Analysis of Red Blood Cell Storage Duration and in-Hospital Mortality Using Time Dependent Exposure: Is the Oldest Blood Bad?
Transfusion. 2017;57((53)):33A.. c26-a02c
Red blood cell storage and in-hospital mortality: a secondary analysis of the INFORM randomised controlled trial
The Lancet. Haematology. 2017;4((11):):e544-e552. e544
BACKGROUND No randomised trials have addressed whether exposure to red blood cells (RBCs) stored longer than 35 days is associated with harm in patients. We aimed to assess the risk of in-hospital mortality associated with transfusing blood stored longer than 35 days. METHODS We did a secondary analysis of the INforming Fresh versus Old Red cell Management (INFORM) trial, a pragmatic, multicentre, randomised controlled trial of patients (≥18 years) admitted to one of six hospitals in Australia, Canada, Israel, and the USA and expected to need RBC transfusions. Patients were randomly assigned (2:1) to receive blood in inventory stored for the longest time (standard care) or the shortest time, using a random allocation schedule and stratified by centre and patient ABO blood group. The primary objective of the INFORM trial was to assess all-cause in-hospital mortality in patients with blood group A and O who were transfused. For our exploratory secondary analysis, we classified individuals into one of three mutually exclusive exposure categories on the basis of the maximum storage duration of any blood unit patients had received on each day in hospital: exclusively exposed to RBCs stored no longer than 7 days, exposed to at least one unit of RBCs stored 8-35 days, and exposed to least one unit of RBCs stored longer than 35 days. Our primary objective was to determine the effect on risk of in-hospital death of time-dependent exposure to RBCs stored longer than 35 days compared with exclusive exposure to RBCs stored no longer than 7 days, both in patients of blood groups A and O and all patients. The INFORM trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN08118744. FINDINGS Between April 2, 2012, and Oct 21, 2015, 31 497 patients were recruited, and 24 736 patients were eligible for inclusion in this analysis. We excluded nine patients for whom information about the storage duration of transfused blood was missing and one patient whose sex was unknown. 4480 (18%) patients were exposed to RBCs with longest storage, 1392 (6%) patients were exposed exclusively to RBCs with shortest storage, and 18 854 (76%) patients were exposed to RBCs stored 8-35 days. Median follow-up was 11 days (IQR 6-20). Exposure to RBCs stored longer than 35 days was not associated with increased risk of in-hospital death compared with exclusive exposure to the freshest RBC units after adjusting for demographic variables, diagnosis category, and blood product use history (in patients with blood group A or O: hazard ratio 0.94, 95% CI 0.73-1.20, p=0.60; in all patients: 0.91, 0.72-1.14, p=0.40). The risk of in-hospital death also did not differ between patients exposed to blood stored 8-35 days and patients exposed to blood stored 7 days or less (in patients with blood group A or O: 0.92, 0.74-1.15, p=0.48; in all patients: 0.90, 0.73-1.10, p=0.29). INTERPRETATION These data provide evidence that transfusion of blood stored for longer than 35 days has no effect on in-hospital mortality, which suggests that current approaches to blood storage and inventory management are reasonable. FUNDING Canadian Institutes for Health Research, Canadian Blood Services, and Health Canada.
Mortality outcomes in patients transfused with fresher versus older red blood cells: a meta-analysis
Vox Sanguinis. 2017;112((3):):268-278
BACKGROUND Among transfused patients, the effect of the duration of red blood cell storage on mortality remains unclear. This study aims to compare the mortality of patients who were transfused with fresher versus older red blood cells. METHODS We performed an updated systematic search in the CENTRAL, MEDLINE, EMBASE and CINAHL databases, from January 2015 to October 2016. RCTs of hospitalized patients of any age comparing transfusion of fresher versus older red blood cells were eligible. We used a random-effects model to calculate pooled risk ratios (RRs) with corresponding 95% confidence interval (CI). RESULTS We identified 14 randomized trials that enrolled 26 374 participants. All-cause mortality occurred in 1219 of 9531 (12.8%) patients who received a transfusion of fresher red blood cells and 1810 of 16 843 (10.7%) in those who received older red blood cells (RR: 1.04, 95% CI: 0.98-1.12, P = 0.90, I2 = 0%, high certainty for ruling out benefit of fresh blood, moderate certainty for ruling out harm of fresh blood). In six studies, in-hospital death occurred in 691 of 7479 (9.2%) patients receiving fresher red cells and 1291 of 14 757 (8.8%) receiving older red cells (RR: 1.06, 95% CI: 0.97-1.15, P = 0.81, I2 = 0%, high certainty for ruling out benefit of fresh blood, moderate certainty for ruling out harm of fresh blood). CONCLUSION Transfusion of fresher red blood cells does not reduce overall or in-hospital mortality when compared with older red blood cells. Our results support the practice of transfusing patients with the oldest red blood cells available in the blood bank.
Informing Fresh versus Old Red Cell Management (INFORM) trial: a large international pragmatic randomized trial
Transfusion. 2016;56((S4)):5A.. p6-030a.
Effect of short-term vs. long-term blood storage on mortality after transfusion
The New England Journal of Medicine. 2016;375((20):):1937-1945
Background Randomized, controlled trials have suggested that the transfusion of blood after prolonged storage does not increase the risk of adverse outcomes among patients, although most of these trials were restricted to high-risk populations and were not powered to detect small but clinically important differences in mortality. We sought to find out whether the duration of blood storage would have an effect on mortality after transfusion in a general population of hospitalized patients. Methods In this pragmatic, randomized, controlled trial conducted at six hospitals in four countries, we randomly assigned patients who required a red-cell transfusion to receive blood that had been stored for the shortest duration (short-term storage group) or the longest duration (long-term storage group) in a 1:2 ratio. Only patients with type A or O blood were included in the primary analysis, since pilot data suggested that our goal of achieving a difference in the mean duration of blood storage of at least 10 days would not be possible with other blood types. Written informed consent was waived because all the patients received treatment consistent with the current standard of care. The primary outcome was in-hospital mortality, which was estimated by means of a logistic-regression model after adjustment for study center and patient blood type. Results From April 2012 through October 2015, a total of 31,497 patients underwent randomization. Of these patients, 6761 who did not meet all the enrollment criteria were excluded after randomization. The primary analysis included 20,858 patients with type A or O blood. Of these patients, 6936 were assigned to the short-term storage group and 13,922 to the long-term storage group. The mean storage duration was 13.0 days in the short-term storage group and 23.6 days in the long-term storage group. There were 634 deaths (9.1%) in the short-term storage group and 1213 (8.7%) in the long-term storage group (odds ratio, 1.05; 95% confidence interval [CI], 0.95 to 1.16; P=0.34). When the analysis was expanded to include the 24,736 patients with any blood type, the results were similar, with rates of death of 9.1% and 8.8%, respectively (odds ratio, 1.04; 95% CI, 0.95 to 1.14; P=0.38). Additional results were consistent in three prespecified high-risk subgroups (patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer). Conclusions Among patients in a general hospital population, there was no significant difference in the rate of death among those who underwent transfusion with the freshest available blood and those who underwent transfusion according to the standard practice of transfusing the oldest available blood. (Funded by the Canadian Institutes of Health Research and others; INFORM Current Controlled Trials number, ISRCTN08118744 .).
Oral tranexamic acid in total knee replacement: results of a randomized study
Vox Sanguinis. 2004;87((Suppl 3):):50.. Abstract No. P 27.5.
The postoperative blood-sparing efficacy of oral versus intravenous tranexamic acid after total knee replacement
Anesthesia & Analgesia. 2004;99((6):):1679-83.
To assess the blood-sparing efficacy of tranexamic acid (TA) administered orally or via a variable IV infusion, 80 healthy patients undergoing elective total knee replacement were studied according to a prospective, controlled, randomized, single-blinded study design. Patients were allocated to one of four treatment groups. In group TA-long, 30 min before deflation of the limb tourniquet, an IV bolus dose of TA 15 mg/kg was administered over 30 min. Thereafter, a constant IV infusion of 10 mg . kg(-1) . h(-1) was administered until 12 h after final deflation of the limb tourniquet. In group TA-short, a similar regimen was followed; however, the constant IV infusion was discontinued 2 h after final deflation of the limb tourniquet (time of discharge from the postanesthesia care unit). Thereafter, oral TA 1 g was administered after 6 and 12 h. In group TA-oral, 60 min before surgery an oral dose of TA 1 g was administered. After surgery, a similar dose of TA was administered every 6 h for the next 18 h. In the control group, TA was not administered. At patient discharge, postoperative allogeneic blood administration was significantly more in group Control when compared with each of the three TA treatment groups. Because oral drug administration is simple and does not require specific infusion equipment, the authors suggest that oral TA is a superior blood-sparing strategy compared with IV drug administration.
A comparative study of the postoperative allogeneic blood-sparing effect of tranexamic acid versus acute normovolemic hemodilution after total knee replacement
Anesthesia & Analgesia. 1999;89((6):):1382-7.
UNLABELLED Both acute normovolemic hemodilution (NVHD) and tranexamic acid (TA) are potentially useful allogeneic blood conservation strategies after total knee replacement. However, the relative efficacy of these blood-sparing techniques is unknown. Therefore, to compare the postoperative allogeneic blood sparing of NVHD and TA after total knee replacement, we investigated 40 patients in a prospective, single-blinded study protocol. In Group TA, 30 min before deflating the limb tourniquet, an IV infusion of TA, 15 mg/kg, was administered over a 30-min period. Thereafter, a constant IV infusion of 10 mg x kg(-1) x hr(-1) was administered until 12 h after deflation of the limb tourniquet. Before induction of anesthesia, NVHD patients were bled to a target hematocrit of approximately 28%. Intravascular blood volume was maintained with lactated Ringer's solution. All autologous blood was transfused at the end of the surgery. Postoperatively, hematocrit was measured daily. In all cases, a hematocrit <27% was the postoperative transfusion trigger. Before discharge, deep vein thrombosis was excluded by Echo Doppler. Three months after surgery, the incidence of delayed thromboembolic events was assessed. The two groups were demographically comparable. In Group NVHD, 843 mL+/-289 of autologous blood was removed. Despite autologous blood transfusion, during the early postoperative period and until the third postoperative day, the NVHD group had significantly (P < 0.01) lower mean hematocrits when compared with the TA group. Thereafter, because of a significantly (P < 0.0008) greater allogeneic blood requirement in the NVHD group, no statistically significant difference in mean hematocrit recordings was noted among the groups. Blood accumulation in the surgical drain 12 h postoperatively, was significantly (P < 0.0008) higher in the NVHD group (259 mL+/-156) when compared with the TA group (110 mL+/-62). Significantly (P < 0.0008) more allogeneic blood was transfused in the NVHD group (19 U/13 patients) when compared with the TA group (2 U/2 patients). No abnormal Echo Doppler studies were reported. During the 3-mo follow-up period, a deep vein thrombosis and pulmonary embolus were documented in one patient in the NVHD group. We conclude that perioperative hemodynamic stability and allogeneic blood sparing is superior after tranexamic acid administration when compared with normovolemic hemodilution. IMPLICATIONS For total knee replacement, when compared with normovolemic hemodilution, tranexamic acid administration is associated with superior perioperative hemodynamic stability and allogeneic blood sparing.