Continuous Positive Airway Pressure Ventilation for Acute Ischemic Stroke
A Randomized Feasibility Study
Background and Purpose—Sleep-related breathing disorders occur frequently after stroke. We assessed the feasibility of continuous positive airway pressure (CPAP) treatment initiated in the first night after stroke.
Methods—In this open-label, parallel-group trial, 50 patients were randomly assigned to the CPAP therapy or to the control group. All patients underwent polysomnography in the fourth night. Intervention patients received CPAP therapy for 3 nights starting the first night after stroke onset and for an additional 4 nights when polysomnography revealed an apnea–hypopnea index >10/hour. The primary end point was feasibility defined as apnea–hypopnea index reduction under CPAP treatment, nursing workload, and CPAP adherence.
Results—The apnea–hypopnea index under CPAP treatment was significantly reduced (32.2±25.3–9.8±6.6, P=0.0001). Nursing workload did not significantly differ between the CPAP (n=25) and the control group (n=25; P=0.741). Ten patients (40.0%) had excellent CPAP use, 14 patients (56.0%) had some use, and 1 patient (4.0%) had no use. There was a trend toward greater National Institutes of Health Stroke Scale score improvement until Day 8 in patients on CPAP (2.00 versus 1.40, P=0.092) and a significantly greater National Institutes of Health Stroke Scale score improvement in patients with excellent CPAP use when compared with control patients (2.30 versus 1.40, P=0.022).
Conclusions—CPAP therapy initiated in the first night after stroke seems to be feasible and was not associated with neurological deterioration.
Sleep-related breathing disorder, including obstructive and central sleep apnea, is a frequent complication after ischemic stroke.1 It occurs in the initial phase of stroke and can improve spontaneously over weeks or months.2 Sleep-related breathing disorder is associated with early neurological worsening and poor outcome.1 The underlying mechanism was assumed to be sleep apnea-induced hypercapnia with subsequent cerebral vasodilatation aside the ischemic area and steal of blood from ischemic areas.3 Continuous positive airway pressure (CPAP) was shown to be feasible and likely to be beneficial for functional recovery when applied in the chronic phase after stroke in patients with obstructive sleep apnea.4 Comprehensive studies on the feasibility and efficacy of CPAP therapy in the acute phase after stroke are lacking so far. CPAP therapy, however, might be of particular benefit early after stroke onset because hemodynamic disturbances due to sleep apnea have markedly detrimental effects at this stage. We therefore conducted a study to assess the feasibility and efficacy of CPAP therapy initiated the first night after stroke.
This study was a randomized, open-label, parallel-group trial with blind assessment of outcomes performed at the comprehensive stroke unit of the University Hospital of Münster, Münster, Germany, a tertiary care center. For a summary of inclusion and exclusion criteria, see online-only Supplemental Table 1 (http://stroke.ahajournals.org). The study was approved by the local ethics committee. All patients gave written informed consent before enrollment. Assessment of baseline measures is described in the Supplemental Methods.
Eligible patients were randomly assigned to the intervention or control group. Intervention patients received noninvasive autoadjust CPAP therapy (pressure support 6–16 cm H2O, full face mask; Horizon, Devilbis) for 3 nights starting the first night after stroke onset. All patients underwent polysomnography the fourth night after stroke onset using a portable cardiorespiratory recording device (Somnoscreen; Somnomedics). Patients in the intervention group with an apnea–hypopnea index (AHI) >10/hour received further CPAP treatment.
The primary end point was feasibility defined by reduction in AHI with CPAP, CPAP adherence, and nursing workload (Supplemental Methods) within the first 3 nights. Therapy adherence was classified into 3 categories as previously published.5 Excellent CPAP use was defined as mean use >4 hours per night in the first 3 nights. Because CPAP treatment might be more beneficial when started early after stroke onset, this category additionally required CPAP use of >4 hours in the first night. Further categories were no use and some use (defined as less than excellent use). Secondary end point was infarct growth between the first day and follow-up imaging measured by diffusion-weighted MRI. As further efficacy end points, the National Institutes of Health Stroke Scale (NIHSS) score improvement on Day 8 was defined. For the description of statistical analyses, see Supplemental Methods.
Between April 2005 and August 2007, 50 patients were randomly assigned to either CPAP therapy plus standard care (n=25) or standard care alone (n=25). Regarding baseline characteristics, no significant differences were observed between the 2 groups (Table 1). Polysomnography results of both groups at Night 4 were similar (online-only Supplemental Table 2), except that there were more patients with sleep apnea in the CPAP group. Under CPAP therapy (1–3 nights), the AHI was significantly reduced when compared with the AHI at polysomnography at Night 4 (32.2±25.3–9.8±6.6, P=0.0001). The nursing workload did not significantly differ between groups (Table 2). Ten patients (40.0%) had excellent use, 14 patients (56.0%) had some use, and 1 patient (4.0%) had no use. Infarct growth did not differ between groups (Table 2). There was a trend toward greater NIHSS improvement until Day 8 in patients on CPAP when compared with control patients (2.00 versus 1.40, P=0.092). NIHSS improvement was significantly greater in patients with excellent CPAP use compared with the control group (2.30 versus 1.40, P=0.022). On assessing factors associated with therapy adherence, we found that a lower NIHSS score was significantly associated with excellent CPAP use (online-only Supplemental Table 3). There was a trend toward reduced CPAP use in patients with neglect and higher age. CPAP adherence in the first night was significantly associated with CPAP adherence in the second (P=0.04) and in the third (P=0.01) night.
The findings of this randomized trial show that CPAP therapy led to a significant AHI reduction in patients with acute stroke without increasing the nursing workload. CPAP adherence was reasonable because 10 patients had an excellent, 14 patients had some, and 1 patient had no CPAP use. For the efficacy outcomes, our study showed a trend toward a NIHSS score improvement for the CPAP group and a significant NIHSS score improvement in patients on CPAP with excellent therapy adherence. So far CPAP therapy for stroke was only investigated in the subacute and chronic phases after stroke.4,6 CPAP adherence in our study is comparable to that reported in these studies.4,5 A recent study showed that CPAP treatment initiated between 3 and 6 days after stroke did not improve clinical outcome at 24 months.6 Pathophysiological considerations suggest that treatment was started too late in this study to improve outcome because a failure of cerebral blood regulation was assumed to mediate the sleep-related breathing disorder-related clinical deterioration, which in turn requires early treatment initiation.
The major limitations of our study are the small sample size and the short time of follow-up as it was not powered to detect significant differences of functional recovery between the groups. Moreover, CPAP-treated patients were more often treated with thrombolysis and patients with excellent CPAP use had lower NIHSS scores on admission. Considering these potential biases, the results on NIHSS score improvement must certainly be interpreted with caution. Furthermore, deviating from the original study protocol, the modified Rankin Scale score at 3 months was not obtained, which further limits conclusions on functional outcome improvement in our study. In addition, the design of our study with the patients being aware of the treatment might result in a bias.
Our study is the first randomized trial that investigated the feasibility of CPAP therapy in patients with acute stroke. Compliance, which is 1 of the major drawbacks of CPAP treatment, was moderate without increasing the nursing workload. CPAP significantly reduced the AHI and might thereby improve clinical outcome after stroke. Our findings warrant further investigation in a larger trial, which potentially should exclude patients of older age, with high NIHSS score, and neglect.
Sources of Funding
This study was supported by Innovative Medizinische Forschung (IMF) of the Medical Faculty of the University of Münster (DZ 110413) and by DeVilbiss.
Bo Norrving, MD, PhD, was the Guest Editor for this paper.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.111.637611/-/DC1.
- Received August 29, 2011.
- Revision received October 18, 2011.
- Accepted October 24, 2011.
- © 2011 American Heart Association, Inc.
- Good DC,
- Henkle JQ,
- Gelber D,
- Welsh J,
- Verhulst S
- Alexandrov AV,
- Nguyen HT,
- Rubiera M,
- Alexandrov AW,
- Zhao L,
- Heliopoulos I,
- et al
- Ryan CM,
- Bayley M,
- Green R,
- Murray BJ,
- Bradley TD
- Bravata DM,
- Concato J,
- Fried T,
- Ranjbar N,
- Sadarangani T,
- McClain V,
- et al
- Parra O,
- Sánchez-Armengol M,
- Bonnin M,
- Arboix A,
- Campos-Rodriguez F,
- Pérez-Ronchel J,
- et al