Do Red-cell Storage Times Affect Outcomes from Blood Transfusion?
July 1, 2008 4 minutes read
Do Red-cell Storage Times Affect Outcomes from Blood Transfusion?
Abstract & Commentary
By Andrew M. Luks, MD, Pulmonary and Critical Care Medicine, University of Washington, Seattle, is Associate Editor for Critical Care Alert.
Dr. Luks reports no financial relationship to this field of study.
Synopsis: This single-center, retrospective study demonstrated that transfusion of packed red blood cells more than 14-days old was associated with an increased risk of post-operative complications and decreased survival in patients undergoing coronary artery bypass grafting or heart valve surgery.
Source: Koch CG, et al. N Engl J Med. 2008;358(12): 1229-1239.
A growing literature suggests that packed red blood cell (PRBC) transfusions are associated with adverse outcomes in a variety of patient populations, but the mechanisms behind the observed effects are not clear. Some reports suggest that transfusion of older red-cell units may be the source of the problem, but the data on this question have been conflicting and limited by the small study sizes and other methodological issues. Koch and colleagues sought to clarify this issue further by conducting a retrospective analysis of a large number of patients who underwent blood transfusion during or around the time of cardiac surgery.
The study population included all individuals 18 years of age and older who underwent coronary-artery bypass grafting or cardiac-valve surgery, or a combination thereof, over an eight year period at a single institution. The eligible subjects were divided into two groups including those who exclusively received PRBC stored for 14 or fewer days ("newer blood") and those who exclusively received PRBC stored for over 14 days ("older blood"). Those patients who received a mix of new and old blood were excluded from the analysis. Comparisons were then made between the "newer blood" and "older blood" groups, with the primary end-point being a composite of serious adverse events such as in-hospital death, myocardial infarction, prolonged mechanical ventilation, pericardial tamponade, renal failure, sepsis and pulmonary embolism among others. The secondary end-point was long-term survival.
The average age of all patients included in the study was 70 years and the median amount of PRBCs transfused to all patients was 2 units. The "newer blood" group included 2872 patients who received a total of 8802 units of blood stored for a median of 11 days while the "older blood group included 3130 patients who received 10,782 units of blood stored for a median of 20 days. The incidence of the composite end-point of adverse outcomes was higher in the "older blood" group than in the "newer blood" group (25.9% vs 22.4%, P = 0.001). Patients who received the "older" blood also had higher rates of in-hospital mortality (2.8% vs 1.7%), need for prolonged mechanical ventilation (9.7% vs 5.6%), renal failure (2.7% vs 1.6%), sepsis (4.0% vs 2.8%), and multi-system organ failure (0.7% vs 0.2%) with all of the observed differences reaching statistical significance.
Patients receiving "older" blood also had lower survival and higher risk of death than patients receiving "newer" blood. One-year survival was 89% in the "older blood" group and 92.9% in the "newer blood" group. Because there were some differences in baseline characteristics between the two groups such as the prevalence of blood types used or the incidence of abnormal left ventricular function, the authors applied a variety of statistical adjustments to the data and did not find any changes in the statistical significance of the observed results.
Commentary
This is a provocative study that adds to our understanding of the risks associated with PRBC transfusion, as it suggests that it may be the age of the transfused red blood cells, rather than the mere act of transfusion, that is the critical factor leading to the adverse outcomes. Exactly how storage time increases risk remains an unanswered question, however. Several mechanisms have been proposed, including decreased red blood cell deformability, depletion of 2,3-diphosphoglycerate and accumulation of pro-inflammatory mediators, but the precise mechanisms have yet to be worked out to explain why the age of the transfused units matters.
The implied message behind these results is that patient outcomes might be improved by restricting our use of PRBC to only those units that have been stored for less than two weeks, the length of time it takes before the changes noted above begin adversely affecting stored PRBC units. It is far too early, however, to change our current transfusion practices in such a manner. For starters, this was a retrospective study and there are serious issues regarding the generalizability of the findings. The data came from a single center and, as a result, all the transfused blood units likely came from a single local blood bank whose practices may not be precisely the same as other centers around the country. More importantly, the study focused on a narrow population of patients and a narrow time window for transfusion: older individuals receiving blood during cardiac surgery. It would be useful to have data from multiple centers and patient populations and, in particular, patients whose blood was not being circulated through cardiopulmonary bypass systems.
Beyond the issue of generalizability of the reported findings, we are also faced with the implications of restricting transfusions to units of blood stored for short periods of time. With blood banks already struggling to maintain adequate blood product supplies, shortening the window for transfusing a given unit might place undue stress on the system. Before any move could be made to shorten storage times, a lot more work must be done to confirm the results of this study and ensure that blood product supplies can be maintained at adequate levels.
Unfortunately, neither of these issues will be solved in the short term and we are, instead, left with a simple, yet proven,1 strategy for protecting our patients from the risk of transfusions—adhering to strict transfusion thresholds and avoiding unnecessary use of these products.
Reference
- Hebert PC, et al. N Engl J Med. 1999;340:409-417.
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