Relative Contributions of Intraoperative Low Dose Ketamine, Lidocaine and Ketamine-Lidocaine Combination in Addition to Intrathecal Morphine for Postoperative Analgesia in Open Liver Resection: A Prospective, Randomized, Four-Arm, Triple Blind, Placebo-Controlled Trial

Background and Aims: Open liver resection requiring an upper abdominal incision is associated with significant opioid use due to postoperative pain. We tested the hypothesis that the intraoperative combination of low dose lidocaine and ketamine would reduce opioid consumption when given in conjunction with intrathecal morphine for liver resection surgery. Methods: In this triple blind, parallel group four-arm placebo-controlled trial, we randomized 124 adult ASA 2 - 4 liver resection patients to receive intraoperative lidocaine 0.33 mg/kg/h (group L), ketamine 70 μg/kg/h (group K), combination of lidocaine 0.33 mg/kg/h and ketamine 70 μg/kg/h (group KL) and saline (group P). All patients received 300 μg intrathecal morphine prior to induction of anesthesia. All infusions were started immediately after intubation and continued until the end of surgery. Primary outcome measurements included opioid consumption at 24-hours. Secondary outcomes included pain scores, opioid consumption at 48 and 72-hours and side effects including nausea, vomiting, dizziness, hallucinations, headaches and signs of local anaesthetic toxicity. Patients were followed up for 12 weeks. Results: There was no difference in the primary outcome of opioid consumption within all 4 groups at rest or movement at 24-hours. Secondary outcome of 48-hour rest pain score was significantly higher in the L group (p = 0.03) but without any difference in opioid use. There was no difference in any other outcomes between the groups at any time points. Conclusions: Low dose lidocaine and its combination with ketamine did not add any analgesic/morphine sparing benefit in the presence of single dose intrathecal morphine in patients with major liver resection.