title: Combinations of morphine with ketamine for patient-controlled analgesia: a new optimization method.
abstract: BACKGROUND
  According to previous studies, the addition of ketamine to morphine for intravenous patient-controlled analgesia (PCA) may be beneficial. The authors developed and applied a new model to optimize the combination of morphine, ketamine, and a lockout interval for PCA after lumbar spine and hip surgery.
  
  
  METHODS
  One-hundred two patients undergoing lumbar spine or hip surgery participated in the study. The analgesic effect of PCA during 48 h after surgery was optimized under restrictions dictated by side effects. Initially, eight combinations of morphine, ketamine (expressed as drug concentration in the solution administered), and a lockout interval (i.e., minimal allowed time between two consecutive PCA boluses) were empirically chosen and investigated. To determine subsequent combinations, an optimization model was applied until three consecutive steps showed no decrease in pain score.
  
  
  RESULTS
  The authors analyzed 12 combinations with an allowed morphine and ketamine range in a PCA solution of 0-2 mg/ml and a lockout interval range of 5-12 min. During the optimization procedure, a reduction in mean pain scores with a low incidence of side effects was observed. The procedure converged to a morphine-to-ketamine ratio of 1:1 and a lockout interval of 8 min.
  
  
  CONCLUSIONS
  Using a novel method to analyze drug combinations, the study supports combinations of morphine with ketamine in a ratio of 1:1 and a lockout interval of 8 min for postoperative PCA following spine and hip surgery.
authors.affiliation: Department of Anesthesiology, Inselspital, 3010 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: Martin
authors.initials: M
authors.lastname: Luginbühl
authors.forename: Michele
authors.initials: M
authors.lastname: Curatolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016058:Analgesia, Patient-Controlled / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage; D019644:Arthroplasty, Replacement, Hip; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D010149:Postoperative Pain / Q000517:prevention & control; D013131:Spine / Q000601:surgery*
chemical_list: D000700:Analgesics; D007649:Ketamine; D009020:Morphine