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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. Abstract Objective:

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slide1

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

slide2
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).

background
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
hypothesis
Hypothesis

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

rationale for bicarbonate
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.

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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
slide7
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).

data analysis
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.
results
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.

discussion hb mediated injury
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.

discussion
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.