daily life activities, a lack of social participation and high risk of hospitalization and death. Despite its severity, OHS is largely underdiagnosed and the health-related costs are higher than those of apnoeic or obese eucapnic patients. The present review discusses the definition, epidemiology, physiopathology and treatment modalities of OHS. Although nocturnal positive airway pressure therapies represent first-line treatment and are effective in improving patient outcomes, there is a need to offer combined treatment strategies and to assess the effect of multimodal therapeutic strategies on morbidity and mortality.

Early mortality rate of morbidly obese patients after tracheotomy.

OBJECTIVES: To 1) determine the early mortality rate (within 30 days) of morbidly obese patients after tracheotomy; 2) determine the difference between the mortality rate after tracheotomy of morbidly obese patients and patients who are not morbidly obese; and 3) determine the difference between the mortality rate after tracheotomy adjusted for case mix index (CMI) of morbidly obese patients and patients who are not morbidly obese. STUDY DESIGN: Retrospective cohort study of 278 patients who had undergone a tracheotomy by the otolaryngology head and neck surgery department from 2004 to 2006. The patients were subdivided into two groups: 1) body mass index (BMI) <35 (n = 229) and 2) BMI > or =35 (morbidly obese) (n = 49). METHODS: Charts reviewed for age, sex, weight, height, BMI, indication for tracheotomy, date of tracheotomy, type of tracheotomy, date of discharge, date of death, length of hospital stay, and CMI. RESULTS: There is a trend toward significance (P = .09) between the mortality rate after tracheotomy of morbidly obese patients (29%) and patients who are not morbidly obese (18%). There is less significance between the adjusted mortality rate based on CMI after tracheotomy when the patient population is divided into morbidly obese patients and patients who are not morbidly obese (P = .12). CONCLUSION: The mortality rate after tracheotomy of morbidly obese patients is greater than patients who are not morbidly obese.

Assessment and management of patients with obesity hypoventilation syndrome.

Obesity hypoventilation syndrome (OHS) is characterized by obesity, daytime hypercapnia, and sleep-disordered breathing in the absence of significant lung or respiratory muscle disease. Compared with eucapnic morbidly obese patients and eucapnic patients with sleep-disordered breathing, patients with OHS have increased health care expenses and are at higher risk of developing serious cardiovascular disease leading to early mortality. Despite the significant morbidity and mortality associated with this syndrome, diagnosis and institution of effective treatment occur late in the course of the syndrome. Given that the prevalence of extreme obesity has increased considerably, it is likely that clinicians will encounter patients with OHS in their clinical practice. Therefore maintaining a high index of suspicion can lead to early recognition and treatment reducing the high burden of morbidity and mortality and related health care expenditure associated with undiagnosed and untreated OHS. In this review we define the clinical characteristics of the syndrome and review the pathophysiology, morbidity, and mortality associated with it. Last, we discuss currently available treatment modalities.

Mortality and prognostic factors in patients with obesity-hypoventilation syndrome undergoing noninvasive ventilation.

OBJECTIVES: The incidence of obesity-hypoventilation syndrome (OHS) has greatly increased over time, but data on long-term outcome are limited. We investigated survival and prognostic factors in these patients undergoing noninvasive positive pressure ventilation (NPPV). DESIGN: Retrospective descriptive analysis of patients with OHS and NPPV up to 10 years. METHODS: Long-term mortality and predictors of survival were assessed. Additionally, we evaluated changes in lung function, blood gas and laboratory parameters 5.7 +/- 2.5 months after initiation of NPPV. RESULTS: 126 patients (BMI 44.6 +/- 7.8 kg m(-2); PaCO(2) 55.5 +/- 7.7 mmHg) were followed for 41.3 +/- 27.6 months. Upon follow-up, blood gases (daytime and nighttime), as well as pulmonary function improved, whilst haemoglobin and BMI decreased (P < 0.001 each). Adherence to NPPV was high (94.5% continuing NPPV 6.5 +/- 2.3 h day(-1)). All-cause mortality was 12.7%, with 1-, 2- and 5-year survival of 97.1%, 92.0% and 70.2%, respectively. In univariate analysis, patients with PaO(2) <50 mmHg, C-reactive protein > or = 5.1 mg L(-1), leucocytes > or = 7.8 x 10(3) microl(-1), or pH > or = 7.44 at baseline had poor prognosis (P < 0.05 each). In Cox multivariate analysis, PaO(2), pH and leucocytes were independent predictors of mortality. Reduction in nocturnal PaCO(2) by > or =23.0% and haemoglobin at follow-up was associated with improved survival (P < 0.05 each) whilst a decrease in pH was a predictor of increased mortality. In contrast, neither baseline BMI nor its change was linked to survival. CONCLUSION: Gas exchange and lung function in OHS were improved after initiation of NPPV. Hypoxemia, high pH and elevated inflammation markers predicted poor survival. Overall, NPPV was well tolerated and survival was excellent when compared with data from historical matched controls.

[Evolution of patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or congestive heart failure in a respiratory monitoring unit]. / Evolución comparativa con ventilación no invasiva de pacientes con EPOC, síndrome de hipoventilación-obesidad e insuficiencia cardíaca congestiva ingresados en una unidad de monitorización respiratoria.

OBJECTIVE: We compared the use of noninvasive ventilation (NIV) for hypercapnic acidosis with hypoxemia in patients with chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), or congestive heart failure (CHF) in a respiratory medicine monitoring unit. The objective was to evaluate each diagnostic groups response to therapy in terms of clinical course and evolution of blood gases. PATIENTS AND METHODS: Prospective, 12-month study of 53 patients with hypercapnic acidosis with hypoxemia. Twenty-seven patients had COPD, 17 OHS, and 9 CHF. Severity was assessed based on initial arterial blood gas analysis. Clinical course was studied by blood gas analysis after conventional treatment and after NIV (1-3 hours and 12-24 hours). Mortality was recorded. All patients received bilevel positive airway pressure support in assist-control mode. RESULTS: No significant differences were observed between mean (SD) initial pH findings in the 3 diagnostic groups: COPD, 7.28 (0.1); OHS, 7.29 (0.09); and CHF, 7.24 (0.07). (nonsignificant differences). After initial conventional treatment, PaCO2 worsened for COPD patients (P = .026) and PaO2 improved for CHF patients (P = .028). After 1 to 3 hours of NIV, pH (P = .002) and PaO2 (P = .041) improved for COPD patients, and pH (P = .03) and PaCO2 (P = .045) improved in OHS patients; no significant changes were observed in CHF patients. After 12 to 24 hours of NIV, the mean pH was 7.36 (0.04) for COPD patients, 7.36 (0.05) for OHS patients, and 7.25 (0.1) for CHF patients (not significant). The mortality rate was 11.1% for COPD, 0% for OHS, and 33.3% for CHS (not significant, P = .076). CONCLUSIONS: In this group of patients with similar initial arterial blood gas values, response to NIV was seen to be better in OHS and COPD than in CHF. That the start of NIV is usually preceded by a poor response to conventional COPD treatment suggests that delaying NIV should be reconsidered.

Evolución comparativa con ventilación no invasiva de pacientes con EPOC, síndrome de hipoventilación-obesidad e insuficiencia cardíaca congestiva ingresados en una unidad de monitorización respiratoria / Evolution of patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or congestive heart failure in a respiratory monitoring unit

OBJETIVO: Hemos realizado un trabajo comparativo en pacientes con enfermedad pulmonar obstructiva crónica (EPOC), síndrome de hipoventilación-obesidad (SHO) e insuficiencia cardíaca congestiva (ICC) sometidos a ventilación no invasiva (VNI) en una unidad de monitorización de neumología por presentar acidosis hipoxémica-hipercápnica. El objetivo ha sido valorar la respuesta clínica y gasométrica en función del diagnóstico. PACIENTES Y MÉTODOS: Se trata de un estudio prospectivo (12 mese de duración) en 53 pacientes con acidosis hipoxémic-hipercápnica, de los que 27 presentaban EPOC; 17, SHO, y 9, ICC. Realizamos un análisis de la gravedad gasométrica inicial, de la evolución gasométrica (tras tratamiento convencional y tras VNI a las 1-3h y 12-24h) y de la mortalidad. Todos ellos recibieron VNI tipo BiPAP en modo asistido-controlado. RESULTADOS: LA presentación gasométrica inicial era similar en las 3 entidades (valores medios +/- desviación estándar de pH, 7,28 +/- 0,1 en la EPOC; 7,29 +/- 0,09 en SHO, y 7,24 +/- 0,07 en ICC; no significativo). Tras tratamiento convencional inicial, en los pacientes con EPOC se observó un empeoramiento de la presión arterial de anhídrido carbónico (p=0,026), y en aquellos con ICC, una mejoría de la presión arterial de oxígeno (p=0,028). Tras el inico de la VNI (1-3h) se produjo una mejoría del pH (p=0,002) y de la presión arterial de oxígeno (p=0,041) en la EPOC, y del pH (p=0,03) y de la presión arterial de anhídrido carbónico (o=0,045) en el SHO; no hubo cambios significativos en la ICC. Tras 12-24h con VNI, el pH fue de 7,36 +/- 0,04 en la EPOC, de 7,36 +/- 0,05 en el SHO y de 7,25 +/- 0,1 (no significativo) en la ICC. La mortalidad fue del 11,1% en la EPOC, del 0% en el SHO y del 33% en la ICC (no significativo; p= 0,076). CONCLUSIONES: Partiendo de una gravedad gasométrica similar, en el SHO y la EPOC se observó una mejor respuesta a la VNI que en la ICC. El inicio de la VNI suele precederse de mala respuesta al tratamiento convencional en la EPOC, lo que haría replantearse la demora para iniciarla

OBJECTIVE: We compared the use of noninvasive ventilation (NIV) for hypercapnic acidosis with hypoxemia in patients with chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), or congestive heart failure (CHF) in a respiratory medicine monitoring unit. The objective was to evaluate each diagnostic groups response to therapy in terms of clinical course and evolution of blood gases. PATIENTS AND METHODS: Prospective, 12-month study of 53 patients with hypercapnic acidosis with hypoxemia. Twenty-seven patients had COPD, 17 OHS, and 9 CHF. Severity was assessed based on initial arterial blood gas analysis. Clinical course was studied by blood gas analysis after conventional treatment and after NIV (1-3 hours and 12-24 hours). Mortality was recorded. All patients received bilevel positive airway pressure support in assist-control mode. RESULTS: No significant differences were observed between mean (SD) initial pH findings in the 3 diagnostic groups: COPD, 7.28 (0.1); OHS, 7.29 (0.09); and CHF, 7.24 (0.07). (nonsignificant differences). After initial conventional treatment, PaCO2 worsened for COPD patients (P=.026) and PaO2 improved for CHF patients (P=.028). After 1 to 3 hours of NIV, pH (P=.002) and PaO2 (P=.041) improved for COPD patients, and pH (P=.03) and PaCO2 (P=.045) improved in OHS patients; no significant changes were observed in CHF patients. After 12 to 24 hours of NIV, the mean pH was 7.36 (0.04) for COPD patients, 7.36 (0.05) for OHS patients, and 7.25 (0.1) for CHF patients (not significant). The mortality rate was 11.1% for COPD, 0% for OHS, and 33.3% for CHS (not significant, P=.076). CONCLUSIONS: In this group of patients with similar initial arterial blood gas values, response to NIV was seen to be better in OHS and COPD than in CHF. That the start of NIV is usually preceded by a poor response to conventional COPD treatment suggests that delaying NIV should be reconsidered