The Effects of CPAP Withdrawal on Cerebral Vascular Reactivity and Brain Oxygenation in OSA

The Effects of Continuous Positive Airway Pressure Therapy Withdrawal on Cerebral Vascular Reactivity and Brain Oxygenation in Patients With Obstructive Sleep Apnoea: A Randomised Controlled Trial

Obstructive sleep apnoea (OSA) is a highly prevalent sleep-related breathing disorder associated with adverse cardiovascular outcome. Underlying mechanisms are subject of debate. A causal relationship between OSA and systemic hypertension as well as peripheral endothelial dysfunction was shown, and there is accumulating evidence from physiologic and observational studies that cerebral autoregulation is insufficient to protect the brain from the nocturnal consequences of OSA. However, there are no data from randomised controlled trials proving a causal relationship between OSA and impaired cerebral vascular reactivity (CVR). The aim of this randomised controlled trial is to study the effects of a short-term CPAP withdrawal, and thus returning OSA, on daytime CVR and brain oxygenation to establish whether there is a causal relationship between OSA and cerebral vascular damage.

Inclusion Criteria:

• Objectively confirmed OSA (at the time of original diagnosis) with an oxygen desaturation index (ODI) and apnoea-hypopnoea-index (AHI) of ≥20/h.
• Currently an oxygen desaturation index (≥4% dips) of ≥15/h during an ambulatory nocturnal pulse oximetry performed on the last night of a four-night period off CPAP.
• Treated with CPAP for more than 12 months
• Device usage >4h per night, >80% of the last 365 days, and AHI<10 with treatment (according to CPAP machine download data).
• Age between 20 and 75 years.
• Written informed consent as documented by signature.

Exclusion Criteria:

• Previous ischemic or haemorrhagic stroke; known cerebral aneurysm or arterio-venous malformation.
• Carotid artery stenosis > 70%
• Use of alpha- and beta-adrenergic blocking medication, antianginal medications, triptans, selective COX-inhibitors
• Unstable, untreated coronary or peripheral artery disease, severe arterial hypertension or hypotension (>180/110 or <90/60mmHg)
• Implanted pacemaker or internal cardiac defibrillator
• Changes in medication during the trial
• Previous ventilatory failure (awake SpO2 <93% andPaCO2>6kPa).
• Obesity hypoventilation syndrome, COPD
• Previously diagnosed with Cheyne-Stokes breathing.
• Current professional driver or any previous sleep related driving accidents.
• Caffeine or nicotine abuse 12 hours before measurements