Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea.

BACKGROUND: Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. METHODS: Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. RESULTS: A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI)  mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. CONCLUSIONS: NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality. TRIAL REGISTRATION NUMBER: NCT01405976; results.

Eficacia a medio y largo plazo de la ventilación no invasiva en el síndrome de hipoventilación-obesidad (estudio Pickwick) / Mid- and Long-Term Efficacy of Non-Invasive Ventilation in Obesity Hypoventilation Syndrome: The Pickwick's Study

El proyecto Pickwick es un estudio prospectivo, aleatorizado, abierto y controlado con grupos en paralelo que intenta dar respuesta a los interrogantes del síndrome de hipoventilación-obesidad (SHO), una enfermedad creciente en los países desarrollados. Para ello, pacientes con SHO fueron divididos en pacientes con índice de apneas-hipoapneas (IAH) ≥30 y <30 mediante polisomnografía. El grupo con IAH≥30 se aleatorizó a tratamiento mediante estilo de vida saludable, ventilación no invasiva (VNI) o presión en la vía aérea positiva continua (CPAP). El grupo con IAH<30, a VNI o estilo de vida saludable. Su objetivo ha sido evaluar la eficacia del tratamiento con ventilación VNI, CPAP y estilo de vida saludable (control) a medio y largo plazo en el SHO, analizando como variable primaria la PaCO2 y los días de hospitalización, respectivamente, y como variables operativas el porcentaje de abandonos por razones médicas y mortalidad. Los objetivos secundarios a medio plazo fueron: 1) evaluar la eficacia clínica-funcional, en calidad de vida, en variables polisomnográficas y ecocardiográficas; 2) investigar la importancia de los episodios apneicos y de la leptina en la génesis de la hipoventilación alveolar diurna y el cambio con los diferentes tratamientos; 3) investigar si las alteraciones metabólicas, bioquímicas y disfunción endotelial vascular dependen de la presencia de apneas e hipoapneas, y 4) cambio de marcadores inflamatorios y de daño endotelial con los tratamientos. Los objetivos secundarios a largo plazo fueron: 1) evaluar la eficacia clínico-funcional y en calidad de vida con VNI y CPAP; 2) cambio de la leptina, marcadores inflamatorios y de daño endotelial con los tratamientos; 3) cambio de la hipertensión pulmonar y otras variables ecocardiográficas, así como en la hipertensión arterial e incidencia de episodios cardiovasculares, y 4) frecuencia de abandonos y mortalidad

The Pickwick project was a prospective, randomized and controlled study, which addressed the issue of obesity hypoventilation syndrome (OHS), a growing problem in developed countries. OHS patients were divided according to apnea-hypopnea index (AHI) ≥ 30 and < 30 determined by polysomnography. The group with AHI ≥ 30 was randomized to intervention with lifestyle changes, noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP); the group with AHI < 30 received NIV or lifestyle changes. The aim of the study was to evaluate the efficacy of NIV treatment, CPAP and lifestyle changes (control) in the medium and long-term management of patients with OHS. The primary variables were PaCO2 and days of hospitalization, and operating variables were the percentage of dropouts for medical reasons and mortality. Secondary medium-term objectives were: (I) to evaluate clinical-functional effectiveness on quality of life, echocardiographic and polysomnographic variables; (II) to investigate the importance of apneic events and leptin in the pathogenesis of daytime alveolar hypoventilation and change according to the different treatments; (III) to investigate whether metabolic, biochemical and vascular endothelial dysfunction disorders depend on the presence of apneas and hypopneasm and (IV) changes in inflammatory markers and endothelial damage according to treatment. Secondary long-term objectives were to evaluate: (I) clinical and functional effectiveness and quality of life with NIV and CPAP; (II) changes in leptin, inflammatory markers and endothelial damage according to treatment; (III) changes in pulmonary hypertension and other echocardiographic variables, as well as blood pressure and incidence of cardiovascular events, and (IV) dropout rate and mortality

Mid- and Long-Term Efficacy of Non-Invasive Ventilation in Obesity Hypoventilation Syndrome: The Pickwick's Study.

The Pickwick project was a prospective, randomized and controlled study, which addressed the issue of obesity hypoventilation syndrome (OHS), a growing problem in developed countries. OHS patients were divided according to apnea-hypopnea index (AHI) ≥30 and <30 determined by polysomnography. The group with AHI≥30 was randomized to intervention with lifestyle changes, noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP); the group with AHI<30 received NIV or lifestyle changes. The aim of the study was to evaluate the efficacy of NIV treatment, CPAP and lifestyle changes (control) in the medium and long-term management of patients with OHS. The primary variables were PaCO2 and days of hospitalization, and operating variables were the percentage of dropouts for medical reasons and mortality. Secondary medium-term objectives were: (i)to evaluate clinical-functional effectiveness on quality of life, echocardiographic and polysomnographic variables; (ii)to investigate the importance of apneic events and leptin in the pathogenesis of daytime alveolar hypoventilation and change according to the different treatments; (ii)to investigate whether metabolic, biochemical and vascular endothelial dysfunction disorders depend on the presence of apneas and hypopneasm and (iv)changes in inflammatory markers and endothelial damage according to treatment. Secondary long-term objectives were to evaluate: (i)clinical and functional effectiveness and quality of life with NIV and CPAP; (ii)changes in leptin, inflammatory markers and endothelial damage according to treatment; (iii)changes in pulmonary hypertension and other echocardiographic variables, as well as blood pressure and incidence of cardiovascular events, and (iv)dropout rate and mortality.