No Benefit of Routine Oxygen in Acute Stroke

September 28, 2017

Routine use of prophylactic oxygen had no benefit or harm in a new large randomized trial in acute stroke patients.

"This is the largest study of oxygen in acute stroke — the best data we have on this issue, and our results do not support the routine use of low-dose oxygen in nonhypoxic acute stroke patients," lead investigator, Christine Roffe, MD, Institute for Science and Technology in Medicine, Keele University, United Kingdom, told Medscape Medical News.

The Stroke Oxygen Study (SO2S) is published in the September 26 issue of JAMA.

The trial randomly assigned 8003 patients with acute stroke (median National Institutes of Health Stroke Scale score of 5) within 24 hours of admission to 3 days of continuous oxygen, nocturnal oxygen, or control.

After 3 months, death and disability did not significantly differ between the combined oxygen groups and  the control group (odds ratio, 0.97) or between the continuous oxygen group and the nocturnal oxygen group (odds ratio, 1.03). No subgroup could be identified that benefited from oxygen, and no significant harms were identified.

The researchers report that this was a large pragmatic trial and included unselected patients with a clinical diagnosis of acute stroke without radiologic confirmation. The sample therefore included ischemic and hemorrhagic strokes and participants who were later found to have mimics or transient ischemic attacks.

More than half of all acute stroke services in the United Kingdom participated, and wide inclusion criteria allowed enrollment of a representative sample of patients with ischemic and hemorrhagic stroke across the whole range of severity.

Dr Roffe explained that the role of oxygen in acute stroke has been controversial for many years. "When we started this trial in 2006, all patients were given high-dose oxygen in the ambulance, and when they got to hospital it may or may not have been continued. The logic was that the brain has been starved of oxygen, so giving oxygen might help and probably wouldn't do any harm. But there was only very limited scientific data, and there had been some studies in MI [myocardial infarction] patients suggesting oxygen may be harmful, so we wanted to look at this in a large randomized trial."

The SO2S trial evaluated the use of low-dose oxygen (2 to 3 L/min) with the aim of keeping oxygen levels in the normal range. This was given for 3 days once the patient was in hospital (medium time of starting treatment was 20 hours from stroke onset). 

"We had a reasonable number of patients who started treatment very early (less than 6 hours from stroke onset), and we didn't see any benefit in those patients either," Dr Roffe commented.

"Our recommendation is therefore not to give oxygen to stroke patients as it doesn't appear to cause any benefit," she added. "While it also doesn't cause any harm, it just appears to be an unnecessary complication. But we still need to monitor oxygen levels [because] if patients become hypoxic then they will need oxygen."

These results are consistent with the latest findings in patients with MI.  A recent large study published in the New England Journal of Medicine also showed no benefit or harm of oxygen in MI.  "The fact that similar results are being seen in both MI and stroke strengthens the likelihood that these findings are correct," Dr Roffe said.  

Dr Roffe noted that practice had changed as the study was ongoing. "People have started questioning whether they should be giving oxygen, and the UK emergency guidelines now recommend that oxygen is not given routinely to acute stroke patients.  However, this was not based on strong scientific evidence. Now we have evidence to support that advice."

She added that the practice of giving oxygen in the ambulance has also fallen out of favor in recent years. "In our study, only about 20% of patients had received oxygen in the ambulance. While we can't say for sure that our results apply to the prehospital use, I think people will extrapolate to this situation and I think it is very unlikely to be beneficial."

Speculating on why oxygen has no benefit, she suggested:  "Low oxygen levels are usually a sign that something else is wrong, such as pneumonia or heart failure, and if we give oxygen we are masking this sign, which means the underlying problem may be missed or treated later than it would have been otherwise."

The researchers also suggest that low-dose oxygen supplementation may not be sufficient to prevent severe desaturations, noting that there was no significant difference in severe desaturations between the treatment and control groups.

They add that a small nonrandomized study comparing high-flow vs low-flow oxygen showed a trend toward lower mortality with high flow that was not statistically significant, but randomized trials of high-flow oxygen treatment in acute stroke have not shown that higher doses of oxygen are associated with better outcomes.

PROOF Trial  

Another trial just starting (PROOF) is evaluating high-dose oxygen in patients with very early acute stroke receiving thrombolysis or thrombectomy.  Dr Roffe explained the theory behind this study: There is a short time during which the ischemic damage is reversible, and oxygen may help the area in the brain surrounding the stroke. 

"This is very different from what we did — we tested physiological doses of oxygen with the aim of keeping levels normal.  The PROOF trial is looking at using very high concentrations of oxygen, which is more like a drug treatment just in one specific group of patients."

The SO 2 trial was funded by the National Institute for Health Research  Health Technology Assessment Programme and the Research for Patient Benefit Programme. Dr Roffe reports receipt of a grant from the Research for Patient Benefit Programme and the Health Technology Assessment Programme of the National Institute for Health Research, receipt of lecture and travel fees from Air Liqude, and independent membership on the data safety and monitoring committee of the PROOF trial. The other authors have disclosed no relevant financial relationships.

JAMA. Published online September 26, 2017. Abstract  

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