The efficacy of guanfacine in reducing perioperative hemodynamic changes and volatile anesthetic requirement

Abstract

Study Objective: To evaluate the efficacy of guanfacine, an α 2-adrenergic agonist, for attenuating hemodynamic changes associated with tracheal intubation or extubation, providing intraoperative hemodynamic stability, and reducing inhalation anesthetic requirement in patients undergoing gynecologic surgery. Design: Randomized, double-blind, placebo-controlled study. Setting: Inpatient gynecology at a university hospital. Patients: 45 women (ASA I) undergoing elective abdominal hysterectomy. Interventions: Guanfacine and placebo supplementation. Oral guanfacine at 0.5 or 1 mg or a placebo (control) 3 hours before induction of anesthesia. Anesthesia was induced with thiamylal 5 mg/kg and vecuronium 0.2 mg/kg, and maintained with isoflurane and 50% nitrous oxide (N 2O) in oxygen. The inspired isoflurane concentration was maintained at 1% during the first 5 minutes following induction of anesthesia and titrated to the concentration required to maintain hemodynamic stability [defined as ±10% of systolic blood pressure (SBP)]. The end-tidal concentration of isoflurane was monitored throughout anesthesia. On completion of surgery, N 2O and isoflurane were discontinued. Following confirmation of recovery from anesthesia and muscle relaxation, the endotracheal tube was removed. Measurements and Main Results: Patients in the control group showed significant increases in SBP and diastolic blood pressure (DBP) and heart rate (HR) associated with tracheal intubation 50 ± 5, 57 ± 6.3, and 45 ± 4.6 (%, mean ± SEM, p < 0.05 for any variables), respectively. Plasma norepinephrine and epinephrine concentrations increased to 382 ± 40 pg/ml and 49 ± 4.2 pg/ml, respectively ( p < 0.05 compared with basal values). These changes were attenuated in patients receiving 1 mg of guanfacine (29 ± 4.2, 33 ± 4.5, 25 ± 3.2, 210 ± 32, and 22 ± 3.5, respectively ( p < 0.05 for any variables compared with placebo group). Higher inspired concentrations of isoflurane (%) were required in the control and 0.5 mg guanfacine-treated groups (1.2 ± 0.05 and 1.0 ± 0.04, respectively) than in the 1 mg guanfacine-treated group (0.62 ± 0.03) for hemodynamic stability ( p < 0.05). Coefficient of variation in HR changes during surgery was 17.2, 13.9, and 8.8 in the placebo, guanfacine 0.5 mg, and guanfacine 1 mg treated groups, respectively. Compared with placebo, guanfacine 1 mg reduced the maximum changes (mean ± SEM) in SBP (7 ± 1.2 vs. 18 ± 2.2) and in HR (23 ± 2.1 vs. 44 ± 3.6) occurring during tracheal extubation. The incidence of perioperative complications was similar among the three groups. Conclusion: Guanfacine 1 mg administered orally proved to be an effective premedicant for providing intraoperative hemodynamic stability, attenuating the increase in BP and HR associated with tracheal intubation and extubation, and reducing anesthetic requirements without increasing the incidence of perioperative complications.