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

• Published in: Contemporary clinical trials 2022-08, Vol.119, p.106811-106811, Article 106811
• Main Authors: Pannu, Sonal R., Haddad, Tyler, Exline, Matthew, Christman, John W., Horowitz, Jeffrey C., Peters, Jonathan, Brock, Guy, Diaz, Philip, Crouser, Elliott D.
• Format: Article
• Language: English
• Subjects: Critical Illness; Electronic alerts; Electronic medical records; Humans; Hyperoxia; Hypoxia; Lung; Mechanical ventilation; Oxygen; Protocol; Randomized clinical trials; Respiration, Artificial
• ISSN: 1551-7144; 1559-2030
• DOI: 10.1016/j.cct.2022.106811

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. We present the methodology for the Titration Of Oxygen Levels (TOOL) trial, an open label, randomized controlled trial of an algorithm-based FiO2 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 FiO2 if SpO2 is ≥94% with FiO2 levels ≥0.4 over 45 min. FiO2 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 FiO2 ≥ 0.4 and SpO2 ≥ 94%. We will also assess proportion of time during mechanical ventilation spent with SpO2