Abstract/Text: Every year, about 75 million units of blood are collected worldwide. Red blood cell (RBC) transfusion is one of the few treatments that adequately restore tissue oxygenation when oxygen demand exceeds supply. Although the respiratory function of blood has been studied intensively, the trigger for RBC transfusion remains controversial, and doctors rely primarily on clinical experience. Laboratory assays that indicate failing tissue oxygenation would be ideal to guide the need for transfusion, but none has proved easy, reproducible, and sensitive to regional tissue hypoxia. The clinical importance of the RBCs storage lesion (ie, the time-dependent metabolic, biochemical, and molecular changes that stored blood cells undergo) is poorly understood. RBCs can be filtered, washed, frozen, or irradiated for specific indications. Donor screening and testing have dramatically reduced infectious risks in the developed world, but infection remains a major hazard in developing countries, where 13 million units of blood are not tested for HIV or hepatitis viruses. Pathogen inactivation techniques are in clinical trials for RBCs, but none is available for use. Despite serious immunological and non-immunological complications, RBC transfusion holds a therapeutic index that exceeds that of many common medications.

Abstract/Text: OBJECTIVE: To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions.
DESIGN: Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.
DATA SOURCES: Cochrane central register of controlled trials, SilverPlatter Medline (1950 to date), SilverPlatter Embase (1980 to date), and Science Citation Index Expanded (1900 to present). Reference lists of identified trials and other systematic reviews were assessed, and authors and experts in transfusion were contacted to identify additional trials.
TRIAL SELECTION: Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding procedure, publication status, or sample size.
DATA EXTRACTION: Two authors independently screened titles and abstracts of trials identified, and relevant trials were evaluated in full text for eligibility. Two reviewers then independently extracted data on methods, interventions, outcomes, and risk of bias from included trials. random effects models were used to estimate risk ratios and mean differences with 95% confidence intervals.
RESULTS: 31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean difference -1.43, 95% confidence interval -2.01 to -0.86) were lower with the restrictive compared with liberal transfusion strategies. Restrictive compared with liberal transfusion strategies were not associated with risk of death (0.86, 0.74 to 1.01, 5707 patients, nine lower risk of bias trials), overall morbidity (0.98, 0.85 to 1.12, 4517 patients, six lower risk of bias trials), or fatal or non-fatal myocardial infarction (1.28, 0.66 to 2.49, 4730 patients, seven lower risk of bias trials). Results were not affected by the inclusion of trials with unclear or high risk of bias. Using trial sequential analyses on mortality and myocardial infarction, the required information size was not reached, but a 15% relative risk reduction or increase in overall morbidity with restrictive transfusion strategies could be excluded.
CONCLUSIONS: Compared with liberal strategies, restrictive transfusion strategies were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion strategies have not been shown to convey any benefit to patients.
TRIAL REGISTRATION: PROSPERO CRD42013004272.

© Holst et al 2015.