Effectiveness of Liposomal Bupivacaine With Bupivacaine Hydrochloride vs Bupivacaine Hydrochloride Alone as a Local Anesthetic for Children Undergoing Ambulatory Urologic Surgery: The Baby ORIOLES Randomized Clinical Trial.

PURPOSE: We sought to determine if the addition of liposomal bupivacaine to bupivacaine hydrochloride improves opioid-free rate and postoperative pain scores among children undergoing ambulatory urologic surgery. MATERIALS AND METHODS: A prospective, phase 3, single-blinded, single-center randomized trial with superiority design was conducted in children 6 to 18 years undergoing ambulatory urologic procedures between October 2021 and April 2023. Patients were randomized 1:1 to receive dorsal penile nerve block (penile procedures) or incisional infiltration with spermatic cord block (inguinal/scrotal procedures) with weight-based liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The primary outcome was opioid-free rate at 48 hours. Secondary outcomes included parents' postoperative pain measure scores, numerical pain scale scores, and weight-based opioid utilization at 48 hours and 10 to 14 days. RESULTS: We randomized 104 participants, with > 98% (102/104) with complete follow-up data at 48 hours and 10 to 14 days. At interim analysis, there was no significant difference in opioid-free rate at 48 hours between arms (60% in the intervention vs 62% in the control group; estimated difference in proportion -1.9% [95% CI, -20%-16%]; P = .8). We observed no increased odds of patients being opioid-free at 48 hours with the intervention compared to the control group (OR 0.96 [95% CI 0.41-2.3]; P = .9). The trial met the predetermined futility threshold for early stopping. There was no difference in parents' postoperative pain measure scores, numerical pain scale scores, or opioid utilization at 48 hours or 10 to 14 days. No difference in adverse events was observed. CONCLUSIONS: The addition of liposomal bupivacaine to bupivacaine hydrochloride did not significantly improve opioid-sparing effect or postoperative pain compared with bupivacaine hydrochloride alone among children ≥ 6 years undergoing ambulatory urologic surgery.

Potentiometric determination of the local anesthetic procaine in pharmaceutical samples.

In this study, a new potentiometric sensor was developed for the determination of the local anesthetic drug procaine in pharmaceutical samples. Procaine (Pr)-Tetraphenlyborate (TPB) ion-pair was synthesized and used as a sensor material. Potentiometric sensors using the synthesized ion pair (Pr-TPB), poly(vinyl chloride) (PVC) and o-nitrophenyloctyl ether (o-NPOE) in different proportions were prepared and their performance properties were tested. Among the prepared sensors, the best potentiometric response characteristics were obtained with the sensor composition Pr-TPB:PVC:o-NPOE in the ratio of 6.0:32.0:62.0 (w/w %). The new procaine sensor developed in the present study had a near-Nernstian behavior of 54.1 ± 3.3 mV/per decade and a low detection limit of 3.18 × 10-5 mol L-1 in the concentration range of 1.0 × 10-1-1.0 × 10-4 mol L-1. Additionally, the sensor had a response time of less than 10 s and could work in a wide pH range for two different concentration values without being affected by pH changes. Finally, the new procaine potentiometric sensor was used to detect procaine in injection samples and successfully determined procaine concentrations with high recoveries.

Voltage-Gated Ion Channels: Structure, Pharmacology and Photopharmacology.

Voltage-gated ion channels are transmembrane proteins responsible for the generation and propagation of action potentials in excitable cells. Over the last decade, advancements have enabled the elucidation of crystal structures of ion channels. This progress in structural understanding, particularly in identifying the binding sites of local anesthetics, opens avenues for the design of novel compounds capable of modulating ion conduction. However, many traditional drugs lack selectivity and come with adverse side effects. The emergence of photopharmacology has provided an orthogonal way of controlling the activity of compounds, enabling the regulation of ion conduction with light. In this review, we explore the central pore region of voltage-gated sodium and potassium channels, providing insights from both structural and pharmacological perspectives. We discuss the different binding modes of synthetic compounds that can physically occlude the pore and, therefore, block ion conduction. Moreover, we examine recent advances in the photopharmacology of voltage-gated ion channels, introducing molecular approaches aimed at controlling their activity by using photosensitive drugs.

Local anesthetics allergy in children: Evaluation of diagnostic tests with Real-Life data.

BACKGROUND: Local anesthetic (LA) drugs are commonly used in clinical practice to provide effective analgesia, including in dentistry and minor surgical procedures. The perception of a high risk of allergy in daily applications leads to the referral of atopic patients and those with other drug allergies to allergy clinics for the evaluation of allergic reactions to LA. The aim of this study was to determine who should be referred to the allergy clinic for LA allergy testing, assess the frequency of LA allergy in pediatric patients, and identify the negative predictive value of skin tests in diagnosis. METHODS: January 2017-July 2023, the clinical and laboratory data, as well as the results of drug allergy tests, of patients referred to our pediatric allergy clinic by dentists and physicians performing minor surgical procedures with suspected LA allergy were retrospectively evaluated. RESULTS: Our study included a total of 153 patients, comprising 84 girls (54.9%) and 69 boys (45.1%), with a mean age of 8.9 (±3.3) years. The most common reason for referral was a history of non-LA drug allergies (n = 66, 43.2%), followed by asthma (n = 25, 16.3%). Hypersensitivity reactions (HRs) with LA were most commonly associated with articaine (n = 7, 4.8%), followed by lidocaine (n = 6, 4.1%). When intradermal tests were evaluated, 17 patients (11.1%) had a positive test result. The positivity for lidocaine was 70.6% (n = 12), and prilocaine was 29.4% (n = 5). Subcutaneous provocation was administered to 109 patients (71.2%), and one patient exhibited local erythema and swelling with prilocaine. CONCLUSION: Although LA allergy is a rare occurrence, consultations of this nature are frequently requested from allergy clinics in real life. Considering the negative predictive value of skin tests performed with LA drugs, the reaction rate appears to be low in patients with atopy or other drug allergies. It is crucial for all relevant healthcare professionals to be knowledgeable about the appropriate approach to suspected LA allergies to avoid unnecessary tests. To the best of our knowledge, our study is the most comprehensive work in the literature that evaluates the results of diagnostic tests in children referred with a suspicion of LA allergy.

Assessing the effectiveness of greater occipital nerve block in chronic migraine: a systematic review and meta-analysis.

BACKGROUND & AIMS: Chronic migraine poses a global health burden, particularly affecting young women, and has substantial societal implications. This study aimed to assess the efficacy of Greater Occipital Nerve Block (GONB) in individuals with chronic migraine, focusing on the impact of local anesthetics compared with placebo. METHODS: A meta-analysis and systematic review were conducted following the PRISMA principles and Cochrane Collaboration methods. Eligible studies included case-control, cohort, and randomized control trials in adults with chronic migraine, adhering to the International Classification of Headache Disorders, third edition (ICHD3). Primary efficacy outcomes included headache frequency, duration, and intensity along with safety assessments. RESULTS: Literature searches across multiple databases yielded eight studies for qualitative analysis, with five included in the final quantitative analysis. A remarkable reduction in headache intensity and frequency during the first and second months of treatment with GONB using local anesthetics compared to placebo has been reported. The incidence of adverse events did not differ significantly between the intervention and placebo groups. CONCLUSION: The analysis emphasized the safety and efficacy of GONB, albeit with a cautious interpretation due to the limited number of studies and relatively small sample size. This study advocates for further research exploring various drugs, frequencies, and treatment plans to enhance the robustness and applicability of GONB for chronic migraine management.

Neddylation signaling inactivation by tetracaine hydrochloride suppresses cell proliferation and alleviates vemurafenib-resistance of melanoma.

Tetracaine, a local anesthetic, exhibits potent cytotoxic effects on multiple cancer; however, the precise underlying mechanisms of its anti-cancer activity remain uncertain. The anti-cancer activity of tetracaine was found to be the most effective among commonly used local anesthetics in this study. After tetracaine treatment, the differentially expressed genes in melanoma cells were identified by the RNAseq technique and enriched in the lysosome signaling pathway, cullin family protein binding, and proteasome signaling pathway through Kyoto Encyclopedia of Genes and Genomes. Additionally, the ubiquitin-like neddylation signaling pathway, which is hyperactivated in melanoma, could be abrogated due to decreased NAE2 expression after tetracaine treatment. The neddylation of the pro-oncogenic Survivin, which enhances its stability, was significantly reduced following treatment with tetracaine. The activation of neddylation signaling by NEDD8 overexpression could reduce the antitumor efficacy of tetracaine in vivo and in vitro. Furthermore, vemurafenib-resistant melanoma cells showed higher level of neddylation, and potential substrate proteins undergoing neddylation modification were identified through immunoprecipitation and mass spectrometry. The tetracaine treatment could reduce drug resistance via neddylation signaling pathway inactivation in melanoma cells. These findings demonstrate that tetracaine effectively inhibits cell proliferation and alleviates vemurafenib resistance in melanoma by suppressing the neddylation signaling pathway, providing a promising avenue for controlling cancer progression.

Sequential administration of peripheral nerve blocks and onabotulinumtoxinA for the treatment of chronic migraine and other headache disorders-A retrospective tolerability and safety study.

OBJECTIVE: To determine the tolerability and safety of concurrent peripheral nerve blocks and onabotulinumtoxinA treatment during a single outpatient clinic procedure visit. BACKGROUND: Procedural interventions are available for the treatment of headache disorders. OnabotulinumtoxinA and peripheral nerve blocks are used as alternatives or in addition to oral therapies to reduce the frequency and intensity of migraine attacks. There is currently a lack of safety data focusing on the sequential administration of local anesthetic via peripheral nerve blocks and onabotulinumtoxinA during a single clinical encounter for the treatment of headache. The primary aim of the study was to determine the safety and tolerability of concurrent peripheral nerve blockade and onabotulinumtoxinA injections during a single outpatient clinic procedure visit. We hypothesized that the dual intervention would be safe and well tolerated by patients with chronic migraine and other headache disorders. METHODS: A retrospective chart review was performed using clinical data from patients seen by multiple providers over a 16-month timeframe at one outpatient headache clinic. Patients were identified by procedure codes and those receiving peripheral nerve block(s) and onabotulinumtoxinA injections during a single encounter within the study period were eligible for inclusion. Inclusion criteria were (1) patients 18 years and older who were (2) receiving both peripheral nerve blocks and onabotulinumtoxinA injections for the treatment of chronic migraine. Patients were excluded if they were under age 18, received their procedure outside of the clinic (emergency room, inpatient ward), or were receiving sphenopalatine ganglion blocks. Age- and sex-matched patients who received one procedure, either peripheral nerve blocks or onabotulinumtoxinA, were used for control. The primary outcome of this safety study was the number of adverse events that occurred in the dual intervention group compared to the single intervention control arms. Information regarding adverse events was gathered via retrospective chart review. If an adverse event was recorded, it was then graded by the reviewer utilizing the Common Terminology Criteria for Adverse Events ranging from Grade 1 Mild Event to Grade 5 Death. Additionally, it was noted whether the adverse event led to treatment discontinuation. RESULTS: In total, 375 patients were considered eligible for inclusion in the study. After age and sex matching of controls, 131 patients receiving dual intervention were able to be compared to 131 patients receiving onabotulinumtoxinA alone and 104 patients receiving dual intervention were able to be compared to 104 patients receiving peripheral nerve block(s) alone. The primary endpoint analysis showed no significant difference in total adverse events between dual intervention compared to nerve blocks alone or onabotulinumtoxinA alone. The number of adverse events that led to treatment discontinuation approached but did not reach statistical significance for those receiving dual intervention versus onabotulinumtoxinA alone in the number of adverse events that led to treatment termination (4.6%, 6/131 vs. 0.8%, 1/131, p = 0.065); however, the number of patients who discontinued therapy was not significantly different between those groups (2.3%, 3/131 vs. 0.8%, 1/131; p = 0.314; odds ratio 0.3 [0-3.2]; p = 0.338). CONCLUSIONS: In this retrospective chart review, there was no significant difference in adverse events or therapy discontinuation between patients receiving sequential peripheral nerve block(s) and onabotulinumtoxinA injections versus those receiving either peripheral nerve block(s) or onabotulinumtoxinA injections alone. As a result, we concluded that the combination procedure is likely safe and well tolerated in routine clinical practice.

Laparoscopic vs. ultrasound-guided transversus abdominis plane (TAP) block in colorectal surgery: a systematic review and meta-analysis of randomized trials.

BACKGROUND: The transversus abdominis plane block (TAPB) is effective for postoperative pain management in patients undergoing colorectal surgery. However, evidence regarding the optimal delivery method, either laparoscopic (L-TAPB) or ultrasound-guided (U-TAPB) is lacking. Our study aimed to compare the effectiveness of these delivery methods. METHODS: We carried out a literature search of PubMed, Cochrane Library, Web of Science, and Google Scholar databases to include randomized studies comparing patients receiving either L-TAPB or U-TAPB during minimally invasive colorectal surgery. The primary endpoint was opioid consumption in the first 24 h after surgery. Risk of bias was assessed with the RoB-2 tool. Effect size was estimated for each study with 95% confidence interval and overall effect measure was estimated with a random effect model. RESULTS: The literature search revealed 294 articles, of which four randomized trials were eligible. A total of 359 patients were included, 176 received a L-TAPB and 183 received a U-TAPB. We established the non-inferiority of L-TAPB, as the absolute difference of - 2.6 morphine-mg (95%CI - 8.3 to 3.0) was below the pooled non-inferiority threshold of 8.1 morphine-mg (low certainty level). No difference in opioid consumption was noted at 2, 6, 12, and 48 h (low to very low certainty level). Postoperative pain, nausea and vomiting were similar between groups at different timepoints (low to very low certainty level). No TAPB-related complications were recorded. Finally, the length of hospital stay was similar between groups. CONCLUSION: For postoperative multimodal analgesia both L-TAPB and U-TAPB may result in little to no difference in outcome in patients undergoing colorectal surgery. Registration Prospero CRD42023421141.

Role of mitochondrial DNA level in epidural-related maternal fever: a single-centre, observational, pilot study.

INTRODUCTION: Epidural analgesia has been associated with intrapartum maternal fever development. Epidural-related maternal fever (ERMF) is believed to be based on a non-infectious inflammatory reaction. Circulating cell-free mitochondrial deoxyribonucleic acid (mtDNA) is one of the possible triggers of sterile inflammatory processes; however, a connection has not been investigated so far. Therefore, this study aimed to investigate cell-free mtDNA alterations in women in labour with ERMF in comparison with non-febrile women. MATERIAL AND METHODS: A total of 60 women in labour were assessed for maternal temperature every 4 h and blood samples were obtained at the beginning and after delivery. Depending on the analgesia and the development of fever (axillary temperature ≥ 37.5 °C), the women were allocated either to the group of no epidural analgesia (n = 17), to epidural analgesia no fever (n = 34) or to ERMF (n = 9). Circulating cell-free mtDNA was analysed in the maternal plasma for the primary outcome whereas secondary outcomes include the evaluation of inflammatory cytokine release, as well as placental inflammatory signs. RESULTS: Of the women with epidural analgesia, 20% (n = 9) developed ERMF and demonstrated a decrease of circulating mtDNA levels during labour (p = 0.04), but a trend towards higher free nuclear DNA. Furthermore, women with maternal pyrexia showed a 1.5 fold increased level of Interleukin-6 during labour. A correlation was found between premature rupture of membranes and ERMF. CONCLUSIONS: The pilot trial revealed an evident obstetric anaesthesia phenomenon of maternal fever due to epidural analgesia in 20% of women in labour, demonstrating counterregulated free mtDNA and nDNA. Further work is urgently required to understand the connections between the ERMF occurrence and circulating cell-free mtDNA as a potential source of sterile inflammation. TRIAL REGISTRATION: NCT0405223 on clinicaltrials.gov (registered on 25/07/2019).

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied a lot recently. This review aims to extensively describe neutrophils functions'; their clinical implications, especially in tumor pathology; the value of clinical markers related to neutrophils; and the implications of neutrophils in onco-anesthesia. This review also aims to describe current evidence on the influence of anesthetic drugs on neutrophils' functions and their potential influence on perioperative outcomes.

Targeted local anesthesia: a novel slow-release Fe3O4-lidocaine-PLGA microsphere endowed with a magnetic targeting function.

PURPOSE: Lidocaine microspheres can prolong the analgesic time to 24-48 h, which still cannot meet the need of postoperative analgesia lasting more than 3 days. Therefore, we added Fe3O4 to the lidocaine microspheres and used an applied magnetic field to attract Fe3O4 to fix the microspheres around the target nerves, reducing the diffusion of magnetic lidocaine microspheres to the surrounding tissues and prolonging the analgesic time. METHODS: Fe3O4-lidocaine-PLGA microspheres were prepared by the complex-emulsion volatilization method to characterize and study the release properties in vitro. The neural anchoring properties and in vivo morphology of the drug were obtained by magnetic resonance imaging. The nerve blocking effect and analgesic effect of magnetic lidocaine microspheres were evaluated by animal experiments. RESULTS: The mean diameter of magnetically responsive lidocaine microspheres: 9.04 ± 3.23 µm. The encapsulation and drug loading of the microspheres were 46.18 ± 3.26% and 6.02 ± 1.87%, respectively. Magnetic resonance imaging showed good imaging of Fe3O4-Lidocain-PLGA microspheres, a drug-carrying model that slowed down the diffusion of the microspheres in the presence of an applied magnetic field. Animal experiments demonstrated that this preparation had a significantly prolonged nerve block, analgesic effect, and a nerve anchoring function. CONCLUSION: Magnetically responsive lidocaine microspheres can prolong analgesia by slowly releasing lidocaine, which can be immobilized around the nerve by a magnetic field on the body surface, avoiding premature diffusion of the microspheres to surrounding tissues and improving drug targeting.

An overview of local anesthetics in over-the-counter products.

Over-the-counter (OTC) local anesthetics have historically been used to alleviate pain in several common conditions including toothache and sore throat. With a rise in chronic conditions and an aging population, there has been an increase in associated chronic pain-related disorders. Individuals with chronic pain often seek OTC treatments for quick and accessible pain relief. There are several common OTC local anesthetics, including benzocaine, lidocaine, and dibucaine, which are readily available to patients in several formulations. In order to appropriately advise patients on the use of local anesthetics, it is important to understand their key characteristics, including the mechanism of action, clinical properties, pharmacokinetics, clinical applications, and adverse reactions, which may occur.

A comparison of steroid dose with or without local anesthetic in lumbar interlaminar epidural steroid injections.

INTRODUCTION: Epidural steroid injections (ESIs) are commonly used as a treatment for lumbar radiculopathy. Currently, most research on comparative efficacy of various steroids in epidural steroid injections is focused on transforaminal ESIs (TFESIs). Through this study, we aimed to compare various steroid doses with or without local anesthetic in interlaminar ESIs (ILESIs). METHODS: We reviewed charts for all adult patients who received ILESIs identified by CPT code 62323 between January 2017 to April 2021. Baseline demographic data including age, sex, BMI, and smoking status were recorded. NRS pain scores before the injection and percentage of pain relief at 1-month follow-up were recorded. We compared percentage of patients reporting pain relief at 1 month follow-up of low-dose dexamethasone alone (5 mg), to low-dose dexamethasone mixed with local anesthetic, and to high-dose dexamethasone (10 mg) mixed with local anesthetic, specifically for ILESIs. RESULTS: Data were available for 311 patients. There was no significant difference in pain relief between the 3 groups at 1 month follow-up. The majority of patients had moderate to significant improvement in pain, supporting the use of ILESIs. Moreover, low-dose steroid with local anesthetic was found to be as efficacious as high-dose steroid alone. Although not statistically significant, the addition of local anesthetic to low-dose or high-dose steroid increased the percentage of patients reporting moderate to significant pain relief. CONCLUSION: ILESIs with non-particulate steroids provide moderate to significant pain improvement in the short term, with low-dose steroid mixed with local anesthetic being as efficacious as a high-dose steroid.

Structure and Pharmacology of Voltage-Gated Sodium and Calcium Channels.

Voltage-gated sodium and calcium channels are evolutionarily related transmembrane signaling proteins that initiate action potentials, neurotransmission, excitation-contraction coupling, and other physiological processes. Genetic or acquired dysfunction of these proteins causes numerous diseases, termed channelopathies, and sodium and calcium channels are the molecular targets for several major classes of drugs. Recent advances in the structural biology of these proteins using X-ray crystallography and cryo-electron microscopy have given new insights into the molecular basis for their function and pharmacology. Here we review this recent literature and integrate findings on sodium and calcium channels to reveal the structural basis for their voltage-dependent activation, fast and slow inactivation, ion conductance and selectivity, and complex pharmacology at the atomic level. We conclude with the theme that new understanding of the diseases and therapeutics of these channels will be derived from application of the emerging structural principles from these recent structural analyses.

Hydration-induced Void-containing Hydrogels for Encapsulation and Sustained Release of Small Hydrophilic Molecules.

Efficient encapsulation and sustained release of small hydrophilic molecules from traditional hydrogel systems have been challenging due to the large mesh size of 3D networks and high water content. Furthermore, the encapsulated molecules are prone to early release from the hydrogel prior to use, resulting in a short shelf life of the formulation. Here, we present a hydration-induced void-containing hydrogel (HVH) based on hyperbranched polyglycerol-poly(propylene oxide)-hyperbranched polyglycerol (HPG-PPG-HPG) as a robust and efficient delivery system for small hydrophilic molecules. Specifically, after the HPG-PPG-HPG is incubated overnight at 4 °C in the drug solution, it is hydrated into a hydrogel containing micron-sized voids, which could encapsulate hydrophilic drugs and achieve 100% drug encapsulation efficiency. In addition, the voids are surrounded by a densely packed polymer matrix, which restricts drug transport to achieve sustained drug release. The hydrogel/drug formulation can be stored for several months without changing the drug encapsulation and release properties. HVH hydrogels are injectable due to shear thinning properties. In rats, a single injection of the HPG-PPG-HPG hydrogel containing 8 µg of tetrodotoxin (TTX) produced sciatic nerve block lasting up to 10 hours without any TTX-related systemic toxicity nor local toxicity to nerves and muscles.

Effects of Local Anesthetics on Liposomal Membranes Determined by Their Inhibitory Activity of Lipid Peroxidation.

In this study, we investigated the effects of drugs on membrane function in which lipid peroxidation was inhibited by the antioxidant Trolox (TRO) in liposomes containing egg yolk lecithin. Local anesthetics (LAs), such as lidocaine (LID) and dibucaine (DIB), were used as model drugs. The effect of LAs on the inhibitory activity of TRO was evaluated by calculating the pI50 from the inhibition constant K calculated by curve fitting. pI50TRO indicates the strength of TRO membrane protective function. pI50LA indicates the strength of LA activity. LAs inhibited lipid peroxidation in a dose-dependent manner and decreased pI50TRO. The effect of DIB on pI50TRO was 1.9 times more than that of LID. This result indicated that LA may improve the fluidity of the membrane, which may facilitate the migration of TRO from the membrane to the liquid phase. As a result, TRO is less likely to suppress lipid peroxidation within the lipid membrane, possibly resulting in a decrease in pI50TRO. The effect of TRO on pI50LA was found to be similar in both, indicating that it did not depend on the type of the model drug. These results suggest that our developed procedure successfully quantified the effects of LAs on lipid membrane functions. We were able to obtain the characteristics of model drugs independent of TRO by simultaneously measuring and analyzing the lipid peroxidation inhibitory activities of TRO and model drugs in liposomes.

Ropivacaine inhibits proliferation and invasion and promotes apoptosis and autophagy in bladder cancer cells via inhibiting PI3K/AKT pathway.

Application of a certain concentration of local anesthetics during tumor resection inhibits the progression of tumor. The effects of ropivacaine in bladder cancer (BC) have never been explored. We explored the effects of ropivacaine on the progression of BC in vitro and in vivo. CCK8 assay and EDU staining was conducted to examine cell proliferation. Flow cytometry and transwell assay were performed to evaluate apoptosis and invasion, respectively. Expression of light chain 3 (LC3) was observed through immunofluorescence. Furthermore, the xenograft tumor model of BC was built to detect the effects of ropivacaine in vivo. IHC and TUNEL assay were conducted to detect cell proliferation and apoptosis in vivo. Ropivacaine inhibited the proliferation of T24 and 5639 cells with the 50% inhibitory concentration (IC50) of 20.08 and 31.86 µM, respectively. Ropivacaine suppressed the invasion ability and induces the apoptosis of cells. Besides, ropivacaine triggers obvious autophagy in BC cells. Moreover, ropivacaine blocks the PI3K/AKT signal pathway in BC cells. The impact of ropivacaine on cell viability, motility, and autophagy was reversed by 740 Y-P, the activator of PI3K/AKT signal pathway. The in vivo experiments demonstrated that ropivacaine inhibited the proliferation and mobility of BC. Ropivacaine has anti-carcinoma effects in BC via inactivating PI3K/AKT pathway, providing a new theoretical reference for the use of local anesthetics in the treatment of BC.

The effect of warming ropivacaine on ultrasound-guided subgluteal sciatic nerve block: a randomized controlled trial.

BACKGROUND: There is a long latent period for the sciatic nerve block before a satisfactory block is attained. Changes in the temperature of local anesthetics may influence the characters of the peripheral nerve block. This study was designed to evaluate the effect of warming ropivacaine on the ultrasound-guided subgluteal sciatic nerve block. METHODS: Fifty-four patients for distal lower limbs surgery were randomly allocated into warming group (group W, n = 27) or room tempeture group (group R, n = 27) with the ultrasound-guided subgluteal sciatic nerve block. The group W received 30 ml of ropivacaine 0.5% at 30℃ and the group R received 30 ml of ropivacaine 0.5% at 23℃. The sensory and motor blockade were assessed every 2 min for 30 min after injection. The primary outcome was the onset time of limb sensory blockade. RESULTS: The onset time of sensory blockade was shorter in group W than in group R (16 (16,18) min vs 22 (20,23) min, p < 0.001), and the onset time of motor blockade was also shorter in group W than in group R (22 (20,24) min vs 26 (24,28) min, p < 0.001). The onset time of sensory blockade for each nerve was shorter in group W than in group R (p < 0.001). No obvious differences for the duration of sensory and motor blockade and the patient satisfaction were discovered between both groups. No complications associated with nerve block were observed 2 days after surgery. CONCLUSIONS: Warming ropivacaine 0.5% to 30℃ accelerates the onset time of sensory and motor blockade in the ultrasound-guided subgluteal sciatic nerve block and it has no influence on the duration of sensory and motor blockade. TRIAL REGISTRATION: The trial was registered on October 3, 2022 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/bin/project/edit?pid=181104 ), registration number ChiCTR2200064350 (03/10/2022).

Local anesthetics systemic toxicity in children: analysis of the French pharmacovigilance database.

PURPOSE: To characterize clinical profile of pediatric local anesthetic (LA) systemic toxicity (LAST) and to identify determinants of life-threatening outcomes. METHODS: Spontaneous reports notified to the French Pharmacovigilance Network were retrieved and followed by a case-by-case review, according to the following criteria: LA as suspected drug, age < 18 years, adverse drug reactions related to nervous system, cardiac, respiratory, psychiatric or general disorders. Multivariate logistic regression analysis was performed to identify factors leading to life-threatening reaction (i.e. continuous seizures or cardiorespiratory arrest). RESULTS: Among 512 cases retrieved, 64 LAST cases were included (neonates 11%, infants 30%, children 36%, adolescents 23%) mainly involving lidocaine (47%), lidocaine + prilocaine (22%) and ropivacaine (14%). Toxicity profiles were neurological (58%), cardiac (11%) or mixed (20%) and 7 patients (11%) developed methemoglobinemia. LAST was life-threatening for 23 patients (36%) and 2 patients died. Doses were above recommendations in 26 patients (41%) and were not different between life-threatening and non-life-threatening cases. The context of use (general and orthopedic surgery, p = 0.006) and the type of LA agent (lidocaine, p = 0.016) were independently associated with a life-threatening outcome. CONCLUSION: In this national retrospective analysis, LAST in children appear to be a rare event. Neurological and cardiac signs were the most frequently reported reactions. LAST in children can be life-threatening, even at therapeutic doses. Although a fatal outcome may anecdotally occur, the vast majority of patients recovered after appropriate medical care.

Alpha-1-acid glycoprotein and its potential impact on local anesthetic dose in neonates.

BACKGROUND: Alpha-1-acid glycoprotein is an acute-phase protein with a high affinity for amide local anesthetics. Compared to adults, neonates have lower concentrations of this glycoprotein in plasma, and are therefore at higher risk of developing local anesthetic toxicity. Alpha-1-acid glycoprotein concentrations rise in adults after surgery as a response to stress as well as in inflammatory conditions. Previous studies have shown that concentrations of alpha-1-acid-glycoprotein in neonates vary postpartum, influenced by gestational age and mode of delivery. AIM: This study aims to determine the concentrations of alpha-1-acid glycoprotein pre- and postoperatively in neonates undergoing major surgery. This information is important for determining safe and effective dosage of local anesthetic in this vulnerable group of patients. METHODS: In this prospective observational study, 25 neonates (median 3 days of age) undergoing major surgery were included. Blood sampling was performed preoperatively and at four occasions postoperatively. Alpha-1-acid-glycoprotein plasma concentrations were analyzed using an immunoturbidimetric assay. Mann-Whitney U test, Kruskal-Wallis and Spearman ranking correlation test were used for the statistical analysis. RESULTS: Higher plasma concentrations of alpha-1-acid-glycoprotein were found 48 h postoperatively compared to preoperatively [median (inter-quartile range) 0.815 g L-1 (0.663-0.983 g L-1 ) vs. 0.300 g L-1 (0.205-0.480 g L-1 p < 0.001)], respectively. It was not possible to detect any influence of sex, postnatal age, gestational age, or delivery mode on alpha-1-acid-glycoprotein concentrations in our data. CONCLUSIONS: Alpha-1-acid-glycoprotein concentrations increase in neonates as a response to surgery regardless of gestational age, sex, or mode of delivery.