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.

Effect of continuous positive airway pressure on the incidence of hypertension and cardiovascular events in nonsleepy patients with obstructive sleep apnea: a randomized controlled trial.

CONTEXT: Continuous positive airway pressure (CPAP) is the first-line treatment for patients with symptomatic obstructive sleep apnea (OSA). However, its indication for all patients with sleep-disordered breathing, regardless of daytime symptoms, is unclear. OBJECTIVE: To evaluate the effect of CPAP treatment on the incidence of hypertension or cardiovascular events in a cohort of nonsleepy patients with OSA. DESIGN, SETTING, AND PATIENTS: Multicenter, parallel-group, randomized controlled trial in 14 teaching hospitals in Spain. Between May 2004 and May 2006, 725 consecutive patients were enrolled who had an apnea-hypopnea index of 20 h(-1) or greater and an Epworth Sleepiness Scale score of 10 or less (scores range from 0-24, with values <10 suggesting no daytime sleepiness). Exclusion criteria were previous cardiovascular event, physical or psychological incapacity, chronic disease, or drug or alcohol addiction. Follow-up ended in May 2009. INTERVENTION: Patients were allocated to receive CPAP treatment or no active intervention. All participants received dietary counseling and sleep hygiene advice. MAIN OUTCOME MEASURES: Incidence of either systemic hypertension (taking antihypertensive medication or blood pressure greater than 140/90 mm Hg) or cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack, hospitalization for unstable angina or arrhythmia, heart failure, or cardiovascular death). RESULTS: Seven hundred twenty-three patients underwent follow-up for a median of 4 (interquartile range, 2.7-4.4) years (1 patient from each group did not receive allocated treatment); 357 in the CPAP group and 366 in the control group were included in the analysis. In the CPAP group there were 68 patients with new hypertension and 28 cardiovascular events (17 unstable angina or arrhythmia, 3 nonfatal stroke, 3 heart failure, 2 nonfatal myocardial infarction, 2 transient ischemic attack, 1 cardiovascular death). In the control group there were 79 patients with new hypertension and 31 cardiovascular events (11 unstable angina or arrhythmia, 8 nonfatal myocardial infarction, 5 transient ischemic attack, 5 heart failure, 2 nonfatal stroke). The hypertension or cardiovascular event incidence density rate was 9.20 per 100 person-years (95% CI, 7.36-11.04) in the CPAP group and 11.02 per 100 person-years (95% CI, 8.96-13.08) in the control group. The incidence density ratio was 0.83 (95% CI, 0.63-1.1; P = .20). CONCLUSIONS: In patients with OSA without daytime sleepiness, the prescription of CPAP compared with usual care did not result in a statistically significant reduction in the incidence of hypertension or cardiovascular events. However, the study may have had limited power to detect a significant difference. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00127348.

[Resources and delays in the diagnosis of sleep apnea-hypopnea syndrome]. / Recursos y demoras en el diagnóstico del síndrome de apneas-hipopneas durante el sueño (SAHS).

OBJECTIVE: The demand for consultations and diagnostic studies for sleep apnea-hypopnea syndrome (SAHS) has increased, and this has led to considerable delays. We therefore need an updated evaluation of the diagnostic situation to serve as a management tool for specialists and health care administrations responsible for solving the problem. The objective of the present study was to carry out a descriptive analysis of the situation regarding the diagnosis of SAHS in Spanish hospitals. METHODS: We undertook a descriptive cross-sectional observational study. Public and private hospitals listed in the Ministry of Health's 2005 catalog of health care institutions were contacted, and those that routinely evaluate patients for SAHS were included in the study. The person in charge of each hospital filled in a questionnaire concerning the availability of resources and waiting periods for diagnosis. RESULTS: Of the 741 hospitals we contacted, 217 routinely evaluated patients for SAHS. In 88% of these, respiratory polygraphy (RP) (n=168) or polysomnography (PSG) (n=97) was available. The mean waiting period was 61 days for consultation and 224 days for RP. The mean number of RP systems was 0.99 per 100,000 inhabitants, while the recommended number is 3 per 100,000 inhabitants. The mean waiting period for PSG was 166 days. The mean number of PSG beds was 0.49 per 100,000 inhabitants, while the recommended number is 1 per 100,000. CONCLUSIONS: We observed a marked inadequacy of resources that has led to unacceptable waiting periods. While there has been a favorable change in the situation regarding SAHS diagnosis compared to previous studies, there is still room for improvement and it is urgent that healt hcare authorities allocate more resources to this public health problem.

Recursos y demoras en el diagnóstico del síndrome de apneas-hipopneas durante el sueño (SAHS) / Resources and delays in the diagnosis of sleep apnea-hypopnea syndrome

Objetivo: La demanda de consultas y estudios diagnósticos del síndrome de apneas-hipopneas durante el sueño (SAHS) se ha incrementado, lo que ha llevado a importantes demoras. Por tanto, es precisa una evaluación actualizada de la situación del diagnóstico que sirva como herramienta de gestión a especialistas y las administraciones sanitarias que tienen la responsabilidad de solventar el problema. El objetivo del presente estudio ha sido realizar un análisis descriptivo de la situación del diagnóstico del SAHS en los hospitales españoles. Métodos: Se ha realizado un estudio descriptivo, observacional y transversal. Se estableció contacto con los centros públicos y privados incluidos en el catálogo de instituciones sanitarias del Ministerio de Sanidad de 2005. Se incluyeron aquellos que evaluaban habitualmente a pacientes con SAHS. El responsable de cada centro rellenó un cuestionario sobre disponibilidad de recursos y demoras para el diagnóstico. Resultados: De los 741 centros con los que se estableció contacto, 217 evaluaban habitualmente a pacientes con SAHS. El 88% disponía de poligrafía respiratoria (PR) (n = 168) o polisomnografía (PSG) (n = 97). La demora media en consulta fue de 61 días, y la demora media para realizar PR, de 224 días. La media de equipos de PR fue de 0,99/100.000 habitantes, cuando lo recomendable es 3/100.000. La demora media para PSG fue de 166 días. La media de camas de PSG fue de 0,49/100.000 habitantes y lo recomendable es 1/100.000. Conclusiones: Se observa una notable deficiencia de recursos que lleva a inaceptables listas de espera. Aunque la situación del diagnóstico de SAHS ha cambiado favorablemente con respecto a estudios previos, sigue siendo mejorable y es imprescindible que las autoridades sanitarias dediquen más recursos a este problema de salud pública

Objective: The demand for consultations and diagnostic studies for sleep apnea-hypopnea syndrome (SAHS) has increased, and this has led to considerable delays. We therefore need an updated evaluation of the diagnostic situation to serve as a management tool for specialists and health care administrations responsible for solving the problem. The objective of the present study was to carry out a descriptive analysis of the situation regarding the diagnosis of SAHS in Spanish hospitals. Methods: We undertook a descriptive cross-sectional observational study. Public and private hospitals listed in the Ministry of Health's 2005 catalog of health care institutions were contacted, and those that routinely evaluate patients for SAHS were included in the study. The person in charge of each hospital filled in a questionnaire concerning the availability of resources and waiting periods for diagnosis. Results: Of the 741 hospitals we contacted, 217 routinely evaluated patients for SAHS. In 88% of these, respiratory polygraphy (RP) (n=168) or polysomnography (PSG) (n=97) was available. The mean waiting period was 61 days for consultation and 224 days for RP. The mean number of RP systems was 0.99 per 100 000 inhabitants, while the recommended number is 3 per 100 000 inhabitants. The mean waiting period for PSG was 166 days. The mean number of PSG beds was 0.49 per 100 000 inhabitants, while the recommended number is 1 per 100 000. Conclusions: We observed a marked inadequacy of resources that has led to unacceptable waiting periods. While there has been a favorable change in the situation regarding SAHS diagnosis compared to previous studies, there is still room for improvement and it is urgent that healt hcare authorities allocate more resources to this public health problem