Extracorporeal membrane oxygenation (ECMO) is an established intervention for respiratory or cardiorespiratory support in children with congenital heart disease (CHD) when all other interventions have failed. Hyperoxia following successful resuscitation has been associated with increased mortality in pediatric and adult studies, including, specifically, hyperoxia during ECMO management. We hypothesized that this effect may be pronounced in patients with lower arterial oxygen saturation at baseline, such as those with cyanotic CHD. We aimed to determine if relative hyperoxia in children with cyanotic single ventricle circulation on Veno-Arterial (VA)- ECMO is a risk factor for mortality in a large multicenter registry analysis.

1. Relative Hyperoxia in Cyanotic Congenital Heart Disease Patients on Veno-Arterial
Extracorporeal Life Support is Associated with Decreased Survival to Hospital Discharge
1Pediatric Critical Care Medicine, Texas Children’s Hospital, Baylor College of Medicine, Houston, TX;
2Department of Cardiology, Boston Children’s Hospital, and Department of Pediatrics, Harvard Medical School, Boston, MA; 3Extracorporeal Life Support Organization, Ann Arbor, Michigan
Thomas P. Fogarty III, MD,1 Renee Willett, MD,2 Peter Rycus, MPH,3 Peta M.A. Alexander, MBBS, FCICM, FRACP,2 Marc Anders,MD1
Background
Extracorporeal membrane oxygenation (ECMO) is an
established intervention for respiratory or cardiorespiratory
support in children with congenital heart disease (CHD)
when all other interventions have failed. Hyperoxia
following successful resuscitation has been associated with
increased mortality in pediatric and adult studies,
including, specifically, hyperoxia during ECMO
management. We hypothesized that this effect may be
pronounced in patients with lower arterial oxygen
saturation at baseline, such as those with cyanotic CHD. We
aimed to determine if relative hyperoxia in children with
cyanotic single ventricle circulation on Veno-Arterial (VA)-
ECMO is a risk factor for mortality in a large multicenter
registry analysis.
Methods
All children (0-18 years) with ICD-9/ICD-10 diagnoses
consistent with cyanotic CHD who received VA-ECMO
support from 2008 to 2017 reported to the Extracorporeal
Life Support Organization (ELSO) registry were included in
this analysis. Only ECMO runs with interpretable arterial
blood gas results available pre-ECMO initiation and 24
hours post-ECMO were included. The primary study
outcome was survival to hospital discharge. Statistical
analyses were carried out using JMP® (version 13, SAS,
Cary, North Carolina, USA).
Results
There were 3,614 patients who met inclusion criteria
during the study period. Of these, 1,717 were excluded for
missing or non-sensical demographic or arterial blood gas
data, and 96 patients were not managed primarily on VA-
ECMO. Thus 1,801 patients were included in the analysis.
Cashen, et al. Hyperoxia and Hypocapnia During Pediatric
Extracorporeal Membrane Oxygenation: Associations With
Complications, Mortality, and Functional Status Among Survivors.
Pediatric Critical Care Medicine, 19(3). March 2018.
Sznycer-Taub, et al. Hyperoxia Is Associated With Poor Outcomes in
Pediatric Cardiac Patients Supported on Venoarterial Extracorporeal
Membrane Oxygenation. Pediatric Critical Care Medicine, 17(4). April
2016.
SELECTED BASELINE CHARACTERISTICS
SURVIVAL BY PaO2 @ 24 HOURS
RESULTS & CONCLUSION
SELECTED REFERENCES
Author Contact: fogarty@bcm.edu
The overall survival to hospital discharge rate was 44.8%. Pre-
ECMO variables associated with improved survival on univariate
analysis (p< 0.05) included first run of ECMO, weight (> 3.27 kg),
age (> 28 days), non–Asian race, cardiac rather than E-CPR
ECMO support, ventilatory pressures (peak inspiratory pressure
(PIP) < 25 cm H2O, PEEP < 5.2 cm H2O, mean airway pressure
(MAP) < 13 cm H2O), pH (> 7.15), no prior to ECMO cardiac
arrest (RR 1.22, 95% CI 1.09-1.38), and higher blood pressure
(systolic blood pressure (SBP) > 55 mmHg, diastolic blood
pressure > 34 mmHg, and mean blood pressure > 40 mmHg).
Variables recorded 24 hours into the ECMO run that were
associated with improved survival on univariate analysis (p<
0.05) included ventilatory pressures (PIP < 24 cm H2O, MAP <
10.8 cm H2O), arterial pH (> 7.39), and PaO2(< 124 mmHg).
By multivariable analysis, the pre-ECMO variables SBP (< 54
mmHg), MAP (> 13 mmHg), Asian race, as well as the 24 hour
variables PIP (> 25 cm H2O), PEEP (> 5.3 cm H2O), pH (< 7.14),
and PaO2 (> 124 mmHg), were all independently associated
with decreased survival to hospital discharge with p-values <
0.05.
In addition to factors related to severity of critical illness at
ECMO cannulation, management of patient ventilation and
oxygenation during ECMO, specifically ongoing acidemia and
relative hyperoxia were associated with decreased survival to
hospital discharge. These findings have implications for the care
of this vulnerable population and warrant further investigation.
VARIABLE SURVIVORS NON-SURVIVORS p
Age (days)* 18 (7-124) 14 (6-113) 0.012
Sex = Male, n (%) 457 (58.1) 545 (55.8) NS
Weight (kg)* 3.54 (3.02-5.2) 3.3 (2.9 – 4.7) 0.05
Race = Non-Asian, n (%) 774 (96.1) 935 (93.9) 0.03
Hours ECMO* 90 (60-136) 140 (81-235) < 0.001
Run Number = 1, n (%) 735 (91.3) 868 (87.1) 0.004
Arterial pO2*
@ Initiation 40 (30-61) 39 (29-54) NS
@ 24 Hours 94 (59-160) 115 (70-189) < 0.001
Arterial pH*
@ Initiation 7.24 (7.13-7.33) 7.23 (7.09-7.32) 0.026
@ 24 Hours 7.42 (7.38-7.46) 7.41 (7.37-7.46) < 0.001
Mean Airway Pressure*
@ Initiation 11 (9-13) 12 (10-15) 0.005
@ 24 Hours 10 (8-12) 11 (9-13) < 0.001
Mean Blood Pressure* @ Initiation 41 (32-51) 38 (30-47) 0.005
*median (IQR); NS = Non-Significant
Kaplan Meier Plot of Survival by PaO2 (at 24 Hours)
A Kaplan Meier Plot was generated using a threshold of PaO2
greater than or less than 124. This threshold was chosen as it
was the best discriminator of mortality on ROC analysis.