the current standard red blood cell ( rbc ) storage time of up to 42 days is not based upon a demonstrable therapeutic benefit , but instead on the observed return of 70% of the viable transfused rbcs at 24 hours after storage for 42 days or less . the structural , biochemical and immunological changes that rbcs undergo during storage are well described , but what remains controversial is the evidence that this storage lesion translates into adverse clinical outcomes for patients receiving older blood . in a previous issue of critical care , ranucci and colleagues report an adverse outcome in infants receiving older blood during cardiopulmonary bypass ( cpb ) . the effects 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 effects also include changes to the microenvironment with reduced levels of s - nitrosohaemoglobin and nitric oxide . prolonged storage prior to transfusion also results in an immunomodulatory effect , first described by opelz and colleagues who demonstrated reduced transplant rejection after stored red cell administration . this effect theoretically increases infection risk , by accumulation of proinflammatory lipids and neutrophil priming , resulting in severely reduced neutrophil function . the 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 definitions 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 . 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 flow . a similar study published in 2004 , however , failed to confirm these findings . offner and colleagues suggested that trauma patients receiving blood stored for > 2 weeks had higher rates of infection and multiorgan failure ; 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 ; yet again , however , these patients were older and received marginally more rbcs . van der watering and colleagues retrospectively reviewed 2,732 patients undergoing cpb ; 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 . their results indicated excess inhospital mortality associated with older blood , but these patients were also more likely to have received more rbcs . these 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 affects measurable outcomes ; whether leucodepletion results in fewer storage associated complications ; the effect of red cell irradiation on relevant outcomes ; and , finally , 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 . dw is a co - investigator in the relieve study ; a feasibility randomized trial comparing restrictive and liberal blood transfusion strategies in intensive care patients .