Gregory M. Vercellotti, MD
Dr. Vercellotti indicated no relevant conflicts of interest.
Study Title: Red Cell Storage Duration Study (RECESS)
Clinical Trials.gov Identifier: NCT00991341
Sponsor: New England Research Institutes
Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
Participating Centers: 26 study locations in the United States
Accrual Goal: 1,696 subjects (enrollment is ongoing)
Study Design: This phase III trial will compare the effects of transfusing red blood cell units stored ≤ 10 days with those stored ≥ 21 days in patients who are undergoing complex cardiac surgery and who are likely to need red blood cell transfusion. The hypothesis being challenged is that patients transfused with red cell units stored for a shorter time have a significantly more favorable clinical outcome compared with patients transfused with units stored for a longer time. The study’s primary outcome measure is change in the composite multiple-organ dysfunction score (MODS) from the pre-operative baseline. The worst post-operative values of each component of MODS will be used to calculate the change in MODS through post-operative day 7, hospital discharge, or death, whichever occurs first. Secondary outcome measures include all-cause mortality through day 28 post-surgery; major in-hospital, post-operative complications (e.g., death, stroke, myocardial infarction, renal failure, culture-proven sepsis/septic shock) through post-operative day 7, hospital discharge, or death, whichever occurs first; major cardiac and pulmonary events; ventilation duration; and a panel of relevant laboratory/clinical measurements.
Rationale: Current U.S. FDA guidelines allow for storage of red cells for up to 42 days. In practice, the average red blood cell storage time is 28 days, with most blood banks adhering to the policy of using the oldest blood first. Concern over the safety of blood transfusion has existed for decades, and recent clinical studies have suggested that storage of blood affects clinical outcomes. For example, in a retrospective study involving patients who had undergone cardiac surgery, 30-day mortality was significantly greater for patients transfused with red blood cells stored for more than 14 days compared with that of patients transfused with blood stored for less than 14 days (Koch CG et al. N Engl J Med. 2008;358:1229-39). But other studies have come to different conclusions as evidenced by a recent randomized control trial of young (7 days or less in storage) versus standard-issue red cell transfusions in premature neonates that showed no difference in outcome (Fergusson DA et al. JAMA. 2012;308:1443-51). The availability of life-saving red blood cell transfusions depends on both the rate of collection and the duration of the acceptable storage period. Thus, reducing the acceptable duration of storage would have an enormous (and potentially calamitous) effect on the blood supply. For this reason, well-designed clinical trials are essential for addressing the issue of storage duration with its far-reaching implications.
Comment: The RECESS trial will provide valuable information on whether blood stored for more than 21 days is suboptimal for cardiac surgery patients, and some of the secondary endpoints of the study may generate new insights into the biologic effects of storage on the properties of red blood cells. However, caution must be exercised when extrapolating the results of the RECESS study to other indications for transfusion. For example, patients with stable, transfusion-dependent MDS may respond differently than patients undergoing cardiac surgery, just as the outcome for neonates, cited above, appears to be different from that of cardiac surgery patients. Still, we must be prepared to deal with definitive studies that demonstrate that stored blood is detrimental, even if the outcome affects only a subgroup of patients. For this reason, continued basic investigation designed to understand the nature of the red cell storage lesion is of paramount importance, as are studies aimed at developing methods both for rejuvenating stored blood and for generating safe, effective blood substitutes.
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