Analgesic effect of preoperative melatonin and vitamin C administration, alone or in combination, in major abdominal surgery; a randomized controlled study

Background & objectives: Several studies have shown that melatonin and vitamin C used as an analgesic adjuvant, can spare opioid use, resulting in a better analgesic profile with fewer adverse effects and shorter hospital stay. However, we found no studies which might have investigated the impact of a combination of both. We compared the effect of melatonin, vitamin C, and their combination on postoperative opioid consumption. Methodology: Sixty patients scheduled for major abdominal surgeries were randomly allocated into three equal groups with 20 patients in each; melatonin group (Group M), vitamin C (Group C), and combined melatonin and vitamin C (Group CM). Two hours before surgery, all patients received the study medications orally, which was continued for 3 days postoperative at the same time of the first administration; Group M received 10 mg of melatonin, Group C received 1 gm of vitamin C, and Group MV received both melatonin (10 mg) and vitamin C (1 gm). The primary outcome was the total morphine consumption in 24 hours postoperatively, with patients, pain scores as measured by Numeric Pain Rating Scale (NPRS), the incidence of postoperative nausea and vomiting (PONV), and postoperative chronic pain as secondary outcomes. Results: Postoperative morphine consumption (in the first 24 hours) was significantly lower in Group CM (16.7 ± 2.4 mg) than in Group M (20.98 ± 1.38 mg), and Group C (24.36 ± 3.12 mg) (P < 0.001). Group CM showed lower pain scores, decreased incidence of PONV, and a longer time to first request for analgesics. However, lower sedation scores were observed. There was no statistical difference among all groups regarding post-operative chronic pain incidence. Conclusion: Combined use of melatonin and vitamin C in patients undergoing major abdominal surgery with mid-line incision provides a synergistic analgesic effect for the postoperative pain management with lower postoperative pain scores, less opioid consumption, and lower incidence of PONV compared to the use of any one of these. Abbreviations: CPSP: Chronic Post-Surgical Pain, NPRS: Numeric Pain Rating Scale, PONV: postoperative nausea and vomiting, TAHBSO: Total Abdominal Hysterectomy with Bilateral Salpingo-Oophorectomy Keywords: Melatonin; major abdominal surgery; Numeric Pain Rating Scale; opioid consumption; postoperative pain; PONV; vitamin C. Citation: Abdelhakim AK, Shaker DSM, Hamimy WI, Attalla MA, Radwan KG, Abdelhady AKM. Anaesth. pain intensive care 2025;29(3):556-664. DOI: 10.35975/apic.v29i3.2790 Received: January 03, 2025; Revised: March 12, 2025; Accepted: March 22, 2025