62 A. G. Beshish et al.: J Extra Corpor Technol 2025, 57, 59 – 65
Functional
Status Scale( FSS) of survivors and development of new morbidity and unfavorable outcomes
Of the 81 survivors, 70( 86.4 %) were from the non-hyperoxia group and 11( 13.6 %) were from the hyperoxia group. New morbidity( change in total FSS 3) was demonstrated in 28.6 %( 20 / 70) of the non-hyperoxia group, and 18.2 %( 2 / 11) of the hyperoxia-group survivors. Unfavorable outcomes( change in total FSS 5) developed in 7.1 %( 5 / 70) of the non-hyperoxia survivors, and 9.1 %( 1 / 11) of the hyperoxia survivors( Table 3). We failed to identify an association between designation as“ hyperoxia” and new morbidity, or unfavorable outcome( Table 3).
Figure 1. Receiver operating characteristic( ROC) curve identifying the optimal discriminatory cut point for mortality was 122 mmHg( sensitivity 41 %, Specificity 86 %).
Figure
2. Flow chart of pediatric patients requiring veno-veno extracorporeal life support( VV-ECLS) stratified based on PaO 2 levels in the first 48-hours while on ECLS.
Outcomes analysis
In univariable analysis, we found that hyperoxia was associated with 4.49 higher odds of mortality( 95 % CI: 1.70, 11.9, p = 0.003)( Table 2). In the multivariable analysis when controlling for age group( neonates vs. pediatrics), BSA, and indication for ECLS, patients in the hyperoxia group had 7.97 higher odds of mortality( 95 % CI: 1.72, 36.86, p = 0.0079). Hyperoxia was not associated with the development of ECLS complications or the development of Stage II or III AKI( Table 2). The association of average PaO 2 and ECLS duration is graphically demonstrated in Figure 3 [ p = 0.107, with a correlation coefficient of �0.16( 95 % CI: �0.33, 0.03)]. A univariable analysis was conducted in relationship to age group( neonatal vs pediatric), ECLS indication( pulmonary vs cardiac) and body surface area( BSA) with each outcome individually and is shown in Supplemental Table 2.
Discussion
In this report, we describe a cohort of pediatric patients supported with VV-ECLS with an overall mortality rate of 26.4 %. Using a ROC curve, a mean PaO 2 of 122 mmHg in the first 48 hours of VV-ECLS was determined to have the optimal discrimination for mortality( sensitivity 41 % and specificity 86 %). Of the 110 VV-ECLS runs, 23( 20.9 %) had PaO 2 > 122 mmHg and were categorized as a hyperoxia group. Patients in the hyperoxia group had 4.5 times higher odds of dying in the unadjusted analysis. This persisted when adjusting for confounders( BSA, ECLS age group, and indication for ECLS) with patients in the hyperoxia group having 7.97 times( 95 % CI: 1.72, 36.86, p = 0.008) higher odds of mortality. While hyperoxia during VV-ECLS may not directly lead to death, we postulate that hyperoxia contributes to comorbidity accumulation that later leads to complications and mortality.
In other critical illness settings, an association between excessive oxygen delivery and poor clinical outcomes has been reported. In patients requiring ECLS for cardiac arrest( CA), hyperoxia( as defined by a mean PaO 2 > 193 mmHg) was associated with increased 30-day mortality and the need for dialysis [ 4, 15, 25 ]. In a large multicenter cohort study of adult patients admitted to the ICU after resuscitation from CA, Kilgannon et al. showed an association between hyperoxia and risk of in-hospital death consistent with a dose-dependent relationship [ 15 ]. In a prospective disease-specific CA database, Elmer and colleagues found exposure to severe hyperoxia was independently associated with inpatient mortality [ 25 ]. Several reports of neonates with asphyxia have demonstrated an association between hyperoxia and an increased risk of brain injury and mortality [ 4, 26, 27 ]. Conversely, Raman et al. in a singlecenter study and systematic review of a heterogeneous cohort of critically ill patients did not demonstrate an association between hyperoxia at the time of admission and mortality [ 28 ]. These reports support earlier findings that hyperoxia is likely associated with worse outcomes, but which populations are at risk remains unclear, and the impact of other clinical variables that may affect oxygenation directly or indirectly. Some of these factors are patient hemoglobin levels, ventilator settings including FiO 2, the health, and age of the oxygenator in the ECLS circuit, ECLS flows, recirculation, and if the patient is