Renal effects of dexmedetomidine during coronary artery bypass surgery: a randomized placebo-controlled study

Abstract

Background: Dexmedetomidine, an alpha₂-adrenoceptor agonist, has been evaluated as an adjunct to anesthesia and for the delivery of sedation and perioperative hemodynamic stability. It provokes dose-dependent and centrally-mediated sympatholysis. Coronary artery bypass grafting (CABG) with extracorporeal circulation is a stressful procedure increasing sympathetic nervous system activity which could attenuate renal function due the interrelation of sympathetic nervous system, hemodynamics and renal function. We tested the hypothesis that dexmetomidine would improve kidney function in patients undergoing elective CABG during the first two postoperative days.

Methods: This was a double-blind, randomized, parallel-group study. Patients with normal renal function and scheduled for elective CABG were randomized to placebo or to infusion of dexmedetomidine to achieve a pseudo steady-state plasma concentration of 0.60 ng/ml. The infusion was started after anesthesia induction and continued until 4 h after surgery. The primary endpoint was creatinine clearance. Other variables included urinary creatinine and output, fractional sodium and potassium excretion, urinary potassium, sodium and glucose, serum and urinary osmolality and plasma catecholamine concentrations. The data were analyzed with repeated-measures ANOVA or Cochran-Mantel-Haenszel test.

Results: Sixty-six of 87 randomized patients were evaluable for analysis. No significant between-group differences were recorded for any indices of renal function except for a mean 74% increase in urinary output with dexmedetomidine in the first 4 h after insertion of a urinary catheter (p < 0.001). Confidence interval examination revealed that the sample size was large enough for the no-difference statement for creatinine clearance.

Conclusions: Use of intravenous dexmedetomidine did not alter renal function in this cohort of relatively low-risk elective CABG patients but was associated with an increase in urinary output.This study was carried out in 1994-1997 and was thus not registered.

Figure 1

Summary of patient disposition.

Figure 2

Perioperative creatinine clearance during the period in the per-protocol cohort (primary efficacy endpoint). Data are expressed as mean ± SD. P < 0.001 for time-trend in both groups; no significant differences between the groups.

Figure 3

Perioperative renal parameters. Creatinine clearance (A) and urinary output (B) in 4-h episodes. Serum creatinine (C) and fractional sodium excretion (D) during the perioperative period. Data are expressed as mean ± SD. CCR = cross clamp removal.

Figure 4

Plasma epinephrine and norepinephrine concentrations during the perioperative period. Data are expressed as mean ± SD.