Positive Airway Pressure Titration in Obesity Hypoventilation Syndrome: Continuous Positive Airway Pressure or Bilevel Positive Airway Pressure

Abstract

In the United States, a third of the adult population is obese and the prevalence of extreme obesity (body mass index [BMI] ≥ 40 kg/m2) is increasing rapidly. From 1986 to 2000, the prevalence of BMI ≥ 40 kg/m2 has quadrupled, and that of BMI ≥ 50 kg/m2 has increased fivefold.1Freedman DS Khan LK Serdula MK et al.Trends and correlates of class 3 obesity in the United States from 1990 through 2000.JAMA. 2002; 288: 1758-1761Crossref PubMed Scopus (387) Google Scholar The obesity epidemic is not only impacting adults in the United States, it is a global phenomenon affecting children and adolescents.2Spritzer DA Obesity epidemic migrates east [letter].Can Med Assoc J. 2004; 171: 1159Crossref PubMed Scopus (16) Google Scholar With such a global epidemic of obesity, the prevalence of obesity hypoventilation syndrome (OHS)—defined as a combination of obesity, awake chronic hypercapnia, and sleep-disordered breathing, in the absence of other known causes of hypercapnia—is likely to increase. In patients with OHS, sleep-disordered breathing can occur in three forms: obstructive apneas and hypopneas, obstructive hypoventilation due to increased upper airway resistance, and central hypoventilation.3Berger KI Ayappa I Chatr-Amontri B et al.Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep.Chest. 2001; 120: 1231-1238Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar4Kessler R Chaouat A Schinkewitch P et al.The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases.Chest. 2001; 120: 369-376Abstract Full Text Full Text PDF PubMed Scopus (330) Google Scholar In approximately 90% of patients with OHS, the sleep-disordered breathing consists predominantly of obstructive apneas and hypopneas (obstructive sleep apnea [OSA]).4Kessler R Chaouat A Schinkewitch P et al.The obesity-hypoventilation syndrome revisited: a prospective study of 34 consecutive cases.Chest. 2001; 120: 369-376Abstract Full Text Full Text PDF PubMed Scopus (330) Google Scholar5Perez de Llano LA Golpe R Ortiz Piquer M et al.Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome.Chest. 2005; 128: 587-594Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar6Mokhlesi B Tulaimat A Faibussowitsch I et al.Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea.Sleep Breath. 2006; (Dec 23; [Epub ahead of print])Google Scholar In patients with OSA and extreme obesity, the prevalence of OHS is as high as 25%.6Mokhlesi B Tulaimat A Faibussowitsch I et al.Obesity hypoventilation syndrome: prevalence and predictors in patients with obstructive sleep apnea.Sleep Breath. 2006; (Dec 23; [Epub ahead of print])Google Scholar7Laaban JP Chailleux E Daytime hypercapnia in adult patients with obstructive sleep apnea syndrome in France, before initiating nocturnal nasal continuous positive airway pressure therapy.Chest. 2005; 127: 710-715Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar Patients with OHS have a lower quality of life with increased health-care expenses and are at higher risk for pulmonary hypertension and early mortality when compared to eucapnic patients with similar degrees of obesity with or without OSA.8Hida W Quality of life in obesity hypoventilation syndrome.Sleep Breath. 2003; 7: 1-2Crossref PubMed Scopus (23) Google Scholar9Nowbar S Burkart KM Gonzales R et al.Obesity-associated hypoventilation in hospitalized patients: prevalence, effects, and outcome.Am J Med. 2004; 116: 1-7Abstract Full Text Full Text PDF PubMed Scopus (395) Google Scholar10Berg G Delaive K Manfreda J et al.The use of health-care resources in obesity-hypoventilation syndrome.Chest. 2001; 120: 377-383Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar Although the optimal management of patients with OHS remains uncertain, early recognition and treatment with positive airway pressure (PAP) therapy reduces the high burden of morbidity and mortality associated with this syndrome.5Perez de Llano LA Golpe R Ortiz Piquer M et al.Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome.Chest. 2005; 128: 587-594Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar10Berg G Delaive K Manfreda J et al.The use of health-care resources in obesity-hypoventilation syndrome.Chest. 2001; 120: 377-383Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar11Heinemann Budweiser S Dobroschke J et al.Non-invasive positive pressure ventilation improves lung volumes in the obesity hypoventilation syndrome.Respir Med. 2006; (Dec 11 [Epub ahead of print])PubMed Google Scholar While PAP is the mainstay of therapy in OHS, there is no standard protocol for its titration.12Stepanski EJ The need for a standardized CPAP titration protocol and follow-up procedures [letter].J Clin Sleep Med. 2005; 1: 311PubMed Google Scholar Continuous positive airway pressure (CPAP) and bilevel PAP, also known as noninvasive positive pressure ventilation, are the two most common modes of delivering PAP. Given that the majority of patients with OHS have concomitant severe OSA, treatment with CPAP seems reasonable.13Rapoport DM Sorkin B Garay SM et al.Reversal of the “Pickwickian syndrome” by long-term use of nocturnal nasal-airway pressure.N Engl J Med. 1982; 307: 931-933Crossref PubMed Scopus (101) Google Scholar14Sullivan CE Berthon-Jones M Issa FG Remission of severe obesity-hypoventilation syndrome after short-term treatment during sleep with nasal continuous positive airway pressure.Am Rev Respir Dis. 1983; 128: 177-181Crossref PubMed Scopus (126) Google Scholar15Mokhlesi B Tulaimat A Evans AT et al.Impact of adherence with positive airway pressure therapy on hypercapnia in obstructive sleep apnea.J Clin Sleep Med. 2006; 2: 57-62Crossref PubMed Scopus (132) Google Scholar In contrast to OSA, the response to CPAP titration in patients with OHS has not been systematically evaluated. In this issue of CHEST (see page 1678), Banerjee and colleagues16Banerjee D Yee BJ Piper AJ et al.Obesity hypoventilation syndrome: Hypoxemia during continuous positive airway pressure.Chest. 2007; 131: 1678-1684Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar provide new insights on the treatment of OHS. These investigators compared the impact of CPAP titration on the sleep architecture, respiratory events, and nocturnal hypoxemia in 23 patients with OHS and 23 patients with eucapnic OSA matched for BMI, apnea-hypopnea index (AHI), and lung function. Both groups were extremely obese with severe sleep-disordered breathing, and those with OHS had significant daytime hypercapnia. The protocol included full-night diagnostic polysomnography followed by a full night of CPAP titration without supplemental oxygen therapy, and CPAP was titrated to eliminate apneas, hypopneas, and any evidence of flow limitation. CPAP resolved sleep-disordered breathing and nocturnal hypoxemia in 57% of patients with OHS. The optimal CPAP pressure of 13.9 ± 3.1 cm H2O was reached within 1 h of sleep onset. CPAP was unable to resolve refractory hypoxemia in 43% of patients with OHS, and these patients had a higher BMI, more severe nocturnal hypoxemia at baseline, and a higher residual AHI during the night of CPAP titration compared to those with successful titration. Overall, CPAP led to significant increase in rapid eye movement sleep and significant reduction in arousal index and AHI in both patients with eucapnic OSA and OHS. What do these results tell us? The fact that more than half of the patients with extreme but stable cases of OHS (based on BMI, AHI, and the level of daytime hypercapnia) were successfully titrated with CPAP—without requiring bilevel PAP or supplemental oxygen—suggests that the majority of patients with milder forms of OHS can be successfully titrated with CPAP as well. However, given the lack of intermediate and long-term follow-up, it is difficult to establish whether outcomes with CPAP therapy would be similar to bilevel PAP therapy. Another limitation was the inability to reduce the AHI to < 25/h in the subgroup of patients with OHS that remained persistently hypoxemic during CPAP titration, suggestive of inadequate titration. It is plausible that higher CPAP pressures could further reduce the AHI and improve nocturnal hypoxemia. It is also important to point out that the findings of Banerjee et al do not apply to the subgroup of patients with OHS (10%) who do not have concomitant OSA. Two questions arise and remain to be addressed: (1) does persistent hypoxemia despite adequate CPAP titration improve with time, and (2) is CPAP plus supplemental oxygen superior to bilevel PAP? These questions are clinically relevant because of the higher costs associated with bilevel PAP and supplemental oxygen therapy. Banerjee and colleagues16Banerjee D Yee BJ Piper AJ et al.Obesity hypoventilation syndrome: Hypoxemia during continuous positive airway pressure.Chest. 2007; 131: 1678-1684Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar have provided convincing evidence that CPAP can be successfully titrated in the majority of patients with stable OHS, and their findings will give impetus for well-designed randomized controlled trials comparing long-term outcomes with different treatment modalities in patients with OHS. In the meantime, bilevel PAP should be considered the treatment of choice in patients with OHS if nocturnal hypoxemia is persistent despite an adequate CPAP titration. For bilevel PAP therapy to be successful, the inspiratory PAP needs to be at least 8 to 10 cm H2O above the final expiratory PAP required to eliminate all obstructive respiratory events.3Berger KI Ayappa I Chatr-Amontri B et al.Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep.Chest. 2001; 120: 1231-1238Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar5Perez de Llano LA Golpe R Ortiz Piquer M et al.Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome.Chest. 2005; 128: 587-594Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar17de Lucas-Ramos P de Miguel-Diez J Santacruz-Siminiani A et al.Benefits at 1 year of nocturnal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome.Respir Med. 2004; 98: 961-967Abstract Full Text Full Text PDF PubMed Scopus (91) Google Scholar Bilevel PAP should also be considered if daytime hypercapnia does not resolve after approximately 1 month of adequate adherence with CPAP therapy and in patients with OHS with acute on chronic respiratory failure. CPAP will also be ineffective in patients with OHS who do not have concomitant OSA (AHI < 5/h). Ultimately, the improvement in symptoms and blood gas levels are directly related to adherence with PAP therapy, and maximum improvement in blood gas levels can be achieved in as early as 2 to 4 weeks.15Mokhlesi B Tulaimat A Evans AT et al.Impact of adherence with positive airway pressure therapy on hypercapnia in obstructive sleep apnea.J Clin Sleep Med. 2006; 2: 57-62Crossref PubMed Scopus (132) Google Scholar Therefore, early follow-up is imperative and should include repeat measurement of arterial blood gas levels and objective assessment of adherence with PAP because patients frequently overestimate adherence. Changing bilevel PAP to CPAP and discontinuing oxygen therapy when no longer indicated can decrease the cost of therapy in patients with OHS.5Perez de Llano LA Golpe R Ortiz Piquer M et al.Short-term and long-term effects of nasal intermittent positive pressure ventilation in patients with obesity-hypoventilation syndrome.Chest. 2005; 128: 587-594Abstract Full Text Full Text PDF PubMed Scopus (238) Google Scholar