The Stroke Oxygen Study (SO2S) - a multi-center, study to assess whether routine oxygen treatment in the first 72 hours after a stroke improves long-term outcome: study protocol for a randomized controlled trial.

BACKGROUND: Mild hypoxia is common in stroke patients and may have significant adverse effects on the ischemic brain after stroke. The use of oxygen treatment is rapidly increasing in European stroke units but is not without side effects. It impedes early mobilization, could pose an infection risk, and may encourage the formation of toxic free radicals, leading to further damage to the ischemic brain. In the Stroke Oxygen Pilot Study (2 or 3 L/min for 72 hours) neurological recovery at one week was better in the oxygen group than in controls, and after correction for difference in baseline stroke severity and prognostic factors, there was a trend to better outcome with oxygen at six months. Oxygen was as effective in mild as in severe strokes.Oxygen saturation is lower at night than during the day, and episodes of oxygen desaturation are common during sleep. Nocturnal oxygen supplementation is likely to reduce the burden of hypoxia without interfering with daytime mobilization and rehabilitation.Before wider use of oxygen supplementation becomes established it is important to obtain better evidence on which patients benefit from such treatment. METHODS: Participants will be randomized to one of three groups: the first will receive continuous oxygen for 72 hours (at a rate of 2 or 3 L/min depending on baseline oxygen saturation), the second group will receive nocturnal oxygen only (at a rate of 2 or 3 L/min depending on baseline oxygen saturation) and the third group will not receive any oxygen (control). A baseline assessment is performed at randomization and a one-week follow-up completed. Outcome data at three, six and twelve months will be obtained via a questionnaire sent to the patient by the trial center. DISCUSSION: This study will provide evidence on the effectiveness of oxygen supplementation for the treatment of stroke and whether nocturnal oxygen is a potentially beneficial therapy regimen. TRIAL REGISTRATION: This trial is registered with the ISRCTN register ID number ISRCTN52416964.

The stroke oxygen pilot study: a randomized controlled trial of the effects of routine oxygen supplementation early after acute stroke--effect on key outcomes at six months.

INTRODUCTION: Post-stroke hypoxia is common, and may adversely affect outcome. We have recently shown that oxygen supplementation may improve early neurological recovery. Here, we report the six-month outcomes of this pilot study. METHODS: Patients with a clinical diagnosis of acute stroke were randomized within 24 h of admission to oxygen supplementation at 2 or 3 L/min for 72 h or to control treatment (room air). Outcomes (see below) were assessed by postal questionnaire at 6 months. Analysis was by intention-to-treat, and statistical significance was set at p ≤ 0.05. RESULTS: Out of 301 patients randomized two refused/withdrew consent and 289 (148 in the oxygen and 141 in the control group) were included in the analysis: males 44%, 51%; mean (SD) age 73 (12), 71 (12); median (IQR) National Institutes of Health Stroke Scale score 6 (3, 10), 5 (3, 10) for the two groups respectively. At six months 22 (15%) patients in the oxygen group and 20 (14%) in the control group had died; mean survival in both groups was 162 days (p = 0.99). Median (IQR) scores for the primary outcome, the modified Rankin Scale, were 3 (1, 5) and 3 (1, 4) for the oxygen and control groups respectively. The covariate-adjusted odds ratio was 1.04 (95% CI 0.67, 1.60), indicating that the odds of a lower (i.e. better) score were non-significantly higher in the oxygen group (p = 0.86). The mean differences in the ability to perform basic (Barthel Index) and extended activities of daily living (NEADL), and quality of life (EuroQol) were also non-significant. CONCLUSIONS: None of the key outcomes differed at 6 months between the groups. Although not statistically significant and generally of small magnitude, the effects were predominantly in favour of the oxygen group; a larger trial, powered to show differences in longer-term functional outcomes, is now on-going. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN12362720; Eudract.ema.europa.eu 2004-001866-41.

The SOS pilot study: a RCT of routine oxygen supplementation early after acute stroke--effect on recovery of neurological function at one week.

UNLABELLED: Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke. METHODS: Patients with a clinical diagnosis of acute stroke were recruited within 24 h of hospital admission between October 2004 and April 2008. Participants were randomized to oxygen via nasal cannulae (72 h) or control (room air, oxygen given only if clinically indicated). Clinical outcomes were assessed by research team members at 1 week. Baseline data for oxygen (n = 148) and control (n = 141) did not differ between groups. RESULTS: The median (interquartile range) National Institutes of Health Stroke Scale (NIHSS) score for the groups at baseline was 6 (7) and 5 (7) respectively. The median Nocturnal Oxygen Saturation during treatment was 1.4% (0.3) higher in the oxygen than in the control group (p<0.001) during the intervention. At 1 week, the median NIHSS score had reduced by 2 (3) in the oxygen and by 1 (2) in the control group. 31% of participants in the oxygen group and 14% in the control group had an improvement of ≥4 NIHSS points at 1 week doubling the odds of improvement in the oxygen group (OR: 2.9). CONCLUSION: Our data show that routine oxygen supplementation started within 24 hours of hospital admission with acute stroke led to a small, but statistically significant, improvement in neurological recovery at 1 week. However, the difference in NIHSS improvement may be due to baseline imbalance in stroke severity between the two groups and needs to be confirmed in a larger study and linked to longer-term clinical outcome. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN12362720; European Clinical Trials Database 2004-001866-41.

A randomized controlled trial of the effect of fixed-dose routine nocturnal oxygen supplementation on oxygen saturation in patients with acute stroke.

BACKGROUND: Mild hypoxia is common in patients with stroke, and associated with worse long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no benefit after acute stroke, but did not report compliance and the effect on oxygenation. The aim of this study was to assess the effect of routine low-flow oxygen supplementation on oxygen saturation (SpO(2)) in patients with acute stroke. METHODS: In all, 63 patients with normoxic stroke and no indications for oxygen treatment were randomized to 2 L/min oxygen supplementation via nasal cannulae overnight or to control (room air) within 72 hours of symptom onset. Additional oxygen was given at the discretion of the clinical team, if medically indicated. SpO(2) was assessed from 22:00 to 09:00 by pulse oximetry. Compliance with the trial treatment and sleep status were recorded by nursing staff. RESULTS: In all, 59 patients were confirmed to have had a stroke and available for overnight monitoring. Six (2 oxygen, 4 control) had no or insufficient oximetry data for analysis. The mean nocturnal SpO(2) was 2.5% higher in the oxygen group (n = 27) than in the control group (n = 26) (P < .001). More patients on oxygen than control subjects had SpO(2) greater than 90% throughout the night (59% v 23%). Patients on oxygen had fewer desaturations than control subjects (oxygen desaturation index 4%, 0.8 v 2.1) (P = .001). Oxygen was found to be in place as prescribed in 71%. Oxygen supplementation was not associated with insomnia or restlessness. No patient in either group was given oxygen for clinical indications. CONCLUSIONS: Nocturnal oxygen supplementation at a rate of 2 L/min increases the mean nocturnal SpO(2) by 2.5% and reduces the number of nocturnal desaturations in patients with acute stroke.