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The effects of clonidine, a centrally acting alpha 2-adrenergic receptor agonist, on depth of fentanyl anesthesia and on cardiovascular response to laryngoscopy and intubation were studied. Twenty-four patients undergoing aortocoronary bypass surgery (ACBS) with a history of arterial hypertension, coronary artery disease (NYHA class 3-4), and well-preserved left ventricular function were assigned randomly to either Group 1 (n = 12), who received standard premedication, or Group 2 (n = 12), who received clonidine 5 micrograms X kg-1 po in addition to standard premedication 90 min before estimated induction time. Depth of anesthesia was assessed by on-line aperiodic computerized analysis of the electroencephalogram (Lifescan EEG Monitor). Fentanyl was administered in 250-micrograms increments to shift the EEG to the 0.5-3-Hz frequency range (delta activity) in all subjects. In both groups, the anesthetic regimen effectively prevented hyperdynamic cardiovascular responses to laryngoscopy and intubation. No significant differences in measured or derived hemodynamic variables were observed between the two groups during the awake control period, except for stroke volume index (SVI), which was significantly greater in Group 1, 44 +/- 9 ml X beat-1 X m-2 compared with Group 2, 35 +/- 3.3 ml X beat-1 X m-2 (P less than 0.05). By contrast, fentanyl requirements in Group 2 were significantly reduced by 45% when compared with Group 1, i.e., from 110 +/- 23 to 61 +/- 19 micrograms X kg-1 (P less than 0.001). The authors conclude that at a similar anesthetic depth, as assessed by the EEG shift into the lower frequency range (0.5-3 Hz), a markedly reduced fentanyl dose effectively prevented the hyperdynamic cardiovascular response to laryngoscopy and intubation in the group of patients premedicated with clonidine. This is likely explained by the known synergistic inhibitory action of opiates and alpha 2-adrenoceptor agonists on central sympathetic outflow.