Should fresh blood be recommended for intensive care patients?

Fresh blood has many potential advantages over older blood, but there is no evidence that these properties translate into clinical benefit for intensive care patients. The observational multicenter study by Karam and colleagues provides some evidence suggesting that blood stored for less than 14 days is better than older blood in terms of new organ failure and reduction in length of stay in pediatric intensive care units. Though in favor of using young blood, this study suffers from several limitations. As a consequence, it is ethical and certainly pertinent to conduct a randomized clinical trial in order to test the hypothesis that fresh blood might reduce mortality. The rationale is strong and the potential benefit of fresh blood is substantial.

As reported in the previous issue of Critical Care, a prospective observational study conducted by Karam and colleagues [1] in 30 North American centers linked length of storage of red blood cell (RBC) units and outcome of critically ill children. Th is study is worth comment ing upon since the literature documents confl icting results. Th e use of 'fresh blood' has several potential advantages over that of older blood. Young blood allows better 24-hour, post-infusion, in vivo recovery [2,3]. Th e RBC lysis releases free hemoglobin that binds nitric oxide (NO), inducing vasoconstriction [2].
Old blood is associated with several alterations either in the supernatants -a decrease of sodium and an increase of potassium [4], decreases of pH and arterial partial pressure of oxygen (PaO 2 ), increases of lactate and arterial partial pressure of carbon dioxide (PaCO 2 ) [2] and procoagulant state [5], and an increased risk of thrombosis [6] -or related to cellular modifi cations such as a decrease of 2,3-DPG (2,3-diphosphoglycerate) [2] content, leading to an increase of hemoglobin oxygen affi nity and a decrease of RBC deformability [2]. All of these alterations in stored RBCs lead to a reduction of O 2 delivery. As a matter of fact, the oxygen uptake was improved after transfusion of fresh blood but was unchanged with older blood (28 days) in the study of Fitzgerald and colleagues [7] and tissue oxygenation was altered in trauma patients transfused with old blood [8].
Given the potential benefi cial eff ects of fresh blood and also the logistical and fi nancial impact of its recommendation, we need strong clinical scientifi c evidence in order to push hard to obtain fresh blood from the blood banks. Th e study by Karam and colleagues [1] is the fi rst prospective multicenter study of its kind (n = 296 pediatric patients, younger than 18 years) to document that blood stored more than 14 days has detrimental eff ects on organ dysfunction (adjusted odds ratio 1.87, 95% confi dence interval 1.04 to 3.27; P = 0.03). Th is result was explained mainly by renal failure and was not associated with a reduction in mortality. It is worth noting that intensive care unit (ICU) length of stay was reduced (by 3.7 days). Accord ingly, the cost-benefi t ratio of fresh blood is probably very favorable.

Methodology
Th is was an observational study, so we cannot be sure that patient groups were perfectly balanced. A matchedcohort study could have better addressed the question. Worse clinical outcome is associated with the number of transfusions independently of the longest length of storage and some patients received several blood transfusions that were not consistently stored for less than 14 days. Th e lack of consistency in the allocated group introduces a bias, but since the oldest blood is considered for defi ning the storage time, this inconsistency does not bias the results in favor of fresh blood. Of note, data on the length of storage were available for only 66% of the patients.

Abstract
Fresh blood has many potential advantages over older blood, but there is no evidence that these properties translate into clinical benefi t for intensive care patients. The observational multicenter study by Karam and colleagues provides some evidence suggesting that blood stored for less than 14 days is better than older blood in terms of new organ failure and reduction in length of stay in pediatric intensive care units. Though in favor of using young blood, this study suff ers from several limitations. As a consequence, it is ethical and certainly pertinent to conduct a randomized clinical trial in order to test the hypothesis that fresh blood might reduce mortality. The rationale is strong and the potential benefi t of fresh blood is substantial.

Quality of the blood
Fresh blood was defi ned as RBC concentrates stored for a period shorter than the median length of storage, resulting in a cutoff value of 14 days. RBCs infused in North America are older than in Europe either in pediatric ICUs (14 days [9], 16 days [10]) or in adults, with a length of storage reaching 33 days in US military hospitals [11]. Leukoreduction is common practice in most Western countries but was performed in only 86% of the transfusions in this study.
Given the design of the study, it is not possible to state that there is a cause-and-eff ect relationship between older RBCs and outcome in critically ill patients. However, these encouraging results justify the large randomized clinical trial of adult patients which is already under way in Canada.

Abbreviations
ICU, intensive care unit; RBC, red blood cell.

Competing interests
The author declares that he has no competing interests.