A study to determine the feasibility of a trial investigating the effect of angiotensin II infusion on kidney damage in cardiac surgical patients

INTERVENTION: Angiotensin II infusion ‐ dose to maintain mean arterial pressure in range of 70‐80mmHg. Dose range 0‐40ng/kg/min (titrated to maintain blood pressure in range). Started post‐induction of anaesthesia and prior to initiation of cardiopulmonary bypass and continued for 48 hours after conclusion of surgery (as a continuous infusion), or until patient goes to the ward if this occurs sooner. Adherence reviewed by monitoring of electronic record. No other drugs administered as part of the intervention. CONDITION: Acute kidney injury; ; Acute kidney injury Anaesthesiology ‐ Other anaesthesiology Cardiovascular ‐ Other cardiovascular diseases Renal and Urogenital ‐ Kidney disease Surgery ‐ Other surgery PRIMARY OUTCOME: Duration of study drug infusion as a percentage of total time. Assessed by patient record and infusion pump review.[Intraoperative and for up to 48 hours postoperative or discharge to ward] Percentage of patients approached who consent to the study. Assessed by screening log.[Prior to randomisation] Protocol compliance. Assessed by patient medical record.[At the conclusion of the study] INCLUSION CRITERIA: Adult > 18 years old; Cardiac surgery using cardiopulmonary bypass including coronary artery bypass grafting (CABG) surgery, valve surgery, combined CABG/valve surgery; Elevated risk of acute kidney injury (AKI) as predicted by a score >3 on the following scale (ie. 3.5 or greater): ‐ haemoglobin < 130g/l (2 points), creatinine >100umol/l (2 points), age > 70 (1.5 points), NYHA 4 (1.5 points), BMI > 30 (1.5points) SECONDARY OUTCOME: "Nephrocheck" biomarkers (composite of tissue inhibitor of metalloproteinases‐2 (TIMP‐2) and insulin‐like growth factor binding protein 7 (IGFBP7)) (additional urine samples taken)[Day 0 (immediate preoperative), Days 1 and 2 post‐operative] Adrenaline maximum dose . As assessed by patient record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Adrenaline total dose. As assessed by patient record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Adverse events ‐ deep venous thrombosis. Assessed using patient medical record[Intraoperative and in first 7 days postoperatively] Adverse events ‐ severe hypertension (mean arterial pressure > 120mmHg with evidence of adverse patient effect, included left ventricular failure or aortic dissection). Assessed using medical record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Aldosterone levels (additional blood samples taken)[Day 0 (immediate preoperative), Days 1 and 2 post‐operative] Angiotensin I levels (additional blood samples taken)[Day 0 (immediate preoperative), Days 1 and 2 post‐operative] Angiotensin II levels (additional blood samples taken)[Day 0 (immediate preoperative), Days 1 and 2 post‐operative] Creatinine clearance (from 6 hour urine collection)[6 hours of urine output collected between immediate postoperative and 6 hours postoperative] Creatinine levels (obtained from routine pathology results as documented in medical record)[Day 0 (immediate preoperative), Days 1 and 2 post‐operative] Duration of time that mean arterial pressure is in target range (70‐80mmHg) as a percentage of total time. As assessed by patient record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Largest change in creatinine between most recent immediate preoperative and postoperative (obtained from routine pathology results as documented in medical record)[Between immediate preoperative creatinine and up to 7 days postoperative] Milrinone maximum dose. As assessed by patient record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Milrinone total dose. As assessed by patient record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Noradrenaline maximum dose. As assessed by patient record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Noradrenaline total dose. As assessed by patient record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Potassium level (obtained from routine pathology results as documented in medical record)[Day 0 (immediate preoperative), Days 1 and 2 post‐operative] Renin (additional blood samples taken)[Day 0 (immediate preoperative), Days 1 and 2 post‐operative] Sodium (obtained from routine pathology results as documented in medical record)[Day 0 (immediate preoperative), Days 1 and 2 post‐operative] Urinary ACE2 (additional urine samples taken)[Day 0 (immediate preoperative), Days 1 and 2 post‐operative] Vasopressin maximum dose. As assessed by patient record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Vasopressin total dose. As assessed by patient record. [Intraoperative and up to 48 hours postoperative or discharge to ward] Volume of colloid or crystalloid fluid given as assessed by patient record and recorded by clinician[Intraoperative and up to 48 hours postoperative or discharge to ward]