title: Restrictive versus liberal transfusion strategy for red blood cell transfusion: systematic review of randomised trials with meta-analysis and trial sequential analysis.
abstract: OBJECTIVE
  To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions.
  
  
  METHODS
  Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials.
  
  
  METHODS
  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.
  Published and unpublished randomised clinical trials that evaluated a restrictive compared with a liberal transfusion strategy in adults or children, irrespective of language, blinding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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  PROSPERO CRD42013004272.
authors: Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark lars.broksoe.holst@regionh.dk.
authors: Lars B
authors: LB
authors: Holst
authors: Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors: Marie W
authors: MW
authors: Petersen
authors: Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors: Nicolai
authors: N
authors: Haase
authors: Department of Intensive Care 4131, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors: Anders
authors: A
authors: Perner
authors: Copenhagen Trial Unit, Centre for Clinical Intervention Research 7812, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors: Jørn
authors: J
authors: Wetterslev
mesh_terms: D017707:Erythrocyte Transfusion / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006801:Humans; D015233:Models, Statistical; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic