Examination of Personalized SpO2 Targets

Each year, 2-3 million critically ill adults in the United States receive invasive mechanical ventilation. In-hospital mortality among critically ill adults receiving mechanical ventilation remains approximately 25-35%. Approaches to care that decrease mortality for critically ill adults receiving invasive mechanical ventilation are urgently needed.

Mechanical ventilation universally involves titrating the fraction of inspired oxygen (FiO2) to maintain arterial oxygen saturation - as assessed by pulse oximetry (SpO2) or blood gas analysis (SaO2) - or arterial oxygen tension (e.g., PaO2). Using higher SpO2 targets (96-100%) provides a margin of safety against hypoxemia, but increases exposure to excess FiO2, hyperoxemia, and tissue hyperoxia, potentially causing oxidative damage and inflammation. Using lower SpO2 targets (88-92%) minimizes these risks but may increase exposure to hypoxemia and hypoxia-induced organ injury. Historically, the effects of higher versus lower SpO2 targets on patient outcomes were unknown.

Our recent randomized trial comparing higher versus lower SpO2 targets among 2,541 critically ill adults receiving mechanical ventilation in the medical intensive care unit (ICU) found that use of a higher versus lower SpO2 target did not result in overall differences in short-term outcomes (e.g., 28-day mortality) or long-term outcomes (e.g., cognition at 12 months). Results have been similar in multiple other large, randomized trials in different settings.

Randomized trials traditionally report the average effect of treatment on outcomes for the overall population. However, the effect of treatment on outcomes may differ for patients with different characteristics. Such nonrandom variation in the magnitude or direction of treatment effect is called heterogeneity of treatment effect. To understand which treatment will produce the best outcomes for a given patient, clinicians and patients need randomized trials to move beyond reporting the average treatment effect to reporting the effect of treatment on outcomes for an individual patient based on the patient's unique characteristics, referred to as individualized treatment effect.

Recently, we used the dataset from our trial of higher versus lower SpO2 targets to develop a statistical model to predict the effect of use of a higher versus lower SpO2 target on 28-day mortality for an individual patient, considering each of the patient's baseline characteristics simultaneously. This statistical model uses 24 patient characteristics available at the time of initiation of invasive mechanical ventilation to predict which SpO2 target will result in the best outcome for that patient. The model inputs are each patient's value for each of the 24 baseline characteristics. The model output is the predicted absolute effect of using a higher or lower SpO2 target on 28-day in-hospital mortality for the patient, conditional on all of the patient's values for the baseline characteristics. To validate the accuracy of this statistical model, we applied it to the dataset from a second, geographically and temporally distinct randomized trial of higher vs lower SpO2 targets. We found that, despite no significant average treatment effect in either trial, the effect of use of a higher versus lower SpO2 target on mortality ranged widely for individual patients, with many patients appearing to benefit from either a lower or a higher SpO2 target.