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medium-dose, and two in the high-dose groups). There was no difference in the severity of echocardiographic ischemia as measured by mean change in wall-motion score among the four study groups. None of the episodes of wall-motion abnormalities were associated with significant ST-segment depression. Cardiac Outcomes During the 1-h dexmedetomidine infusion preceding induction of anesthesia, no severe bradycardia, new conduction defects, sinus pauses, new dysrhythmias, or ischemic episodes were detected from the continuous 12-lead ECG or Holter recordings. No patient had a myocardial infarction according to the 12-lead ECG and CK-MB data. Postoperatively, there were no cardiac-related mortality, episodes of unstable angina, sinus pauses, or life-threatening dysrhythmias. Radiologic signs of increased pulmonary interstitial fluid developed in four patients. In one patient (placebo group), the increase in pulmonary fluid content was attributed to excessive administration of intravenous fluids and, in another patient (medium-dose group), to pneumonia. The other two patients (medium- and high-dose groups), both with a history of congestive heart failure, were clinically judged to have signs of congestive heart failure. Three patients were treated postoperatively with intravenous nitroglycerin by the attending clinician: two patients in the placebo group received nitroglycerin during the study drug infusion, one for an ST-segment depression and one for an elevated CK-MB level; and one patient in the high-dose group received nitroglycerin after the study drug infusion for shortness of breath and onset of atrial fibrillation. No discernible trends were noted in any of the biochemistry, hematology, or urinalysis results for the dexmedetomidine groups relative to the placebo group. Sedation and Analgesia After the 1-h infusion preceding induction of anesthesia, all patients in the medium- and high-dose groups fell asleep but were easily arousable. During the second postoperative day, there was no clinically observable sedation from the study drug. Postoperative VAS pain scores were similar among groups, and postoperative morphine requirements did not differ. Adverse Events Ten patients had adverse events: three in the placebo group, and one, three, and three, respectively, in the low-, medium-, and high-dose groups. The ten patients had a total of 13 adverse events None of these events was life-threatening, and all could be accounted for by the patient's underlying disease (atrial fibrillation, transient ischemic attack) or complications expected secondary to the surgical procedures (pneumothorax, cellulitis). Summary of Adverse Events Given as a premedication to healthy patients, dexmedetomidine blunts the hemodynamic response to intubation, increases hemodynamic stability, decreases anesthetic requirements, and decreases the level of circulating catecholamines by up to 90%. These effects may benefit vascular surgery patients documented to have a high prevalence of CAD. The sympatholysis caused by dexmedetomidine has potential to increase the incidence of bradycardia and hypotension. The current study evaluated, in a preliminary manner, the effects of dexmedetomidine in high-risk patients undergoing vascular surgery. This study also is the first to administer dexmedetomidine as a continuous perioperative infusion over a 2-day period to cover the duration of most perioperative stress and hemodynamic lability. Our results suggest that a perioperative dexmedetomidine infusion to a targeted plasma concentration of 0.45 ng/ml can be used in high-risk vascular surgical patients if other drugs are given to offset the depression of heart rate and blood pressure. In accordance with the studies in healthy patients, we found that dexmedetomidine decreased blood pressure by 20% in vascular surgery patients. Because the present study focused on vascular surgery patients with or at risk for CAD, one concern was that the decrease in sympathetic tone might result in an intolerably large decrease in blood pressure. However, there were no clinically adverse effects due to the decrease in blood pressure in any of our patients. Postoperatively, there was
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