Autotitrating Bilevel Positive Airway Pressure in Large Vessel Steno-Occlusive Stroke Patients With Suspected Sleep Apnea: A Multicenter Randomized Controlled Study.

Kristian Barlinn,Heinz Reichmann,Ulf Bodechtel,Lars-Peder Pallesen,Oleg Y Chernyshev,Jessica Barlinn,Andrei V Alexandrov,Milan Vosko,Miriam Wienecke,Stanislava Jakubicek,Timo Siepmann,Volker Puetz,Anne W Alexandrov,Robert Mikulik,Wiebke Hermann,Xina Graehlert

doi:10.3389/fneur.2021.667494

Abstract

Background: We hypothesized that autotitrating bilevel positive airway pressure (auto-BPAP) favorably affects short-term clinical outcomes in hyperacute ischemic stroke.Methods: In a multicenter, randomized, controlled trial patients with large vessel steno-occlusive stroke and clinically suspected sleep apnea were allocated to auto-BPAP or standard stroke care alone. Auto-BPAP was initiated within 24 h from stroke onset and performed over 48 h during diurnal and nocturnal sleep. Sleep apnea was assessed using cardiorespiratory polygraphy. Primary endpoint was early neurological improvement on National Institutes of Health Stroke Scale (NIHSS) score at 72 h. Safety and tolerability of BPAP, functional independence [modified Rankin Scale (mRS) 0–2], stroke recurrence, and mortality at 90 days were assessed.Results: Due to low recruitment, the trial was prematurely stopped after 24 patients had been randomized (auto-BPAP, n = 14; control, n = 10): median baseline NIHSS 13 (5.5–18), 88% large vessel occlusion, and 12% large vessel stenosis. Polygraphy confirmed sleep apnea in 64% of auto-BPAP and 88% of control patients (p = 0.34). Adherence to auto-BPAP was achieved by 9 of the 14 (64%) patients. Between auto-BPAP and control patients, no differences were observed in early neurological improvement (median NIHSS change: −2.0, IQR = 7 points vs. −0.5, IQR = 3 points), 90 days functional independence (21 vs. 30%, p = 0.67), stroke recurrence (0 vs. 20%, p = 0.16), and death (14 vs. 20%, p = 1.0). No safety concerns were identified.Conclusions: In this prematurely terminated trial, auto-BPAP was safe but did not show an effect on short-term clinical outcomes in selected ischemic stroke patients. Its tolerability, however, may be limited in hyperacute stroke care and needs to be improved before larger trials are conducted.Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01812993.

Highlights

70% of stroke patients suffer from sleep apnea, and its presence is associated with early neurological worsening, adverse clinical outcomes, and increased mortality [1]
The primary objective of this study was to test the hypothesis that patients with large vessel steno-occlusive stroke and suspected sleep apnea may benefit from noninvasive ventilation with auto-bilevel positive airway pressure (BPAP) initiated within 24 h of symptom onset
Known sleep apnea currently on noninvasive ventilation, and premorbid modified Rankin scale score ≥3 were excluded from the study

Summary

Introduction

70% of stroke patients suffer from sleep apnea, and its presence is associated with early neurological worsening, adverse clinical outcomes, and increased mortality [1]. We recently hypothesized that intermittent hypercapnia in ischemic stroke patients with sleep apnea may further compromise perfusion in potentially salvageable brain tissue when vasodilation in the nonaffected brain region leads to blood flow diversion from ischemic area to the nonischemic regions [1]. This cerebral blood flow steal phenomenon was shown to be evident in ischemic stroke patients with large vessel occlusion and excessive daytime sleepiness, and it was associated with a four-fold risk of neurological deterioration, possibly the clinical surrogate for penumbra progression of infarction [5, 6]. We hypothesized that autotitrating bilevel positive airway pressure (auto-BPAP) favorably affects short-term clinical outcomes in hyperacute ischemic stroke

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Conclusion