Targeting Normoxia in Neonates With Cyanotic Congenital Heart Disease in the Intra-operative and Immediate Post-operative Period

Oxidative stress (OS) reflects an imbalance between the production and accumulation of reactive oxygen species. Oxidation of lipids leads to the generation of lipid peroxides which can be detected as Thiobarbituric acid reactive substances (TBARS). Thus, levels of serum TBARS were assessed in participants as indicators of OS.

TBARS levels were assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline pre-operative sample and described as a fold-of-change from baseline. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as TBARS level at each PO time point / TBARS at baseline.

The mean values of the fold of change from baseline between the two groups at each PO time-point were compared.

The count of each of the adverse events within 30 days after the index cardiac surgery, listed here: mortality, cardiac arrest, need for mechanical circulatory support, seizures (clinical or subclinical based on EEG), and need for dialysis is presented below.

Calculated as number of days in the hospital after surgery.

This composite measure reflects the number of days alive and not admitted to the ICU. Non-survivors at day 30 were considered to have no ICU-free days.

The composite endpoint assessed in this study combines in-hospital mortality, cardiac arrest, ECMO, seizures, and dialysis and reflects the number of participants affected by one or more of these outcomes.

Per NCT03229538, a composite mortality, major morbidity and length of stay global rank endpoint with endpoints ranked according to severity. For this endpoint, each randomized patient will be assigned a rank based upon their most-severe outcome. Rank of 91= Post-operative length of stay > 90 days, 92= Post-op cardiac arrest, multi-system organ failure, renal failure with temporary dialysis, or prolonged ventilator support, 93= Reoperation for bleeding, unplanned delayed sternal closure, or post-op unplanned interventional cardiac catheterization, 94= Post-operative mechanical circulatory support or unplanned cardiac reoperation (exclusive of reoperation for bleeding), 95= Renal failure with permanent dialysis, neurologic deficit persistent at discharge, or respiratory failure requiring tracheostomy; 96= Heart transplant (during hospitalization); 97= Operative mortality. Ranks 1 through 90 correspond to the post-operative length of stay in days. A lower score means a better outcome.

Protein carbonyls are generated upon oxidation of proteins and are a marker of oxidative stress. Serum protein carbonyl contents were assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline sample and described as a fold-of-change from baseline. The mean values of the fold of change from baseline between the two groups at each PO time-point were compared. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as Protein Carbonyl level at each PO time point / Protein Carbonyl at baseline.

TAC assays measure serum antioxidants in biological samples. Therefore, lower values reflect depletion of antioxidants in the setting of oxidative stress. Serum TAC was assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline sample and described as a fold-of-change from baseline. The mean values of the fold of change from baseline between the two groups at each PO time-point were compared. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as TAC level at each PO time point / TAC at baseline.

8-isoprostane is a stable oxidative stress marker formed by non-enzymatic perioxidation of lipids. Serum levels of 8-isoprostane were assessed at three separate time points in the first 24 hours after surgery (2, 6, and 24 hours). Each participant's post-operative (PO) samples were normalized to their baseline sample and described as a fold-of-change from baseline. The mean values of the fold of change from baseline between the two groups at each PO time-point were compared. The fold-of-change describes how much a quantity changes between an original and a subsequent measurement and is calculated as 8-isoprostane level at each PO time point / 8-isoprostane at baseline.