1 Supplementary Digital Content: Randomisation to a Liberal versus Conservative Oxygenation Target: Redox Responses in Critically ill Children Contents: Supplementary Table 1 Page 2 Supplementary Table 2 Page 3 Supplementary Table 3 Page 4 Supplementary Table 4 Page 5

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1 Supplementary Digital Content: Randomisation to a Liberal versus Conservative Oxygenation Target: Redox Responses in Critically ill Children

Contents:

Supplementary Table 1 Page 2 Supplementary Table 2 Page 3 Supplementary Table 3 Page 4 Supplementary Table 4 Page 5

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Supplementary Table 1: Numbers of samples not available for analysis and reason.

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3 Supplementary Table 2: Beta coefficient following multi-variable mixed effect regression analysis, with biomarker as the response variables, SpO2-time area under the curve, age, and a time point and allocation interaction term as the fixed effects variables and patient identifiers as the random effects variables. All continuous values and SpO2-time area under the curve values were log transformed for the purposes of the model given skewed distributions. The model used time point and allocation as a categorical variables, with the beta coefficient of time-point 2 in relation to time-point 1, and liberal in relation to conservative arms as the output.

There is a positive association between SpO2-time area under the curve and IMA (both log transformed), but no significant associations between the MDA, Nitrate/nitrite and HIF1α, and SpO2-time area under the curve.

Biomarker Beta

coefficient

95% Confidence Interval IMA

SpO2-time AUC Time point (2 cf 1)

Allocation (Liberal cf Conservative) Time point 2 * Liberal arm

Age in years

0.07 -0.10 0.04

0 -0.03

0.01, 0.12 -0.26, 0.06 -0.9, 0.18 -0.17, 0.17 -0.06, -0.01 TBARS

Age in years

0.01 0.04 0.07 0.06 -0.02

-0.09, 0.10 -0.23, 0.31 -0.16, 0.31 -0.23, 0.35 -0.06, 0.01 Nitrate/nitrite

Age in years

-3 x 10-6 -0.60 -0.36 0.86 -0.04

-0.19, 0.19 -1.17, -0.08

-0.78, 0.06 0.32, 1.43 -0.11, 0.02 HIF-1α

Age in years

0.01 -0.91 -1.17 0.76 0.04

-0.41, 0.42 -2.03, 0.22 -2.22, -0.12

-0.42, 1.88 -0.08, 0.15

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Supplementary Table 3: Supplementary Table 3: Demographic information of age and sex of participants with samples available.

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5 Biomarker Liberal

group mean Conservative

group mean Standard

deviation Effect

size Sample size (per group) IMA

- Timepoint 1 - Timepoint 2

0.0104 0.0103

0.0093 0.0099

0.0035 0.0022

0.3239 0.1707

174 621 TBARS

5.56 5.93

5.08 5.46

3.09 2.83

0.16 0.17

729 640 RONS

87.0 103.6

117.9 49.3

74.1 50.7

-0.42 1.07

105 17 HIF-1a

0.02 0.02

0.10 0.09

0.10 0.11

0.52 0.64

67 46

Supplementary table 4: Sample size estimates needed to detect a difference with 80% and a two-sided alpha of 0.05 for each biomarker measured. The sample size was scaled up by 15% to account for non-parametric tests.