Reduction of the minimum alveolar concentration of isoflurane by dexmedetomidine.

BACKGROUND: alpha 2-Adrenergic agonists have been shown to reduce anesthetic requirements of other anesthetics, and they may even act as complete anesthetics by themselves at high doses in animal models. The present study was designed to define the interaction of intravenous infusion of dexmedetomidine, an alpha 2-adrenergic agonist, and isoflurane in patients having surgery by using the minimum alveolar concentration (MAC) of isoflurane as the measure of anesthetic potency. METHODS: Forty-nine women scheduled for abdominal hysterectomy were randomly allocated to receive either a placebo infusion (n = 16) or a two-stage infusion of dexmedetomidine with target plasma concentration of 0.3 ng/ml (n = 17) or 0.6 ng/ml (n = 16). The study drug infusion was commenced 15 min before induction of anesthesia with thiopental and alfentanil and was continued until skin incision. The end-tidal concentration of isoflurane for each patient was predetermined according to the "up-down" method of Dixon, and it was maintained for at least 15 min before the patient's response to skin incision was assessed. RESULTS: The MAC of isoflurane was 0.85% end-tidal in the control group, 0.55% end-tidal with the low dose of dexmedetomidine, and 0.45% end-tidal with the high dose of dexmedetomidine. CONCLUSIONS: The MAC of isoflurane in the control group was lower than that reported previously in similar patients having surgery, probably due to anesthesia induction with thiopental and alfentanil. Nevertheless, with the high dose of dexmedetomidine, the MAC of isoflurane was still 47% less than that without dexmedetomidine.

Dexmedetomidine premedication before intravenous regional anesthesia in minor outpatient hand surgery.

STUDY OBJECTIVE: To assess the efficacy and safety of intravenous (i.v.) dexmedetomidine, an alpha-2 agonist, as a premedication before i.v. regional anesthesia. DESIGN: Randomized, double-blind, placebo-controlled study with two parallel groups. SETTING: Day-case surgery unit, Department of Surgery, Turku University Hospital, Turku, Finland. PATIENTS: 30 healthy ASA physical status I outpatients scheduled for minor hand surgery with i.v. regional anesthesia. INTERVENTIONS: Patients were assigned to one of two groups to receive either dexmedetomidine 1 microgram/kg i.v. (n = 15) or saline placebo i.v. (n = 15) 10 minutes before exsanguination and inflation of a tourniquet. Regional blockade was induced with 0.5% lidocaine 3 mg/kg (maximum 200 mg). Additional fentanyl 1 microgram/kg intraoperatively and oxycodone 0.05 mg/kg postoperatively were administered for analgesia if needed. MEASUREMENTS AND MAIN RESULTS: Dexmedetomidine preoperatively induced 16% to 20% decreases in systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), and heart rate (p < 0.001), which were mainly abolished within the 4-hour postoperative follow-up period. A clinically significant decrease in arterial oxygen saturation was not observed. The subjective intensity of pain during tourniquet inflation was similar in both groups, but fewer intraoperative (p = 0.009) opioid analgesics were needed in the dexmedetomidine group. Dexmedetomidine decreased sympathoadrenal responses: plasma norepinephrine concentration decreased to one-fourth of the baseline level (p < 0.001), and one of its main metabolites, 3,4-dihydroxyphenylglycol, decreased by 27% (p < 0.001). Dexmedetomidine also prevented an increase in plasma epinephrine concentration following tourniquet inflation (p = 0.003). Dexmedetomidine induced subjective sedation (p = 0.002), but the Maddox Wing test did not show any statistically significant differences between the groups. General effectiveness was graded superior in the dexmedetomidine group (p < 0.001). CONCLUSIONS: Dexmedetomidine is an effective premedication before i.v. regional anesthesia because it reduces patient anxiety, sympathoadrenal responses, and opioid analgesic requirements.

Intramuscular dexmedetomidine premedication--an alternative to midazolam-fentanyl-combination in elective hysterectomy?

Sedation, anxiolysis, intubation responses and fentanyl anaesthetic requirements were investigated in a double-blind, randomized study in twenty ASA I-II elective hysterectomy patients. Ten patients received dexmedetomidine 2.5 micrograms kg-1 i.m. 60 min before induction and saline placebo i.v. 2 min prior to induction (= DP group). Ten patients received midazolam 0.08 mg kg-1 i.m. 60 min and fentanyl 1.5 micrograms kg-1 i.v. (= MF group) 2 min before induction of anaesthesia with thiopentone 4 mg kg-1. Anaesthesia was maintained with 70% nitrous oxide in oxygen and with fentanyl 2 micrograms kg-1 i.v. increments according to predetermined criteria. Both premedications induced sedation (P < 0.01 in both groups) and anxiolysis (P < 0.01 in DP vs P < 0.05 in MF group) without any differences between the groups. Haemodynamic changes following tracheal intubation did not significantly differ between the groups. Intraoperatively systolic and diastolic arterial pressure were 15% and 13% lower in DP group (P < 0.01 and P < 0.05 for drug effect), the mean heart rate was approximately 9 beats min-1 lower in DP group (n.s.). Fentanyl was required more often in MF group: median 3.5 (QD 1.5) vs. 2.5 (QD 0.5) times in DP group (P < 0.05), the total amount being 57% smaller in DP group: 0.03 (QD 0.01) vs. 0.07 (QD 0.02) micrograms kg-1 min-1 (P < 0.05). Postoperative course and analgesic requirements were similar in both groups. Dexmedetomidine premedication may offer an alternative to current anaesthesia practice in elective hysterectomy.

Intramuscular dexmedetomidine as premedication for general anesthesia. A comparative multicenter study.

BACKGROUND: Dexmedetomidine is a new potent and selective alpha 2-agonist that might prove useful as a preanesthetic agent. METHODS: A randomized, double-blind study design was used in 192 ASA physical status 1 and 2 patients scheduled for elective abdominal hysterectomy, cholecystectomy, or intraocular surgery under general anesthesia. Intramuscular injection of 2.5 micrograms/kg dexmedetomidine administered 60 min before and intravenous saline placebo 2 min before induction of anesthesia (DEXPLA group, n = 64) was compared with a combination of 0.08 mg/kg intramuscular midazolam 60 min and 1.5 micrograms/kg intravenous fentanyl 2 min before induction (MIDFENT group, n = 64), or a combination of intramuscular dexmedetomidine and intravenous fentanyl (DEXFENT group, n = 64). After thiopental induction, anesthesia was maintained with 70% N2O/O2, and fentanyl was administered according to clinical and cardiovascular criteria. Patients undergoing cholecystectomy received additional enflurane. RESULTS: Dexmedetomidine and midazolam induced comparable preoperative sedation and anxiolysis. The DEXFENT combination blunted the increases in blood pressure and heart rate induced by tracheal intubation more efficiently when compared with the DEXPLA and MIDFENT groups, in which approximately 25 mmHg and 15 beats/min greater increases were observed. The intraoperative fentanyl requirements were greater in MIDFENT patients when compared with both dexmedetomidine groups, in which 56% (DEXFENT group) and 31% (DEXPLA group) less fentanyl, respectively, was needed. Intraoperatively, fluids or vasopressors for hypotension and glycopyrrolate for bradycardia were administered more often to patients receiving dexmedetomidine than to those who did not. Postoperatively, there were no differences in oxygen saturation, analgesic, or antiemetic requirements, but dexmedetomidine-induced blood pressure and heart rate reductions were still evident at the end of the 3-h follow-up period. Bradycardia as an adverse event was reported more frequently in dexmedetomidine patients (20% in the DEXPLA and 33% in the DEXFENT groups) than in MIDFENT patients (8%). CONCLUSIONS: The results suggest that pretreatment with a single intramuscular injection of 2.5 micrograms/kg dexmedetomidine is efficacious, but significantly increases the incidence of intraoperative hypotension and bradycardia in ASA physical status 1 or 2 patients.

Dexmedetomidine reduces intraocular pressure, intubation responses and anaesthetic requirements in patients undergoing ophthalmic surgery.

We studied the effects of a single i.v. dose of dexmedetomidine, a highly selective and specific alpha 2 adrenoceptor agonist, on intraocular pressure (IOP), haemodynamic and sympathoadrenal responses to laryngoscopy and tracheal intubation, and on anaesthetic requirements in ophthalmic surgery. Thirty ASA I-II patients undergoing cataract surgery were allocated randomly to receive either dexmedetomidine 0.6 microgram kg-1 or saline placebo i.v. 10 min before induction of anaesthesia in a double-blind design. After dexmedetomidine there was a 34% (95% confidence interval (CI) 27-43%) reduction in IOP (P less than 0.001) and 62% (CI 57-68%) decrease in plasma noradrenaline concentrations (P less than 0.001). After intubation, maximum heart rate was 18% (CI 3-33%, P = 0.036) and the maximum IOP 27% (CI 11-43%, P = 0.005) less in the dexmedetomidine group compared with the patients treated with placebo. Within 10 min after intubation, maximum systolic and diastolic arterial pressures were also significantly (P = 0.013 and P = 0.020) smaller in the dexmedetomidine group. The induction dose of thiopentone was smaller (23% (CI 20-26%) P = 0.012), and the use of isoflurane or fentanyl supplements during anaesthesia was less frequent in the dexmedetomidine group. The patients premedicated with dexmedetomidine recovered faster from anaesthesia (P = 0.042). These results suggest that dexmedetomidine may be a useful anaesthetic adjunct in ophthalmic surgery.

A comparison of dexmedetomidine, and alpha 2-adrenoceptor agonist, and midazolam as i.m. premedication for minor gynaecological surgery.

The effects of i.m. dexmedetomidine 1.0 micrograms kg-1, a new alpha 2-adrenoceptor agonist, were compared with those of i.m. midazolam 0.08 mg kg-1 and placebo on vigilance, anaesthetic requirements, haemodynamic state and plasma catecholamine concentrations in a double-blind placebo-controlled study in 107 healthy (ASA physical status I-II) women undergoing cervical dilatation and uterine curettage. The premedicants were administered i.m. 60 min before induction of anaesthesia with thiopentone. Nitrous oxide 70% in oxygen and thiopentone were used for maintenance. Both premedicants were tolerated well and no serious haemodynamic or other adverse events occurred. Dexmedetomidine caused moderate reductions in arterial pressure (maximally by 20%) and heart rate (maximally by 15%). Atropine was administered to two dexmedetomidine-premedicated patients because of bradycardia less than 45 beat min-1. Both premedicants decreased the plasma concentrations of noradrenaline by about 50%, but only dexmedetomidine attenuated the catecholamine response to anaesthesia and surgery. The thiopentone requirements were decreased significantly (P = 0.003) by both dexmedetomidine (17%) and midazolam (19%). Recovery times were 11.3 (SD 4.2) min after midazolam, 8.5 (5.2) min after dexmedetomidine and 5.6 (11.4) min after placebo (P = 0.006 between midazolam and placebo groups, other differences ns).