Liberal oxygenation in paediatric intensive care: retrospective analysis of high-resolution SpO2 data

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Severe hypoxia is detrimental during critical illness, but hyperoxia has also been associated with adverse outcomes [13]. Harm from hyperoxia may be a biological consequence of oxidative damage or reflect iatrogenic injury resulting from more aggressive care. ARDSnet protocols include conservative oxygenation targets (arterial oxygen saturation (SpO2) 88–95%) [4] in recognition of the fact that the harms of high inspired oxygen fractions (FiO2) and ventilation volumes and pressures may outweigh any advantage of an additional buffer against hypoxia.

Where does this balance of harm and benefit of oxygenation lie on the paediatric intensive care unit (PICU)? As part of preliminary work towards our Oxy-PICU trial for conservative versus liberal oxygenation targets, we investigated current practice at a large general PICU over 12 months. Children were selected on the basis of a measured actual oxygen content in arterial blood (PaO2):FiO2 ratio (PF) of <300 mmHg (8217 values in 326 children). This criterion excluded children likely to have high SpO2 values without supplemental oxygen or ventilator support. We analysed SpO2 data at 5-s intervals in the 1 h before and after 5096 PF values of <300 mmHg from 227 children with available data: a total of 7,352,388 SpO2 values were collected using the Etiometry T3 system (Etiometry Inc., Allston, MA). Concurrent hourly FiO2 and mean airway pressure (MAP) data were collected from the electronic health record. SpO2 data were analysed in four groups based on a FiO2 of ≥ or <0.6, and a MAP of ≥ or <16 cmH2O in the hour of measurement. The SpO2 distributions were compared using the Kolmogorov–Smirnov test. A multi-level linear regression model was used to test whether the SpO2 (dependent variable), FiO2 and MAP (as categorical fixed effect variables) relationship was skewed by individual patients (random effects variable). Any crude mortality effect of oxygenation was sought by comparing the mean SpO2 value over the first 48 h of admission according to survival status at discharge. All data were processed using Microsoft Excel (Microsoft Corp., Redmond, WA) and R (http://www.r-cran.org).

The distribution of SpO2 values are shown in Fig. 1. In all four combinations of FiO2 and MAP, 99–100% was the modal SpO2; 26.4% of all SpO2 values were 99 or 100%, and 70.8% were >95%. Each of the four distributions were significantly different to each other (Kolmogorov–Smirnov p < 0.001), with the greatest difference observed between high and low FiO2 groups. The multi-level regression model confirmed that high FiO2 was associated with lower SpO2 regardless of individual patients. There were no significant differences between the 48-h mean SpO2 values in those who died or survived (see Electronic Supplementary Material).

Fig. 1
figure1

SpO2 distributions according to FiO2 and MAP. The top left panel shows the SpO2 distribution when FiO2 ≥ 0.6 and MAP < 16 cm H2O; the top right panel with FiO2 ≥ 0.6 and MAP ≥ 16; the bottom left panel FiO2 < 0.6 and MAP < 16: bottom right panel FiO2 < 0.6 and MAP ≥ 16. All four distributions differ significntly according to the Kolmogorov–Smirnov test, with the greatest difference between FiO2 < 0.6 and MAP ≥ 16, i.e. top and bottom panels (high vs. low FiO2 D-statistic 0.12, p < 2.2 × 10−16; high vs. low MAP D-statistic 0.05, p < 2.2 × 10−16)

These data demonstrate (1) current practice is for very liberal oxygenation above the recommended targets even in children with low PF ratios; (2) children receiving higher treatment levels (FiO2 ≥0.6, MAP >16 cmH2O) have a slightly lower SpO2 distribution, an effect more pronounced with high FiO2 than with high MAP.

These high-resolution data demonstrate that PICU practice does not follow what clinicians report [5], recent evidence [3] or existing guidelines [4]. A pragmatic clinical trial of oxygenation targets in critically ill children is necessary, and can reasonably include a control group with >94% SpO2 to reflect current practice.

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Correspondence to Samiran Ray.

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Conflicts of interest

Sainath Raman is a co-investigator and Mark Peters is the Chief Investigator on Oxy-PICU: a randomised feasibility multiple centre trial of conservative versus liberal oxygenation targets in critically ill children, funded by Great Ormond Street Hospital Children’s Charity. The other investigators are Dr. P Ramnarayan, Prof M Grocott, Dr. D Harrision, Prof Kathy Rowan, P Mouncey, Dr. S Eaton, Dr. D Inwald, Dr. J Pappachan and N and S Heinoch.

Funding

This work was undertaken at Great Ormond Street Hospital/UCL Institute of Child Health, which received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centre’s funding scheme.

Ethical approval

The study was registered with the Institutional Audit Department (ref 2013). Individual patient consent was not sought as this is a retrospective observational study and no patient identifiable data is reported.

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Ray, S., Rogers, L., Raman, S. et al. Liberal oxygenation in paediatric intensive care: retrospective analysis of high-resolution SpO2 data. Intensive Care Med 43, 146–147 (2017). https://doi.org/10.1007/s00134-016-4606-y

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Keywords

  • Paediatric Intensive Care Unit
  • Mean Airway Pressure
  • High FiO2
  • Lower SpO2
  • Pragmatic Clinical Trial