Intraoperative High-Dose Dexamethasone and Severe AKI after Cardiac Surgery

Abstract

Administration of prophylactic glucocorticoids has been suggested as a strategy to reduce postoperative AKI and other adverse events after cardiac surgery requiring cardiopulmonary bypass. In this post hoc analysis of a large placebo-controlled randomized trial of dexamethasone in 4465 adult patients undergoing cardiac surgery, we examined severe AKI, defined as use of RRT, as a primary outcome. Secondary outcomes were doubling of serum creatinine level or AKI-RRT, as well as AKI-RRT or in-hospital mortality (RRT/death). The primary outcome occurred in ten patients (0.4%) in the dexamethasone group and in 23 patients (1.0%) in the placebo group (relative risk, 0.44; 95% confidence interval, 0.19 to 0.96). In stratified analyses, the strongest signal for potential benefit of dexamethasone was in patients with an eGFR,15 ml/min per 1.73 m 2 . In conclusion, compared with placebo, intraoperative dexamethasone appeared to reduce the incidence of severe AKI after cardiac surgery in those with advanced CKD. 26: 294726: -295126: , 201526: . doi: 10.1681 Acute kidney injury is one of the most ominous complications after cardiac surgery with cardiopulmonary bypass (CPB). Approximately 1% of patients undergoing cardiac surgery require RRT for severe postoperative AKI, and experience strikingly high in-hospital mortality rates exceeding 40%. 1-3 Less severe AKI is far more common and identifies patients still at increased risk of shortand long-term mortality, prolonged length of hospital stay, and higher hospital costs. 4,5 The pathogenesis of AKI after cardiac surgery is complex and includes patient-related factors such as age and comorbidities (e.g., CKD and diabetes mellitus) as well as surgical factors such as type of procedure and duration of CPB. [6][7][8] Cardiac surgery results in a postoperative systemic inflammatory response syndrome due to a variety of factors including surgical trauma, exposure of blood to the artificial surface of the bypass circuit, tissue hypoperfusion, hemolysis, hemodilution, blood transfusion, and hypothermia. 9-12 Inflammation is believed to play a key role in the pathophysiology of AKI after cardiac surgery with CPB. A number of proinflammatory pathways are activated during CPB and can lead to leukocyte extravasation, lipid peroxidation, renal medullary congestion, and tubular cell injury. 1,9 Multiple strategies have been proposed to attenuate the inflammatory response after cardiac surgery with CPB, including the use of glucocorticoids. To date, the effect of glucocorticoids on AKI after cardiac surgery has been evaluated as a primary outcome in 14 randomized controlled trials, the largest of which included 216 patients. 3 A meta-analysis of these studies (which included a total of 888 patients) concluded that glucocorticoids have no protective effect on AKI after cardiac surgery. 3 However, these studies were underpowered, particularly to detect severe AKI. J Am Soc NephrolWe therefore conducted a post hoc analysis of severe AKI in the Dexamethasone for Cardiac Surgery (DE...

End Points for Clinical Trials in Acute Kidney Injury

“…Specifically, urgent RRT following cardiac surgery occurs almost exclusively in patients with CKD stages 4 and 5: in a post hoc analysis of a randomized controlled trial of 4465 adult patients who underwent cardiac surgery, we found that AKI requiring RRT occurred in 0 out of 2247 patients with a baseline eGFR>60 mL/min/1.73 m2, 5 out of 1816 patients (0.3%) with CKD stage 3, 11 out of 300 patients (3.7%) with CKD stage 4, and 17 out of 102 patients (16.7%) with CKD stage 5. 34 …”

Long‐term outcomes and cost effectiveness of high‐dose dexamethasone for cardiac surgery: a randomised trial

“…However, analysis of pre-specified secondary outcomes indicated that high-dose dexamethasone was associated with fewer respiratory complications and reduced postoperative length of stay in the hospital. Also, dexamethasone resulted in a reduced incidence of severe acute kidney injury in patients with advanced chronic kidney disease [7].…”

Effect of methylprednisolone on acute kidney injury in patients undergoing cardiac surgery with a cardiopulmonary bypass pump: a randomized controlled trial

“…9 In a post-hoc analysis of the Dexamethasone for Cardiac Surgery Trial, use of intravenous dexamethasone (a corticosteroid) was associated with a significant relative risk (RR) reduction for dialysis use during the hospital stay (although there were few outcome events and all occurred in patients with chronic kidney disease). 5,10 We conducted a prespecified substudy of the Steroids in Cardiac Surgery (SIRS) trial 11 to test the effect of intraoperative RESEARCH Effect of methylprednisolone on acute kidney injury in patients undergoing cardiac surgery with a cardiopulmonary bypass pump: a randomized controlled trial METHODS: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014); patients were recruited from 79 centres in 18 countries. Eligibility criter ia included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I.…”