Safety of a Restrictive versus Liberal Approach to Red Blood Cell Transfusion on the Outcome of AKI in Patients Undergoing Cardiac Surgery: A Randomized Clinical Trial
Authors: Garg Amit X. , Badner Neal , Bagshaw Sean M. , Cuerden Meaghan S. , Fergusson Dean A. , Gregory Alexander J. , Hall Judith , Hare Gregory M. T. , Khanykin Boris , McGuinness Shay , Parikh Chirag R. , Roshanov Pavel S. , Shehata Nadine , Sontrop Jessica M. , Syed Summer , Tagarakis George I. , Thorpe Kevin E. , Verma Subodh , Wald Ron , Whitlock Richard P. , Mazer C. David ,   for the TRICS Investigators and Perioperative Anesthesia Clinical Trials Group
Published: June 2019

Significance Statement
Safely reducing red blood cell transfusions could prevent transfusion-related adverse effects. Both anemia and transfusion may harm the kidney, but how reducing transfusions might affect AKI risk is unknown. To investigate this issue, the authors conducted a prespecified kidney substudy of a multinational, randomized noninferiority trial of 4531 patients undergoing cardiac surgery with cardiopulmonary bypass. Patients were randomized to a restrictive approach for receiving red blood cell transfusion (transfuse if hemoglobin<7.5 g/dl) or a more liberal approach (transfuse if hemoglobin<9.5 g/dl). Patients in the restrictive group received 38% fewer transfusions than patients in the liberal group (1.8 versus 2.9 transfusions, on average, respectively), and both approaches were equally safe with respect to AKI risk. Results were similar in patients with preoperative CKD.

Background
Safely reducing red blood cell transfusions can prevent transfusion-related adverse effects, conserve the blood supply, and reduce health care costs. Both anemia and red blood cell transfusion are independently associated with AKI, but observational data are insufficient to determine whether a restrictive approach to transfusion can be used without increasing AKI risk.

Methods
In a prespecified kidney substudy of a randomized noninferiority trial, we compared a restrictive threshold for red blood cell transfusion (transfuse if hemoglobin<7.5 g/dl, intraoperatively and postoperatively) with a liberal threshold (transfuse if hemoglobin<9.5 g/dl in the operating room or intensive care unit, or if hemoglobin<8.5 g/dl on the nonintensive care ward). We studied 4531 patients undergoing cardiac surgery with cardiopulmonary bypass who had a moderate-to-high risk of perioperative death. The substudy’s primary outcome was AKI, defined as a postoperative increase in serum creatinine of ≥0.3 mg/dl within 48 hours of surgery, or ≥50% within 7 days of surgery.

Results
Patients in the restrictive-threshold group received significantly fewer transfusions than patients in the liberal-threshold group (1.8 versus 2.9 on average, or 38% fewer transfusions in the restricted-threshold group compared with the liberal-threshold group; P<0.001). AKI occurred in 27.7% of patients in the restrictive-threshold group (624 of 2251) and in 27.9% of patients in the liberal-threshold group (636 of 2280). Similarly, among patients with preoperative CKD, AKI occurred in 33.6% of patients in the restrictive-threshold group (258 of 767) and in 32.5% of patients in the liberal-threshold group (252 of 775).

Conclusions
Among patients undergoing cardiac surgery, a restrictive transfusion approach resulted in fewer red blood cell transfusions without increasing the risk of AKI.