Longer-term survival, quality of life, and cost-effectiveness of conservative versus liberal oxygenation targets in critically ill children: a pre-specified analysis from Oxy-PICU, a multicentre, open, parallel-group, randomised controlled trial.

Background: Peripheral oxygen saturation (SpO₂) above 94% is typical in children in paediatric intensive critical care units (PICUs) who are receiving invasive ventilation and supplemental oxygen. In a previous report from the Oxy-PICU trial, we showed that lower (conservative) oxygenation targets (SpO₂ 88-92%) are beneficial, showing small but statistically significant differences in duration of organ support and large but non-significant cost reductions at 30 days. In this pre-specified analysis of the Oxy-PICU trial, we compare longer-term outcomes and cost-effectiveness of conservative versus liberal (SpO₂ >94%) oxygenation targets in children with emergency PICU admission.

Methods: Oxy-PICU was a pragmatic, multicentre, open-label, randomised controlled trial in England and Scotland. Eligible children were older than 38 weeks and younger than 16 years and had been admitted for emergency care in one of 15 participating PICUs, where they received invasive respiratory support for abnormal gas exchange. Participants were randomly assigned (1:1) to either a conservative oxygenation target (SpO₂ 88-92%) or liberal oxygenation target (SpO₂ >94%). Survival status was assessed at 90 days and 1 year, and health-related quality of life (HRQoL), quality-adjusted life-years (QALYs), health-care costs, and incremental net monetary benefit were assessed at 1 year after the index hospital admission and randomisation. HRQoL was measured with age-appropriate Paediatric Quality of Life Generic Core Scales and mapped onto the Child Health Utility 9D index score. HRQoL and survival data were combined to construct QALYs. Costs at 1 year were derived from use of hospital, outpatient, and community health services. The trial was registered in the ISRCTN registry (ISRCTN92103439).

Findings: 2040 children were enrolled between Sept 1, 2020 and May 15, 2022. 1868 (91·6%) children were included in the 90-day survival analysis; of these 930 (49·8%) had been assigned liberal oxygen and 938 (50·2%) conservative oxygen. 1867 (91·5%) children were included in the 1-year survival analysis; 930 (49·8%) had been assigned liberal oxygenation and 937 (50·2%) conservative oxygen. At 90 days, 35 (3·7%) patients in the conservative oxygenation group and 45 (4·8%) patients in the liberal oxygenation group had died (adjusted hazard ratio [aHR] 0·75 [95% CI 0·48 to 1·17]). By 1 year, 52 (5·5%) patients in the conservative oxygenation group and 66 (7·1%) patients in the liberal oxygenation group had died (aHR 0·77 [95%CI 0·53 to 1·10]). Overall, mean HRQoL, life-years, and QALYs at 1 year were similar in the two groups. The adjusted incremental effect on cost of conservative oxygenation versus liberal oxygenation was -£879 (95% CI -9036 to 7278), whereas the incremental difference in QALYs was estimated at 0·001 (-0·010 to 0·011), leading to an incremental net monetary benefit of £894 (-7290 to 9078) associated with conservative oxygenation relative to liberal oxygenation. These results did not vary by age (<12 months vs ≥12 months), comorbidity at baseline, age-adjusted heart rate, or haemoglobin level at admission and were robust to alternative assumptions.

Interpretation: Compared with usual care (SpO₂ >94%) for invasively ventilated children who are admitted as an emergency to a PICU, conservative oxygenation (SpO₂ 88-92%) was not associated with differences in longer-term survival, costs, or cost-effectiveness. Taken together with previous findings of Oxy-PICU that conservative oxygenation compared with liberal oxygenation leads to better patient-centred and parent-centred outcomes at 30 days, these findings support the use of conservative oxygenation targets for this population.

Funding: UK National Institute for Health and Social Care Research Health Technology Assessment Programme.