THirose, selleck catalog OT, YK and TS participated in data interpretation. HO had a major impact on the interpretation of data and critical appraisal of the manuscript. THamasaki performed the statistical analysis and helped to draft the manuscript. All authors read and approved the final manuscript.AcknowledgementsNo one other than the authors contributed substantially to the performance of this study or to the drafting of the manuscript. The authors received no funding for this study. The contents of this manuscript were originally presented at the 30th Annual Meeting of the Surgical Infection Society in Las Vegas, NV, USA, 17 to 20 April 2010.
Anemia is extremely common in the critically ill [1] and is associated with poor outcomes [2-5].

It is therefore not surprising that 19 to 53% of all patients admitted to adult ICUs receive at least one unit of allogeneic red blood cells (RBCs) [1,6-8].Several publications have highlighted that the administration of RBCs and the hemoglobin trigger used for the administration of RBCs may affect patient morbidity and mortality [9-18]. More recently, the age of RBCs has been the focus of concern as a potential cause of increased morbidity and mortality [10]. A recent review summarizing data from 27 different studies in adult patients, however, concluded that it is difficult to determine whether there is a relationship between the age of transfused RBCs and mortality [19].The mechanism responsible for the possible adverse effects of RBCs may relate to the development of storage lesions over time.

During storage, in a way that increases over time, important biochemical changes occur: a reduction in 2,3-diphosphoglycerate, hypocalcemia, cell lysis, release of free hemoglobin, changes in nitric oxide levels, alterations in pH [20,21], and increases in lipids [22], complement [23] and cytokines [24]. These changes are accompanied by increased membrane fragility, which can compromise microcirculatory flow and lead to increased red cell-endothelial cell interaction and inflammatory cytokine release [20,21]. Such changes, which serve as potential explanations for more unfavorable outcomes, may be particularly disadvantageous to critically ill patients with a higher mortality risk. In this group, indirect evidence has linked the transfusion of older RBCs with adverse clinical consequences [25].

Unfortunately, all such evidence has been retrospective and/or focused on specific patient groups. The robustness GSK-3 of the relationship between the age of RBCs and adverse clinical outcome is thus limited both in strength and generalizability. Yet if this link exists, the public health consequences are great, given that the transfusion of RBCs is a common treatment in the critically ill. Furthermore, exposure to even a single unit of older RBCs might be associated with unfavorable outcome independent of the effect of volume of transfused RBCs and other confounding factors.