Conservative versus liberal oxygenation targets in critically ill children: the Oxy-PICU RCT

Background: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practised but is associated with harm in observational studies. Objectives: To evaluate the clinical and cost-effectiveness of a conservative oxygenation target of peripheral oxygen saturation 88-92% compared with peripheral oxygen saturation > 94% in critically ill children admitted to paediatric intensive care unit as an emergency. Design and setting: A pragmatic, open, multicentre, parallel-group, randomised clinical trial conducted in 15 National Health Service paediatric intensive care units and associated emergency transport services across England and Scotland. Participants: Children aged > 38 weeks corrected gestational age and < 16 years, enrolled within 6 hours of being accepted for admission to paediatric intensive care unit as an emergency; receiving invasive mechanical ventilation with supplemental oxygen; and in face-to-face contact with paediatric intensive care unit or emergency transport services staff. Interventions: Adjustment of ventilator and inspired oxygen settings aiming to achieve peripheral oxygen saturation 88-92% (conservative oxygenation) or peripheral oxygen saturation > 94% (liberal oxygenation) during invasive mechanical ventilation. Main outcome measures: Primary outcomes: duration of organ support at 30 days, with death by day 30 ranked as the worst outcome (clinical effectiveness) and incremental costs, quality-adjusted life-years and net monetary benefit at 12 months (cost-effectiveness). Secondary outcomes: incremental costs at 30 days; mortality at paediatric intensive care unit discharge, 30 days, 90 days and 12 months; time to liberation from ventilation; duration of organ support; length of paediatric intensive care unit and hospital stay; functional status at paediatric intensive care unit discharge; and health-related quality of life at 12 months. Results: = 0.04 Wilcoxon rank-sum test, adjusted odds ratio 0.84 (95% confidence interval 0.72 to 0.99)]. Both components of the composite primary outcome and secondary outcomes favoured conservative oxygenation. Average costs at 30 days strongly indicated lower costs with conservative oxygenation. Longer-term estimated incremental costs and quality-adjusted life-years were lower and net monetary benefit marginally favoured conservative oxygenation but with wide uncertainty [incremental costs -£879 (95% confidence interval -9036 to 7278); quality-adjusted life-years 0.001 (-0.010 to 0.011); net monetary benefit £894 (95% confidence interval -7290 to 9078)]. Limitations: Exclusion of two large paediatric intensive care unit populations, due to a lack of equipoise and the number of participants excluded because of not being able to obtain deferred consent. Future work: Future work should focus on identification of the mechanisms underlying the observed benefit; trials of intermediate or lower peripheral oxygen saturation values in individuals at higher risk; and identification of individualised treatment effects in relation to oxygen therapy. Conclusions: A conservative oxygenation target resulted in a greater probability of a better outcome in terms of duration of organ support at 30 days or death. Longer-term survival and health-related quality of life were consistent with the primary outcome. While conservative oxygenation is likely to reduce costs in the short term, longer-term cost-effectiveness was surrounded with wide uncertainty. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR127547.