Effect of Routine Low-Dose Oxygen Supplementation on Death and Disability in Adults With Acute Stroke

Abstract

IMPORTANCE Hypoxia is common in the first few days after acute stroke, is frequently intermittent, and is often undetected. Oxygen supplementation could prevent hypoxia and secondary neurological deterioration and thus has the potential to improve recovery. OBJECTIVE To assess whether routine prophylactic low-dose oxygen therapy was more effective than control oxygen administration in reducing death and disability at 90 days, and if so, whether oxygen given at night only, when hypoxia is most frequent, and oxygen administration is least likely to interfere with rehabilitation, was more effective than continuous supplementation. DESIGN, SETTING, AND PARTICIPANTSIn this single-blind randomized clinical trial, 8003 adults with acute stroke were enrolled from 136 participating centers in the United Kingdom within 24 hours of hospital admission if they had no clear indications for or contraindications to oxygen treatment (first patient enrolled April 24, 2008; last follow-up January 27, 2015).INTERVENTIONS Participants were randomized 1:1:1 to continuous oxygen for 72 hours (n = 2668), nocturnal oxygen (21:00 to 07:00 hours) for 3 nights (n = 2667), or control (oxygen only if clinically indicated; n = 2668). Oxygen was given via nasal tubes at 3 L/min if baseline oxygen saturation was 93% or less and at 2 L/min if oxygen saturation was greater than 93%. MAIN OUTCOMES AND MEASURESThe primary outcome was reported using the modified Rankin Scale score (disability range, 0 [no symptoms] to 6 [death]; minimum clinically important difference, 1 point), assessed at 90 days by postal questionnaire (participant aware, assessor blinded). The modified Rankin Scale score was analyzed by ordinal logistic regression, which yields a common odds ratio (OR) for a change from one disability level to the next better (lower) level; OR greater than 1.00 indicates improvement.RESULTS A total of 8003 patients (4398 (55%) men; mean [SD] age, 72 [13] years; median National Institutes of Health Stroke Scale score, 5; mean baseline oxygen saturation, 96.6%) were enrolled. The primary outcome was available for 7677 (96%) participants. The unadjusted OR for a better outcome (calculated via ordinal logistic regression) was 0.97 (95% CI, 0.89 to 1.05; P = .47) for oxygen vs control, and the OR was 1.03 (95% CI, 0.93 to 1.13; P = .61) for continuous vs nocturnal oxygen. No subgroup could be identified that benefited from oxygen. At least 1 serious adverse event occurred in 348 (13.0%) participants in the continuous oxygen group, 294 (11.0%) in the nocturnal group, and 322 (12.1%) in the control group. No significant harms were identified.CONCLUSIONS AND RELEVANCE Among nonhypoxic patients with acute stroke, the prophylactic use of low-dose oxygen supplementation did not reduce death or disability at 3 months. These findings do not support low-dose oxygen in this setting.

Handling Oxygenation Targets in the Intensive Care Unit (HOT‐ICU)—Protocol for a randomised clinical trial comparing a lower vs a higher oxygenation target in adults with acute hypoxaemic respiratory failure

“…Based on supplementary analysis, the authors of the systematic review concluded that treatment with oxygen could become unfavourable in acutely ill patients if resulting in an SpO 2 above 94%‐96%. However, this specific upper target of SpO 2 is not supported by the trials with the highest weight in the mortality analysis, as these studies effectively all investigated normoxaemia vs hyperoxaemia with SpO 2 above 94%‐96% in the conservative oxygenation groups. Nevertheless, this upper SpO 2 target has recently been implemented in a clinical guideline on oxygen therapy .…”

Intensive care doctors’ preferences for arterial oxygen tension levels in mechanically ventilated patients

“…Randomised clinical trials outside the ICU have found that oxygen supplementation to non‐hypoxic patients with acute myocardial infarction does not change long‐term outcome, and may increase myocardial damage and thus, the preferred liberal approach may not be beneficial. Trials on oxygen supplementation in non‐hypoxic patients with acute stroke outside the ICU have failed to show long‐term benefit of oxygen supplementation . Therefore, no evidence supports a more liberal approach in patients with cerebral ischaemia.…”

Oxygen therapy for acutely ill medical patients: a clinical practice guideline

“…The evidence in patients with initially higher SpO 2 (>92%) is more certain because most patients in the trials had a baseline SpO 2 above 92%. For example, in the largest of eight trials of patients with stroke only 240 patients (3.1% of 7677 participants) had an initial SpO 2 of 90-93.9% 16. For myocardial infarction, six trials enrolled 7898 patients: in the largest trial, 1062 patients (16.0%) had an initial SpO 2 ≤94% 17.…”