A. Saini et al.: J Extra Corpor Technol 2026, 58, 32 – 38 33
exposure to hyperoxia during ECLS can further exacerbate tissue injury and inflammation, leading to worsened outcomes in patients supported by ECLS.
Previous studies have reported an association between hyperoxia during ECLS or cardiopulmonary bypass with increased mortality in pediatric patients [ 9 – 11 ]. However, it remains unclear whether the deleterious effect of hyperoxia occurs beyond a specific threshold or follows a dose-dependent effect, with evidence supporting both possibilities [ 4, 10 ]. Furthermore, the definition of hyperoxia varies across studies. This study aims to expand on these findings by focusing exclusively on pediatric patients supported by VA – ECMO across all indications to determine the association between hyperoxia and poor outcomes. Furthermore, hyperoxia was stratified into three distinct levels of severity( mild, moderate, and severe) to investigate a potential threshold for predicting adverse outcomes.
Materials and methods
This single-center retrospective cohort study included all neonatal and pediatric patients who required VA – ECLS between January 1st, 2014, and December 31st, 2019, at Children’ s Healthcare of Atlanta( CHOA), a free-standing, university-affiliated quaternary children’ s hospital. Eligible patient encounters were identified through an internal ECLS database. Preterm neonates( gestational age < 37 weeks) as well as patients less than 2 kg at time of ECMO initiation were excluded. The primary objective was to assess whether hyperoxia during VA – ECLS is associated with increased in-hospital mortality. The secondary objective was to determine whether hyperoxia is associated with higher odds of complications and morbidity using standardized and generalizable definitions. The study was approved by the CHOA Institutional Review Board( IRB # 00001239), with informed consent waived.
Data and definitions
All consecutive patients who required VA – ECLS during their index hospitalization in the neonatal, pediatric, and cardiac intensive care units were included in the study. For patients with multiple ECLS courses, only the first ECLS run was included. Demographic data, clinical characteristics, and ECLS-related variables were collected. The indication for ECLS was categorized as cardiac, extracorporeal cardiopulmonary resuscitation( E – CPR), or respiratory based on the extracorporeal life support organization( ELSO) categorization. All arterial blood gas( ABG) measurements obtained during the first 48 h of ECLS initiation were reviewed for the partial pressure of oxygen( PaO 2). Normoxia was defined as PaO 2 of 100 mmHg. Hyperoxia was categorized based on the single highest PaO 2 value as mild( PaO 2: 101 – 200 mmHg), moderate( PaO 2: 201 – 300 mmHg), and severe( PaO 2 > 300 mmHg). These categories were chosen to create clinically relevant strata based on prior studies [ 9, 10 ]. ECLS complications based on definitions from the ELSO registry were documented, including cardiovascular, hematologic, mechanical, renal, neurologic, metabolic, and infectious complications [ 12 ]. Additionally, the incidence of Acute kidney injury( AKI) was recorded using the KDIGO scoring criteria [ 13 ]. The primary outcome was all-cause inhospital ECLS mortality. Secondary outcomes included a composite measure of cardiovascular or renal complications( per ELSO definitions), incidence of AKI, and change in Functional Status Scale( FSS) score.
Functional Status Scale( FSS)
The FSS consists of 6 main domains: mental status, sensory, communications, motor function, feeding, and respiratory. Each domain is scored from 1( normal) to 5( severe dysfunction), with a total FSS score range of 6 – 30 [ 14 ]. Baseline and discharge FSS scores were determined retrospectively from clinical documentation, blinded to hyperoxia status. Newborns without a stable baseline function were assigned an FSS score of 6. This applied to all infants 2 days old at admission and those transferred from another facility between 3 to 6 days of age [ 15 ]. New morbidity was defined as an increase in the total FSS score of 3 points, while an unfavorable functional outcome was defined as an increase of 5points [ 16 ].
Clinical management
For patients < 40 kg, ECLS circuits were blood primed with packed red blood cells, 25 % albumin, sodium-bicarbonate, calcium-gluconate, and heparin. The initial ABG was obtained at the clinical team’ s discretion, typically 30 min after ECLS cannulation, followed by hourly ABGs for the first 3 h. Subsequent ABGs were obtained every 3 – 6 h and 30 min after any adjustment in ECLS support. Our center does not follow a standardized protocol for PaO 2 targets, and the variations described reflect standard clinical care. Typical pH and PaCO 2 goals at our institution are 7.35 – 7.45 and 35 – 45 mmHg, respectively. While these are general goals, there was no standardized protocol or timeline to achieve them, and management was at the discretion of the clinical team.
Statistical analysis
Continuous variables were reported as median with interquartile ranges( IQR) and compared using Kruskal Wallis test. Categorical variables were expressed as numbers and percentages and compared using a chi-square test. The impact of hyperoxia on primary and secondary outcome variables was assessed using univariable and multivariable logistic regression, adjusting for BSA, age group, and indication for ECLS. A subgroup analysis was performed for neonates to investigate differential effects in this population. The results were reported as unadjusted and adjusted odds ratios( OR) with corresponding 95 % confidence intervals( CI). Statistical analysis was conducted using SAS software, version 9.4M8( Cary, NC: SAS Institute Inc; 2023), with a significance level set at p < 0.05.
Results
A total of 229 patients were supported on VA – ECLS during the study period, with neonates comprising 73.4 % of the cohort. The median age and weight were 2.5 months