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A rapid increase in isoflurane concentration can induce tachycardia and hypertension and increase plasma catecholamine concentrations. To investigate a possible mechanism, we measured hemodynamic responses to isoflurane administered via mask; we also administered clonidine for premedication, lidocaine topically to the nasal mucosa, or lidocaine intravenously to evaluate the effect of these drugs on the hemodynamic responses.Forty ASA physical status 1 patients (aged 20-30 yr) scheduled for elective oral surgery participated in the study. Thirty patients were randomly allocated to one of three groups: a control group, a group receiving 3-4 µg · kg-1 of oral clonidine for premedicatlon, and a group receiving 2 ml of 4% lidocaine spray to the nasal mucosa. Ten patients were assigned nonrandomly to a group receiving intravenous lidocaine continuously (0.4 mg · kg-1 bolus followed by 30 µg · kg-1 · min-1 ) after the initial randomized experiments were done to test whether systemic lidocaine blunts the responses to inhaled isoflurane. Anesthesia was induced with thlamylal, after which inhalation of 1% isoflurane in 100% oxygen via mask was begun. The inspired concentration of isoflurane was increased by 1% every 5 min to a maximum of 4%. During normocapnia and without surgical stimulation, heart rate and systolic blood pressure were measured every minute for 20 min before and during isoflurane inhalation. Plasma catecholamine concentrations were measured before and at each isoflurane concentration.In the control and Intravenous lidocaine groups, an increase in isoflurane concentration from 2% to 3% significantly increased systolic blood pressure (peak changes of 16 ± 5 and 15 ± 6 mmHg, respectively) and heart rate (peak changes of 23 ± 3 and 13 ± 4 beats · min -1, respectively). A change in concentration to 4%, however, did not significantly alter hemodynamics. Blood pressure and heart rate responses to a change to 3% Isoflurane were significantly blunted in the groups receiving clonidine (peak changes of 4 ± 4 mmHg and 8 ± 3 beats · min-1, respectively) or nasal lidocaine (peak changes of 2 ± 1 mmHg and 4 ± 2 beats · min-1, respectively) compared with the control group. In all groups, plasma epinephrine and norepinephrlne concentrations increased after administration of 2% and 1% Isoflurane, respectively. Plasma lidocaine concentrations were 0.3-1.3 µg · kg-1 in the nasal lidocaine group and 0.6-1.5 µg · kg-1 in the intravenous lidocaine group.Stepwise increases in isoflurane concentration elicited hypertension and tachycardia as well as increments in plasma catecholamine concentrations during mask anesthesia. Nasal administration of lidocaine and clonidine premedicatlon significantly blunted the circulatory responses to isoflurane. intravenous lidocaine did not significantly weaken the responses to changes in isoflurane concentration.