Bicarbonate in Cardiac Surgery - Full Text View

Purpose

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.

Condition	Intervention	Phase
Acute Kidney Injury	Drug: Sodium Bicarbonate Drug: Sodium Chloride	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase IIb Multiple Blind Randomized Controlled Trial of Sodium Bicarbonate in Cardiac Surgery at High-risk of Acute Kidney Injury

Resource links provided by NLM:

MedlinePlus related topics: Heart Surgery

Drug Information available for: Sodium bicarbonate Sodium chloride Chlorine

U.S. FDA Resources

Further study details as provided by Austin Health:

Primary Outcome Measures:

Proportion of patients developing an increase in serum creatinine greater than 25% or 44 mmol/L (0.5 mg/dL) postoperative increase in serum creatinine after adjustment for relevant baseline variables [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mean changes in serum creatinine after adjustment for relevant baseline variables [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
mean changes in serum cystatin C after adjustment for relevant baseline variables [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
mean changes in urinary neutrophil gelatinase-associated lipocalin (NGAL)after adjustment for relevant baseline variables [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
Duration of ventilation [ Time Frame: Until time of extubation from mechanical ventilation ] [ Designated as safety issue: No ]
Proportion of patients developing any of the RIFLE criteria: R, I or F [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
Incidence of post-operative atrial fibrillation [ Time Frame: within first five postoperative days ] [ Designated as safety issue: No ]
Duration of stay in the intensive care unit (ICU) [ Time Frame: from admission to the ICU ] [ Designated as safety issue: No ]
Duration of stay in hospital [ Time Frame: from admission to discharge from hospital ] [ Designated as safety issue: No ]
90-day mortality [ Time Frame: during 90 days postoperatively ] [ Designated as safety issue: No ]
Change in electrolyte status from baseline to peak [ Time Frame: within first 24-48hrs postoperatively ] [ Designated as safety issue: Yes ]

Enrollment:	427
Study Start Date:	April 2009
Study Completion Date:	January 2012
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 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 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).
Placebo Comparator: 2 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).	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).

Arms

Assigned Interventions

Active Comparator: 1

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 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).

Placebo Comparator: 2

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).

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).

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Eligibility

Ages Eligible for Study:	70 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age above 70 years
Pre-existing renal impairment (preoperative plasma creatinine concentration > 1.4 mg/dL
New York Heart Association class III/IV or impaired left ventricular function (left ventricular ejection fraction < 50%)
Valvular surgery or concomitant valvular and coronary artery bypass graft surgery
Redo cardiac surgery
Insulin-dependent diabetes mellitus

Exclusion Criteria:

End stage renal disease (plasma creatinine concentration > 3.4 mg/dL)
Emergency cardiac surgery
Planned off-pump cardiac surgery
Known blood-borne infectious disease
Chronic inflammatory disease on immunosuppression
Chronic moderate to high dose corticosteroid therapy (> 10 mg/d prednisone or equivalent)
Enrolled in conflicting research study
Age < 18 years

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00878956

Locations

Australia, Victoria
Austin Hospital
Melbourne, Victoria, Australia, 3084
Warringal Private Hospital
Melbourne, Victoria, Australia, 3084
New Zealand
Auckland City Hospital
Auckland, New Zealand
Waikato Hospital
Hamilton, New Zealand

Sponsors and Collaborators

Austin Health

Investigators

Principal Investigator:	Rinaldo Bellomo, MD, FRACP	Austin Hospital, Melbourne Australia
Study Chair:	Frank van Haren, MD	Waikato Hospital, Hamilton, New Zealand
Study Chair:	Shay McGuinness, MB ChB, FRCA, FANZCA	Auckland City Hospital, Auckland New Zealand

More Information

No publications provided

Responsible Party:	Rinaldo Bellomo, Director of ICU Research, Austin Health
ClinicalTrials.gov Identifier:	NCT00878956 History of Changes
Other Study ID Numbers:	H2007/02808
Study First Received:	April 8, 2009
Last Updated:	July 31, 2012
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Austin Health:

Cardiac surgery
Cardiopulmonary bypass
Oxidative stress
Acute renal dysfunction
Sodium bicarbonate

Additional relevant MeSH terms:

Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on May 23, 2013