title: Combinations of bupivacaine, fentanyl, and clonidine for lumbar epidural postoperative analgesia: a novel optimization procedure.
abstract: BACKGROUND
  The authors developed and applied a method to optimize the combination of bupivacaine, fentanyl, and clonidine for continuous postoperative lumbar epidural analgesia.
  
  
  METHODS
  One hundred eighteen patients undergoing knee or hip surgery participated in the study. Postoperative epidural analgesia during 48 h after surgery was optimized under restrictions dictated by side effects. Initially, eight combinations of bupivacaine, fentanyl, and clonidine (expressed as drug concentration in the solution administered) were empirically chosen and investigated. To determine subsequent combinations, an optimization model was applied until three consecutive steps showed no decrease in pain score. For the first time in a clinical investigation, a regression model was applied when the optimization procedure led to combinations associated with unacceptable side effects.
  
  
  RESULTS
  The authors analyzed 12 combinations with an allowed bupivacaine concentration range of 0-2.5 mg/ml, a fentanyl concentration range of 0-5 microg/ml, and a clonidine concentration range of 0-5 microg/ml. The best combinations of bupivacaine, fentanyl, and clonidine concentrations were 1.0 mg/ml-1.4 microg/ml-0.5 microg/ml, 0.9 mg/ml-3.0 microg/ml-0.3 microg/ml, 0.6 mg/ml-2.5 microg/ml-0.8 microg/ml, and 1.0 mg/ml-2.4 microg/ml-1.0 microg/ml, respectively, all producing a similarly low pain score. The incidence of side effects was low. The application of the regression model to combinations associated with high incidence of motor block successfully directed the optimization procedure to combinations within the therapeutic range.
  
  
  CONCLUSIONS
  The results support further study of the combinations of bupivacaine, fentanyl, and clonidine mentioned above for postoperative analgesia after knee and hip surgery. This novel optimization method may be useful in clinical research.
authors.affiliation: Division of Pain Therapy, Department of Anesthesiology, Inselspital, Bern, Switzerland. gorazd.sveticic@insel.ch
authors.forename: Gorazd
authors.initials: G
authors.lastname: Sveticic
authors.forename: Andrea
authors.initials: A
authors.lastname: Gentilini
authors.forename: Urs
authors.initials: U
authors.lastname: Eichenberger
authors.forename: Eleonora
authors.initials: E
authors.lastname: Zanderigo
authors.forename: Valentina
authors.initials: V
authors.lastname: Sartori
authors.forename: Martin
authors.initials: M
authors.lastname: Luginbühl
authors.forename: Michele
authors.initials: M
authors.lastname: Curatolo
mesh_terms: D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015360:Analgesia, Epidural / Q000009:adverse effects; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002045:Bupivacaine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006615:Hip / Q000601:surgery; D006801:Humans; D007717:Knee / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009407:Nerve Block; D019637:Orthopedic Procedures; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*; D012044:Regression Analysis
chemical_list: D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D004338:Drug Combinations; D003000:Clonidine; D005283:Fentanyl; D002045:Bupivacaine