Effective remimazolam loading dose for adequate sedation in regional anesthesia.

PURPOSE: Remimazolam is a novel ultrashort-acting sedative considered appropriate for continuous infusion during surgical procedures. Nevertheless, information regarding its loading dose for sedation during surgery is limited. We aimed to determine the 90% effective dose (ED90) of the remimazolam loading dose for sedation in patients undergoing limb surgery under regional anesthesia. METHODS: We included 50 patients aged 19-80 yr undergoing limb surgery under regional anesthesia. After regional anesthesia, remimazolam besylate was administered at the assigned dose. For ten minutes after the initiation of loading, the level of sedation was evaluated using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. The primary outcome was the ED90 based on whether patients reached a MOAA/S score of ≤ 3 points (loss of response to verbal command) within ten minutes. The secondary outcomes were the ED50 and the estimated effect site and plasma concentration at the time of achieving successful sedation. RESULTS: In total, 49 patients were included in the final analysis, and adequate sedation with the assigned loading dose was successful in 42 patients. The log-logistic function showed that the ED90 and ED50 were 0.617 mg·kg-1·hr-1 (95% confidence interval [CI], 0.511 to 0.722; 98% CI, 0.492 to 0.741) and 0.438 mg·kg-1·hr-1 (95% CI, 0.335 to 0.541; 98% CI, 0.315 to 0.560), respectively. CONCLUSION: The ED90 of the remimazolam loading dose to achieve adequate sedation in patients undergoing limb surgery under regional anesthesia was 0.617 mg·kg-1·hr-1 (95% CI, 0.511 to 0.722; 98% CI, 0.492 to 0.741). STUDY REGISTRATION: ClinicalTrials.gov (NCT05340335); first posted 22 April 2022.

RéSUMé: OBJECTIF: Le remimazolam est un nouveau sédatif à action ultracourte considéré comme approprié pour la perfusion continue pendant les interventions chirurgicales. Néanmoins, les informations concernant sa dose de charge pour la sédation pendant la chirurgie sont limitées. Notre objectif était de déterminer la dose efficace à 90 % (DE90) de la dose de charge de remimazolam pour la sédation chez la patientèle bénéficiant d'une chirurgie d'un membre sous anesthésie régionale. MéTHODE: Cinquante personnes âgées de 19 à 80 ans bénéficiant d'une chirurgie des membres sous anesthésie régionale ont été incluses. Après l'anesthésie régionale, du bésylate de remimazolam a été administré à la dose assignée. Pendant dix minutes après le début de la charge, le niveau de sédation a été évalué à l'aide de l'échelle modifiée d'évaluation de la vigilance/sédation par l'observateur (MOAA/S). Le critère d'évaluation principal était la DE90 selon que les patient·es ont atteint un score MOAA/S de ≤ 3 points (perte de réponse à la commande verbale) dans les dix minutes. Les critères d'évaluation secondaires étaient la DE50 et l'estimation du site d'effet et de la concentration plasmatique au moment de l'obtention d'une sédation réussie. RéSULTATS: Au total, 49 personnes ont été incluses dans l'analyse finale, et une sédation adéquate avec la dose de charge assignée a été couronnée de succès chez 42 d'entre elles. La fonction log-logistique a montré que les DE90 et DE50 étaient de 0,617 mg·kg−1·h−1 (intervalle de confiance [IC] à 95 %, 0,511 à 0,722; IC 98 %, 0,492 à 0,741) et 0,438 mg·kg−1·h−1 (IC 95 %, 0,335 à 0,541; IC 98 %, 0,315 à 0,560), respectivement. CONCLUSION: La DE90 de la dose de charge de remimazolam pour obtenir une sédation adéquate chez les personnes bénéficiant d'une chirurgie des membres sous anesthésie régionale était de 0,617 mg·kg−1·h−1 (IC 95 %, 0,511 à 0,722; IC 98 %, 0,492 à 0,741). ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05340335); première publication le 22 avril 2022.

Effect of Remimazolam- versus Propofol-Based Total Intravenous General Anesthesia on Intraoperative Hemodynamic Stability for Major Spine Surgery in the Prone Position: A Randomized Controlled Trial.

Background and Objectives: Remimazolam offers advantages over propofol in terms of hemodynamic stability. However, it remains unclear whether remimazolam-based total intravenous anesthesia (TIVA) can reduce intraoperative hypotension compared to propofol-based TIVA, especially after prone positioning. In this study, we compared the effects of remimazolam- and propofol-based TIVA on intraoperative hemodynamic stability in patients undergoing surgery in the prone position. Materials and Methods: This study randomly assigned patients undergoing major spinal surgery in the prone position to the propofol or remimazolam group. Target-controlled infusion (2-3.5 µg/mL for induction and 2-3 µg/mL for maintenance) was used in the propofol group and continuous infusion (6 mg/kg/h for induction and 1-2 mg/kg/h for maintenance) was used in the remimazolam group; target-controlled infusion (3-5 ng/mL) of remifentanil was performed in both groups. The primary outcomes were the incidence of hypotensive episodes during the first hour after prone positioning. The secondary outcomes included the incidence of severe hypotension and the total amount of inotropic or vasopressor medication. Systolic and mean arterial pressure, heart rate, cardiac index and output, stroke volume, stroke volume variation, and pleth variability index were also evaluated. These variables were recorded per minute for the first 10 min after prone positioning, and every 10 min thereafter. Results: The study enrolled 94 patients (47 patients in each group). The incidence of hypotension or severe hypotension did not differ significantly between the two groups during the first hour after prone positioning. The total amount of ephedrine administered during the first hour after prone positioning was lesser (p = 0.020) and the mean arterial pressure during the initial 10 min after prone positioning was higher in the remimazolam group (p = 0.003). Conclusions: Our study uncovered no significant differences in the incidence of hypotension between remimazolam- and propofol-based TIVA in patients undergoing major spine surgery in prone position.

Evaluating the Clinical Utility of Brachial Plexus Block for Reducing Opioid Exposure in Pediatric Elbow Fracture Surgery: A Retrospective Cohort Study.

Background and Objectives: Reducing opioid exposure in common pediatric surgeries is of paramount importance. This study aimed to assess the efficacy of regional nerve blocks in reducing opioid exposure while preserving high success rates. Materials and Methods: We conducted a retrospective matched cohort study (1:1) including patients with elbow fractures < 12 years old who underwent treatment with percutaneous pinning. Patients were divided into general-anesthesia (GA) and GA-followed-by-supraclavicular-brachial-plexus-block (GA-SCB) groups. The primary outcome was the number of patients administered postoperative rescue opioids. The secondary outcomes included intraoperative and postoperative opioid administration, the time to first request for rescue analgesia, pain scores, block success rate, block performing time, and block-related complications. Results: In a total of 478 patients, 363 underwent percutaneous pinning, and 86 were cohort-matched (GA: n = 43, GA-SCB: n = 43). On the first postoperative day, 34 (79.0%) patients in the GA group were administered postoperative rescue opioids, compared with 12 (27.9%) in the GA-SCB group (p < 0.001). All the patients in the GA-SCB group were opioid-free during the intraoperative period. No SCB-associated complications were observed. Total opioid consumption was significantly lower in the GA-SCB group than in the GA group until the first postoperative day (GA vs. GA-SCB, 3.2 ± 3.0 mg vs. 0.9 ± 1.8 mg, p < 0.001). Conclusions: SCB application in pediatric patients who underwent elbow fracture surgery significantly reduced opioid exposure and had a high success rate when performed using ultrasound guidance by an expert. Furthermore, the complication risk and surgical delay were minimal.

Comparison of the Analgesic Efficacy between Arthroscopically Placed Continuous Suprascapular Nerve Block and Ultrasound-guided Continuous Superior Trunk Block: A Double-blinded Randomized Controlled Trial.

BACKGROUND: Single-shot suprascapular nerve block and superior trunk block have been reported to provide a noninferior analgesic effect after shoulder surgery with a lesser incidence of hemidiaphragmatic paresis compared with interscalene brachial plexus block. This study hypothesized that continuous suprascapular nerve block provides noninferior analgesia with minimal effects on diaphragmatic movement compared with continuous superior trunk block in patients undergoing arthroscopic shoulder surgery. METHODS: 100 patients were randomized undergoing arthroscopic shoulder surgery between December 2020 and October 2021 into continuous suprascapular nerve block and continuous superior trunk block groups. Before the surgery, patients received either a single-shot superior trunk block or subomohyoid suprascapular nerve block. Thereafter, a superior trunk catheter was inserted by anesthesiologists in patients in the continuous superior trunk block group, and a posterior suprascapular nerve catheter was inserted with arthroscopic assistance during the surgery by surgeon in the continuous suprascapular nerve block group. The primary outcome was the postoperative pain score at postoperative 24 h, and the incidence of hemidiaphragmatic paresis was also compared. RESULTS: Overall, 98 patients were included in the final analysis. The worst and resting pain scores at postoperative 24 h in the continuous suprascapular nerve block group were inferior compared with those in the continuous superior trunk block group in the test with a noninferiority margin of 1 (worst pain score: mean difference, 0.9; 95% CI, 0.1 to 1.7; resting pain score: mean difference, 0.5; 95% CI, 0.0 to 1.0). However, the continuous suprascapular nerve block group had a significantly lower incidence of hemidiaphragmatic paresis at postoperative 24 h than the continuous superior trunk block group. CONCLUSIONS: Continuous suprascapular nerve block provides statistically inferior analgesia compared to the continuous superior trunk block; however, the continuous suprascapular nerve block had a minimal effect on the phrenic nerve function.

A comparison of the continuous supraclavicular brachial plexus block using the proximal longitudinal oblique approach and the interscalene brachial plexus block for arthroscopic shoulder surgery: A randomised, controlled, double-blind trial.

BACKGROUND: Continuous interscalene brachial plexus block (ISB) is widely used for arthroscopic shoulder surgery, but the incidence of hemidiaphragmatic paresis (HDP) has been reported to reach 100%. Several methods, including injections distal to the C5-C6 nerve roots, have been attempted to reduce the HDP incidence. However, catheter placement distal to the C5-C6 nerve roots interferes with the surgical site. OBJECTIVE: Our primary objective was to describe a new technique, the supraclavicular brachial plexus block (SCB), using the proximal longitudinal oblique approach (PLO-SCB), which can facilitate catheter placement and, when compared with ISB, to test whether this would provide noninferior analgesia and spare the phrenic nerve. DESIGN: Prospective, randomised, double-blind study. SETTING: Operating rooms, postanaesthesia care unit, and wards. PATIENTS: Seventy-six patients aged 20 to 80 years scheduled for arthroscopic shoulder surgery. INTERVENTIONS: Patients were randomly assigned to the continuous PLO-SCB (n = 40) or the continuous ISB (n = 40) groups. All patients received an initial low-volume single-injection (5 ml 0.75% ropivacaine) followed by a patient-controlled infusion of 0.15% ropivacaine. MAIN OUTCOME MEASURES: The primary outcomes were the incidence of HDP and pain scores. Secondary outcomes were respiratory function, postoperative analgesic consumption, sensory and motor function, and complications. RESULTS: The HDP incidence was significantly lower in the PLO-SCB group than in the ISB group at 30 min after block injection: 0% (0 of 38 patients) and 73.7% (28 of 38 patients), respectively (P < 0.001). Similarly, at 24 h after surgery, the incidences were 23.7% (9 of 38 patients) and 47.4% (18 of 38 patients) in the PLO-SCB and ISB groups, respectively (P = 0.002). Median [IQR] NRS pain scores at rest measured after surgery in the ISB and PLO-SCB groups were similar: immediately after surgery, 1 [0 to 2] vs. 1 [0 to 1], P = 0.06); at 30 min, 2 [0.25 to 2] vs. 1 [0 to 2], P = 0.065); and at 24 h 2 [0.25 to 3] vs. 1 [0 to 3], P = 0.47, respectively. CONCLUSION: For major shoulder surgery, compared with continuous ISB, continuous PLO-SCB was more sparing of diaphragmatic and respiratory function while providing noninferior analgesia. Catheter placement via the PLO approach is feasible without interfering with the surgical field. TRIAL REGISTRATION: Registered by the Clinical Trial Registry of Korea (Seoul, Korea; KCT0004759, http: cris.nih.go.kr, principal investigator: Hyungtae Kim).

Short-term high-dose intravenous iron reduced peri-operative transfusion after staggered bilateral total knee arthroplasty: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: Staggered bilateral total knee arthroplasty, two procedures performed 4-7 days apart during a single hospitalization, has an increased risk of blood transfusion. This observational study aimed to evaluate whether immediate post-operative single, high-dose intravenous iron supplementation could reduce transfusion requirements and facilitate anaemia recovery in patients. MATERIALS AND METHODS: We retrospectively analysed 131 patients who underwent staggered bilateral total knee arthroplasty. The ferric carboxymaltose (FCM) group received 1000 mg of FCM after the first operation. The non-FCM group did not receive intravenous iron. The transfusion rate and post-operative complications were compared between the groups. The anaemia rate was evaluated pre-operatively, during hospitalization, and 5 weeks after the second total knee arthroplasty. RESULTS: The FCM group comprised 78 patients (59.5%). The rate (21.8% vs. 47.2%, p = 0.004) and amount of transfusion (0 [0-2] vs. 0 [0-0], p = 0.001) was significantly lower in the FCM group than in the non-FCM group. Although both groups' pre-operative haemoglobin concentrations were not significantly different, the FCM group demonstrated higher haemoglobin values 5 weeks post surgery (12.25 ± 0.83 mg/dl vs. 11.48 ± 1.36 mg/dl, p < 0.001). More non-FCM patients developed moderate to severe anaemia at 5 weeks post surgery (p < 0.001). The mortality and complication rates were not significantly different. CONCLUSIONS: Immediate post-operative, high-dose, intravenous iron treatment may contribute to reduced transfusion rates, facilitate haemoglobin recovery after staggered bilateral total knee arthroplasty, and minimize the development of moderate to severe anaemia.

Immediate intravenous iron administration improves anaemia recovery following total knee arthroplasty: A propensity-matched analysis.

BACKGROUND AND OBJECTIVES: Patients who undergo total knee arthroplasty (TKA) have a risk of postoperative anaemia. This observational study evaluated whether single-dose intravenous ferric carboxymaltose (FCM) administered immediately after TKA facilitates the correction of anaemia. MATERIALS AND METHODS: We retrospectively analysed 722 patients who underwent primary TKA. The FCM group receiving 1000 mg intravenous FCM within one postoperative hour was compared with the non-FCM group that did not receive the medication. A propensity score matching with multiple logistic regression analysis was used to minimize intergroup differences in the baseline characteristics and postoperative blood loss. The rate and severity of postoperative anaemia were compared between the groups, along with haemoglobin (Hb) value, transfusion rate and complications. RESULTS: After propensity score matching, 231 patients were included in each group. In the FCM group, the rate of anaemia at postoperative day (POD) 7 (p = 0.021) and postoperative week (POW) 5 (p < 0.001) and the transfusion rate were significantly lower (p = 0.008). The rate of moderate to severe anaemia at POW-5 was also significantly lower in the FCM group (p < 0.001). In patients without preoperative anaemia (n = 322), the transfusion rate and rate and severity of anaemia at POD-7 and POW-5 were significantly lower in the FCM group than in the non-FCM group. CONCLUSION: Postoperative intravenous FCM administration facilitated recovery of surgery-related anaemia by improving Hb and may reduce the need for transfusion in TKA patients. Preoperative non-anaemic patients could also benefit from accelerated recovery by intravenous iron treatment.

Interaction between Dexamethasone, Ropivacaine, and Contrast Media Used in Interventional Pain Treatment: Considerations in Safety.

Background and Objectives: Although epidural steroid injections are used as an effective treatment, this technique is associated with rare but serious ischemic complications, especially when particulate steroids are used. However, recent studies have reported that even if non-particulate steroids are used, particulates are formed by the interaction with some local anesthetics (LA), causing ischemic complications. This observational study evaluated commonly used combinations of non-particulate steroids and LA with contrast media via microscopic analysis and analyzed the chemical properties of each mixture to identify the correlation of particulate formation. Materials and Methods: Commonly used clinical non-particulate and particulate steroids, contrast media, and LA agent combinations were evaluated macroscopically and microscopically. The pH values were also measured at both room temperature (26 °C) and body temperature (36 °C). Where particulates were observed, the particulate size was measured. Results: Macroscopically, the mixture of non-particulate steroid and ropivacaine had a slightly cloudy appearance at all concentrations, but there was no visible particulate. However, when observed under a microscope, the pH-dependent particulate formation was observed at all concentration combinations tested. (0.1% ropivacaine: from 19 µm to 70 µm, and 0.2% ropivacaine: from 37 µm to 108 µm at room temperature (26 °C)). When contrast media was mixed or the temperature was raised to body temperature (36 °C), the number and size of the particulates decreased or dissolved. Conclusions: The combination of ropivacaine and dexamethasone, a non-particulate steroid, mainly used in epidural injections, forms particulates. However, when mixed with contrast media, particulates are dissolved because of changes in pH and factors affecting particulate formation. In fluoroscopy-guided injections, the use of contrast media could resolve particulate formation.

Postoperative Pain Control After Arthroscopic Rotator Cuff Repair: Arthroscopy-Guided Continuous Suprascapular Nerve Block Versus Ultrasound-Guided Continuous Interscalene Block.

PURPOSE: To compare the clinical efficacy and safety of arthroscopy-guided continuous suprascapular nerve block and ultrasound-guided continuous interscalene block in postoperative analgesia in patients undergoing arthroscopic rotator cuff repair. METHODS: A prospective study was performed between March and November 2020. In total, 76 patients were enrolled and divided into 2 groups: in the 38 patients of group 1 (arthroscopy-guided continuous suprascapular nerve block), an indwelling catheter was introduced via the Neviaser portal under arthroscopic view before closing the portal at the end of the surgery; and in the 38 patients of group 2 (ultrasound-guided continuous interscalene block), an indwelling catheter was inserted and directed toward the interscalene brachial plexus prior to the surgery under ultrasound guidance. The primary outcome was the pain score measured by the visual analog scale at postoperative 24 hours during admission. Comparisons were conducted at different time points (postoperative 4, 8, 24, and 48 hours). The secondary outcome was any of these events: neurologic complications, such as sensory/motor change in the upper extremities; hemidiaphragmatic paresis; dyspnea; dysphonia; and Horner's syndrome. Opioid usage until postoperative 3 weeks was compared between the groups. RESULTS: The visual analog scale scores in groups 1 and 2 were comparable at each postoperative time point (analysis of variance, P = .919; trends, P = .132). Neurologic deficits were more common in group 2 than in group 1 (8 vs 32 patients, P < .001). Decreased excursion of the diaphragm was more common in group 2 (partial or complete paresis of the hemidiaphragm: 1 vs 29 patients, P < .001). Opioid consumption was similar in both groups (morphine milligram equivalents per kilogram; 1.75 vs 1.55, P = .195). CONCLUSIONS: Our findings show that arthroscopy-guided continuous suprascapular nerve block is not inferior to ultrasound-guided continuous interscalene block for postoperative pain control after arthroscopic rotator cuff repair while showing fewer temporary neurologic complications. LEVEL OF EVIDENCE: Level II, prospective cohort study, interventional study.

Comparison of General and Spinal Anaesthesia on Systemic Inflammatory Response in Patients Undergoing Total Knee Arthroplasty: A Propensity Score Matching Analysis.

Background and Objectives: Some of the postoperative complications following orthopaedic surgeries are associated with a systemic inflammatory response (SIR), which varies depending on the anaesthetic technique. We aimed to compare the effects of general and spinal anaesthesia on the SIR after total knee arthroplasty (TKA), based on C-reactive protein (CRP) levels, the platelet-lymphocyte ratio (PLR), and the neutrophil-lymphocyte ratio (NLR). Materials and Methods: Patients who underwent TKA between January 2014 and December 2018 were included. Electronic medical records of the patients were retrospectively reviewed and analysed. To reduce the impact of potential confounding factors, we performed propensity score matching according to the anaesthetic technique. Results: A total of 1311 TKA cases were analysed. After propensity score matching, the maximal CRP value and changes in CRP levels in the general anaesthesia group were higher than those in the spinal anaesthesia group. However, the maximal NLR and PLR and the changes in NLR and PLR were not different between the two groups. There were no differences in postoperative clinical outcomes. Conclusion: Spinal anaesthesia tended to induce a lower inflammatory response than general anaesthesia when considering CRP levels in patients undergoing TKA. However, the effects of anaesthetic techniques on the overall outcomes were not significant.

Ultrasound-Guided Anterior Approach to a Sciatic Nerve Block: Influence of Lower Limb Positioning on the Visibility and Depth of the Sciatic Nerve.

OBJECTIVES: We aimed to identify the optimal lower limb position for an ultrasound (US)-guided anterior approach to a sciatic nerve block. METHODS: We included 45 patients who met the following criteria: American Society of Anesthesiologists physical status of 1 to 3, age between 18 and 80 years, and scheduled to undergo knee surgery that required a sciatic nerve block. The lower limbs of each patient were placed in the following 4 positions: N, neutral; ER, external rotation of the hip (angle, 45°); ER/F15, ER (angle, 45°) and flexion (angle, 15°) of the hip; and ER/F45, ER (angle, 45°) and F (angle, 45°) of the hip. An investigator acquired US scans of the sciatic nerve in each position, and the visibility score and depth of the sciatic nerve from the skin were analyzed. RESULTS: The visibility scores were significantly higher in positions ER/F15 and ER/F45 than in positions ER and N (P < .0001). However, there was no difference between the visibility scores in positions ER/F15 and ER/F45 (P = .0959). The depth of the sciatic nerve from the skin decreased with ER and an increase in the F angle of the hip (overall P < .0001). CONCLUSIONS: Based on the visibility score and depth from the skin, ER of the hip to 45° with a greater F angle (45° versus 15°) of the hip appears to be the optimal position for an US-guided anterior approach to a sciatic nerve block.

Remote Ischemic Preconditioning and Diazoxide Protect from Hepatic Ischemic Reperfusion Injury by Inhibiting HMGB1-Induced TLR4/MyD88/NF-κB Signaling.

Remote ischemic preconditioning (RIPC) is known to have a protective effect against hepatic ischemia-reperfusion (IR) injury in animal models. However, the underlying mechanism of action is not clearly understood. This study examined the effectiveness of RIPC in a mouse model of hepatic IR and aimed to clarify the mechanism and relationship of the ATP-sensitive potassium channel (KATP) and HMGB1-induced TLR4/MyD88/NF-κB signaling. C57BL/6 male mice were separated into six groups: (i) sham-operated control, (ii) IR, (iii) RIPC+IR, (iv) RIPC+IR+glyburide (KATP blocker), (v) RIPC+IR+diazoxide (KATP opener), and (vi) RIPC+IR+diazoxide+glyburide groups. Histological changes, including hepatic ischemia injury, were assessed. The levels of circulating liver enzymes and inflammatory cytokines were measured. Levels of apoptotic proteins, proinflammatory factors (TLR4, HMGB1, MyD88, and NF-κB), and IκBα were measured by Western blot and mRNA levels of proinflammatory cytokine factors were determined by RT-PCR. RIPC significantly decreased hepatic ischemic injury, inflammatory cytokine levels, and liver enzymes compared to the corresponding values observed in the IR mouse model. The KATP opener diazoxide + RIPC significantly reduced hepatic IR injury demonstrating an additive effect on protection against hepatic IR injury. The protective effect appeared to be related to the opening of KATP, which inhibited HMGB1-induced TRL4/MyD88/NF-kB signaling.

The preventive effect of resiniferatoxin on the development of cold hypersensitivity induced by spinal nerve ligation: involvement of TRPM8.

BACKGROUND: Resiniferatoxin (RTX) is a potent analog of capsaicin and activates transient receptor potential (TRP) vanilloid type (TRPV) 1. In the current study, we investigated the preventive effect of perineural RTX on the development of cold hypersensitivity induced by spinal nerve ligation (SNL) in rats. Furthermore, we examined the association between the expression level of TRPV1, TRP ankyrin type (TRPA) 1 and TRP melastatin type (TRPM) 8 in the dorsal root ganglion (DRG) and cold hypersensitivity after SNL. RESULTS: RTX pretreatment prevented the development of SNL-induced hypersensitivity to mechanical, thermal, and cold stimuli. Western blot analysis 4 weeks after RTX pretreatment showed that RTX pretreatment decreased the protein expression level of SNL-induced TRPM8, but not TRPV1 or TRPA1, in the DRG of SNL rats. Immunofluorescent analysis revealed that up-regulated TRPM8-stained neurons after SNL co-localized with neurofilament 200-positive neurons located in the DRG. CONCLUSIONS: Pretreatment with perineural RTX significantly inhibits SNL-induced mechanical, thermal, and cold hypersensitivity. The antinociceptive effect of perineural RTX, especially on cold hypersensitivity, may be related to the suppression of TRPM8 expression in DRG.

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.

The neuromuscular effects of rocuronium under sevoflurane-remifentanil or propofol-remifentanil anesthesia: a randomized clinical comparative study in an Asian population.

BACKGROUND: We conducted a prospective, randomized, multicenter study to evaluate the differences in the blocking effect of different doses of rocuronium between sevoflurane- or propofol-remifentanil anesthesia in an Asian population. METHODS: A total of 368 ASA I-II patients was enrolled. Anesthesia was induced with 2.0 mg/kg propofol and 0.1 µg/kg/min remifentanil (TIVA) or 5.0 vol.% sevoflurane with 0.1 µg/kg/min remifentanil (SEVO). Tracheal intubation was facilitated at 180 s after the administration of rocuronium at 0.3, 0.6, or 0.9 mg/kg and then intubation condition was evaluated. The time to maximum block and recovery profile were monitored by TOF stimulation of the ulnar nerve and by recording the adductor pollicis response using acceleromyography. RESULTS: The numbers of patients with clinically acceptable intubation conditions were 41, 82, and 97 % (TIVA) and 34, 85, and 90 % (SEVO) at each dose of rocuronium, respectively. There were no significant differences in the time to maximum block between groups at each rocuronium dose. There were significant differences in the recovery to a train-of-four ratio of 90 % between the groups: 42.7 (19.5), 74.8 (29.9), and 118.4 (35.1) min (TIVA) and 66.5 (39.3), 110.2 (43.5), and 144.4 (57.5) min (SEVO) at 0.3, 0.6, and 0.9 mg/kg, respectively (P < 0.001). CONCLUSIONS: There are no significant differences in intubation conditions between propofol-remifentanil and sevoflurane-remifentanil anesthesia at the same dose of rocuronium. The type of anesthetic does not significantly influence the time to maximum block by rocuronium. Rocuronium at a dose of 0.9 mg/kg should be used for better intubation conditions with both anesthesia regimens in an Asian population. TRIAL REGISTRATION: UMIN-CTR Clinical Trial ( http://www.umin.ac.jp/ctr/index.htm ; UMIN#000007289 ; date of registration 14(th) February 2012).

Perineural pretreatment of bee venom attenuated the development of allodynia in the spinal nerve ligation injured neuropathic pain model; an experimental study.

BACKGROUND: Diluted bee venom (BV) is known to have anti-nociceptive and anti-inflammatory effects. We therefore assessed whether perineural bee venom pretreatment could attenuate the development of neuropathic pain in the spinal nerve ligation injured animal model. METHODS: Neuropathic pain was surgically induced in 30 male Sprague Dawley rats by ligation of the L5 and L6 spinal nerves, with 10 rats each treated with saline and 0.05 and 0.1 mg BV. Behavioral testing for mechanical, cold, and thermal allodynia was conducted on postoperative days 3 to 29. Three rats in each group and 9 sham operated rats were sacrificed on day 9, and the expression of transient receptor potential vanilloid type 1 (TRPV1), ankyrin type 1 (TRPA1), and melastatin type 8 (TRPM8) receptors in the ipsilateral L5 dorsal root ganglion was analyzed. RESULTS: The perineural administration of BV to the spinal nerves attenuated the development of mechanical, thermal, and cold allodynia, and the BV pretreatment reduced the expression of TRPV1, TRPA1, TRPM8 and c - Fos in the ipsilateral dorsal root ganglion. CONCLUSION: The current study demonstrates that the perineural pretreatment with diluted bee venom before the induction of spinal nerve ligation significantly suppresses the development of neuropathic pain. Furthermore, this bee venom induced suppression was strongly related with the involvement of transient receptor potential family members.

Comparison of analgesic effect of pericapsular nerve group block and supra-inguinal fascia iliaca compartment block on dynamic pain in patients with hip fractures: a randomized controlled trial.

BACKGROUND: Patients with hip fracture often experience severe pain, particularly during movement or slight positional change, prior to the occurrence of surgery. It is essential to explore the appropriate analgesic methods before surgery in patients with hip fracture, especially those capable of alleviating dynamic pain. Pericapsular nerve group (PENG) block was introduced as a useful technique for hip analgesia. In this study, we aimed to compare the reduction in dynamic pain between the PENG block and supra-inguinal fascia iliaca compartment block (SIFICB). METHODS: This prospective trial included 80 hip fracture patients aged ≥19 years, with an American Society of Anesthesiologists Physical Status of 1-4 and a baseline dynamic pain score ≥4 on the numerical rating scale. The patients were randomly allocated into the PENG block (n=40) and SIFICB group (n=40). For the PENG block and SIFICB, 20 mL and 30 mL of 0.3% ropivacaine was used, respectively. The primary outcome was reduction in dynamic pain scores at 30 min following the peripheral nerve block. Dynamic pain score was evaluated when the leg was passively raised. RESULTS: A total of 79 patients were included in the final analysis, and the reductions in pain score during hip flexion were 3.1±2.4 and 2.9±2.5 in the PENG block and SIFICB groups, respectively, which was statistically insignificant (p=0.75). Moreover, no significant differences were observed in any of the outcomes. CONCLUSIONS: PENG block and SIFICB could effectively provide analgesia for dynamic pain in patients with hip fractures, with no significant difference between the two groups. TRIAL REGISTRATION NUMBER: NCT04677348.