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Background: Surgical and laparoscopic techniques are two different methods for the removal of gall bladder. Today, laparoscopic cholecystectomy is a preferred method for short-term hospitalization and early return to function related to minimal invasive surgical technique. However, patients still complain of significant postoperative pain, secondary inflammation of the diaphragm and the nociceptive genus of the annoying membrane's peritoneum. Multimodal analgesia is necessary for managing pain after laparoscopic cholecystectomy. Magnesium sulfate is a new emerging medication for the management of acute pain. There are no previous reports to compare the analgesic effect of intraperitoneal instillation of bupivacaine plus morphine hydrochloride and bupivacaine plus magnesium sulfate for postoperative pain after laparoscopic cholecystectomy. Aim: The purpose of this study is to compare the analgesic effect of intraperitoneal instillation of bupivacaine plus morphine hydrochloride versus bupivacaine plus magnesium sulfate in patients undergoing laparoscopic cholecystectomy under general anesthesia for better pain relief and less opioid consumption during the first 24 hours. Methods: Following the approval of the Institutional Review Board of An-Najah National University and written informed consent from patients undergoing laparoscopic cholecystectomy, hundred patients between 18 and 60 years old, American Society of Anesthesiologist (ASA) Grades I and II, were randomized to one of the following groups by the sealed envelope: (Mo group) (n=50) receiving intraperitoneal instillation of 30 ml 0.25% bupivacaine and 3 mg morphine and (Mg group) (n=50) receiving intraperitoneal instillation of 0.25% bupivacaine plus 50 mg/kg magnesium sulfate to a total volume of 30 ml. Medications were given after peritoneal wash and suctioning through intraperitoneal instillation. A drug solution is prepared by a doctor who does not participate in the study. All patients received the same anesthesia method, general anesthesia was administered. The induction protocol was standard for all patients. Patients were monitored for electrocardiogram (ECG), heart rate, blood oxygenation (SpO2%) and noninvasive blood pressure (NIBP). Postoperative pain was evaluated using visual analog scale (pain score of 0-10). The participants were evaluated for 24 hours after the operation with the registration of abdominal pain. The postoperative pain outcome was reported at 0 and 30 min, 1, 4, 8, 12, 16 and 24 hours. The cut-off value for VAS is 4 for indication of rescue medication. At VAS ≥ 4, rescue analgesics were administered on request (20 mg of pethidine) intravenously in Post Anesthetic Care Unit (PACU) and 50 mg intramuscularly in the surgical ward. Results: Patients' characteristics of age, gender and BMI were comparable in the two groups. There was no significant difference between the groups regarding the duration of the surgery. The demographic parameters (age, gender and BMI) have no effect on the mean of VAS (p value>0.05). There are significant differences between Mo and Mg groups in the total VAS score (p value<0.05). In the Mo group, the mean of total VAS (2.09) was significantly lower than the mean of total VAS in the Mg group (2.71); which means that patients in the Mo group had significantly less intensity of pain than patients in the Mg group (p=0.006). There is a significant difference between the number (percent) of patients complaining of moderate to severe postoperative pain in Mo group 15/50 (30%) compared to Mg group 25/50 (50%) (p=0.0423). When estimating the size of the treatment effect of morphine hydrochloride plus bupivacaine, found that the relative risk reduction of moderate to severe pain postoperatively is 0.40. There is also a significant difference between the number (percent) of patients complained of drowsiness in Mo Group 7/50 (14%) compared to Mg group 18/50 (36%) (p=0.0115). There are no significant differences between the two study groups regarding nausea, vomiting, dizziness and urinary retention. Patients in Mo group consume less rescue analgesic dose M (± SD) (64.29 mg+22.04) compared to patients in Mg group M (± SD) (74.40 mg+25.67) without significant relationship between both doses (p-value=0.163). Blood pressure, heart rate and oxygen saturation were examined as hemodynamic parameters. The result showed that no significant relationship between these parameters and VAS (p-value>0.05). Conclusion: Intraperitoneal instillation of combination of bupivacaine with morphine hydrochloride is superior to bupivacaine plus magnesium sulfate to reduce the intensity and incidence of postoperative pain in patients undergoing laparoscopic cholecystectomy surgery without significant increase of side effects. This peripheral effect of opioid provides a new approach to pain relief that can have major clinical benefits. Recommendation: Based on the results of this study, it is recommended to consider the intraperitoneal instillation of morphine hydrochloride with bupivacaine as a standard application for laparoscopic cholecystectomy surgery to reduce postoperative pain.

international journal of anesthesiology and pain medicine

Comparison of Intra-Peritoneal Instillation of Bupivacaine and Morphine Hydrochloride versus Bupivacaine and Magnesium Sulfate for Post-Operative Pain Relief after Laparoscopic Cholecystectomy, A Randomized Double-Blind Comparison Study