title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01586923.
authors.affiliation: Child Health and Development Centre, Makerere University, Kampala, Uganda.
authors.forename: Aggrey
authors.initials: A
authors.lastname: Dhabangi
authors.affiliation: Mulago Hospital, Kampala, Uganda.
authors.forename: Brenda
authors.initials: B
authors.lastname: Ainomugisha
authors.affiliation: University Health Network Laboratory Medicine Program, University of Toronto, Toronto, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Cserti-Gazdewich
authors.affiliation: Uganda Cancer Institute, Makerere University, Kampala, Uganda.
authors.forename: Henry
authors.initials: H
authors.lastname: Ddungu
authors.affiliation: Uganda National Blood Transfusion Service, Kampala, Uganda.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Kyeyune
authors.affiliation: Uganda National Blood Transfusion Service, Kampala, Uganda.
authors.forename: Ezra
authors.initials: E
authors.lastname: Musisi
authors.affiliation: Mulago Hospital Department of Paediatrics, Makerere University, Kampala, Uganda.
authors.forename: Robert
authors.initials: R
authors.lastname: Opoka
authors.affiliation: Blood Transfusion Service, Harvard Medical School, Massachusetts General Hospital, Boston.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Stowell
authors.affiliation: Blood Transfusion Service, Harvard Medical School, Massachusetts General Hospital, Boston.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Dzik
mesh_terms: D000140:Acidosis, Lactic / Q000097:blood / Q000209:etiology / Q000628:therapy*; D000740:Anemia / Q000097:blood* / Q000150:complications / Q000628:therapy; D001921:Brain / Q000378:metabolism*; D002675:Child, Preschool; D017707:Erythrocyte Transfusion / Q000379:methods / Q000401:mortality; D004912:Erythrocytes / Q000502:physiology; D005260:Female; D006441:Hemoglobin A / Q000378:metabolism; D006801:Humans; D007223:Infant; D007773:Lactates / Q000097:blood; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology*; D063868:Patient Outcome Assessment; D012044:Regression Analysis; D013048:Specimen Handling / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome; D014454:Uganda
chemical_list: D007773:Lactates; D006441:Hemoglobin A