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Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.

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PURPOSE: To assess the role of dexmedetomidine as an adjuvant to local anesthetics (LA) in enhancing the duration and quality of peribulbar blocks for ophthalmic surgeries. DESIGN: Systematic review with meta-analysis and trial sequential analysis Methods: We systematically searched MEDLINE, Embase, and Cochrane for randomized controlled trials (RCTs) involving adult patients undergoing ophthalmic surgery under peribulbar block, comparing LA alone versus LA + dexmedetomidine. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were computed using a random effects model. Sensitivity and trial-sequential analyses (TSA) were performed to assess inconsistencies, weight type II and II errors, and estimate the required information size of the samples for all endpoints. RESULTS: Sixteen RCTs (1,220 patients) were included. Compared with LA alone, dexmedetomidine was associated with prolonged (1) motor block duration (MD 65.01 minutes, p<0.001) and (2) sensory block duration (MD 81.94 minutes, p<0.001); (3) reduced intraocular pressure (IOP) (MD -2.6 mmHg, p<0.001), and (4) decreased need for supplemental injections (RR 0.44, p=0.007). Additionally, dexmedetomidine showed (5) longer time to analgesic request (MD 97.15 minutes, p<0.001) and (6) increased surgeon satisfaction (RR 1.52, p=0.01). Sensitivity analyses and TSA were consistent across all endpoints, and the required information size was achieved for most endpoints, indicating that pooled analyses were reliable and sample sizes were sufficient. CONCLUSIONS: Compared with LA alone, dexmedetomidine significantly prolonged sensory and motor block duration and the time to the first analgesic request; decreased IOP and the need for supplemental injections, while increasing surgeon satisfaction.

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Several statistical models have been proposed in recent years, among them is the semiparametric regression. In medicine, there are several situations in which it is impracticable to consider a linear regression for statistical modeling, especially when the data contain explanatory variables that present a nonlinear relationship with the response variable. Another common situation is when the response variable does not have a unimodal shape, and it is not possible to adopt distributions belonging to the symmetric or asymmetric classes. In this context, a semiparametric heteroskedastic regression is proposed based on an extension of the normal distribution. Then, we show the usefulness of this model to analyze the cost of prostate cancer surgery. The predictor variables refer to two groups of patients such that one group receives a multimodal local anesthetic solution (Preemptive Target Anesthetic Solution) and the second group is treated with neuraxial blockade (spinal anesthesia/traditional standard). The other relevant predictor variables are also evaluated, thus allowing for the in-depth interpretation of the predictor variables with a nonlinear effect on the dependent variable cost. The penalized maximum likelihood method is adopted to estimate the model parameters. The new regression is a useful statistical tool for analyzing medical data.

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The chemical structure of piperidine has a unique ability to combine with other molecular fragments. This fact makes it possible to actively use it as an effective basis for the creation of new drug-like substances. Thus, the aim of the current investigation was to study the acute toxicity, local anesthetic potency, and antiarrhythmic activity of the two new synthesized piperidine derivatives under laboratory codes LAS-286 and LAS-294 (local anesthetic substances). The Bulbring & Wajda animal model and method of determining the nociception threshold during electrical stimulation was used to investigate the action of the substance during infiltration anesthesia. An antiarrhythmic activity was observed by the aconitine-induced rat arrhythmia model. Additionally, these compounds were studied in relation to molecular docking to delineate the structure-activity relationships. The tested piperidine derivatives had a low toxicity in the subcutaneous and intravenous administration routes. The experimental results showed a higher prolonged and pronounced local anesthetic activity for LAS-286 at a 0.5% concentration, compared to the reference preparations. The low dosage of 0.1 mg/kg of LAS-294 demonstrated a pronounced preventive antiarrhythmic effect in 90% of cases on the development of mixed arrhythmia, caused by aconitine. The results of molecular docking confirmed a higher binding affinity of the tested piperidines with the Nav1.4 and Nav1.5 macromolecules. The results of the present study are very promising, because these piperidines have shown a high biological activity, which can suggest a potential therapeutic application in the future.

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The aim of this study was to compare the intra and postoperative analgesic effects of sacrococcygeal epidural levobupivacaine with those of lumbosacral levobupivacaine in feline ovariohysterectomy. Thirty-six cats were premedicated with intramuscular acepromazine (0.05 mg/kg) and meperidine (6 mg/kg). Anesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. The cats were randomly assigned one of the three treatments receiving 0.33% levobupivacaine (0.3 mL/kg) into the sacrococcygeal (S-C group, n=12) or lumbosacral (L-S group, n=12) epidural space, or the same volume of 0.9% saline solution into one of the epidural approaches (Control group, n=12). Intraoperatively, cardiorespiratory variables, end-tidal isoflurane concentration (FE´ISO), and fentanyl requirements were recorded. Postoperative pain was assessed by the UNESP (Universidade Estadual Paulista)-Botucatu multidimensional composite pain scale and the Glasgow feline composite measure pain scale up to 8 hr post-extubation. Morphine was administered as rescue analgesia. Overall FE´ISO and fentanyl requirements were lower in the L-S and S-C compared to the Control (P=0.002-0.048, respectively). There was no significant difference in the cardiorespiratory variables during anesthesia, postoperative pain and rescue analgesia among groups. The time to standing after anesthesia was prolonged in the L-S and S-C groups than in the Control (P<0.001). Lumbosacral and sacrococcygeal epidural levobupivacaine resulted in similar decreases in isoflurane requirements and intraoperative fentanyl supplementation in the cats, with no postoperative benefits.

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The use of tumescent anesthesia with lidocaine can provide better intra- and postoperative analgesia that would benefit extensive reconstructive surgery. However, lidocaine can interfere with the healing process. Therefore, this study aimed to assess the local interference of the healing of induced and closed skin defects in a geometric pattern associated with the use of tumescent anesthesia with lidocaine in rabbits. Furthermore, we assessed its influence on cardiorespiratory parameters and postoperative analgesia. This study included 27 rabbits divided into three groups: GC (without the use of tumescence), GS (use of tumescence with 0.9% NaCl solution), and GL (use of tumescent anesthesia with lidocaine). There was no statistically significant intergroup difference in any stage of the wound healing process on macroscopic evaluations, in the angiogenesis process, or in the process of collagenization and fibroblast deposition. There were significant differences in heart rate (lower in GL), respiratory rate (higher in GC), mean arterial pressure (higher in GL), and expired concentration of isoflurane (lower in GL). There was no significant intergroup difference in the von Frey filament test or the visual analog scale score used to evaluate postoperative analgesia. We concluded that tumescent anesthesia with lidocaine does not impair postoperative tissue repair. Its use features benefits such as reducing the volume of inhaled anesthetic, maintaining the anesthesia plan, stable heart and respiratory rates, and lower hypotension during the surgical procedure.

O uso da anestesia por tumescência com lidocaína pode proporcionar melhor analgesia transoperatória e pós-operatória, o que seria um benefício em cirurgias reconstrutivas extensas. Entretanto, a lidocaína pode interferir na cicatrização. Diante disso, delineou-se um estudo a fim de avaliar a interferência local da cicatrização de defeitos cutâneos induzidos e fechados em padrão de figura geométrica, associado ao emprego de anestesia por tumescência com lidocaína em coelhos. Ademais, avaliar sua influência em parâmetros cardiorrespiratórios e na analgesia pós-operatória. Foi realizado um estudo com 27 coelhos, separados em três grupos, compreendidos em GC (sem o emprego de tumescência), GS (emprego de tumescência com solução NaCl 0.9%) e GL (emprego de anestesia por tumescência com lidocaína). Não houve diferença estatística em nenhuma etapa do processo cicatricial da ferida entre os grupos, tampouco nas avaliações macroscópicas, e no processo de angiogênese, ou ainda no processo de colagenização e deposição de fibroblastos. Houve diferença significativa na frequência cardíaca (menor no GL) e na respiratória (maior no GC), na pressão arterial média (maior no GL) e na concentração expirada de isoflurano (menor no GL). Não houve diferença significativa entre os grupos no teste de filamentos de von Frey e na Escala Visual Analógica, utilizados para avaliar a analgesia pós-operatória. Conclui-se que anestesia por tumescência com lidocaína não prejudica a regeneração tecidual após a cirurgia. O seu uso oferece benefícios como a diminuição do volume de anestésico inalatório, manutenção do plano anestésico, estabilidade das frequências cardíaca e respiratória, além de menor hipotensão durante o procedimento cirúrgico.

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Background: Mastitis is an inflammation of the mammary gland or udder, regardless of its origin, severity, or evolution. Bilateral total mastectomy is indicated in cases of chronic suppurative mastitis, gangrenous mastitis, udder neoplasm or hyperplasia. For mastectomy, the supine position is recommended and, as it is a long-term procedure, general anesthesia was chosen together with the tumescence technique with the objective of transanesthetic and postoperative analgesia. The present report aims to report the general anesthesia protocol used for 2 goats submitted to bilateral total mastectomy associated with a locoregional block by tumescence, a technique not described in the goat species. Cases: Two female goats, mixed breed, approximately 3 years old, were admitted to the Hospital Veterinário de Grandes Animais (HVGA) of the Universidade Federal Rural do Rio de Janeiro (UFRRJ), with a history of recurrent mastitis. There was an increase in udder volume and the presence of purulent secretion during milking. One of the animals had given birth about 20 days ago. Surgical treatment through bilateral total mastectomy was recommended for both animals, as they did not present a satisfactory response to antimicrobial therapy, excessive enlargement and functional loss of the mammary system. For the procedure, food fasting for 48 h and water fasting for 24 h was established. The anesthetic protocols used consisted of previous sedation with xylazine1 [Xilazin® - 0.05 mg/kg, IM] anesthetic induction with ketamine2 [Ketalex® - 10 mg/kg, IV] and midazolam3 [Dormire® - 0.1 mg/kg, IV]. Orotracheal intubation and connection to the anesthetic circuit were performed for maintenance through inhalation anesthesia with isoflurane4 (Forane®) and oxygen therapy. Then, in bottle of lactated ringer's solution5 [Linhamax® - 500 mL], lidocaine 2%6 without vasoconstrictor [Lidovet® - 40 mL] and adrenaline7 [Adren® - 25 mg/mL, 0.5 mL] were added, 10 mL/kg of the solution were injected into the subcutaneous tissue of the region of the mammary chains utilizing a Klein cannula after local antisepsis. After the administration of the tumescent solution, it was observed that the area involved is presented with the formation of a gel and there is minimal bleeding, compared to the conventional technique. The animals were monitored for the degree of analgesia, recording vital signs every 15 min at the end of the surgery, dipyrone9 [D-500® - 25 mg/kg, IV], morphine7 [Sulfato de Morfina® - 0.1 mg/kg, SC], and meloxicam10 [Maxican® 0.5 mg/kg, IM, 3 consecutive days] for postoperative analgesia. Additionally, tetanus serum1 [Vencosat® - 50,000 IU, single dose] and of oxytetracycline¹ [Oxitetraciclina LA® - 10 mg/kg, IM, 5 applications on alternate days)]. In the following 24 h, no signs of pain were observed on palpation of the surgical wound in the animals, but goat 1 was apathetic and inappetent, with improvement in the clinical picture only 48 h after surgery. Discussion: The choice of the surgical procedure resulted in an improvement in the clinical conditions of the animals and the anesthetic protocol using inhalation anesthesia and locoregional block (tumescence) proved to be efficient to perform in goats, contributing to transanesthetic and postoperative analgesia, being easily applied to ruminants that need surgical interventions in the region of mammary chains.

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BACKGROUND: Infraclavicular brachial plexus nerve block is a commonly performed anesthesiology technique in the upper extremity. Local anesthetics may be administered at different temperatures for both neuraxial and peripheral nerve blocks. We aimed to evaluate the effects of the temperature of the local anesthetic at the time of administration on the onset and duration of sensory and motor blocks in infraclavicular brachial plexus nerve block. METHODS: A total of 80 patients undergoing elective upper extremity surgery were randomly assigned to one of the following groups using a computer-based randomization software; low temperature (4 °C) (Group L, n = 26), room temperature (25 °C) (Group R, n = 27) and warmed (37 °C) (Group W, n = 27). A 1:1 mixture of 2% lidocaine and 0.5% bupivacaine was used as local anesthetic. Infraclavicular brachial plexus nerve block was performed under ultrasound guidance in all patients preoperatively. The onset and duration of sensory and motor blocks were recorded. RESULTS: Each group had different onset of motor (p < 0.001) and sensory (p < 0.001) blocks. The duration of motor block was similar between groups (p = 221). However, a significant difference was found in the duration of sensory block between group L (399.1 ± 40.8 min) and group R (379.6 ± 27.6 min) (p = 0.043). There was no complication related to nerve block procedure. CONCLUSIONS: The administration of the local anesthetic at lower temperatures may prolong the onset of both motor and sensory blocks in infraclavicular brachial plexus nerve block.

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OBJECTIVES: This randomized, triple-blind, crossover clinical trial aimed to evaluate the efficacy, onset, length of pulp and soft tissue anesthesia, and pain during injection of 2% buffered articaine and 4% non-buffered articaine solutions. METHODS: Each volunteer received two maxillary supraperiosteal anesthesia infiltrations in canine area. The infiltrations were performed at two different sessions using a different local anesthetic solution for each session, and the anesthetic injection speed was always 1 mL/min. The assessment of the onset and length of pulpal and soft tissue anesthesia was performed with the pulp electrical test "pulp tester" and the esthesiometer kit, respectively. Volunteers marked pain during injection on a visual analog scale (VAS). The anesthetics solutions pH was evaluated through the pH meter equipment. RESULTS: There was no difference between the two anesthetic solutions (onset of soft tissue anesthesia, p = 0.5386; length of soft tissue anesthesia, p = 0.718; onset of pulpal anesthesia, p = 0.747; length of pulpal anesthesia, p = 0.375), except for pain during the injection which was lower when buffered 2% articaine was used (p = 0.001) and the pH. The pH analysis revealed that the solutions differed from one another (p < 0.01). CONCLUSION: The 2% buffered articaine solution provided the same anesthetic properties then 4% unbuffered articaine with a great reduction in pain during injection. CLINICAL RELEVANCE: The possibility of use 2% buffered articaine solution instead of 4% articaine maintaining the same anesthetic properties with a great reduction in pain during injection and half of the anesthetic salt concentration.

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Epidural anesthesia minimizes perioperative pain in dogs. It is considered that epidural solution dispersion in cadavers is similar to alive dogs. The objective of the anatomical study was to compare the dispersion of 0.2 mL/kg 0.25% bupivacaine and iohexol via lumbar epidural (L1-L2) under fluoroscopic guidance in 10 thawed cadavers (GC) and 13 female dogs (G0.25) (5-15 kg; body score 4/5). The objective of the clinical study was to evaluate postoperative analgesic consumption and sedation for 6 h after extubation of dogs submitted to ovariohysterectomy when using 0.25% (G0.25; n = 10) bupivacaine with the intraoperative use of fentanyl (GF; n = 10). Parametric data were compared by the t-test and non-parametric data by the Mann Whitney test. Pain and sedation scores were evaluated over time by the Friedman test, followed by the Dunn test. Alive dogs presented greater epidural dispersion (17 ± 3 vertebrae) than thawed cadavers (11 ± 4 vertebrae; p = 0.002). All dogs treated with fentanyl and only one dog treated with 0.25% epidural bupivacaine presented pain scores above the cut-off point of the Glasgow Composite Measure Pain Scale Short-Form (GCMPS-SF) and required postoperative rescue analgesia up to 6 h after extubation. The sedation score was higher at all postoperative moments compared to preoperative moments in the G0.25 and GF, except for evaluations performed at 5 and 6 h after extubation in the GF. Greater sedation was observed immediately after extubation in the GF compared to the G0.25, and there was greater sedation in the G0.25 compared to the GF from 3 to 6 h after extubation. The conclusion of the anatomical study was that L1-L2 epidural bupivacaine dispersion is lower in canine thawed cadavers than in alive dogs. Conclusion of the clinical study was that lumbar epidural anesthesia improved postoperative analgesia and produced longer postoperative sedation when compared to fentanyl.