Preoperative epidural ketamine in combination with morphine does not have a clinically relevant intra- and postoperative opioid-sparing effect

In this prospective, randomized, and double-blinded clinical trial, we eval uated the efficacy of preincisional administration of epidural ketamine wit h morphine compared with epidural morphine alone for postoperative pain rel ief after major upper-abdominal surgery. We studied 50 ASA I and III patien ts undergoing major upper-abdominal procedures. These patients were randoml y allocated to one of the two treatment groups: patients in Group 1 receive d epidural morphine 50 mug/ kg, whereas those in Group 2 received epidural ketamine 1 mg/kg combined with 50 mug/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 f or pain assessment observed patients for 48 h after surgery. Additional dos es of epidural morphine were provided when the visual analog scale score wa s more than 4. Analgesic requirements and side effects were compared betwee n the two groups. There were no differences between the two groups with res pect to age, sex, weight, or duration or type of the surgical procedures. T he intraoperative morphine requirement was significantly (P = 0.018) less i n 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 requi rement of analgesia was significantly (P = 0.021) longer (median, 17 h; ran ge, 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 i n 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 develop ed 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 (r educed intraoperative morphine consumption and prolonged time for first req uirement 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.