title: Sympathetic neural activation evoked by mu-receptor blockade in patients addicted to opioids is abolished by intravenous clonidine.
abstract: BACKGROUND
  Mu-opioid receptor blockade by naloxone administered for acute detoxification in patients addicted to opioids markedly increases catecholamine plasma concentrations, muscle sympathetic activity (MSA), and is associated with cardiovascular stimulation despite general anesthesia. The current authors tested the hypothesis that the alpha2-adrenoceptor agonist clonidine (1) attenuates increased MSA during mu-opioid receptor blockade for detoxification, and (2) prevents cardiovascular activation when given before detoxification.
  
  
  METHODS
  Fourteen mono-opioid addicted patients received naloxone during propofol anesthesia. Clonidine (10 microg x kg(-1) administered over 5 min + 5 microg x kg(-1) x h(-1) intravenous) was infused either before (n = 6) or after (n = 6) naloxone administration. Two patients without immediate clonidine administration occurring after naloxone administration served as time controls. Muscle sympathetic activity (n = 8) in the peroneal nerve, catecholamine plasma concentrations (n = 14), arterial blood pressure, and heart rate were assessed in awake patients, during propofol anesthesia before and after mu-opioid receptor blockade, and after clonidine administration.
  
  
  RESULTS
  Mu-receptor blockade markedly increased MSA from a low activity (burst frequency: from 2 burst/min +/- 1 to 24 +/- 8, means +/- SD). Similarly, norepinephrine (41 pg/ml +/- 37 to 321 +/- 134) and epinephrine plasma concentration (13 pg/ml +/- 6 to 627 +/- 146) significantly increased, and were associated with, increased arterial blood pressure and heart rate. Clonidine immediately abolished both increased MSA (P < 0.001) and catecholamine plasma concentrations (P < 0.001). When clonidine was given before mu-opioid receptor blockade, catecholamine plasma concentrations and hemodynamic variables did not change.
  
  
  CONCLUSIONS
  Administration of the alpha2-adrenoceptor agonist clonidine decreases both increased MSA and catecholamine plasma concentrations observed after mu-opioid receptor blockade for detoxification. Furthermore, clonidine pretreatment prevents the increase in catecholamine plasma concentration that otherwise occurs during mu-opioid receptor blockade.
authors.affiliation: Abteilung für Anästhesiologie und Intensivmedizin, Universitätsklinikum, Essen, Germany. peter.kienbaum@uni-essen.de
authors.forename: Peter
authors.initials: P
authors.lastname: Kienbaum
authors.forename: Thorsten
authors.initials: T
authors.lastname: Heuter
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
authors.forename: Norbert
authors.initials: N
authors.lastname: Scherbaum
authors.forename: Markus
authors.initials: M
authors.lastname: Gastpar
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000758:Anesthesia; D002395:Catecholamines / Q000097:blood; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors*; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D002395:Catecholamines; D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D003000:Clonidine