title: The effect of clonidine or midazolam premedication on perioperative responses during ketamine anesthesia.
abstract: The use of ketamine as a sole anesthetic induces marked central sympathetic stimulation, causing increased heart rate, blood pressure (BP), and oxygen consumption (VO2). Both alpha 2-agonists and benzodiazepines have been used to attenuate these potentially harmful ketamine-induced responses. This double-blind, randomized, placebo-controlled study was designed to compare the perioperative metabolic, hemodynamic, and sympathoadrenal responses to IM clonidine (2 micrograms/kg) and midazolam (70 micrograms/kg) premedication during ketamine anesthesia. VO2 was measured continuously using indirect calorimetry in 30 ASA physical status I patients. The patients received ketamine, mivacurium, and fentanyl for the induction of anesthesia. Anesthesia was maintained using a ketamine infusion and fentanyl boluses i.v. Preoperatively, both VO2 and BP decreased significantly after the administration clonidine and midazolam compared with placebo (P < 0.01). Intraoperatively, VO2 was higher in the midazolam group than in the placebo and clonidine groups (P < 0.05). Postoperatively, there were no significant differences in BP and VO2, although they stayed at lower level in the clonidine group during the whole postoperative period. Clonidine decreased pre- and postoperative plasma catecholamine concentrations (P < 0.05). Our results indicate that a midazolam-ketamine combination may induce potentially harmful metabolic stimulation, whereas the sympatholytic effects of clonidine on ketamine-anesthetized patients may be beneficial, as perioperative VO2 was decreased.
  
  
  CONCLUSIONS
  Ketamine causes sympathetic stimulation with an ensuing increase in oxygen consumption. Anticipating that clonidine might attenuate this response, we measured oxygen consumption in patients undergoing surgery during ketamine anesthesia. Patients treated with a clonidine-ketamine combination had lower intra- and postoperative oxygen consumption than those treated with a midazolam-ketamine combination.
authors.affiliation: Department of Anesthesiology, Turku University Hospital, Finland.
authors.forename: M T
authors.initials: MT
authors.lastname: Taittonen
authors.forename: O A
authors.initials: OA
authors.lastname: Kirvelä
authors.forename: R
authors.initials: R
authors.lastname: Aantaa
authors.forename: J H
authors.initials: JH
authors.lastname: Kanto
mesh_terms: D000759:Adjuvants, Anesthesia / Q000627:therapeutic use*; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000328:Adult; D000758:Anesthesia / Q000379:methods*; D000778:Anesthetics, Dissociative / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood / Q000378:metabolism; D003000:Clonidine / Q000627:therapeutic use*; D004311:Double-Blind Method; D004347:Drug Interactions; D004837:Epinephrine / Q000097:blood; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008874:Midazolam / Q000627:therapeutic use*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D010919:Placebos; D011292:Premedication
chemical_list: D000759:Adjuvants, Anesthesia; D000316:Adrenergic alpha-Agonists; D000778:Anesthetics, Dissociative; D010919:Placebos; D002245:Carbon Dioxide; D007649:Ketamine; D003000:Clonidine; D008874:Midazolam; D010100:Oxygen; D009638:Norepinephrine; D004837:Epinephrine