A Post Hoc Analysis of Osmotherapy Use in the Erythropoietin in Traumatic Brain Injury Study-Associations With Acute Kidney Injury and Mortality
Critical care medicine. 2021
OBJECTIVES Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and mortality are unknown. DESIGN A post hoc analysis of the erythropoietin trial in traumatic brain injury (ClinicalTrials.gov NCT00987454) including daily data on mannitol and hypertonic saline use. SETTING Twenty-nine university-affiliated teaching hospitals in seven countries. PATIENTS A total of 568 patients treated in the ICU for 48 hours without acute kidney injury of whom 43 (7%) received mannitol and 170 (29%) hypertonic saline. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We categorized acute kidney injury stage according to the Kidney Disease Improving Global Outcome classification and defined acute kidney injury as any Kidney Disease Improving Global Outcome stage-based changes from the admission creatinine. We tested associations between early (first 2 d) mannitol and hypertonic saline and time to acute kidney injury up to ICU discharge and death up to 180 days with Cox regression analysis. Subsequently, acute kidney injury developed more often in patients receiving mannitol (35% vs 10%; p < 0.001) and hypertonic saline (23% vs 10%; p < 0.001). On competing risk analysis including factors associated with acute kidney injury, mannitol (hazard ratio, 2.3; 95% CI, 1.2-4.3; p = 0.01), but not hypertonic saline (hazard ratio, 1.6; 95% CI, 0.9-2.8; p = 0.08), was independently associated with time to acute kidney injury. In a Cox model for predicting time to death, both the use of mannitol (hazard ratio, 2.1; 95% CI, 1.1-4.1; p = 0.03) and hypertonic saline (hazard ratio, 1.8; 95% CI, 1.02-3.2; p = 0.04) were associated with time to death. CONCLUSIONS In this post hoc analysis of a randomized controlled trial, the early use of mannitol, but not hypertonic saline, was independently associated with an increase in acute kidney injury. Our findings suggest the need to further evaluate the use and choice of osmotherapy in traumatic brain injury.
Erythropoiesis-stimulating agents in critically ill trauma patients: a systematic review and meta-analysis
Annals of Surgery. 2016;265((1):):54-62
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.