April 5, 2018



Results from systematic review with meta-analysis and Trial Sequential Analysis

About 35 to 50 percent of our ICU patients are transfused with red blood cells (RBCs) during their admission (1).
RBC are issued from donated whole blood, and stored until further use for a maximum of 35-42 days, depending on national regulations, with blood cells suspended in a preservative solution. It is common practice to use older units first, in order to avoid waste, however whenever RBC are stored, ex vivo rheological and biochemical changes occur. Uniformly referred to as the “storage lesion”, these ex vivo changes may have clinical consequences such as causing fragile RBCs with an increased risk of leakage and haemolysis, gas-transport-ability changes, or rheology property changes, among others.

Many questions arise about the use of these RBCs, such as “Are critically ill patients more susceptible to the deleterious effects of RBC’s storage lesion? Are fresher RBCs better?”

In a recent study, Sofie L. Rygård et al. aimed to answer these questions. Her group conducted a systematic review with meta-analysis and Trial Sequential Analysis (TSA) to investigate the effects of shorter versus longer storage time of transfused RBCs on outcomes in ICU patients (2).

Pre-defined primary outcomes were all-cause mortality and the proportion of patients with one or more severe adverse events. Secondary outcomes were health-related quality of life, proportion of patients with post-transfusion infections occurring after randomisation, proportion of patients with renal failure, proportion of patients with thromboembolic events, all as defined in the included trials. Outcomes were primarily assessed at day 90, or at the time point closest to day 90.

Seven RCTs with (a total of 18,283 ICU patients), six observational studies and few other publications were included. Only two trials (ABLE and TRANSFUSE) were judged as having an overall low risk of bias (3,4). They observed no effects of fresher versus older blood on death (relative risk 1.04, 95% confidence interval (CI) 0.97 to 1.11); adverse events (1.26, 0.76 to 2.09; 7332 patients) or post-transfusion infections (1.07, 0.96 to 1.20; 7332 patients). The results were unchanged by including trials with high risk of bias. Trial Sequence Analysis confirmed the results and the required information size was reached for mortality for a relative risk change of 20%.

Despite significant difference in the evaluated trial, the strength of this review is the strict methodology it followed, utilising the Cochrane collaboration recommendation and PRISMA-statement, with GRADE evaluations of quality of evidence for outcomes.

Article review was prepared by Paul Abraham (Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France) on behalf of the EJRC.



  1. Vincent JL, Baron J-F, Reinhart K, Gattinoni L, Thijs L, Webb A, et al. Anaemia and blood transfusion in critically ill patients. JAMA. 2002 Sep 25;288(12):1499–507.
  2. Rygård SL, Jonsson AB, Madsen MB, Perner A, Holst LB, Johansson PI, et al. Effects of shorter versus longer storage time of transfused red blood cells in adult ICU patients: a systematic review with meta-analysis and Trial Sequential Analysis. Intensive Care Med. 2018 Feb;44(2):204–17. (FREE ACCESS link)
  3. Lacroix J, Hébert PC, Fergusson DA, Tinmouth A, Cook DJ, Marshall JC, et al. Age of transfused blood in critically ill adults. N Engl J Med. 2015 Apr 9;372(15):1410–8.
  4. Cooper DJ, McQuilten ZK, Nichol A, Ady B, Aubron C, Bailey M, et al. Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults. N Engl J Med. 2017 09;377(19):1858–67. http://www.nejm.org/doi/full/10.1056/NEJMoa1707572


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