Lower Saturation Targets Research Articles

Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial: Study Protocol and Statistical Analysis Plan

IntroductionCritically ill patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) are at risk of developing severe arterial hyperoxia, which has been associated with increased mortality. Lower saturation targets in this population may lead to deleterious episodes of severe hypoxia. This manuscript describes the protocol and statistical analysis plan for the Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial. DesignThe BLENDER trial is a pragmatic, multicentre, registry-embedded, randomised clinical trial., registered at ClinicalTrials.gov (NCT03841084) and approved by The Alfred Hospital Ethics Committee project ID HREC/50486/Alfred-2019. Participants and settingPatients supported by VA ECMO for cardiogenic shock or cardiac arrest who are enrolled in the Australian national ECMO registry. InterventionThe study compares a conservative oxygenation strategy (target arterial saturations 92–96%) with a liberal oxygenation strategy (target 97–100%). Main Outcome MeasuresThe primary outcome is the number of intensive care unit (ICU)-free days for patients alive at day 60. Secondary outcomes include duration of mechanical ventilation, ICU and hospital mortality, the number of hypoxic episodes, neurocognitive outcomes, and health economic analyses. The 300-patient sample size enables us to detect a 3-day difference in ICU-free days at day 60, assuming a mean ICU-free days of 11 days, with a risk of type 1 error of 5% and power of 80%. Data will be analysed according to a predefined analysis plan. Findings will be disseminated in peer-reviewed publications. ConclusionsThis paper details the protocol and statistical analysis plan for the BLENDER trial, a registry-embedded, multicentre interventional trial comparing liberal and conservative oxygenation strategies in VA ECMO.

Abstract 14185: Targeting Lower Oxygen Saturation Parameters in Premature Infants Does Not Increase Incidence of Pulmonary Hypertension in the Neonatal Intensive Care Unit

Introduction: Lower oxygen saturation targets in preterm infants have been associated with decreased incidence of bronchopulmonary dysplasia (BPD) but increased risk of pulmonary hypertension (PH). Studies have shown that targets of <90% are associated with higher incidence of PH, however data on the optimal saturation target >90% are lacking. In this study, we compared the rate of BPD and PH in two cohorts with saturation targets of 94-98% and 92-97%. We hypothesized that BPD rate would be lower and PH rate would be unchanged at the lower saturation target. Methods: We performed a retrospective cohort study comparing PH and BPD rates among two cohorts of infants born at ≤32 weeks gestation at Brigham and Women’s Hospital: cohort 1 with saturation target of 94-98% (n = 129, July 2017-July 2018), cohort 2 with saturation target of 92-97% (n = 124, July 2018-July 2019). PH was defined by echocardiographic evidence of systolic septal flattening or right ventricular pressure ≥35 mmHg (estimated by tricuspid regurgitant jet velocity or shunt velocity) at gestational age (GA) ≥36 weeks. Comparisons between groups were carried out by Chi-square test, t-test, and multivariable logistic regression. Results: Subjects had a GA of 23-32 weeks; 46% were female. Groups did not differ with respect to GA, sex, or birth weight. There was no difference in rate of PH (2.4% vs. 4.2%, p = 0.12) or BPD (25% vs. 20%, p = 0.31) between cohort 1 and cohort 2. Other clinical parameters were not different between groups, including presence of patent ductus arteriosus, presence of atrial septal defect, use of diuretics, or use of steroids. After controlling for GA, birth weight, sex, and diagnosis of BPD using logistic regression, there was no difference in rate of PH between groups (p = 0.47), but there was a positive association of BPD with PH (OR 3.45; 95% CI, 1.18-10.09; p = 0.02). Conclusions: A lower oxygen saturation target was not associated with a higher rate of PH or lower rate of BPD in preterm infants. The overall rate of PH was much lower than rates previously reported at saturation targets <90%. Given our low incidence of PH, and the lack of a significant difference in rate of PH between groups, a saturation target of 92-97% may be safe while also minimizing need for supplemental oxygen in this population.

Reduced rate of treated retinopathy of prematurity after implementing lower oxygen saturation targets.

To evaluate an implementation of lower oxygen saturation targets with retinopathy of prematurity (ROP) as primary outcome, in infants at the lowest extreme of prematurity. Retrospective cohort including infants born at 22-25 weeks of gestation in 2005-2015 (n = 325), comparing high (87-93%) and low (85-90%) targets; infants transferred early were excluded from the main analysis to avoid bias. Overall survival was 76% in high saturation era, and 69% in low saturation era (p = .17). Treatment-requiring ROP was less common in low saturation group (14% vs 28%, p < .05) with the most prominent difference in the most immature infants. Including deceased infants in the analysis, necrotizing enterocolitis was more frequent in low saturation era (21% vs 10%, p < .05). Implementing lower saturation targets resulted in a halved incidence of treatment-requiring ROP; the most immature infants seem to benefit the most. An association between lower oxygenation and necrotizing enterocolitis cannot be excluded.

Algorithms that eliminate the effects of calibration artefact and trial-imposed offsets of Masimo oximeter in BOOST-NZ trial.

The displayed readings of Masimo pulse oximeters used in the Benefits Of Oxygen Saturation Targeting (BOOST) II and related trials in very preterm babies were influenced by trial-imposed offsets and an artefact in the calibration software. A study was undertaken to implement new algorithms that eliminate the effects of offsets and artefact. In the BOOST-New Zealand trial, oxygen saturations were averaged and stored every 10s up to 36weeks' post-menstrual age. Two-hundred and fifty-seven of 340 babies enrolled in the trial had at least twoweeks of stored data. Oxygen saturation distribution patterns corresponding with a +3% or -3% offset in the 85-95% range were identified together with that due to the calibration artefact. Algorithms involving linear and quadratic interpolations were developed, implemented on each baby of the dataset and validated using the data of a UK preterm baby, as recorded from Masimo oximeters with the original software and a non-offset Siemens oximeter. Saturation distributions obtained were compared for both groups. There were a flat region at saturations 85-87% and a peak at 96% from the lower saturation target oximeters, and at 93-95 and 84% respectively from the higher saturation target oximeters. The algorithms lowered the peaks and redistributed the accumulated frequencies to the flat regions and artefact at 87-90%. The resulting distributions were very close to those obtained from the Siemens oximeter. The artefact and offsets of the Masimo oximeter's software had been addressed to determine the true saturation readings through the use of novel algorithms. The implementation would enable New Zealand data be included in the meta-analysis of BOOST II trials, and be used in neonatal oxygen studies.

Oxygen for Newborns: How Much is Too Much?

International guidelines for newborn resuscitation recommend the use of 100% oxygen. However, high concentrations of oxygen after asphyxiation activate reactive oxygen species that may contribute to a number of morbidities. Animal models have been useful in describing their mechanisms, but only large-scale clinical trials can provide evidence that may be used to alter clinical practice. It has been demonstrated that neonates recover faster when resuscitated with room air as opposed to pure oxygen and neonatal mortality rates are improved. Increases in saturation are equal with oxygen and room air resuscitation. Studies of normal oxygen saturation immediately after birth suggest that clinicians may unnecessarily be rushing to high saturations. In the first weeks of life, lower saturation targets in preterm infants reduce retinopathy of prematurity and pulmonary complications and may improve growth. The neonatologist would be well served to think of oxygen as a medication, and use it sparingly.