Oxygen-saturation targets in extremely preterm infants.

Abstract

Commentary on: Tarnow-Mordi W, Stenson B, Kirby A, Juszczak E, Donoghoe M, Deshpande S, et al. Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants. N Engl J Med 2016; 374: 749–60. Oxygen-saturation target range in extremely preterm infants is an important question of the daily practice in the NICUs, because significant complications such as ROP and BPD can be associated with oxygen exposure outside physiological boundaries. Observational data suggested that saturation <90% was associated with lower rate of ROP without increased rate of CP or death 1. These data led to practice change: targeting lower oxygen saturations in the NICUs without strong evidence of its safety and efficacy from large RCTs. To answer the question whether a lower saturation target range (85–89%) is superior to a higher saturation target range (91–95%) on an outcome of death or major disability at 18–24 months corrected age, five comparative effectiveness trials of oxygen saturation targeting in infants <28 weeks' gestation (the Neonatal Oxygen Prospective Meta-analysis (NeOProM) Collaboration) were designed. The trials were planned similarly and enrolled ~5000 preterm infants <28 weeks of gestation. The report presented the outcomes of two of these trials, the Australian and U.K. BOOST-II trials in children up to a corrected age of two years. As previously reported 2, the NeOProM trials encountered several problems: (i) an oxygen-saturation calibration problem was found in the pulse oximeters used in two of the NeOProM trials (COT, UK BOOST-II): approximately a third fewer oxygen-saturation values between 87 and 90% were displayed than expected, and values >87% were shifted up by 1–2% points; (ii) additionally, when the SUPPORT trial found that targeting the lower oxygen-saturation range resulted in significantly lower rate of ROP, but higher mortality at discharge compared with the higher oxygen-saturation range 3, the BOOST-II trial was stopped early, because the safety monitoring committees found that the pooled safety analysis of the two trials showed similar results to SUPPORT at 36 weeks' postmenstrual age; (iii) none of the NeOProM trials managed to keep the infants' oxygen saturation in the target range: all median oxygen saturations were higher (>89%) than the predetermined in the lower saturation target group, and there was also significant overlap in oxygen saturations achieved. This meta-analysis of the two BOOST-II trials 4 confirms the findings of the SUPPORT that targeting lower oxygen saturation does not increase major disability, however, increases the rate of death. The authors conclude that at present, the most rigorously evaluated evidence for policy is that targeting an oxygen saturation of 91–95% is safer than targeting an oxygen saturation of 85–89%. However, controversy still remains around dynamic saturation target ranges and alarm settings 2 over the neonatal period. Tissue oxygenation, which depends on multiple factors, including oxygen saturation, is affected by foetal haemoglobin concentration and blood haemoglobin level, along with several other factors. Although the quality of the existing evidence has been graded as moderate to low 5, we think that until more sophisticated methods and individual patient data are available, targeting oxygen saturation between 91 and 95% is a reasonable initial approach for extremely preterm infants. Still, in units with low rates of mortality and but high rates of severe ROP, lower saturation targets have been suggested 2. https://ebneo.org/2017/01/oxygen-saturation-targets-in-extremely-preterm-infants None. None.