Randomization to a Liberal Versus Conservative Oxygenation Target: Redox Responses in Critically Ill Children.
Pediatr Crit Care Med
; 24(3): e137-e146, 2023 03 01.
Article
en En
| MEDLINE
| ID: mdl-36728001
ABSTRACT
RATIONALE Optimal 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. OBJECTIVES:
To 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.DESIGN:
Mechanistic substudy nested within the Oxygen in PICU (Oxy-PICU) pilot randomized feasibility clinical trial ( ClinicalTrials.gov NCT03040570).SETTING:
Three U.K. mixed medical and surgical PICUs in university hospitals. PATIENTS Seventy-five eligible patients randomized to the Oxy-PICU randomized feasibility clinical trial.INTERVENTIONS:
Randomization to a conservative (Sp o2 88-92%) versus liberal (Sp o2 > 94%) peripheral oxygenation target. MEASUREMENTS AND MAINRESULTS:
Blood 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.CONCLUSIONS:
On 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_muertes_prevenibles
Asunto principal:
Enfermedad Crítica
/
Nitratos
Tipo de estudio:
Clinical_trials
Límite:
Child
/
Humans
Idioma:
En
Revista:
Pediatr Crit Care Med
Asunto de la revista:
PEDIATRIA
/
TERAPIA INTENSIVA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Reino Unido