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.

Long-term myocardial effects of noninvasive ventilation in patients with obesity hypoventilation syndrome.

INTRODUCTION: Chronic effects of noninvasive ventilation on myocardial function in patients with obesity hypoventilation syndrome (OHS) are scarcely understood. The aim of the present study was to evaluate the long-term effects of volume-targeted bilevel positive airway pressure ventilation (BiPAP) on cardiac parameters and myocardial biomarkers in patients with OHS. METHODS: Clinically stable patients with OHS referred to the tertiary center for the initiation of long-term BiPAP therapy were consecutively enrolled. At baseline, all participants underwent overnight cardiorespiratory polygraphy. BiPAP therapy using volume-targeted spontaneous/timed mode delivered via an oro-nasal mask was initiated. Beat-to-beat noninvasive monitoring by impedance cardiography was used to assess heart function at baseline and after 3 and 12 months of BiPAP use. Serum troponin 1, N-Terminal Pro-B-Type Natriuretic Peptide (NT-ProBNP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) were monitored. RESULTS: Thirteen patients (10 men; mean age, 55.8 ± 9.8 years; mean body mass index of 47.8 ± 5.9 kg/m2) were recruited. From baseline to 3, and to 12 months of BiPAP use, left ventricular stroke volume (SV), ejection time (LVET), and ejection time index significantly increased (P = 0.030; P < 0.001; P = 0.003, respectively), while heart rate and systolic time ratio significantly decreased (P = 0.004; P = 0.034, respectively). Reductions in serum NT-proBNP, IL-6 and TNF-α were observed (P = 0.045; P = 0.018; P = 0.003, respectively). No significant changes in serum troponin were detected throughout the study. CONCLUSIONS: The present findings of increased SV, in association with lengthening of LVET, reductions of NT-proBNP and reductions in circulatory inflammatory markers in patients with stable OHS and chronic moderate-to-severe daytime hypercapnia treated with BiPAP over 1 year support the role of this therapeutic mode in such patients.

Comparison of Percutaneous Coronary Intervention Outcomes Among Patients With Obstructive Sleep Apnea, Chronic Obstructive Pulmonary Disease Overlap, and Pickwickian Syndrome (Obesity Hypoventilation Syndrome).

Background Obstructive sleep apnea (OSA) is often present in coronary artery disease patients and confers a high risk of complications following percutaneous coronary interventions (PCI). The impact of two commonly associated comorbid conditions, chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome (OHS, Pickwickian syndrome) in OSA patients undergoing PCI has never been studied. Methods The National Inpatient Sample (NIS; 2007-2014) was queried using the International Classification of Diseases, Clinical Modification 9 (ICD-9-CM) codes to compare baseline characteristics, comorbidities, and outcomes in adults undergoing PCI with OSA, COPD-overlap syndrome, and OSA+OHS. Results Of a total of 4,792,177 PCI-related inpatient encounters, OSA, OSA-COPD overlap syndrome, and OSA+OHS were found to be present in 153,706 (median age 62 years, 79.4% male), 65135 (median age 65 years, 66.0% male), and 2291 (median age 63 years, 58.2% males) patients, respectively. The OHS+OSA cohort, when compared to the COPD-OSA and OSA cohorts, was found to have the worst outcomes in terms of all-cause mortality (2.8% vs. 1.5% vs. 1.1%), hospital stay (median 6 vs. 3 vs. 2 days), hospital charges ($147, 209 vs. $101,416 vs. $87,983). Complications, including cardiogenic shock (7.3% vs. 3.4% vs. 2.6%), post-procedural myocardial infarction (11.2% vs. 7.1% vs. 6.0%), iatrogenic cardiac complications (6.1% vs. 3.5% vs. 3.7%), respiratory failure, acute kidney injury, infections, and pulmonary embolism, were also significantly higher in patients with OHS+OSA. Adjusted multivariable analysis revealed equivalent results with OHS+OSA having worse outcomes than OSA-COPD and OSA. Conclusion Concomitant OHS and COPD were linked to worse clinical outcomes in patients with OSA undergoing PCI. Future prospective studies are warranted to fully understand related pathophysiology, evaluate and validate long-term outcomes, and formulate effective preventive and management strategies.

A Clinical Encounter With Pickwickian Syndrome.

The clinical syndrome described in the literature as "Pickwickian syndrome" is characterized by a combination of sleep-disordered breathing, obesity, and daytime hypercapnia; the condition is also known as obesity hypoventilation syndrome (OHS). This syndrome is a diagnosis of exclusion after every other possible etiology is ruled out. Patients can present both with an exacerbation of or a chronic state of progressive dyspnea. In this report, we describe the case of a 62-year-old morbidly obese female with a BMI of 42 Kg/m2, who presented with progressively worsening breathlessness. An arterial blood gas (ABG) analysis revealed severe hypoxia with hypercarbia. A sleep study [polysomnography (PSG)] of the patient was performed, which revealed an apnea-hypopnea index (AHI) of 58.2, and the patient was diagnosed as having OHS after all other possible cardiorespiratory etiologies were ruled out. The patient was promptly managed with non-invasive ventilatory (NIV) support along with supportive management and was prescribed overnight NIV and subsequently discharged in stable condition.

Adherence to Positive Airway Pressure Therapy in Obesity Hypoventilation Syndrome.

Because of the prevalence of extreme obesity in the United States, there has been an increase in prevalence of obesity hypoventilation syndrome (OHS). There is limited information on the characteristics and pattern of positive airway pressure (PAP) adherence in patients with OHS compared with eucapnic patients with obstructive sleep apnea (OSA). This article discusses in detail the impact of PAP therapy on outcomes in patients with OHS, compares adherence between continuous PAP and noninvasive ventilation in OHS, and compares PAP adherence in patients with OHS to patients with moderate to severe OSA enrolled in clinical trials designed to improve CPAP adherence.

The Role of Positive Airway Pressure Therapy in Adults with Obesity Hypoventilation Syndrome. A Systematic Review and Meta-Analysis.

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable complication of severe obesity. Although weight loss is an accepted component of management, it is difficult to achieve and sustain the degree of weight loss necessary to reverse OHS. As such, positive airway pressure (PAP) during sleep has become the cornerstone therapy for most patients with OHS. However, the value of PAP therapy remains uncertain.Objective: To perform a systematic review to determine whether adults with OHS should be treated with PAP therapy or not.Methods: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. MEDLINE, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that compared PAP therapy (i.e., continuous PAP or noninvasive ventilation) to no PAP therapy in patients with OHS. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to appraise the quality of evidence.Results: The search identified 2,994 unique articles. The full text of 56 articles was reviewed, and 25 studies were selected, including 3 randomized trials, 12 nonrandomized comparative studies, and 10 randomized and nonrandomized studies without a comparator group. Sample size ranged from 21 to 1,527 patients. PAP was associated with increased resolution of OHS and improvements in mortality, gas exchange, daytime sleepiness, sleep quality, quality of life, and emergency department visits. Nearly half of patients experienced trivial adverse effects related to PAP therapy. Certainty in the estimated effects was low or very low for most outcomes.Conclusions: The panel made a conditional (i.e., weak) recommendation that PAP therapy during sleep be offered to patients with OHS to improve outcomes. This recommendation was based on very low-quality evidence.

The Effect of Hospital Discharge with Empiric Noninvasive Ventilation on Mortality in Hospitalized Patients with Obesity Hypoventilation Syndrome. An Individual Patient Data Meta-Analysis.

Rationale: Hospitalized patients with acute-on-chronic hypercapnic respiratory failure due to obesity hypoventilation syndrome (OHS) have increased short-term mortality. It is unknown whether prescribing empiric positive airway pressure (PAP) at the time of hospital discharge reduces mortality compared with waiting for an outpatient evaluation (i.e., outpatient sleep study and outpatient PAP titration).Objectives: An international, multidisciplinary panel of experts developed clinical practice guidelines on OHS for the American Thoracic Society. The guideline panel asked whether hospitalized adult patients with acute-on-chronic hypercapnic respiratory failure suspected of having OHS, in whom the diagnosis has not yet been made, should be discharged from the hospital with or without empiric PAP treatment until the diagnosis of OHS is either confirmed or ruled out.Methods: A systematic review with individual patient data meta-analyses was performed to inform the guideline panel's recommendation. Grading of Recommendations, Assessment, Development, and Evaluation was used to summarize evidence and appraise quality.Results: The literature search identified 2,994 articles. There were no randomized trials. Ten studies met a priori study selection criteria, including two nonrandomized comparative studies and eight nonrandomized noncomparative studies. Individual patient data on hospitalized patients who survived to hospital discharge were obtained from nine of the studies and included a total of 1,162 patients (1,043 discharged with PAP and 119 discharged without PAP). Empiric noninvasive ventilation was prescribed in 91.5% of patients discharged on PAP, and the remainder received empiric continuous PAP. Discharge with PAP reduced mortality at 3 months (relative risk 0.12, 95% confidence interval 0.05-0.30, risk difference -14.5%). Certainty in the estimated effects was very low.Conclusions: Hospital discharge with PAP reduces mortality following acute-on-chronic hypercapnic respiratory failure in patients with OHS or suspected of having OHS. Well-designed clinical trials are needed to confirm this finding.

Noninvasive Ventilation versus CPAP as Initial Treatment of Obesity Hypoventilation Syndrome.

Rationale: Obesity hypoventilation syndrome (OHS) is an undesirable consequence of obesity. Treatment consists of weight loss and positive airway pressure (PAP) therapy. However, the preferred mode of PAP is uncertain.Objectives: To perform a systematic review to determine whether PAP therapy should be initiated as noninvasive ventilation (NIV) or continuous PAP (CPAP) in ambulatory patients with OHS.Methods: This systematic review informed an international, multidisciplinary panel of experts who had converged to develop a clinical practice guideline on OHS for the American Thoracic Society. MEDLINE, the Cochrane Library, and Embase were searched from January 1946 to March 2019 for studies that compared initial treatment with NIV to CPAP in OHS. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to appraise the quality of evidence.Results: The search identified 2,994 potentially relevant articles, the full text of 21 articles was reviewed, and five articles were selected. The five articles included three randomized trials (one reported as two articles) and an observational study. The sample size ranged from 36 to 225 subjects. The evidence showed no differences in mortality, cardiovascular events, and healthcare resource use between patients with OHS treated with NIV or CPAP. Both PAP modalities were similarly effective in improving gas exchange, the need for supplemental oxygen, daytime sleepiness, sleep quality, quality of life, dyspnea, and sleep-disordered breathing. There was also no significant difference in adherence to NIV or CPAP therapy. Certainty in the estimated effects was low or very low for some outcomes. Therefore, the conditional recommendation was based on very low-quality evidence.Conclusions: The panel made a conditional (i.e., weak) recommendation that CPAP rather than NIV be offered as the first-line treatment to stable ambulatory patients with OHS and coexistent severe obstructive sleep apnea (OSA). The effectiveness of CPAP is similar to that of NIV, but NIV is more costly and requires more resources than CPAP. Given that approximately 70% of patients with OHS have coexistent severe OSA, this recommendation applies to the great majority of patients with stable OHS, but it should not be extrapolated to patients with OHS without severe OSA. Patients of advanced age, with poor lung function, or with greater or recent acute ventilatory failure may not respond adequately to CPAP.

Lesson of the month 1: Obesity hypoventilation (Pickwickian) syndrome: a reversible cause of severe pulmonary hypertension.

Obesity hypoventilation syndrome (OHS) is a condition in which an individual with a body mass index >30 kg/m2 develops daytime alveolar hypoventilation (defined as a resting PaCO2 >45 mmHg) that cannot be attributed to other pathologies. It is a condition with increasing prevalence and rising cost to healthcare systems worldwide. Right heart failure and pulmonary hypertension are well-known complications of this syndrome. Here, we present the case of a female patient with OHS who presented to our centre with severe pulmonary hypertension, which resolved with appropriate treatment. We also review this clinical condition and its diagnosis and management.

Obesity hypoventilation syndrome in obstructive sleep apnea patients in the United Arab Emirates: a retrospective cross-sectional study.

OBJECTIVES: To estimate the frequency of symptoms of obesity hypoventilation syndrome (OHS) in patients with obstructive sleep apnoea (OSA) and to evaluate comorbidities associated with OHS. DESIGN: Retrospective study based on patients' medical records and on further sleep tests performed in the study centre during the inclusion visit. SETTING: Respiratory Care Unit and Sleep Disorder Centre of the Zayed Military Hospital United Arab Emirates. PARTICIPANTS: All patients referred to the study centre for a suspicion of sleep-disordered breathing. MAIN OUTCOME MEASURES: Prevalence of OSA and OSA + OHS and comorbidities in patients with OSA and OHS. RESULTS: A total of 212 adult patients participated in the study. Of these, 107 patients (50.5% [43.8-57.1% CI 95%]) fulfilled diagnostic criteria for OSA, and the majority were men (79.4%). Among patients with OSA, 18 patients (16.8% [10.8-25.1% CI 95%]) fulfilled diagnostic criteria for OHS. In this group, women were more frequently affected than men (31.8% [7/22] vs. 12.9% [11/85], respectively; p = 0.03) and tended to be older than affected men, with a mean age of 55 ± 10.6 years versus 46 ± 13 for men. After adjustment for gender, OHS was significantly associated with hypertension (OR = 3.5; p = 0.03), diabetes mellitus (OR = 4.6; p = 0.02), ischaemic heart disease (OR = 5.1; p = 0.04) and pulmonary hypertension (OR = 16.1; p = 0.001). CONCLUSION: OHS is a common condition in obese patients in the UAE and is associated with an increased risk of cardiovascular comorbidities and diabetes.

Charles Dickens: impact on medicine and society.

In 1836 Charles Dickens published the first installment of The Posthumous Papers of the Pickwick Club. In this novel he introduces the reader to a character, Joe, the Fat Boy who is obese, sleepy, difficult to arouse, snores, and has peripheral edema. This description so intrigued the medical field that many hypotheses about the symptoms were examined, but it was not until 120 years after the novel was published that physicians started to interrelate these features and a new field of medicine emerged. Although he is best known for this description, Dickens impacted medicine and medical care in many ways. Besides his brilliant clinical descriptions (many of which were unrecognized in his day) and his activities as a social reformer, he was instrumental in facilitating the development of homeless shelters for women, the first pediatric hospital in the United Kingdom, and the development of orthopedics.

La neurología en un personaje de Dickens: síndrome pickwickiano, apneas hipopneas del sueño e hipertensión intracraneal

En muchos casos, la literatura de ficción se ha adelantado a la ciencia. Charles Dickens (1812-1870) pobló su obra con un tropel de notables personajes. Como la mayoría de los grandes novelistas, le adornaban finos dotes de observación y una extraordinaria capacidad descriptiva. Uno de sus protagonistas secundarios se ganó un puesto en los anales de la medicina. El logro de esta empresa se da al presentarnos la figura de un sirviente gordo y somnoliento llamado Joe, que a pesar de tener un pequeño y breve rol en el capítulo 54 de sus “Pickwick Papers” (1836), ha trascendido al lenguaje médico diario. La cómica caricatura que caracteriza al individuo obeso, sobrevivió en el ámbito de la medicina como un caso clásico de apneas del sueño: el síndrome de Pickwick o más precisamente, el síndrome Pickwickiano. Debieron transcurrir más de 120 años para que Burwell y sus colaboradores, hallaran una explicación fisiopatológicaal fenotipo de Joe, ese “niño gordinflón, rosado y roncador con la respiración entrecortada, eternamente somnoliento”,describiendo así, la presencia del síndrome apneashipopneas del sueño e hipoventilación alveolar en el sujeto obeso. La presencia de hipertensión intracraneal es otro de sus infrecuentes componentes. Describimos una serie de cuatro pacientes

In many cases, fictional literature has preceded science. Charles Dickens (1812-1870) filled his novels with anumber of noteworthy characters. As most great novelists, he possessed fine observation skills and an extraordinary capacity for description. In fact, one of his secondary characters gained a place in the world of medicine. From the “Pickwick Papers” (1836), Joe, the overweight and lazy servant, in spite of his brief appearance in chapter 54, has transcended to become part of the physician’s every day lingo. The amusing depiction that characterizes the overweight individual, survived in the medical world as the classic case of sleep apneas, the Pickwick syndrome or more precisely, the Pickwickian syndrome. After 120 years Burwell and his collaborators found a physiopathological explanation to the phenotype of Joe, ¨that fat and red-faced, chubby, plump and wheeze boy, in a state of somnolence”, so describing the presence of sleep apneas hypopneas and alveolar hypoventilation in obese individuals. The presence of intracranial hypertension is another of its infrequent components. We described a series of 4 of such cases.