Reference:  Peters MJ, et al. Conservative versus liberal oxygenation targets in critically ill children (Oxy-picu): a UK multicentre, open, parallel-group, randomised clinical trial. Lancet. December 2023 Guest Skeptic:  Dr. Anireddy Reddy is a pediatric intensive care attending physician in the Department of Anesthesiology and Critical Care Medicine at Children’s Hospital of Philadelphia. Dr. Anireddy Reddy Case: A 3-year-old girl presents to the emergency department (ED) with fever and respiratory distress. Her parents tell you that she has been sick for almost a week and her symptoms seem to be getting worse. In the past few days, her appetite has decreased, and she is breathing harder. On your exam, you note that she is very tired and can barely keep her eyes open. Her oxygen saturation is 78% on room air. She is breathing at a rate of 70 breaths per minute with diffuse retractions and nasal flaring. Your ED team quickly intubates her and places her on a ventilator. There is some improvement in her oxygen saturation to 92% and she is drawing adequate tidal volumes. The respiratory therapist asks you whether you want to increase the FiO2 to improve her oxygen saturation while awaiting transport to the pediatric intensive care unit. Background: Oxygen is one of the most prescribed therapies. Sometimes it almost feels like a knee-jerk reaction. We see that pulse ox saturation is low and the first thing we do is apply some form of oxygen.  But like many interventions, there are potential harms and benefits. Yes, we purposely use the language of potential harms and benefits rather than risk and benefits. Using the term “risk” implies that a negative outcome may or may not happen. While the term “benefits” implies a positive outcome. It’s unbalanced. Too much oxygen has not been shown to improve outcomes in some conditions and has been associated with harm in others. Our guidelines for the treatment of pediatric acute respiratory distress syndrome also recommend a target saturation of 88-92%. Clinical Question: What is the optimal target for systematic oxygen in critically ill children receiving invasive ventilation? Reference:  Peters MJ, et al. Conservative versus liberal oxygenation targets in critically ill children (Oxy-picu): a UK multicentre, open, parallel-group, randomised clinical trial. Lancet. December 2023 Population: Children >38 weeks corrected gestational age and younger than 16 years enrolled within 6 hours of being admitted to the Pediatric Intensive Care Unit (PICU) and receiving invasive mechanical ventilation with supplemental oxygen Excluded: known or suspected congenital cardiac disease or sickle cell disease, known pulmonary hypertension, when brain pathology/injury was the primary reason for admission, not expected to survive ICU admission, receiving long-term invasive mechanical ventilation prior, or have end-of-life care plans with limitations in resuscitation Intervention: Conservative oxygenation, defined as a target peripheral oxygen saturation (SpO2) of 88% to 92%. Comparison: Liberal oxygenation, defined as target SpO2 >94% Outcome:  Primary Outcome: Duration of organ support at 30 days. This was a rank-based endpoint scored 1 to 30, and 31 if the patient died. Major components of organ support included respiratory (invasive and non-invasive), cardiovascular (vasoactives and fluid boluses), renal support, analgesia/sedation, transfusion, neurological, and metabolic support. Details can be found in the supplemental material. Secondary Outcomes: Mortality at PICU discharge, time to liberation from invasive mechanical ventilation, duration of organ support, length of PICU and acute hospital stay, functional status at PICU discharge, incremental costs at 30 days Trial: Pragmatic, multicentre, open-label, randomized controlled trial Authors’ Conclusions: “Among invasively ventilated children who were admitted a...