title: The combination of epidural clonidine and S(+)-ketamine did not enhance analgesic efficacy beyond that for each individual drug in adult orthopedic surgery.
abstract: OBJECTIVE
  To evaluate the benefit of epidural clonidine and S(+)-ketamine combination through the epidural route in adult orthopedic surgery.
  
  
  METHODS
  Randomized double-blinded study.
  
  
  METHODS
  Teaching hospital.
  
  
  METHODS
  Scheduled to undergo knee surgery, 56 American Society of Anesthesiologists physical status 1 and 2 adult patients.
  
  
  METHODS
  Patients were randomized to 1 of 4 groups to receive the combined epidural-intrathecal technique. A 10-mL epidural injection of either study drug or normal saline was first administered to all patients. Intrathecal anesthesia was performed with 15 mg of bupivacaine. The control group (CG) received epidural saline. The 0.1-mg/kg S(+)-ketamine epidural group received 0.1 mg/kg epidural S(+)-ketamine. The 0.5-microg/kg clonidine epidural group received 0.5 microg/kg epidural clonidine. The S(+)-ketamine/clonidine group received 0.1 mg/kg epidural S(+)-ketamine plus 0.5 microg/kg epidural clonidine.
  
  
  RESULTS
  Pain and adverse effects were evaluated by visual analog scale. Rescue analgesics were available to patients. The groups were demographically similar. Sensory level to pinprick, surgical and anesthetic time, and visual analog scale scores for pain at first rescue medication were similar among the groups. The time to first rescue analgesic (minute) was lowest in CG (P < .005). The CG required more rescue analgesics in 24 hours than any of the other groups (P < .0005). Patients who received either epidural clonidine, S(+)-ketamine, or both displayed similar analgesia. The frequency of adverse effects was similar among groups (P > .05).
  
  
  CONCLUSIONS
  The association of epidural clonidine or S(+)-ketamine did not result in a greater analgesic effect in the model of acute postoperative pain studied, although the interaction of epidural clonidine and S(+)-ketamine is not attributable to sharing of a common second messenger system.
authors.affiliation: Department of Biomechanic, Medicine and Rehabilitation of the Locomotor Members, Teaching Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo 14015 110, Brazil. grlauret@fmrp.usp.br
authors.forename: Gabriela R
authors.initials: GR
authors.lastname: Lauretti
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Rodrigues
authors.forename: Cleber A J
authors.initials: CA
authors.lastname: Paccola
authors.forename: Anita L
authors.initials: AL
authors.lastname: Mattos
mesh_terms: D000328:Adult; D000368:Aged; D015360:Analgesia, Epidural; D000700:Analgesics / Q000008:administration & dosage*; D003000:Clonidine / Q000008:administration & dosage*; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures; D010149:Postoperative Pain / Q000188:drug therapy
chemical_list: D000700:Analgesics; D007649:Ketamine; D003000:Clonidine