Comparison of the effects of preoperative melatonin or vitamin C administration on postoperative analgesia

Abstract

The analgesic benefit of melatonin and vitamin C as primary or adjuvant agents has been reported in various studies; however, their analgesic effects in the treatment of postoperative pain remain unclear. Thus, we aimed to evaluate the effect of single preoperative dose of oral melatonin or vitamin C administration on postoperative analgesia. In this study, we recruited 165 adult patients undergoing elective major abdominal surgery under general anesthesia. Patients were randomly divided into three equal (n = 55) groups. One hour before surgery, patients received orally melatonin (6 mg) in group M, vitamin C (2 g) in group C, or a placebo tablet in group P. Pain, sedation, patient satisfaction, total morphine consumption from a patient-controlled analgesia device, supplemental analgesic requirement, and the incidence of nausea and vomiting were recorded throughout 24 h after surgery. The mean pain score and total morphine consumption were found significantly lower in both M and C groups compared with group P (p < 0.001). There were no significant differences between group M and C with respect to pain scores (p = 0.117) and total morphine consumption (p = 0.090). Patients requested less supplemental analgesic and experienced less nausea and vomiting in groups M and C compared with group P. In conclusion, preoperative oral administration of 6 mg melatonin or 2 g vitamin C led to a reduction in pain scores, total morphine consumption, supplemental analgesic requirement, and the incidence of nausea and vomiting compared with placebo.

Effect of Melatonin on Postoperative Pain and Perioperative Opioid Use: A Meta‐analysis and Trial Sequential Analysis

“…Figure 1 shows the flow diagram of the selection of included studies. According to the inclusion and exclusion criteria, 15 studies with a total of 1,102 patients were included in the final analysis 15–21,24–31 . The dosage of melatonin ranged from 1 mg to 10 mg.…”

“…The number of subjects in the trials ranged from 33 to 139. Subjects in the studies underwent orthopedic procedures (4 trials 16,21,25,26 ), cataract surgery (4 trials 18,20,28,29 ), elective laparoscopic cholecystectomy (2 trials 17,24 ), total abdominal hysterectomy (2 trials 30,31 ), major abdominal surgery (1 trial 15 ), open prostatectomy (1 trial 19 ), and extraction of the third molars (1 trial 27 ). The detailed information of the included trials is shown in Table 1.…”

“…Four studies 17,26,27,30 were judged to be at low risk of bias in all domains. Ten trials 15,18–21,24,25,28,29,31 had an unclear risk of bias, mostly related to allocation concealment. One trial 16 had a high risk of bias, related to random sequence generation and allocation concealment.…”

“…We defined the postoperative period from the end of the operation to discharge but not more than 72 hours. Three studies 15–17 reported morphine consumption for postoperative analgesic rescue; 4 studies 18–21 recorded intraoperative fentanyl consumption. The equianalgesic dose ratio of fentanyl to morphine was 1:100 in this article 22 .…”

Glutathione and Glutathione-Like Sequences of Opioid and Aminergic Receptors Bind Ascorbic Acid, Adrenergic and Opioid Drugs Mediating Antioxidant Function: Relevance for Anesthesia and Abuse

“…Ascorbic acid is another potentially valuable compound that may protect both glutathione and the glutathione-like regions of opioid and adrenergic receptors [ 122 ]. Indeed, oddly enough, ascorbic acid has been found to have antinociceptive effects at high doses [ 123 , 124 , 125 ], to be an opiate-sparing adjunctive addition to opioid analgesics [ 126 , 127 , 128 ], and to moderate some of the effects of withdrawal in opioid addicts [ 129 , 130 , 131 ]. These effects make sense from the perspective of ascorbic acid and opioids mimicking each other’s binding patterns to glutathione and glutathione-like regions of opioid and aminergic receptors.…”