Renoprotective Effects of Dexmedetomidine Preconditioning in CABG Surgery

Acute kidney injury (AKI) is one of the most frequent complications of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB). Even small postoperative rises in serum creatinine are associated with longer intensive care stay and higher mortality. Ischemia-reperfusion injury, the systemic inflammatory response elicited by contact of blood with the bypass circuit, and heightened perioperative sympathetic activity are believed to contribute to its development.

Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist used as a sedative and anesthetic adjunct. It attenuates sympathetic outflow and has shown anti-inflammatory and organ-protective properties in experimental models and in some cardiac surgical populations, but whether it reduces AKI after on-pump CABG surgery has not been established.

This is a prospective, randomized, double-blind, placebo-controlled, single-center trial in adults undergoing elective CABG surgery with CPB. One hundred patients aged 18-80 years, ASA physical status II or III, with a preoperative serum creatinine below 1.5 mg/dL are allocated 1:1 to a dexmedetomidine group (n=50) or a control group (n=50). Patients in the dexmedetomidine group receive a loading dose of 1 microgram/kg over 15 minutes after central venous catheterization, followed by a maintenance infusion of 0.5 microgram/kg/h until the start of CPB. Patients in the control group receive an equal volume of 0.9% sodium chloride over the same period and with the same infusion scheme. In both groups the infusion is stopped when CPB begins; no study drug is given during bypass or postoperatively. Anesthesia, surgery, CPB conduct, fluid and vasoactive therapy, and postoperative intensive care follow a standardized protocol with identical numerical thresholds in both groups, applied by clinicians unaware of group allocation.

The primary outcome is the incidence of postoperative AKI within the first 72 hours, staged according to the serum creatinine criteria of the KDIGO 2012 classification. Secondary outcomes are systemic inflammatory markers (white blood cell count, neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, C-reactive protein, procalcitonin), vasoactive drug requirement quantified by the vasoactive-inotropic score, need for renal replacement therapy, time to extubation, intensive care unit and hospital length of stay, and 30-day and 90-day mortality. All patients are followed until postoperative day 90.

All variables assessed in the study are parameters obtained as part of routine clinical care in this patient population; no additional intervention or additional laboratory test is performed for study purposes.

Inclusion criteria

• Age 18 to 80 years
• Scheduled for elective coronary artery bypass graft surgery with cardiopulmonary bypass at the study center
• American Society of Anesthesiologists (ASA) physical status class II or III
• Preoperative serum creatinine below 1.5 mg/dL
• Written informed consent obtained at the preoperative visit

Exclusion criteria

• Left main coronary artery stenosis greater than 50%
• Severe valvular dysfunction
• Severe left ventricular hypertrophy or cardiomyopathy
• Arrhythmia causing significant hemodynamic compromise
• Left ventricular ejection fraction below 35%
• Acute coronary syndrome or cardiovascular surgery within the preceding month
• Estimated glomerular filtration rate below 15 mL/min/1.73 m2
• Nephropathy due to uncontrolled hypertension and/or diabetes mellitus
• Treatment of hypertension with a combination of an angiotensin-converting enzyme inhibitor, a diuretic and an alpha-2 adrenergic agonist
• Morbid obesity
• Hepatic dysfunction attributable to substance abuse or alcoholism
• Previous severe drug allergy during administration of dexmedetomidine