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

• Published in: JAMA : the journal of the American Medical Association 2015-12, Vol.314 (23), p.2514-2523
• Main Authors: Dhabangi, Aggrey, Ainomugisha, Brenda, Cserti-Gazdewich, Christine, Ddungu, Henry, Kyeyune, Dorothy, Musisi, Ezra, Opoka, Robert, Stowell, Christopher P, Dzik, Walter H
• Format: Article
• Language: English
• Subjects: Acidosis, Lactic - blood; Acidosis, Lactic - etiology; Acidosis, Lactic - therapy; Anemia; Anemia - blood; Anemia - complications; Anemia - therapy; Blood transfusions; Brain - metabolism; Child, Preschool; Childrens health; Erythrocyte Transfusion - methods; Erythrocyte Transfusion - mortality; Erythrocytes; Erythrocytes - physiology; Female; Hemoglobin A - metabolism; Humans; Infant; Lactates - blood; Male; Oxygen Consumption - physiology; Patient Outcome Assessment; Regression Analysis; Specimen Handling - methods; Time Factors; Treatment Outcome; Uganda
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2015.13977

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