Oxy-PICU pilot study: Safety and feasibility of a clinical trial of permissive hypoxia in paediatric critical illness
Background
Around 19,000 critically ill children are admitted to paediatric intensive care units (PICU) each year in the UK. Of these, around 75% of will receive breathing support via supplementary oxygen, often in conjunction with a ventilator. It is known that adding too much oxygen can injure the lungs and possibly other parts of the body. Current advice is not to use oxygen to achieve ‘normal’ blood oxygen levels (also called oxygen saturations) when the lungs are sick but to aim a few percentage points lower (88-97%). Despite this, these recommendations are not usually followed and doctors and nurses tend to aim for higher numbers – most often 97-100%.
Oxy-PICU aims to find out whether children who come to intensive care in an emergency who need both ventilation and extra oxygen should be treated with oxygen at a lower level (88-92%, which is still within the recommended range) or at the level currently used (95-100%). Before conducting a large, expensive clinical trial, we conducted a pilot study to address the question ‘can a large clinical trial be done?’.
Design
This pilot study tested whether it was possible to conduct the large-scale trial. We undertook an open, parallel-group pilot randomised clinical trial of children receiving mechanical ventilation with supplementary oxygen who were admitted as an emergency to one of three paediatric intensive care units. A ‘research without prior consent’ approach was employed. Children were randomly assigned to a liberal oxygen saturation target of >94% or a conservative oxygen saturation target of 88-92%. Key outcomes looked at were measures of whether conducting a large scale clinical trial was feasible, including: recruitment rate, protocol adherence and acceptability, between group separation of oxygen saturations, and safety.
Results
Overall, 119 children (75% of all those eligible) were randomised between April and July 2017 representing a rate of 10 patients per month per site. On average, time to randomisation from first contact with an intensive care team was ~2 hours. Consent to continue in the study was obtained in 107 cases (90%); parents/legal representatives were supportive of the consent process. On average, oxygen saturations in the conservative oxygen saturations target group were 2.7% lower (95% confidence interval 1.3-4.0% p<0.001) than in the liberal oxygen saturations group. Due to the small number of patients, there were no significant between group differences in clinical outcomes including length of stay, duration of organ support or mortality. Two adverse events were reported in the liberal oxygen saturation target group.
Conclusion
Our pilot study shows that conducting a definitive clinical trial of peripheral oxygen saturation targets is feasible in critically ill children.
Who led the study?
Professor Mark Peters, Great Ormond Street Hospital for Children NHS Foundation Trust
Who funded the study?
Great Ormond Street Hospital Children’s Charity
Publications
Jones GAL, Eaton S, Orford M, Ray S, Wiley D, Ramnarayan P, Inwald D, Grocott MPW, Griksaitis M, Pappachan J, O'Neill L, Mouncey PR, Harrison DA, Rowan KM, Peters MJ. Randomization to a Liberal Versus Conservative Oxygenation Target: Redox Responses in Critically Ill Children. Pediatr Crit Care Med 2023; 24(3):e137-e46. http://dx.doi.org/10.1097/pcc.0000000000003175 Peters MJ, Jones GAL, Wiley D, Wulff J, Ramnarayan P, Ray S, Inwald D, Grocott M, Griksaitis M, Pappachan J, O'Neill L, Eaton S, Mouncey PR, Harrison DA, Rowan KM. Conservative versus liberal oxygenation targets in critically ill children: the randomised multiple-centre pilot Oxy-PICU trial. Intensive Care Med 2018; . http://dx.doi.org/10.1007/s00134-018-5232-7 Jones GAL, Ramnarayan P, Raman S, Inwald D, Grocott MPW, Eaton S, Ray S, Griksaitis MJ, Pappachan J, Wiley D, Mouncey PR, Wulff J, Harrison DA, Rowan KM, Peters MJ. Protocol for a randomised pilot multiple centre trial of conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU). BMJ Open 2017; 7(12):e019253. http://dx.doi.org/10.1136/bmjopen-2017-019253
