Protocol for a Randomized Multiple Center Trial of Conservative Versus Liberal Oxygenation Targets in Critically Ill Children (Oxy-PICU): Oxygen in Pediatric Intensive Care

Abstract

OBJECTIVES: Oxygen administration is a fundamental part of pediatric critical care, with supplemental oxygen offered to nearly every acutely unwell child. However, optimal targets for systemic oxygenation are unknown. Oxy-PICU aims to evaluate the clinical effectiveness and cost-effectiveness of a conservative peripheral oxygen saturation (Sp o 2 ) target of 88–92% compared with a liberal target of more than 94%. DESIGN: Pragmatic, open, multiple-center, parallel group randomized control trial with integrated economic evaluation. SETTING: Fifteen PICUs across England, Wales, and Scotland. PATIENTS: Infants and children age more than 38 week-corrected gestational age to 16 years who are accepted to a participating PICU as an unplanned admission and receiving invasive mechanical ventilation with supplemental oxygen for abnormal gas exchange. INTERVENTION: Adjustment of ventilation and inspired oxygen settings to achieve an Sp o 2 target of 88–92% during invasive mechanical ventilation. MEASUREMENTS and MAIN RESULTS: Randomization is 1:1 to a liberal Sp o 2 target of more than 94% or a conservative Sp o 2 target of 88–92% (inclusive), using minimization with a random component. Minimization will be performed on: age, site, primary reason for admission, and severity of abnormality of gas exchange. Due to the emergency nature of the treatment, approaching patients for written informed consent will be deferred to after randomization. The primary clinical outcome is a composite of death and days of organ support at 30 days. Baseline demographics and clinical status will be recorded as well as daily measures of oxygenation and organ support, and discharge outcomes. This trial received Health Research Authority approval on December 23, 2019 (reference: 272768), including a favorable ethical opinion from the East of England—Cambridge South Research Ethics Committee (reference number: 19/EE/0362). Trial findings will be disseminated in national and international conferences and peer-reviewed journals.

The Local and Systemic Exposure to Oxygen in Children With Severe Bronchiolitis on Invasive Mechanical Ventilation: A Retrospective Cohort Study

“…Furthermore, overly restrictive targets have even been identified as potentially dangerous in preterm neonates ( 24 ). The ongoing Oxy-PICU trial will provide first evidence on the effects, including on long-term outcomes, in children ( 25 ).…”

Admission Pao 2 and Mortality Among PICU Patients and Select Diagnostic Subgroups

“…Given the clear association between hyperoxemia and mortality, there is great interest in investigating whether reducing oxygen exposure can improve outcomes. A randomized controlled trial of conservative versus liberal oxygenation targets in critically ill children is currently underway, entitled the Oxy-PICU trial (24, 25). The trial is being conducted among 15 PICUs in England, Wales, and Scotland.…”

The United Kingdom Paediatric Critical Care Society Study Group: The 20-Year Journey Toward Pragmatic, Randomized Clinical Trials

“…The stringent test of feasibility was applied in the pilot RCT, and data on anticipated recruitment rates, acceptability of the consent model, and point estimates of outcome measures were obtained (14). Informative pilot work was also a key factor behind the successful recruitment of 2,040 children to the Oxygen targets on PICU (OXY-PICU) trial (conservative versus liberal oxygenation targets in PICU) from September 2020 to May 2022, including during the COVID-19 pandemic (12, 13).…”

“…2). Now, consider, first, the size of recently completed pragmatic RCTs, including: effect of a sedation and ventilator liberation protocol versus usual care on duration of invasive mechanical ventilation (8,843 patients from 18 PICUs) (8), FIRST-ABC Step-up and Step-down trials (1,200 patients from 24 PICUs) (9, 10), and Oxygen targets on PICU (OXY-PICU) trial (2,040 patients from 15 PICUs) (12). Add two other planned RCTs: the PRotocolised Evaluation of permiSSive blood pressure targets versus Usual caRE (PRESSURE) trial (protocolized evaluation of permissive blood pressure targets versus usual care, International Standard Randomised Controlled Trial Number [ISRCTN] 20609635); which opened in September 2021 and aims to recruit 1,900 intubated patients receiving vasoactive infusions for shock in 17 PICUs; and the no routine gastric residual monitoring to guide enteral feeding in PICU (GASTRIC-PICU; ISRCTN pending) trial that will open in 2023 and aims to recruit 4,700 patients from 25 PICUs in the United Kingdom and Switzerland (7).…”

“…1). To date, the SG has led 13 different multicenter studies and RCTs, spanning a variety of study designs, methodologies, and scale (Table 1) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In this Special Article for Pediatric Critical Care Medicine, we outline the successes and challenges faced by the PCCS-SG since 2005.…”