title: Clonidine for treatment of postoperative pain: a dose-finding study.
abstract: The aim of this double-blind randomized study was to evaluate the optimal intravenous dose of clonidine administrated during the peri-operative period, after lumbar hemilaminectomy for herniated disk repair. The "optimal intravenous dose" was defined as that providing minimal analgesic request, stable haemodynamic profile and a minimal sedation score during 12h after extubation. Eighty adult patients, ASA physical status I-II, undergoing lumbar hemilaminectomy for herniated disk (L(4)-L(5), L(5)-S(1)) were included in the study. All the patients were randomly assigned to one of four study groups (A, B, C, D), 20 patients each. The same standardized general anaesthesia was performed for each group. Thirty minutes before the end of surgery, group A, B and C patients received three different loading doses of intravenous clonidine (5 microg/kg, 3 microg/kg, 2 microg/kg respectively), followed by the same infusion of intravenous clonidine (0.3 microg/kg per hour). Group D patients received a bolus dose and a continuous infusion of NaCl 0.9%. In the recovery unit, postoperative pain was treated by a patient-controlled analgesia device, containing morphine. Pain relief was evaluated by the total morphine requirement during the postoperative period. Systolic blood pressure (SBP), heart rate and sedation were also noted during the first 12h postoperatively. Intravenous clonidine decreased morphine requirements in a dose-dependent manner. Group A, B, C and D patients requested 5 +/- 2, 11 +/- 3, 19 +/- 4 and 29 +/- 8 doses of morphine respectively. Clonidine also affected SBP in a dose-related manner. Group A, B and C patients had an SBP decrease respectively of 26 +/- 3%, 7 +/- 4% and 2 +/- 2% compared with basic values while, at the same time, in group D patients no SBP variation was registered. In conclusion, this study demonstrates that, when sedation and analgesic effect of clonidine is required, 3 microg/kg bolus dose followed by a continuous infusion of 0.3 microg/kg per hour has to be considered the optimal intravenous dose. The higher dose of intravenous clonidine (5 microg/kg) produced better analgesia but the degree of hypotension and sedation was more severe and longer lasting; it required ephedrine administration and careful monitoring of the patient. On the other hand, the bolus of intravenous clonidine 2 microg/kg (group C) was less effective in terms of pain relief but with similar side-effects to the 3 microg/kg dosage (group B).
authors.affiliation: Department of Anaesthesiology and Pain Medicine, University of L'Aquila, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Marinangeli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ciccozzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Donatelli
authors.forename: Alcide
authors.initials: A
authors.lastname: Di Pietro
authors.forename: Giorgio
authors.initials: G
authors.lastname: Iovinelli
authors.forename: Narinder
authors.initials: N
authors.lastname: Rawal
authors.forename: Antonella
authors.initials: A
authors.lastname: Paladini
authors.forename: Giustino
authors.initials: G
authors.lastname: Varrassi
mesh_terms: D000328:Adult; D000700:Analgesics / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D018681:Anesthetics, General / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003000:Clonidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007405:Intervertebral Disc Displacement / Q000601:surgery*; D007796:Laminectomy / Q000009:adverse effects*; D008159:Lumbar Vertebrae / Q000601:surgery*; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects; D010149:Postoperative Pain / Q000188:drug therapy* / Q000503:physiopathology; D012894:Sleep Stages / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D018681:Anesthetics, General; D009020:Morphine; D003000:Clonidine