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where it has been associated with increased morbidity and mortality [ 2, 4 – 14 ]. Although the negative effects of hyperoxia and its association with adverse outcomes are known, the level at which PaO 2 becomes deleterious may differ depending on the clinical situation. Potential influencing factors include the duration of exposure, the patient’ s age, the underlying baseline physiology of the patient, and the overall pathophysiology of the disease process [ 4, 5, 9, 13 – 17 ].
Given the lack of a clear definition of hyperoxia from prior reports, we aimed to evaluate a high-risk patient population who required VV-ECLS for respiratory failure in a high-volume ECLS center. We intended to determine the ranges of PaO 2 exposure and the potential association between exposure to hyperoxia and poor outcomes. Our primary aim was to determine if hyperoxia while on VV-ECLS was associated with increased mortality using a derived cut-point within our cohort. Our secondary aim was to determine if hyperoxia during VV-ECLS is associated with greater odds of morbidity using the Functional Status Scale( FSS), and the development of complications while on ECLS, including acute kidney injury( AKI).
Materials and methods
This is a single-center retrospective cohort study that included all patients who required VV-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. An internal ECLS database was queried, and eligible patient encounters were identified. The study was approved by the CHOA Institutional Review Board( IRB # 00001239, approval date: 10 / 11 / 2022). Informed consent was waived.
Data and definitions
All consecutive patients who required VV-ECLS support in index hospitalization were included. Demographic features, clinical characteristics, and ECLS variables were collected. All arterial blood gases were obtained from the patient arterial line during the first 48 h while on ECLS. The primary outcome was defined as all-cause ECLS mortality. The secondary outcome variables included FSS, AKI( Stage II or Stage III, as defined by the KDIGO criteria) [ 18 ], and major complications. Major complications were defined as the presence of either cardiovascular, renal, or mechanical complications.
Functional Status Scale( FSS)
The FSS consists of six main domains: mental status, sensory, communications, motor function, feeding, and respiratory. Functional status for each domain was categorized from a normal score of 1 to very severe dysfunction with a score of 5, giving total FSS scores ranging from 6 to 30 as previously described [ 19 ]. Functional status scoring for this study involved retrospectively scoring baseline status( i. e., on admission) and again at hospital discharge by examining the appropriate documentation. FSS score determination was blinded from hyperoxia status. Newborns who had never achieved a stable baseline function were assigned an FSS score of 6. This was operationalized by assigning a baseline FSS score of 6 to all admissions for infants 0 – 2 days old and transfers from another facility for infants 3 – 6 days old as previously reported [ 20 – 23 ]. New morbidity was defined as an increase in the total score of 3 points, and unfavorable functional outcome was defined as an increase of 5 [ 24 ].
Clinical management
All circuits were blood primed before the start of ECLS with packed red blood cells, 25 % albumin, sodium-bicarbonate, calcium-gluconate, and heparin for patients < 40 kg. It is common practice for ABGs to be obtained at the discretion of the clinical team, most typically 30 min after initial ECLS-cannulation, and then hourly for the first 3 h. Subsequently, they are typically obtained every 3 – 6 h and 30 min after an adjustment in ECLS support. Target gas exchange parameters are not dictated by protocol at our center. Goal PaO 2 ranges have no established normal and the variation we describe is derived from measurements occurring during clinical care. Goal PaCO 2 was 35 – 45 mmHg, and goal pH was 7.35 – 7.45. Once patients are placed on ECLS, the ventilator is placed on“ rest settings” of the following: ventilator mode pressure control, peak inspiratory pressure 20 cm H 2 O, peak end-expiratory pressure 10 cm H 2 O, respiratory rate 20 / min, inspiratory time 1 s, and FiO 2 30 %. Statistical analysis
Statistical analysis was conducted using SAS version 9.0 software, with a significance level set at p < 0.05. The diagnostic utility of mean PaO 2 in predicting mortality was evaluated using Youden’ s index( J = sensitivity + specificity � 1) and receiver operating characteristic( ROC) curves. The study population was stratified into hyperoxia and non-hyperoxia groups based on the optimal cut-off value for mean PaO 2, determined by maximizing the J value. Fisher’ s exact test was employed for comparing categorical variables, while Student’ s t-test and the nonparametric Wilcoxon rank-sum test were used for continuous variables, as appropriate. Additionally, a scatterplot was generated to examine the relationship between mean PaO 2, duration of ECLS run, and survival, with Spearman’ s correlation coefficient reported. To assess the impact of hyperoxia on mortality and AKI, univariable and multivariable logistic regression analyses were performed, adjusting for BSA, age group, and indication for ECLS in the multivariable analysis that were determined a priori. The results are presented as odds ratios( OR) with corresponding 95 % confidence intervals( CI). Results
During the study period, 110 VV-ECLS runs. The median age was 4.9 months( IQR: 0.1, 105.4), and the weight was 5.4 kg( IQR: 3.4, 35.0) with an almost even distribution of males and females. The majority of patients were neonates( 57.3 %). The median time from admission to cannulation was 39.0 h( IQR: 3.0, 116.0) with a median run duration of 140.5 h( IQR: 98.0, 287.0). Overall mortality rate was 26.4 %( Table 1). Supplemental Table 1 shows the relationship of