Oxygen therapy with SpO2 94%-98% may reduce mortality compared to therapy with SpO2 97%-100% in patients admitted to intensive care unit

EBM Focus - Volume 11, Issue 43

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Reference - JAMA 2016 Oct 18;316(15):1583 (level 2 [mid-level] evidence)

  • Guidance regarding target oxygen saturation values in critically ill patients receiving oxygen therapy is limited and hyperoxia appears to be common in patients in intensive care units (ICU).
  • Compared to oxygen therapy with arterial oxyhemoglobin saturation (SpO2) target of 97%-100%, oxygen therapy with a lower target SpO2 of 94%-98% was associated with reduced rate of ICU mortality, new shock or liver failure, and bacteremia in a randomized trial of 480 adults in an ICU.
  • The benefits of oxygen therapy with a lower target oxygenation level observed in this trial may be overestimated, but the results support careful management of oxygen saturation levels to avoid hyperoxic states in critically ill patients.

For critically ill patients receiving oxygen therapy, there is limited data to guide the oxygenation targets and studies suggest that liberal use of oxygen therapy resulting in hyperoxia is common (Respir Care 2012 Nov;57(11):1887, J Crit Care 2013 Oct;28(5):647). Two previous randomized trials investigating mortality following lower versus higher oxygenation strategies have been performed and no benefit has been found from higher oxygenation targets with possible harm reported in patients having surgery for cancer (JAMA 2009 Oct 14;302(14):1543, Anesth Analg 2012 Oct;115(4):849, Am J Respir Crit Care Med 2016 Jan 1;193(1):43). To further investigate optimal oxygenation targets, a recent trial randomized 480 adults (median age 64 years) admitted to an ICU with an expected stay > 72 hours to lower oxygen therapy with SpO2 target of 94%-98% versus higher therapy with SpO2 target of 97%-100%.

Primary analyses were conducted in 434 patients with an ICU stay > 72 hours and ≥ 1 arterial blood gas analysis per day. At baseline, comorbidities were slightly lower in the group with a lower target oxygenation level. The lower target oxygenation level was associated with better outcomes including lower ICU mortality which was 11.6% with lower target therapy vs. 20.2% with higher target therapy (p = 0.03, NNT 12), and lower rates of new shock which occurred in 3.7% vs. 10.6% (p = 0.006, NNT 15), new liver failure in 1.9% vs. 6.4% (p = 0.02, NNT 23), and bacteremia in 5.1% vs. 10.1% (p = 0.049, NNT 20). There were no significant differences between groups in new respiratory failure, renal failure, or respiratory infection with microbiologic documentation, surgical site infection, or ICU or hospital length of stay. These results were consistent with the planned interim and intention-to-treat analyses. Due to hospital damage caused by an earthquake, the trial was terminated early and the target number of 660 enrolled patients was not met.

In this trial, oxygenation in the SpO2 94%-98% range resulted in substantially lower rate of ICU mortality, new shock, new liver failure and bacteremia in critically ill patients. The trial had a number of methodologic limitations including early trial termination unrelated to preplanned stopping rules, multiple posthoc analyses, small baseline differences in comorbidities, and failure to adjust the statistical analysis for multiple outcome measures. All of these factors have the potential to overestimate the effect of the intervention and, therefore, the large differences in outcomes reported should be viewed with caution. In fact, the authors state that all outcomes other than ICU mortality should be viewed as exploratory in nature. Overall however, the evidence to date would support careful management of oxygen saturation levels to avoid hyperoxic states in critically ill patients.

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