Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia

Princess Igwe, Mercer University College of Pharmacy

Red blood cells (RBCs) are considered to be the most widely transfused blood component and can be stored in storage units for up to 42 days. However, long-term storage of RBCs and the effect this has on safety and efficacy of transfusion is considered controversial.1 It is suggested that during storage, RBCs may undergo changes that impair the capacity for tissue oxygenation.2

It is suggested that severe anemia results in insufficient tissue oxygenation and lactic acidosis and that blood transfusion may alleviate these effects, however the effect of blood storage duration on the efficacy RBC transfusion is unclear.3

Effect of Transfusion of Red Blood Cells With Longer vs Shorter Storage Duration on Elevated Blood Lactate Levels in Children With Severe Anemia4
Design Randomized noninferiority trial; N = 290
Objective To determine if longer-storage red blood cell (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
Study Groups RBC units stored 25 to 35 days (longer-storage group; n = 145) vs one to 10 days (shorter-storage group; n = 145)
Methods Children (aged six to 60 months), most with malaria or sickle cell disease in Kampala, Uganda, with a hemoglobin level of 5 g/dL or lower and a lactate level of 5 mmol/L or higher, were assigned to receive RBC units stored 25 to 35 days or one to 10 days. All units were leukoreduced prior to storage. All patients received 10 mL/kg of RBCs during hours zero through two and, if indicated per protocol, an additional 10 mL/kg during hours four through six.
Duration February 2013 to May 2015
Primary Outcome Measure The proportion of patients with a lactate level of 3 mmol/L or lower at eight hours using a margin of noninferiority equal to an absolute difference of 25%
Baseline Characteristics Characteristics Longer RBC Storage Shorter RBC Storage
Age, median (IQR), mo 25.5 (15.0-39.9) 26.5 (18.5-39.6)
Sex, No. (%) Girls: 67 (46)

Boys: 78 (54)

Girls: 71 (49)

Boys: 74 (51)

BMI, mean (SD) 15.1 (1.9) 15.2 (1.9)
Arterial oxygen saturation, mean (SD), % 97.5 (3.7) 97.2 (5.2)
Hemoglobin, mean (SD), g/dL 3.7 (1.3) 3.6 (1.3)
Lactate, mean (SD), mmol/L 9.5 (3.4) 9.2 (3.4)
Sickle cell disease, No. (%) 21 (14.5) 18 (12.4)
Other severe anemia, No. (%) 10 (6.9) 14 (9.6)
IQR = interquartile range
  • 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 < 0.001), meeting the prespecified margin of noninferiority.
  • Mean lactate levels were not statistically different between the two groups at zero, two, four, six, eight, or 24 hours. Kaplan-Meier analysis and global nonlinear regression revealed no statistical difference in lactate reduction between the two groups.
Adverse Events Common Adverse Events Related to Infusion: hives (one [0.7%] patient in longer-storage group); and facial edema (one [0.7%] patient in shorter-storage group)
Serious Adverse Events: No deaths related to infusion; Death unrelated to transfusion (3 [2.1%] in longer-storage group, 5 [3.6%] in shorter-storage group)
Percentage that Discontinued due to Adverse Events: Zero
Study Author Conclusions 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.

In this study, RBC transfusion improved tissue oxygenation and decreased lactic acidosis in children by reducing blood lactate levels. It was found that longer storage duration of RBCs was not inferior to shorter storage duration, meaning that there were no clinically important differences between the two storage groups. Further studies are needed in different patient groups in order to assess tissue oxygenation and lactate clearance following RBC transfusion using RBCs of different storage durations.


  1. D’alessandro A, Liumbruno G, Grazzini G, Zolla L. Red blood cell storage: the story so far. Blood Transfus. 2010;8(2):82-8. doi: 2450/2009.0122-09.
  2. Bennett-Guerrero E, Veldman  TH, Doctor  A,  et al.  Evolution of adverse changes in stored red blood cells. Proc Natl Acad Sci U S A. 2007;104(43):17063-17068. doi: 10.1073/pnas.0708160104.
  3. Brunskill SJ, Wilkinson  KL, Doree  C, Trivella  M, Stanworth    Transfusion of fresher vs older red blood cells for all conditions. Cochrane Database Syst Rev. 2015;5:CD010801. doi: 10.1002/14651858.CD010801.pub2.
  4. Dhabangi A, Ainomugisha B, Cserti-gazdewich C, et al. 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. JAMA. 2015;314(23):2514-2523. doi:10.1001/jama.2015.13977.



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