The Effect of Nefopam Infusion during Laparascopic Cholecystectomy on Postoperative Pain

Abstract

Background: While recovery from remifentanil is fast due to its rapid metabolism, it can induce hyperalgesia by activation of N-methyl-D-aspartic acid (NMDA) receptors. Therefore, administration of NMDA receptor antagonists such as ketamine is effective in relieving hyperalgesia caused by remifentanil. A previous study showed that nefopam administration before anesthesia combined with low-dose remifentanil reduced pain and analgesic consumption during the immediate postoperative period. We hypothesized that intraoperative infusion of nefopam during laparoscopic cholecystectomy would be as effective as ketamine in controlling pain during the acute postoperative period after sevoflurane and remifentanil based anesthesia.Methods: Sixty patients scheduled to undergo laparoscopic cholecystectomy were randomly divided into three groups. General anesthesia was maintained with sevoflurane and effect-site target concentration of remifentanil (4 ng/ml) in all patients. An intravenous bolus of nefopam (0.3 mg/kg) was given, followed by continuous infusion (65 µg/kg/h) in Group N (n=20). An intravenous bolus of ketamine (0.3 mg/kg) was administered, followed by continuous infusion (180 µg/kg/h) in Group K (n=20), and Group C received a bolus and subsequent infusion of normal saline equal to the infusion received by Group K (n=20). We compared postoperative Visual Analogue Scale (VAS) scores and analgesic requirements over the first 8 postoperative hours between groups.Results: The pain scores (VAS) and fentanyl requirements for 1 h after surgery were significantly lower in the nefopam and ketamine groups compared with the control group (p<0.05). There were no differences between the nefopam and ketamine groups. The three groups showed no differences in VAS scores and number of analgesic injections from 1 to 8 h after surgery.Conclusion: Intraoperative nefopam infusion during laparoscopic cholecystectomy reduced opioid requirements and pain scores (VAS) during the early postoperative period after remifentanil-based anesthesia.

<p>The Antiallodynic Effect of Nefopam on Vincristine-Induced Neuropathy in Mice</p>

“…22 Nefopam is a non-opioid, non-steroidal benzoxazocinederived analgesic that inhibits monoamine reuptake in the central nervous system. 25,26 It indirectly modulates the NMDA receptor, inhibiting c-Fos expression in the dorsal horn of the spinal cord and relieving allodynia in rats. 11 Nefopam was first introduced as an antidepressant and anticonvulsant and was then reported to be efficacious in postsurgical hyperalgesia.…”

Why mu‐opioid agonists have less analgesic efficacy in neuropathic pain?

“…Dexmedetomidine, a selective α 2 ‐adrenergic agonist, also reduced opioid‐induced hyperalgesia in rats (Yuan et al., ; Zheng et al., ) and humans (Lee, Kim, & Kim, ) by potentiating noradrenergic inhibition in the spinal cord. Nefopam, a monoamine reuptake inhibitor, successfully opposed the hyperalgesic effects of opioids in humans (Choi et al., ; Kim et al., ). These results suggest the clinical interest of using drugs that modulate the activity of NMDA receptors and monoamine system to disrupt sensitization processes underlying pain hypersensitivity, and consequently restoring the analgesic efficacy of opioid agonists under neuropathic pain conditions.…”

Nefopam and its Role in Modulating Acute and Chronic Pain

“…Intravenous administered Nefopam determines a strong inhibition of the nociceptive flexion reflex in humans [21]. Studies has shown that it has opioid-sparing effects (it reduces de opioid consumption after cholecystectomy [22], cardiac surgery [11], upper and lower abdominal surgery [23,24], hysterectomy [25], palliative interventions [26,27], breast cancer surgery [28], nasal surgery, orthopedic interventions [29,30], by 30-40% [2] and that 20 mg of Nefopam is equipotent with almost 6-12 mg Morphine and 50 mg of Meperidine [31] having the same analgesic potency as nonsteroidal anti-inflammatory drugs.…”