Fluid Overload and Extracorporeal Membrane Oxygenation: Is Renal Replacement Therapy a Buoy or an Anchor?*

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Excerpt

The use of extracorporeal membrane oxygenation (ECMO) to support children with cardiac and respiratory failure, refractory to conventional medical management, has evolved significantly over the last decade. However, despite growing experience and considerable advances in the materials and techniques, mortality remains high (1). Identifying potentially modifiable risk factors is an important initial step in developing practice strategies that could help improve future outcomes.
Fluid therapy is an essential component of the management of critically ill patients. Children undergoing ECMO support typically receive large volumes of fluid in the form of fluid resuscitation, blood products, nutrition, and medications. This cumulative fluid delivery frequently exceeds fluid loss, leading to a net positive fluid balance. Accumulating data has consistently shown hazardous effect of fluid overload (FO) on outcomes in both adult and pediatric critically ill populations including acute lung injury, sepsis, acute kidney injury (AKI), and in perioperative settings (2–5).
The study by Selewski et al (6) in this issue of Pediatric Critical Care Medicine is the largest cohort to date to evaluate the impact of FO in pediatric ECMO. It is a retrospective observational cohort of pediatric ECMO patients from six PICUs in the United States and Canada over a 5-year period. Data were collected from chart review and the Extracorporeal Life Support Organization (ELSO) Registry database, with 20% of the patients excluded due to inability to match their data with the registry database. The study included over 700 patients (60% neonates). Over half of the patients had pulmonary indications for ECMO, followed by cardiac (26%) and extracorporeal cardiopulmonary resuscitation (18%), with about 70% of the overall cohort receiving veno-arterial ECMO support. AKI was present in 75% of the patients, and renal replacement therapy (RRT) was used in about half of the cohort.
FO was evaluated using four different fluid metrics: cumulative %FO at ECMO initiation, peak %FO during ECMO, cumulative %FO at ECMO discontinuation, and change of %FO during ECMO. FO was common with about half the patients having %FO greater than 10% at ECMO initiation and almost two third of the patients with peak %FO greater than 20% during ECMO. The cohort had a median 13.6% increase of %FO during ECMO support. All four FO metrics were significantly higher in those who did not survive to hospital discharge (42%). This negative association was consistent in the multivariate analysis adjusting for important confounders and markers of severity of illness. Subgroup analyses of the neonatal population and patients receiving RRT showed comparable results. In addition to the impact on mortality, cumulative %FO at ECMO initiation and peak %FO during ECMO were independently associated with longer ECMO duration.
As recognized by the authors, a significant limitation of the study (6) was the exclusion of 20% of the patients due to inability to match their data with the ELSO database, which could have introduced some selection bias. As well, the majority of the patients in the study cohort were neonates, while this subgroup of patients account for a minority of patients in modern pediatric ECMO programs. AKI was diagnosed based on the creatinine criteria with no utilization of urine output. That could have led to under recognition of AKI, especially with the potential dilutional effect of FO on creatinine (7). Although the authors adjusted for important confounders, they were not able to include a severity of illness score in the analysis or adjust for postoperative cardiac bypass indications.
This large multicenter study adds to the accumulating evidence suggesting that, at least following initial resuscitation, a threshold may exist beyond which fluid accumulation becomes unhelpful or possibly harmful.

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