May 01, 2019
4 min read

Noninvasive ventilation, CPAP yield similar long-term effectiveness in obesity hypoventilation syndrome

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In a new study from the Spanish Sleep Network, treatment with noninvasive ventilation or continuous positive airway pressure resulted in a similar number of hospitalization days per year during 5 years of follow-up in patients with obesity hypoventilation syndrome and severe obstructive sleep apnea.

During a median follow-up of 5.44 years, the number of hospitalization days per year — the primary outcome of the trial — was 1.63 days per patient-year among those assigned continuous positive airway pressure (CPAP) compared with 1.44 days per patient-year among those assigned noninvasive ventilation (adjusted RR = 0.78; 95% CI, 0.34-1.77).

This is the first long-term trial to compare the effectiveness of CPAP with noninvasive ventilation. The open-label, randomized controlled trial enrolled participants at 16 sites in Spain. Those enrolled were referred for pulmonary consultations due to suspected but untreated obesity hypoventilation syndrome or obstructive sleep apnea. In total, 100 patients were assigned to noninvasive ventilation and 115 to CPAP. The current data focus on 97 patients assigned noninvasive ventilation and 107 assigned CPAP.

“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,” Juan F. Masa, MD, PhD, with the respiratory department at San Pedro de Alcántara Hospital in Cáceres, Spain, and colleagues wrote in The Lancet.

However, “case-by-case follow-up assessment is recommended,” the researchers noted.

Similar outcomes

The data also revealed no significant differences in secondary outcomes of hospital resource utilization. During follow-up, 45% of the CPAP group vs. 53% of the noninvasive ventilation group reported at least one hospitalization (aHR = 1.12; 95% CI, 0.73-1.72), 62% of the CPAP group vs. 60% of the noninvasive ventilation group reported at least one emergency visit (aHR = 0.92; 95% CI, 0.62-1.35) and 6% of the CPAP group vs. 4% of the noninvasive ventilation group reported an ICU admission (aHR = 0.81; 95% CI, 0.22-3.06).

Fifteen percent of the CPAP group and 11% of the noninvasive ventilation group died during follow-up (aHR = 0.82; 95% CI, 0.36-1.87). The predominant cause of mortality was cardiovascular events. Cardiovascular-related mortality occurred in 56% of those assigned CPAP vs. 54% assigned noninvasive ventilation. The overall rate of cardiovascular events during follow-up was 15% in the CPAP group vs. 18% in the noninvasive ventilation group (aHR = 1.17; 95% CI, 0.56-2.42).


“This finding suggests that either treatment might reduce morbidity and mortality due to respiratory causes but has less effect on cardiovascular outcomes. However, it is important to acknowledge that without a control group in our trial, it is difficult to assess the long-term effect of continuous positive airway pressure or noninvasive ventilation therapy on cardiovascular outcomes in patients with obesity hypoventilation syndrome,” Masa and colleagues wrote. “Importantly, despite adequate adherence to positive airway pressure therapy, cardiovascular event rate remains clinically significant and highlights the importance of a holistic approach that includes emphasis not only on positive airway pressure therapy but also on body weight reduction, increased level of activity and appropriate management of comorbidities.”

In other results, patients assigned CPAP or noninvasive ventilation experienced improvements in blood pressure. Body weight was reduced at a similar rate in both groups. Improvements in clinical symptoms including dyspnea, lower-extremity edema, nocturia, fatigue, daytime sleepiness and headache were observed with both treatments.

The rate and occurrence of adverse events were similar in both groups.

Overall adherence to treatment was similar with both modalities, with most patients using CPAP or noninvasive ventilation for a median of 6 hours per day.

In a post hoc analysis, a higher level of adherence to either treatment modality was linked to fewer hospitalization days and lower hospital resource utilization and mortality, and the cost of CPAP was lower than noninvasive ventilation. However, the researchers cautioned that this analysis was exploratory.

‘Individualized management plan’

Obesity, which is a common cause of chronic respiratory failure, has an estimated prevalence of about 0.5% in the United States. Treatment of obesity hypoventilation syndrome, defined as a combination of obesity, daytime hypercapnia during wakefulness and sleep-disordered breathing in the absence of another cause of hypoventilation, remains a challenge, according to the researchers. Patients with obesity hypoventilation syndrome generally have increased cardiovascular and respiratory morbidity compared with patients with eucapnic obstructive sleep apnea, often resulting in higher risk for mortality, hospital admissions and health resource utilization. For the current study, obesity hypoventilation syndrome was defined as obesity with a BMI of at least 30 kg/m2, stable hypercapnic respiratory failure, no evidence of chronic obstructive pulmonary disease on spirometry, and no evidence of neuromuscular, chest wall or metabolic disease that could explain hypoventilation. The mean age in the CPAP group was 60 years and in the noninvasive ventilation group was 65 years. The CPAP group equally comprised men and women, but there were more women in the noninvasive ventilation group (63%).


Diagnosing this syndrome “provides important prognostic information and allows the delivery of focused risk management strategies,” Patrick B. Murphy, MBBS, PhD, Amanda J. Piper, BAppSc, MEd, PhD, and Nicholas Hart, MBBS, BSc, PhD, wrote in a related commentary published in The Lancet. Murphy and Hart are from the Lane Fox Respiratory Service at St. Thomas’ Hospital in London and Piper is from the NIHR Biomedical Research Center at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London.

“Furthermore, a proportion of patients with obesity hypoventilation syndrome will not have severe obstructive sleep apnea and so will require more careful consideration of ventilatory management as their cardiometabolic risks differ from those with severe obstructive sleep apnea. The treatment of obesity hypoventilation syndrome should continue as an individualized management plan incorporating weight loss, cardiometabolic risk reduction and a bespoke ventilatory plan,” Murphy and colleagues wrote in the commentary.

“The latter might now, with these data, more commonly start or finish with continuous positive airway pressure therapy with noninvasive ventilation utilized when respiratory failure is refractory or there are high-risk features, such as previous decompensated respiratory failure.” – by Katie Kalvaitis

Disclosures: The study was funded by the Instituto de Salud Carlos III, Spanish Respiratory Foundation and Air Liquide Spain. The authors report no relevant financial disclosures.