Amit X Garg1, Andrea Kurz2, Daniel I Sessler2, Meaghan Cuerden1, Andrea Robinson3, Marko Mrkobrada1, Chirag R Parikh4, Richard Mizera3, Philip M Jones1, Maria Tiboni3, Adrià Font5, Virginia Cegarra5, Maria Fernanda Rojas Gomez6, Christian S Meyhoff7, Tomas VanHelder3, Matthew T V Chan8, David Torres9, Joel Parlow10, Miriam de Nadal Clanchet11, Mohammed Amir12, Seyed Javad Bidgoli13, Laura Pasin14, Kristian Martinsen15, German Malaga16, Paul Myles17, Rey Acedillo1, Pavel S Roshanov1, Michael Walsh3, George Dresser1, Priya Kumar18, Edith Fleischmann19, Juan Carlos Villar20, Thomas Painter21, Bruce Biccard22, Sergio Bergese23, Sadeesh Srinathan24, Juan P Cata25, Vincent Chan26, Bhupendra Mehra27, Duminda N Wijeysundera26, Kate Leslie28, Patrice Forget29, Richard Whitlock3, Salim Yusuf3, P J Devereaux3. 1. London Health Sciences Centre and Western University, London, Ontario, Canada. 2. Cleveland Clinic, Cleveland, Ohio. 3. McMaster University, Hamilton Health Sciences Centre, St Joseph's Healthcare and the Population Health Research Institute, Hamilton, Ontario, Canada. 4. Yale University School of Medicine, New Haven, Connecticut. 5. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 6. Fundación Oftalmológica de Santander, Bucaramanga, Colombia. 7. Herlev Hospital and the University of Copenhagen, Copenhagen, Denmark. 8. Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. 9. Clinica Santa Maria, Universidad de los Andes, Santiago, Chile. 10. Kingston General Hospital, Kingston, Ontario, Canada. 11. Hospital Vall d'Hebron, Barcelona, Spain. 12. Shifa International Hospitals Limited, Islamabad, Pakistan. 13. CHU Brugmann, Brussels, Belgium. 14. San Raffaele Scientific Institute, Milan, Italy. 15. Vejle Hospital, Vejle, Denmark. 16. Hospital Nacional Cayetano Heredia, Lima, Peru. 17. Monash University, Melbourne, Australia. 18. University of North Carolina Medical School, Chapel Hill. 19. Vienna General Hospital and the Medical University of Vienna, Vienna, Austria. 20. Fundación Cardioinfantil and the Universidad Autónoma de Bucaramanga, Bogotá, Colombia. 21. Royal Adelaide Hospital, Adelaide, Australia. 22. Nelson R. Mandela School of Medicine, Durban, South Africa. 23. Ohio State University Medical Center, Columbus. 24. University of Manitoba, Winnipeg, Canada. 25. University of Texas and MD Anderson Cancer Center, Houston. 26. University Health Network and the University of Toronto, Toronto, Ontario, Canada. 27. Mahatma Gandhi Institute of Medical Sciences, Wardha, India. 28. Royal Melbourne Hospital, Melbourne, Australia. 29. Cliniques Universitaires Saint-Luc and the Université Catholique de Louvain, Brussels, Belgium.
Abstract
IMPORTANCE: 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. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: 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. MAIN OUTCOMES AND MEASURES: 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. RESULTS: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). CONCLUSIONS AND RELEVANCE: Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01082874.
RCT Entities:
IMPORTANCE: 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. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: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. MAIN OUTCOMES AND MEASURES: 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. RESULTS: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). CONCLUSIONS AND RELEVANCE: Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01082874.
Authors: Rey R Acedillo; Ron Wald; Eric McArthur; Danielle Marie Nash; Samuel A Silver; Matthew T James; Michael J Schull; Edward D Siew; Michael E Matheny; Andrew A House; Amit X Garg Journal: Clin J Am Soc Nephrol Date: 2017-07-20 Impact factor: 8.237
Authors: Michael R Mathis; Bhiken I Naik; Robert E Freundlich; Amy M Shanks; Michael Heung; Minjae Kim; Michael L Burns; Douglas A Colquhoun; Govind Rangrass; Allison Janda; Milo C Engoren; Leif Saager; Kevin K Tremper; Sachin Kheterpal; Michael F Aziz; Traci Coffman; Marcel E Durieux; Warren J Levy; Robert B Schonberger; Roy Soto; Janet Wilczak; Mitchell F Berman; Joshua Berris; Daniel A Biggs; Peter Coles; Robert M Craft; Kenneth C Cummings; Terri A Ellis; Peter M Fleishut; Daniel L Helsten; Leslie C Jameson; Wilton A van Klei; Fabian Kooij; John LaGorio; Steven Lins; Scott A Miller; Susan Molina; Bala Nair; William C Paganelli; William Peterson; Simon Tom; Jonathan P Wanderer; Christopher Wedeven Journal: Anesthesiology Date: 2020-03 Impact factor: 7.892