Craig J French1, Neil J Glassford, Dashiell Gantner, Alisa M Higgins, David James Cooper, Alistair Nichol, Markus B Skrifvars, Georgina Imberger, Jeffrey Presneill, Michael Bailey, Rinaldo Bellomo. 1. *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.
Abstract
OBJECTIVE: To perform a meta-analysis of all relevant randomized controlled trials assessing the effect of erythropoiesis-stimulating agents (ESAs) in critically ill trauma patients. BACKGROUND: ESAs have effects beyond erythropoiesis. The administration of the ESA epoetin alfa to critically ill trauma patients has been associated with a reduction in mortality. METHODS: We 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). RESULTS: We 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%). CONCLUSIONS: The 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.
OBJECTIVE: To perform a meta-analysis of all relevant randomized controlled trials assessing the effect of erythropoiesis-stimulating agents (ESAs) in critically ill traumapatients. BACKGROUND: ESAs have effects beyond erythropoiesis. The administration of the ESA epoetinalfa to critically ill traumapatients has been associated with a reduction in mortality. METHODS: We 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). RESULTS: We identified 9 eligible studies that randomly assigned 2607 critically illpatients 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%). CONCLUSIONS: The administration of ESAs to critically ill traumapatients 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.