Red Blood Cells (RBCs) are transfused primarily to increase oxygen use by cells to prevent the development of shock in critically ill patients. Inadequate treatment of shock will increase the risk of multiple organ failure and mortality through multiple cell death pathways. RBC units can be stored for up to 42 days based upon RBC survival data within the central circulation. There is no data indicating RBCs stored up to 42 days are efficacious in improving oxygen use at the cellular level during shock. Preliminary evidence indicates that in critically ill populations, including children, increased RBC storage duration reduces its efficacy and may increase the risk of organ failure and mortality. The Age of Blood in Children in Pediatric Intensive Care Units (ABC-PICU) trial has been designed to determine if the use of RBCs of short storage duration improves outcomes in this population. ABC-PICU is a multicenter international, pragmatic, double-blind, randomized controlled clinical trial comparing the risk of New or Progressive Multiple Organ Dysfunction Syndrome (NPMODS) in 1538 critically ill children transfused either RBCs of decreased storage age or standard issue RBCs (oldest in inventory first). We hypothesize that transfusion of RBCs stored for 7 days (compared to standard issue RBCs) will result in improved clinical outcomes by decreasing NPMODS.
Specific Aim 1 : Determine whether transfusion of RBC units 7 days compared to standard issue (mean 17- 21 days) RBC units decreases the risk of NPMODS in critically ill children. The primary outcome measure NPMODS is defined as the proportion of patients who develop NPMODS or die during the 28 days after randomization.
Specific Aim 2 : Secondary outcomes will include morbidity and measures to include;transfusion reactions, adverse thrombotic events, nosocomial infections, mechanical ventilation and ICU free days, and mortality at multiple time intervals. If this adequately powered trial does not indicate RBC storage age effects outcomes, the results would reassure clinicians and blood bankers regarding the efficacy and safety of RBC transfusions in critically ill children. If results indicate that RBCs 7 days improve outcomes this will: 1) indicate that prolonged storage has clinical consequences and may influence the modification of regulatory policies on RBC storage;2) potentially influence policies regarding the storage age of RBCs allocated to critically ill children and;3) spark investment in research of RBC storage and rejuvenation solutions to mitigate any potential adverse effects of storage. Positive results would also encourage research directed at understanding the mechanisms underlying the improved outcomes in children transfused RBCs of decreased storage age.

Public Health Relevance

RBC transfusions are common in critically ill children. Current licensing of RBC storage solutions does not require direct evidence of efficacy in improving oxygen use or non-infectious safety. Mounting data suggests that in critically ill patients the use of older RBCs increases the risk of death or organ failure. This study will definitively determine if the use of fresher RBCs cn improve outcomes in critically ill children. (End of Abstract)

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HL116383-02
Application #
8700501
Study Section
Clinical Trials Review Committee (CLTR)
Program Officer
Mondoro, Traci
Project Start
2013-07-15
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$1,619,967
Indirect Cost
$257,840
Name
Washington University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130