Local Anesthetic Potency Research Articles

Scorpion Neurotoxin: An Analgesic Antitumor Peptide Down-Regulates VGSCs and Exhibits Local Anesthetic Potency during Sciatic Nerve Block

Background: Some neurotoxins inhibit nerves strongly. Saxitoxins and tetrodotoxin exhibit strong affinity for various voltage-gated sodium channels (VGSCs), including Nav 1.7, but low affinity for Nav 1.8. Emerging data suggests AGAP mediate analgesia by binding voltage-independently to sodium channel site-3. Objective: This study examined AGAP's mechanism and analgesic efficacy during sciatic nerve block. Methods: In rats, partial sciatic nerve ligation caused rapid and persistent mechanical hyperalgesia. Mechanical hyperalgesia after medication delivery was assessed with von Frey filaments. Western blot and immunohistochemical staining assessed VGSC expression following drug treatment. Results: The data showed that lidocaine and AGAP increased paw withdrawal threshold compared to control rats. Compared to the control group, lidocaine or AGAP inhibited VGSCs. Conclusion: This study suggested that AGAP inhibits VGSCs to elicit lidocaine-like analgesia.

Experimental study of local anesthetic and antiarrhythmic activities of fluorinated ethynylpiperidine derivatives.

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.

Ascorbic acid reduces Ropivacaine-induced myotoxicity in cultured human osteoporotic skeletal muscle cells

BackgroundOsteoporosis is a worldwide health issue. Loss of bone mass is a potential risk factor for fragility fractures, and osteoporotic fractures place a considerable burden on society. Bone and muscle represent a functional unit in which the two tissues are intimately interconnected. Ropivacaine is a potent local anesthetic used in clinical practice for intraoperative anesthesia and postoperative pain management, in particular for hip surgery. When injected, Ropivacaine can diffuse locally through, in particular in surrounding skeletal muscle tissue, causing dose-dependent cytotoxicity, oxidative stress and myogenesis impairment. Based on those evidences, we focused our attention on Ropivacaine-induced cytotoxicity on cultured human myoblasts.MethodsPrimary human myoblasts and myotubes from healthy subjects, osteoarthritic and osteoporotic patients (OP) were cultured in the presence of Ropivacaine. In some experiments, ascorbic acid (AsA) was added as a potent antioxidant agent. Cell viability and ROS levels were evaluated to investigate the myotoxic activity and Real-Time PCR and Western blot analysis carried out to investigate the expression of proliferation and myogenic markers.ResultsA dose-dependent decrease of cell viability was observed after Ropivacaine exposure in both OP myoblasts and myotubes cultures, whereas those effects were not observed in the presence of Propofol, a general anesthetic. The adding of AsA reduced Ropivacaine negative effects in OP myoblast cultures. In addition, Ropivacaine exposure also increased ROS levels and upregulated Nox4 expression, an enzyme primarily implicated in skeletal muscle ROS generation. AsA treatment counteracted the oxidant activity of Ropivacaine and partially restored the basal condition in cultures. Positive myogenic markers, such as MyoD and Myf5, were downregulated by Ropivacaine exposure, whereas myostatin, a negative regulator of muscle growth and differentiation, was upregulated. The phenotypic deregulation of myogenic controllers in the presence of Ropivacaine was counteracted by AsA treatment.ConclusionsOur findings highlight the oxidative stress-mediated myotoxic effect of Ropivacaine on human skeletal muscle tissue cell cultures, and suggest treatment with AsA as valid strategy to mitigate its negative effects and allowing an ameliorated functional skeletal muscle recovery in patients undergoing hip replacement surgery for osteoporotic bone fracture.

Fabrication of a controlled-release delivery system for relieving sciatica nerve pain using an ultrasound-responsive microcapsule.

Lidocaine, a potent local anesthetic, is clinically used in nerve block and pain management. However, due to its short half-life, repeated administration is required. For this reason, here we designed and prepared a lidocaine-encapsulated polylactic acid-glycolic acid (Lidocaine@PLGA) microcapsule with ultrasound responsiveness to relieve the sciatica nerve pain. With a premixed membrane emulsification strategy, the fabricated lidocaine-embedded microcapsules possessed uniform particle size, good stability, injectability, and long-term sustained release both in vitro and in vivo. More importantly, Lidocaine@PLGA microcapsules had the function of ultrasonic responsive release, which made the drug release controllable with the effect of on-off administration. Our research showed that using ultrasound as a trigger switch could promote the rapid release of lidocaine from the microcapsules, achieving the dual effects of long-term sustained release and short-term ultrasound-triggered rapid release, which can enable the application of ultrasound-responsive Lidocaine@PLGA microcapsules to nerve root block and postoperative pain relief.

Comparative evaluation of anesthetic efficacy and hemodynamic effects of intrathecal isobaric bupivacaine versus intrathecal isobaric levobupivacaine in the lower abdominal and lower limb surgeries

Background: The most frequently utilized approach in patients undergoing lower abdominal and lower limb procedures is spinal anesthesia with bupivacaine. Aims and Objectives: The aim of the study was to compare the anesthetic efficacy and hemodynamic effects of isobaric bupivacaine and isobaric levobupivacaine for spinal anesthesia. Materials and Methods: In our study, 80 patients (43 – male and 37 – female) between the ages of 18 and 70 years at Sri Venkateswaraa Medical College Hospital and Research Centre, Ariyur, Puducherry, were enrolled and split into Group I and Group II following approval by an ethical committee and written informed consent. Individuals in Group I were given 3 mL of preservative free 0.5% isobaric bupivacaine (Anawin™, bupivacaine hydrochloride, Neon laboratories, India), and Group II patients were given 3 mL of 0.5% isobaric levobupivacaine (Levoanawin™, levobupivacaine hydrochloride, Neon laboratories, India) for spinal anesthesia. A complete preanesthetic checkup was performed the day before surgery. Results: In this study, we observed no significant correlation between height, weight, and surgery duration. We discovered a statistically substantial distinction in motor and sensory blockade between the bupivacaine (Group I) and levobupivacaine (Group II) groups. In this study, Group I (50% of patients) had a lower occurrence of hypotension than Group II (20% of patients), indicating a statistically significant variation between the groups. Conclusion: When compared to levobupivacaine, individuals in the bupivacaine group required more administration of the vasoactive medicine ephedrine and the sympathomimetic drug atropine. Levobupivacaine is less cardiotoxic, neurotoxic, and equally potent local anesthetic compared to its racemate.

Validated HPTLC Method for the Estimation of Oxetacaine in Pharmaceutical Formulations

Oxetacaine is a potent local anesthetics used to relieve pain associated with peptic ulcer. The current method details about a rapid, accurate and precise HPTLC technique for the assessment of Oxetacaine in Pharmaceutical formulation. Chromatographic resolution was carried out on precoated HPTLC plates (Silica gel 60 F254 on Aluminum plate) employing methanol: water: glacial acetic acid (8: 1.8: 0.2 v/v/v) as mobile phase. Densitometric assessment was carried out at 220nm [Camag TLC Scanner III with winCATs software (version – 1.3.4)]. The drug was identified with a Rf value of 0.61. The reliability of the projected method was ascertained by evaluating various validation parameters as per ICH guidelines. The proposed technique can evaluate ten or more formulation units concurrently in a single run and affords a more rapid and cost-effective QC tool for regular analysis of Oxetacaine in pharmaceutical formulations.

Delivery of local anaesthetics by a self-assembled supramolecular system mimicking their interactions with a sodium channel.

Site-1 sodium channel blockers (S1SCBs) act as potent local anaesthetics, but they can cause severe systemic toxicity. Delivery systems can be used to reduce the toxicity, but the hydrophilicity of S1SCBs makes their encapsulation challenging. Here, we report a self-assembling delivery system for S1SCBs whose design is inspired by the specific interactions of S1SCBs with two peptide sequences on the sodium channel. Specifically, the peptides were modified with hydrophobic domains so that they could assemble into nanofibres that facilitated specific binding with the S1SCBs tetrodotoxin, saxitoxin and dicarbamoyl saxitoxin. Injection of S1SCB-carrying nanofibres at the sciatic nerves of rats led to prolonged nerve blockade and to reduced systemic toxicity, with benign local-tissue reaction. The strategy of mimicking a molecular binding site via supramolecular interactions may be applicable more broadly to the design of drug delivery systems for receptor-mediated drugs.

Comparison of Chloroprocaine Versus Lidocaine With Epinephrine, Sodium Bicarbonate, and Fentanyl for Epidural Extension Anesthesia in Elective Cesarean Delivery: A Randomized, Triple-blind, Noninferiority Study

(Anesth Analg. 2021;132:666–675) To facilitate intrapartum cesarean delivery anesthesia, patients with ongoing neuraxial labor analgesia receive a more potent local anesthetic through the epidural catheter to establish surgical anesthesia. When this technique is successful, patients can forego other neuraxial or general anesthesia for cesarean delivery. The study institution uses 2 anesthetic solutions for epidural extension anesthesia: 3% chloroprocaine (CP), or a mixture of 2% lidocaine, epinephrine, sodium bicarbonate, and fentanyl (LEBF). Since the mixture takes time to prepare, CP is used for unanticipated emergencies on labor and delivery. This randomized, triple-blind, noninferiority study aimed to compare the surgical anesthesia onset times of CP and LEBF for epidural extension anesthesia for cesarean delivery.

A clinical comparative study of dexmedetomidine as an adjuvant to 2% plain lignocaine and 2% lignocaine with 1:200,000 adrenaline as local anesthetic agents for surgical removal of impacted mandibular third molars.

Introduction:Dexmedetomidine is a selective alpha-2 adrenoceptor agonist. It is conventionally used as a sedative in the intensive care unit. However, recently, the application of dexmedetomidine as an adjuvant to a local anesthetic agent has been studied. The present study intends to evaluate the effectiveness of dexmedetomidine as an adjuvant to 2% plain lignocaine for surgical removal of impacted mandibular third molar and to compare the efficacy of dexmedetomidine with 2% plain lignocaine with 2% lignocaine and 1:200000 adrenaline.Materials and Methods:A total of 80 patients who required surgical removal of impacted mandibular third molar extraction were included in the study. Patients were randomly divided into two groups using a computer-generated table. Patients in the study group received 2% plain lignocaine with 1 mcg/ml dexmedetomidine. Patients in the control group received 2% lignocaine with 1:200000 adrenaline. The parameters evaluated were onset and duration of action, pulse rate, blood pressure, oxygen saturation, and blood loss.Results:Onset of action was faster and the duration of action was longer when dexmedetomidine was used with lignocaine as a local anesthetic agent. The vital parameters in both the groups were stable. Bleeding at the surgical site was less in the dexmedetomidine group.Conclusion:The study concluded that the combination of dexmedetomidine with lignocaine enhances the local anesthetic potency of lignocaine when injected for nerve blocks.

A Comparative Study Evaluating the Efficacy of Lignocaine and Dexmedetomidine with Lignocaine and Adrenaline in Third Molar Surgery.

The aim of this study was to compare the anesthetic efficacy, duration of action, pain, and cardiovascular effects of dexmedetomidine when added to 2% lignocaine hydrochloride in bilateral symmetrical impacted third molars. This study comprised of 40 healthy patients who required extraction of identical bilateral impacted lower third molars. The left side of the patients was designated as test side where patients received local anesthesia with lignocaine plus dexmedetomidine (2% lignocaine + dexmedetomidine 1μ/ml), and the right side of the patients was designated as control side where patients received local anesthesia with lignocaine plus adrenaline (2% lignocaine in 1:80,000 adrenaline). Both surgical interventions were performed at two different appointments with a minimum time interval of 2weeks. The time to onset and duration of action were noted as primary outcome variables, while the secondary outcome variables included pain and hemodynamic changes associated with dexmedetomidine if any. Onset of action of the local anesthesia was found to be faster in addition to having a relatively longer duration of action when the newer drug dexmedetomidine was added to lignocaine when compared with the conventional combination of lignocaine and adrenaline (P < 0.05). There were no significant changes in the systolic blood pressure, diastolic blood pressure, and heart rate from the baseline following the injection of dexmedetomidine. The study demonstrated that the combination of dexmedetomidine with lignocaine enhances the local anesthetic potency of lignocaine without significant systemic effects when locally injected into oral mucosa.

A Randomized Controlled Trial: Comparison of 4% Articaine versus 0.5% Bupivacaine for Ambulatory Orthopedic Surgery under Supraclavicular Block.

Background Articaine has been used in many dental and ophthalmic outpatient procedures. In the era of ultrasound-guided regional techniques, we searched for short and potent local anesthetic for patients undergoing ambulatory upper limb procedures. However, studies about articaine efficacy in brachial plexus block are limited. In this study, we compared its safety and efficacy against bupivacaine as a commonly used anesthetic agent for ultrasound-guided supraclavicular brachial plexus block. Methods This randomized prospective study was performed at Ain Shams University Hospital from January to March 2020. A total of 117 patients aged 20 to 60 years, with the American Society of Anesthesiologists physical status I and II, were enrolled in the study. Patients were randomly allocated into two groups: in group A, patients received 30 ml articaine 2%, and in group B, patients received 30 ml of bupivacaine 0.5%. We measured motor and sensory block duration as a primary outcome. Other secondary outcomes such as onset of block, duration of analgesia, patient satisfaction, and time to home discharge readiness were also measured. Results We analyzed data collected from 97 patients. The motor block duration was significantly shorter in group A (165.73 ± 20.33 min) than in group B (220.27 ± 37.73 min). The onset of motor block was faster in group A (8.73 ± 4.33 min), and the postoperative VAS score was lower in group B. Patients in group A achieved an earlier home discharge of 289.67 ± 2.73 min. Conclusion Earlier resolution of articaine block makes it more favorable than bupivacaine for ambulatory surgery. This trial is registered with (NCT04189198).

A primer on tissue pH and local anesthetic potency.

The relationship between pH, pKa, and degree of local anesthetic ionization is quantified by the Henderson-Hasselbalch equation. As presented in standard textbooks, the effect of pH on the degree of ionization of any particular local anesthetic is not immediately clear due to the x-axis displaying pH - pKa, which requires conversion to pH, based on the pKa for each local anesthetic, a complex process. We present a graphical solution that clarifies the interrelationships between pH, pKa, and degree of ionization by plotting pKa on the x-axis versus the percentage of unionized local anesthetic on the y-axis. The vertical intercept from the x-axis to the pH curves allows rapid and accurate estimation of the degree of ionization of any local anesthetic of known pKa.

Regional Anesthesia for Pediatric Ophthalmic Surgery: A Review of the Literature.

Ophthalmic pediatric regional anesthesia has been widely described, but infrequently used. This review summarizes the available evidence supporting the use of conduction anesthesia in pediatric ophthalmic surgery. Key anatomic differences in axial length, intraocular pressure, and available orbital space between young children and adults impact conduct of ophthalmic regional anesthesia. The eye is near adult size at birth and completes its growth rapidly while the orbit does not. This results in significantly diminished extraocular orbital volumes for local anesthetic deposition. Needle-based blocks are categorized by relation of the needle to the extraocular muscle cone (ie, intraconal or extraconal) and in the cannula-based block, by description of the potential space deep to the Tenon capsule. In children, blocks are placed after induction of anesthesia by a pediatric anesthesiologist or ophthalmologist, via anatomic landmarks or under ultrasonography. Ocular conduction anesthesia confers several advantages for eye surgery including analgesia, akinesia, ablation of the oculocardiac reflex, and reduction of postoperative nausea and vomiting. Short (16 mm), blunt-tip needles are preferred because of altered globe-to-orbit ratios in children. Soft-tip cannulae of varying length have been demonstrated as safe in sub-Tenon blockade. Ultrasound technology facilitates direct, real-time visualization of needle position and local anesthetic spread and reduces inadvertent intraconal needle placement. The developing eye is vulnerable to thermal and mechanical insults, so ocular-rated transducers are mandated. The adjuvant hyaluronidase improves ocular akinesia, decreases local anesthetic dosage requirements, and improves initial block success; meanwhile, dexmedetomidine increases local anesthetic potency and prolongs duration of analgesia without an increase in adverse events. Intraconal blockade is a relative contraindication in neonates and infants, retinoblastoma surgery, and in the presence of posterior staphylomas and buphthalmos. Specific considerations include pertinent pediatric ophthalmologic topics, block placement in the syndromic child, and potential adverse effects associated with each technique. Recommendations based on our experience at a busy academic ophthalmologic tertiary referral center are provided.

Fenestrations control resting-state block of a voltage-gated sodium channel

Potency of drug action is usually determined by binding to a specific receptor site on target proteins. In contrast to this conventional paradigm, we show here that potency of local anesthetics (LAs) and antiarrhythmic drugs (AADs) that block sodium channels is controlled by fenestrations that allow drug access to the receptor site directly from the membrane phase. Voltage-gated sodium channels initiate action potentials in nerve and cardiac muscle, where their hyperactivity causes pain and cardiac arrhythmia, respectively. LAs and AADs selectively block sodium channels in rapidly firing nerve and muscle cells to relieve these conditions. The structure of the ancestral bacterial sodium channel NaVAb, which is also blocked by LAs and AADs, revealed fenestrations connecting the lipid phase of the membrane to the central cavity of the pore. We cocrystallized lidocaine and flecainide with NavAb, which revealed strong drug-dependent electron density in the central cavity of the pore. Mutation of the contact residue T206 greatly reduced drug potency, confirming this site as the receptor for LAs and AADs. Strikingly, mutations of the fenestration cap residue F203 changed fenestration size and had graded effects on resting-state block by flecainide, lidocaine, and benzocaine, the potencies of which were altered from 51- to 2.6-fold in order of their molecular size. These results show that conserved fenestrations in the pores of sodium channels are crucial pharmacologically and determine the level of resting-state block by widely used drugs. Fine-tuning drug access through fenestrations provides an unexpected avenue for structure-based design of ion-channel-blocking drugs.

PO-465 Effect of pain management drugs in metastatic prostate cancer: in vitro studies

IntroductionMetastatic castration-resistant prostate cancer (mCRPC) presents no curative treatment, being the median life expectancy of this patients about 14–20 months. Docetaxel (Doc) remains the current first line treatment of mCRPC, increasing the median overall survival by 13.6 months. During this time, the major impairing life-altering quality complication is cancer-induced pain. Local anaesthetics (LA) as morphine (Mor), lidocaine (Lid), ropivacaine (Rop) and levobupivacaine (Lev) are used to minimise pain. Several studies report the antiproliferative, cytotoxic and sensitisation to chemotherapy effects of LA in a variety of other cancers this project aims to study the effect of pain management drugs combined with docetaxel for treatment of mCRPC.Material and methodsCytotoxic effects of LA and Doc in monotherapy were evaluated in one cell line of mCRPC (PC3) by incubating the cells with various concentrations of Mor (175.2 and 350.5 nM), Lid 2% (426.7 and 853.4 nM), Rop (36.4, 72.9, 136.7 and 273.3 nM), Lev (43.3, 86.7 and 173.4 nM) and Doc (0.01–500 nM) during 48 and 72 hours. Afterwards cell proliferation was determined using sulforhodamine B (SRB) assay. To study the effect of LA combined with Doc, cells were incubated with LA in the previous concentrations for 72 hours, then a concentration of Doc that leads to 80% of maximal response (EC80) was added. After 48 and 72 hours SRB assay was performed.Results and discussionsResults indicate that, after 48 hour, there is a higher decrease in cell proliferation to 85.03%±2.75, 83.73%±2.17% and 85.43%±3.68, relatively to control, when higher concentrations of Lid, Rop and Lev were added, respectively. Results showed that the EC80 of Doc is 1.51 and 0.81 nM, for 48 and 72 hour respectively. Preliminary results of combined therapy demonstrate that the combination of Doc with the highest concentrations of Rop and Lev resulted in a significant decrease in cell proliferation to 57.22% and to 54.22%, respectively.ConclusionThese preliminary results suggest that Rop and Lev, the most potent LA, are the most effective drugs in sensitise PC3 cells to chemotherapy with docetaxel, potentiating the therapeutic effects.The authors would like to thank Foundation for Science and Technology (FCT) (Strategic Project CNC.IBILI UID/NEU/04539/2013) through partnership arrangement PT2020 – COMPETE 2020 – Operational Thematic Program for Competitiveness and Internationalisation (POCI) (POCI-01–0145-FEDER-007440) for financial support.

Dexmedetomidine as an Additive to Local Anesthesia: A Step to Development in Dentistry

The study aimed to compare the effect of dexmedetomidine added to lidocaine against epinephrine added to lidocaine on local anesthetic potency and to look for future prospects of dexmedetomidine as an additive to local anesthesia in dentistry. The study included 25 healthy volunteers in whom extraction of all first premolars was scheduled as part of their orthodontic treatment plan. In this split-mouth, double-blind, crossover, randomized controlled trial, patients were randomized into 2 groups: Group 1 received injection lidocaine plus dexmedetomidine, and group 2 was administered lidocaine plus epinephrine. Patients were assessed for the onset of action of anesthesia, duration of analgesia, pain perception, and vital signs. The mean values (±standard deviations) for the onset of anesthetic action in groups 1 and 2 were 113±24.9 and 141±34.8seconds, respectively, for the mandible. For the maxilla, the mean values were 113±24.9seconds for group 1 and 165±43.8seconds for group 2. The duration of anesthesia was longer in group 1 (lidocaine plus dexmedetomidine), in which the requirement for the first analgesic on request was seen after a longer time interval, when compared with group 2 (lidocaine plus epinephrine).Pain perception elicited statistically significant results with less perception of pain in group 1 (lidocaine plus dexmedetomidine). The vital parameters remained stable, and the results were not statistically significant. In this study, we observed that the addition of dexmedetomidine to lidocaine for maxillary and mandibular nerve blocks significantly prolonged the block duration and shortened the onset of action, as well as improved postoperative analgesia in terms of the need for fewer analgesics in the postoperative period. Furthermore, the vital parameters remained stable and no complications were encountered. The findings were supportive of the use of dexmedetomidine as an adjunct to local anesthetics in dental procedures.

Efficacy of caudal levopubivacaine versus bupivacaine in children undergoing lower abdominal surgery: a prospective randomized controlled study

Background Postoperative pain in pediatrics causes psychological and physiological problems; thus, preemptive analgesia is important, even in newborns. Caudal block is a useful adjuvant with general anesthesia and for postoperative analgesia for infraumbilical operations. Levobupivacaine is less cardiotoxic, less neurotoxic, and an equally potent local anesthetic compared with its racemate. Aim Our aim is to compare the efficacy of caudally administered isobaric levobupivacaine 0.25% versus isobaric bupivacaine 0.25% in children undergoing lower abdominal surgery. Patients and methods This study was carried out on 60 children, 1–10 years, American Society of Anesthesiologists I–II, scheduled for elective lower abdominal surgery. Patients were randomized into two equal groups (30 patients in each group): group I: bupivacaine group: patients received 1 ml/kg bupivacaine 0.25%. Group II: levobupivacaine group: patients received 1 ml/kg levobupivacaine 0.25%. The onset time of sensory block, heart rate, mean arterial blood pressure, and respiratory rate were recorded intraoperatively. Postoperative pain was assessed using the Children’s and Infant’s Postoperative Pain Scale; time of postoperative first rescue of analgesia and duration of motor blockade were determined by the Bromage score postoperatively. Results There was no significant difference between both groups in the onset time of sensory block, hemodynamics (heart rate and mean arterial pressure), and respiratory rate. Children’s and Infant’s Postoperative Pain Scale was significantly lower in group I at 120 and 180 min postoperatively. The Bromage score was significantly lower in group ІІ at 15, 30, and 60 min postoperatively. Time till administration of first-rescue analgesia was significantly shorter in group II than group I. Conclusion Using similar doses, bupivacaine produced a higher incidence of residual motor block and longer analgesic block than levobupivacaine. Thus, levobupivacaine is more suitable for short operations and could make it preferable for day case surgery. However, bupivacaine is still more suitable for prolonged operations.

Hollow Silica Nanoparticles Penetrate the Peripheral Nerve and Enhance the Nerve Blockade from Tetrodotoxin.

The efficacy of tetrodotoxin (TTX), a very potent local anesthetic, is limited by its poor penetration through barriers to axonal surfaces. To address this issue, we encapsulated TTX in hollow silica nanoparticles (TTX-HSN) and injected them at the sciatic nerve in rats. TTX-HSN achieved an increased frequency of successful blocks, prolonged the duration of the block, and decreased the toxicity compared to free TTX. In animals injected with fluorescently labeled HSN, the imaging of frozen sections of nerve demonstrated that HSN could penetrate into nerve and that the penetrating ability of silica nanoparticles was highly size-dependent. These results demonstrated that HSN could deliver TTX into the nerve, enhancing efficacy while improving safety.

Synthesis, biological evaluation, and molecular docking of ropivacaine analogs as local anesthetic agents

Two series of ropivacaine analogs (4a–4q, 7a–7c) were synthesized, and their biological activities were evaluated as local anesthetic agents. Most of the compounds displayed detectable local anesthetic characteristics. Among them, compound 4l showed significant efficacy with sciatic nerve block, infiltration, corneal surface, and spinal anesthetic activities. It was as potent as the reference compound ropivacaine. Dissociation constants of these compounds were 5.9–7.9. In addition, molecular docking modeling on compound 4l and ropivacaine was performed to delineate structural requirements and potential mechanisms for the local anesthetic activity. This study provides valuable new information for our ongoing endeavor to design more potent local anesthetics.

Regional blocks carried out during general anesthesia or deep sedation: myths and facts.

More patients will accept regional blocks if these are performed during sedation or general anesthesia. This review discusses regional anesthesia in sedated or anesthetized patients. As complications of regional blocks are rare, regional anesthesia can be considered aswell-tolerated. Awake patients will notice only a minority of needle-to-nerve contacts, that renders the notion of a 'live monitor' obsolete. Using high-resolution ultrasound, the needle can be advanced to an extraepineural position for injection, thus strictly avoiding needle-to-nerve contact or intraepineural injection of local anesthetic. Rare cases of intoxication manifest more immediately when the patient is awake but some general anesthesia drugs reduce the seizure-inducing potency of local anesthetics, and hemodynamic signs of intoxication are also detectable under general anesthesia, allowing for faster cardiopulmonary resuscitation as the patient is anesthetized already. With the use of ultrasound guidance in skilled hands, it is a reasonable option to perform neuraxial and peripheral regional blocks in sedated or anesthetized patients. Performing the procedure safely and effectively requires an adequate level of experience with the specific block technique in question.