Risk of Acute Kidney Injury in Patients Randomized to a Restrictive Versus Liberal Approach to Red Blood Cell Transfusion in Cardiac Surgery: A Substudy Protocol of the Transfusion Requirements in Cardiac Surgery III Noninferiority Trial

Amit X Garg, Nadine Shehata, Shay McGuinness, Richard Whitlock, Dean Fergusson, Ron Wald, Chirag Parikh, Sean M Bagshaw, Boris Khanykin, Alex Gregory, Summer Syed, Gregory M T Hare, Meaghan S Cuerden, Kevin E Thorpe, Judith Hall, Subodh Verma, Pavel S Roshanov, Jessica M Sontrop, C David Mazer, Amit X Garg, Nadine Shehata, Shay McGuinness, Richard Whitlock, Dean Fergusson, Ron Wald, Chirag Parikh, Sean M Bagshaw, Boris Khanykin, Alex Gregory, Summer Syed, Gregory M T Hare, Meaghan S Cuerden, Kevin E Thorpe, Judith Hall, Subodh Verma, Pavel S Roshanov, Jessica M Sontrop, C David Mazer

Abstract

Background: When safe to do so, avoiding blood transfusions in cardiac surgery can avoid the risk of transfusion-related infections and other complications while protecting a scarce resource and reducing costs. This protocol describes a kidney substudy of the Transfusion Requirements in Cardiac Surgery III (TRICS-III) trial, a multinational noninferiority randomized controlled trial to determine whether the risk of major clinical outcomes in patients undergoing planned cardiac surgery with cardiopulmonary bypass is no greater with a restrictive versus liberal approach to red blood cell transfusion.

Objective: The objective of this substudy is to determine whether the risk of acute kidney injury is no greater with a restrictive versus liberal approach to red blood cell transfusion, and whether this holds true in patients with and without preexisting chronic kidney disease.

Design and setting: Multinational noninferiority randomized controlled trial conducted in 73 centers in 19 countries (2014-2017).

Patients: Patients (~4800) undergoing planned cardiac surgery with cardiopulmonary bypass.

Measurements: The primary outcome of this substudy is perioperative acute kidney injury, defined as an acute rise in serum creatinine from the preoperative value (obtained in the 30-day period before surgery), where an acute rise is defined as ≥26.5 μmol/L in the first 48 hours after surgery or ≥50% in the first 7 days after surgery.

Methods: We will report the absolute risk difference in acute kidney injury and the 95% confidence interval. We will repeat the primary analysis using alternative definitions of acute kidney injury, including staging definitions, and will examine effect modification by preexisting chronic kidney disease (defined as a preoperative estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2).

Limitations: It is not possible to blind patients or providers to the intervention; however, objective measures will be used to assess outcomes, and outcome assessors will be blinded to the intervention assignment.

Results: Substudy results will be reported by the year 2018.

Conclusions: This substudy will provide generalizable estimates of the risk of acute kidney injury of a restrictive versus liberal approach to red blood cell transfusion in the presence of anemia during cardiac surgery done with cardiopulmonary bypass.

Trial registration: www.clinicaltrials.gov; clinical trial registration number NCT 02042898.

Trial registration: ClinicalTrials.gov NCT02042898.

Keywords: acute kidney injury; anemia; cardiac surgery; cardiopulmonary bypass; transfusion.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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