We’ve long been advocates of using oxygen therapy wisely, using it only in patients with documented hypoxemia and titrating it to appropriate oxygenation targets without producing hyperoxemia. We’ve detailed in multiple columns the potential downsides of hyperoxemia (see list at the end of today’s column).
A new study (Girardis 2016) randomized ICU patients to “conventional” care (where oxygen therapy was used to achieve SpO2 levels 97-100%) or “conservative” oxygen therapy (where oxygen therapy was titrated to target SpO2 levels of 94-98%). ICU mortality in the conservative group was 11.6% compared to 20.2% in the conventional group, a relative risk reduction of 57% and absolute risk reduction of 8.6%! Total hospital mortality was also significantly lower in the conservative group. Patients in the conservative group also had fewer episodes of shock, liver failure, and bacteremia.
Sounds great, doesn’t it? While the reported results showed a lower ICU mortality for patients in the conservative group, various aspects of the study raise many questions, appropriately brought out in the accompanying editorial (Ferguson 2016). First of all, there were differences in the illness severity of patients at baseline, favoring the conservative group so some of the lower mortality in that group may have been due to lower severity of illness. Secondly, the trial was terminated early, purportedly because of difficulty recruiting patients and because the interim results so strongly favored the conservative group. Clinical trials that are terminated early tend to overestimate the treatment effect. Thirdly, the modified intention-to-treat analysis used excluded patients who were randomized but did not remain in the ICU for at least 72 hours and those who did not have at least one ABG analysis per day. And, though differences in deaths were statistically significant, the total number of deaths was small. And this was a single center study so generalization may not be appropriate.
Botom line: these results need to be validated in another (preferably multicenter) trial of sufficient size with appropriate randomization. But while we are waiting for such a study, we concur with the editorialist that careful titration of oxygen therapy to achieve physiologically normal levels and avoid hyperoxia makes sense.
Some of our prior columns on potential harmful effects of oxygen:
April 8, 2008 “Oxygen as a Medication”
January 27, 2009 “Oxygen Therapy: Everything You Wanted to Know and More!”
October 6, 2009 “Oxygen Safety: More Lessons from the UK”
July 2010 “Cochrane Review: Oxygen in MI”
December 6, 2011 “Why You Need to Beware of Oxygen Therapy”
February 2012 “More Evidence of Harm from Oxygen”
March 2014 “Another Strike Against Hyperoxia”
June 17, 2014 “SO2S Confirms Routine O2 of No Benefit in Stroke”
December 2014 “Oxygen Should Be AVOIDed”
August 11, 2015 “New Oxygen Guidelines: Thoracic Society of Australia and NZ”
Girardis M, Busani S, Damiani E, et al. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care UnitThe Oxygen-ICU Randomized Clinical Trial. JAMA 2016; Online First October 5, 2016
Ferguson ND. Oxygen in the ICU. Too Much of a Good Thing? JAMA 2016; Published online October 05, 2016