A Post Hoc Analysis of Osmotherapy Use in the Erythropoietin in Traumatic Brain Injury Study-Associations With Acute Kidney Injury and Mortality

1 Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 2 Division of Intensive Care, Department of Anaesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital and University of Helsinki, Finland. 3 Department of Emergency Care and Services, Helsinki University Hospital and University of Helsinki, Finland. 4 Centre for Integrated Critical Care, The University of Melbourne, Melbourne, VIC, Australia. 5 Transfusion Research Unit, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. 6 Department of Physiology and Pharmacology, Section of Anaesthesia and Intensive Care, Karolinska Institutet, Stockholm, Sweden. 7 Department of Intensive Care, Western Health, Melbourne, VIC, Australia. 8 Department of Intensive Care, Royal Melbourne Hospital, Melbourne, VIC, Australia. 9 School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland. 10 St Vincent's University Hospital, Dublin, Ireland. 11 Department of Intensive Care and Hyperbaric Medicine, The Alfred, Melbourne, VIC, Australia. 12 Department of Anaesthesia and Intensive Care, Hôpitaux universitaires Paris Sud (HUPS), Université Paris Sud XI, Paris, France. 13 Departement d'anesthésie-réanimation, Hopital de la Cavale Blanche, Boulevard Tanguy Prigent, CHRU de Brest, Univeristé de Bretagne Occidental, Brest, France. 14 King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. 15 Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand. 16 Department of Anesthesiology and Intensive Care, Kuopio University Hospital & University of Eastern Finland, Kuopio, Finland. 17 Department of Intensive Care, Austin Health, Melbourne, VIC, Australia.

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.
Study details
Language : eng
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