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).

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 Between Preoperative and Intraoperative Administration of Nefopam for Acute and Chronic Postoperative Pain in Colon Cancer Patients: A Prospective, Randomized, Double-Blind Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The Effect of Nefopam Infusion during Laparascopic Cholecystectomy on Postoperative Pain.

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

Does continuous wound infiltration enhance baseline intravenous multimodal analgesia after posterior spinal fusion surgery? A randomized, double-blinded, placebo-controlled study.

PURPOSE: There has been a growing interest in continuous local anaesthetic wound infiltration as a non-opioid technique for postoperative pain relief. The impact of this modality on baseline analgesia after spinal fusion surgery has however been inconclusive. We tested whether continuous wound infiltration with ropivacaine can enhance postoperative analgesia compared to a baseline intravenous multimodal analgesia protocol after spinal fusion surgery. METHODS: In this randomized, double-blinded, placebo-controlled study, a multiholed 19-gauge catheter was placed at the end of the surgical procedure through the wound to permit the continuous administration (8 ml/h) of ropivacaine 0.2 % (ropivacaine group; n = 19 patients) or saline (control group; n = 20 patients) during the first 48 postoperative hours (H48). Both groups received intraoperative low-dose ketamine, a combination of acetaminophen, non-steroidal anti-inflammatory drug, and nefopam over the same postoperative period, and morphine delivered by a patient-controlled analgesia (PCA) device. RESULTS: Morphine consumption was comparable between the two groups both at H48, 38 mg (26:52) (median, 25th:75th percentile) (control group) versus 43 mg (19:74) (ropivacaine group), and at H24, 18 mg (16:22) versus 22 mg (9:35) respectively. Pain scores at rest and during mobilization, quality of postoperative sleep, and morphine-related side effects were comparable between the two groups at H24 and H48. CONCLUSION: Our findings indicate that no additional analgesia was provided with continuous wound infiltration of ropivacaine compared to a baseline intravenous multimodal analgesia protocol after spinal fusion surgery. TRIAL REGISTRATION: Clinicaltrials.gov #NCT01743794.

THE USE OF DEXMEDETOMIDINE IN COMBINATION NEFOPAM FOR POSTOPERATIVE ANALGESIA AFTER LAPAROSCOPIC CORRECTION OF MORBID OBESITY.

AIM: To study the possibility of using a combination of dexmedetomidine with nefopam for postoperative analgesia in patients with morbid obesity after bariatric surgery in anesthesia quality aspects and theimpact of the study on the combination during the inflammatory response to surgical trauma. SUBJECTS AND METHODS: A prospective cohort study of 48 patients with obesity. RESULTS: Based on the analysis of hemodynamic parameters, evaluation of pain using a numeric rating scale pain concluded that selective agonist of o-2 adrenergic dexmedetomidine in combination with nefopam provides effective postoperative pain relief in patients who underwent bariatric surgery, and is not a factor for suppression of postoperative inflammatory response Unlike the effects of ketorolac tromethamine, do not always provide a sufficient level of analgesia and reduce the rate of growth in the level of IL-6. CONCLUSION: The combination of dexmedetomidine with nefopam provides sufficient analgesic effect after bariatric surgery, with noted a more rapid onset of analgesia than with ketorolac. Postoperative analgesia and dexmedetomidine nefopam, unlike the use of ketorolac tromethamine, are not violated ratio of interleukins 1 and 6 was not a factor and suppression of postoperative acute phase inflammatory response.

A Randomized Clinical Trial of Nefopam versus Ketorolac Combined With Oxycodone in Patient-Controlled Analgesia after Gynecologic Surgery.

OBJECTIVES: Nefopam is a centrally-acting non-opioid analgesic, which has no effect on bleeding time and platelet aggregation. There has been no study about nefopam and oxycodone combination for postoperative analgesia. In this study, we present efficacy and side effects of nefopam/oxycodone compared with ketorolac/oxycodone in patient-controlled analgesia (PCA) after gynecologic surgery. METHODS: 120 patients undergoing gynecologic surgery were divided randomly into two groups: Nefopam group treated with oxycodone 1 mg and nefopam 1 mg bolus; and Ketorolac group treated with oxycodone 1 mg and ketorolac 1.5 mg bolus. After the operation, a blinded observer assessed the pain with a numeric rating scale (NRS), infused PCA dose and sedation score at 1, 4, 24, and 48 h, nausea, vomiting, headache, shivering, pruritus and delirium at 6, 24 and 48 h, and satisfaction at 48 h after the operation. RESULTS: Nefopam group showed less nausea than Ketorolac group within 6 h after the operation. There were no significant differences in demographic data and other complications between both groups. At 48 h after operation, satisfaction and the infused PCA volumes of Nefopam group (34.0± 19.7 ml) showed no significant differences compared to Ketorolac group (30.7± 18.4 ml, P-value= 0.46). CONCLUSION: Nefopam showed a similar efficacy and lower incidence of nausea within 6 h after the operation to that of ketorolac in PCA. Nefopam may be a useful analgesic drug for the opioid-based PCA after gynecologic surgery. Further evaluation of accurate equivalent dose of nefopam as well as pharmacokinetics of bolus administration is required.

Nefopam as an adjunct to intravenous patient-controlled analgesia after renal transplantation: a randomised trial.

BACKGROUND: Nefopam has been used as an adjuvant to opioid analgesia after operation. We investigated the efficacy of nefopam as an adjunct to fentanyl-based intravenous patient-controlled analgesia (IV PCA) on post-operative pain relief in patients undergoing renal transplantation. METHODS: Ninety-eight patients undergoing elective renal transplantation were randomised into two groups: nefopam or control groups. The former received nefopam (160 mg in 200 ml at a rate of 4 ml/h) whereas the latter received normal saline during the first 48 h after reperfusion of grafted kidney. Pain intensity scores, cumulative dose of fentanyl, and the incidence of adverse events were assessed at 1, 6, 12, 24, and 48 h post-operatively. Serum creatinine and estimated glomerular filtration rate were evaluated on post-operative days 1, 2, 4, and 7. RESULTS: The cumulative fentanyl consumption during the first 48 h after operation was 19% less in the nefopam group than that in the control group (1005 ± 344 µg vs. 1246 ± 486 µg, mean ± SD; P = 0.006). Pain intensity scores at rest and on coughing were significantly lower in the nefopam group throughout the first 12 and 48 h after operation, respectively. Adverse events and early graft function were comparable between the groups, except a significantly lower incidence of drowsiness observed in the nefopam group (4% vs. 21%, P = 0.027). CONCLUSION: In combination with fentanyl PCA, nefopam reduced post-operative fentanyl consumption with superior analgesia after renal transplantation.

Mechanical Antiallodynic Effect of Intrathecal Nefopam in a Rat Neuropathic Pain Model.

Nefopam has a pharmacologic profile distinct from that of opioids or other anti-inflammatory drugs. Several recent studies demonstrate that nefopam has a mechanism of action similar to those of anti-depressants and anticonvulsants for treating neuropathic pain. The present study investigates the mechanical antiallodynic effect of nefopam using immunohistochemical study and western blot analysis in a rat neuropathic pain model. Twenty-eight male Sprague-Dawley rats were subjected to left fifth lumbar (L5) spinal nerve ligation and intrathecal catheter implantation, procedures which were not performed on the 7 male Sprague-Dawley rats in the sham surgery group (group S). Nefopam, either 10 or 100 µg/kg (group N10 or N100, respectively), and normal saline (group C) were intrathecally administered into the catheter every day for 14 days. The mechanical allodynic threshold of intrathecal nefopam was measured using a dynamic plantar aesthesiometer. Immunohistochemistry targeting cluster of differentiation molecule 11b (CD11b) and glial fibrillary acidic protein (GFAP) was performed on the harvested spinal cord at the level of L5. Extracellular signal-regulated kinase 1/2 (ERK 1/2) and cyclic adenosine monophosphate response element binding protein (CREB) were measured using western blot analysis. The N10 and N100 groups showed improved mechanical allodynic threshold, reduced CD11b and GFAP expression, and attenuated ERK 1/2 and CREB in the affected L5 spinal cord. In conclusion, intrathecal nefopam reduced mechanical allodynia in a rat neuropathic pain model. Its mechanical antiallodynic effect is associated with inhibition of glial activation and suppression of the transcription factors' mitogen-activated protein kinases in the spinal cord.

Nefopam and meperidine are infra-additive on the shivering threshold in humans.

BACKGROUND: Induction of therapeutic hypothermia is often complicated by shivering. Nefopam, a nonsedative benzoxazocine analgesic, reduces the shivering threshold (triggering core temperature) with minimal side effects. Consequently, nefopam is an attractive drug for inducing therapeutic hypothermia. However, nefopam alone is insufficient and thus needs to be combined with another drug. Meperidine also reduces the shivering threshold. We therefore determined whether the combination of nefopam and meperidine is additive, infra-additive, or synergistic on the shivering threshold. METHODS: Ten volunteers were each studied on 4 randomly assigned days. In random order, they were given the following treatments: (1) control, no drug; (2) nefopam to a target concentration of 0.1 µg/mL; (3) meperidine to a target concentration of 0.1 µg/mL; and (4) both nefopam and meperidine at target concentrations of 0.1 µg/mL each. Lactated Ringer's solution at 4°C was infused to decrease core temperature while mean skin temperature was kept near 30.5°C. The core temperature that increased oxygen consumption >25% defined the shivering threshold. RESULTS: Nefopam reduced the shivering thresholds by 0.7°C ± 0.3°C compared with no drug. Meperidine reduced the shivering thresholds by 0.4°C ± 0.3°C compared with no drug. When combined, the shivering threshold decreased by only 0.6°C ± 0.4°C, which was about half what would have been expected based on the individual effects of each drug (P < 0.001). The effect of combined nefopam and meperidine on the shivering threshold was thus infra-additive. CONCLUSIONS: The combination of nefopam and meperidine should be avoided for induction of therapeutic hypothermia. Better options would be combinations of drugs that are at least additive or even synergistic.

Pharmacokinetics of dexamethasone and nefopam administered alone or in combination using a newly developed prefilled multi-drug injector in rats.

BACKGROUND/AIM: It is significant for patients with traumatic brain injury (TBI) to receive prehospital emergency treatment as early as possible to reduce mortality. Therefore, a new prefilled multi-drug injector was developed to improve the treatment of TBI. Here, we studied the pharmacokinetics of dexamethasone (DXM) and nefopam using the injector to investigate the significance of drug interactions and the necessity of dose adjustment. METHODS: Rats were administered DXM and nefopam intramuscularly alone or in combination using the injector. The concentrations of DXM and nefopam were measured by means of HPLC. The noncompartmental approach was used to calculate pharmacokinetic parameters. RESULTS: All animals appeared to tolerate the injection very well. The maximum concentration 90% confidence interval (CI) of nefopam was in the bioequivalence range when nefopam was co-administered with DXM. However, the AUC 90% CI of nefopam was out of the range. A statistically significant alteration was also observed in the clearance of nefopam. The co-administration exhibited no significant influence on the pharmacokinetic parameters of DXM. CONCLUSIONS: These results indicate that the co-administration of DXM and nefopam using the prefilled multi-drug injector significantly alters some pharmacokinetic parameters of nefopam and has a minor effect on DXM pharmacokinetics.

To enhance the efficiency of nefopam transdermal iontophoresis by using a novel method based on ion-exchange fiber.

BACKGROUND: In the system of the iontophoresis, the external electric field made the ions in the system moving directly, then, the current was generated. Because the current was contributed by all ions in the system, and the small ions with large amount often had higher conductibility than the drug ions, the fraction of the total current contributed by the drug ions was often low. It was the main reason for the generally low efficiency of the transdermal iontophoretic drug delivery. OBJECTIVES: The objective of this study was to find a novel method to increase the fraction of the total current contributed by the drug ions so as to enhance the drug's iontophoretic delivery. METHOD: Iontophoretic transport of nefopam hydrochloride solution and iontophoretic transport of nefopam assisted by ion-exchange materials, including ion-exchange resin, ion-exchange membrane and ion-exchange fiber, across the rat skin were investigated. RESULTS: Both in vitro and in vivo iontophoretic transport experiments showed that the efficiency of the nefopam-fiber iontophoretic system for nefopam permeating across rat skin was the highest among four iontophoretic systems (nefopam solution, nefopam-resin, nefopam-membrane and nefopam-fiber). CONCLUSION: The results of this study suggested that there was an enhancement of nefopam across rat skin by ion-exchange fibers in ion-exchange fibers assisted iontophoresis. The present study has demonstrated the potential of a new approach of using ion-exchange fibers to improve the efficiency of the transdermal iontophoresis for cationizable drugs.

Slow injection of nefopam reduces pain intensity associated with intravenous injection: a prospective randomized trial.

PURPOSE: We aimed to investigate the frequency and severity of pain associated with intravenous injection of nefopam and to determine whether a slow rate of administration can effectively reduce such pain. METHODS: We used a solution containing 30 mg nefopam diluted to 20 ml in saline. In all, 102 adult patients undergoing minor surgery were randomly allocated to one of three administration groups: A (60 ml/h, n = 34); B (120 ml/h, n = 34); or C (180 ml/h, n = 34). All patients scored the maximal pain experienced during the 120-s infusion period, using the visual analogue scale (VAS) and the verbal pain score (VPS). Adverse events including phlebitis were recorded. RESULTS: Eighty-three patients (29 in group A, 27 each in groups B and C) were included in the final analysis. The incidence of injection pain was lower in group A (86.2 %) than in groups B (96.3 %) and C (100 %), but this difference was not statistically significant. The proportion of patients with a tolerable level of pain (VAS 0-3 and VPS 0-1) was significantly higher in group A (79.3 %) versus groups B (7.4 %) and C (3.7 %). The mean VAS scores for groups A, B, and C were 2.2 ± 1.3, 5.1 ± 1.6, and 7.2 ± 1.7, respectively, and these differences were statistically significant. CONCLUSIONS: At the slower rate of infusion (60 ml/h) of the 1.5 mg/ml nefopam solution, injection pain intensity was attenuated to a significantly greater degree than at the faster rates.

[Thrombocytopenia and postoperative analgesia].

OBJECTIVE: To develop effective and safe measures of postoperative multimodal analgesia (optimizing the use of narcotic analgesics) in surgical treatment of hematological patients with thrombocytopenia. DESIGN: A pilot and prospective comparative controlled study. METHODS: We studied 27 patients with acquired thrombocytopenia who underwent laparoscopic splenectomy. Three schemes of anesthesia were used: 1) Nefopam 20 mg/day + trimeperidin (n = 7); 2) Paracetamol 4 g/day + trimeperidin (n = 10); 3) paracetamol + trimeperidin + glucocorticosteroids (GC) (through treatment of the underlying disease) (n = 10). Analgesic properties and effect of each scheme were assessed according to a rating scale of pain NRS (10 points) and VAS (100 points) studied. Additionally we evaluated the effect of nefopam and paracetamol on the functional properties of platelets and hemostasis, platelet levels while monitoring and indicators of thromboelastogram (TEG). RESULTS: Application of paracetamol + trimeperidin accompanied with effectively reducing of postoperative pain (less than 5 points on the NRS). The level of postoperative pain was lower in patients who were treated with corticosteroids within the therapy of the underlying disease before surgery and who continued to receive it in postoperative period (2-3 points NRS). Nefopam use in the perioperative period is not only inferior to the analgesic effect of paracetamol, but also causes frequent side effects. Consumption of narcotic analgesic--trimeperidin when applying nefopam averaged 43 mg/day, the appointment of paracetamol--28 mg/day, using a combination of paracetamol + GC--20 mg/day. Thus, GC within the underlying disease treatment substantially reduces the need for opioid analgesics. A monitoring of the number of platelets and TEG did not shows negative effect of paracetamol and nefopam on platelet and plasma hemostasis. CONCLUSIONS: Nefopam and paracetamol may be used in patients with thrombocytopenia, as do not affect the hemostasis and platelet count. Application of postoperative analgesia scheme paracetamol + trimeperidin in patients receiving corticosteroids provides the maximum reduction of pain with the least consumption of narcotic analgesics.

[Postoperative analgesia with nefopam and non-steroidal anti-inflammatory drugs in patients after surgery for tumors of head and neck].

MATERIALS AND METHODS: 83 adult patients included in the study were divided into two groups. Patients of the group-1 (n-49) had medium level of pain after cancer head and neck surgery. Patients of the group-2 (n-34) had severe pain. Three first postoperative days their post-operative multimodal analgesia started with tenoxycam 20 mg i.m. after induction of anesthesia, then every 24 hour (58 patients). 25 patients got ketoprofen 100 mg i.m. every 8-12 hours instead of tenoxycam. All patients had nefopam 30 mg i.m. 30 min prior the end of surgery procedure, and every 8 hours afterwards. 7 patients of the group-1 had more than 4 pain scores (day 1), 4 patients--at the day 2. They received tramadol or paracetamol additionally. 7 patients (group-2) also had up to 5 pain scores on the day 1, 5 patients had 4 pain scores on the day 2, and 3 patients 4 pain scores on the day 3. All that patients received additional analgesia with tramadol or trimeperidine once a day. 8.4% of patients suffered from adverse reactions (tachycardia, PONV and sweating). CONCLUSION: This method of multimodal postoperative analgesia is very simple and fairly efficient.

Ondansetron does not attenuate the analgesic efficacy of nefopam.

OBJECTIVES: The aim of this study was to investigate if there is any interaction between ondansetron and nefopam when they are continuously co-administrated during patient-controlled intravenous analgesia (PCIA). METHODS: The study was a prospective, randomized, controlled, non-inferiority clinical trial comparing nefopam-plus-ondansetron to nefopam alone. A total of 230 postoperative patients using nefopam for PCIA, were randomly assigned either to a group receiving continuous infusion of ondansetron (Group O) or to the other group receiving the same volume of normal saline continuously (Group N). Postoperative pain intensity scores, the sum of pain intensity difference over 24 hours postoperatively (SPID24hr), the incidence of adverse events, and the total consumption of nefopam were evaluated respectively. RESULTS: Postoperative pain was treated successfully in both groups. The mean SPID24hr scores were 95.6 mm in Group N and 109.3mm in Group O [95% confidence interval (CI) -14.28, 24.32]. The lower margin of the 95% CI was above the pre-determined non-inferiority margin (-30mm) for SPID24hr, which indicated that nefopam-plus-ondansetron was not worse than the nefopam alone in term of analgesic efficacy. In addition, there was no statistical difference between the two groups in term of cumulative consumption of nefopam. Compared with Group N, postoperative vomiting was significantly reduced in Group O during the postoperative 24 hours (P < 0.05). Less rescue antiemetics were given to patients in Group O than those receiving nefopam alone (P < 0.05). There were no differences in postoperative nausea between the two groups. CONCLUSION: Nefopam-plus-ondansetron is not inferior to nefopam alone in relieving the pain in PCIA after minimally invasive surgery. In addition, adverse events are reduced without compromising analgesic efficacy.

[Ketoprophen and nefopam combination for postoperative analgesia with minimal use of narcotic analgesics in cardio-surgical patients].

4 combinations of analgesia were studied: 1) Nefopam and patient-controlled analgesia (PCA) with Trimeperidine; 2) Ketoprofen (100 microg each 12 hours intramuscular) and PCA with Trimeperidine; 3) Nefopam, Ketoprofen and PCA with Trimeperidine; 4) PCA with Trimeperidine as monotherapy in early postoperative period in cardio-surgical patients. 80 patients (age from 40 to 70) were divided into 4 groups, 20 patients in each group. Administration of Nefopam and Ketoprofen before extubation reduced the intensity of pain syndrome (in average on 90%) and promoted the early stirring up of patients. Combination of Nefopam and Ketoprofen provided the most expressed analgesic and opioids-saving effects. In this group average amount of Trimeperidine per 24 hours was 14.7 microg that was 4.9 times less than in group of PCA with Trimeperidine as monotherapy. Dynamics of maximal inspiratory capacity of the lungs in the first three groups was better than in group of PCA with Trimeperidine as monotherapy beginning from 6th hour of study. In common undesirable effects was connected with Trimeperidine administration and depended on its dose. The frequency of nausea, vomit, dizziness and weakness was authentically higher in the group of PCA with Trimeperidine as monotherapy than in other groups.

[The use of central acting analgesic nefopam in postoperative analgesia in cardiac surgery patients].

A prospective, randomized, comparative study was conducted. 3 analgesia protocols were used: 1) patient controlled analgesia (PCA) with trimeperidine in combination with a nefopam constant infusion; 2) PCA with trimeperidine in combination with a nefopam bolus; 3) PCA with trimeperidine separately during early postoperative period in cardiac surgery patients. The study included 60 patients agedf rom 40 to 65 years of age (20 patients in each group). The analgesia efficacy was evaluated with a 5-point verbal rating scale (VRS) for pain intensity and inspiratory lung capacity (ILC), measured with incentive spirometer. The safety of nefopam during early postoperative period in cardiac surgery patients was shown. The combination of nefopam and trimeperidine led to a more pronounced analgetic effect. Trimeperidine consumption was significantly lower in nefopam groups than in the group of isolated PCA. Wholly adverse effects were associated with trimeperidine and were dose-related The incidence of nausea, vomiting, dizziness, weakness, bowel paresis was significantly higher in isolated PCA group than in the other two groups.

Compartmental pharmacokinetics of nefopam during mild hypothermia.

BACKGROUND: Nefopam is a non-opioid, non-steroidal, centrally acting analgesic which has an opioid-sparing effect. It also reduces the threshold (triggering core temperature) for shivering without causing sedation or respiratory depression. The drug is therefore useful as both an analgesic and to facilitate induction of therapeutic hypothermia. However, compartmental pharmacokinetics during hypothermia are lacking for nefopam. METHODS: We conducted a prospective, randomized, blinded study in eight volunteers. On two different occasions, one of two nefopam concentrations was administered and more than 30 arterial blood samples were gathered during 12 h. Plasma concentrations were determined using gas chromatography/mass spectrometry to investigate the pharmacokinetics of nefopam with non-linear mixed-effect modelling. RESULTS: A two-compartment mammillary model with moderate inter-individual variability and inter-occasional variability independent of covariates was found to best describe the data [mean (SE): V(1)=24.13 (2.8) litre; V(2)=183.34 (13.5) litre; Cl(el)=0.54 (0.07) litre min(-1); Cl(dist)=2.84 (0.42) litre min(-1)]. CONCLUSIONS: The compartmental data set describing a two-compartment model was determined and could be implemented to drive automated pumps. Thus, work load could be distributed to a pump establishing and maintaining any desired plasma concentration deemed necessary for a treatment with therapeutical hypothermia.