title: Synergistic interaction between fentanyl and bupivacaine given intrathecally for labor analgesia.
abstract: BACKGROUND
  Lipophilic opioids and local anesthetics are often given intrathecally in combination for labor analgesia. However, the nature of the pharmacologic interaction between these drugs has not been clearly elucidated in humans.
  
  
  METHODS
  Three hundred nulliparous women randomly received 1 of 30 different combinations of fentanyl and bupivacaine intrathecally using a combined spinal-epidural technique for analgesia in the first stage of labor. Visual analogue scale pain scores were recorded for 30 min. Response was defined by percentage decrease in pain score from baseline at 15 and 30 min. Dose-response curves for individual drugs were fitted to a hyperbolic dose-response model using nonlinear regression. The nature of the drug interaction was determined using dose equivalence methodology to compare observed effects of drug combinations with effects predicted by additivity.
  
  
  RESULTS
  The derived dose-response models for individual drugs (doses in micrograms) at 15 min were: Effect = 100 × dose / (13.82 + dose) for fentanyl, and Effect = 100 × dose / (1,590 + dose) for bupivacaine. Combinations of fentanyl and bupivacaine produced greater effects than those predicted by additivity at 15 min (P < 0.001) and 30 min (P = 0.015) (mean differences, 9.1 [95% CI, 4.1-14.1] and 6.4 [95% CI, 1.2-11.5] units of the normalized response, respectively), indicating a synergistic interaction.
  
  
  CONCLUSIONS
  The pharmacologic interaction between intrathecal fentanyl and bupivacaine is synergistic. Characterization and quantification of this interaction provide a theoretical basis and support for the clinical practice of combining intrathecal opioids and local anesthetics.
authors.affiliation: From the Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China (W.D.N.K., K.S.K., F.F.N., K.K.L.N., R.S., and A.L.).
authors.forename: Warwick D
authors.initials: WD
authors.lastname: Ngan Kee
authors.forename: Kim S
authors.initials: KS
authors.lastname: Khaw
authors.forename: Floria F
authors.initials: FF
authors.lastname: Ng
authors.forename: Karman K L
authors.initials: KK
authors.lastname: Ng
authors.forename: Rita
authors.initials: R
authors.lastname: So
authors.forename: Anna
authors.initials: A
authors.lastname: Lee
mesh_terms: D000328:Adult; D016362:Analgesia, Obstetrical / Q000379:methods*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000008:administration & dosage*; D002045:Bupivacaine / Q000008:administration & dosage*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage*; D006801:Humans; D007278:Injections, Spinal; D048949:Labor Pain / Q000175:diagnosis / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D011247:Pregnancy; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D005283:Fentanyl; D002045:Bupivacaine