Effect of Continuous Positive Airway Pressure on Stroke Rehabilitation: A Pilot Randomized Sham-Controlled Trial

Abstract

Study Objectives: Obstructive sleep apnea (OSA) predicts poor functional outcome after stroke and increases the risk for recurrent stroke. Less is known about continuous positive airway pressure (CPAP) treatment on stroke recovery. Methods: In a pilot randomized, double-blind, sham-controlled trial, adult stroke rehabilitation patients were assigned to auto-titrating or sham CPAP without diagnostic testing for OSA. Change in Functional Independence Measure (FIM), a measure of disability, was assessed between rehabilitation admission and discharge. Results: Over 18 months, 40 patients were enrolled and 10 withdrew from the study: 7 from active and 3 from sham CPAP (p > 0.10). For the remaining 30 patients, median duration of CPAP use was 14 days. Average CPAP use was 3.7 h/night, with at least 4 h nightly use among 15 patients. Adherence was not influenced by treatment assignment or stroke severity. In intention-to-treat analyses (n = 40), the median change in FIM favored active CPAP over sham but did not reach statistical significance (34 versus 26, p = 0.25), except for the cognitive component (6 versus 2.5, p = 0.04). The on-treatment analyses (n = 30) yielded similar results (total FIM: 32 versus 26, p = 0.11; cognitive FIM: 6 versus 2, p = 0.06). Conclusions: A sham-controlled CPAP trial among stroke rehabilitation patients was feasible in terms of recruitment, treatment without diagnostic testing and adequate blinding-though was limited by study retention and CPAP adherence. Despite these limitations, a trend towards a benefit of CPAP on recovery was evident. Tolerance and adherence must be improved before the full benefits of CPAP on recovery can be assessed in larger trials. I NTRO DUCTI O N Stroke is the leading cause of long-term disability in the UnitedStates, yet treatments that improve function after stroke are limited. Obstructive sleep apnea (OSA) is increasingly recognized as a risk factor for ischemic and hemorrhagic stroke, 1,2 with prevalence after stroke or transient ischemic attack estimated to be over 70%.3 Stroke patients with OSA compared to those without have worse functional outcome, longer hospitalization and rehabilitation stays, and higher mortality. [4][5][6][7][8][9] Despite the high risk of sleep apnea among patients with stroke and the implications for both stroke recovery and recurrent stroke, few stroke survivors undergo screening, testing, or treatment for OSA. 10 Barriers to evaluation and treatment involve OSA awareness among stroke survivors and clinical providers, access to in-laboratory polysomnography (PSG) testing, and the lack of consensus among stroke providers on the ideal timing for sleep testing.Treatment with continuous positive airway pressure (CPAP) among patients diagnosed with OSA is associated with improved functional and motor outcome after stroke, 11 but trials are limited by poor CPAP tolerance and adherence. 12,13 Compared to the general OSA population, patients with acute stroke are typically older with more functional disability and may have more diffic...

Sleep‐disordered breathing and poststroke outcomes

“…4 Pilot RCTs have evaluated the effect of CPAP on functional and cognitive outcomes, with mixed results. 6,16,18,[20][21][22][23][24] The majority of trials were conducted in stroke rehabilitation units or a limited number of hospitals, with sample sizes ranging from 30 to 252. Our results now suggest that functional and cognitive outcomes are reasonable targets for larger, adequately powered trials of the effectiveness of CPAP in improving stroke outcomes.…”

“…[16][17][18][19][20][21][22][23][24][25] If treatment with CPAP is shown to improve stroke outcomes in a larger, adequately powered clinical trial, treatment of SDB may be a viable, cost-efficient intervention strategy to improve stroke recovery. [16][17][18][19][20][21][22][23][24][25] If treatment with CPAP is shown to improve stroke outcomes in a larger, adequately powered clinical trial, treatment of SDB may be a viable, cost-efficient intervention strategy to improve stroke recovery.…”

“…Small randomized clinical trials (RCTs) have demonstrated that treatment of SDB with continuous positive airway pressure (CPAP) in select groups of stroke/transient ischemic attack (TIA) patients may improve functional outcome, cognitive outcome, neurologic recovery, and depressive symptoms, although results have not been conclusive. [16][17][18][19][20][21][22][23][24][25] If treatment with CPAP is shown to improve stroke outcomes in a larger, adequately powered clinical trial, treatment of SDB may be a viable, cost-efficient intervention strategy to improve stroke recovery. Observational data on the association of SDB with a variety of stroke outcomes could inform the most appropriate endpoints for future recovery trials of SDB treatment in stroke patients.…”

Impact of obstructive sleep apnoea and intermittent hypoxia on cardiovascular and cerebrovascular regulation

“…In cross-sectional analyses, Arzt et al (2005) found that subjects with an AHI of 5-19.9 had lower odds (OR = 0.49) whereas subjects with an AHI ࣙ 20 had higher odds (OR = 3.8) to have suffered a stroke than individuals without OSA (AHI ࣘ 5) after controlling for age, sex, BMI, alcohol consumption, cigarette smoking, hypertension and diabetes. Similarly, a recent double-blind randomized controlled trial comparing CPAP to sham-CPAP treatment of OSA in stroke patients found no significant benefit of CPAP on a functional independence measure aimed at assessing global disability (Khot et al 2016). Likewise, Yaggi et al (2005) reported OSA patients to be at higher risk of stroke compared with OSA-free control subjects [hazard ratio (HR) = 1.97] after controlling for age, sex, race, smoking status, alcohol consumption, BMI, diabetes, hyperlipidaemia, atrial fibrillation and hypertension.…”

“…In a longitudinal component consisting of a 4 year follow-up, after controlling for age, sex and BMI, subjects with an AHI between 5 and 19.9 at baseline had lower odds (OR = 0.29) whereas subjects with an AHI ࣙ 20 had higher odds (OR = 3.1) of suffering a first ever stroke compared with subjects with an AHI ࣘ 5, although these differences were not statistically significant. Unfortunately, these two randomized controlled trials (Ryan et al 2011;Khot et al 2016) had relatively small sample sizes and thus were likely to be statistically underpowered to observe an improvement in function. In addition, a stepwise increase in stroke risk and all-cause mortality was observed for increasing OSA severity, with the HR being 1.75 for mild OSA (AHI = 4-12), 1.74 for moderate OSA (AHI = 13-36) and 3.30 for severe OSA (AHI ࣙ 36) compared with individuals with an AHI ࣘ 3.…”