Perioperative Aspirin and Clonidine and Risk of Acute Kidney Injury
Authors: Amit X. Garg, Andrea Kurz, Daniel I. Sessler, Meaghan Cuerden, Andrea Robinson, Marko Mrkobrada, Chirag R. Parikh, Richard Mizera, Philip M. Jones, Maria Tiboni, Adrià Font, Virginia Cegarra, Maria Fernanda Rojas Gomez, Christian S. Meyhoff, Tomas VanHelder, Matthew T. V. Chan, David Torres, Joel Parlow, Miriam de Nadal Clanchet, Mohammed Amir, Seyed Javad Bidgoli, Laura Pasin, Kristian Martinsen, German Malaga, Paul Myles, Rey Acedillo, Pavel S. Roshanov, Michael Walsh, George Dresser, Priya Kumar, Edith Fleischmann, Juan Carlos Villar, Thomas Painter, Bruce Biccard, Sergio Bergese, Sadeesh Srinathan, Juan P. Cata, Vincent Chan, Bhupendra Mehra, Duminda N. Wijeysundera, Kate Leslie, Patrice Forget, Richard Whitlock, Salim Yusuf, P. J. Devereaux
Journal: JAMA (2014)

Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm.To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury.A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013.Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery.Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 μmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery.Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58).Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury.clinicaltrials.gov Identifier: NCT01082874.