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This study was designed to determine if oral clonidine or lidocaine, injected into the scalp before head-holder (H-H) insertion, would attenuate the hemodynamic effects associated with intubation and H-H placement. Thirty-four patients undergoing skull base procedures were randomized to four groups. Group 1 received clonidine 5 mcg/kg po before surgery with 10 to 15 ml of 1% lidocaine infiltrated at pin insertion sites; Group 2 received clonidine with saline infiltration; Group 3 received a placebo preoperatively and had lidocaine infiltrated at pin sites; and Group 4 received a placebo with saline infiltrated. All patients had a standard anesthetic titrated to a 10 to 14 Hz EEG endpoint during laryngoscopy and H-H placement. Mean arterial pressure (MAP) was similar between groups during intubation, but heart rate (HR) increased in patients who did not receive clonidine. H-H application increased HR and MAP in Group 4. HR also increased after H-H placement in patients who received oral clonidine, while patients receiving scalp lidocaine or both clonidine and scalp lidocaine had little change in either value. Clonidine attenuated HR increases after laryngoscopy but not after H-H placement. Lidocaine injected at the pin sites reduced HR, and MAP increased after H-H insertion. The combination of oral clonidine and scalp lidocaine blunted hemodynamic responses to both intubation and H-H placement.