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Background and Objectives : Kidney transplantation (KT) is an important treatment modality for renal failure. However, moderate-to-severe pain often occurs in KT recipients. Multimodal analgesia using combined analgesic measures has been recommended to enhance postoperative recovery. This retrospective study explored the additional analgesic efficacy of paracetamol and nefopam infusions in living-donor KT recipients who received a transversus abdominis plane (TAP) block. Materials and Methods : Consecutive living-donor KT recipients at our institute between January 2020 and March 2022 were divided into groups that received a TAP block with paracetamol and nefopam infusions (Group TA) or a TAP block without analgesics (Group T) during surgery. Following propensity-score (PS) matching, 103 patients were included in each group. Postoperative pain intensity assessed using the visual analog scale (VAS), opioid consumption via patient-controlled analgesia (PCA) devices over 24 h, and postoperative outcomes were compared between the two groups. Results : VAS pain intensity at rest was lower in group TA than in group T at 1 and 6 h after surgery [1 h: 29 (15-41) vs. 41 (29-51) mm, p < 0.001; 6 h: 32 (23-43) vs. 40 (32-54) mm, p < 0.001]. The VAS pain intensity during coughing was lower in group TA [1 h: 46 (30-58) vs. 59 (48-69) mm, p < 0.001; 6 h: 51 (40-63) vs. 60 (45-71) mm, p < 0.001]. Moreover, PCA consumptions during the first 6 h and between 6-24 h post-surgery was significantly lower in group TA. Other postoperative outcomes did not differ between the two groups. Conclusions : Multimodal analgesia with intraoperative paracetamol and nefopam infusions improved postoperative pain control in living-donor KT recipients who received a preoperative TAP block. Our findings demonstrate the efficacy of paracetamol and nefopam infusions in KT recipients.

The present study investigates the utilization of a supramolecular deep eutectic solvent (SUPRADES), consisting of sulfated-β-cyclodextrin (S-β-CD) and citric acid (CA), as a chiral selector (CS) in capillary electrophoresis for the enantiomeric separation of nefopam (NEF) and five cathinone derivatives (3-methylmethcathinone [3-MMC], 4-methylmethcathinone [4-MMC], 3,4-dimethylmethcathinone [3,4-DMMC], 4-methylethcathinone [4-MEC], and 3,4-methylendioxycathinone [MDMC]). A significant improvement in enantiomeric separation of the target analytes was observed upon the addition of S-β-CD-CA to the background electrolyte (BGE), leading to a baseline separation of all analytes. In particular, the optimum percentage of S-β-CD-CA, added to the BGE, was determined to be 0.075% v/v for NEF (R s  = 1.5) and 0.050% v/v for three out of five cathinone derivatives (R s  = 1.5, 1.6, and 2.4 for 3-MMC, 4-MEC, and 3,4-DMMC, respectively). In the case of 4-MMC and MDMC, a higher percentage of the CS, equal to 0.075% and 0.10% v/v, respectively, was required to achieve baseline separation (R s  = 1.5, 1.9 for MDMC and 4-MMC, respectively). The outcomes of the present study highlight the potential effectiveness of using SUPRADES as a CS in electrophoretic enantioseparations., (© 2024 The Author(s). Electrophoresis published by Wiley‐VCH GmbH.)

Pain is a common public health problem and remains as an unmet medical need. Currently available analgesics usually have limited efficacy or are accompanied by many adverse side effects. To achieve satisfactory pain relief by multimodal analgesia, new combinations of nefopam and gabapentinoids (pregabalin/gabapentin) were designed and assessed in inflammatory, osteoarthritis and neuropathic pain. Isobolographic analysis was performed to analyze the interactions between nefopam and gabapentinoids in carrageenan-induced inflammatory pain, mono-iodoacetate-induced osteoarthritis pain and paclitaxel-induced peripheral neuropathic pain in mice. The anti-inflammatory effect and motor performance of monotherapy or their combinations were evaluated in the carrageenan-induced inflammatory responses and rotarod test, respectively. Nefopam (1, 3, 5, 10, 30 mg/kg, p.o.), pregabalin (3, 6, 12, 24 mg/kg, p.o.) or gabapentin (25, 50, 75, 100 mg/kg, p.o.) dose-dependently reversed mechanical allodynia in three pain models. Isobolographic analysis indicated that the combinations of nefopam and gabapentinoids exerted synergistic anti-nociceptive effects in inflammatory, osteoarthritis, and neuropathic pain mouse models, as evidenced by the experimental ED 50 (median effective dose) falling below the predicted additive line. Moreover, the combination of nefopam-pregabalin/gabapentin alleviated carrageenan-induced inflammation and edema, and also prevented gabapentinoids-related sedation or ataxia by lowering their effective doses. Collectively, the co-administration of nefopam and gabapentinoids showed synergistic analgesic effects and may result in improved therapeutic benefits for treating pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Multimodal analgesia is central to pain management after total knee arthroplasty (TKA). This study aimed to evaluate the efficacy of adding oral nefopam to multimodal analgesia for post-TKA pain management., Methods: In this prospective, double-blind, placebo-controlled, randomized trial, 100 patients who underwent TKA at our hospital were randomized to either the nefopam or the control group. After surgery, patients in the nefopam group received 200 mg of celecoxib, 150 mg of pregabalin, and 40 mg of nefopam twice daily to control postoperative pain. Patients in the control group received 200 mg of celecoxib, 150 mg of pregabalin, and a placebo. Oxycodone hydrochloride (10 mg) was used as the rescue analgesic. If the pain remained poorly controlled, 10 mg of morphine hydrochloride was injected subcutaneously as a secondary rescue analgesic. The primary outcome was the postoperative consumption of oxycodone and morphine as rescue analgesics. Secondary outcomes were postoperative pain assessed using the visual analogue scale (VAS), functional recovery assessed by the range of knee motion and ambulation distance, time until hospital discharge, indicators of liver function, and complication rates., Results: Patients in the nefopam group had significantly lower postoperative oxycodone and morphine consumption within 24 hours after surgery and during hospitalization, lower VAS pain scores at rest and during motion within 24 h after surgery, better functional recovery on postoperative days 1 and 2, and a shorter hospital stay. However, the absolute reduction in 0 to 24 h opioid consumption, VAS pain scores, and knee range of motion did not exceed the reported minimal clinically important difference. Both groups had similar indicators of liver function and complication rates., Conclusions: Adding oral nefopam to multimodal analgesia resulted in statistically significant improvements in opioid consumption, VAS pain scores, and functional recovery. However, the amount of improvement may not be clinically important., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Nefopam and propacetamol are the most commonly used analgesics in postoperative multimodal analgesic regimens. Distinct mechanisms are involved in each drug's anti-nociceptive effects. No studies have compared pain relief efficacy between the two drugs in patients undergoing transplantation surgery. Here, we investigated whether the administration of nefopam or propacetamol to healthy living kidney donors who underwent rectus sheath block (RSB) for parietal pain could reduce the subsequent opioid dose necessary to produce adequate analgesia., Methods: This prospective, randomized controlled trial included 72 donors undergoing elective hand-assisted living donor nephrectomy into two groups: propacetamol (n = 36) and nefopam (n = 36). Intraoperative RSB was performed in all enrolled donors. The primary outcome was the total volume of intravenous opioid-based patient-controlled analgesia (PCA) used on postoperative day 1 (POD 1). Additionally, the Numeric Rating Scale scores for flank (visceral) and umbilicus (parietal) pain at rest and during coughing were compared, and the Korean adaptation of the Quality of Recovery-15 Questionnaire (QoR-15 K) was evaluated on POD 1., Results: Both groups had similar preoperative and intraoperative characteristics. On POD 1, the total amount of PCA infusion was significantly lower in the nefopam group than in the propacetamol group (44.5 ± 19.3 mL vs. 70.2 ± 29.0 mL; p < 0.001). This group also reported lower pain scores at the flank and umbilical sites and required fewer rescue doses of fentanyl in the post-anesthesia care unit. However, pain scores and fentanyl consumption in the ward were comparable between groups. The QoR-15 K scores were similar between groups; there were substantial improvements in breathing, pain severity, and anxiety/depression levels in the nefopam group. The incidences of postoperative complications, including sweating and tachycardia, were similar between groups., Conclusion: Compared with propacetamol, nefopam provides a greater analgesic effect for visceral pain and enhances the effects of blocks that reduce the opioid requirement in living kidney donors with parietal pain managed by RSB., Trial Registration: The trial was registered prior to patient enrollment in the clinical trial database using the Clinical Research Information Service (registration no. KCT0007351 , Date of registration 03/06/2022)., (© 2024. The Author(s).)

Background: Video-assisted thoracoscopic surgery (VATS) is a minimally invasive procedure. However, some patients still experience severe pain after VATS. Pain after VATS can disturb deep breathing and coughing, and can increase postoperative pulmonary complications. Therefore, multidisciplinary pain management is emphasized for enhanced recovery after VATS. Nefopam is a centrally-acting, non-opioid, non-steroidal analgesic drug, and its pain reduction effect in many surgeries has been reported. We sought to determine whether administration of nefopam is effective as multimodal analgesia in VATS., Methods: This study enrolled patients aged 19 years or older, and scheduled for elective VATS lobectomy with American Society of Anesthesiologists (ASA) physical class I-III. Forty-six participants were randomly divided into a group receiving nefopam (group N), and a control group (group O) in a 1:1 ratio. The study participants, and the researcher collecting the data were blinded to the group allocation. For the group N, nefopam 20 mg was administered before surgical incision and also at the end of surgery while chest tube was inserted. For the group O, normal saline 100 mL was administered. The primary outcome of this study was the pain score, by verbal numerical rating scale, at rest and upon coughing., Results: Forty-five participants (group N =22, group O =23) were involved in the statistical analysis. Nefopam reduced pain at rest at 0 h [8 (IQR, 5-10) vs . 4 (IQR, 2-7), P=0.01], and at 0-1 h [5 (IQR, 5-8) vs . 3 (IQR, 2-5), P=0.001]. Pain upon coughing decreased with nefopam at 0 h [9 (IQR, 6-10) vs . 6 (IQR, 2-8), P=0.009], 0-1 h [6 (IQR, 5-8) vs . 5 (IQR, 2-6), P=0.001], and at 12-24 h [4 (IQR, 3-7) vs . 3 (IQR, 1-4), P=0.03]. Injection of 20 mg of nefopam before incision and at the end of surgery relieved postoperative pain at 0 h, 1 h at rest and at 0 h, 1 h, 12-24 h with coughing after VATS., Conclusions: Therefore, nefopam can serve as a useful component of multimodal analgesia for pain management after VATS., Trial Registration: ClinicalTrials.gov (NCT05173337)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-30/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background/Objectives : Immediate breast reconstruction surgery (BRS) often leads to significant postoperative pain, necessitating effective analgesia. This study aimed to compare the analgesic efficacy of patient-controlled analgesia (PCA) containing nefopam with that of PCA containing opioids alone in patients undergoing BRS. Methods : A prospective, double-blind, randomized controlled trial was conducted on 120 patients undergoing immediate BRS after mastectomy. Patients were randomly allocated to receive PCA with fentanyl alone (Group F: fentanyl 10 mcg/kg), fentanyl and nefopam (Group FN: fentanyl 5 mcg/kg + nefopam 1 mg/kg), or nefopam alone (Group N: nefopam 2 mg/kg). Pain intensity (expressed in VASr and VASm), opioid consumption, and opioid-related complications were assessed. Results : PCA with nefopam, either alone or in combination with opioids, demonstrated non-inferior analgesic efficacy compared to PCA with fentanyl alone. At 24 h postoperatively, the VASr scores were 2.9 ± 1.0 in Group F, 3.1 ± 1.2 in Group FN, and 2.8 ± 0.9 in Group N ( p = 0.501). At the same timepoint, the VASm scores were 4.1 ± 1.2 in Group F, 4.5 ± 1.5 in Group FN, and 3.8 ± 1.4 in Group N ( p = 0.129). Significant differences among the three groups were observed at all timepoints except for PACU in terms of the total opioid consumption ( p < 0.0001). However, there were no significant differences in opioid-related complications among the three groups. Conclusions : PCA with nefopam, whether alone or in combination with opioids, offers non-inferior analgesic efficacy compared to PCA with fentanyl alone in patients undergoing immediate BRS.

Background and Objectives : This study explored how nefopam, a non-opioid analgesic in a multimodal regimen, impacts postoperative pain, opioid use, and recovery quality in single-port robot-assisted laparoscopic cholecystectomy (RALC) patients with a parietal pain block, addressing challenges in postoperative pain management. Materials and Methods : Forty patients scheduled for elective single-port RALC were enrolled and randomized to receive either nefopam or normal saline intravenously. Parietal pain relief was provided through a rectus sheath block (RSB). Postoperative pain was assessed using a numeric rating scale (NRS) in the right upper quadrant (RUQ) of the abdomen, at the umbilicus, and at the shoulder. Opioid consumption and recovery quality, measured using the QoR-15K questionnaire, were also recorded. Results : The 40 patients had a mean age of 48.3 years and an average body mass index (BMI) of 26.2 kg/m 2 . There were no significant differences in the pre- or intraoperative variables between groups. Patients receiving nefopam reported significantly lower RUQ pain scores compared to the controls, while the umbilicus and shoulder pain scores were similar. Rescue fentanyl requirements were lower in the nefopam group in both the PACU and ward. The QoR-15K questionnaire scores for nausea and vomiting were better in the nefopam group, but the overall recovery quality scores were comparable between the groups. Conclusions : Nefopam reduces RUQ pain and opioid use post-single-port RALC with a parietal pain block without markedly boosting RSB's effect on umbilicus or shoulder pain. It may also better manage postoperative nausea and vomiting, underscoring its role in analgesia strategies for this surgery.

Introduction Pain after orthopedic surgeries represents a special concern in patients with fractures. The use of multimodal analgesia significantly reduced the opioid need and reduced the risk of their side effects. Objectives This study compared the effectiveness and safety of methocarbamol and nefopam in the reduction of post-operative pain for patients undergoing orthopedic surgeries. Method This prospective, double-blind, randomized controlled trial took place at Al-Sader Teaching Hospital in Basrah, Iraq, from the first of February 2022 to the end of October 2023. The study aimed to assess the post-operative pain relief efficacy and safety of intramuscular nefopam (20 mg) and intravenous methocarbamol (1 g) in 110 adults (aged 18-65) undergoing elective orthopedic surgeries. Exclusions were made for allergies to the drugs, substance abuse history, and severe hepatic or renal impairment. Participants were randomized into two groups, with pain intensity measured at one hour, six hours, and 12 hours post-operation using the visual analog scale (VAS). Side effects were also evaluated. Statistical analysis was done using SPSS 27, with a significance level set at p<0.05 and a 95% confidence interval (CI). Results  In this study, we conducted a rigorous comparison between two groups, methocarbamol and nefopam, to evaluate their efficacy and safety in post-operative pain management. We started by ensuring that the groups were well-matched in terms of age, gender distribution, and body mass index (BMI). The results showed remarkable similarities in mean age, gender distribution, and BMI, supported by robust p-values, affirming the effective matching of the two groups. Moving to pain management, we observed a significant advantage in favor of methocarbamol. At all-time intervals (one hour, six hours, and 12 hours post-operation), methocarbamol consistently demonstrated lower mean VAS scores compared to nefopam. These differences were highly statistically significant, underscoring the superior pain relief efficacy of methocarbamol. Exploring side effects, we found no statistically significant disparities in the occurrence of nausea and vomiting between the two groups. However, there was a noticeable trend toward higher tachycardia incidence in the nefopam group, though it did not reach statistical significance. Conclusion The present study showed a higher efficacy of methocarbamol in post-operative pain reduction in comparison to nefopam. No serious side effects were observed with both drugs., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Al-Nasrawi et al.)

The aim of this study was to analyze postoperative consumption of analgesics during hospitalization following colorectal surgery for endometriosis. We conducted a retrospective study at Tenon University Hospital, Paris, France from February 2019 to December 2021. One hundred sixty-two patients underwent colorectal surgery: eighty-nine (55%) by robotic and seventy-three (45%) by conventional laparoscopy. The type of procedure had an impact on acetaminophen and nefopam consumed per day: consumption for colorectal shaving, discoid resection, and segmental resection was, respectively, 2(0.5), 2.1(0.6), 2.4(0.6) g/day (p = 10-3), and 25(7), 30(14), 31(11) mg/day (p = 0.03). The total amount of tramadol consumed was greater following robotic surgery compared with conventional laparoscopy (322(222) mg vs 242(292) mg, p = 0.04). We observed a switch in analgesic consumption over the years: tramadol was used by 70% of patients in 2019 but only by 7.1% in 2021 (p < 10-3); conversely, ketoprofen was not used in 2019, but was consumed by 57% of patients in 2021 (p < 10-3). A history of abdominal surgery (OR = 0.37 (0.16-0.78, p = 0.011) and having surgery in 2020 rather than in 2019 (OR = 0.10 (0.04-0.24, p < 10 -3 )) and in 2021 than in 2019 (OR = 0.08 (0.03-0.20, p < 10 -3 )) were the only variables independently associated with the risk of opioid use. We found that neither clinical characteristics nor intraoperative findings had an impact on opioid consumption in this setting, and that it was possible to rapidly modify in-hospital analgesic consumption modalities by significantly reducing opioid consumption in favor of NSAIDS or nefopam., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Postoperative residual pain and dysesthesia in patients with lumbar spinal stenosis (LSS) can reduce patient satisfaction. We investigated the effects of nefopam on dysesthesia, postoperative pain, and satisfaction in patients with LSS who underwent spine surgery. A total of 73 patients were randomly assigned to two groups: the nefopam group ( n = 35), receiving a 20 mL normal saline-based solution containing nefopam 20 mg, and the control group ( n = 38), which received 20 mL of normal saline 1 h before the end of the operation. Postoperative incisional pain, dysesthesia scores, and overall satisfaction with postoperative pain management were evaluated. The severity of dysesthesia within 12 and 24 h in the nefopam group was significantly lower than that in the control group (2.3 ± 1.9 and 1.7 ± 1.6 vs. 3.3 ± 2.1, and 2.6 ± 1.9, respectively; p = 0.029 and p = 0.048). Satisfaction scores for postoperative pain management were significantly higher in the nefopam group (3.7 ± 0.6 vs. 3.1 ± 1.0, respectively; p = 0.006). The administration of nefopam effectively reduced the severity of dysesthesia within 24 h of surgery in geriatric patients undergoing spine surgery and increased patient satisfaction with postoperative pain management.

Background: Catheter-related bladder discomfort (CRBD) is a frequent occurrence following urinary catheterization during surgical procedures, as well as a commonly experienced bladder pain syndrome after surgery. There have been various studies on drugs and interventions to manage CRBD, but their comparative efficacy and safety are still a topic of debate. We conducted a meta-analysis to assess the efficacy and safety of nefopam for managing postoperative CRBD. Methods: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted to find randomized controlled trials (RCTs) on using nefopam in postoperative CRBD. The study employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Data analysis was performed using RevMan version 5.4.1. Results: Five RCTs with 405 patients were analyzed to evaluate the efficacy of nefopam on postoperative CRBD. Short-term and long-term periods were defined as within 6 h and longer than 12 h after surgery, respectively. The incidence and severity of CRBD were compared between the two groups during these time periods. The analysis proved that nefopam reduced the short-term incidence of postoperative CRBD (RR 0.36; 95% CI, 0.18-0.70; p = 0.003, I 2 = 78%) and the long-term incidence (RR 0.49; 95% CI, 0.32-0.74; p = 0.0007, I 2 = 0%) significantly. We compared the incidence of moderate-to-severe CRBD between groups based on the scaling system (none, mild, moderate, and severe). This was used to assess the severity of postoperative CRBD. The results showed that patients in the nefopam group had a significantly lower incidence of moderate-to-severe CRBD compared to those in the placebo group in the short-term (RR 0.19; 95% CI, 0.10-0.34; p < 0.00001; I 2 = 0%). However, there were no significant differences between the two groups in the incidence of moderate-to-severe CRBD in the long-term (RR 0.61; 95% CI, 0.21-1.76; p = 0.36; I 2 = 0%). There were no significant variations in the occurrence of adverse events between the nefopam and control groups, mainly including postoperative nausea and vomiting (PONV) (RR 1.14; 95% CI, 0.40-3.21; p = 0.81), and tachycardia (RR 0.25; 95% CI, 0.03-2.11, p = 0.20). Conclusion: The findings of this meta-analysis indicate that nefopam significantly reduced the incidence of short or long-term postoperative CRBD. Nefopam decreased the severity of postoperative CRBD, particularly significantly reducing the occurrence of moderate to severe CRBD in the short-term. Overall, patients have good tolerance and no apparent side effects. Systematic Review Registration : identifier PROSPERO (CRD42023475012)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chi, Wu, Lou, Ma, Wu and Cui.)

Introduction: Shivering is a common side effect after general anesthesia. Risk factors are hypothermia, young age and postoperative pain. Severe complications of shivering are rare but can occur due to increased oxygen consumption. Previous systematic reviews are outdated and have summarized the evidence on the topic using only pairwise comparisons. The objective of this manuscript was a quantitative synthesis of evidence on pharmacological interventions to treat postanesthetic shivering., Evidence Acqusition: Systematic review and frequentist network meta-analysis using the R package netmeta. Endpoints were the risk ratio (RR) of persistent shivering at one, five and 10 minutes after treatment with saline/placebo as the comparator. Data were retrieved from Medline, Embase, Central and Web of Science up to January 2022. Eligibility criteria were: randomized, controlled, and blinded trials comparing pharmacological interventions to treat shivering after general anesthesia. Studies on shivering during or after any type of regional anesthesia were excluded as well as sedated patients after cardiac surgery., Evidence Synthesis: Thirty-two trials were eligible for data synthesis, including 28 pharmacological interventions. The largest network included 1431 patients. The network geometry was two-centered with most comparisons linked to saline/placebo or pethidine. The best interventions were after one minute: doxapram 2 mg/kg, tramadol 2 mg/kg and nefopam 10 mg, after 5 minutes: tramadol 2 mg/kg, nefopam 10 mg and clonidine 150 µg and after 10 minutes: nefopam 10 mg, methylphenidate 20 mg and tramadol 1 mg/kg, all reaching statistical significance. Pethidine 25 mg and clonidine 75 µg also performed well and with statistical significance in all networks., Conclusions: Nefopam, tramadol, pethidine and clonidine are the most effective treatments to stop postanesthetic shivering. The efficacy of doxapram is uncertain since different doses showed contradictory effects and the evidence for methylphenidate is based on a single comparison in only one network. Furthermore, both lack data on side effects. Further studies are needed to clarify the efficacy of dexmedetomidine to treat postanesthetic shivering.

Study Design: This was a randomized double-blind controlled study., Purpose: This study was designed to evaluate the effects of intravenous nefopam regarding its ability to reduce morphine consumption and postoperative pain and improve recovery in patients undergoing open spine surgery., Overview of Literature: Multimodal analgesia, including nonopioid medications, is essential for pain management in spine surgery. Evidence regarding the use of intravenous nefopam in open spine surgery as part of enhanced recovery after surgery is lacking., Methods: In this study, 100 patients undergoing lumbar decompressive laminectomy with fusion were randomized into two groups. The nefopam group received 20-mg intravenous nefopam diluted in 100-mL normal saline intraoperatively, followed by 80-mg nefopam diluted in 500-mL normal saline, administered as a continuous infusion postoperatively for 24 hours. The control group received an identical volume of normal saline. Postoperative pain was managed using intravenous morphine via patient-controlled analgesia. Morphine consumption in the first 24 hours was recorded as the primary outcome. Secondary outcomes, including postoperative pain score, postoperative function, and length of hospital stay (LOS), were assessed., Results: No statistically significant differences in the total morphine consumption and postoperative pain score in the first 24 hours postoperatively between the two groups. At the post-anesthesia care unit (PACU), the nefopam group demonstrated lower pain scores while at rest (p =0.03) and upon movement (p =0.02) than the normal saline group. However, the severity of postoperative pain between the two groups was similar from postoperative day 1 to day 3. LOS was significantly shorter in the nefopam group than in the control group (p <0.01). The time to first sitting and walking and PACU discharge between the two groups were comparable., Conclusions: Perioperative intravenous nefopam demonstrated significant pain reduction during the early postoperative period and shortened LOS. Nefopam is considered safe and effective as a part of multimodal analgesia in open spine surgery.

Background and Aims: Intravenous nefopam reduces postoperative pain and opioid consumption but can cause infusion-related pain. We aimed to investigate whether lidocaine can effectively reduce this pain., Material and Methods: This prospective, randomized, double-blind, controlled, intrasubject comparison trial included 42 patients (20-60 years) undergoing elective surgery under regional or peripheral anesthesia. In the postanesthesia care unit, two 50 mL syringes containing nefopam (20 mg) diluted in saline (100 mL) were sequentially infused in 15 min into venous catheters in the left and right arms. Patients were randomly assigned to the "left side" or "right side" group based on the arm in which a bolus of 1% lidocaine (2 mL) (study group) was administered before nefopam infusion. Normal saline (2 mL) was administered on the control side. Numerical Rating Scale scores and the incidence of pain (scores > 3) and nausea or vomiting were recorded at 1, 5, 10, and 15 min., Results: The analysis included 42 patients (84 infusions). Compared with the placebo, lidocaine lowered the mean infusion-related pain at 1 (0.07 vs. 2.21, P < 0.001), 5 (2 vs. 4.21, P < 0.001), 10 (2.02 vs. 3.95, P < 0.001), and 15 min (1.62 vs. 3.16, P = 0.003). At 5 min, significantly higher percentages of infusion sites with moderate and higher pain scores (> 3) were observed on the control side (30.95% vs. 14.29%, P = 0.000). Seven patients exhibited nausea or vomiting (16.7%)., Conclusion: For the nefopam infusion rate and concentration that we used, a 20 mg lidocaine pretreatment bolus significantly reduces infusion-related pain., Competing Interests: In 2019, Dr. Marvin was a speaker for DKSH, a distributor for nefopam in Thailand., (Copyright: © 2022 Journal of Anaesthesiology Clinical Pharmacology.)

Background: Catheter-related bladder discomfort (CRBD) is a common postoperative bladder pain syndrome. Many drugs and interventions for managing CRBD have been studied, but their comparative effectiveness remains controversial. We made a study to assess the comparative effectiveness of interventions included Ketorolac, Lidocaine, Chlorpheniramine, Gabapentin, Magnesium, Nefopam, Oxycodone, Parecoxib, Solifenacin, Tolterodine, Bupivancaine, Dexmedetomidine, Hyoscine N-butyl bromide, Ketamine, Penile nerve block on urological postoperative CRBD., Methods: We performed a network meta-analysis via Aggregate Data Drug Inormation System software included 18 studies with 1816 patients and assessed the risk of bias by Cochrane Collaboration tool. The incidence of moderate to severe CRBD at 0, 1, and 6 h after surgery and the incidence severe CRBD at 1 h after surgery were compared., Result: The number of best rank is 0.48(Nefopam) and 0.22(Nefopam) in the incidence of moderate to severe CRBD at 1 h and incidence severe CRBD at 1 h. More than half of studies at unclear or high risk of bias., Conclusion: Nefopam reduced the incidence of CRBD and prevented severe events, but limited by the small number of studies for each intervention and heterogeneous patients., (© 2023. The Author(s).)

Purpose: Transurethral resection of prostate (TURP) with postoperative catheter traction can lead to significant catheter-related bladder discomfort (CRBD). This condition causes many postoperative complications and low patient satisfaction. This study aimed to evaluate the effectiveness of preoperative single-dose intravenous nefopam on the incidence and severity of CRBD and its adverse effects., Methods: This randomized, controlled, double-blind study included patients who underwent TURP under spinal anesthesia with postoperative urinary catheter traction. Patients were allocated into nefopam (NF) and normal saline (NS) groups. Twenty mg of nefopam in normal saline solution (NSS) 100 mL or NSS 100 mL were given intravenously before TURP. The primary outcome was the incidence of CRBD., Results: Seventy-three patients were randomized into NF (n = 37) and NS (n = 36) groups. There were 35 and 33 patients in the NF and NS groups, respectively, in the final analysis. The incidences of CRBD were 45.71% and 84.85% in the NF and NS groups at 6 h after operation, respectively, OR 0.54 (95% CI 0.36, 0.73), while before the end of catheter traction, the corresponding incidences were 37.14% and 75.76%, respectively, OR 0.49 (95% CI 0.28, 0.84). The CRBD scores were statistically significantly lower in the NF group at both time points. Morphine consumptions and adverse effects were not different between groups. Patient satisfaction was higher in the NF group., Conclusions: Single-dose nefopam significantly reduced the incidence and severity of CRBD in patients undergoing TURP with urinary catheter traction at 6 h after the procedure and before the end of catheter traction without increasing the adverse effects., (© 2022. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Study Design: Randomized double-blind control study., Purpose: To evaluate the effects of nefopam on reducing morphine consumption and postoperative pain in patients undergoing minimally invasive spine surgery (MISS) and to evaluate its effects on enhanced recovery after spine surgery., Overview of Literature: Enhanced recovery after surgery (ERAS) has become a major goal for spine surgery. Multimodal pain management combining non-opioid analgesics is a key element of this. However, there is little evidence regarding the use of nefopam in spine surgery as part of an ERAS protocol., Methods: One hundred patients undergoing MISS were randomized into two groups. Patients in the nefopam group received 20 mg of intravenous nefopam diluted in 100 mL of normal saline intraoperatively, followed by 80 mg of nefopam diluted in 500 mL of normal saline, given as a continuous infusion postoperatively for 24 hours. The control group received an identical volume of normal saline. Postoperative pain was managed by patient-controlled analgesia in the form of intravenous morphine. Morphine consumption in the first 24 hours was recorded as a primary outcome. Secondary outcomes regarding ERAS were also collected., Results: There were no significant differences in either total morphine consumption or postoperative pain score in the first 24 hours postoperatively between patients receiving nefopam and the control group. Morphine consumption in patients receiving nefopam was 13.54±10.64 mg compared with 15.86±16.2 mg in the control group (p=0.41). Time to postanesthetic care unit discharge, times to first sitting and walking, length of hospital stay, as well as duration of Foley catheter use and time until drain removal were also similar. There were no serious adverse effects of nefopam compared with normal saline., Conclusions: Nefopam did not significantly reduce opioid consumption or postoperative pain score. Adding nefopam as part of multimodal analgesia did not show beneficial effects for enhancing recovery after spine surgery.

Artisanal and small-scale mining activities are most evident among communities surrounding the Acupan River in Itogon Benguet. The mining activities include manual extraction of gold ores, use of improvised ball/rod mills and sluice boxes, and metallurgical processing such as cyanidation, carbon-in-pulp (CIP) and amalgamation. This study evaluates the influence of small-scale mining and the geology/mineralization of the Acupan Au-Ag-Te deposit to the water quality of the Acupan River and to the possible human exposures to Hg within the small-scale mining community. Different water quality parameters were monitored along selected sites along the Acupan River for a year and the results showed that the low average values of dissolve oxygen (DO) (2.54-4.53 mg L -1 ) and the relatively high average values of pH (8.84-10.10), sulfate (300.00-1133.33 mg L -1 ), nitrate (11.33-134.67 mg L -1 ), arsenic (As) (0.227-0.574 mg L -1 ) and mercury (Hg) (0.004-0.054 mg L -1 ) have exceeded the acceptable criteria limit of the Department of Environment and Natural Resources for Class C waters. The exceeded values are noted to occur in areas where extensive small-scale mining activities are being done and have affected as well the downstream areas. To test possible human contamination in the use of Hg, hair samples from 56 volunteers were analyzed for total Hg (T-Hg) following standard protocols. The T-Hg concentrations in hair samples are mostly inorganic and are determined in various parameters such as sex, geographic location, occupation, age, fish consumption and localization in hair. Though not significantly different, higher Hg values are noted in males (1.280 ± 0.446 ng mg -1 ) than among females (0.651 ± 0.163 ng mg -1 ) as well as those with ages 41-50 years (3.130 ± 2.330 ng mg -1 ) as compared to other age groups. The higher amounts of inorganic Hg in human hairs could be attributed to the discrete yet prevalent use of amalgamation. The findings of this study emphasize the need for better regulations of the small-scale mining activities and for stricter implementation of the total ban on the use of Hg in ore processing to ensure better water quality of Acupan River as well as the health and safety of the communities surrounding the river., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Although nefopam has been reported to have opioid-sparing and analgesic effects in postsurgical patients, its effectiveness in video-assisted thoracoscopic surgery (VATS) is unknown., Objectives: This study aimed to investigate the opioid-sparing and analgesic effects of perioperative nefopam infusion for lung resection., Study Design: Double-blinded randomized controlled trial., Setting: Operating room, postoperative recovery room, and ward at a single tertiary university hospital., Methods: Ninety patients scheduled for elective VATS for lung resection were randomized to either the nefopam (group N) or control group (group C). Group N received 20 mg nefopam over 30 minutes immediately after the induction of anesthesia. Nefopam was administered continuously for 24 hours postoperative, using a dual-channel elastomeric infusion pump combined with fentanyl-based intravenous patient-controlled analgesia. Group C received the same volume of normal saline as nefopam solution administered in the same manner. The primary outcome measure was fentanyl consumption for the first postoperative 24 hours. The secondary outcome measures were the cumulative fentanyl consumption during the first postoperative 48 hours, pain intensity at rest and during coughing evaluated using an 11-point numeric rating scale, quality of recovery at postoperative time points 24 hours and 48 hours, and the occurrence of analgesic-related side effects during the first postoperative 24 hours and postoperative 24 to 48 hour period. Variables related to chronic postsurgical pain (CPSP) were also investigated by telephone interviews with patients at 3 months postoperative. This prospective randomized trial was approved by the appropriate institutional review board and was registered in the ClinicalTrials.gov registry., Results: A total of 83 patients were enrolled. Group N showed significantly lower fentanyl consumption during the first postoperative 24 hours and 48 hours (24 hours: median difference: -270 µg [95%CI, -400 to -150 µg], P < 0.001); 48 hours: median difference: -365 µg [95% CI: -610 to -140 µg], P < 0.001). Group N also showed a significantly lower pain score during coughing at 24 hours postoperative (median difference, -1 [corrected 95% CI: -2.5 to 0], adjusted P = 0.040). However, there were no significant between-group differences in the postoperative quality of recovery, occurrence of analgesic-related side effects, length of hospital stay, and occurrence of CPSP., Limitations: Despite the significant opioid-sparing effect of perioperative nefopam infusion, it would have been difficult to observe significant improvements in other postoperative outcomes owing to the modest sample size., Conclusion: Perioperative nefopam infusion using a dual-channel elastomeric infusion pump has a significant opioid-sparing effect in patients undergoing VATS for lung resection. Therefore, it could be a feasible option for multimodal analgesia in these patients.

Nefopam is a centrally acting non-opioid analgesic, and its efficacy in multimodal analgesia has been reported. This study aimed to assess the analgesic efficacy of intraoperative nefopam on postoperative pain after video-assisted thoracoscopic surgery (VATS) for lung cancer. Participants were randomly assigned to either the nefopam or the control group. The nefopam group received 20 mg of nefopam after induction and 15 min before the end of surgery. The control group received saline. The primary outcome was cumulative opioid consumption during the 6 h postoperatively. Pain intensities, the time to first request for rescue analgesia, adverse events during the 72 h postoperatively, and the incidence of chronic pain 3 months after surgery were evaluated. Ninety-nine patients were included in the analysis. Total opioid consumption during the 6 h postoperatively was comparable between the groups (nefopam group [ n = 50] vs. control group [ n = 49], 19.8 [13.5-25.3] mg vs. 20.3 [13.9-27.0] mg; median difference: -1.55, 95% CI: -6.64 to 3.69; p = 0.356). Pain intensity during the 72 h postoperatively and the incidence of chronic pain 3 months after surgery did not differ between the groups. Intraoperative nefopam did not decrease acute postoperative opioid consumption or pain intensity, nor did it reduce the incidence of chronic pain after VATS., Competing Interests: The authors declare no conflict of interest.

Background: One of the most undesirable results after total knee arthroplasty (TKA) is severe immediate postoperative pain, resulting in patient dissatisfaction. We aimed to evaluate nefopam's analgesic efficacy after primary TKA along with related outcomes, including morphine consumption and adverse events., Methods: We conducted a double-blind, randomized controlled trial of patients undergoing unilateral primary TKA, comparing 24 hours of 80 mg of continuous intravenous nefopam to placebo infusion. A 100-mm Visual Analog Scale (VAS) for pain-at-rest and in-motion ≤48 hours was the primary outcome measure. Secondary outcomes were morphine and antiemetic consumption, adverse events, and functional outcomes: time-to-walk, timed up-and-go test, postoperative knee range of motion at 24 and 48 hours, time-to-discharge, and patient satisfaction scores., Results: Patients in the nefopam group had significantly lower VAS at rest 6 hours postop (20.3 ± 27.3 vs 35 ± 24.3, P = .01). Other timepoints and in-motion VAS did not significantly differ. Total morphine consumption (0-48 hours) was 37% less, significantly lower, in the nefopam group (5.3 ± 4.5 vs 8.4 ± 7.5 mg, P = .03). Antiemetic consumption was also 61% lower in the nefopam group but not statistically significant (0.8 ± 2.3 vs 2.0 ± 3.8 mg, P = .08). There were no variations in adverse events, functional outcomes, and satisfaction scores between groups., Conclusion: Continuous nefopam administration as part of multimodal analgesia for 24 hours post-TKA produced a significant analgesic effect but only within the first 6 hours. However, there was a notable reduction in morphine use 48 hours postop. Nefopam is a useful agent for contemporary pain control after TKA., Level of Evidence: Therapeutic Level I., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: The adjuvant-induced arthritis (AIA) model is widely used in research to investigate arthritis pathogenesis. Hind paw inflammation is the main outcome in this model with high loss of mobility function partly related to pain. However, analgesics such as non-steroidal anti-inflammatory drugs or opioid drugs interfere with the inflammation process related to arthritis, thus reducing their beneficial use in this model. Therefore, we investigated the effect of nefopam on arthritis development in order to improve pain management in the AIA model., Methods: Female Lewis rats were randomly divided into two groups, and each group received an injection of Mycobacterium butyricum on defining day (D) 0. At D6, rats ( n = 10) received nefopam (intraperitoneally or orally) or NaCl 0.9% IP or 1% sucrose in water ( n = 5 for each). Rats were monitored with the arthritic index (AI) and ankle circumference. Pain was assessed by scoring based on behavioral indicators. Histology, RT-qPCR, and microcomputed tomography were performed., Results: The clinical parameter AI and ankle circumference were not different in both groups at various time points. However, pain score was significantly lower in the nefopam group at the early stage of the disease. At a later stage of the disease, inflammation was mildly lower whereas bone erosion and bone loss parameters increased in the nefopam group., Conclusion: Nefopam provided a slight reduction in the level of pain at the arthritis onset without reducing arthritis severity and bone loss in the rat AIA model. However, it should be administrated orally for a shorter period to avoid inflammation reduction in the long run., Competing Interests: HM reports non-financial support from Medac related to this work. Medac provided for free the nefopam. HM reports personal fees and non-financial support from AbbVie; personal fees from Accord; personal fees from Amgen; grants, personal fees and non-financial support from Biogen; grants, personal fees, and non-financial support from Bristol Myers Squibb; personal fees and non-financial support from Cell Trion Healthcare; grants and non-financial support from Fresenius Kabi; personal fees and non-financial support from Galapagos; non-financial support from Janssen; grants personal fees, and non-financial support from Lilly; personal fees and non-financial support from MSD; grants, personal fees, and non-financial support from Nordic Pharma; personal fees, non-financial support and other from Novartis; grants, personal fees and non-financial support from Pfizer; personal fees from Roche Chugai; grants, personal fees, and non-financial support from Sanofi, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dalix, Maalouf, Linossier, Vanden-Bossche, Peyroche and Marotte.)

Introduction: nefopam is a non-opioid, centrally-acting analgesic, frequently prescribed in France for acute pain and postoperatively. Only intravenous (IV) formulation is available, however the off-label oral use is frequent in surgical and medical patients. There is no data on the actual in-hospital prescription preferences in French physicians regarding nefopam. We wish to identify nefopam prescription habits for acute and chronic pain among hospital physicians., Methods: an online survey was sent to physicians via professional emails. Frequency of prescription, indication, preferred and prescribed administration route, dose regimen, and personal perception of the nefopam tolerance and efficiency were examined., Results: a total of 527 responses were analysed. Nefopam was mostly prescribed by senior hospital physicians, for acute pain, orally (85%), 20 mg/6h with 120 mg maximal daily dose. For chronic pain, the oral administration was more frequent. More than half of prescribers considered the efficacy of the oral route was similar to intravenous, and better tolerated compared to intravenous administration. Forty-eight percent of responders would change their prescription attitude in case of oral route approval of nefopam., Conclusion: oral prescription of intravenous formulation of nefopam is frequent, especially for acute pain, and has the same dose and regimen pattern as for intravenous route. Prescribers consider oral nefopam efficient and safe for patients. Regulatory actions regarding the oral nefopam prescription authorization and duration of such prescription are needed., Competing Interests: The authors declare no competing interests., (Copyright: Thomas Schulz et al.)

Aim of the Study: The use of nefopam is constantly increasing in France. The objectives of this study were to quantify the intensity of the drug dependence signal, to identify the populations at risk and the risk factors of dependence., Methods: All serious and non-serious cases of misuse, abuse, drug dependence, overdose and withdrawal syndrome reported to the French Addictovigilance Network since 1988 were reviewed. An analysis of nefopam reimbursement data from the French national EGB (échantillon généraliste des bénéficiaires) database for the period 2006-2017 was also performed., Results: The drug dependence profile of nefopam is close to that of a psychostimulant. Our literature review and the analysis of spontaneous reports confirm the risk of abuse and dependence of nefopam. In addition to a frequent psychiatric history (depression, psychosis, anxiety), nearly half of the patients also present addictive disorders, including more than one-third with opioid-dependence. In almost half of the 120 reported cases, the main adverse reaction was dependence and the frequency of serious effects was greater than 40%. In nearly 70% of the reported cases, the use was associated with chronic pain, which might explain the prolonged use. Moreover, the analysis of data on the reimbursement of nefopam in the general population showed that one French person out of two, having a prescription for nefopam, presented chronic pain. However, nefopam is only indicated in the treatment of acute painful conditions. Although it does not seem to be associated with a greater risk of abuse or dependence, taking the drug orally is another very frequent off-label use that needs to be regulated., Conclusion: In France, the prescription of nefopam outside of its marketing authorization is regrettable, because it contributes to the development of abuse and drug dependence., (Copyright © 2021 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Background: The use of paracetamol or nefopam for postoperative pain control is limited by the need of high doses associated with unwanted effects. Previous works suggest positive interactions between both compounds that may be exploited to obtain potentiation of antinociception., Methods: Mechanical and heat antinociception induced by oral doses of paracetamol, nefopam or their combination was studied by isobolographic analysis in a murine model of postsurgical pain. The effective doses that produced 50% antinociception (ED 50 ) were calculated from the log dose-response curves for each compound. Subsequently, the effects of ED 8.7 s, ED 12.5 s, ED 17.5 s and ED 35 s of nefopam and paracetamol combined were assessed., Results: Oral paracetamol induced dose-dependent relief of postoperative sensitivity and showed higher efficacy reducing mechanical hypersensitivity (ED 50 177.3 ± 15.4 mg/kg) than heat hyperalgesia (ED 50 278.6 ± 43 mg/kg). Oral nefopam induced dose-dependent antinociception with similar efficacy for mechanical and heat hypersensitivity (ED 50 s 5.42 ± 0.81 vs. 5.83 ± 0.72). Combinations of increasing isoeffective doses revealed that combined ED 17.5 s (85.76 mg/kg paracetamol and 1.9 mg/kg nefopam) and ED 35 s (132.67 mg/kg and 3.73 mg/kg) showed synergistic effects leading to 75% and 90% mechanical antinociception, respectively. These mixtures were defined by interaction indexes of 0.43 and 0.41 and ratios 45:1 and 35:1 paracetamol:nefopam, respectively. The same combinations showed additive effects for the inhibition of incisional thermal hyperalgesia., Conclusions and Limitations: This work describes a synergistic antinociceptive interaction between low doses of nefopam and paracetamol for the treatment of postoperative hypersensitivity to peripheral stimuli. The promising results obtained on reflexive nociceptive responses of young male mice subjected to plantar surgery highlight the interest of further research evaluating the effects of this mixture on the affective-motivational component of pain and in females and additional age groups. Confirmation of pain-relieving efficacy and safety of this oral combination clinically available in European and Asian countries could provide a useful tool for postsurgical pain management., Significance: Early postoperative pain is currently undertreated and has been recognized as a relevant source of chronic postsurgical pain. Oral efficient treatments could facilitate fast-track surgeries and patient recovery at home. Here, we identify in a mouse model of postoperative pain a potent synergistic oral combination consisting of low paracetamol and nefopam doses that provides relief of postsurgical hypersensitivity to mechanical and thermal stimuli. Oral multimodal paracetamol-nefopam mixtures represent a potential clinically available pharmacological strategy for the relief of incisional sensitivity and the promotion of patient recovery., (© 2021 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC®.)

Introduction: Opioid analgesia for acute painful conditions has come under increasing scrutiny with the public health crisis of opioid overdose, leading clinicians to seek nonopioid alternatives, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen (paracetamol)., Areas Covered: This perspective evaluates recent clinical trials of nonopioids, opioids, and combination therapy for use in acute pain. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) often provide adequate analgesia, although these agents are not without risks. Combination therapy using a small amount of opioid together with a nonopioid pain reliever has been shown effective and reduces opioid consumption., Expert Opinion: The short-term use of opioids under close clinical supervision, such as in-hospital use of opioid analgesics for postoperative pain, may be appropriate, but even here, combination therapy or nonopioid therapy may be preferred. The use of opioids even for acute pain of short duration has been questioned. The ideal analgesic has yet to be developed, but effective pain control pharmacological regimens for acute pain are available.

Background and Objectives : We investigated the non-inferiority of patient-controlled analgesia (PCA), using either nefopam alone or combined nefopam-fentanyl for postoperative analgesia in patients undergoing laparoscopic cholecystectomy. Materials and Methods : In this prospective, randomized, controlled study, 78 patients were allocated to receive nefopam 240 mg (Group N240) or nefopam 120 mg with fentanyl 600 μg (Group NF), equivalent to fentanyl 1200 μg, with a total PCA volume of 120 mL. Patients were given a loading dose (0.1 mL/kg) from the PCA device along with ramosetron (0.3 mg) and connected to a PCA device with a background infusion rate of 2 mL/h, bolus dose amount set at 2 mL, and lockout interval set at 15 min. Pain scores were obtained using the numeric rating scale (NRS) at 30 min after recovery room (RR) admission, as well as 8 and 24 h postoperatively. The primary outcome was analgesic efficacy evaluated using NRS-rated 8 h postoperatively. Other evaluated outcomes included the incidence rate of bolus demand, rescue analgesic and antiemetic requirements, and postoperative adverse effects. Results : NRS scores were not significantly different between the groups throughout the postoperative period ( p = 0.539). NRS scores of group N240 were not inferior to those of group NF at 30 min after RR admission, or at 8 and 24 h postoperatively (mean difference [95% CI], -0.05 [-0.73 to 0.63], 0.10 [-0.29 to 0.50], and 0.28 [-0.06 to 0.62], respectively). Postoperative adverse effects were not significantly different between the two groups ( p = 1.000) and other outcomes were also not significantly different between the two groups ( p ≥ 0.225). Conclusions : PCA using nefopam alone has a non-inferior and effective analgesic efficacy and produces a lower incidence of postoperative adverse effects compared to a combination of fentanyl and nefopam after laparoscopic cholecystectomy.

Opioid-sparing effects of nefopam during patient-controlled analgesia (PCA) are well demonstrated. We hypothesized that postoperative pain control with an opioid-equivalent dose of nefopam as a single analgesic agent for PCA would not be inferior to fentanyl in laparoscopic gynecologic surgery. In total, 135 patients were randomly assigned to the N (nefopam 200 mg), NF (fentanyl 500 mcg + nefopam 100 mg), and F (fentanyl 1000 mcg) groups ( n = 45 patients per group). The primary outcome was the numerical rating scale (NRS) score at rest at 6 h postoperatively, and the non-inferiority limit was set to 1. Secondary outcomes were pain severity and incidence of nausea and vomiting for 48 h postoperatively. Mean differences (MD) in primary outcome between the N and F groups were 0.4 (95% confidence interval (CI) -0.5 to 1.3). The upper limit of 95% CI exceeded the non-inferiority limit. The N group showed higher pain scores than the NF group (MD, 1.1; 95% CI, 0.3-1.9) in pairwise comparisons. No significant intergroup differences were observed in the cumulative dose of PCA usage and incidence of postoperative nausea and vomiting (PONV). In laparoscopic gynecological surgery, nefopam alone showed limited efficacy for postoperative pain control.

Introduction: At present, health facilities are forced to switch to outpatient care. While it lends itself well to this organizational arrangement, first ray surgery is broadly considered as painful by patients, who are often reluctant to this treatment. The evolution of post-operative pain in patients who underwent operations for first ray surgery from D0 to D15 were studied. Secondly, the duration of the oral analgesic treatment, the patient's satisfaction level, and searched for complications were assessed., Methods: This is an observational, single-center and single-operator study. Between July and December 2019, forty patients who underwent first ray surgery (hallux valgus or rigidus) and eligible for outpatient treatment were included. The surgical technique of the hallux valgus treatment consisted of open surgery via double metatarsal and phalangeal osteotomy. The hallux rigidus surgery consisted of arthrodesis using an open dorsal plate. Home monitoring was carried out by a healthcare provider (e-HORUS). The protocol provided for pain management by means of a diffuser of Nefopam IV for a maximum of 5 days, combined with alleviating oral analgesics 1 and 2 and NSAIDs. The pain was evaluated on D0, D1, D3, D5, D8 and D15, using a numerical scale (NS) from 0 to 10. The degree of patient satisfaction was recorded at 1 month., Results: 35 patients were followed. 5 patients were excluded due to incomplete data. The series included 26 women and 9 men, with an average age of 59.9 years. There were 30 hallux valgus and 5 hallux rigidus. The pain analyzed by the NS was 5.37 on D0, 3.34 on D1, 1.83 on D3, 1.43 on D5, 1.06 on D8 and 2.2 on D15. The average duration of Nefopam infusions was 3.89 days, and the average duration of oral analgesics was 17.7 days. The tolerance of the treatment was satisfactory in 79% of the cases. 69% of patients were very satisfied with the management of their pain. There were no scar complications or infections. No re-hospitalization was necessary. 3 algoneurodystrophies were identified. The existence of fibromyalgia or Parkinsonian syndrome was correlated with higher pain., Discussion-Conclusion: Pain management after outpatient first ray surgery using the injectable Nefopam protocol was satisfactory in the majority of cases, with a high degree of patient satisfaction. This protocol is routinely offered to our patients who must undergo first ray surgery., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Pain control and quality of recovery (QoR) at home remains a challenge after ambulatory shoulder arthroscopy. This study aims to assess the QoR and pain relief using a sequential implementation strategy for rescue analgesic drugs., Methods: After institutional review board approval, patients (>18 years, American Society of Anesthesiology [ASA] score 1-3 stable) scheduled for ambulatory surgery under general anesthesia with a single-shot interscalene nerve block were enrolled. After discharge, patients received standard information regarding the postoperative recovery and care consisting of a multimodal analgesic regime (acetaminophen and ketoprofen for 5 days). The first 48 postoperative hours allowed us to compare 3 different rescue drug regimes with a control group, in sequential order: tramadol (control group), tramadol + nefopam, immediate-release oxycodone (IR), and extended-release oxycodone (ER). The primary endpoint was the QoR 40 score at 48 hours after surgery. Secondary endpoints were pain relief and adverse events over a 7-day period. An intention-to-treat statistical analysis was performed with sequential analysis (as an interim analysis) every 20 patients. Results were recorded as medians and interquartiles (25-75)., Results: We analyzed 109 patients with similar characteristics among groups. The QoR 40 scores were similar for the tramadol group (168 [161-172]), the tramadol + nefopam group (161 [151-173], P = .09), and the IR group (164 [153-169], P = .17), but higher for the ER group (176 [167-181], P = .03). Concerning adverse events, drugs were interrupted more frequently in the tramadol + nefopam group (36 %). In the ER group, a higher quality of postoperative relief was attained in the domains of pain and sleep., Conclusion: The present study shows that a combination of IR and ER oxycodone over a short period of time (<48 hours) is associated with a better QoR at home after ambulatory shoulder surgery., (Copyright © 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Despite rapid advancements in laparoscopic surgical techniques and perioperative management, postoperative pain remains a significant clinical issue. We examined the analgesic efficacy of nefopam as an adjuvant in patient-controlled analgesia (PCA) for acute postoperative pain in patients undergoing laparoscopic colorectal cancer surgery. We retrospectively analyzed the medical records of 120 patients who did or did not receive 80 mg of nefopam as an adjuvant in fentanyl PCA; they were allocated to the nefopam ( n = 60) or non-nefopam group ( n = 60). The demographic, clinical, and anesthetic data, with data on pain severity and opioid administration at the postoperative anesthesia care unit (PACU) on postoperative days (PODs) 1, 3, and 5, were compared between the groups. The pain score and opioid administration did not differ at the PACU or on PODs 1, 3, or 5. The day of PCA discontinuation, time to pass flatus, length of the hospital stay, and incidence of nausea/vomiting, dizziness, and headache also did not differ between the groups. Fentanyl PCA with 80 mg of nefopam as an adjuvant did not have a superior analgesic effect after laparoscopic colorectal cancer surgery.

The present study investigated the effects of intrathecal nefopam on the pain behavior and on the extracellular levels of serotonin (5-HT), norepinephrine (NE), and glutamate in the spinal cord, in a rat model of pain induced by formalin. Nefopam was intrathecally administered 10 min prior to the formalin test to assess its antinociceptive effects. In another cohorts of animals, dihydroergocristine, yohimbine, or (RS)-α-Methylserine-O-phosphate (MSOP), a serotonergic, α-2 adrenergic receptor, or group III metabotropic glutamate receptor antagonist, respectively, were administered prior to the application of nefopam in the formalin test. Microdialysis studies were conducted to measure the extracellular levels of 5-HT, NE, and glutamate in the spinal cord following nefopam administration. Intrathecal nefopam reduced formalin-induced behavior in both phases of the test. The blockade of serotonergic or adrenergic receptors partially reversed the analgesic effects of nefopam in the first phase of the formalin test whereas MSOP reversed these effects in both phases. The microdialysis results revealed that intrathecal nefopam significantly increased 5-HT and NE levels and attenuated the formalin-induced release of glutamate in the spinal cord. Thus, the present data suggest that the increase in the extracellular levels of 5-HT and NE, and reductions in glutamate release in the spinal cord, may have contributed to the analgesic effects of nefopam., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Nefopam is a non-opioid, non-steroidal, central acting drug used effectively for postoperative pain. The efficacy of nefopam for cancer pain remains unclear. We aimed to evaluate the analgesic efficacy of nefopam for cancer pain in a randomized controlled trial. Methods : Patients with moderate to severe cancer pain (n=40) were randomly divided into two groups. The nefopam group (n=20) received three 20 mg doses of nefopam every 8 hours. The placebo group (n=20) received normal saline. Intravenous patient-controlled analgesia with morphine was given for breakthrough pain for 48 hours. The primary outcome was significant pain reduction. Secondary outcomes were morphine consumption over 48 hours and incidence of side effects. Results: The nefopam group showed pain reduction at 12 hours (65% of patients), 24 hours (80%), 36 hours (85%), and 48 hours (65%). The placebo group showed pain reduction at 12 hours (70%), 24 hours (75%), 36 hours (80%), and 48 hours (60%). However, there were no statistically significant differences between the groups (p>0.05). The median dosage of morphine consumption in 48 hours was lower in the nefopam group (25.5 mg) compared with the placebo group (37 mg), but this was not statistically significant (p=0.499). There were no statistically significant differences in blood pressure and heart rate between the groups. Side effects in both groups were comparable. Conclusions: At dosage of 60 mg in 24 hours, nefopam did not provide significant pain reduction in moderate to severe cancer pain patients. However, there was a trend of reduced opioid consumption. Further studies with larger sample sizes, longer duration, or higher doses of nefopam are warranted. Registration: Thai Clinical Trail Registry (TCTR) ID TCTR20181016001; registered on 12 October 2018., Competing Interests: No competing interests were disclosed., (Copyright: © 2020 Pasutharnchat K et al.)

Introduction: Nefopam has been reported to be effective in postoperative pain control with an opioid-sparing effect, but the use of nefopam can lead to nausea and vomiting. To prevent these side effects, droperidol can be mixed with nefopam. In intensive care units, high concentrations of nefopam and droperidol in syringes can be used with a continuous flow., Objectives: The first objective of this work was to study the physicochemical stability of a nefopam solution 2.5 mg/mL diluted in NaCl 0.9% in polypropylene syringes immediately after preparation and after 6, 24 and 48 hours at room temperature. The second objective was to study the physicochemical stability of mixtures of nefopam 2.5 mg/mL and droperidol 52 µg/mL diluted in NaCl 0.9% in polypropylene syringes at room temperature over 48 hours., Materials and Methods: Three syringes for each condition were prepared. For each time of analysis, three samples for each syringe were prepared and analysed by high performance liquid chromatography coupled to photodiode array detection. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection (turbidimetry by UV spectrophotometry). pH values were measured at each time of analysis., Results: Solutions of nefopam at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL, diluted in NaCl 0.9%, without protection from light, retained more than 90% of the initial concentration after 48 hours storage at 20-25°C. No modification in visual or subvisual evaluation and pH values were observed., Conclusion: Nefopam solutions at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL diluted in NaCl 0.9% were stable over a period of 48 hours at room temperature. These stability data provide additional knowledge to assist intensive care services in daily practice., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chemotherapy-induced neuropathic pain is a disabling condition following cancer treatment. Vincristine has more neurotoxicity than other vinca alkaloid agents. This study evaluated the correlation of different doses of nefopam with antiallodynic effects in a mouse vincristine neuropathy model., Methods: A peripheral neuropathic mouse model was made by intraperitoneal injection of vincristine (0.1 mg/kg/day; 5-day-on, 2-day-off schedule over 12 days). After the development of allodynia, mice were injected intraperitoneally with 0.9% normal saline (NS group) or various doses (10, 30, 60 mg/kg) of nefopam (Nefopam group). We examined allodynia using von Frey hairs pre-administration and at 30, 60, 90, 120, 180, 240 mins, and 24 hrs after drug administration. We also measured the neurokinin-1 receptor concentrations in the spinal cord to confirm the antiallodynic effect of nefopam after drug administration., Results: The peripheral neuropathic mouse model showed prominent mechanical allodynia. Intraperitoneal nefopam produced a clear dose-dependent increase in paw withdrawal threshold compared with pre-administration values and versus the NS group. The concentration of neurokinin-1 receptor was significantly decreased in the Nefopam group (P<0.05)., Conclusion: Intraperitoneally administered nefopam yielded a dose-dependent attenuation of mechanical allodynia and decreased neurokinin-1 receptor concentration, suggesting that the neurokinin-1 receptor is involved in the antiallodynic effects of nefopam in vincristine neuropathy., Competing Interests: The authors declare no competing interests., (© 2020 Lee et al.)

Background: Head-to-head comparisons of combinations of more than one non-opioid analgesic (NOA) with morphine alone, for postoperative analgesia, are lacking. The objective of this multicentre, randomised, double-blind controlled trial was to compare the morphine-sparing effects of different combinations of three NOAs-paracetamol (P), nefopam (N), and ketoprofen (K)-for postoperative analgesia., Methods: Patients from 10 hospitals were randomised to one of eight groups: control (C) received saline as placebo, P, N, K, PN, PK, NK, and PNK. Treatments were given intravenously four times a day during the first 48 h after surgery, and morphine patient-controlled analgesia was used as rescue analgesia. The outcome measures were morphine consumption, pain scores, and morphine-related side-effects evaluated 24 and 48 h after surgery., Results: Two hundred and thirty-seven patients undergoing a major surgical procedure were included between July 2013 and November 2016. Despite a failure to reach a calculated sample size, 24 h morphine consumption [median (inter-quartile range)] was significantly reduced in the PNK group [5 (1-11) mg] compared with either the C group [27 (11-42) mg; P<0.05] or the N group [21 (12-29) mg; P<0.05]. Results were similar 48 h after surgery. Patients experienced less pain in the PNK group compared with the C, N, and P groups. No difference was observed in the incidence of morphine-related side-effects., Conclusions: Combining three NOAs with morphine allows a significant morphine sparing for 48 h after surgery associated with superior analgesia the first 24 h when compared with morphine alone., Clinical Trial Registration: EudraCT: 2012-004219-30; NCT01882530., (Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Catheter-related bladder discomfort (CRBD) is one of the most difficult symptoms during the postoperative period. Nefopam is a non-narcotic analgesic agent, which also has anticholinergic action. This study was performed to evaluate the effects of nefopam on CRBD in male patients undergoing robotic nephrectomy. A total of 109 male patients were randomly divided into two groups: the control group ( n = 55) received 20 mL of normal saline, and the nefopam group ( n = 54) received 20 mg of nefopam 1 h before the end of the operation. At postoperative times of 20 min, 1 h, 2 h, and 6 h, the severity of CRBD was measured using an 11-point numeric rating scale, respectively. The severity of CRBD in the nefopam group was significantly lower than that in the control group at 20 min (4.8 ± 1.3 vs. 2.3 ± 1.0, respectively, p = 0.012) and at 1, 2, and 6 h (3.5 ± 1.2, 2.7 ± 0.9, and 2.5 ± 1.0 vs. 4.1 ± 0.8, 1.6 ± 0.8, and 1.3 ± 0.6, respectively, p < 0001). Intraoperative nefopam administration reduced the severity of CRBD in patients undergoing robotic nephrectomy.

Background: Postoperative nausea and vomiting (PONV) frequently occurs following bimaxillary orthognathic surgeries. Compared to opioids, Nefopam is associated with lower incidences of PONV, and does not induce gastrointestinal tract injury, coagulopathy, nephrotoxicity, or fracture healing dysfunction, which are common side effects of Nonsteroidal anti-inflammatory drugs. We compared nefopam- and fentanyl-induced incidence of PONV in patients with access to patient-controlled analgesia (PCA) following bimaxillary orthognathic surgeries., Methods: Patients undergoing bimaxillary orthognathic surgeries were randomly divided into nefopam and fentanyl groups. Nefopam 120 mg or fentanyl 700 µg was mixed with normal saline to a final volume of 120 mL. Patients were given access to nefopam or fentanyl via PCA. Postoperative pain intensity and PONV were measured at 30 minutes and 1 hour after surgery in the recovery room and at 8, 24, 48, and 72 hours after surgery in the ward. The frequency of bolus delivery was compared at each time point., Results: Eighty-nine patients were enrolled in this study, with 48 in the nefopam (N) group and 41 in the fentanyl (F) group. PONV occurred in 13 patients (27.7%) in the N group and 7 patients (17.1%) in the F group at 8 hours post-surgery (P = 0.568), and there were no significant differences between the two groups at any of the time points. VAS scores were 4.4 ± 2.0 and 3.7 ± 1.9 in the N and F groups, respectively, at 8 hours after surgery (P = 0.122), and cumulative bolus delivery was 10.7 ± 13.7 and 8.6 ± 8.5, respectively (P = 0.408). There were no significant differences in pain or bolus delivery at any of the remaining time points., Conclusion: Patients who underwent bimaxillary orthognathic surgery and were given nefopam via PCA did not experience a lower rate of PONV compared to those that received fentanyl via PCA. Furthermore, nefopam and fentanyl did not provide significantly different postoperative pain control., Competing Interests: DECLARATION OF CONFLICTING INTERESTS: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To determine the effect of various methods of perioperative analgesia on the rate of failed back surgery syndrome in patients operated on for spinal stenosis., Material and Methods: A total of 122 patients were operated on for spinal stenosis in 2010-2016. The patients were assigned to groups according to the type of received analgesia: Group K (n=19) underwent analgesia on-demand. Patients in the PMA group (n=21) received preventive multimodal analgesia (PMA) with ketoprofen, paracetamol and morphine. Patients in the PMA+PG (n=20) and PMA+N (n=20) groups additionally received pregabalin and nefopam, respectively. Patients in the PMA+E group (n=22) received continuous epidural analgesia with a combination of ropivacaine and morphine. In patients in the PMA+I group (n=20), the wound was infiltrated with ropivacaine and ketorolac., Results and Conclusion: In Group K, analgesia was not adequate during five postoperative days. Analgesia with PMA resulted in significant pain reduction during three postoperative days compared to Group K. Wound infiltration in addition to PMA was followed by more significant pain relief during six postoperative hours (compared to the PMA group). Administration of pregabalin or nefopam, as well as epidural analgesia, did not improve quality of postoperative analgesia. Five to seven months after the surgery, 66% (57; 75%) of patients had low back and/or leg pain; 41% (32; 50%) of patients had leg pain. Among patients suffering from pain, 32-41% patients had the severe chronic pain syndrome that resulted in sleep disorder, disability and significant deterioration of quality of life. The rate of failed back surgery syndrome did not depend on the perioperative analgesia regimen.

Background: Catheter-related bladder discomfort (C.R.B.D.) is a risk factor for emergence agitation and delirium in postoperative phase. It may be resistant to conventional analgesic therapy such as opioids. This study evaluated the role of preoperative treatment using intravenous 20 mg nefopam in reducing the incidence and severity of C.R.B.D. during the first postoperative 24 h after urinary catheterization when compared with placebo., Methods: Seventy adult males undergoing elective transurethral resection of bladder tumor requiring urinary bladder catheterization intraoperatively were randomly divided into two groups of 35 patients. In the intervention group (Group N), intravenous 20 mg nefopam in 100 mL normal saline was administered before spinal anesthesia. The placebo group (Group P) received intravenous normal saline 100 mL instead. The incidence and severity of side-effects, including C.R.B.D. at 1, 2, 6, and 24 h after surgery, was evaluated., Results: The incidence of C.R.B.D. was reduced in Group N compared with Group P during the first postoperative 24 h (6/33 [18.2%] vs 22/35 [62.9%], Group N vs Group P, p = .000). The severity of C.R.B.D. also varied significantly at postoperative 1, 2, and 6 h. The use of postoperative analgesics was reduced in Group N compared with Group P (8/33 [24.2%] vs 25/35 [71.4%], Group N vs Group P, p = .000)., Conclusions: The preoperative administration of single-dose intravenous nefopam reduced the incidence and severity of C.R.B.D. in the early postoperative period in patients undergoing T.U.R.-B. under spinal anesthesia.

Objective Nefopam is thought to reduce postoperative pain; however, the evidence is insufficient. The recommended dose is 20 mg, and the median effective dose (ED50) in the surgical setting reportedly ranges from 17 to 28 mg. However, nefopam frequently produces inadequate postoperative analgesia. We evaluated the ED50 of nefopam as a single agent in patients undergoing laparoscopic cholecystectomy. Methods Twenty-nine patients were scheduled for laparoscopic cholecystectomy. Postoperative pain was evaluated using a numerical pain scale (NPS). When the NPS score was >3, patients were administered a predetermined dose of nefopam. The dose was calculated using the up-and-down allocation technique based on the previous response. The initial dose was 28 mg, with adjustment intervals of 5 mg. An effective response was defined as a decrease in the NPS score to <3 at 30 minutes after infusion. Results The ED50 of nefopam was 62.1 mg (95% confidence interval, 52.9-72.9 mg). Eight patients reported pain upon injection, and three were excluded due to severe injection pain and phlebitis. Conclusions The estimated ED50 was higher than the predetermined dose based on previous studies. We recommend that the dose of nefopam be chosen after careful consideration of individual variations and clinical settings.

Background: Neurodegeneration is associated with changes in basal cellular function due to the dysregulation of autophagy. A recent study introduced the involvement of autophagy during spinal nerve ligation (SNL). Nefopam has shown potential for reducing neuropathic pain, but the underlying mechanisms are unknown. Here, we investigated the effects of nefopam on neuropathic pain development following SNL, focusing on the involvement of autophagy., Methods: The functional role of nefopam in capsaicin-induced autophagy was assessed by human glioblastoma M059 K cells. The neuropathic pain model was used to determine whether the effect of nefopam on pain control was mediated through autophagy control. Neuropathic pain was induced by L5 and L6 SNL in male rats randomized into three groups: Group S (sham-operated), Group C (received normal saline), and Group E (received nefopam). A behavioral test using a von Frey was examined. Expression changes of autophagy in response to nefopam was analyzed in spinal cord tissues (L4-L6) by immunoblotting and immunohistochemistry., Results: The paw withdrawal threshold examined on days 3, 5, 7, and 14 post-SNL was significantly higher in Group E than in Group C. SNL increased the levels of microtubule-associated protein 1 light chain 3B (LC3B-1), with concomitant reduction of sequestosome 1 (SQTSM1/p62), compared with Group S, indicating that SNL induced autophagy. These effects were reversed by nefopam injection, and the results were confirmed by immunohistochemistry for LC3-I/II. Furthermore, SNL-mediated JNK activation was markedly decreased following nefopam injection. Hematoxylin and eosin staining on Day 14 post-SNL revealed that SNL caused lymphocyte infiltration and oligodendrocyte localization in the substantia gelatinosa of the dorsal gray horn, which were reduced by nefopam injection., Conclusion: Collectively, the mode of action of nefopam on neuropathic pain appears to be associated with downregulation of phospho-JNK and autophagy, as well as modulation of the immune response.

Background: Patients who undergo urinary catheterization may experience postoperative catheter-related bladder discomfort (CRBD). Previous studies have indicated that drugs with antimuscarinic effects could reduce the incidence and severity of CRBD. Accordingly, this study was carried out to investigate whether nefopam, a centrally acting analgesic with concomitant antimuscarinic effect, reduces the incidence and severity of CRBD., Methods: Sixty patients with American Society of Anesthesiologists physical status I and II and aged 18-70 years who were scheduled to undergo elective ureteroscopic litholapaxy participated in this double-blinded study. Patients were divided into control and nefopam groups, comprising 30 patients each. In the nefopam group, 40 mg nefopam in 100 ml of 0.9% saline was administered intravenously. In the control group, only 100 ml of 0.9% saline was administered. All patients had a urethral catheter and ureter stent inserted during surgery. The incidence and severity of CRBD, numerical rating scale (NRS) score of postoperative pain, rescue pethidine dose, and side effects were recorded in the post-anesthesia care unit after surgery., Results: The incidence (P = 0.020) and severity (P < 0.001) of CRBD were significantly different between the control group and the nefopam group. The NRS score of postoperative pain (P = 0.006) and rescue dose of pethidine (P < 0.001) were significantly higher in the control group than in the nefopam group., Conclusions: Intravenous administration of nefopam in patients scheduled to undergo ureteroscopic litholapaxy reduced the incidence and severity of CRBD, NRS score of postoperative pain and analgesic requirements.