Feasibility of a definitive trial of peripheral oxygenation targets in critically ill children: pilot Oxy-PICU trial

EJRC Article Review

Although peripheral oxygen saturation (SpO₂) monitoring is universal, the optimum target for ventilated critically ill children is uncertain. Lower SpO₂targets at 85-89% is favoured in preterm infants [1]. In adults, reported mean number needed to harm using liberal oxygen strategy is 71 [2], with results of the ICU-ROX trial awaited.

Peters et al. conducted an open pilot randomised controlled trial (RCT) to determine the safety and feasibility of a definitive multicentre RCT to address the hypothesis that interventions to raise SpO₂>94% may be associated with harm [3]. 119 children >38 weeks completed gestation and <16 years old, who received invasive/non-invasive ventilation and oxygen supplementation between April and July 2017 in three PICUs were randomised to either liberal (>94%) or conservative (88-92%) SpO₂target groups. Randomisation was carried out within the first 6 hours of face-to-face encounter with PICU staff or the transport team. The primary outcomes were feasibility of recruitment, acceptability of interventions, protocol adherence, between-group separation, and safety.

Mean time to randomisation was 1.9 hours (SD 2.2), which was effective and timely. Consent to continue with the study after randomisation was obtained in 107 cases (90%); this was well received by parents/guardians with encouraging feedback. The median (IQR) of time-weighted individual mean SpO₂was 97.5% (96.2-98.4%) in the liberal group, and 94.9% (92.6-97.1%) in the conservative group (difference 2.7%, 95% CI 1.3–4.0%, p<0.001). Higher than planned SpO₂ in the conservative group was partly due to minimum oxygen already delivered by transport ventilators, or intrinsic SpO₂in patients breathing air. Importantly, there were no significant between-group differences in length of PICU stay, ventilator-free days at 30 days, duration of cardiovascular, renal support and sedatives used, and mortality. There were no safety issues noted.

The strengths of the study lie in the effectiveness of the eligibility criteria in identifying patients and the willingness of clinical staff to engage with the protocol. Between-group separation with similar characteristics was achieved. Weaknesses include the difficulty in generalising the results with exclusion of congenital heart disease, and lack of blinding of clinical staff. The study was unable to control oxygen dose before randomisation. Other haemodynamic changes may alter the balance between oxygen delivery and consumption.

Take Home Messages

• The conservative approach resulted in almost three times more patients on FiO₂21 compared to the liberal approach
• The intervention was deemed acceptable by clinicians and parents, as were protocol adherence
• Between-group separation was achieved, but could be improved.
• Recruitment for a larger RCT is feasible using methods similar to the pilot trial

This article review was prepared by Dr Justin WANG and Dr Amy Chan-Dominy (EJRC member), Paediatric Intensive Care Unit, Royal Brompton & Harefield NHS Foundation Trust, London, on behalf of the ESICM Journal Review Club.

References

1. Tarnow-Mordi M, Stenson B, Kirby A et al. Outcomes of two trials of Oxygen-Saturation Targets in Preterm Infants – The BOOST II Australia and United Kingdom Collaborative Groups. N Engl J Med 2016 Feb;374:749–760.
2. Chu DK, Kim LH, Young PJ et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 2018 Apr;391:1693-1705.
3. Peters MJ, Jones GAL, Wiley D et al. Conservative versus liberal oxygenation targets in critically ill children: the randomised multiple-centre pilot Oxy-PICU trial. Intensive Care Med 2018 Aug;33:1240-8.