Bicarbonate in Cardiac Surgery

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). 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.

Conditions

• Acute Kidney Injury

Interventions

DRUG

Sodium Bicarbonate

In all patients body weight adjusted dose of study medication will be achieved by infusion of sodium bicarbonate at a dose of 0.5 mmol/kg body weight (=bolus) diluted in 250 mL over 1 hour immediately after the induction of anesthesia, prior to the first surgical incision followed by continuous intravenous infusion of 0.2 mmol/kg/hr (=maintenance) diluted in 1000 mL 23 hours (total dose of 5 mmol/kg over 24 hours).

DRUG

Sodium Chloride

In all patients body weight adjusted dose of study medication will be achieved by infusion of sodium chloride at a dose of 0.5 mmol/kg body weight (=bolus) diluted in 250 mL over 1 hour immediately after the induction of anesthesia, prior to the first surgical incision followed by continuous intravenous infusion of 0.2 mmol/kg/hr (=maintenance) diluted in 1000 mL 23 hours (total dose of 5 mmol/kg over 24 hours).

Sponsors & Collaborators

• Austin Health

  lead OTHER_GOV

Principal Investigators

• Rinaldo Bellomo, MD, FRACP · Austin Hospital, Melbourne Australia

• Frank van Haren, MD · Waikato Hospital, Hamilton, New Zealand

• Shay McGuinness, MB ChB, FRCA, FANZCA · Auckland City Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-04-30

Primary Completion

2011-06-30

Completion

2012-01-31

Countries

• Australia
• New Zealand

Study Locations