title: Clonidine produces a dose-dependent impairment of baroreflex-mediated thermoregulatory responses to positive end-expiratory pressure in anaesthetized humans.
abstract: BACKGROUND
  Perioperative hypothermia is common and results from anaesthesia-induced inhibition of thermoregulatory control. Hypothermia is blunted by baroreceptor unloading caused by positive end-expiratory pressure (PEEP), and is mediated by an increase in the vasoconstriction threshold. Premedication with clonidine impairs normal thermoregulatory control. We therefore determined the effect of clonidine on PEEP-induced hypothermia protection.
  
  
  METHODS
  Core temperature was evaluated in patients undergoing combined general and epidural anaesthesia for lower abdominal surgery. They were assigned to an end-expiratory pressure of zero (ZEEP) or 10 cm H(2)O PEEP. The PEEP group was divided into three blinded subgroups that received placebo (Cl-0), clonidine 150 microg (Cl-150) and clonidine 300 microg (Cl-300) respectively. Placebo or clonidine was given orally 30 min before surgery. We evaluated core temperature and thermoregulatory vasoconstriction. We also determined plasma epinephrine, norepinephrine, angiotensin II concentrations and plasma renin activity.
  
  
  RESULTS
  Core temperature after 180 min of anaesthesia was 35.1 (0.4) degrees C in the ZEEP group. PEEP significantly increased final core temperature to 35.8 (0.5) degrees C (Cl-0 group). Clonidine produced a linear, dose-dependent impairment of PEEP-induced hypothermia protection: final core temperatures were 35.4 (0.3) degrees C in the Cl-150 group and 35.0 (0.6) degrees C in the Cl-300 group. Similarly, clonidine produced a linear and dose-dependent reduction in vasoconstriction threshold: Cl-0, 36.4 (0.3) degrees C; Cl-150, 35.8 (0.3) degrees C; Cl-300, 35.4 (0.6) degrees C. Plasma norepinephrine, angiotensin II concentrations and renin activity were consistent with the thermoregulatory responses.
  
  
  CONCLUSIONS
  Baroreceptor unloading by PEEP normally moderates perioperative hypothermia. However, clonidine premedication produces a linear, dose-dependent reduction in this benefit.
authors.affiliation: Department of Anesthesiology, Kyoto Prefectural University of Medicine, Kyoto, Japan. toshim@koto.kpu-m.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Mizobe
authors.forename: Y
authors.initials: Y
authors.lastname: Nakajima
authors.forename: M
authors.initials: M
authors.lastname: Sunaguchi
authors.forename: H
authors.initials: H
authors.lastname: Ueno
authors.forename: D I
authors.initials: DI
authors.lastname: Sessler
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000768:Anesthesia, General; D000804:Angiotensin II / Q000097:blood; D017704:Baroreflex / Q000187:drug effects*; D001833:Body Temperature Regulation / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007035:Hypothermia / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D011292:Premedication; D012083:Renin / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D000804:Angiotensin II; D012083:Renin; D003000:Clonidine; D009638:Norepinephrine