Use of Bicarbonate to Reduce the Incidence of Acute Renal Failure After Cardiac Surgery

Study Overview
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Brief Summary
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The purpose of this study is to determine if the incidence of acute renal failure (ARF) in high risk patients who undergo coronary artery bypass grafting (CABG) is reduced by treating patients in the perioperative period with intravenous (IV) sodium bicarbonate. Patients will be randomized in a 50:50 allocation to receive either IV sodium bicarbonate or IV normal saline. The volume of fluid given in each arm of the study is equal. All other interventions in those patients will be according to standard cardiothoracic anesthesia protocol at our institution.

Detailed Description
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This is a randomized, controlled, single center study in patients felt to be at high risk for ARF following CABG surgery. Patients who have met the selection criteria noted below will be randomized to one of two treatment arms: I) Patients allocated to the sodium bicarbonate (NaHCO3) arm will receive a 0.150 M NaHCO3 solution prepared in a sterile water base. An initial bolus of 0.150 M NaHCO3 at 5.0 ml/kg will be given over fifteen minutes prior to surgery. Following the bolus, the 0.150 M NaHCO3 infusion will be run at 1.0 ml/kg/hr during the procedure and for six (6) hours afterwards. The NaHCO3 infusion will then be decreased to 0.4 ml/kg/hr for a further twelve (12) hours. The goal in the NaHCO3 arm is to provide a total dose of approximately 2.5-3.0 mEq/kg of sodium bicarbonate. This dose was determined from prior studies and found to lead to a slight increase in the serum bicarbonate level post-operatively. Anecdotally, the metabolic stress of CABG surgery often leads to a decline in the serum bicarbonate level in patients not treated with alkali therapy. II) Patients allocated to the normal saline (NS) arm will receive an initial bolus consisting of 0.154 M NaCl (NS) at 5.0 ml/kg given over fifteen minutes prior to surgery. Following the bolus, these patients will receive NS (0.154 M) at a rate of 1.0 ml/kg/hour during the procedure and for six (6) hours afterwards. The rate will then be decreased to 0.4 ml/kg/hour for a further twelve (12) hours as done in the NaHCO3 treatment arm above. There will be a maximum rate of infusion of 125 mL/min used in both study arms to avoid volume overload issues in morbidly obese patients. There will be no other deviation from standard protocol when treating these patients undergoing CABG at our institution. The standard protocol is dictated by both the cardiothoracic surgeons and anesthesiologists involved with each individual case. The purpose of this study is to compare the incidence of ARF (maximal change in SCr) in high risk patients undergoing CABG when treated with either a NS or NaHCO3 maintenance infusion. This study will test the hypothesis that treatment with NaHCO3 may have a protective effect over NS in preventing AFR following CABG in a high risk population.

Official Title
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Reduction of Acute Renal Failure Associated With Cardiovascular Surgery: A Randomized Study Comparing Sodium Bicarbonate to Normal Saline

Conditions
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Kidney Failure, Acute, Renal Replacement Therapy

Intervention / Treatment
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* Drug: Sodium bicarbonate
* Other: Normal saline
* Other: Bicarbonate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Calculated GFR ≤ 60 ml/min/m2 (MDRD) OR Any combination of two (2) of the following: Age ≥ 70 Complex surgery (any of the following): CABG/Valve Redo operation Deep hypothermic arrest ≥ 2 valves History of PVD surgery EF < 35% Presence of diabetes mellitus Prior kidney transplant Exclusion Criteria: Age < 18 Pre-existing ESRD (dialysis patients) Pre-op GFR ≤ 15 ml/min/m2 Pre-op bicarbonate level ≥ 30 mEq/L Emergency surgery (unable to effectively consent) Pregnancy Heart transplant (OHT) Aortic surgery (proximal or distal)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Bicarbonate administration | Drug: Sodium bicarbonate<br>* IV bicarbonate given with amount based on patient weight<br>Other: Bicarbonate<br>* IV bicarbonate, dosed by weight<br>|
| Placebo Comparator: 2<br>Normal saline administration | Other: Normal saline<br>* IV Normal saline with volume given determined by patient weight<br>Other: Placebo<br>* Normal saline, with volume given based on patient weight<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Developed Acute Kidney Injury Within 72 Hours | Number (percentage) of patients who developed acute kidney injury within 72 hours, defined by an increase in serum creatinine level of 0.3 mg/dl from baseline | 72 hours post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in GFR Over 72 Hours Post Operatively | 25% or greater change in serum creatinine level | 72 hours | 
| Length of Hospital Stay | Length of hospital stay in days | Until hospital discharge, up to 30 days | 
| Number of Participants With Need for Dialysis | Number of participants needing dialysis | Until hospital discharge, up to 30 days | 
| Mortality | Number of patients who died during the hospitalization | Until hospital discharge, up to 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Renal Failure, Cardiac Surgery, Sodium Bicarbonate, Length of Stay, Mortality