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VASCULAR SURGEON RESEARCH
Dexmedetomidine, a highly selective alpha 2-adrenergic agonist, increases perioperative hemodynamic stability in healthy patients but decreases blood pressure and heart rate. The goal of this study was to evaluate, in a preliminary manner, the hemodynamic effects of perioperatively administered dexmedetomidine in surgical patients at high risk for coronary artery disease. Twenty-four vascular surgery patients received a continuous infusion of placebo or one of three doses of dexmedetomidine, targeting plasma concentrations of 0.15 ng/ml (low dose), 0.30 ng/ml (medium dose), or 0.45 ng/ml (high dose) from 1 h before induction of anesthesia until 48 h postoperatively. All patients received standardized anesthesia and hemodynamic management. Blood pressure, heart rate, and Holter ECG were monitored; additional monitoring included continuous 12-lead ECG preoperatively, anesthetic concentrations and myocardial wall motion (echocardiography) intraoperatively, and cardiac enzymes postoperatively. Preoperatively, there was a decrease in heart rate (low dose 11%, medium dose 5%, high dose 20%) and systolic blood pressure (low dose 3%, medium dose 12%, high dose 20%) in patients receiving dexmedetomidine. Intraoperatively, dexmedetomidine groups required more vasoactive medications to maintain hemodynamics within predetermined limits. Postoperatively, demedetomidine groups had less tachycardia (minutes/monitored hours) than the placebo group (placebo 23 min/h; low dose 9 min/h, P = 0.006; medium dose 0.5 min/h, P = 0.004; high dose 2.3 min/h, P = 0.004). Bradycardia was rare in all groups. There were no myocardial infarctions or discernible trends in the laboratory results. Infusion of dexmedetomidine up to a targeted plasma concentration of 0.45 ng/ml appears to benefit perioperative hemodynamic management of surgical patients undergoing vascular surgery but required greater intraoperative pharmacologic intervention to support blood pressure and heart rate. Key words: Dexmedetomidine: hemodynamics. Dose-effect. Heart: coronary artery disease. Sympathetic nervous system, alpha2-adrenergic agonist: dexmedetomidine. SURGICAL and postoperative stress evoke an endocrine response that manifests as stimulation of the hypothalamus-pituitary-adrenal axis, renin-angiotensin axis, and the sympathetic nervous system. Stimulation of the sympathetic nervous system increases the levels of circulating plasma norepinephrine and epinephrine, increasing blood pressure and heart rate] and the incidence of postoperative complications. The hyperdynamic changes predispose the myocardium to ischemia, especially in the patient population with decreased reserve for coronary blood flow. Perioperative ischemia is associated with a significant increase in postoperative morbidity and mortality. Attenuating the perioperative stress response could decrease the incidence of myocardial ischemia and thereby reduce the incidence of perioperative morbidity and mortality in patients at high risk for myocardial ischemia. Several clinical studies suggest that alpha2-adrenergic agonists might be effective in blunting the perioperative stress response and that clonidine may have perioperative antiischemic effects. Dexmedetomidine is an alpha2-adrenergic agonist with a 10-fold greater alpha2/alpha1-receptor selectivity than clonidine. In healthy volunteers, dexmedetomidine decreases circulating catecholamines by up to 90% and, like clonidine, has antinociceptive and sedative effects. In healthy surgical patients, dexmedetomidine increases hemodynamic stability, decreases anesthetic requirements, and blunts the hyperdynamic response to intubation. The sympatholysis also results in potentially adverse clinical effects, such as a decrease in blood pressure and bradycardia. Such hemodynamic changes might not be tolerated by patients with vascular disease or severe myocardial
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