Multiple Indication Review: Liberal vs Conservative Oxygen Therapy in Acutely Ill Patients

Readers of the News Blog may know that we advocate the examination of evidence in its totality beyond the silos of individual diagnoses and conditions – if the underlying mechanism of a phenomenon or the hypothesis to be tested is common across these conditions. This can be achieved by a multiple indication review, a systematic review that examines the effects of an intervention or variable across different conditions.[1] Earlier this year Chu and colleagues published an excellent example of a multiple indication review, in which they examined evidence from randomised controlled trials (RCTs) that have compared liberal versus conservative use of oxygen in adults with acute illness.[2] They identified 25 RCTs including a total of 16,037 patients across neurological conditions (stroke and traumatic brain injury), sepsis, emergency surgery, critical care and cardiac conditions (myocardial infarction and cardiac arrest). A meta-analysis of this evidence across all conditions showed that liberal use of oxygen increased the risk of in-hospital death by 21% (relative risk 1.21, 95% CI 1.03 to 1.41) compared with a more conservative use. A similar, although slightly smaller increase in risk was also found for 30-day mortality and mortality at the longest follow-up of individual trials.

The findings were homogeneous within and across different conditions, and were supported by a meta-regression showing positive correlation between relative risk of in-hospital mortality and percentage point increase in SpO₂(peripheral oxygen saturation). Liberal use of oxygen did not offer any benefits for reducing disability for patients suffering from stroke and traumatic brain injuries, nor did it reduce hospital length of stay and hospital-acquired infections for acute medical admissions. The only notable difference is that a liberal strategy of oxygen therapy was associated with reduced hospital-acquired infections for acute surgical admissions (RR 0.50, 95% CI 0.36 to 0.69). This finding was based on data from two RCTs that were terminated early and the authors urged further investigation in this patient population. Taken together, it appears too much of oxygen is not good for acutely ill patients. This conclusion, while contradicting some conventional wisdom, is also supported by several plausible mechanisms through which very high level of oxygen could damage our body such as causing acute lung injury and triggering inflammatory responses.[3] “Establishing the optimum range of oxygen saturation that minimises the competing risks of hypoxaemia and hyperoxaemia”, as the authors suggested, seems to be the way forward.

— Yen-Fu Chen, Principle Research Fellow

References:

1. Chen YF, Hemming K, Chilton PJ, Gupta KK, Altman DG, Lilford RJ. Scientific hypotheses can be tested by comparing the effects of one treatment over many diseases in a systematic review. J Clin Epidemiol. 2014; 67(12): 1309-19.
2. Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. 2018; 391: 1693-705.
3. Hafner S, Beloncle F, Koch A, Radermacher P, Asfar P. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care.2015; 5(1): 42.