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ObjectiveTo perform a meta-analysis of all relevant randomized controlled trials assessing the effect of erythropoiesis-stimulating agents (ESAs) in critically ill trauma patients.BackgroundESAs have effects beyond erythropoiesis. The administration of the ESA epoetin alfa to critically ill trauma patients has been associated with a reduction in mortality.MethodsWe performed a systematic review and meta-analysis with trial sequential analysis. We searched Medline, Medline in Process, and other nonindexed citations, EMBASE, and the Cochrane Database from inception until September 9, 2015, for randomized controlled trials comparing ESAs to placebo (or no ESA).ResultsWe identified 9 eligible studies that randomly assigned 2607 critically ill patients after trauma to an ESA or placebo (or no ESA). Compared with placebo (or no ESA), ESA therapy was associated with a substantial reduction in mortality [risk ratio (RR) 0.63, 95% confidence interval (CI) 0.49-0.79, P = 0.0001, I = 0%). In patients with traumatic brain injury, ESA therapy did not increase the number of patients surviving with moderate disability or good recovery (RR 1.00, 95% CI 0.88-1.15, P = 0.95, I = 0%). With the dosing regimens employed in the included studies, ESA therapy did not increase the risk of lower limb proximal deep venous thrombosis (RR 0.97, 95% CI 0.72-1.29, P = 0.78, I = 0%).ConclusionsThe administration of ESAs to critically ill trauma patients is associated with a significant improvement in mortality without an increase in the rate of lower limb proximal deep venous thrombosis. Given the worldwide public health significance of these findings research to validate or refute them is required.

Original publication





Annals of surgery

Publication Date





54 - 62


*Departments of Anaesthesia and Intensive Care, Western Health, Gordon Street, Footscray, Melbourne, Australia †Department of Intensive Care, Austin Hospital, Heidelberg, Melbourne, Australia ‡Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia §Department of Intensive Care, The Alfred, Melbourne, Australia ¶St Vincent's University Hospital, Dublin, Ireland ||Royal Brisbane and Women's Hospital, Brisbane, Australia **The University of Melbourne, Parkville, Melbourne, Australia ††Division of Intensive Care, Department of Anesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital and Helsinki University, Helsinki, Finland.


Humans, Wounds and Injuries, Critical Illness, Hematinics, Treatment Outcome, Models, Statistical