From MedPage Today
By Charles Bankhead, Staff Writer, MedPage Today
Published: August 13, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.
Obstructive sleep apnea (OSA) and its associated complications recurred rapidly after discontinuation of continuous positive airway pressure (CPAP), results of a small randomized trial showed.
After two weeks without CPAP, the number of arousal events per hour had more than tripled, and apnea-hypopnea events had increased 17-fold. Both measures remained unchanged in patients who continued CPAP.
OSA returned within days after stopping CPAP, as did subjective sleepiness, but objective measures of sleepiness did not change significantly.
By the end of the study, endothelial function had decreased significantly, and morning blood pressure, heart rate, and urinary catecholamines all increased significantly compared with patients who remained on CPAP.
"We found that CPAP withdrawal was associated with a return of OSA by the first night," Malcolm Kohler, MD, of University Hospital Zurich in Switzerland, and coauthors reported online in the American Journal of Respiratory and Critical Care Medicine.
The principal implications of the findings relate to clinical research in OSA, including studies of the physiologic effects of OSA and response to novel therapies, the authors added. The effect of CPAP withdrawal on sleep-disordered breathing and cardiovascular risk factors requires further study.
The effects of CPAP withdrawal on patients with diagnosed OSA previously have been evaluated only in uncontrolled trials, limiting the ability to draw definitive conclusions. The authors sought to clarify the effects in a randomized, controlled trial to examine a two-week trial of CPAP discontinuation.
Investigators queried a database of patients with OSA treated with CPAP and a sleep disorders center. Eligible adult patients had an oxygen desaturation index (ODI) >10/h in their initial sleep study and after four nights without CPAP, had used CPAP for more than 12 months, and had an average compliance of at least four hours per night.
After enrollment, all patients resumed CPAP for at least seven days and then were randomized to continue CPAP or switch to subtherapeutic CPAP for two weeks.
Investigators assessed patients' pulse oximetry nightly throughout the study period. Subjective sleepiness was evaluated at baseline and two weeks by means of the Epworth sleepiness score, and objective sleepiness was determined by a sleep resistance challenge at baseline and two weeks.
Patients completed a simulated driving test and a reaction-time task at baseline and two weeks to assess psychomotor performance at baseline and after two weeks.
Flow-mediated dilation was measured by ultrasound to assess endothelial function. Blood pressure and heart rate were measured three times daily through the study. Blood samples obtained at baseline and after two weeks were used to measure markers of systemic inflammation, insulin resistance, and lipids.
Patients provided 12-hour urine specimens at baseline and after two weeks for assessment of urinary catecholamines.
Investigators randomized 41 patients, 40 of whom completed the study. One patient in the subtherapeutic group dropped out after four days because of intolerable daytime symptoms.
Baseline characteristics, including sleep characteristics, did not differ significantly between groups.
When the study ended, patients in the subtherapeutic group had significant changes in multiple parameters compared with patients on continuous CPAP, including:
•Average arousal incidents - +20.7/h versus -0.6/h, P<0.001
•Apnea-hypopnea events - +33.8/h versus 0.4/h, P<0.001
•ODI events - +26.3/h versus -0.2, P<0.001
•Epworth score - +2.0 versus -0.7, P=0.001
•Morning blood pressure - +6.2/+4.4 versus -2.3/-2.5 mmHg, P=0.016, P=0.008
•Morning heart rate - +6.3 versus 0.0 bpm, P=0.035
•Flow-mediated dilation - -3.2% versus -1.7%, P<0.001
•Norepinephrine - +11.5 versus +0.9 nmol/mmol, P=0.012
Psychomotor performance did not change significantly in response to CPAP withdrawal, nor did markers of systemic inflammation, insulin resistance, or cholesterol.
The study was supported by the Swiss National Science Foundation and the Swiss Society of Pneumology.