Children supported by extracorporeal membrane oxygenation (ECMO) are at high risk for both bleeding and clotting complications. Anticoagulation therapy is prescribed to reduce the risk of clot formation, and blood products are administered to manage and prevent bleeding. However, the prophylactic transfusion of blood products in children on ECMO is associated with poorer outcomes, suggesting a potential need to limit these strategies, if clinically feasible. Despite the associated harm, there are no evidence-based recommendations to guide these strategies for pediatric ECMO patients.
The Pediatric ECMO Anticoagulation Collaborative (PEACE) recently brought together international experts to develop systematic review-informed, modified Delphi consensus for prophylactic transfusion strategies. Marianne Nellis, M.D., M.S., a pediatric critical care medicine specialist at NewYork-Presbyterian and Weill Cornell Medicine, co-led the subgroup looking at transfusion strategies for children on ECMO.
Below, Dr. Nellis discusses developing recommendations for prophylactic transfusion in children on ECMO.
Background
In 2021, the Extracorporeal Life Support Organization (ELSO) released recommendations for transfusion and anticoagulation management in adults and children. Unfortunately, there was insufficient evidence to make any evidence-based statements. Therefore, only expert consensus statements were released from a relatively small group of experts. The PEACE collaborators felt it was important to establish evidence-based standards or broad-based expert consensus statements that clinicians could adhere to, especially during interventional clinical trials. Our hope is that these standards could help further research within the ECMO community.
Methods
To do this, we performed a structured literature search of studies between 1988 and 2020 that assessed the use of prophylactic blood product transfusion in pediatric ECMO patients. Evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Over two years, a panel of 48 experts met to develop evidence-based recommendations. If there were no randomized controlled trials, which is often the case in pediatric ECMO patients, the panel could only make expert-based consensus statements.
I, in collaboration with Oliver Karam, M.D., PhD, chief of pediatric critical care medicine at Yale School of Medicine, were leading an NIH-funded pilot trial of platelet transfusion thresholds for ECMO. Because of this and our previous epidemiologic work in transfusion medicine, we were asked to lead the subgroup investigating prophylactic transfusion strategies for children on ECMO. We, along with a group of experts in pediatric critical care, cardiac critical care, and transfusion medicine, reviewed the literature and developed consensus statements on what should be the transfusion thresholds for nonbleeding children on ECMO.
Consensus Statements and Good Practice Recommendations
Unfortunately, we found no strong evidence for any of the topics we assessed, including anticoagulation and transfusion for bleeding children. All statements that we developed were expert consensus statements and good practice recommendations.
One important good practice recommendation made was to take measures to minimize the overall transfusion volume in the patient, especially since many of these children have congenital heart disease and may need to have a transplant later. Minimizing the blood products these children are exposed to early on can enhance their ability to match for an organ in the future. We also recommended that the decision to transfuse red blood cells should take into consideration the patient’s whole clinical context and not just be based on hemoglobin alone.
While we don't yet have strong evidence suggesting doing specified things one way or the other, there is now broad-based expert consensus of what should be considered in causing benefit or harm so that bedside providers and clinical leaders can try to align their hospital policies with those recommendations.
— Dr. Marianne Nellis
Outside of my assigned group within PEACE, one of the major questions in ECMO management is which anticoagulant should be used. Many sites have moved from heparin to bivalirudin without much evidence to support this change. Because of this, we included a statement indicating that physicians can consider using bivalirudin in place of heparin in centers that have experience using it and have the means to try it, but there is currently not enough evidence to suggest all centers make this change.
While we don't yet have strong evidence suggesting doing specified things one way or the other, there is now broad-based expert consensus of what should be considered in causing benefit or harm so that bedside providers and clinical leaders can try to align their hospital policies with those recommendations.
Future Directions
Collaboration is important for future clinical trials. The PEACE collaborative recognized this and believed that we should come together and work collaboratively in new ways to standardize not only our work but also our data collection. The PEACE collaborative also identified research priorities backed by the expert community.
For me personally, I (along with Dr. Karam) received NIH funding for a pilot clinical trial to test platelet transfusions for children on ECMO. We recently enrolled the last patient into that trial, and we are now moving forward to a larger trial, including 90 centers across the world and 1,400 children, to understand better when children need platelet transfusions and if we can use lower thresholds than we currently use safely.
