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      The efficacy and safety of nefopam for pain relief during laparoscopic cholecystectomy : A meta-analysis

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      Author(s): , PhD a , , PhD b , , PhD b , ∗
      Editor(s):
      Publication date (Electronic):
      Journal: Medicine
      Publisher: Wolters Kluwer Health
      Keywords: laparoscopic cholecystectomy, meta-analysis, nefopam, pain management

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          Abstract

          Background:

          Pain control after laparoscopic cholecystectomy (LC) has become an important topic. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of nefopam for pain management after LC.

          Methods:

          PubMed, Medline, Embase, ScienceDirect, and the Cochrane Library were searched up to November 2017 for comparative articles involving nefopam and placebo for reducing postoperative pain after LC. Primary outcomes were postoperative pain scores and opioid consumption. Secondary outcomes were length of hospital stay, opioid-related adverse effects, and postoperative complications. We assessed statistical heterogeneity for each RCT by using a standard Chi 2 test and the I 2 statistic. The meta-analysis was undertaken using Stata 12.0.

          Results:

          A total of 215 patients were analyzed across 4 RCTs. We found that there were significant differences between nefopam and placebo groups regarding the postoperative pain scores and opioid requirements at 6, 12, and 24 hours. Moreover, there was a decreased risk of opioid-related adverse effects in the nefopam groups. No significant differences were identified in terms of the incidence of postoperative complications.

          Conclusion:

          Intravenous nefopam infusion resulted in significant reduction in postoperative pain scores and opioid requirements while decreasing opioid-related adverse effects. Additionally, no increased risk of venous thromboembolism was found. The current evidence suggests that more RCTs will be needed in further investigations.

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          Most cited references22

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          Nefopam blocks voltage-sensitive sodium channels and modulates glutamatergic transmission in rodents.

          Marc Verleye, Nathalie André, Isabelle Heulard … (2004)
          In order to specify the nature of interactions between the analgesic compound nefopam and the glutamatergic system, we examined the effects of nefopam on binding of specific ligands on the three main subtypes ionotropic glutamate receptors: N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), or quisqualic acid (QA) and kainic acid (KA) in rat brain membrane preparations. Functionally, we investigated the effects of nefopam against the seizures induced by agonists of these excitatory glutamate receptors in mice. Since the synaptic release of glutamate mainly depends upon the activation of membrane voltage-sensitive sodium channels (VSSCs), the nature of interactions between nefopam and these ionic channels was studied by evaluating the effects of nefopam on binding of 3H-batrachotoxinin, a specific ligand of the VSSCs in rat brain membrane preparations. The functional counterpart of the binding of nefopam on VSSCs was evaluated by its effects on the 22Na uptake-stimulated by veratridine on human neuroblastoma cells and in the maximal electroshock test in mice. Nefopam showed no affinity for the subtypes of ionotropic glutamate receptors up to 100 microM. On the other hand, nefopam was effective against NMDA, QA and KA induced clonic seizures in mice. Nefopam displaced 3H-batrachotoxinin and inhibited the uptake of 22Na in the micromolar range and it protected mice against electroshock induced seizures. Nefopam may block the VSSCs activity: consequently, at the presynaptic level, this effect led to a reduction of glutamate release and at the postsynaptic level, it led to a decrease of the neuronal excitability following activation of the glutamate receptors.
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            Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection.

            M Gillon, C Josse, O Mimoz … (2001)
            In order to compare the morphine-sparing effect, analgesic efficacy and tolerance of nefopam and propacetamol given at their highest recommended doses, 120 patients undergoing elective hepatic resection were randomly assigned to receive postoperative intravenous patient-controlled analgesia with morphine alone, or in combination with nefopam (20 mg.4 h-1) or propacetamol (2 g.6 h-1). Compared with the control group (43 [7-92] mg), median [range] cumulative morphine consumption for 24 h after the study started was halved in the nefopam group (21 [3-78] mg, p <0.001) and 20% lower in the propacetamol group (35 [6-84] mg, p = 0.15). Analgesia was superior in the nefopam group despite the lower morphine consumption. Adverse effects were comparable in the three groups, except for significantly more nausea in the control group (39% vs. 17 and 26% in the nefopam and propacetamol groups, respectively) and more sweating in the nefopam group (17% vs. 0 and 3% in the control and propacetamol groups, respectively). Overall patient satisfaction was better (p < 0.001) in patients given nefopam (97%) than those receiving morphine alone (82%) or propacetamol (74%).
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              The Effect of Nefopam on Postoperative Fentanyl Consumption: A Randomized, Double-blind Study

              Jee Moon, Sang Choi, Shin Young Lee … (2016)
              Background Nefopam is a non-opioid, non-steroidal, centrally acting analgesic drug. The concomitant use of opioids and nefopam is believed to have many advantages over the administration of opioids alone for postoperative pain management. We conducted a randomized, double-blind study to determine the fentanyl-sparing effect of co-administration of nefopam with fentanyl for postoperative pain management via patient controlled analgesia (PCA). Methods Ninety female patients who underwent laparoscopic total hysterectomy under general anesthesia were randomized into 3 groups, Group A, fentanyl 1,000 µg; Group B, fentanyl 500 µg + nefopam 200 mg; and Group C, fentanyl 500 µg + nefopam 400 mg, in a total volume of 100 ml PCA to be administered over the first 48 h postoperatively without basal infusion. The primary outcome was total fentanyl consumption during 48 h; secondary outcomes included pain scores and incidence of side effects. Results Eighty-one patients were included in the analysis. The overall fentanyl-sparing effects of PCA with concomitant administration of nefopam during the first 48 h postoperatively were 54.5% in Group B and 48.9% group C. Fentanyl use was not significantly different between Groups B and C despite the difference in the nefopam dose. There were no differences among the three groups in terms of PCA-related side effects, although the overall sedation score of Group B was significantly lower than that of Group A. Conclusions The concomitant administration of nefopam with fentanyl for postoperative pain management may allow reduction of fentanyl dose, thereby reducing the risk of opioid-related adverse effects.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Medicine (Baltimore)
                Journal ID (iso-abbrev): Medicine (Baltimore)
                Journal ID (publisher-id): MEDI
                Title: Medicine
                Publisher: Wolters Kluwer Health
                ISSN (Print): 0025-7974
                ISSN (Electronic): 1536-5964
                Publication date Collection: March 2018
                Publication date (Electronic): 09 March 2018
                Volume: 97
                Issue: 10
                Electronic Location Identifier: e0089
                Affiliations
                [a ]Department of Endoscopy Center
                [b ]Department of Gastrointestinal Surgery, China–Japan Union Hospital of Jilin University, Jilin, China.
                Author notes
                [∗ ]Correspondence: Shihou Sheng, Department of Gastrointestinal Surgery, China–Japan Union Hospital of Jilin University, Jilin 130000, China (e-mail: z89999845@ 123456126.com ).
                Article
                Publisher ID: MD-D-17-07244 Accession ID: 00089
                DOI: 10.1097/MD.0000000000010089
                PMC ID: 5882431
                PubMed ID: 29517677
                SO-VID: 4eada9fc-9ca1-4089-8cb8-4d8d4e91c0fd
                Copyright © Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

                History
                Date received : 21 November 2017
                Date revision received : 10 February 2018
                Date accepted : 13 February 2018
                Categories
                Subject: 7100
                Subject: Research Article
                Subject: Systematic Review and Meta-Analysis
                Custom metadata
                OPEN-ACCESS TRUE

                Keywords: laparoscopic cholecystectomy,meta-analysis,nefopam,pain management
                Data availability:
                Keywords: laparoscopic cholecystectomy, meta-analysis, nefopam, pain management

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