Sodium Bicarbonate in Cardiac Surgery Study

• Status: Terminated
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: All

Summary

With over one million operations a year, cardiac surgery with cardiopulmonary bypass is one of the most common major surgical procedures worldwide (1). Acute kidney injury is a common and serious postoperative complication of cardiopulmonary bypass and may affect 25% to 50% of patients (2-4). Acute kidney injury carries significant costs (4) and is independently associated with increased morbidity and mortality (2,3). Even minimal increments in plasma creatinine are associated with an increase in mortality (5,6).

Multiple causes of cardiopulmonary bypass-associated acute kidney injury have been proposed, including ischemia-reperfusion, generation of reactive oxygen species, hemolysis and activation of inflammatory pathways (7-10). COMT LL genotype appears to increase the risk of vasodilatory shock and AKI after cardiac surgery. To date, no simple, safe and effective intervention to prevent cardiopulmonary bypass-associated acute kidney injury in a broad patient population has been found (11-14).

Urinary acidity may enhance the generation and toxicity of reactive oxygen species induced by cardiopulmonary bypass (10,15). Activation of complement during cardiac surgery (16) may also participate in kidney injury. Urinary alkalinization may protect from kidney injury induced by oxidant substances, iron-mediated free radical pathways, complement activation and tubular hemoglobin cast formation (9,17,18). Of note, increasing urinary pH - in combination with N-acetylcysteine (19,20) or without (21) - has recently been reported to attenuate acute kidney injury in patients undergoing contrast-media infusion.

In a pilot double-blind, randomized controlled trial the investigators found sodium bicarbonate to be efficacious, safe, inexpensive and easy to administer. These findings now need to be confirmed or refuted by further clinical investigations in other geographic and institutional settings.

Accordingly, the investigators hypothesized that urinary alkalinization might protect kidney function in patients at increased risk of acute kidney injury undergoing cardiopulmonary bypass needs to be confirmed in an international multicenter, double-blind, randomized controlled trial of intravenous sodium bicarbonate.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Austin Health

Criteria

Inclusion Criteria:

• Cardiac surgical patients in whom the use of cardiopulmonary bypass was planned and:

• Written informed consent of patient

• Age >18 years

• And having at least one ore more of the following risk factors for postoperative AKI:

• Age =/>70 years

• Preoperative plasma creatinine >120 µmol/L New York Heart Association class III / IV or LVEF <35%

• Insulin dependent diabetes mellitus

• Valve surgery (with or without coronary artery bypass graft)

• Redo cardiac surgery

Exclusion Criteria:

• Cardiac surgical patients will not be considered eligible if:

• An emergency operation is indicated (within 24 hours after hospital admission or on intra-aortic balloon pump) or

• Pregnancy is confirmed or breastfeeding is present or

• A renal allograft is present or

• Preoperative acute renal failure within 6 weeks (acute rise in serum creatinine >50% from baseline) is present or

• Pre-operative end stage renal disease (serum creatinine >300 µmol/L) is present or

• Chronic moderate to high dose corticosteroid therapy (>10 mg/d prednisone or equivalent) is present