A. G. Beshish et al.: J Extra Corpor Technol 2025, 57, 59 – 65 63
Table 2. Outcomes of patients undergoing VV-ECLS using a univariable and multivariable regression analysis. Outcomes
PaO 2 < 122 mmHg( n = 87)
PaO 2 > 122 mmHg( n = 23)
OR( 95 % CI) p-value aOR a( 95 % CI)
0.003 7.97( 1.72 – 36.86)
Adjusted p-value
0.008
Mortality |
29( 33.3 %) |
12( 52.2 %) |
4.49( 1.70 – 11.91) |
|
|
|
Any renal, cardiovascular |
71( 81.6 %) |
23( 100 %) |
– |
– |
– |
– |
or mechanical |
|
|
|
|
|
|
complication |
|
|
|
|
|
|
Stage II / III AKI |
50( 54.5 %) |
11( 47.8 %) |
0.69( 0.45 – 1.93) |
0.476 |
0.62( 0.18 – 2.07) |
0.431 |
a Adjusted for age group, BSA, and indication for ECLS.
Figure
3. Scatterplot illustrating the relationship of average PaO 2, VV-ECLS run duration, and mortality in the VV-ECLS cohort.
sedated and paralyzed to decrease oxygen consumption. These are all real-life factors that affect the patient at the bedside. It would be extremely useful to control for all of these factors but in reality, the degree of impact of each factor is different for each patient. This supports the importance of this study and future studies to help understand the true impact of oxygen on patient outcomes and the biological systems of the body.
Despite a slew of published data, there is no generally accepted level that defines pathologic hyperoxia, as it may vary by patient population and clinical context [ 25 ]. Poor outcomes may occur when PaO 2 exceeds a certain threshold of antioxidation systems of the body resulting in reactive oxygen species( ROS) production, and activation of inflammatory pathways which result in cellular injury and death [ 29 ]. This effect may be more pronounced in neonates, infants, and children due to the immature antioxidant defenses which renders them more susceptible to ROS [ 4 ]. Furthermore, the effect of hyperoxia may be more pronounced in patients who are critically ill. When critically ill patients are placed on ECLS they are exposed to a relative hyperoxia state. This exposure to supraphysiologic oxygen may overwhelm the already depleted antioxidant system and result in increased morbidity and mortality. In our study, we show that patients in the hyperoxia group were older( 1.6 months vs. 105.4 months, p = 0.001, and weighed more( 28.3 kg vs. 4.3 kg, p = 0.002), and were more likely to be neonates. It appears that in the clinical setting and in particular patients in the neonatal ICU, the providers are more vigilant about limiting oxygen exposure due to the abundance of literature supporting hyperoxia exposure and outcomes in the neonatal population. In the older patient population who are supported on VV-ECLS in our study the most common diagnosis is acute respiratory distress syndrome( ARDS) while in the neonatal population, the most common diagnosis is persistent pulmonary hypertension of the newborn( PPHN), and neonatal respiratory distress syndrome. This shows the importance of a prospective study in both the pediatric and neonatal populations to further identify the appropriate cut-off in each patient population.
Because there is no accepted definition of hyperoxia in pediatric patients supported by VV-ECLS, we used a ROC curve analysis in this specific cohort to determine which PaO 2 values may be associated with an adverse outcome. This similar strategy was employed by Sznycer-Taub et al. and Beshish et al. in two separate reports. Sznycer-Taub and colleagues evaluated hyperoxia in pediatric cardiac patients( neonates and infants) supported on VA-ECMO and found that aPaO 2 of 193 mmHg in the first 48 h was determined to have good discriminatory ability with regard to 30-day mortality [ 4 ]. Using a similar strategy, Beshish and colleagues showed that a PaO 2 of 313 mmHg for infants undergoing cardiac surgery utilizing cardiopulmonary bypass was independently associated with 30-day mortality [ 9 ]. Although the ECLS modality is slightly different from the prior reports as we describe our experience with VV-ECLS, our cut-off definition of hyperoxia was PaO 2 of 122 mmHg. The sensitivity of our cut point was 41 %, which is slightly low, and we think that this can be better identified with a larger patient population and a homogenous patient population. To do this is extremely challenging for a single center due to the low numbers of VV-ECLS runs in each center. Despite that, we showed the patients in the hyperoxia group had almost eight times higher odds of mortality when adjusting for confounding variables. This is the first report of an association between PaO 2 level and mortality in patients requiring VV- ECLS and highlights an important modifiable risk factor that clinicians can adjust when taking care of these critically ill