title: A direct search procedure to optimize combinations of epidural bupivacaine, fentanyl, and clonidine for postoperative analgesia.
abstract: BACKGROUND
  The authors applied an optimization model (direct search) to find the optimal combination of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate for continuous postoperative epidural analgesia.
  
  
  METHODS
  One hundred ninety patients undergoing 48-h thoracic epidural analgesia after major abdominal surgery were studied. Combinations of the variables of bupivacaine dose, fentanyl dose, clonidine dose, and infusion rate were investigated to optimize the analgesic effect (monitored by verbal descriptor pain score) under restrictions dictated by the incidence and severity of side effects. Six combinations were empirically chosen and investigated. Then a stepwise optimization model was applied to determine subsequent combinations until no decrease in the pain score after three consecutive steps was obtained.
  
  
  RESULTS
  Twenty combinations were analyzed. The optimization procedure led to a reduction in the incidence of side effects and in the mean pain scores. The three best combinations of bupivacaine dose (mg/h), fentanyl dose (microg/h), clonidine dose (microg/h), and infusion rate (ml/h) were: 9-21-5-7, 8-30-0-9, and 13-25-0-9, respectively.
  
  
  CONCLUSIONS
  Given the variables investigated, the aforementioned combinations may be the optimal ones to provide postoperative analgesia after major abdominal surgery. Using the direct search method, the enormous number of possible combinations of a therapeutic strategy can be reduced to a small number of potentially useful ones. This is accomplished using a scientific rather than an arbitrary procedure.
authors.affiliation: Department of Anesthesiology, University of Bern, Inselspital, Switzerland. michele.curatolo@insel.ch
authors.forename: M
authors.initials: M
authors.lastname: Curatolo
authors.forename: T W
authors.initials: TW
authors.lastname: Schnider
authors.forename: S
authors.initials: S
authors.lastname: Petersen-Felix
authors.forename: S
authors.initials: S
authors.lastname: Weiss
authors.forename: C
authors.initials: C
authors.lastname: Signer
authors.forename: P
authors.initials: P
authors.lastname: Scaramozzino
authors.forename: A M
authors.initials: AM
authors.lastname: Zbinden
mesh_terms: 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*; D000768:Anesthesia, General; 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*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy*
chemical_list: D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D004338:Drug Combinations; D003000:Clonidine; D005283:Fentanyl; D002045:Bupivacaine