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1.
Pain Physician ; 25(6): 491-500, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36122258

RESUMO

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


Assuntos
Analgésicos não Narcóticos , Nefopam , Analgésicos/uso terapêutico , Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Fentanila/uso terapêutico , Humanos , Nefopam/efeitos adversos , Nefopam/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Estudos Prospectivos , Solução Salina/uso terapêutico , Cirurgia Torácica Vídeoassistida
2.
J Anesth ; 36(4): 506-513, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35732849

RESUMO

PURPOSE: Remifentanil is useful in balanced anesthesia; however, there is concern regarding opioid-induced hyperalgesia. The effect of remifentanil on rebound pain, characterized by hyperalgesia after peripheral nerve block has rarely been studied. This study evaluated whether intraoperative remifentanil infusion may increase postoperative analgesic requirement in patients receiving preoperative interscalene brachial plexus block (IBP). METHODS: Sixty-eight patients undergoing arthroscopic shoulder surgery under general anesthesia were randomly allocated to remifentanil (R) or control (C) group. Preoperative IBP with 0.5% ropivacaine 15 mL was performed in all patients. Intraoperative remifentanil was administered only in the R group. Postoperative pain was controlled using intravenous patient-controlled analgesia (IV-PCA) and rescue analgesics. The primary outcome was the dosage of fentanyl-nefopam IV-PCA infused over 24 h postoperatively. The secondary outcomes included the numeric rating scale (NRS) score recorded at 4-h intervals over 24 h, amount of rescue analgesics and total postoperative analgesics used over 24 h, occurrence of intraoperative hypotension, postoperative nausea and vomiting (PONV) and delirium. RESULTS: The dosage of fentanyl-nefopam IV-PCA was significantly less in C group than R group for postoperative 24 h. Fentanyl 101 [63-158] (median [interquartile range]) µg was used in the C group, while fentanyl 161 [103-285] µg was used in the R group (median difference 64 µg, 95% CI 10-121 µg, P = 0.02). Nefopam 8.1 [5.0-12.6] mg was used in the C group, while nefopam 12.9 [8.2-22.8] mg was used in the R group (median difference 5.1 mg, 95% CI 0.8-9.7 mg, P = 0.02). The total analgesic consumption: the sum of PCA consumption and administered rescue analgesic dose, converted to morphine milligram equivalents, was higher in the R group than C group (median difference 10.9 mg, 95% CI 3.0-19.0 mg, P = 0.01). The average NRS score, the incidence of PONV and delirium, were similar in both groups. The incidence of intraoperative hypotension was higher in R group than C group (47.1% vs. 20.6%, P = 0.005). CONCLUSIONS: Remifentanil administration during arthroscopic shoulder surgery in patients undergoing preoperative IBP increased postoperative analgesic consumption.


Assuntos
Artroplastia do Ombro , Bloqueio do Plexo Braquial , Delírio , Hipotensão , Nefopam , Analgésicos , Analgésicos Opioides/uso terapêutico , Fentanila/uso terapêutico , Humanos , Hiperalgesia/tratamento farmacológico , Nefopam/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/epidemiologia , Remifentanil
3.
Pan Afr Med J ; 41: 213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721644

RESUMO

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


Assuntos
Dor Aguda , Analgésicos não Narcóticos , Dor Crônica , Nefopam , Analgésicos não Narcóticos/uso terapêutico , Hospitais , Humanos , Nefopam/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico
4.
Eur J Clin Pharmacol ; 78(6): 897-906, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35218404

RESUMO

OBJECTIVE: Catheter-related bladder discomfort (CRBD) is a common complication of intraoperative urinary catheterization. Various studies have evaluated the efficacy of different interventions in postoperative CRBD. The present review was performed to assess the efficacy of these interventions. METHODS: PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases were systematically searched to identify randomized controlled trials (RCTs) investigating the efficacy of different drugs for the prevention of postoperative CRBD. This review evaluated the incidence and severity of CRBD after different interventions at 0, 1, 2, and 6 h postoperatively. RESULTS: Forty-five studies including 31 different drugs were analyzed. Eleven drugs were investigated in more than two RCTs, of which dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and pudendal nerve block (PNB) generally showed significantly higher efficacy than controls postoperatively. Solifenacin only showed significant efficacy compared with the control at 0 h, and intravenous lidocaine only showed significant efficacy compared with the control at 6 h. There were insufficient trials to draw conclusions regarding atropine, butylscopolamine, chlorpheniramine, clonidine, darifenacin, diphenhydramine, glycopyrrolate, intravesical bupivacaine, ketamine-haloperidol, pethidine-haloperidol, ketorolac, lidocaine-prilocaine cream, magnesium, hyoscine n-butyl bromide, oxycodone, paracetamol, parecoxib, trospium, resiniferatoxin, or amikacin. However, all but pethidine-haloperidol and chlorpheniramine showed some efficacy at various time points compared with controls. CONCLUSION: This review suggests that dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and PNB are effective in preventing postoperative CRBD. Considering the efficacy and adverse effects of all drugs, dexmedetomidine and gabapentin were ranked best.


Assuntos
Dexmedetomidina , Ketamina , Nefopam , Tramadol , Clorfeniramina/farmacologia , Clorfeniramina/uso terapêutico , Dexmedetomidina/uso terapêutico , Gabapentina/farmacologia , Gabapentina/uso terapêutico , Haloperidol/uso terapêutico , Humanos , Lidocaína , Meperidina/farmacologia , Meperidina/uso terapêutico , Nefopam/farmacologia , Nefopam/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Pregabalina/farmacologia , Tartarato de Tolterodina/farmacologia , Tartarato de Tolterodina/uso terapêutico , Tramadol/uso terapêutico , Bexiga Urinária/cirurgia , Cateteres Urinários/efeitos adversos
5.
J Arthroplasty ; 37(5): 845-850, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35121091

RESUMO

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


Assuntos
Antieméticos , Artroplastia do Joelho , Nefopam , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Antieméticos/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Método Duplo-Cego , Humanos , Morfina/uso terapêutico , Nefopam/efeitos adversos , Nefopam/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Estudos Prospectivos
6.
Medicina (Kaunas) ; 57(4)2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33801705

RESUMO

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


Assuntos
Colecistectomia Laparoscópica , Nefopam , Analgesia Controlada pelo Paciente , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Fentanila/uso terapêutico , Humanos , Nefopam/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Estudos Prospectivos
7.
Eur J Pain ; 25(8): 1770-1787, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33909343

RESUMO

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.


Assuntos
Analgésicos não Narcóticos , Nefopam , Acetaminofen , Animais , Modelos Animais de Doenças , Sinergismo Farmacológico , Feminino , Humanos , Masculino , Camundongos , Dor Pós-Operatória/tratamento farmacológico
8.
Therapie ; 76(6): 527-537, 2021.
Artigo em Francês | MEDLINE | ID: mdl-33618914

RESUMO

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


Assuntos
Estimulantes do Sistema Nervoso Central , Dor Crônica , Nefopam , Transtornos Relacionados ao Uso de Substâncias , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dor Crônica/tratamento farmacológico , Bases de Dados Factuais , França/epidemiologia , Humanos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
9.
F1000Res ; 9: 516, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32934804

RESUMO

Background : The incidence of moderate to severe pain is high among patients undergoing spinal surgery. Nefopam can be used as an adjuvant analgesic postoperatively after spine surgery. The study aimed to assess the analgesic efficacy and side effects of nefopam on 24-hour postoperative morphine consumption after spine surgery. Methods : The study is a randomized, double-blinded, placebo-controlled trial. A total of 96 patients were randomized into 4 treatment groups, 24 each. In group 1, patients received normal saline before surgical incision and before the end of surgery. In group 2, patients received 30 mg nefopam before surgical incision and normal saline before the end of surgery. In group 3, patients received normal saline before surgical incision and 30 mg of nefopam before the end of surgery. In group 4, patients received 30 mg of nefopam in both timings. Patient-controlled analgesia morphine was used for the postoperative period. Outcomes were to determine 24-hour morphine consumption and incidence of side effects.  Results : Of 96 patients enrolled, 21 in placebo-placebo, 22 in nefopam-placebo, 22 in placebo-nefopam and 21 in nefopam-nefopam groups completed the study.  Analysis of the Kruskal-Wallis test on the intention-to-treat basis shows no significant difference in 24-hour postoperative morphine consumption between four groups, which were 18 [IQR 13.5-29], 20 [IQR 11-28.3], 17 [IQR 11.5-28.5], 13 [IQR 8.5-18.5] mg., respectively (p = 0.223). Incidence of side effects, including tachycardia, sedation, sweating and nausea/ vomiting, did not differ. Conclusions : Adding perioperative nefopam to opioid analgesic does not improve analgesic efficacy in patients who underwent spine surgery. Registration : Thai Clinical Trials Registry ID TCTR20171115001; registered on 15 November 2017.


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Nefopam/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Fusão Vertebral , Idoso , Método Duplo-Cego , Feminino , Humanos , Vértebras Lombares , Masculino , Pessoa de Meia-Idade
10.
Curr Pain Headache Rep ; 24(8): 41, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32529416

RESUMO

PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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.


Assuntos
Mastectomia , Neuralgia/terapia , Dor Pós-Operatória/terapia , Inibidores da Liberação da Acetilcolina/uso terapêutico , Analgésicos/uso terapêutico , Anestesia por Condução , Anestésicos Locais/uso terapêutico , Antidepressivos Tricíclicos/uso terapêutico , Braço , Axila , Toxinas Botulínicas Tipo A/uso terapêutico , Terapia por Estimulação Elétrica/métodos , Gabapentina/uso terapêutico , Gânglios Espinais , Humanos , Memantina/uso terapêutico , Nefopam/uso terapêutico , Bloqueio Nervoso , Neuralgia/diagnóstico , Neuralgia/epidemiologia , Manejo da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Inibidores de Captação de Serotonina/uso terapêutico , Parede Torácica , Pontos-Gatilho
11.
F1000Res ; 9: 378, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32551097

RESUMO

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


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Dor do Câncer/tratamento farmacológico , Nefopam/uso terapêutico , Neoplasias , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Dor Pós-Operatória/tratamento farmacológico
12.
Neurosci Lett ; 731: 135057, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32450186

RESUMO

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.


Assuntos
Ácido Glutâmico/metabolismo , Nefopam/farmacologia , Antagonistas da Serotonina/farmacologia , Medula Espinal/efeitos dos fármacos , Animais , Formaldeído/farmacologia , Ácido Glutâmico/farmacologia , Masculino , Norepinefrina/farmacologia , Dor/tratamento farmacológico , Serotonina/metabolismo , Serotonina/farmacologia , Transmissão Sináptica/efeitos dos fármacos
13.
Eur J Hosp Pharm ; 27(e1): e69-e73, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32296509

RESUMO

Introduction: Nefopam has been reported to be effective in postoperative pain control with an opioid-sparing effect, but the use of nefopam can lead to nausea and vomiting. To prevent these side effects, droperidol can be mixed with nefopam. In intensive care units, high concentrations of nefopam and droperidol in syringes can be used with a continuous flow. Objectives: The first objective of this work was to study the physicochemical stability of a nefopam solution 2.5 mg/mL diluted in NaCl 0.9% in polypropylene syringes immediately after preparation and after 6, 24 and 48 hours at room temperature. The second objective was to study the physicochemical stability of mixtures of nefopam 2.5 mg/mL and droperidol 52 µg/mL diluted in NaCl 0.9% in polypropylene syringes at room temperature over 48 hours. Materials and methods: Three syringes for each condition were prepared. For each time of analysis, three samples for each syringe were prepared and analysed by high performance liquid chromatography coupled to photodiode array detection. The method was validated according to the International Conference on Harmonisation Q2(R1). Physical stability was evaluated by visual and subvisual inspection (turbidimetry by UV spectrophotometry). pH values were measured at each time of analysis. Results: Solutions of nefopam at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL, diluted in NaCl 0.9%, without protection from light, retained more than 90% of the initial concentration after 48 hours storage at 20-25°C. No modification in visual or subvisual evaluation and pH values were observed. Conclusion: Nefopam solutions at 2.5 mg/mL and the mixture of nefopam 2.5 mg/mL with droperidol 52 µg/mL diluted in NaCl 0.9% were stable over a period of 48 hours at room temperature. These stability data provide additional knowledge to assist intensive care services in daily practice.


Assuntos
Droperidol/química , Unidades de Terapia Intensiva/normas , Nefopam/química , Polipropilenos/química , Seringas/normas , Fenômenos Químicos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Droperidol/análise , Humanos , Nefopam/análise , Soluções Farmacêuticas/análise , Soluções Farmacêuticas/química , Polipropilenos/análise
14.
Mikrochim Acta ; 187(1): 55, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848716

RESUMO

An electrochromatographic capillary was modified with graphene oxide (GO), and the coating was characterized by scanning electron microscopy, energy dispersive X-ray spectrometry, and Fourier transform infrared spectra. By utilizing maltodextrin (MD) as the chiral selector, the basic chiral drugs nefopam (NEF), amlodipine (AML), citalopram hydrobromide (CIT), econazole (ECO), ketoconazole (KET) and cetirizine hydrochloride (CET) can be enantiomerically separated on this CEC. Compared with an uncoated silica capillary, the resolutions are markedly improved (AML: 0.32 → 1.45; ECO: 0.55 → 1.89; KET: 0.88 → 4.77; CET: 0.81 → 2.46; NEF: 1.46 → 2.83; CIT: 1.77 → 4.38). Molecular modeling was applied to demonstrate the mechanism of enantioseparation, which showed a good agreement with the experimental results. Graphical abstractSchematic representation of the preparation of graphene oxide-modified capillary (GO@capillary) for enantioseparation of drug enantiomers. The monolayered GO was used as the coating of the GO@capillary. Then the capillary was applied to construct capillary electrochromatography system with maltodextrin for separation of basic chiral drugs.


Assuntos
Grafite/química , Polissacarídeos/química , Anlodipino/química , Anlodipino/isolamento & purificação , Eletrocromatografia Capilar , Cetirizina/química , Cetirizina/isolamento & purificação , Citalopram/química , Citalopram/isolamento & purificação , Econazol/química , Econazol/isolamento & purificação , Cetoconazol/química , Cetoconazol/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Nefopam/química , Nefopam/isolamento & purificação , Tamanho da Partícula , Propriedades de Superfície
15.
Mikrochim Acta ; 187(1): 51, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848718

RESUMO

Poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monoliths were used as a support to grow a zeolitic imidazolate framework-8 (ZIF-8) via layer-by-layer self-assembly. Pepsin, acting as as chiral selector, was covalently linked to the surface of the amino-modified ZIF-8 through the Schiff base method. The material was characterized by scanning electron microscopy, thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy and elemental analysis. The pepsin-ZIF-8-poly(GMA-co-EDMA) column was utilized to the enantioseparation of the racemic forms of hydroxychloroquine (HCQ), chloroquine (CHQ), hydroxyzine (HXY), nefopam (NEF), clenbuterol (CLE) and amlodipine (AML). In comparison with a pepsin-poly(GMA-co-EDMA) monolithic column (without self-assembled ZIF-8 nanoparticles), the resolution is strongly enhanced (HCQ: 0.34 → 2.50; CHQ: 0.45 → 1.97; HXY: 0.39 → 1.43; NEF: 0.27 → 0.81; CLE: 0 → 0.81; AML: 0.16 → 0.72). Effects of self-assembly layers of ZIF-8, pepsin concentration, buffer pH values and applied voltage were investigated with hydroxychloroquine as the model analyte. The reproducibility of run-to-run, day-to-day and column-to-column were explored, and found to be satisfactory. Graphical abstractSchematic representation of capillary electrochromatography (CEC) systems with a pepsin-zeolitic imidazolate framework-8 (ZIF-8) modified poly(glycidyl methacrylate)-co-(ethylene dimethacrylate) [poly(GMA-co-EDMA)] monolithic column as stationary phases for separation of basic racemic drugs. ZIF-8 modified column was prepared via layer-by-layer self-assembly.


Assuntos
Etilenoglicóis/química , Estruturas Metalorgânicas/química , Metacrilatos/química , Anlodipino/análise , Eletrocromatografia Capilar , Cloroquina/análise , Clembuterol/análise , Hidroxicloroquina/análise , Hidroxizina/análise , Estrutura Molecular , Nefopam/análise , Tamanho da Partícula , Estereoisomerismo , Propriedades de Superfície
16.
Asian J Anesthesiol ; 57(3): 66-84, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31842530

RESUMO

Shivering is a common postoperative complication that occurs after both general and regional anesthesia even in the cases when hypothermia during surgery has been averted. Patients describe it as a highly unpleasant experience, while clinicians are concerned due to its adverse effects such as increased oxygen consumption. In this article, we present a summary of the pathophysiological mechanisms involved in postoperative shivering (POS), risk factors, and inadvertent effects. The major objective of this article was to review the existing literature on the effi ciency of various drug interventions as a prophylactic measure against POS. Since α2-adrenergic, opioid, anticholinergic, and serotonergic pathways are thought to play a role in the pathogenesis of POS, a wide variety of drugs has been investigated in this regard. Although the methodological diversity of the study designs and regimens does not support drawing defi nite conclusions, there is evidence indicating a benefi cial effect of dexmedetomidine, ketamine, tramadol, meperidine, dexamethasone, nefopam, granisetron, and ondansetron in the prevention of POS. The purpose of this review is to provide a thorough insight on various drug options and to serve as an aid for clinicians for careful analysis of the advantages and disadvantages of each regimen to decide which regimen will be ideally suited for the medical profi le of each patient.


Assuntos
Complicações Pós-Operatórias/prevenção & controle , Tremor por Sensação de Frio/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/uso terapêutico , Humanos , Nefopam/uso terapêutico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Tramadol/uso terapêutico
17.
World J Surg ; 43(12): 3191-3197, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31485809

RESUMO

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.


Assuntos
Analgésicos não Narcóticos/administração & dosagem , Dor Crônica/tratamento farmacológico , Neoplasias do Colo/cirurgia , Nefopam/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Adulto , Idoso , Método Duplo-Cego , Feminino , Fentanila/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Prospectivos
18.
Sci Rep ; 9(1): 9005, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227757

RESUMO

ß-catenin protein needs to be precisely regulated for effective fracture repair. The pace of fracture healing slows with age, associated with a transient increase in ß-catenin during the initial phase of the repair process. Here we examined the ability of pharmacologic agents that target ß-catenin to improve the quality of fracture repair in old mice. 20 month old mice were treated with Nefopam or the tankyrase inhibitor XAV939 after a tibia fracture. Fractures were examined 21 days later by micro-CT and histology, and 28 days later using mechanical testing. Daily treatment with Nefopam for three or seven days but not ten days improved the amount of bone present at the fracture site, inhibited ß-catenin protein level, and increased colony forming units osteoblastic from bone marrow cells. At 28 days, treatment increased the work to fracture of the injured tibia. XAV939 had a more modest effect on ß-catenin protein, colony forming units osteoblastic, and the amount of bone at the fracture site. This data supports the notion that high levels of ß-catenin in the early phase of fracture healing in old animals slows osteogenesis, and suggests a pharmacologic approach that targets ß-catenin to improve fracture repair in the elderly.


Assuntos
Consolidação da Fratura/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Nefopam/farmacologia , Fraturas da Tíbia/metabolismo , beta Catenina/metabolismo , Analgésicos não Narcóticos/farmacologia , Animais , Masculino , Camundongos Endogâmicos C57BL , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Tanquirases/antagonistas & inibidores , Tanquirases/metabolismo , Tíbia/efeitos dos fármacos , Tíbia/lesões , Tíbia/metabolismo , Fraturas da Tíbia/fisiopatologia , Fatores de Tempo
19.
Br J Anaesth ; 122(6): e98-e106, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915987

RESUMO

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


Assuntos
Analgésicos não Narcóticos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Morfina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Acetaminofen/uso terapêutico , Idoso , Analgesia Controlada pelo Paciente/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Cetoprofeno/uso terapêutico , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Morfina/efeitos adversos , Nefopam/uso terapêutico , Medição da Dor/métodos , Cuidados Pós-Operatórios/métodos , Resultado do Tratamento
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