title: Prophylactic use of epidural mepivacaine/morphine, systemic diclofenac, and metamizole reduces postoperative morphine consumption after major abdominal surgery.
abstract: BACKGROUND
  Surgical trauma induces nociceptive sensitization leading to amplification and prolongation of postoperative pain. While preemptive analgesic treatment with numerous agents has been successful in experimental animals, results of human studies remain conflicting. The authors used a multimodal approach for preemptive analgesia before abdominal surgery: diclofenac and metamizole inhibit prostaglandin synthesis, thus influencing peripheral sensitization; epidural local anesthetics induce conduction block, epidural opioids inhibit nociceptive synaptic transmission, and metamizole induces descending inhibition. The interaction of these drugs might suppress spinal nociceptive sensitization and postoperative analgesic demand.
  
  
  METHODS
  One hundred forty-two patients scheduled for major abdominal surgery were randomly assigned to one of three groups and studied prospectively. Epidural catheters in groups 1 and 2 were placed at interspaces T8-T10, the position of the catheter was confirmed by epidurography, and sensory testing after administration of 5 ml mepivacaine 1%. Group 1 received 75 mg intramuscular diclofenac, 1000 mg intravenous metamizole, 5.3 +/- 1 mg epidural morphine, and 15-20 ml mepivacaine 1% 85 +/- 41 min before skin incision. Epidural analgesia was maintained by injections of 0.1 ml.kg-1.h-1 mepivacaine 1%. Group 2 patients received the balanced analgesia regimen before wound closure (221 +/- 86 min after skin incision). Group 3 patients did not receive any study substances. General anesthesia was induced with 5 mg/kg thiopental and 2 micrograms/kg fentanyl and maintained with enflurane and nitrous oxide. Postoperative analgesia consisted of patient-controlled intravenous morphine over 5 days.
  
  
  RESULTS
  Median visual analog scale pain intensities were < 3 cm and did not differ among the groups. Morphine consumption per hour on postoperative day 2 was 0.8 +/- 0.1 mg/h (group 1) < 1.2 +/- 0.1 mg/h (group 2) = 1.1 +/- 0.1 mg/h (group 3) and cumulative morphine consumption (in mg) on the morning of day 5 was 95 +/- 9 (group 1) < 111 +/- 11 (group 2) < 137 +/- 10 (group 3).
  
  
  CONCLUSIONS
  A significant reduction of patient controlled analgesia requirements could be achieved by our preincisional balanced analgesia regimen compared to application before wound closure. The more distinct difference between patients receiving balanced analgesia and those in the control group is based on the analgesic action of the study substances, which lasted about 14 h.
authors.affiliation: Department of Anesthesiology, University of Ulm, Germany.
authors.forename: M G
authors.initials: MG
authors.lastname: Rockemann
authors.forename: W
authors.initials: W
authors.lastname: Seeling
authors.forename: C
authors.initials: C
authors.lastname: Bischof
authors.forename: D
authors.initials: D
authors.lastname: Börstinghaus
authors.forename: P
authors.initials: P
authors.lastname: Steffen
authors.forename: M
authors.initials: M
authors.lastname: Georgieff
mesh_terms: D000005:Abdomen / Q000601:surgery; D000328:Adult; D000368:Aged; D015360:Analgesia, Epidural; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000008:administration & dosage*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004008:Diclofenac / Q000008:administration & dosage*; D004177:Dipyrone / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008619:Mepivacaine / Q000008:administration & dosage*; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D010149:Postoperative Pain / Q000517:prevention & control*; D012119:Respiration / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D000779:Anesthetics, Local; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D004177:Dipyrone; D009020:Morphine; D008619:Mepivacaine