Efficacy of Repeated Intraperitoneal Administration of Levobupivacaine in Pain and Opioid Consumption After Elective Laparoscopic Cholecystectomy: A Prospective Randomized Placebo-controlled Trial Eleni Melidi, MD,* Artemisia Papadima, MD, PhD,* Aggeliki Pandazi, MD, PhD,w and George Zografos, MD, PhDz Purpose: To estimate the effect of intraperitoneal levobupivacaine on postoperative pain and analgesic requirements, during the first 24 hours after elective laparoscopic cholecystectomy (LC). Materials and Methods: In this prospective, randomized, placebo- controlled study, 73 consecutive patients scheduled for LC were randomized into 2 groups. In the local anesthetic group 36 patients received 10 mL of 0.5% levobupivacaine intraperitoneally at the end of the LC and at 4 hours postoperatively, whereas in the pla- cebo group 37 patients received 10 mL of 0.9% normal saline. Visual analog scale pain scores, analgesic consumption, side-effects, and vital signs were recorded for 24 hours postoperatively. Results: In the local anesthetic group lower visual analog scale pain scores were observed postoperatively, both at rest and at movement (P-values compared with placebo, 0.012 and <0.001, respectively). Fentanyl consumption was greater in the placebo group (P-value <0.001). Conclusions: Intraperitoneal administration of 10 mL 0.5% levo- bupivacaine after LC is effective in reducing postoperative pain and decreasing opioid consumption. Key Words: intraperitoneal, laparoscopic cholecystectomy, local anesthetics, levobupivacaine, pain (Surg Laparosc Endosc Percutan Tech 2016;26:295–300) L aparoscopic cholecystectomy (LC), a minimally access procedure, is the treatment of choice for symptomatic gallstone disease. 1 Although associated with less pain, earlier recovery and hospital discharge compared with the open procedure, the severity of postoperative pain is often still significant. 2 The use of opioids is associated with side effects, such as nausea and vomiting, respiratory depres- sion, and constipation. 3 To avoid these adverse effects, studies have investigated the administration of local anes- thetics (LA) by various routes. Although numerous studies have reported a significant reduction in postoperative pain after the use of intraperitoneal analgesia, others reported no benefit. 4 The primary aim of this study was to determine the efficacy of repeated intraperitoneal levobupivacaine infu- sion on postoperative analgesia and opioid requirements during the first 24 hours after elective LC, as part of a multimodal analgesic approach. Secondary endpoints were assessment of safety of this technique and level of patient overall satisfaction. MATERIALS AND METHODS This study was conducted in the Anesthesiology Department of “Hippocration” General Hospital of Athens and the 1st Propaedeutic University Surgery Department of the Medical School of the National and Kapodistrian University of Athens. The study protocol was approved by the local ethics committee and informed consent was signed by all patients preoperatively. Exclusion criteria were: (1) acute cholecystitis at the time of surgery; (2) conversion to open surgery; (3) American Society of Anesthesiology classification III or IV; (4) change in the anesthesia protocol; (5) patient refusal. All surgical procedures were scheduled for weekday working hours, conducted by the same surgical team and discharge was planned for the morning after surgery. A total of 73 patients were randomized with Bernoulli tables of random sequences to receive 2 separate doses of either 10 mL of 0.5% levobupivacaine intraperitoneally (LA group), or 10 mL of 0.9% normal saline instead (placebo group). The LA group consisted of 36 patients and the placebo group of 37 patients. All patients were premedicated orally with 1.5 mg of bromazepam and 40 mg of omeprazol the night before the operation and 1 hour before the operation. Before induction to anesthesia, all patients received 2.5 mg of midazolam, 4 mg of ondansetron, and 40 mg of parecoxib intravenously (IV). According to the mutual anesthesia protocol, induction to anesthesia was achieved by administrating propofol (2 mg/kg IV) and remifentanil (1 mcg/kg IV). Rocuronium (0.6 mg/kg IV) was then administered as muscle relaxant. Anesthesia was main- tained with sevoflurane in a mixture of O 2 to air (FiO 2 = 50%) and remifentanil in continuous infusion (0.2 to 0.5 mcg/kg/min IV). Meperidine (1 mg/kg, intramuscularly) was administered after induction and Received for publication November 20, 2015; accepted June 2, 2016. From the *Department of Anesthesiology, “Hippocration” General Hospital; w2nd University Department of Anesthesiology, “Attikon” General Hospital; and z1st University Department of Propaedeutic Surgery, “Hippocration” General Hospital, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece. The authors declare no conflicts of interest. Reprints: Eleni Melidi, MD, Department of Anesthesiology, “Hippocration” General Hospital, Gorgopotamou 6, 15341, Agia Paraskevi, Athens, Greece (e-mail: elmelidi@yahoo.gr). Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved. ORIGINAL ARTICLE Surg Laparosc Endosc Percutan Tech  Volume 26, Number 4, August 2016 www.surgical-laparoscopy.com | 295 Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved.