• Gareth A L Jones, Simon Eaton, Michael Orford, Samiran Ray, Daisy Wiley, Padmanabhan Ramnarayan, David Inwald, GrocottMichael P WMPWAnaesthesia Perioperative and Critical Care Research Group, Southampton NIHR Biomedical Research Centre, University Hospital Southampton/ University of Southampton, Southampton, United Kingdom., Michael Griksaitis, John Pappachan, Lauran O'Neill, Paul R Mouncey, David A Harrison, Kathryn M Rowan, Mark J Peters, and Oxy-PICU Investigators of the Paediatric Critical Care Society Study Group (PCCS-SG).
• Respiratory Critical Care and Anaesthesia Unit, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.
• Pediatr Crit Care Me. 2023 Mar 1; 24 (3): e137e146e137-e146.

RationaleOptimal systemic oxygenation targets in pediatric critical illness are unknown. A U-shaped relationship exists between blood oxygen levels and PICU mortality. Redox stress or iatrogenic injury from intensive treatments are potential mechanisms of harm from hyperoxia.ObjectivesTo measure biomarkers of oxidative status in children admitted to PICU and randomized to conservative (oxygen-hemoglobin saturation [Sp o2 ] 88-92%) versus liberal (Sp o2 > 94%) peripheral oxygenation targets.DesignMechanistic substudy nested within the Oxygen in PICU (Oxy-PICU) pilot randomized feasibility clinical trial ( ClinicalTrials.gov : NCT03040570).SettingThree U.K. mixed medical and surgical PICUs in university hospitals.PatientsSeventy-five eligible patients randomized to the Oxy-PICU randomized feasibility clinical trial.InterventionsRandomization to a conservative (Sp o2 88-92%) versus liberal (Sp o2 > 94%) peripheral oxygenation target.Measurements And Main ResultsBlood and urine samples were collected at two timepoints: less than 24 hours and up to 72 hours from randomization in trial participants (March 2017 to July 2017). Plasma was analyzed for markers of ischemic/oxidative response, namely thiobarbituric acid-reactive substances (TBARS; lipid peroxidation marker) and ischemia-modified albumin (protein oxidation marker). Total urinary nitrate/nitrite was measured as a marker of reactive oxygen and nitrogen species (RONS). Blood hypoxia-inducible factor (HIF)-1a messenger RNA (mRNA) expression (hypoxia response gene) was measured by reverse transcription- polymerase chain reaction. Total urinary nitrate/nitrite levels were greater in the liberal compared with conservative oxygenation group at 72 hours (median difference 32.6 μmol/mmol of creatinine [95% CI 13.7-93.6]; p < 0.002, Mann-Whitney test). HIF-1a mRNA expression was increased in the conservative group compared with liberal in less than 24-hour samples (6.0-fold [95% CI 1.3-24.0]; p = 0.032). There were no significant differences in TBARS or ischemia-modified albumin.ConclusionsOn comparing liberal with conservative oxygenation targets, we show, first, significant redox response (increase in urinary markers of RONS), but no changes in markers of lipid or protein oxidation. We also show what appears to be an early hypoxic response (increase in HIF-1a gene expression) in subjects exposed to conservative rather than liberal oxygenation targets.Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

26 keywords...

hide…