Transfusion of red blood cells stored for shorter versus longer duration for all conditions.

BACKGROUND: Red blood cell (RBC) transfusion is a common treatment for anaemia in many conditions. The safety and efficacy of transfusing RBC units that have been stored for different durations before a transfusion is a current concern. The duration of storage for a RBC unit can be up to 42 days. If evidence from randomised controlled trials (RCT) were to indicate that clinical outcomes are affected by storage duration, the implications for inventory management and clinical practice would be significant. OBJECTIVES: To assess the effects of using red blood cells (RBCs) stored for a shorter versus a longer duration, or versus RBCs stored for standard practice duration, in people requiring a RBC transfusion. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, PubMed (for epublications), LILACS, Transfusion Evidence Library, Web of Science CPCI-S and four international clinical trial registries on 20 November 2017. SELECTION CRITERIA: We included RCTs that compared transfusion of RBCs of shorter versus longer storage duration, or versus standard practice storage duration. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. MAIN RESULTS: We included 22 trials (42,835 participants) in this review.The GRADE quality of evidence ranged from very low to moderate for our primary outcome of in-hospital and short-term mortality reported at different time points.Transfusion of RBCs of shorter versus longer storage duration Eleven trials (2249 participants) compared transfusion of RBCs of shorter versus longer storage duration. Two trials enrolled low birth weight neonates, two enrolled children with severe anaemia secondary to malaria or sickle cell disease, and eight enrolled adults across a range of clinical settings (intensive care, cardiac surgery, major elective surgery, hospitalised in-patients, haematology outpatients). We judged only two trials to be at low risk of bias across all domains; most trials had an unclear risk for multiple domains.Transfusion of RBCs of shorter versus longer storage duration probably leads to little or no difference in mortality at seven-day follow-up (risk ratio (RR) 1.42, 95% confidence interval (CI) 0.66 to 3.06; 1 trial, 3098 participants; moderate quality evidence) or 30-day follow-up (RR 0.85, 95%CI 0.50 to 1.45; 2 trials, 1121 participants; moderate quality evidence) in adults undergoing major elective cardiac or non-cardiac surgery.For neonates, no studies reported on the primary outcome of in-hospital or short-term mortality. At 40 weeks gestational age, the effect of RBCs of shorter versus longer storage duration on the risk of death was uncertain, as the quality of evidence is very low (RR 0.90, 95% CI 0.41 to 1.85; 1 trial, 52 participants).The effect of RBCs of shorter versus longer storage duration on the risk of death in children with severe anaemia was also uncertain within 24 hours of transfusion (RR 1.50, 95% CI 0.43 to 5.25; 2 trials, 364 participants; very low quality evidence), or at 30-day follow-up (RR 1.40, 95% CI 0.45 to 4.31; 1 trial, 290 participants; low quality evidence).Only one trial, in children with severe anaemia (290 participants), reported adverse transfusion reactions. Only one child in each arm experienced an adverse reaction within 24 hours of transfusion.Transfusion of RBCs of shorter versus standard practice storage duration Eleven trials (40,588 participants) compared transfusion of RBCs of shorter versus standard practice storage duration. Three trials enrolled critically ill term neonates; two of these enrolled very low birth weight neonates. There were no trials in children. Eight trials enrolled critically ill and non-critically ill adults, with most being hospitalised. We judged four trials to be at low risk of bias across all domains with the others having an unclear risk of bias across multiple domains.Transfusion of RBCs of shorter versus standard practice storage duration probably leads to little or no difference in adult in-hospital mortality (RR 1.05, 95% CI 0.97 to 1.14; 4 trials, 25,704 participants; moderate quality evidence), ICU mortality (RR 1.06, 95% CI 0.98 to 1.15; 3 trials, 13,066 participants; moderate quality evidence), or 30-day mortality (RR 1.04, 95% CI 0.96 to 1.13; 4 trials, 7510 participants;moderate quality evidence).Two of the three trials that enrolled neonates reported that there were no adverse transfusion reactions. One trial reported an isolated case of cytomegalovirus infection in participants assigned to the standard practice storage duration group. Two trials in critically ill adults reported data on transfusion reactions: one observed no difference in acute transfusion reactions between arms (RR 0.67, 95% CI 0.19 to 2.36, 2413 participants), but the other observed more febrile nonhaemolytic reactions in the shorter storage duration arm (RR 1.48, 95% CI 1.13 to 1.95, 4919 participants).Trial sequential analysis showed that we may now have sufficient evidence to reject a 5% relative risk increase or decrease of death within 30 days when transfusing RBCs of shorter versus longer storage duration across all patient groups. AUTHORS' CONCLUSIONS: The effect of storage duration on clinically important outcomes has now been investigated in large, high quality RCTs, predominantly in adults. There appears to be no evidence of an effect on mortality that is related to length of storage of transfused RBCs. However, the quality of evidence in neonates and children is low. The current practice in blood banks of using the oldest available RBCs can be continued safely. Additional RCTs are not required, but research using alternative study designs, should focus on particular subgroups (e.g. those requiring multiple RBC units) and on factors affecting RBC quality.

The age of blood in pediatric intensive care units (ABC PICU): study protocol for a randomized controlled trial.

BACKGROUND: The "Age of Blood in Children in Pediatric Intensive Care Unit" (ABC PICU) study is a randomized controlled trial (RCT) that aims to determine if red blood cell (RBC) unit storage age affects outcomes in critically ill children. While RBCs can be stored for up to 42 days in additive solutions, their efficacy and safety after long-term storage have been challenged. Preclinical and clinical observational evidence suggests loss of efficacy and lack of safety of older RBC units, especially in more vulnerable populations such as critically ill children. Because there is a belief that shorter storage will improve outcomes, some physicians and institutions systematically transfuse fresh RBCs to children. Conversely, the standard practice of blood banks is to deliver the oldest available RBC unit (first-in, first-out policy) in order to decrease wastage. METHODS/DESIGN: The ABC PICU study, is a double-blind superiority trial comparing the development of "New or Progressive Multiple Organ Dysfunction Syndrome" (NPMODS) in 1538 critically ill children randomized to either transfusion with RBCs stored for ≤ 7 days or to standard-issue RBCs (oldest in inventory). Patients are being recruited from 52 centers in the US, Canada, France, Italy, and Israel. DISCUSSION: The ABC PICU study should have significant implications for blood procurement services. A relative risk reduction of 33% is postulated in the short-storage arm. If a difference is found, this will indicate that fresher RBCs do improve outcomes in the pediatric intensive care unit population and would justify that use in critically ill children. If no difference is found, this will reassure clinicians and transfusion medicine specialists regarding the safety of the current system of allocating the oldest RBC unit in inventory and will discourage clinicians from preferentially requesting fresher blood for critically ill children. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT01977547 . Registered on 6 November 2013.

Age of transfused blood in critically ill adult trauma patients: a prespecified nested analysis of the Age of Blood Evaluation randomized trial.

BACKGROUND: Blood transfusion is common in the resuscitation of patients with traumatic injury. However, the clinical impact of the length of storage of transfused blood is unclear in this population. STUDY DESIGN AND METHODS: We undertook a prespecified nested analysis of 372 trauma victims of the 2510 critically ill patients from 64 centers treated as part of the Age of Blood Evaluation (ABLE) randomized controlled trial. Patients were randomized according to their trauma status to receive either a transfusion of fresh blood stored not more than 7 days or standard-issue blood. Our primary outcome was 90-day all-cause mortality. RESULTS: Overall, 186 trauma patients received fresh blood and 186 received standard-issue blood. Adherence to transfusion protocol was 94% (915/971) for all fresh blood transfused and 100% (753/753) for all standard-issue blood transfused. Mean ± SD blood storage duration was 5.6 ± 3.8 days in the fresh group and 22.7 ± 8.4 days in the standard-issue group (p < 0.001). Ninety-day mortality in the fresh group was 21% (38/185), compared to 16% (29/184) in the standard-issue group, with an unadjusted absolute risk difference of 5% (95% confidence interval [CI], -3.1 to 12.6) and an adjusted absolute risk difference of 2% (95% CI, -3.5 to 6.8). CONCLUSION: In critically ill trauma patients, transfusion of fresh blood did not decrease 90-day mortality or secondary outcomes, a finding similar to the overall population of the ABLE trial.

Transfusion of fresher versus older red blood cells for all conditions.

BACKGROUND: Red blood cell transfusion is a common treatment for anaemia in many clinical conditions. One current concern is uncertainty as to the clinical consequences (notably efficacy and safety) of transfusing red blood cell units that have been stored for different durations of time before a transfusion. If evidence from randomised controlled trials were to indicate that clinical outcomes are affected by storage age, the implications for inventory management and clinical practice would be significant. OBJECTIVES: To assess the effects of using fresher versus older red blood cells in people requiring a red blood cell transfusion. SEARCH METHODS: We ran the search on 29th September 2014. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO), PubMed (for e-publications), three other databases and trial registers. SELECTION CRITERIA: We included randomised controlled trials comparing fresher red blood cell transfusion versus active transfusion of older red blood cells, and comparing fresher red blood cell transfusion versus current standard practice. All definitions of 'fresher' and 'older'/'standard practice' red blood cells were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted from the trial report data on adverse red blood cell transfusion reactions, when reported. MAIN RESULTS: We included 16 trials (1864 participants) in the review. Eight trials (279 participants) compared transfusion of fresher red blood cells versus transfusion of older stored red blood cells ('fresher' vs 'older'). Eight trials (1585 participants) compared the transfusion of fresher red blood cells versus current standard practice ('fresher' vs 'standard practice'). Five trials enrolled neonates, one trial enrolled children and 12 trials enrolled adults. Overall sample sizes were small: only two trials randomly assigned more than 100 participants.We performed no meta-analyses for a variety of reasons: no uniform definition of 'fresher' or 'older' red blood cell storage; overlap in the distribution of the age of red blood cells; and heterogeneity in measurements and reporting of outcomes of interest to this review. We tabulated and reported results by individual trial. Overall risk of bias was low or unclear, with four incidences of high risk of bias: in allocation concealment (three trials) and in incomplete outcome data (one trial).No trial measured all of the outcomes of interest in this review. Four trials comparing 'fresher' with 'older' red blood cells reported the primary outcome: mortality within seven days (one study; 74 participants) and at 30 days (three trials; 62 participants). Six trials comparing 'fresher' with 'standard practice' red blood cells reported the primary outcome: mortality within seven days (three studies; 159 participants) and at 30 days (three trials; 1018 participants). All 10 trials reported no clear differences in mortality at either time point between intervention arms.Three trials comparing 'fresher' with 'standard practice' red blood cells reported red blood cell transfusion-associated adverse events. No adverse reactions were reported in two trials, and one incidence of cytomegalovirus (CMV) infection was described in the 'standard practice' arm in one trial.Overall the trials reported no clear difference between either of the intervention comparisons in long-term mortality (three trials; 478 participants); clinically accepted measures of multiple organ dysfunction (two trials: 399 participants); incidence of in-hospital infection (two trials; 429 participants); duration of mechanical ventilation (three trials: 95 participants); and number of participants requiring respiratory organ support (five trials; 528 participants) or renal support (one trial; 57 participants). The outcome 'physiological markers of oxygen consumption or alterations in microcirculation' was reported by 11 studies, but the measures used were highly varied, and no formal statistical analysis was undertaken. AUTHORS' CONCLUSIONS: Several factors precluded firm conclusions about the clinical outcomes of transfusing red blood cell units that have been stored for different periods of time before transfusion, including differences in clinical population and setting, diversity in the interventions used, methodological limitations and differences in how outcomes were measured and reported.No clear differences in the primary outcome - death - were noted between 'fresher' and 'older' or 'standard practice' red blood cells in trials that reported this outcome. Findings of a large number of ongoing trials will be incorporated into this review when they are published.Updates of this review will explore the degree of overlap in trials between 'fresher', 'older' and 'standard practice' storage ages of red blood cells and will consider whether the size of any observed effects is dependent on recipient factors such as clinical background, patient age or clinical presentation.

From the Journal archives: The red blood cell storage lesion: past, present, and future.

PURPOSE: This retrospective observational study was performed to determine if the age of transfused units of red blood cells (RBCs) was related to mortality. The study included 31 transfused patients admitted to the intensive care unit during 1992 with severe sepsis (i.e., sepsis associated with organ dysfunction, hypoperfusion, or hypotension). PRINCIPAL FINDINGS: Nineteen of 31 patients (61%) died. On average, non-survivors received older RBC units than survivors. In non-survivors, the median age of the units was 24 days (range 7-36 days), whereas the median age in survivors was 21 days (range 5-35 days). Analyzing outcomes according to different age categories revealed that survivors received 85% of units that were less than ten days old, whereas non-survivors received 76% of units that were more than 20 days old. These differences were statistically significant (P < 0.0001). CONCLUSIONS: The authors concluded that the duration of storage of RBCs is directly related to the risk of mortality among transfused patients with severe sepsis. Recognizing the limitations of their small retrospective study that did not adjust for confounders, they also stated that further studies are needed to confirm or refute this association.

Erythrocyte storage duration is not associated with increased mortality in noncardiac surgical patients: a retrospective analysis of 6,994 patients.

BACKGROUND: More than 5 million patients receive erythrocyte transfusions in the United States every year. Previous studies linked the storage duration of allogeneic erythrocytes to the risk of severe postoperative complications, especially after cardiac or trauma surgery. Limited data are available for noncardiac surgical patients. We therefore evaluated the association between storage duration of transfused erythrocytes and postoperative all-cause mortality among general surgery patients. METHODS: Perioperative data corresponding to 63,319 adult, general surgery patients were obtained from our registry and merged with blood product data. Patients receiving solely leukocyte-reduced, allogeneic erythrocyte transfusions were included. Multivariable Cox proportional hazards regression was used to characterize the relationship between median erythrocyte storage duration and postoperative mortality rate, adjusting for characteristics plausibly influencing the storage duration of erythrocytes. RESULTS: Of the 6,994 patients included in the final analysis, 23, 44, 11, 9, and 13% received 1, 2, 3, 4, and ≥5 erythrocyte units, respectively. The authors found no evidence that increasing median storage duration was associated with a difference in the risk of postoperative mortality (hazard ratio, 0.99 [0.94-1.04]; P = 0.64). Analyzing the mean storage duration of erythrocyte units as a function of year of transfusion, the authors demonstrate a relevant decrease in utilization of the oldest blood units, whereas young blood storage duration remains nearly unchanged. CONCLUSION: The authors' study supports the recent literature in surgical and medical patients and underlines the importance of sufficiently powered randomized trials to finally resolve the erythrocyte storage duration debate.

The impact of plasma preparations and their storage time on short-term posttransfusion mortality: a population-based study using the Scandinavian Donation and Transfusion database.

BACKGROUND: The treatment of coagulopathy and bleeding in severe trauma requires rapid delivery of large amounts of plasma to emergency wards. The resulting need for adequate supplies of nonfrozen or thawed plasma has consequences for storage strategies. Using extensive population data from a setting where both fresh-frozen plasma (FFP) and cold-stored liquid plasma were used, this study investigates whether there is an association between short-term mortality after receipt of FFP or liquid plasma of different storage times. METHODS: A cohort of 84,986 Swedish patients was followed up from first recorded allogenic plasma transfusion for 14-day mortality. Associations with exposure to FFP were expressed as relative risks adjusted for patient characteristics, total transfusions, hospital, and calendar year. For non-FFP, the units given to patients who died and matched patients who survived were compared for their duration of storage. RESULTS: The relative risk of exposure to FFP was 1.19 (95% confidence interval: 1.12-1.27, p < 0.0001), with the risk elevation confined to the earlier calendar years of the study. There was no evidence of any effect of storage time of non-FFP. In analyses of all plasma types, FFP from male donors had lowest risk. CONCLUSIONS: Compared with exclusive use of never-frozen plasma, FFP was associated with increased short-term mortality in the era before leukocyte depletion. FFP from female donors had a significantly higher risk than male FFP. For non-FFP, duration of storage was unrelated to mortality. These findings can help to inform policies for managing high plasma demand in critical care.

The effect of blood storage duration on in-hospital mortality: a randomized controlled pilot feasibility trial.

BACKGROUND: Whether the duration of storage of blood has an impact on patient outcomes remains controversial. The objective was to determine feasibility of a comparative effectiveness trial to evaluate duration of storage of blood before transfusion on in-hospital mortality. STUDY DESIGN AND METHODS: A single-center randomized controlled trial was performed at an acute care hospital in Canada between June and December 2010, involving consecutive hospitalized patients needing blood transfusion. Patients (n=910) were randomly assigned in a 1:2 ratio to receive freshest available versus standard-issue (oldest available) blood. Four feasibility criteria were measured: proportion of eligible patients randomized, contrast in age of blood between treatment groups, real-time data acquisition, and trial impact on blood outdating. In-hospital mortality was also reported. RESULTS: A total of 1075 of 1129 patients (95.2%) were eligible and 910 of 1075 (84.7%) were randomized: 309 received freshest available blood (1157 units), and 601 received standard-age blood (2369 units). Contrast in mean age of the oldest blood transfused between groups was 14.6 days: 12.0 (standard deviation [SD], 6.8) days in the fresh arm and 26.6 (SD, 7.8) days in the standard arm. Weekly recruitment and event reporting were achieved for all patients. The blood outdate rate was 0.10%. In-hospital mortality was 10.5%: 35 deaths (11.3%) in the fresh arm and 61 deaths (10.1%) in the standard arm (odds ratio, 1.13; 95% confidence interval [CI], 0.73, 1.76). CONCLUSION: It is feasible to conduct a large comparative effectiveness trial comparing the effect of freshest available versus standard-issue blood on in-hospital mortality. The wide CI around the estimate for in-hospital mortality supports the need for a large trial.

Duration of red blood cell storage and outcomes following orthotopic liver transplantation.

Liver transplantation may be complicated by massive intraoperative bleeding, and red blood cell (RBC) transfusions may be required. The storage duration or age of transfused RBCs has been shown to affect the morbidity and mortality of critically ill, trauma, and cardiac surgery patients. Here we investigate the effect of RBC age on the outcomes of liver transplant patients. Five hundred thirty-one patients underwent orthotopic liver transplantation between January 1, 2000 and August 15, 2010. The patient demographics, the Model for End-Stage Liver Disease-sodium (MELD-Na) score, and the number and age of RBC units were evaluated with univariate and multivariate models of outcomes, which included mortality rates 2 years after transplantation, postoperative infections, and organ rejection. In a univariate analysis, the number of RBC units (but not the RBC age) was associated with increased 2-year mortality, an increased risk of infection, and a decreased risk of organ rejection. Only the number of RBC units was associated with increased 2-year mortality in a multivariate Cox regression model. The mortality risk was decreased by two-thirds for patients who received <10 U of RBCs versus those who received ≥10 U (hazard ratio = 0.33, 95% confidence interval = 0.16-0.69, P = 0.003). The number of transfused RBC units was not associated with the risk of infection or organ rejection in a multivariate logistic regression model. In conclusion, the RBC age is not associated with infection, organ rejection, or death in liver transplant patients. Patients who receive more blood have an increased risk of death. In a multivariate model, the MELD-Na score was not associated with increased mortality, and this is consistent with previous studies demonstrating that the MELD-Na score is a poor predictor of long-term survival after transplantation.

Transfusion of older stored blood and risk of death: a meta-analysis.

BACKGROUND: Blood for transfusion is stored for up to 42 days. Older blood develops lesions and accumulates potentially injurious substances. Some studies report increasing toxicity as blood ages. We assessed the safety of transfused older versus newer stored blood. STUDY DESIGN AND METHODS: PubMed, Scopus, and Embase were searched using terms new and old and red blood cell and storage through May 6, 2011, for observational and randomized controlled studies comparing outcomes using transfused blood having longer and shorter storage times. Death was the outcome of interest. RESULTS: Twenty-one studies were identified, predominantly in cardiac surgery (n=6) and trauma (n=6) patients, including 409,966 patients. A test for heterogeneity of these studies' results was not significant for mortality (I(2)=3.7%, p=0.41). Older blood was associated with a significantly increased risk of death (odds ratio, 1.16; 95% confidence interval [CI], 1.07-1.24). Using available mortality data, 97 (95% CI, 63-199) patients need to be treated with only new blood to save one life. Subgroup analysis of these trials indicated that the increased risk was not restricted to a particular type of patient, size of trial, or amount of blood transfused. CONCLUSION: Based on available data, use of older stored blood is associated with a significantly increased risk of death.

Effect of storage time of transfused plasma on early and late mortality after coronary artery bypass grafting.

OBJECTIVES: Because some concern has been raised about the storage time of red blood cells and outcomes after cardiac surgery, we investigated whether longer storage time of transfused plasma increases the risk for early or late mortality among patients who have undergone coronary artery bypass grafting. METHODS: We retrospectively analyzed the data of all 10,626 patients who underwent isolated coronary artery bypass grafting in Catharina Hospital, Eindhoven, The Netherlands, between January 1998 and December 2007. All patients who received at least 1 unit of plasma intraoperatively or during the first 5 postoperative days were studied. They were divided into 3 groups (only younger plasma, only older plasma, and any older plasma groups) according to the storage time of the plasma (cutoff point, 323 days). RESULTS: After we had excluded 122 patients who were unavailable for follow-up, we found that 375 of the remaining patients (n = 745) received only younger plasma 370 patients received any older plasma, and 200 patients received only older plasma (mean follow-up, 1565 ± 1137 days; median follow-up, 1629 days). The storage time of plasma, when entered as either a continuous variable or a dichotomous variable, was a risk factor for early but not late mortality. Log-rank testing revealed no statistical difference in long-term survival among the groups. CONCLUSIONS: Longer storage time of plasma is a risk factor for early but not late mortality among patients who have undergone coronary artery bypass grafting.

Effect of duration of red blood cell storage on early and late mortality after coronary artery bypass grafting.

OBJECTIVES: Recently, concern has been expressed about the transfusion of older red blood cells after cardiac surgery. We tested the hypothesis that longer storage of transfused red blood cells increases the risk of early and late mortality in patients who undergo coronary artery bypass grafting. METHODS: We retrospectively analyzed data of patients who underwent isolated coronary artery bypass grafting between January 1998 and December 2007 in Catharina Hospital, Eindhoven, The Netherlands, and received up to 10 U of red blood cells intraoperatively or during the first 5 postoperative days. The patients were divided into 3 groups according to the storage time of the red blood cells, with a cutoff point of 14 days, as follows: "only younger blood" (n = 1422), "only older blood" (n = 1719), and at least 1 U of older RBCs ("any older blood"; n = 2175). RESULTS: The mean follow-up time was 1693 ± 1058 days (range, 0-3708 days). The median follow-up time was 1629 days. Univariate and multivariate logistic regression analyses revealed that the number of transfused units but not the storage time of blood entered either as a continuous variable or as a dichotomous variable with a cutoff point of 14 days was a risk factor for early mortality. Neither the number of transfused units nor the storage time was an independent risk factor for late mortality. Log-rank testing revealed no statistical difference in survival among the groups. CONCLUSIONS: The storage time of transfused red blood cells is not a risk factor for early or late mortality in patients who undergo coronary artery bypass grafting.

Association of mortality with age of blood transfused in septic ICU patients.

PURPOSE: To determine, retrospectively, the age of packed red blood cell (PRBC) units transfused to patients admitted to the ICU with the diagnosis of severe sepsis and to correlate this variable with outcome. METHODS: All patients admitted to the ICU during 1992 with a diagnosis of severe sepsis were selected retrospectively. The criteria for the diagnosis of severe sepsis and septic shock were based on established guidelines. For each patient the total number of PRBC units transfused, the number of units transfused before, during and after the septic episode, and the age of each PRBC unit transfused were recorded. RESULTS: Of the 31 patients admitted to the ICU with severe sepsis, 19 died and 12 survived. No statistical differences between survivors and nonsurvivors were found with respect to age, sex, number of days in ICU, duration of sepsis, incidence of septic shock, admission Apache II score or total number of PRBC units transfused. During sepsis the median age of PRBC units transfused to survivors was 17 days (range 5-35) vs 25 days (range 9-36) for nonsurvivors (P < 0.0001). A negative correlation (r = -0.73) was found between the proportion of PRBC units of a given age transfused to survivors and increasing age of PRBC. CONCLUSION: This is the first study to report a correlation of mortality with the age of PRBC transfused. The cause of this association is unclear. If this association is confirmed by a prospective randomised trial it would have major implications for the use of PRBC in severe sepsis.