Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.
OBJECTIVE
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.


METHODS
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.


METHODS
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.


METHODS
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
Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury.


BACKGROUND
clinicaltrials.gov Identifier: NCT01082874.
London Health Sciences Centre and Western University, London, Ontario, Canada.
Amit X
AX
Garg
Cleveland Clinic, Cleveland, Ohio.
Andrea
A
Kurz
Cleveland Clinic, Cleveland, Ohio.
Daniel I
DI
Sessler
London Health Sciences Centre and Western University, London, Ontario, Canada.
Meaghan
M
Cuerden
McMaster University, Hamilton Health Sciences Centre, St Joseph's Healthcare and the Population Health Research Institute, Hamilton, Ontario, Canada.
Andrea
A
Robinson
London Health Sciences Centre and Western University, London, Ontario, Canada.
Marko
M
Mrkobrada
Yale University School of Medicine, New Haven, Connecticut.
Chirag R
CR
Parikh
McMaster University, Hamilton Health Sciences Centre, St Joseph's Healthcare and the Population Health Research Institute, Hamilton, Ontario, Canada.
Richard
R
Mizera
London Health Sciences Centre and Western University, London, Ontario, Canada.
Philip M
PM
Jones
McMaster University, Hamilton Health Sciences Centre, St Joseph's Healthcare and the Population Health Research Institute, Hamilton, Ontario, Canada.
Maria
M
Tiboni
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Adrià
A
Font
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Virginia
V
Cegarra
Fundación Oftalmológica de Santander, Bucaramanga, Colombia.
Maria Fernanda Rojas
MF
Gomez
Herlev Hospital and the University of Copenhagen, Copenhagen, Denmark.
Christian S
CS
Meyhoff
McMaster University, Hamilton Health Sciences Centre, St Joseph's Healthcare and the Population Health Research Institute, Hamilton, Ontario, Canada.
Tomas
T
VanHelder
Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
Matthew T V
MT
Chan
Clinica Santa Maria, Universidad de los Andes, Santiago, Chile.
David
D
Torres
Kingston General Hospital, Kingston, Ontario, Canada.
Joel
J
Parlow
Hospital Vall d'Hebron, Barcelona, Spain.
Miriam de Nadal
Mde N
Clanchet
Shifa International Hospitals Limited, Islamabad, Pakistan.
Mohammed
M
Amir
CHU Brugmann, Brussels, Belgium.
Seyed Javad
SJ
Bidgoli
San Raffaele Scientific Institute, Milan, Italy.
Laura
L
Pasin
Vejle Hospital, Vejle, Denmark.
Kristian
K
Martinsen
Hospital Nacional Cayetano Heredia, Lima, Peru.
German
G
Malaga
Monash University, Melbourne, Australia.
Paul
P
Myles
London Health Sciences Centre and Western University, London, Ontario, Canada.
Rey
R
Acedillo
London Health Sciences Centre and Western University, London, Ontario, Canada.
Pavel S
PS
Roshanov
McMaster University, Hamilton Health Sciences Centre, St Joseph's Healthcare and the Population Health Research Institute, Hamilton, Ontario, Canada.
Michael
M
Walsh
London Health Sciences Centre and Western University, London, Ontario, Canada.
George
G
Dresser
University of North Carolina Medical School, Chapel Hill.
Priya
P
Kumar
Vienna General Hospital and the Medical University of Vienna, Vienna, Austria.
Edith
E
Fleischmann
Fundación Cardioinfantil and the Universidad Autónoma de Bucaramanga, Bogotá, Colombia.
Juan Carlos
JC
Villar
Royal Adelaide Hospital, Adelaide, Australia.
Thomas
T
Painter
Nelson R. Mandela School of Medicine, Durban, South Africa.
Bruce
B
Biccard
Ohio State University Medical Center, Columbus.
Sergio
S
Bergese
University of Manitoba, Winnipeg, Canada.
Sadeesh
S
Srinathan
University of Texas and MD Anderson Cancer Center, Houston.
Juan P
JP
Cata
University Health Network and the University of Toronto, Toronto, Ontario, Canada.
Vincent
V
Chan
Mahatma Gandhi Institute of Medical Sciences, Wardha, India.
Bhupendra
B
Mehra
University Health Network and the University of Toronto, Toronto, Ontario, Canada.
Duminda N
DN
Wijeysundera
Royal Melbourne Hospital, Melbourne, Australia.
Kate
K
Leslie
Cliniques Universitaires Saint-Luc and the Université Catholique de Louvain, Brussels, Belgium.
Patrice
P
Forget
McMaster University, Hamilton Health Sciences Centre, St Joseph's Healthcare and the Population Health Research Institute, Hamilton, Ontario, Canada.
Richard
R
Whitlock
McMaster University, Hamilton Health Sciences Centre, St Joseph's Healthcare and the Population Health Research Institute, Hamilton, Ontario, Canada.
Salim
S
Yusuf
McMaster University, Hamilton Health Sciences Centre, St Joseph's Healthcare and the Population Health Research Institute, Hamilton, Ontario, Canada.
P J
PJ
Devereaux
D058186:Acute Kidney Injury / Q000517:prevention & control*; D000279:Administration, Cutaneous; D000284:Administration, Oral; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects*; D003000:Clonidine / Q000008:administration & dosage* / Q000009:adverse effects; D003404:Creatinine / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011183:Postoperative Complications; D012306:Risk
D058647:Adrenergic alpha-2 Receptor Agonists; D010975:Platelet Aggregation Inhibitors; D003404:Creatinine; D003000:Clonidine; D001241:Aspirin