New versus old blood - the debate continues

Since the inception of blood banking, refinements in laboratory processes have allowed for progressively longer storage times of red blood cells. Whilst advantageous for the logistics of stock management, the clinical impact of the duration of red blood cell storage prior to transfusion remains uncertain, and a topic of growing interest.


Eff ects of blood storage
Th e eff ects of storage on RBCs include changes in potassium (increased levels), 2,3-diphosphoglycate (decreased levels), lactate (increased levels), pH (decreased values), glucose (decreased levels), adenosine triphosphate (decreased levels), methaemoglobin (increased levels), red cell structure (from biconcave disc, to echinocytes and then to spherocytes), and therefore red cell deformability. Storage eff ects also include changes to the micro environment with reduced levels of S-nitrosohaemoglobin and nitric oxide. Prolonged storage prior to transfusion also results in an immunomodulatory eff ect, fi rst described by Opelz and colleagues who demonstrated reduced transplant rejection after stored red cell administration [2]. Th is eff ect theoretically increases infection risk, by accumulation of proinfl am matory lipids and neutrophil priming, resulting in severely reduced neutrophil function.
Th e evidence that prolonged storage of RBCs contributes to demonstrable adverse outcomes remains controversial, however, and is hampered by many small retrospective studies with potential selection bias; most evidence is also confounded by relatively recent changes in practice such as leucodepletion of RBCs. Moreover, there is still no consensus on what constitutes old blood, with studies using variable defi nitions of 5, 12, 14 or 21 days. None of the prospective studies to date have shown a correlation between the age of RBCs and adverse outcome. Two new studies in progress should provide further data -the Age of Blood Evaluation study (Canadian Clinical Care Trials Group) in trauma/ intensive care patients and the Red Cell Storage Age Study (US National Heart, Lung, and Blood Institute's Transfusion Medicine/Hemostasis Clinical Trials Network) in cardiac surgery patients.

Intensive care studies
Marik and Sibbald reported in 1993 that older RBCs were associated with a reduced intragastric pHi value (a surrogate for gut ischaemia) and postulated that impaired deformability of RBCs impeded microvasculature fl ow [3]. A similar study published in 2004, however, failed to confi rm these fi ndings [4]. Off ner and colleagues suggested that trauma patients receiving blood stored for >2 weeks had higher rates of infection and multiorgan failure [5]; but these patients also received a greater volume of transfusion, were older and had more severe injuries. More recently, Zallen and colleagues reported in a cohort of 63 trauma patients that those who received older blood had a higher risk of developing multiorgan failure [6]; yet again, however, these patients were older and received marginally more RBCs. univariate analysis, but not multivariate analysis, suggested a correlation between storage time and survival. In 2008 Koch and colleagues evaluated an even larger patient group of cardiac surgical cases who received RBCs either ≤14 days old or >15 days old [8]. Th eir results indicated excess inhospital mortality associated with older blood, but these patients were also more likely to have received more RBCs.
Th ese retrospective studies are now added to by that of Ranucci and colleagues in a previous issue of Critical Care, who evaluated outcome in 239 infants receiving blood as either a CPB pump prime or an intra/postoperative top-up transfusion according to whether this blood was ≤4 days old or older. Of 192 infants receiving CPB prime blood, the authors concluded that older blood recipients were more likely to have pulmonary complications. After adjusting for other possible confounders, the RBC storage time remained an independent predictor of major morbidity, although the same association was not found for patients receiving RBCs after CPB.
Red cell transfusion in the critically ill continues to raise many questions -including whether the storage duration of red cells aff ects measurable outcomes; whether leucodepletion results in fewer storage associated complications; the eff ect of red cell irradiation on relevant outcomes; and, fi nally, the appropriate target haemoglobin level in the preoperative, bleeding and stable critically ill patient.
Clearly, more robust evidence from prospective trials is required to support the therapeutic use of blood transfusion in the critically ill, or uncertainty will remain. Abbreviations CPB, cardiopulmonary bypass; RBC, red blood cell.