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The objective designated to discover the analgesic effect of nefopam in the normal (non-stressed) chickens and its possible alteration due to hydrogen peroxide (H2O2)-induced oxidative stress (OS) in 7-14 day old chickens. The analgesia of nefopam has been increased by 47% in the stressed chickens by measuring the analgesic Median Effective Dose (ED50) value. This value was 9.10 mg/kg, IM in the normal chickens where it became 4.80 mg/kg, IM in stressed chickens. There is a significant rise in the antinociceptive action of nefopam 18 mg/kg, IM by 88% in the stressed group of chickens in comparison with the normal one elicited by an electro-stimulation and formaldehyde 0.05 ml of 0.1% tests for induction of nociception. The observations showed several significant stimulatory modifications in the neurobehaviour when nefopam treated with a subtle dosage 1 mg/kg, IM in the stressed chickens concerning the latency to move, squares crossed and time of the tonic immobility response test. Significant damage was detected in the liver function when nefopam injected at 18 mg/kg, IM in stress chickens in comparison to normal one by 28, 33 and 65% as estimated through Alkaline phosphatase (ALP), Aspartate trans-aminase (AST) and Alanine trans-aminase (ALT) concentrations in the serum, respectively. The sum of data findings indicated that H2O2-inducedOS increased the analgesic activity of nefopam in the chickens; despite the changes occur on the neurobehaviour and liver function. The dose of nefopam should be reduced when preparing the therapeutic regimen in the stressed animals.

В статье представлены сведения, которые расширяют знания о механизмах развития синдрома периферической и центральной сенситизации, а также о механизме развития послеоперационной мышечной дрожи. На основании детального их анализа указаны ведущие механизмы действия препарата Нефопам для предупреждения и лечения вышеупомянутых синдромов. Определено место Нефопама в программах послеоперационного обезболивания как средства предупреждения и лечения острой толерантности к опиоидам. Приведены результаты собственного опыта применения этого препарата в отделениях интенсивной терапии г. Киева.

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).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.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.

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.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).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.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.

Background: Pain management of fractures in emergency room requires multimodal analgesia including nefopam. Oral or parenteral administration of this molecule can be performed. Aim of the study: The main aim of the study was to compare the efficiency of oral and intravenous nefopam in traumatic fracture pain, in emergency unit. Methods: A prospective, comparative, randomized study was conducted in Emergency Department of the Hospital University of J.R. Andrianavalona. This study was conducted in two groups (oral and intravenous groups) of patients presenting fracture pain, over a period of six months. The primary endpoint was the analgesic efficiency. Comparison and correlation tests were used (SigmaPlot® 10.0). Results: The study population was aged 29 [18 - 70] years, mostly men (sex ratio: 6.3). Oral nefopam significantly decreased the pain by 1.5 to 2 points. The decrease in pain intensity with oral nefopam was significant from 20th minute to 90th minute (p

Emergence agitation (EA), also referred to as emergence delirium, can have clinically significant consequences. The mechanism of EA remains unclear. The proposed risk factors of EA include age, male sex, type of surgery, emergency operation, use of inhalational anesthetics with low blood–gas partition coefficients, long duration of surgery, anticholinergics, premedication with benzodiazepines, voiding urgency, postoperative pain, and the presence of invasive devices. If preoperative or intraoperative objective monitoring could predict the occurrence of agitation during emergence, this would help to reduce its adverse consequences. Several tools are available for assessing EA.However, there are no standardized clinical research practice guidelines and its incidence varies considerably with the assessment tool or definition used. Total intravenous anesthesia, propofol, μ-opioid agonists, N-methyl-D-aspartate receptor antagonists, nefopam, α2-adrenoreceptor agonists, regional analgesia, multimodal analgesia, parent-present induction, and preoperative education for surgery may help in preventing of EA. However, it is difficult to identify patients at high risk and apply preventive measures in various clinical situations.The risk factors and outcomes of preventive strategies vary with the methodologies of studies and patients assessed.This review discusses important outcomes of research on EA and directions for future research.

Highly traumatic surgical interventions for head and neck tumors were performed in 62 adult patients under conditions of multimodal opioid-free general anesthesia, which included dexmedetomidine, lidocaine, nefopam, and sevoflurane. In 18 cases, due to trismus II – IV degree, fibro optic nasotracheal intubation was used, in 10 patients with laryngeal stenosis, the operation was started with tracheotomy under local anesthesia. In all 28 cases, local anesthesia was supplemented by sedation with intravenous (IV) administration of dexmedetomidine and lidocaine, which was enhanced by the addition of sub-drug doses (10–20 mg) of ketamine. Consciousness and spontaneous breathing were preserved in all observations. Before intubation, propofol and rocuronium were added, and at the stage of the main operation, against the background of intravenous infusion of dexmedetomidine and lidocaine, inhalation of sevoflurane vapors (1–1.5 MAC). In 62 cases, the course of the operation and anesthesia was smooth, awakening and restoration of spontaneous breathing occurred after the end of the operation. Postoperative pain relief for the first two days was in the form of a continuous iv infusion of a 3-component mixture of 1% lidocaine and two non-opioid analgesics (nefopam and tenoxicam) using a disposable elastomeric pump. In the next 3-4 days, they switched to intramuscular administration of nefopam and tenoxicam. The quality of pain relief was high, without clinically significant complications. Only in three cases, at the beginning of mastering the technique, it was necessary to resort to an additional single injection of promedol or tramadol.

BACKGROUND Laparoscopic cholecystectomy (LC) is the optimal approach for patients with symptomatic cholecystolithiasis. Although LC has some advantages, many patients experience postoperative pain. METHODS In this review, we aimed to study the available information and meta-analyses of pharmacological methods of postoperative pain management in patients undergoing LC. Two researchers conducted a literature search in multiple databases (PubMed, Web of Science, Science Direct, Scopus, EMBASE, and Cochrane Library). Papers on pharmacological management of postoperative pain for patients undergoing LC were considered eligible. All meta-analyses, with or without a systematic search, were included in our review. The researchers read the study titles and abstracts to identify relevant articles and appraise the full-text manuscripts. Of 145 papers, the full-text of 11 articles, which met the inclusion criteria, was studied. Information, including the authors' names, publication data, type of review, patients' characteristics, interventions, outcomes, sample size, pooled effect size, publication bias, and statistical and methodological heterogeneity, was extracted. The collected data were presented descriptively, without further statistical analysis. RESULTS AND CONCLUSIONS Very low to low-quality evidence indicated that pharmacological agents, such as nonsteroidal anti-inflammatory drugs, lidocaine, parecoxib, nefopam, dexamethasone, and magnesium sulfate, could decrease pain intensity in patients undergoing LC. Moreover, moderate to high-quality evidence showed that intravenous infusion of ketamine and opioids, as well as pregabalin, was effective in pain control. Further, robust clinical trials are needed with several arms (eg, pharmacological agents) to compare the efficacy and safety of analgesics under similar clinical conditions and to find optimal regimens for pain management in patients undergoing LC.

Background Identifying the optimal treatment in an acute postoperative setting remains a challenge. Multiple analgesic options are available, but comparing outcomes is limited by a lack of head-to-head trials. In addition, decisions based on efficacy only do not take drug safety into account. In such cases, multi-criteria decision analysis (MCDA) can be utilized to quantify and compare the efficacy and safety data of various drugs. Methodology The efficacy-safety profiles of eight parenteral, postoperative analgesics (acetaminophen, diclofenac, ketorolac, metamizole, morphine, nefopam, parecoxib, tramadol) widely used in Europe were evaluated using an MCDA model that included 17 criteria: three for efficacy and 14 for safety. Each drug was scored on each criterion on a scale from 0 (worst) to 100 (best), according to published data and the judgment of an expert panel. A weighting process was then applied to standardize the impact of each criterion and adjust drugs' preference scores accordingly, normalizing them on the 0-100 scale. Sensitivity analyses were also performed, including a model in which analgesic profiles were compared when opioid sparing effect was set at a zero value for all drugs. Results In the primary model, efficacy and safety had relative weightings of 64% and 36%, respectively. Efficacy and safety criteria with the highest values were pain relief (relative weight, 29%) and gastrointestinal effects (12%). Parecoxib received the highest overall score (93), followed by diclofenac (80), and ketorolac (75). Morphine scored the lowest (57), due to the lack of an opioid sparing effect. When opioid sparing was given a zero rating, parecoxib remained the highest scoring analgesic (93), followed by diclofenac (80), metamizole (76), and morphine (76). Parecoxib remained the most preferred analgesic in several other sensitivity analyses. Conclusion This MCDA-based assessment suggests that parecoxib has the most favorable efficacy-safety profile among the assessed postoperative analgesics.

Background and objectives Patient-controlled analgesia often involves combinations of multiple drugs. This study aimed to determine the stability of drug mixtures commonly used for intravenous patient-controlled analgesia. Materials and methods We examined four of the most commonly used drug combinations in intravenous patient-controlled analgesia at our institution. Mixtures contained fentanyl (400 μg), either oxycodone (10 mg) or hydromorphone (4 mg), nefopam (20 mg), and either ondansetron (10 mg) or ramosetron (0.3 mg). Each drug mixture was diluted in 0.9% saline and stored in a portable patient-controlled analgesia system at room temperature (24 °C) for 96 h. Physical attributes including color, turbidity, and precipitation were assessed using digital imaging and optical microscopy. Sterility testing was conducted to assess for microbiological contamination. The pH of each mixture was monitored for up to 96 h after mixing. The concentration of each drug in the mixture was also evaluated using high-performance liquid chromatography. Results All mixtures remained colorless and transparent with no visible sediment for 96 h. After 14 days of culture, none of the samples showed bacterial or fungal growth. The pH for all mixtures was maintained between 4.17 and 5.19, and the mean pH change in any mixture was less than 0.4 over the study period. The concentration of each drug remained between 90 and 110% of the initial value for 96 h after mixing. Conclusion Four drug mixtures commonly used for intravenous patient-controlled analgesia are physiochemically stable and remain sterile for 96 h after mixing.

Nefopam is a non-opioid, centrally acting, non-steroidal analgesic drug. It is used to treat mild to moderate painful conditions. Although developed about five decades ago, its use has gained resurgence in recent years. This study was designed to investigate the effects of different analgesic doses of nefopam on the liver and kidneys of mice. Forty albino mice were divided into four groups of 10 mice for each group. Group 1, 2 &3 received a daily intraperitoneal injection of Nefopam at 10, 20, and 30 mg/kg doses, respectively. The fourth group (control group) received injections of normal saline. After two weeks of treatment, the animals were weighed and sacrificed, and then blood was collected for liver enzymes analysis and renal function test as well as histological assessment. The results revealed that the bodyweight increase ratio was significantly lower in group 3 (P-value 0.05) of Nefopam on the kidneys. Nefopam is well tolerable by the liver at low analgesic doses but may have detrimental effects at higher analgesic doses and prolonged duration of intake.

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 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.

Objective: To evaluate the synergistic effect of a Selective Serotonin Reuptake Inhibitor (SSRI) and a Selective Cyclooxygenase 2 Inhibitor (ISCOx-2) in the management of After Rachianesthesia Headache in Obstetric Care. Patients and Methods: This was an experimental double-blind, randomized, multi-center clinical trial of non-inferiority clinical trials over a 12-month period (May 1, 2018 to April 30, 2019) in six hospitals in southeastern DR Congo, including all patients undergoing surgery or analgesia on spinal anesthesia for obstetrical indication and with headache characteristic of a dural breccia, with no known causes, contraindications to experimental products and informed consent to been obtained. The patients were divided into four different groups depending on the protocol used, namely: Group A = Rehydration + Paracetamol, Group B = Rehydration + Celecoxib, Group C = Rehydration + Nefopam and Group 4 = Rehydration + Celecoxib + Nefopam (Study Group). Using the Statview II software, the statistical analyzes of data obtained from the different tests were made using the ANOVA test for comparing the averages of different samples using the Fisher test. Verification of the normality of the samples was made by the Kurtosis and Skewness flattening and asymmetry test. Results: The protocol associating Celecoxib and Nefopam significantly demonstrates its effectiveness in reducing CPRAOs in the first two days with a gradual decrease in anxiety and length of stay. In addition, the majority of patients (75.6%) had a high overall level of satisfaction with this protocol. Conclusion: The Nefopam-Celecoxib combination shows its effectiveness in the early reduction of these CPRAOs, anxiety and length of stay with a high overall level of patient satisfaction. Given the good tolerance and accessibility of these products, we strongly suggest the use of this protocol for its validation in our environment and elsewhere, although it is desirable to continue research on other non-explored alien pathways.

The present study was designed as a prospective, randomized, double-blind clinical trial to evaluate the effects of preoperatively administered nefopam on postoperative acute hyperalgesia and the long-term painful sequelae compared to intraoperative administration. One hundred and fifty patients undergoing elective laparoscopic colectomy were enrolled. Group 1 (post-incisional nefopam) patients received saline at 30 min before skin incision followed by intraoperative administration of 20 mg nefopam at 1 h after incision. Group 2 (pre-incisional nefopam) patients were administered 20 mg nefopam before skin incision and received saline after skin incision. At postoperative 2, 6, 24, 48, and 72 h, fentanyl consumption and pain intensities at rest and during deep breathing were evaluated by visual analog scale (VAS). The incidence of the long-term painful sequelae after surgery was evaluated more than one year after surgery. Cumulative fentanyl consumption during postoperative 72 h was similar between Group 1 and Group 2 (1534 ± 698 μg, 95% CI 1367–1702 μg vs. 1442 ± 721 μg, 95% CI 1266–1618 μg, P = 0.197). VAS pain scores at rest were comparable between the two groups, but VAS scores during deep breathing were significantly lower in Group 2 than in Group 1. Six and five patients complained of mild pain (pain rating 1) at the surgical site in Group 1 and 2, respectively. Preoperatively administered nefopam reduced exertional pain compared to intraoperative administration although postoperative analgesic consumption was similar between two groups. It may be helpful to conduct early ambulation and deep breathing during the acute postoperative period in patients undergoing intestinal surgery. Trial registration No: KCT0001656.

Introduction: Pharmacological methods using variety of drugs like pethidine, morhine, tramadol, clonidine, doxapram, ketansarine, nefopam, neostigmine, magnesium sulfate have been tried in post spinal shivering. Aim of the present study was to compare the two drugs pethidine and dexmedetomidine for the control of intraoperative shivering under spinal anaesthesia. Materials and Methods: A prospective randomized study where total 80 patients of either gender aged between 20-60 years, ASA grade of I -II and patients who develop shivering of grade 2-3 (Crossley and Mahajan scale) after spinal anaesthesia were enclosed within the study after getting informed consent. The patients were randomized into two groups of 40 patients each. Group D- Dexmedetomidine group received single intravenous bolus dose of dexmeditomidine 0.5mcg/kg over 5 min. Group P -Pethidine group patients received 0.5mg/kg Pethidine IV over 5 min. The time was accurately noted in seconds from drug administration to the disappearance of shivering. Patients were monitored at intervals of 1 minute, 3min, 5min and thenceforth 10, 20 and 30 minutes until finish of surgery. Patients were intently monitored for failure of the drug, recurrence of shivering and side effects such as nausea, vomiting, bradycardia (20% of baseline), giddiness and sedation score will be recorded. Chi-square test was accustomed to evaluate categorical factors. Results: Dexmedetomidine group had significant reduction in time needed to control shivering and disappearance of shivering after drug administration. Conclusion: Through this study we tend to found that the time taken for control of shivering was shorter with Dexmedetomidine as compared to Pethidine. Side effects were less with Dexmedetomidine as compared to Pethidine. Keywords: Pethidine, Dexmedetomidine, Spinal anaesthesia, Shivering.

Open cardiac surgery may cause severe postoperative pain. The authors hypothesized that patients receiving a bundle of care using continuous erector spinae plane blocks (ESPB) would have decreased perioperative opioid consumption and improved early outcome parameters compared with standard perioperative management.A consecutive, patient-matched, controlled before-and-after study.Two tertiary teaching hospitals.The study comprised 67 consecutive patients undergoing elective cardiac surgery with cardiopulmonary bypass.In a controlled before-and-after trial, this study compared a historical group of 20 consecutive open cardiac surgery patients matched with a prospective group of 47 consecutive patients receiving continuous bilateral ESPB (0.25 mL/kg/side of ropivacaine 0.5%) after general anesthesia induction. For postoperative analgesia, both groups received paracetamol. The control group received intravenous (IV) morphine, 0.5 mg/h, and IV nefopam, 100 mg/24 h. In the ESPB group, 8 hours after the loading dose, catheters were connected to a pump infusing intermittent automatic boluses of ropivacaine 0.2% every 6 hours. If needed, for both groups, rescue analgesia was provided with IV ketorolac, 30 mg, and IV morphine, 30 µg/kg.Morphine consumption in the first 48 hours was significantly decreased in the ESPB group (40 [25-45] mg in the control group compared with 0 [0-0] mg in the ESPB group [p0.001]) as was intraoperative sufentanil (0.8 [0.6-0.9] µg/kg/h and 0.2 [0.16-0.3] µg/kg/h, respectively; p0.001). Times to chest tube removal, first mobilization, pain (Visual Analogue Scale) values 2 hours after chest tube removal, pain values at rest 1 month after surgery, and postoperative adverse events were significantly decreased in the ESPB group. There was no difference for extubation time and pain during first mobilization.The authors report for the first time that the use of a bundle of care including a continuous bilateral ESPB is associated with a significant decrease in intraoperative and postoperative opioid consumption, optimized rapid patient mobilization, and chest tube removal after open cardiac surgery.

International audience; 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 (interquartile range)] was significantly reduced in the PNK group [5 (1-11) mg] compared with either the C group [27 (11-42) mg; P

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 (ED50 ) were calculated from the log dose-response curves for each compound. Subsequently, the effects of ED8.7 s, ED12.5 s, ED17.5 s and ED35 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 (ED50 177.3 ± 15.4 mg/kg) than heat hyperalgesia (ED50 278.6 ± 43 mg/kg). Oral nefopam induced dose-dependent antinociception with similar efficacy for mechanical and heat hypersensitivity (ED50 s 5.42 ± 0.81 vs. 5.83 ± 0.72). Combinations of increasing isoeffective doses revealed that combined ED17.5 s (85.76 mg/kg paracetamol and 1.9 mg/kg nefopam) and ED35 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.

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). Conclusion: 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.

BackgroundIt is speculated that opioid-free anesthesia may provide adequate pain control while reducing postoperative opioid consumption. However, there is currently no evidence to support the speculation. The authors hypothesized that opioid-free balanced anesthetic with dexmedetomidine reduces postoperative opioid-related adverse events compared with balanced anesthetic with remifentanil.MethodsPatients were randomized to receive a standard balanced anesthetic with either intraoperative remifentanil plus morphine (remifentanil group) or dexmedetomidine (opioid-free group). All patients received intraoperative propofol, desflurane, dexamethasone, lidocaine infusion, ketamine infusion, neuromuscular blockade, and postoperative lidocaine infusion, paracetamol, nefopam, and patient-controlled morphine. The primary outcome was a composite of postoperative opioid-related adverse events (hypoxemia, ileus, or cognitive dysfunction) within the first 48 h after extubation. The main secondary outcomes were episodes of postoperative pain, opioid consumption, and postoperative nausea and vomiting.ResultsThe study was stopped prematurely because of five cases of severe bradycardia in the dexmedetomidine group. The primary composite outcome occurred in 122 of 156 (78%) dexmedetomidine group patients compared with 105 of 156 (67%) in the remifentanil group (relative risk, 1.16; 95% CI, 1.01 to 1.33; P = 0.031). Hypoxemia occurred 110 of 152 (72%) of dexmedetomidine group and 94 of 155 (61%) of remifentanil group patients (relative risk, 1.19; 95% CI, 1.02 to 1.40; P = 0.030). There were no differences in ileus or cognitive dysfunction. Cumulative 0 to 48 h postoperative morphine consumption (11 mg [5 to 21] versus 6 mg [0 to 17]) and postoperative nausea and vomiting (58 of 157 [37%] versus 37 of 157 [24%]; relative risk, 0.64; 95% CI, 0.45 to 0.90) were both less in the dexmedetomidine group, whereas measures of analgesia were similar in both groups. Dexmedetomidine patients had more delayed extubation and prolonged postanesthesia care unit stay.ConclusionsThis trial refuted the hypothesis that balanced opioid-free anesthesia with dexmedetomidine, compared with remifentanil, would result in fewer postoperative opioid-related adverse events. Conversely, it did result in a greater incidence of serious adverse events, especially hypoxemia and bradycardia.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New

Background. Nefopam is a non-NSAIDs and opioid sparing centrally acting drug which is effective for a multimodal postoperative analgesia. The present study aimed to evaluate the analgesic efficacy of nefopam combined with parecoxib for gynecologic surgery. Methods. This randomized double-blinded control trial recruited participants (n = 72) who underwent gynecologic surgeries and divided them into either a nefopam or control group. The study group received parecoxib 40 mg plus nefopam 20 mg, while the control group received parecoxib 40 mg plus normal saline solution intravenously during open abdominal gynecological surgery. Both groups then received either nefopam or normal saline every 6 hours postoperatively for 24 hours. Intravenous patient-controlled analgesia with morphine was given for breakthrough pain within 24 h. The participants were evaluated for morphine consumption within 24 hours and postoperative pain using a verbal numerical rating scale (VNRS) at a postanesthetic care unit, at 6-, 12-, and 24-hour postoperative periods. Adverse effects were recorded. Results. Morphine consumption within 24 hours and adverse effects were not significantly different between both groups. Mean difference and 95% confident interval of morphine consumption between both groups was 1.00 (−4.56, 4.76), P = 0.97 . The VNRS on movement at 6 hours after surgery of the nefopam group was significantly different from that of the control group [mean (SD), 4.14 (2.11) vs. 5.14 (1.80), P = 0.04 ]. The VNRS of the nefopam group at 12 hours after operation during resting and on movement was significantly different from that of the control group ([mean (SD), 1.47 (1.80) vs. 2.54 (2.15), P = 0.03 ], [mean (SD), 3.22 (1.84) vs 4.17 (1.74), P = 0.03 ]), respectively. Conclusions. The combined administration of nefopam and parecoxib during gynecologic surgery slightly reduced the VNRS at 6 and 12 hours postoperatively more than treatment with parecoxib.

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.

Supplemental Digital Content is available in the text., Objectives: This systematic review and meta-analysis addresses the efficacy and safety of nonopioid adjunctive analgesics for patients in the ICU. Data Sources: We searched PubMed, Embase, the Cochrane Library, CINAHL Plus, and Web of Science. Study Selection: Two independent reviewers screened citations. Eligible studies included randomized controlled trials comparing efficacy and safety of an adjuvant-plus-opioid regimen to opioids alone in adult ICU patients. Data Extraction: We conducted duplicate screening of citations and data abstraction. Data Synthesis: Of 10,949 initial citations, we identified 34 eligible trials. These trials examined acetaminophen, carbamazepine, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium sulfate, nefopam, nonsteroidal anti-inflammatory drugs (including diclofenac, indomethacin, and ketoprofen), pregabalin, and tramadol as adjunctive analgesics. Use of any adjuvant in addition to an opioid as compared to an opioid alone led to reductions in patient-reported pain scores at 24 hours (standard mean difference, –0.88; 95% CI, –1.29 to –0.47; low certainty) and decreased opioid consumption (in oral morphine equivalents over 24 hr; mean difference, 25.89 mg less; 95% CI, 19.97–31.81 mg less; low certainty). In terms of individual medications, reductions in opioid use were demonstrated with acetaminophen (mean difference, 36.17 mg less; 95% CI, 7.86–64.47 mg less; low certainty), carbamazepine (mean difference, 54.69 mg less; 95% CI, 40.39–to 68.99 mg less; moderate certainty), dexmedetomidine (mean difference, 10.21 mg less; 95% CI, 1.06–19.37 mg less; low certainty), ketamine (mean difference, 36.81 mg less; 95% CI, 27.32–46.30 mg less; low certainty), nefopam (mean difference, 70.89 mg less; 95% CI, 64.46–77.32 mg less; low certainty), nonsteroidal anti-inflammatory drugs (mean difference, 11.07 mg less; 95% CI, 2.7–19.44 mg less; low certainty), and tramadol (mean difference, 22.14 mg less; 95% CI, 6.67–37.61 mg less; moderate certainty). Conclusions: Clinicians should consider using adjunct agents to limit opioid exposure and improve pain scores in critically ill patients.

Postmastectomy pain syndrome (PMPS) remains poorly defined, although it is applied to chronic neuropathic pain following surgical procedures of the breast, including mastectomy and lumpectomy in breast-conserving surgery. It is characterized by persistent pain affecting the anterior thorax, axilla, and/or medial upper arm following mastectomy or lumpectomy. Though the onset of pain is most likely to occur after surgery, there may also be a new onset of symptoms following adjuvant therapy, including chemotherapy or radiation therapy. The underlying pathophysiology is likely multifactorial, although exact mechanisms have yet to be elucidated. In this regard, neuralgia of the intercostobrachial nerve is currently implicated as the most common cause of PMPS. Numerous pharmacological options are available in the treatment of PMPS, including gabapentinoids, tricyclic antidepressants, selective serotonin reuptake inhibitors, NMDA receptor antagonists, and nefopam (a non-opioid, non-steroidal benzoxazocine analgesic). Minimally invasive interventional treatment including injection therapy, regional anesthesia, botulinum toxin, and neuromodulation has been demonstrated to have some beneficial effect. A comprehensive update highlighting current perspectives on the treatment of postmastectomy pain syndrome is presented with emphasis on treatments currently available and newer therapeutics currently being evaluated to alleviate this complex and multifactorial condition.

Pain is a very important issue to take into account during hospitalization. Nefopam, a centrally acting analgesic, has a relative safety pharmacological profile with few and well-tolerated side effects, being used to treat acute or chronic pain. It inhibits the central reuptake of serotonin, norepinephrine and dopamine and modulates the sodium and calcium channels having only few contraindications. Nefopam can be part of balanced analgesia along with others non-opioids agents in order to reduce the opioid consumption and their complications, to control postoperative pain and to reduce the risk of neuropathic pain appearance. In order to avoid its adverse reactions, a slow infusion is always recommended. Nefopam has its role in preventing the shivering appearance during neuraxial or general anesthesia, can modulate the emergence agitation after nasal and maxillofacial surgery and can inhibit the sever hiccup during mechanical ventilation. Some cases about fatal overdoses are reported in the literature.

Background Patient-controlled epidural analgesia (PCEA) is known to provide good postoperative analgesia in many types of surgery including laparoscopic surgery. However, no study has compared PCEA with patient-controlled intravascular analgesia (PCIA) in laparoscopic radical prostatectomy (LARP). In this study, the efficacy and side effects of PCEA and PCIA after LARP were compared. Methods Forty patients undergoing LARP were randomly divided into two groups: 1) a PCEA group, treated with 0.2% ropivacaine 3 ml and 0.1 mg morphine in the bolus; and 2) a PCIA group, treated with oxycodone 1 mg and nefopam 1 mg in the bolus. After the operation, a blinded observer assessed estimated blood loss (EBL), added a dose of rocuronium, performed transfusion, and added analgesics. The numeric rating scale (NRS), infused PCA dose, and side effects were assessed at 1, 6, 24, and 48 h. Results EBL, added rocuronium, and added analgesics in the PCEA group were less than those in the PCIA group. There were no significant differences in side-effects after the operation between the two groups. Patients were more satisfied with PCEA than with PCIA. The NRS and accumulated PCA count were lower in PCEA group. Conclusions Combined thoracic epidural anesthesia could induce less blood loss during operations. PCEA showed better postoperative analgesia and greater patient satisfaction than PCIA. Thus, PCEA may be a more useful analgesic method than PICA after LARP.

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 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: Nefopam is a non-opioid, non-steroidal analgesic drug with fewer adverse effects than narcotic analgesics and nonsteroidal anti-inflammatory drugs, and is widely used for postoperative pain control. Because nefopam sometimes causes side effects such as nausea, vomiting, somnolence, hyperhidrosis and injection-related pain, manufacturers are advised to infuse it slowly, over a duration of 15 minutes. Nevertheless, pain at the injection site is very common. Therefore, we investigated the effect of warmed carrier fluid on nefopam injection-induced pain. Methods: A total of 48 patients were randomly selected and allocated to either a control or a warming group. Warming was performed by diluting 40 mg of nefopam in 100 ml of normal saline heated to 31-32°C using two fluid warmers. The control group was administered 40 mg of nefopam dissolved in 100 ml of normal saline stored at room temperature (21-22°C) through the fluid warmers, but the fluid warmers were not activated. Results: The pain intensity was lower in the warming group than in the control group (P ＜ 0.001). The pain severity and tolerance measurements also showed statistically significant differences between groups (P ＜ 0.001). In the analysis of vital signs before and after the injection, the mean blood pressure after the injection differed significantly between the groups (P = 0.005), but the heart rate did not. The incidence of hypertension also showed a significant difference between groups (P = 0.017). Conclusions: Use of warmed carrier fluid for nefopam injection decreased injection-induced pain compared to mildly cool carrier fluid. (Korean J Pain 2018; 31: 102-8)

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.

Background Nefopam is used to improve postoperative hypothermia in the field of plastic and aesthetic surgery. However, there is a paucity of data about its adverse hemodynamic effects and safety. We therefore assessed its adverse hemodynamic effects in patients undergoing plastic and aesthetic surgery. Methods We conducted a single-center retrospective study of 148 patients, in whom we measured hemodynamic parameters using sphygmomanometry (systolic blood pressure [SBP], diastolic blood pressure [DBP], arterial blood pressure [ABP], and heart rate [HR]). Moreover, we also assessed myocardial oxygen demand using the rate pressure product (RPP). Results The patients included 96 men and 52 women, with a mean age of 34.7±8.5 years. There were no significant differences in SBP, DBP, ABP, HR, or RPP before and after nefopam administration (P>0.05). However, a significant difference was found in the number of the patients with an HR of >100 beats per minute or with an RPP of >12 U before and after nefopam administration (P=0.001). Conclusions Surgeons should consider the possibility of tachycardia and increased blood pressure in the management of postoperative hypothermia in patients with cardiac arrhythmia, ischemic heart disease, or essential hypertension. Nonetheless, further prospective, large-scale, multi-center, randomized, controlled studies are warranted to confirm our results.

Nefopam is a non-opioid, non-steroidal, central analgesic thought to act via multiple mechanisms including potent inhibition of serotonin–norepinephrine reuptake and modulation of voltage-sensitive calcium and sodium channels. There has been a resurgence in its use for postoperative pain and neuropathic pain. Dosing route-dependent metabolism and clinical effects have been described following intravenous and oral nefopam. N-desmethylnefopam and nefopam N-oxide are metabolites of clinical interest. We sought to develop a joint pharmacokinetic model to simultaneously describe the plasma and urinary pharmacokinetics of nefopam and the two metabolites following an oral pharmacological dose of [14C]-nefopam to healthy volunteers, and to estimate inter-individual variability in their pharmacokinetics. Pharmacokinetic data for the parent and metabolites were analyzed simultaneously using NONMEM® (nonlinear mixed-effect modeling) v7.3. The modeling process evaluated, in part, one- and two-compartment linear pharmacokinetic models for nefopam and a single compartment for each of the two metabolites. Pathways for presystemic metabolism of both metabolites were explored. The final structural model simultaneously described the plasma and urinary pharmacokinetics of nefopam and the two metabolites. It consists of a central compartment for nefopam and for each of the two metabolites, as well as a peripheral compartment for the parent, and the associated urine compartments. The rapid formation and appearance of the N-oxide in plasma, characterized by concentrations that peak earlier than the parent, could be described by presystemic formation in the gastrointestinal tract. A descriptive, robust and predictive parent–metabolite model has been developed using a population mixed-effects approach to characterize the pharmacokinetics of nefopam and its metabolites simultaneously in healthy subjects following oral administration of nefopam. The model may be used for dose selection, analysis of sparse data, identification of intrinsic and extrinsic factors, and to model the clinical effects of each analyte.

Background/aim: We performed this prospective randomized double-blind study to compare the effects of nefopam versus ketorolac in intravenous fentanyl-based patient-controlled analgesia (PCA) after shoulder arthroscopic orthopedic surgery. Materials and methods: Ninety-two patients were randomly divided into two groups to receive intravenous PCA. Patients were assigned to either the nefopam group (nefopam 120 mg and fentanyl 20 µg/kg) or the ketorolac group (ketorolac 2 mg/kg and fentanyl 20 µg/kg). Pain was assessed on a visual analogue scale (VAS) and a numeric rating scale (NRS). Additionally, patient satisfaction, adverse events, and vital signs were monitored. Results: There were no significant differences in VAS score (P = 0.48) or NRS score (P = 0.15) between the two groups. Similarly, patient satisfaction did not differ between the two groups [8.5(0.8) vs. 8.2(1.0), P = 0.14]. There were no statistically significant differences in the incidence of nausea (P = 0.72), vomiting (P = 0.46), urinary retention (P = 0.82), sweating (P = 0.49), or dizziness (P = 0.45) between the two groups. Likewise, there were no differences in heart rate [78.2(7.7) vs. 75.2(6.5), P = 0.18] or SpO2 [98.4(1.8) vs. 98.5(1.9), P = 0.83]. Conclusion: Nefopam is an appropriate alternative for co-administration with fentanyl-based PCA in patients who have difficulty using nonsteroidal antiinflammatory drugs.

Background We compared the analgesic efficacy and side effects of ketorolac and nefopam that were co-administered with fentanyl via intravenous patient-controlled analgesia. Methods One hundred and sixty patients scheduled for laparoscopic cholecystectomy were randomly assigned to ketorolac (Group K) or nefopam (Group N) groups. The anesthetic regimen was standardized for all patients. The analgesic solution contained fentanyl 600 µg and ketorolac 180 mg in Group K, and fentanyl 600 µg and nefopam 120 mg in Group N. The total volume of analgesic solution was 120 ml. Postoperative analgesic consumption, recovery of pulmonary function, and pain intensities at rest and during the forced expiration were evaluated at postoperative 2, 6, 24, and 48 h. The postoperative side effects of analgesics were recorded. Results Cumulative postoperative analgesic consumptions at postoperative 48 h were comparable (Group K: 93.4 ± 24.0 ml vs. Group N: 92.9 ± 26.1 ml, P = 0.906) between the groups. Pain scores at rest and during deep breathing were similar at the time of each examination. The recovery of pulmonary function showed no significant differences between the groups. Overall, postoperative nausea and vomiting incidence was higher in Group N compared with Group K (59% vs. 34%, P = 0.015). The other side effects were comparable between both groups. Conclusions Analgesic efficacies of ketorolac and nefopam that were co-administered with fentanyl for postoperative pain management as adjuvant analgesics were similar. However, postoperative nausea and vomiting incidence was higher in the nefopam-fentanyl combination compared with the ketorolac-fentanyl combination.

Effectiveness of different methods of analgesia was studied in 34 aged patients suffering chronic low back pain. All patients were at age 60 to 86 and were randomized into N-group in which nefopam (60 mg rectally) was administrated and K-group that included patients who received ketoprofen (100 mg rectally). The end-points of this prospective study were decrease of pain intensity after analgesics administration, contentment of therapy, and characteristics of side effects of medications taking (twice daily for three days). We found that pain intensity decreases by 6,3±1,6 in N-group and 6,1±1,3 in K- group (p0.05 in comparison between groups). No significant differences between groups were in estimation of therapy contentment. No side effects were registered. Thus, our data proved the equal effectiveness of central nonopioid analgesic nefopam and nonselective cyclooxygenise inhibitor ketoprofen for achievement of good analgesia in aged patients with chronic low back pain.

Prospective research was made to evaluate the efficiency of nefopam in anasthesiology manual- analgosedation with preserved consciousness- during anticataractal and antiglaucoma operations. The research involved 2 groups of patients: with nefopam analgesia and tramadol analgesia. Data of research includes evaluation of the dynamics of hemodynamic information and oxygenation, rate of intraoperation critical incidents (oculocardiac syndrome, other arrhythmias, hypertension and hypotension). By verbal pain assessment scale we have compared the level of intraoperation analgesia. We get the following results: combination of nefopam and droperidol provides analgosedation which is more hemodynamic stable and has significantly lower intraoperation critical incidents then analgosedation of tramadol. Nefopam has undesirable side effects like temperate increase in heart rate and pain during injection along the vein in combination with ketorolac. Sufficient dose for analgesia at old-aged patients in ophthalmosurgical practice is 10 mg of nefopam.

Background Nefopam is a centrally acting analgesic which has a theoretical risk of stopping lactation due to its anticholinergic and dopaminergic effects. The aim of this study was to evaluate the effect of nefopam on lactation and to investigate potential adverse effects on newborns. Methods Seventy-two women, scheduled to undergo a caesarean delivery under spinal anaesthesia and wanting to breastfeed, were randomised to one of two groups: nefopam (20mg, six hourly) or paracetamol (1g, six hourly). In both groups, postoperative analgesia was supplemented with ketoprofen (50mg, six hourly) in conjunction with intrathecal morphine 0.1mg. The primary outcome was onset of lactation, estimated by weighing the newborns before and after feeding; by maternal perception of breast fullness and based on serum prolactin concentration 48hours postpartum. Secondary outcomes were neonatal adverse effects evaluated by neurobehavioural score at 12, 24, 48, and 72hours after birth. Statistical analyses were performed using Chi-squared, Fisher exact and Student t tests as appropriate. P Results The difference in the weight of the newborn before and after each feed, maternal perception of breast fullness and serum prolactin did not significantly differ between groups. The volume of artificial milk given to newborns of mothers in the nefopam group on days two and three was significantly greater than for the paracetamol group. Neurobehavioural scores were comparable at each time point. Conclusion Nefopam does not appear to delay the onset of lactation or present any clear risk to the newborn.

Patients with Neurofibromatosis type 1 display delayed fracture healing and the increased deposition of fibrous tissue at the fracture site. Severe cases can lead to non-union and even congenital pseudarthrosis. Neurofibromatosis type 1 is caused by a mutation in the NF1 gene and mice lacking the Nf1 gene show a fracture repair phenotype similar to that seen in patients. Tissue from the fracture site of patients with Neurofibromatosis type 1 and from mice deficient in the Nf1 gene both show elevated levels of β-catenin protein and activation of β-catenin mediated signaling. Constitutively elevated β-catenin leads to a delayed and fibrous fracture repair process, and (RS)-5-methyl-1-phenyl-1,3,4,6-tetrahydro-2,5-benzoxazocine (Nefopam, a centrally-acting, non-narcotic analgesic agent) inhibits β-catenin mediated signaling during skin wound repair. Here we investigate Nefopam's potential as a modulator of bone repair in mice deficient in Nf1. Mice were treated with Nefopam and investigated for bone fracture repair. Bone marrow stromal cells flushed from the long bones of unfractured mice were treated with Nefopam and investigated for osteogenic potential. Treatment with Nefopam was able to lower the β-catenin level and the Axin2 transcript level in the fracture calluses of Nf1 deficient mice. Cultures from the bone marrow of Nf1-/- mice had significantly lower osteoblastic colonies and mineralized nodules, which was increased when cells were cultured in the presence of Nefopam. Fracture calluses were harvested and analyzed 14days and 21days after injury. Nf1-/- calluses had less bone, less cartilage, and higher fibrous tissue content than control calluses. Treatment with Nefopam increased the bone and cartilage content and decreased the fibrous tissue content in Nf1-/- calluses. These findings present a potential treatment for patients with Neurofibromatosis 1 in the context of bone repair. Since Nefopam is already in use in patient care, it could be rapidly translated to the clinical setting.

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.

International audience; AbstractIntroduction : 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.