Enantiomeric separation of nefopam and cathinone derivatives using a supramolecular deep eutectic solvent as a chiral selector in capillary electrophoresis.

The present study investigates the utilization of a supramolecular deep eutectic solvent (SUPRADES), consisting of sulfated-ß-cyclodextrin (S-ß-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-ß-CD-CA to the background electrolyte (BGE), leading to a baseline separation of all analytes. In particular, the optimum percentage of S-ß-CD-CA, added to the BGE, was determined to be 0.075% v/v for NEF (Rs = 1.5) and 0.050% v/v for three out of five cathinone derivatives (Rs = 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 (Rs = 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.

Comparison of analgesic effectiveness between nefopam and propacetamol in living kidney donors following rectus sheath block after hand-assisted living donor nephrectomy: a prospective, randomized controlled trial.

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).

Nefopam as a multimodal analgesia in thoracoscopic surgery: a randomized controlled trial.

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).

The synergistic anti-nociceptive effects of nefopam and gabapentinoids in inflammatory, osteoarthritis, and neuropathic pain mouse models.

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 ED50 (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.

Impact of Intraoperative Nefopam on Postoperative Pain, Opioid Use, and Recovery Quality with Parietal Pain Block in Single-Port Robotic Cholecystectomy: A Prospective Randomized Controlled Trial.

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/m2. 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.

Comparison of Nefopam-Based Patient-Controlled Analgesia with Opioid-Based Patient-Controlled Analgesia for Postoperative Pain Management in Immediate Breast Reconstruction Surgery: A Randomized Controlled Trial.

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.

Evaluating the Efficacy of Methocarbamol and Nefopam in Orthopedic Surgical Pain.

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.

Efficacy of Oral Nefopam on Multimodal Analgesia in Total Knee Arthroplasty: A Prospective, Double-Blind, Placebo-Controlled, Randomized Trial.

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.

The systematic review and meta-analysis evaluated the efficacy and safety of nefopam for catheter-related bladder discomfort based on randomized controlled trials.

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, I2 = 78%) and the long-term incidence (RR 0.49; 95% CI, 0.32-0.74; p = 0.0007, I2 = 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; I2 = 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; I2 = 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).

Effect of Nefopam on Dysesthesia, Postoperative Pain, and Satisfaction in Patients with Lumbar Spinal Stenosis Undergoing Spine Surgery: A Double-Blind, Randomized Study.

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.

Postoperative analgesic efficacy of nefopam after anorectal surgery: a retrospective observational study

Objective: To examine the effectiveness of nefopam on postoperative pain control after anorectal surgeries. Methods: We retrospectively reviewed the electronic medical records of patients who underwent anorectal surgeries from January 2019 to March 2022 at two medical centers. The data were divided into nefopam and conventional groups. The primary outcome was the number of patients who requested additional opioids in the 24-h postoperative period. The secondary outcomes were numeric rating pain scores (NRPS) within a 24-h postoperative period and analgesic drugs-related side effects. Results: Eighty-seven patients in the conventional group and 60 in the nefopam group were recruited. The nefopam group reported less additional opioid consumption than the conventional group in all dimensions of analysis, including overall, adjusted to anesthetic techniques and types of surgery. However, these did not reach statistical significance (P = 0.093). Only patients in the nefopam group who underwent hemorrhoidectomy under TIVA or spinal anesthesia significantly required fewer additional opioids (P = 0.016, 60% mean difference). Similarly, the 24-h postoperative morphine consumption was lower in the nefopam group (mean difference = -3.4, 95%CI: 0.72,6.08). Furthermore, significantly lower NRPS were reported in the nefopam group during the 12-18 h postoperative period (P = 0.009). On the other hand, analgesic drugs related side effects were similar in both groups. Conclusions: The administration of nefopam after major anorectal surgery is beneficially evident in reducing postoperative opioid requirements. (AU)

Intravenous lidocaine bolus for reducing nefopam-induced venous pain: A randomized, intrasubject comparison trial.

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.

Perioperative Intravenous Nefopam on Pain Management and Ambulation after Open Spine Surgery: A Randomized Double-Blind Controlled Study.

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.

Comparative effectiveness of interventions for managing urological postoperative catheter-related bladder discomfort: a systematic review and network meta-analysis.

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.

Single-dose intravenous nefopam on postoperative catheter-related bladder discomfort in patients undergoing transurethral resection of prostate: a randomized, double-blind placebo-controlled trial.

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.

Effect of Continuous Infusion of Intravenous Nefopam on Postoperative Opioid Consumption After Video-assisted Thoracic Surgery: A Double-blind Randomized Controlled Trial.

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.

The Lack of Analgesic Efficacy of Nefopam after Video-Assisted Thoracoscopic Surgery for Lung Cancer: A Randomized, Single-Blinded, Controlled Trial.

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.

Nefopam prescribing preferences in French hospitals: results of a survey.

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.

Improvement of Pain Management by Nefopam in a Rat Adjuvant-Induced Arthritis Model.

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.

Analgesic Effect of Intravenous Nefopam for Postoperative Pain in Minimally Invasive Spine Surgery: A Randomized Prospective Study.

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.