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.

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

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

Postoperative Pain Management in Coronary Artery Bypass Grafting: An Integrative Review.

PURPOSE: To identify pharmacological and nonpharmacological interventions adopted for pain relief in the postoperative period of coronary artery bypass graft surgery. DESIGN: Integrative review. METHODS: Studies published in English, Spanish, and Portuguese from January 2010 to December 2019 in Cumulative Index to Nursing and Allied Health Literature (CINAHL), Latin American and Caribbean Literature on Health Science, PubMed, and Web of Science. Two hundred studies were identified and eleven were included. Methodological analysis was performed using the Medical Education Research Study Quality Instrument. FINDINGS: The studies found were organized into three thematic categories: pharmacological interventions (methadone, morphine, lidocaine gel, remifentanil, sufentanil, and nefopam), nonpharmacological interventions (low-level laser therapy, light-emitting diode, Class IV laser, and transcutaneous nerve stimulation) and anesthetic techniques (dexmedetomidine, ultrasound-guided pectoral nerve block, high thoracic epidural analgesia, and perioperative parasternal block with levobupivacaine). CONCLUSIONS: A greater tendency to use drug strategies for postoperative pain relief was identified. The drugs used demonstrated efficacy and safety in the treatment of pain, with the exception of nefopam, which showed little benefit in this population. Nonpharmacological interventions, used as adjuvants to drug treatment, were shown to be safe, effective, and well tolerated by the patients.

The effect of the addition of nefopam to intraoperative ketoprofen and acetaminophen on postoperative morphine requirements after laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Few studies investigated the use of nefopam for pain control after laparoscopic cholecystectomy in the context of multimodal analgesia. The aim of this study was to evaluate the effect of adding nefopam to ketoprofen and acetaminophen given before the end of laparoscopic cholecystectomy. METHODS: In this double-blind, controlled study, 90 patients undergoing laparoscopic cholecystectomy during sevoflurane-dexmedetomidine-based anesthesia were randomized to receive either ketoprofen and acetaminophen or nefopam, ketoprofen, and acetaminophen for postoperative pain control before the end of surgery. The primary outcome was total morphine consumption in the Postanesthesia Care Unit (PACU). RESULTS: PACU morphine consumption was significantly lower in the experimental group compared to the control group (0.9±1.8 mg vs. 2.3±2.4 mg, respectively; P=0.004, Cohen's d=0.63). In the experimental group, a smaller proportion of patients received morphine in PACU (24% vs. 60%, respectively; P=0.001), morphine during the first 24 hours after surgery (47% vs. 77%, respectively; P=0.004), and acetaminophen on the floor (76% vs. 93%, respectively; P=0.039) compared with the control group. The average pain score during PACU stay was also significantly lower in the experimental group (1.7±2.0 vs. 2.7±2.0, P=0.01). Median time to first morphine requirement (44.0 minutes, 95% CI [(31.96 to, 52.21)] was shorter in the control group than in the experimental group (higher than the 90 minutes-last time point taken in PACU). CONCLUSIONS: Adding nefopam to ketoprofen and acetaminophen before the end of laparoscopic cholecystectomy provides a reduction in morphine consumption with superior analgesia in PACU.

Postoperative analgesia of intraoperative nefopam in patients undergoing anterior cervical spine surgery: A prospective randomized controlled trial.

BACKGROUND: Nefopam is a non-opioid, non-nonsteroidal anti-imflammatory drug, analgesic drug that inhibits the reuptake of serotonin, norepinephrine, and dopamine. It is widely used as an adjuvant for pain. This study investigated whether the intraoperative, intravenous infusion of nefopam (20 mg) reduces postoperative morphine consumption, pain scores, and alleviates neuropathic pain in patients undergoing cervical spine surgery. METHODS: A prospective, paralleled design, randomized study was conducted on 50 patients (aged 18-75 years) in a university-based hospital. The patients were assigned to an intervention or a control group (25 patients in each). The intervention group received a 1-hour infusion of nefopam (20 mg) before the end of surgery. The control group received normal saline (NSS). The outcome measures were morphine consumption during the first 24 postoperative hours, numerical rating scale (NRS) pain scores, and scores for the Thai version of the Neuropathic Pain Symptom Inventory (NPSI-T) in patients with neuropathic pain and adverse drug reactions. The NPSI-T scores were assessed on the preoperative day, postoperative day 1, 3, 15, and 30. The outcome assessors were blinded to group allocation. RESULTS: Fifty patients were analyzed. During the first 24 postoperative hours, morphine consumption was 8 mg (nefopam) and 12 mg (NSS; P = .130). The intervention and control groups demonstrated no significant differences in the median NRS scores or total NPSI-T scores or adverse drug reactions. CONCLUSIONS: A single, intraoperative infusion of 20 mg of nefopam did not significantly reduce postoperative (24 hours) morphine consumption in patients undergoing anterior cervical spine surgery.

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

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

Analgesic efficacy of intravenous nefopam after spine surgery: a randomized, double-blind, placebo-controlled trial.

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.

Analgesic efficacy of nefopam for cancer pain: a randomized controlled study.

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.

A Comprehensive Review of the Diagnosis, Treatment, and Management of Postmastectomy Pain Syndrome.

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.

Pharmacological Approach for the Prevention of Postoperative Shivering: A Systematic Review of Prospective Randomized Controlled Trials

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.

Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study.

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.

Effects of nefopam with fentanyl in intravenous patient-controlled analgesia after arthroscopic orthopedic surgery: a prospective double-blind randomized trial

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.

Intraoperative Nefopam Reduces Acute Postoperative Pain after Laparoscopic Gastrectomy: a Prospective, Randomized Study.

BACKGROUND: We assessed whether intraoperative nefopam would reduce opioid consumption and relieve postoperative pain in patients undergoing laparoscopic gastrectomy. METHODS: The 60 enrolled patients were randomly assigned to the control (n = 32) or nefopam (n = 28) group. All patients were blinded to their group assignment. We administered 100 ml of normal saline only (control group) or 20 mg of nefopam mixed in 100 ml normal saline (nefopam group) after anesthesia induction and at the end of surgery. The cumulative amount of fentanyl via intravenous patient-controlled analgesia (PCA), incidence of rescue analgesic medication, and numerical rating scale (NRS) for postoperative pain were evaluated along with the total remifentanil consumption. RESULTS: The mean infusion rate of remifentanil was significantly lower in the nefopam group (0.08 ± 0.05 µg/kg/min) than in the control group (0.13 ± 0.06 µg/kg/min) (P < 0.001). Patients in the nefopam group required less fentanyl via intravenous PCA than those in the control group during the first 6 h after surgery (323.8 ± 119.3 µg vs. 421.2 ± 151.6 µg, P = 0.009). Additionally, fewer patients in the nefopam group than in the control group received a rescue analgesic during the initial 6 h postoperatively (78.6 vs. 96.9%, P = 0.028). The NRS measured while patients were in the post-anesthetic care unit was significantly lower in the nefopam group than in the control group (3.8 ± 1.1 vs. 4.8 ± 1.4, P = 0.012). The subsequent NRS obtained after patients had been transferred to the general ward was comparable between the two groups during the following postoperative period. CONCLUSIONS: Intraoperative nefopam decreased postoperative pain and opioid consumption in the acute postoperative period after laparoscopic gastrectomy. Hence, nefopam may be considered as a component of multimodal analgesia after laparoscopic gastrectomy.

The Effect of Intraoperative Nefopam Administration on Acute Postoperative Pain and Chronic Discomfort After Robotic or Endoscopic Assisted Thyroidectomy: A Randomized Clinical Trial.

BACKGROUND: Acute postoperative pain and chronic discomfort are reported after robotic or endoscopic thyroidectomy. The purpose of this prospective, randomized, and double-blinded clinical trial was to investigate whether intraoperative infusion of nefopam decreases acute postoperative pain and chronic discomfort following either a robotic or endoscopic thyroidectomy via the bilateral axillo-breast approach (BABA). METHODS: Patients were randomized into two groups: The control group (n = 29) or the nefopam group (n = 29). Patients in each group were infused with the same volume of saline or nefopam (0.2 mg/kg bolus, 120 µg/kg/h continuous infusion) during surgery. Acute postoperative pain, the need for rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 h postoperatively. Chronic pain and discomfort was recorded at 3 months after surgery. RESULTS: Patients in the nefopam group reported lower pain scores in the neck, as well as the axilla and anterior chest areas at 1, 6, 24, and 48 h postoperatively, when compared with the control group (P < 0.05 at each time points). Rescue analgesics were required less in the nefopam group than in the control group (1.4 [1] vs. 2.3 [1.5]; P = 0.001). The degree of chronic pain and discomfort were relatively lower in the nefopam group (P < 0.05). CONCLUSION: We report that intravenous nefopam infusion during surgery decreased acute postoperative pain and the need for rescue analgesics, as well as chronic discomfort, following BABA robotic or endoscopic thyroidectomy without adverse events.

The effect of preoperative nefopam treatment on postoperative catheter-related bladder discomfort in patients undergoing transurethral bladder tumor resection: a randomized double-blind study.

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

Non-opioid analgesics in adults after major surgery: systematic review with network meta-analysis of randomized trials.

BACKGROUND: Morphine, and analgesics other than morphine (AOM), are commonly used to treat postoperative pain after major surgery. However, which AOM provides the best efficacy-safety profile remains unclear. METHODS: Randomized trials of any AOM alone or any combination of AOM compared with placebo or another AOM in adults undergoing major surgery and receiving morphine patient-controlled analgesia were included in a network meta-analysis. The outcomes were morphine consumption, pain, incidence of nausea, vomiting at 24 h and severe adverse effects. RESULTS: 135 trials (13,287 patients) assessing 14 AOM alone or in combination were included. For all outcomes, comparisons with placebo were over-represented. Few trials assessed combinations of two AOM and none the combination of three or more. Network meta-analysis found morphine consumption reduction was greatest with the combination of two AOM (acetaminophen + nefopam, acetaminophen + NSAID, and tramadol + metamizol): -23.9 (95% CI -40;-7.7), -22.8 (-31.5;-14) and -19.8 (35.4;-4.2) mg per 24 h, respectively. For AOM used alone, morphine consumption reduction was greatest with α-2 agonists, NSAIDs, and COX-2 inhibitors. When considering the risk of nausea, NSAIDs, corticosteroids and α-2 agonists used alone were the most efficacious (OR 0.7 [95% CI: 0.6-0.8], 0.36 [0.18-0.79], 0.41 [0.15-.64], respectively). The paucity of severe adverse effects data did not allow assessment of efficacy-safety balance. CONCLUSIONS: A combination of aetaminophen with either an NSAID or nefopam was superior to most AOM used alone, in reducing morphine consumption. Efficacy was best with three AOM used alone (α-2 agonists, NSAIDs and COX-2 inhibitors) and least with tramadol and acetaminophen. There is insufficient trial data reporting adverse events. CLINICAL TRIAL REGISTRATION: PROSPERO: CRD42013003912.

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 Antiallodynic Effects of Nefopam Are Mediated by the Adenosine Triphosphate-Sensitive Potassium Channel in a Neuropathic Pain Model.

BACKGROUND: Nefopam hydrochloride is a centrally acting compound that induces antinociceptive and antihyperalgesic properties in neuropathic pain models. Previous reports have shown that activation of adenosine triphosphate (ATP)-sensitive and calcium-activated potassium (KATP and KCa2+) channels has antiallodynic effects in neuropathic pain. In the present study, we evaluated the relationship between potassium channels and nefopam to determine whether the antiallodynic effects of nefopam are mediated by potassium channels in a neuropathic pain model. METHODS: Mechanical allodynia was induced by spinal nerve ligation (SNL) in rats, and the paw withdrawal threshold (PWT) was evaluated by the use of von Frey filaments. Nefopam was administered intraperitoneally before or after SNL. We assessed the relationship between nefopam and intrathecal injection of the KCa2+ channel antagonists apamin and charybdotoxin, and the KATP channel blocker glibenclamide to assess their abilities to reverse the antiallodynic effects of nefopam. In addition, we evaluated whether the KATP channel opener pinacidil had antiallodynic effects and promoted the antiallodynic effects of nefopam. RESULTS: Administration of nefopam before and after SNL induced significant antiallodynic effects (P < .01, respectively), which were significantly reduced by glibenclamide (P < .01). Pinacidil improved the antiallodynic effects of nefopam (P < .01); however, apamin and charybdotoxin had little effects on the antiallodynic properties of nefopam. CONCLUSIONS: The antiallodynic effects of nefopam are increased by a KATP channel agonist and reversed by a KATP channel antagonist. These data suggest that the KATP channel is involved in the antiallodynic effects of nefopam in a neuropathic pain model.

Preventive Analgesic Efficacy of Nefopam in Acute and Chronic Pain After Breast Cancer Surgery: A Prospective, Double-Blind, and Randomized Trial.

Breast cancer surgery is known to cause severe acute postoperative pain, which can persist for a long time. We administered nefopam preventively to patients undergoing lumpectomy with axillary lymph node dissection or sentinel lymph node biopsy, and evaluated its efficacy on acute and chronic postoperative pain.Enrolled patients were assigned to the nefopam (n = 41) or the control (n = 42) group. Before initiating the operation, 20 mg of nefopam was given to the patients of the nefopam group, and normal saline was used in the control group. Ketorolac was given at the end of surgery, and meloxicam was prescribed in the postoperative period to all patients in both groups. Pain was assessed using a numerical rating scale (NRS), and the rescue analgesic drug was given when the NRS was >5. Implementation of postoperative chemotherapy, radiotherapy (RT), or hormone therapy was evaluated.The NRS of postoperative pain was significantly lower in the nefopam than in the control group in the postanesthetic care unit (4.5 ±â€Š2.2 vs 5.7 ±â€Š1.5, respectively; P = 0.01), at postoperative 6 h (3.0 ±â€Š1.6 vs 4.5 ±â€Š1.3, respectively; P < 0.001), and at postoperative 24 h (3.1 ±â€Š1.1 vs 3.8 ±â€Š1.5, respectively; P = 0.01) with reduced use of rescue analgesic drugs. Significantly fewer patients suffered from chronic postoperative pain in the nefopam than in the control group at postoperative 3 months (36.6% vs 59.5%, P = 0.04). Considering only the cohort without postoperative adjuvant RT, the difference in the proportion of patients reporting chronic pain increased (23.5% in the nefopam group vs 61.5% in the control group, P = 0.04).Preventive nefopam was helpful in reducing the acute postoperative pain, with reduced use of rescue analgesic drugs, and it contributed to reduced occurrence of chronic pain at postoperative 3 months after breast cancer surgery.