1. Sodium bicarbonate to prevent increases in serum creatinine after cardiac surgery: A pilot double- blind, randomized controlled trial Critical Care Medicine Volume 37(1), January 2009, pp 39-47

2. Abstract Objective: To test whether perioperative sodium bicarbonate infusion can attenuate postoperative increases in serum creatinine in cardiac surgical patients. Design: Double-blind, randomized controlled trial. Setting: Operating rooms and intensive care unit at a tertiary hospital. Patients: Cohort of 100 cardiac surgical patients at increased risk of postoperative acute renal dysfunction. Intervention: Patients were randomized to either 24 hrs of intravenous infusion of Na bicarbonate (4 mmol/kg) or Na chloride (4 mmol/kg).

3. Background Acute renal dysfunction after CP bypass Ischemia-reperfusion, Generation of reactive oxygen species, Hemolysis, Activation of inflammatory pathways Good to have simple, safe, and effective intervention to prevent cardiopulmonary bypass-associated acute renal dysfunction

4. Hypothesis Alkalinization might protect kidney function in patients at increased risk of acute renal dysfunction undergoing cardiopulmonary bypass

5. Rationale for Bicarbonate IMP pathogenic mechanisms of AKI after CP bypass: Urinary acidity may enhance the generation and toxicity of reactive oxygen species induced by cardiopulmonary bypass. Activation of complement during cardiac surgery may also participate in renal injury. How Bicarbonate helps: Urinary alkalinization may protect from renal injury induced by Oxidant substances, iron-mediated free radical pathways, Complement activation, and tubular hemoglobin cast formation.

6. Inclusion and exclusion criteria Inclusion criteria. Cardiac surgical patients in whom the use of cardiopulmonary bypass was planned and having one ore more of the following risk factors for postoperative acute kidney injury ● Age above 70 years ● Preexisting renal impairment (preoperative plasma creatinine concentration 120 mol/ ● New York Heart Association class III/IV or impaired left ventricular function (left ventricular ejection fraction 35%) ● Valvular surgery or concomitant valvular and coronary artery bypass graft surgery ● Redo cardiac surgery ● Insulin-dependent Type 2 diabetes mellitus Exclusion criteria. ● End stage renal disease (plasma creatinine concentration 300 mol/L) ● Emergency cardiac surgery ● Planned off-pump cardiac surgery ● Known blood-bourne infectious disease ● Chronic inflammatory disease on immunosuppression ● Chronic moderate to high dose corticosteroid therapy (10 mg/day prednisone or equivalent) ● Enrolled in conflicting research study ● Age 18 years

7. Methods Design: Double-blind, randomized controlled trial. Setting: Operating rooms and intensive care unit at a tertiary hospital. Patients: Cohort of 100 cardiac surgical patients at increased risk of postoperative acute renal dysfunction. Intervention: Patients were randomized to either 24 hrs of intravenous infusion of Na bicarbonate (4 mmol/kg) or Na chloride (4 mmol/kg).

12. Data Analysis All data were analyzed according to the intention-to-treat principle. Continuous data were tested for normal distribution using histograms. Between-group comparisons for Continuous data were performed with the use of the Student’s t test or the Mann-Whitney U test Categorical data with the use of Fisher’s exact test or chi-square test where appropriate. All tests were two-tailed and we considered a p value <0.05 to indicate statistical significance.

18. Results Na + bicarbonate infusion was associated with An absolute risk reduction for acute renal dysfunction of 20% Significant attenuation in the post-op increase of plasma urea, urinary NGAL (a marker of oxidative stress) and urinary NGAL/urinary creatinine ratio.

19. Discussion: Hb mediated injury Animal Models: Hemoglobin infusion causes acute renal failure Urinary alkalinization or hemoglobin blockade with haptoglobin attenuates free hemoglobin-induced kidney injury Red blood cell hemolysate Is a potent mitogen for renal tubular epithelial cells, Free ferrous ions causes hydroxyl radical formation and lipid peroxidation. Free-radical production catalyzed by free ferrous ions is most active at acid pH. Aciduria converts hemoglobin to methemoglobin, which precipitates, forms distal casts, and induces acute kidney injury.

20. Discussion At neutral or alkaline pH induced by sodium bicarbonate, more free ferric ions precipitate as insoluble ferric hydroxides, reducing the production of injurious hydroxyl radicals. Urinary alkalinization with sodium bicarbonate might have protected patients from free hemoglobin-mediated kidney injury.

21. Conclusion