title: Preoperative epidural ketamine in combination with morphine does not have a clinically relevant intra- and postoperative opioid-sparing effect.
abstract: In this prospective, randomized, and double-blinded clinical trial, we evaluated the efficacy of preincisional administration of epidural ketamine with morphine compared with epidural morphine alone for postoperative pain relief after major upper-abdominal surgery. We studied 50 ASA I and II patients undergoing major upper-abdominal procedures. These patients were randomly allocated to one of the two treatment groups: patients in Group 1 received epidural morphine 50 microg/kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 microg/kg of morphine 30 min before incision. Intraoperative analgesia was provided in addition, with IV morphine, and the requirement was noted. A blinded observer using a visual analog scale for pain assessment observed patients for 48 h after surgery. Additional doses of epidural morphine were provided when the visual analog scale score was more than 4. Analgesic requirements and side effects were compared between the two groups. There were no differences between the two groups with respect to age, sex, weight, or duration or type of the surgical procedures. The intraoperative morphine requirement was significantly (P = 0.018) less in Group 2 patients (median, 6.8 mg; range, 3-15 mg) compared with patients in Group 1 (median, 8.3 mg; range, 4.5-15 mg). The time for the first requirement of analgesia was significantly (P = 0.021) longer (median, 17 h; range, 10-48 h) in Group 2 patients than in Group 1 (median, 12 h; range, 4-36 h). The total number of supplemental doses of epidural morphine required in the first 48 h after surgery was comparable (P = 0.1977) in both groups. Sedation scores were similar in both groups. One patient in Group 2 developed hallucinations after study drug administration. None of the patients in either group developed respiratory depression. Other side effects, such as pruritus, nausea, and vomiting, were also similar in both groups. Although the addition of ketamine had synergistic analgesic effects with morphine (reduced intraoperative morphine consumption and prolonged time for first requirement of analgesia), there was no long- lasting preemptive benefit seen with this combination (in terms of reduction in supplemental analgesia) for patients undergoing major upper-abdominal procedures.
  
  
  CONCLUSIONS
  Ketamine added to epidural morphine given before surgery can decrease postoperative pain by its preemptive effect, opioid potentiation, and prevention of acute opioid tolerance. A single epidural bolus of 1 mg/kg of ketamine with morphine given before major upper-abdominal surgery did not result in a clinically relevant reduction in postoperative pain relief.
authors.affiliation: Department of Anesthesiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 021115, USA. chundhar_@hotmail.com
authors.forename: B
authors.initials: B
authors.lastname: Subramaniam
authors.forename: K
authors.initials: K
authors.lastname: Subramaniam
authors.forename: D K
authors.initials: DK
authors.lastname: Pawar
authors.forename: B
authors.initials: B
authors.lastname: Sennaraj
mesh_terms: D000005:Abdomen / Q000601:surgery; D000328:Adult; D015360:Analgesia, Epidural / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage*; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000768:Anesthesia, General; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007430:Intraoperative Care; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage*; D010149:Postoperative Pain / Q000517:prevention & control*; D011182:Postoperative Care; D011229:Preanesthetic Medication / Q000379:methods*; D011446:Prospective Studies
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D007649:Ketamine; D009020:Morphine