Bicarbonate in Cardiac Surgery

Renal impairment following cardiopulmonary bypass is common. While most of these patients do not require either short or long term renal replacement, the mortality of patients with acute renal failure is substantially greater than those who do not develop renal dysfunction. In a pilot double-blind, randomized controlled trial we 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. There is evidence that sodium bicarbonate affects the cardiovascular, respiratory and immune systems and may be of benefit to patients undergoing cardiac surgery. Study Design - overview and rationale Patients will be randomised to receive sodium bicarbonate from the induction of anaesthesia until 24 hours postoperatively, or a placebo (sodium chloride). Serum creatinine is the most commonly used clinical indicator of renal function along with urine output. Both will be measured for several days postoperatively - the time period during which renal impairment is most likely to develop. Randomisation The randomisation will be based on random numbers generated by computer. Once consent is obtained, the allocation of either treatment with sodium bicarbonate or placebo will be organised by an independent person (clinical trials pharmacist) who will dispense the coded and blinded infusion bags (shrink-wrapped in extra black plastic bags). This will be delivered to the anaesthetic staff looking after the patient in theatre, and the ICU nurse caring for the patient postoperatively. 20 ml samples of heparinised blood and urine will be taken from the arterial line or urine catheter. Samples will be taken immediately after the preoperative insertion of the arterial/urine catheter, at 6, 24, 48, 72, 96 and 120 hours after commencement of cardiopulmonary bypass. Immediately following collection, the preoperative, 6 and 24 hour blood and urine will be centrifuged at low speed to separate the plasma from the cellular components. Urine and plasma will be stored in aliquots at -70 degrees prior to batch analysis. The following variables will be obtained: Code for patient, gender and age. Date and time of admission to ICU Operative procedure and date and time on and off cardiopulmonary bypass Preoperative assessment of left ventricular function, Comorbidities, Pre-, intra- and post-operative medication, Markers of renal function as described above, Doses of frusemide administered (or rate of frusemide infusion) Use of inotropes or vasopressors Cardiac output whenever measured for clinical purposes in the first 24 hours postoperatively Requirement of renal replacement therapy Urine output in each 6 hour period during the presence of urine catheter Acid base status and electrolytes at baseline, 6 and 24 hours after commencement of cardiopulmonary bypass, Time of intubation and extubation, Date and time of arrival on and discharge from ICU and hospital, death Resources required The principle of the study has been discussed with the involved cardiac anaesthetists, cardiac surgeons, intensivists and intensive care nurses, who have offered their co-operation. ICU research nurse to allocate patients and collect clinical data. Pharmacy will be required to prepare drug and placebo infusion bags. Clinical pathology will be required to perform 24 hour creatinine clearance estimation (in addition to those tests clinically indicated) Protocol violations All protocol violations will be recorded. It will then be decided whether the nature of such violation had been such that the patient should be excluded from primary data analysis. Such evaluation will be blinded to treatment. Withdrawal The treating clinician will have the right to withdraw the patient from the study if he or she believes that continued participation is jeopardising the patient's well being. Ethical Issues Sodium bicarbonate used in this study is considered to be very safe as has been demonstrated by its widespread clinical use in the management of critically ill patients with metabolic acidosis. We consider the potential benefit of this treatment theoretically significant. Given the balance of benefits and risks, we consider it ethical to proceed and seek informed consent. Indemnity This is an investigator-initiated study and, accordingly, no commercial sponsor's indemnity has been provided. Informed consent will be obtained from the patient prior to the operation by one of the investigators or the ICU research nurse. The clinical care of a patient who does not consent for any reason will not be affected.