Rationale and design of a randomized controlled clinical trial; Titration of oxygen levels (TOOL) during mechanical ventilation

Background: Both hyperoxemia and hypoxemia are deleterious in critically ill patients. Targeted oxygenation is recommended to prevent both of these extremes, however this has not translated to the bedside. Hyperoxemia likely persists more than hypoxemia due to absence of immediate discernible adverse effects, cognitive biases and delay in prioritization of titration. Methods: We present the methodology for the Titration Of Oxygen Levels (TOOL) trial, an open label, randomized controlled trial of an algorithm-based FiO(2) titration with electronic medical record-based automated alerts. We hypothesize that the study intervention will achieve targeted oxygenation by curbing episodes of hyperoxemia while preventing hypoxemia. In the intervention arm, electronic alerts will be used to titrate FiO(2) if SpO(2) is >= 94% with FiO(2) levels >= 0.4 over 45 min. FiO(2) will be titrated per standard practice in the control arm. This study is being carried out with deferred consent. The sample size to determine efficacy is 316 subjects, randomized in a 1:1 ratio to the intervention vs. control arm. The primary outcome is proportion of time during mechanical ventilation spent with FiO(2) >= 0.4 and SpO(2) >= 94%. We will also assess proportion of time during mechanical ventilation spent with SpO(2) < 88%, duration of mechanical ventilation, length of ICU and hospital stay, hospital mortality, and adherence to electronic alerts as secondary outcomes. Conclusion: This study is designed to evaluate the efficacy of a high fidelity, bioinformatics-based, electronic medical record derived electronic alert system to improve targeted oxygenation in mechanically ventilated patients by reducing excessive FiO(2) exposure.