Intraperitoneal Dextromethorphan and Levo-Bupivacaine Mixture for Reduction of Postoperative Visceral Hyperalgesia and Cytokine Production in Patients Undergoing Laparoscopic Cholecystectomy

Purpose: To assess the efficacy and safety of intraperitoneal administration of a dextromethorphan-levo-bupivacaine mixture in different volumes and doses on hemodynamics, postoperative pain intensity and types, opioid consumption and cytokine levels in patients undergoing elective laparoscopic cholecystectomy.Methods: Seventy-five patients ASA grade I and II undergoing laparoscopic cholecystectomy under general anaesthesia were studied. The patients were allocated into one of three groups according to dose and volume of intraperitoneal^administered mixture: Large volume and dose of dextromethorphan and levo-bupivacaine 0.125% mixture (120ml with90mg of dextromethorphan), small volume and dose of dextromethorphan and levo-bupivacaine 0.125% mixture (60mlwith 45mg of dextromethorphan) and control group in whichlevo-bupivacaine 0.125% 60ml was administered. Intravenouspatient controlled analgesia (I.V. PCA) with morphine wasinitiated and maintained for 24 hours. Pain was assessed for24 hours by visual analogue scale. Stress response to surgery was evaluated by cytokine levels including tumour necrosisfactor a (TNF-a) and interleukin-ip (IL-1P). Side effects, sedation level and morphine consumption were also recorded.Results: Demographic data were similar. Pain intensity(intra-abdominal and shoulder pains) was lower in largevolume and dose of dextromethorphan-levo-bupivacainemixture (LDL) group when compared to other two groups.The addition of dextromethorphan to levo-bupivacaine inlarge volume and dose of dextromethorphan-levo-bupivacainemixture (LDL) and small volume and dose of dextromethorphan-levo-bupivacaine mixture (SDL) groups resulted in better control of pain than intraperitoneal levo-bupivacaine (control group) alone. Shoulder pain was better controlledthan intra-abdominal pain. Postoperative morphine consumptionby I.V-PCA was less in LDL group with decreased numberof repeated requests. TNF-a and I L - l p levels were significantlyless in LDL and SDL groups up to 24 hours postoperativelywhen compared to control group with no significant changes at 12 hours to preoperative levels indicating decreasedstress response to surgery.Conclusion: The use of intraperitoneal large volume and dose of dextromethorphan (90mg) in 120ml of levobupivacaine0.125% resulted in better postoperative controlof pain intensity, opioid consumption and cytokine release in response to surgical stress when compared to either smallvolume and dose of dextromethorphan (45mg) in 60ml oflevo-bupivacaine mixture or levo-bupivacaine 60ml alone.