Massive transfusion in cardiac surgery: the impact of blood component ratios on clinical outcomes and survival
Transfusion. 2016;56((S4)):3A.. p1-030a.
B-type natriuretic peptide and plasma hemoglobin levels following transfusion of shorter-storage versus longer-storage red blood cells: results from the TOTAL randomized trial
American Heart Journal. 2016;183:129-136
Prior studies have suggested that transfusion of stored red blood cells (RBCs) with increased levels of cell-free hemoglobin might reduce the bioavailability of recipient nitric oxide (NO) and cause myocardial strain. METHODS Ugandan children (ages 6-60 months) with severe anemia and lactic acidosis were randomly assigned to receive RBCs stored 1-10 days versus 25-35 days. B-type natriuretic peptide (BNP), vital signs, renal function test results, and plasma hemoglobin were measured. Most children had either malaria or sickle cell disease and were thus at risk for reduced NO bioavailability. RESULTS Seventy patients received RBCs stored 1-10 days, and 77 received RBCs stored 25-35 days. The median (interquartile range) cell-free hemoglobin was nearly 3 times higher in longer-storage RBCs (26.4 [15.5-43.4] mumol/L) than in shorter-storage RBCs (10.8 [7.8-18.6] mumol/L), P < .0001. Median (interquartile range) BNP 2 hours posttransfusion was 156 (59-650) pg/mL (shorter storage) versus 158 (59-425) pg/mL (longer storage), P = .76. BNP values 22 hours posttransfusion were 110 (46-337) pg/mL (shorter storage) versus 96 (49-310) pg/mL (longer storage), P = .76. Changes in BNP within individuals from pretransfusion to 2 hours (or 22 hours) posttransfusion were not significantly different between the study groups. BNP change following transfusion did not correlate with the concentration of cell-free hemoglobin in the RBC supernatant. Blood pressure, blood urea nitrogen, creatinine, and change in plasma hemoglobin were not significantly different in the 2 groups. CONCLUSION In a randomized trial among children at risk for reduced NO bioavailability, we found that BNP, blood pressure, creatinine, and plasma hemoglobin were not higher in patients receiving RBCs stored for 25-35 versus 1-10 days.
The impact of red blood cell storage duration on tissue oxygenation in cardiac surgery
Journal of Thoracic & Cardiovascular Surgery. , 2016 Nov 19.. 2016;153((3):):610-619 e2
OBJECTIVE Although storage alters red blood cells, several recent, randomized trials found no differences in clinical outcomes between patients transfused with red blood cells stored for shorter versus longer periods of time. The objective of this study was to see whether storage impairs the in vivo ability of erythrocytes to traverse the microcirculation and deliver oxygen at the tissue level. METHODS A subset of subjects from a clinical trial of cardiac surgery patients randomized to receive transfusions of red blood cells stored <10 days or >21 days were assessed for thenar eminence and cerebral tissue hemoglobin oxygen saturation (StO2) via the use of near-infrared spectroscopy and sublingual microvascular blood flow via side-stream darkfield videomicroscopy. RESULTS Among 55 subjects, there was little change in the primary endpoint (thenar eminence StO2 from before to after transfusion of one unit) and the change was similar in the 2 groups: +1.7% (95% confidence interval, -0.3, 3.8) for shorter-storage and +0.8% (95% confidence interval, -1.1, 2.9) for longer-storage; P = .61). Similarly, no significant differences were observed for cerebral StO2 or sublingual microvascular blood flow. These parameters also were not different from preoperatively to 1 day postoperatively, reflecting the absence of a cumulative effect of all red blood cell units transfused during this period. CONCLUSIONS There were no differences in thenar eminence or cerebral StO2, or sublingual microcirculatory blood flow, in cardiac surgery patients transfused with red blood cells stored <10 days or >21 days. These results are consistent with the clinical outcomes in the parent study, which also did not differ, indicating that storage may not impair oxygen delivery by red blood cells in this setting.Copyright Â© 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
Tissue oxygenation by transfusion in severe anemia with lactic acidosis (TOTAL): a prospective, randomized, non-inferiority trial of blood storage duration
Blood. 2015;126((23)): Abstract No. 769.
Effect of transfusion of red blood cells with longer vs shorter storage duration on elevated blood lactate levels in children with severe anemia: the TOTAL randomized clinical trial
IMPORTANCE Although millions of transfusions are given annually worldwide, the effect of red blood cell (RBC) unit storage duration on oxygen delivery is uncertain. OBJECTIVE To determine if longer-storage RBC units are not inferior to shorter-storage RBC units for tissue oxygenation as measured by reduction in blood lactate levels and improvement in cerebral tissue oxygen saturation among children with severe anemia. DESIGN, SETTING, AND PARTICIPANTS Randomized noninferiority trial of 290 children (aged 6-60 months), most with malaria or sickle cell disease, presenting February 2013 through May 2015 to a university-affiliated national referral hospital in Kampala, Uganda, with a hemoglobin level of 5 g/dL or lower and a lactate level of 5 mmol/L or higher. INTERVENTIONS Patients were randomly assigned to receive RBC units stored 25 to 35 days (longer-storage group; n=145) vs 1 to 10 days (shorter-storage group; n=145). All units were leukoreduced prior to storage. All patients received 10 mL/kg of RBCs during hours 0 through 2 and, if indicated per protocol, an additional 10 mL/kg during hours 4 through 6. MAIN OUTCOMES AND MEASURES The primary outcome was the proportion of patients with a lactate level of 3 mmol/L or lower at 8 hours using a margin of noninferiority equal to an absolute difference of 25%. Secondary measures included noninvasive cerebral tissue oxygen saturation during the first transfusion, clinical and laboratory changes up to 24 hours, and survival and health at 30 days after transfusion. Adverse events were monitored up to 24 hours. RESULTS In the total population of 290 children, the mean (SD) presenting hemoglobin level was 3.7 g/dL (1.3) and mean lactate level was 9.3 mmol/L (3.4). Median (interquartile range) RBC unit storage was 8 days (7-9) for shorter storage vs 32 days (30-34) for longer storage without overlap. The proportion achieving the primary end point was 0.61 (95% CI, 0.52 to 0.69) in the longer-storage group vs 0.58 (95% CI, 0.49 to 0.66) in the shorter-storage group (between-group difference, 0.03 [95% CI, -0.07 to ], P<.001), meeting the prespecified margin of noninferiority. Mean lactate levels were not statistically different between the 2 groups at 0, 2, 4, 6, 8, or 24 hours. Kaplan-Meier analysis and global nonlinear regression revealed no statistical difference in lactate reduction between the 2 groups. Clinical assessment, cerebral oxygen saturation, electrolyte abnormalities, adverse events, survival, and 30-day recovery were also not significantly different between the groups. CONCLUSIONS AND RELEVANCE Among children with lactic acidosis due to severe anemia, transfusion of longer-storage compared with shorter-storage RBC units did not result in inferior reduction of elevated blood lactate levels. These findings have relevance regarding the efficacy of stored RBC transfusion for patients with critical tissue hypoxia and lactic acidosis due to anemia. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01586923.
Effects of red-cell storage duration on patients undergoing cardiac surgery
New England Journal of Medicine. 2015;372((15):):1419-29.
BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion.METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge.RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group.CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).
Randomized trial results: red cell storage age is not associated with a significant difference in multiple-organ dysfunction score or mortality in transfused cardiac surgery patients
Transfusion. 2014;54((S2)):15A.. Abstract No. P2-030A.
Addressing the question of the effect of RBC storage on clinical outcomes: the Red Cell Storage Duration Study (RECESS) (Section 7)
Transfusion and Apheresis Science. 2010;43((1):):107-16.
The question of whether storage of red blood cells (RBCs) alters their capacity to deliver oxygen and affects patient outcomes remains in a state of clinical equipoise. Studies of the changes which occur while RBCs are stored have led to several physiologically plausible hypotheses that these changes impair RBC function when the units are transfused. Although there is some evidence of this effect in vivo from animal model experiments, the results of several largely retrospective patient studies have not been consistent. Some studies have shown an association between worse clinical outcomes and transfusion of RBC which have been stored for longer periods of time, while others have found no effect. Three multicenter, randomized, controlled trials have been developed to address this important, but currently unanswered, question. Two clinical trials, one in low birth weight neonates and the other in intensive care unit patients, are enrolling subjects in Canada (the Age of Red Blood Cells in Premature Infants; the Age of Blood Study). The third trial, which is being developed in the United States, is the Red Cell Storage Duration Study (RECESS). This is a multicenter, randomized, controlled trial in which patients undergoing complex cardiac surgical procedures who are likely to require RBC transfusion will be randomized to receive RBC units stored for either 10 or fewer days or 21 or more days. Randomization will only occur if the blood bank has enough units of RBC of both storage times to meet the crossmatch request; hence, subjects randomized to the 21 day arm will receive RBC of the same storage time as they would have following standard inventory practice of oldest units out first. The primary outcome is the change in the Multiple Organ Dysfunction Score (MODS), a composite measure of multiorgan dysfunction, by day 7. Secondary outcomes include the change in the MODS by day 28, all-cause mortality, and several composite and single measures of specific organ system function. The estimated total sample size required will be 1434 evaluable subjects (717 per arm).
An open-label, randomized, parallel-group study of perioperative epoetin alfa versus standard of care for blood conservation in major elective spinal surgery: safety analysis
STUDY DESIGN Prospective, open-label, randomized, parallel-group study at 80 centers. OBJECTIVE To demonstrate there is no clinically important additional risk for deep vein thrombosis with perioperative use of epoetin alfa versus standard of care in spine surgery without prophylactic anticoagulation. SUMMARY OF BACKGROUND DATA Trials of epoetin alfa in orthopedic surgery that demonstrated no additional risk of thrombovascular events included perioperative pharmacologic anticoagulation. METHODS Subjects received epoetin alfa 600 U/kg subcutaneously once weekly starting 3 weeks before spinal surgery plus standard of care for blood conservation, or standard of care alone. Perioperative anticoagulation therapy was not permitted; mechanical deep vein thrombosis prophylaxis was allowed. Doppler imaging for deep vein thrombosis was done on postoperative day 4 (or day of discharge), or for suspected deep vein thrombosis. Deep vein thrombosis was diagnosed by Doppler result or adverse event report. The criterion for no additional risk of deep vein thrombosis was a 1-sided 97. 5% upper confidence limit < or =4% between groups. RESULTS Of the 680 subjects analyzed (340 in each treatment group), 16 (4. 7%) in the epoetin alfa group and 7 (2. 1%) in the standard of care group had a diagnosis of deep vein thrombosis either by Doppler or by adverse event report with normal Doppler. The between-group difference was 2. 6% (97. 5% upper confidence limit, 5. 4%). Deep vein thrombosis confirmed by Doppler (4. 1% vs. 2. 1%), other clinically relevant thrombovascular events (1. 5% vs. 0. 9%), and all adverse events combined (76. 5% vs. 73. 2%) occurred with similar frequency in the 2 treatment groups. CONCLUSION This study documented a higher incidence of deep vein thrombosis and similar rates of other clinically relevant thrombovascular events with epoetin alfa versus standard of care for blood conservation in subjects who did not receive prophylactic anticoagulation before spinal surgery. Antithrombotic prophylaxis should be considered when erythropoietin is used in the surgical setting.
Ultrasound-enabled topical anesthesia for pain reduction of phlebotomy for whole blood donation
BACKGROUND Ultrasound-facilitated delivery of topical anesthetics has been used to achieve effective anesthesia within 5 minutes for venipuncture and the insertion of intravenous access devices, but has never been studied for blood donation. STUDY DESIGN AND METHODS This study was a single-center, prospective, randomized, sham treatment-controlled, single-blinded clinical evaluation. Repeat donors were randomly assigned to undergo treatment with ultrasound and topical anesthetic or sham ultrasound and placebo anesthetic before phlebotomy for whole blood donation. The primary outcome measures were pain assessments using the Verbal Categorical Scale (VCS) and the Visual Analogue Scale and the assessment of skin irritation at the target site. RESULTS One-hundred subjects were enrolled and all completed the study. Compared to the sham/placebo control group, donors receiving ultrasound/anesthetic had lower pain scores on the VCS (1. 81 +/- 0. 67 vs. 2. 17 +/- 0. 68; p = 0. 01) and Visual Analog Scale (17. 2 +/- 15. 5 vs. 27. 6 +/- 19. 5; p = 0. 006). The proportion of subjects in the treatment group who experienced skin irritation (8%) was similar to that in the control group (2%; p = 0. 20). CONCLUSION Ultrasound-enhanced delivery of topical anesthetic was demonstrated to be a safe means of quickly achieving clinically meaningful reduction in the pain of phlebotomy for whole blood donation compared to sham/placebo treatment.