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.

Frequency of nocturnal hypoxia in clinically stable patients during stroke rehabilitation.

OBJECTIVE: Sleep disordered breathing is common in patients with cerebrovascular disease. Nocturnal hypoxia may lead to daytime tiredness and cognitive impairment, thus affecting progress. This study assessed the prevalence of nocturnal hypoxia during rehabilitation from stroke. DESIGN: Prospective observational trial. SETTING: The stroke rehabilitation wards of the North Staffordshire Hospital, UK and of Kreiskrankenhaus Grevenbroich, Germany. SUBJECTS: Adult patients on a stroke rehabilitation ward, 10 days to 3 months (mean 32 days, SD18) after stroke onset (n = 160). Age and local environment-matched controls (n = 156) without a history of stroke were recruited from the community at both centres. MAIN MEASURES: Pulse oximetry was performed overnight on the day of enrolment from 21:00 to 09:00. The baseline awake oxygen saturation, the mean nocturnal oxygen saturation, the lowest nocturnal oxygen saturation and the 4% Oxygen Desaturation Index were calculated for each participant. RESULTS: The mean baseline awake oxygen saturation of stroke patients was at 95.3% (SD 1.7), 0.5% lower than that of controls (P = 0.005, independent t-test). The group means of the mean nocturnal oxygen saturation for stroke patients were 0.5% lower (at 93.8% SD 2.2) than controls (P = 0.03, independent t-test). The mean lowest nocturnal oxygen saturation was at 79.4% (SD 9.9), 5.9% lower than that of the controls (P<0.001, independent t-test). Considerably more stroke patients (n = 67, 42%) than controls (n = 24, 15%) had > or =10 desaturations below the baseline per hour (P<0.001 chi-square test). CONCLUSION: Clinically stable stroke patients enrolled in rehabilitation programmes have lower oxygen saturation and more nocturnal desaturations than non-stroke controls.

Day-night differences in oxygen saturation and the frequency of desaturations in the first 24 hours in patients with acute stroke.

BACKGROUND: Hypoxia is common after acute stroke. Most studies of oxygenation after stroke were done at night. The objective of this study was to determine whether there are differences in oxygenation between day and night early after stroke. METHODS: Patients with an acute stroke were recruited within 24 hours of admission. Patients who were hypoxic (oxygen saturation < 90%) were excluded. Oxygen saturation was assessed by pulse oximetry over 24 hours. Daytime recordings were taken from 9 am to 9 pm and nighttime recordings from 10 pm to 6 am. Respiratory rate and sleep/awake status were recorded twice during the day and the night. RESULTS: Forty patients were recruited (mean age 77 years [range 55-93 years], 53% men; median [range] Glasgow Coma Scale score 15 [10-15] and Scandinavian Stroke Scale score 31 [4-56]; 80% cerebral infarcts, 20% hemorrhages). The median (range) respiratory rate was 20 (14-30) breaths/min in the day and 18 (12-32) breaths/min in the night (P < .01, Wilcoxon paired test). The median (range) oxygen saturation was 95.5% (87%-98.6%) in the day and 94.3% (80%-98%) at night (P < .001, Wilcoxon paired test). The median (range) 4% oxygen desaturation index was 1.7 (0.0, 18.0) in the day and 3.0 (0.0, 39.4) at night (P < .001, Wilcoxon paired test). Respiratory rate, oxygen saturation, and 4% oxygen desaturation index during the day and night were strongly correlated. CONCLUSIONS: All indicators of oxygenation assessed in this study were significantly worse at night than in the day. Because daytime and nighttime results were strongly correlated, borderline hypoxia during the day is strongly predictive of overt hypoxia at night.

Development of a conversion factor to facilitate comparison of National Institute of Health Stroke Scale scores with Scandinavian Stroke Scale scores.

BACKGROUND: The National Institute of Health Stroke Scale (NIHSS) and the Scandinavian Stroke Scale (SSS) are commonly used in clinical stroke trials. Use of different scales in trials makes comparison of outcomes difficult. METHODS: Adult patients with an acute stroke were recruited within 24 h of onset, and NIHSS, SSS and Glasgow Coma Scale scores were assessed at baseline and repeated at 1 week. RESULTS AND CONCLUSIONS: A total of 144 patients were included (46% males, mean age = 73 years). At presentation the median SSS score was 38 (2-58), and a week later 40 (4-58), the median NIHSS score at presentation was 5 (0-29) and a week later 3 (0-27). Changes in both scales were strongly correlated, r = 0.76, p < 0.001. Both were good predictors of mortality. Linear regression analysis produced an equation relating the two: SSS = 50 - 2 x NIHSS.

The effect of different doses of oxygen administration on oxygen saturation in patients with stroke.

INTRODUCTION: American Stroke guidelines suggest that oxygen saturation after acute stroke should be maintained at 95% or higher. European recommendations include a dose of 2 to 4 L/minute via nasal cannulae. These recommendations are not based on controlled clinical studies. No consensus exists among stroke physicians regarding how much oxygen should be administered and which route should be selected. The aim of this study was to assess the effects of different doses and routes of oxygen administration on oxygen saturation in patients with stroke. METHODS: Patients were recruited within 72 hours of admission with acute stroke. Oxygen saturation was assessed by pulse oximetry (Minolta Pulsox 3i) for 30 minutes on room air (baseline), 2 and 3 L/minute of oxygen via nasal cannulae, 24 and 35% oxygen via face mask, and, finally, on room air. Patients were asked about their preferred route of oxygen administration. RESULTS: Twenty-one patients with a mean age of 72.3 years (range: 46-87 years) were recruited. A total of 24% oxygen (face mask) increased saturation by 1%, 2 L/minute (nasal cannulae) and 35% (face mask) led to a 2% increase, and 3 L/minute (nasal cannulae) resulted in a 3% increase in saturation compared to baseline (p < 0.001). Oxygen saturations were similar in the first and last half-hours. Oxygen treatment has no significant effect on respiratory and heart rates. Most patients (71%) preferred nasal cannulae to face masks. CONCLUSIONS: In our patient population, there was a close dose-response relationship between the amount of oxygen given and the resultant changes in oxygen saturation.

Unexpected nocturnal hypoxia in patients with acute stroke.

BACKGROUND AND PURPOSE: Patients who have had a stroke are at risk of hypoxia through alterations in the central regulation of respiration, through aspiration, and through respiratory muscle weakness. Sleep-related breathing disorders are common and may lead to episodes of nocturnal hypoxia even when daytime oxygenation is normal. The aim of this study was to assess the prevalence of unexpected nocturnal hypoxia in stroke patients. METHODS: Consecutive adult patients with stroke were recruited within 72 hours of admission to hospital. Patients with indications for oxygen treatment were excluded. Older adults from the local community were recruited as control subjects. Oxygenation was assessed by pulse oximetry (Minolta 3i) for 5 minutes when awake before bedtime and continuously from 11 pm until 7 am. RESULTS: Of the 238 potentially eligible stroke patients, 120 were excluded because they required oxygen, 118 were recruited, and 100 had adequate pulse oximetry data. The mean+/-SD age was 74+/-8 years for stroke patients and 72+/-8 years for control subjects (n=85). Mean awake oxygen saturation (So2) was 94.5+/-1.7% for the stroke group and 95.8+/-1.7% for the control group (P<0.001). Mean nocturnal So2 was 93.5+/-1.9% in stroke patients and 94.3+/-1.9% in control subjects (P<0.01). Stroke patients had a higher oxygen desaturation index (ODI 4%) (8.9 versus 2.1, P<0.001). In addition, 23% of stroke patients spent >30 minutes with So2 <90% during the night. CONCLUSIONS: Oxygen saturation at night is approximately 1% lower than when awake. Almost a quarter of stroke patients who are normoxic at screening during the day spend >30 minutes with an oxygen saturation <90%.

Randomised, cross-over, placebo controlled trial of magnesium citrate in the treatment of chronic persistent leg cramps.

BACKGROUND: Nocturnal leg cramps are common and distressing. The only treatment of proven effectiveness is quinine, but this has a number of side effects. Magnesium salts have been shown to reduce leg cramp distress in pregnancy. This study tests whether magnesium citrate is effective in the treatment of leg cramps in non-pregnant individuals by conducting in a randomised, double-blind, cross-over placebo-controlled trial. MATERIAL/METHODS: Volunteers suffering regular leg cramps were recruited. Magnesium citrate equivalent to 300 mg magnesium and matching placebo were given for 6 weeks each. The number of cramps recorded in the cramp diary during the final 4 weeks of magnesium and placebo treatment, severity and duration of cramps and the participants' subjective assessment of effectiveness were analysed. RESULTS: In subjects who started with placebo (n=29) the median (95% CI) number of cramps was 9 (6-17) on placebo and 5 (4-8) on magnesium. For the group starting with magnesium (n=17) the median no of cramps was 9 (5-13) on magnesium and 8 (4-14) on placebo. There was no significant carry-over effect (p=0.88), but a highly significant period effect (p=0.008). There was a trend towards less cramps on magnesium (p=0.07). There was no difference in cramp severity and duration between the groups. Significantly more subjects thought that the treatment had helped after magnesium than after placebo 36 (78%) and 25 (54%) respectively, (p=0.03). Diarrhoea was recorded as a side effect of magnesium. CONCLUSIONS: The results suggest that magnesium may be effective in treatment of nocturnal leg cramps. Further evaluation is recommended.