By Kathryn Radigan, MD, MSc
Assistant Professor, Pulmonary Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL
Dr. Radigan reports no financial relationships relevant to this field of study.
SYNOPSIS: Critically ill patients transfused with red blood cells less than eight days old do not experience better outcomes than patients transfused with standard-issue red cells.
SOURCE: Lacroix J, et al. Age of transfused blood in critically ill adults. N Engl J Med 2015;372:1410-1418.
The transfusion of fresh red blood cells in critically ill patients may improve oxygen delivery and minimize exposure to the toxins and bioactive byproducts related to prolonged storage. With the Age of Blood Evaluation (ABLE) trial, Lacroix et al sought to determine if there was a benefit to the transfusion of fresh red blood cells as opposed to standard-issue red cells. In this multicenter, randomized, blinded trial conducted between March 2009 and May 2014 at 64 centers in Canada and Europe, 1211 patients were assigned fresh red blood cells and 1219 patients were assigned standard-issue red blood cells. The primary outcome measure was 90-day mortality. The fresh red blood cells were stored for a mean of 6.1 ± 4.9 days, and the standard-issue red cells were stored 22.0 ± 8.4 days (P < 0.001). After 90 days, 448 patients (37%) in the fresh red blood cell group had died while 430 patients (35.3%) in the standard-blood group had died (absolute risk difference: 1.7%; 95% confidence interval [CI], -2.1 to 5.5). The hazard ratio for death in the fresh red blood cell group as compared to the standard-blood group was not significant at 1.1 (95% CI, 0.9 to 1.2; P = 0.38). There were also no significant differences in secondary outcomes, including major illnesses, length of hospital stay, transfusion reactions, and duration of respiratory, hemodynamic, or renal support.
COMMENTARY
Anemia is overwhelmingly common in the ICU. Up to 90% of critically ill patients develop anemia by their third day of admission.1 In fact, 20-40% of critically ill patients are transfused with an average of 2-5 units of red cells per patient.2 Even though transfusion in the ICU is common, it is associated with increased risk of morbidity and mortality. Red blood cells can be stored for up to 42 days, and this storage is often associated with adverse changes in erythrocytes and their preservation media. These changes may influence erythrocyte oxygen affinity, ability to change shape, membrane stability, and a number of other factors that may affect the efficacy of transfusion.
As there is concern for the potential harmful effects of this stored blood in critically ill patients, there have been multiple animal studies, observational studies, and single-center studies with conflicting findings. The ABLE trial as described above clearly showed that transfusion of fresh red blood cells compared to standard-issue red blood cells did not decrease 90-day mortality among critically ill patients. In addition, there were no differences in secondary outcomes. Most importantly, the trial followed a restrictive transfusion strategy with a mean pre-transfusion hemoglobin level of 7.7 g/dL. The results of the ABLE trial are consistent with several other randomized, controlled trials that compared different durations of red cell storage and found no difference in mortality rates. Although the conclusions from this trial appear to be clear, the TRANSFUSE trial is an additional, multicenter trial being conducted in Australia and New Zealand, consisting of 5000 critically ill patients with a primary outcome of 90-day mortality; completion of the trial is expected in 2016.
The ABLE trial supports the notion that the relative expiration date of red blood cells is not important. For now, we should not have to worry that standard-issue red cells are harming our patients and should continue to focus our attention on limiting transfusions to circumstances supported by evidence-based medicine.
REFERENCES
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Corwin HL, et al. Efficacy and safety of epoetin alfa in critically ill patients. N Engl J Med 2007;357:965-976.
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Cohen B, Matot I. Aged erythrocytes: A fine wine or sour grapes? Br J Anaesth 2013;111 Suppl 1:i62-70.