Exploring the effects of eugenol, menthol, and lidocaine as anesthetics on zebrafish glucose homeostasis.

Zebrafish (Danio rerio) are widely employed as an experimental model in various scientific fields. The investigation of glucose metabolism dysfunctions has gained recent significant prominence. Considering that certain anesthetics may impact glycemic levels, it is imperative to carefully select an anesthetic that does not induce such side effects, thereby mitigating potential adverse influences on research outcomes. In this sense, this study aimed to evaluate potential glucose alterations and induction and recovery times resulting from the use of eugenol, menthol and lidocaine as anesthetics in zebrafish. A total of 150 adult male and female zebrafish were divided into ten groups, comprising a control group euthanized by rapid chilling, and three groups anesthetized with low (40 mg/L eugenol, 60 mg/L menthol, 100 mg/L lidocaine), intermediate (60 mg/L eugenol, 90 mg/L menthol, 225 mg/L lidocaine), and high (80 mg/L eugenol, 120 mg/L menthol, 350 mg/L lidocaine) anesthetic concentrations. Glucose levels and induction and recovery times were assessed. The findings reveal that eugenol and menthol did not cause glucose level alterations at any of the investigated concentrations, while lidocaine caused a non-concentration-dependent hyperglycemia. Eugenol and menthol also exhibited similar recovery times at different concentrations, while lidocaine recovery times were concentration-dependent. This study, therefore, concludes that eugenol and menthol are safe and satisfactory anesthetics for use in zebrafish research involving glucose analyses, while lidocaine use can cause biases due to altered glucose levels and safety concerns. Researchers should, therefore, carefully consider anesthetic selection to ensure reliable results in zebrafish assessments.

The potencies and neurotoxicity of intrathecal levobupivacaine in a rat spinal model: Effects of concentration.

This study was aimed at examining the anesthetic effects and spinal cord injuries in the rats by intrathecal injection of levobupivacaine at different concentrations. Rats with successful intrathecal cannulation were selected and randomly divided into six groups (n = 72), and administered 0.1 mL of 0.125%, 0.25%, 0.5%, or 0.75% levobupivacaine, saline or 5% lidocaine via intrathecal catheters. The potency of levobupivacaine was evaluated by walking behavior. To identify the motor and sensory function, walking behavior and paw withdrawal thresholds (PWTs) were measured once a day. After 7 days, the L4-5 spinal cord segments were removed for histological examination. The onset time of 0.125% levobupivacaine intrathecal injection was 70.0 ± 8.9 s, and the maintenance time was 9.5 ± 1.8 min. The onset time of 0.75% levobupivacaine intrathecal injection was significantly shortened to 31.0 ± 5.5 s, and the maintenance time was significantly extended to 31.3 ± 5.4 min. The severe injury was observed in the 5% lidocaine group, while milder injury was observed in the 0.75% levobupivacaine group. The damage in the 0.5% levobupivacaine group was mild, and there were no histological abnormalities in the 0.125%, 0.25% levobupivacaine and saline groups. The neurotoxicity of intrathecally administered levobupivacaine was concentration dependent. In addition, higher concentrations of levobupivacaine were associated with shorter onset and longer maintenance times. The clinical concentration of levobupivacaine should not exceed 0.5% to avoid potential damage.

Etomidate-Induced Myoclonus in Sprague-Dawley Rats Involves Neocortical Glutamate Accumulation and N -Methyl- d -Aspartate Receptor Activity.

BACKGROUND: Etomidate-induced myoclonus, a seizure-like movement, is of interest to anesthetists. However, its origin in the brain and its underlying mechanism remain unclear. METHODS: Adult male Sprague-Dawley rats were anesthetized with etomidate, propofol, or lidocaine plus etomidate. We assessed the incidence of myoclonus, behavioral scores, and levels of glutamate and γ-aminobutyric acid (GABA) in the neocortex and hippocampus. To determine the origin and how N -methyl- d -aspartate receptors (NMDARs) modulate etomidate-induced neuroexcitability, the local field potential and muscular tension were monitored. Calcium imaging in vitro and immunoblotting in vivo were conducted to investigate the mechanisms underlying myoclonus. RESULTS: The incidence of etomidate (1.5 mg/kg in vivo)-induced myoclonus was higher than that of propofol (90% vs 10%, P = .0010) and lidocaine plus etomidate (90% vs 20%, P = .0050). Etomidate at doses of 3.75 and 6 mg/kg decreased the mean behavioral score at 1 (mean difference [MD]: 1.80, 95% confidence interval [CI], 0.58-3.02; P = .0058 for both), 2 (MD: 1.60, 95% CI, 0.43-2.77; P = .0084 and MD: 1.70, 95% CI, 0.54-2.86; P = .0060), 3 (MD: 1.60, 95% CI, 0.35-2.85; P = .0127 and MD: 1.70, 95% CI, 0.46-2.94; P = .0091) minutes after administration compared to etomidate at a dose of 1.5 mg/kg. In addition, 0.5 and 1 µM etomidate in vitro increased neocortical intracellular calcium signaling; this signaling decreased when the concentration increased to 5 and 10 µM. Etomidate increased the glutamate level compared to propofol (mean rank difference: 18.20; P = .003), and lidocaine plus etomidate (mean rank difference: 21.70; P = .0002). Etomidate in vivo activated neocortical ripple waves and was positively correlated with muscular tension amplitude (Spearman's r = 0.785, P < .0001). Etomidate at 1.5 mg/kg decreased the K-Cl cotransporter isoform 2 (KCC2) level compared with propofol (MD: -1.15, 95% CI, -1.47 to -0.83; P < .0001) and lidocaine plus etomidate (MD: -0.64, 95% CI, -0.96 to -0.32; P = .0002), DL-2-amino-5-phosphopentanoic acid (AP5) suppressed these effects, while NMDA enhanced them. CONCLUSIONS: Etomidate-induced myoclonus or neuroexcitability is concentration dependent. Etomidate-induced myoclonus originates in the neocortex. The underlying mechanism involves neocortical glutamate accumulation and NMDAR modulation and myoclonus correlates with NMDAR-induced downregulation of KCC2 protein expression.

Mixture effects of tetrodotoxin (TTX) and drugs targeting voltage-gated sodium channels on spontaneous neuronal activity in vitro.

Tetrodotoxin (TTX) potently inhibits TTX-sensitive voltage-gated sodium (NaV) channels in nerve and muscle cells, potentially resulting in depressed neurotransmission, paralysis and death from respiratory failure. Since a wide range of pharmaceutical drugs is known to also act on NaV channels, the use of medicines could predispose individuals to a higher susceptibility towards TTX toxicity. We therefore first assessed the inhibitory effect of selected medicines that act on TTX-sensitive (Riluzole, Chloroquine, Fluoxetine, Valproic acid, Lamotrigine, Lidocaine) and TTX-resistant (Carbamazepine, Mexiletine, Flecainide) NaV channels on spontaneous neuronal activity of rat primary cortical cultures grown on microelectrode arrays (MEA). After establishing concentration-effect curves, binary mixtures of the medicines with TTX at calculated NOEC, IC20 and IC50 values were used to determine if pharmacodynamic interactions occur between TTX and these drugs on spontaneous neuronal activity. At IC20 and IC50 values, all medicines significantly increased the inhibitory effect of TTX on spontaneous neuronal activity of rat cortical cells in vitro. Subsequent experiments using human iPSC-derived neuronal co-cultures grown on MEAs confirmed the ability of selected medicines (Carbamazepine, Flecainide, Riluzole, Lidocaine) to inhibit spontaneous neuronal activity. Despite the need for additional experiments using human iPSC-derived neuronal co-cultures, our combined data already highlight the importance of identifying and including vulnerable risk groups in the risk assessment of TTX.

Effects of Intracameral Drugs and Dyes on Corneal Endothelial Cell Apoptosis in a Rat Model: An In Vivo and In Vitro Analysis.

Objectives: To evaluate the effects of intracameral drugs and dyes on rat corneal endothelial apoptosis and cell morphology. Materials and Methods: The right eyes of 72 rats were injected intracamerally with 1% lidocaine, 0.01% adrenaline, triamcinolone acetonide (TA) 4 mg/mL, 1% trypan blue (TB), 0.5% indocyanine green (ICG), and fortified balanced salt solution as control. Corneal samples were taken 1 day and 1 week post-injection. Corneal endothelial apoptosis was assessed by the TUNEL technique, and the ratio of apoptotic cells in each group was compared with the control. Corneal endothelial cell morphology was evaluated in each specimen by transmission electron microscopy. Results: The mean apoptotic endothelial cell ratio was significantly higher at 1 day and 1 week after intracameral adrenaline injection when compared to controls (p=0.03 and 0.021, respectively). TB caused a significantly higher apoptotic cell ratio when compared to controls at 1 week after injection (p=0.043). Lidocaine caused a higher apoptotic cell ratio compared to TA and ICG at 1 week, although not statistically significant (p=0.058, 0.09, 0.69, respectively). In all experimental specimens, transmission electron microscopy showed morphological changes associated with apoptosis. Conclusion: This study showed that intracameral adrenaline, TB, and lidocaine injections may have toxic effects on corneal tissue, as indicated by ultrastructural and histopathological alterations. Therefore, these agents should be used with caution in intraocular surgery.

Analysis of the long non-coding RNA and mRNA expression profiles associated with lidocaine-induced neurotoxicity in the spinal cord of a rat model.

Neurotoxicity is thought to be one of the causes of lidocaine-associated neurological complications; however, the mechanisms underlying lidocaine-related neurotoxicity are still unclear. Long non-coding RNAs (lncRNAs) are novel mediators of neurotoxicity, and their role in lidocaine-induced neurotoxicity needs to be explored. Here, we established a rat model of lidocaine-induced neurotoxicity via the repetitive intrathecal administration of 10% lidocaine. Thereafter, microarray and bioinformatics analyses were performed to evaluate the changes in lncRNA and mRNA expression profiles in the lumbar spinal cord of the treated rats. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was also employed for verification. The lidocaine-treated rats (group L) showed elevated paw withdrawal threshold (PWT) as well as histopathological injuries in the lumbar spinal cord compared with the control saline-treated rats (group N). Further, relative to group N, microarray analysis showed 179 and 675 differentially expressed lncRNAs (DElncRNAs) and DEmRNAs in the lumbar spinal cord of rats in the group L, respectively. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the DEmRNAs showed that the most significantly enriched functions and pathways were those associated with cell cycle and immuno-inflammatory processes. Furthermore, coding-noncoding co-expression analysis showed multiple lncRNAs that were co-expressed with factors that regulate inflammation. Additionally, by constructing a preliminary competitive endogenous RNA (ceRNA) network analysis, we established a regulatory network of the lncRNAs and mRNAs that are potentially involved in lidocaine-induced neurotoxicity. In conclusion, our findings provide new insights into the molecular mechanisms of lidocaine-induced neurotoxicity; this has significance with respect to the identification of novel therapeutic targets.

Chondrotoxic effects of intra-articular injection of local anaesthetics in the rabbit temporomandibular joint.

The aim of this study was to investigate the chondrotoxic effects of a single-dose intra-articular injection of articaine, lidocaine, and bupivacaine on the rabbit temporomandibular joint (TMJ). Twenty-four rabbits were divided into four groups: control (group 1), articaine (group 2), lidocaine (group 3), and bupivacaine (group 4). Synovial fluid samples and venous blood were taken to evaluate matrix metalloproteinase 3 (MMP-3) levels. One millilitre of local anaesthetic solution was injected in the study groups and saline solution in the control group. The rabbits were euthanized after 4 weeks and the mandibular condyles and articular discs were evaluated. On histological examination, the study group samples had irregular joint surfaces, decreased collagen, and a thinner cartilage layer. Apoptotic cells were evaluated with the TUNEL method. TUNEL-positive apoptotic cell counts were higher in all study groups compared to the control group, and the difference was significant (P < 0.001). The mean preoperative serum MMP-3 level for all groups was 5.71 ± 3.33 ng/mL, while the mean postoperative level was 22.61 ± 6.36 ng/mL; this difference was significant (P < 0.001). A single-dose intra-articular injection of local anaesthetic had apoptotic effects on chondrocytes, leading to degenerative changes in the TMJ articular structures. Articaine was found to have less harmful effects than lidocaine and bupivacaine. Intra-articular injection of local anaesthetics should be limited in the TMJ because of the potential toxic effects.

Long Noncoding RNA LINC01347 Modulated Lidocaine-Induced Cytotoxicity in SH-SY5Y Cells by Interacting with hsa-miR-145-5p.

Local anesthetics, including lidocaine (Lid), are widely used in clinical settings but new evidence suggested that they may induce strong neurological side-effects in human brains. In this work, we used an in vitro model to examine the functional modulations of a long non-coding RNA (lncRNA), LINC01347 on Lid-induced cytotoxicity in SH-SY5Y cells. SH-SY5Y cells were maintained in vitro and treated with Lid to induce cytotoxicity. Dynamic expression of LINC01347, in response to Lid treatment or lentivirus-mediated overexpression, was examined by quantitative real-time PCR. The effects of LINC01347 overexpression on Lid-induced cell death, LDH, caspase, and autophagy activities were evaluated. A potential downstream target of LINC01347, human microRNA-145-5p (hsa-miR-145-5p), was evaluated in SH-SY5Y cells. Hsa-miR-145-5p was subsequently upregulated to explore its functional correlation with LINC01347 in modulating Lid-induced SH-SY5Y cytotoxicity. Lid caused cell death and downregulated LINC01347 expression in SH-SY5Y cells in vitro. LINC01347 overexpression reduced Lid-induced cell death, LDH and caspase augmentation, and LC3B accumulation. Hsa-miR-145-5p was discovered to be closely affiliated with LINC01347. Its upregulation partially restored Lid-induced cytotoxic effects in LINC01347-overexpressed SH-SY5Y cells. Our study presented strong evidence showing lncRNA LINC01347 modulated lidocaine-induced cytotoxicity in SH-SY5Y cells by interacting with hsa-miR-145-5p.

Pediatric Toxidrome Simulation Curriculum: Lidocaine-Induced Methemoglobinemia.

Introduction: Lidocaine is a common local anesthetic used during minor procedures performed on pediatric patients. A rare but toxic and life-threatening side effect of lidocaine is methemoglobinemia. It should be considered in children who are hypoxic after exposure to an oxidizing agent. Methods: We developed this simulation case for pediatric emergency medicine (PEM) fellows, but it can be adapted for interprofessional simulation. The case involved a 1-month-old male with hypoxia and resulting central cyanosis after exposure to lidocaine. The team performed an initial evaluation and intervention, collected a history, and developed a differential diagnosis for hypoxia and central cyanosis in an infant. Methemoglobinemia was confirmed by CO-oximetry. Preparatory materials, a debriefing guide, and scenario evaluation forms assisted with facilitation. Results: Fifty-six participants (including 18 PEM fellows) completed this simulation across four institutions. Participants rated the scenario on a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree), finding it to be relevant to their work (median = 5) and realistic (median = 5). After participation in the simulation, learners felt confident in their ability to recognize methemoglobinemia (median = 4) and implement a plan to stabilize an infant with hypoxia (median = 4). Discussion: This simulation represents a resource for learners in the pediatric emergency department. It teaches the recognition and management of an infant with lidocaine toxicity and resultant methemoglobinemia. It uses experiential learning to teach and reinforce a systematic approach to the evaluation and management of a critically ill infant with acquired methemoglobinemia.

Differences in Cytotoxicity of Lidocaine, Ropivacaine, and Bupivacaine on the Viability and Metabolic Activity of Human Adipose-Derived Mesenchymal Stem Cells.

PURPOSE: We evaluated biological effects of distinct local anesthetics on human adipose-derived mesenchymal stem cells when applied to reduce periprocedural pain during mesenchymal stem cell injections. METHODS AND MATERIALS: Metabolic activity (MTS assay), viability (Live/Dead stain), and gene expression (quantitative real-time reverse-transcriptase polymerase chain reaction) were measured in mesenchymal stem cells incubated with various concentrations of lidocaine, ropivacaine, or bupivacaine during a 12-hr time course. RESULTS: Cell viability and metabolic activity decreased in a dose, time, and substance-specific manner after exposure to lidocaine, ropivacaine, and bupivacaine, with ropivacaine being the least cytotoxic. Cell viability decreases after brief exposure (<1.5 hrs) at clinically relevant concentrations (eg, 8 mg/ml of lidocaine, 2.5 mg/ml of ropivacaine or bupivacaine). Mesenchymal stem cells exposed to local anesthetics change their expression of mRNA biomarkers for stress response (EGR1, EGR2), proliferation (MKI67, HIST2H4A), ECM (COL1A1, COL3A1), and cell surface marker (CD105). CONCLUSIONS: Local anesthetics are cytotoxic to clinical-grade human mesenchymal stem cells in a dose-, time-, and agent-dependent manner and change expression of ECM, proliferation, and cell surface markers. Lidocaine and bupivacaine are more cytotoxic than ropivacaine. Single-dose injections of local anesthetics may affect the biological properties of mesenchymal stem cells in vitro but may not affect the effective dose of MSCs in a clinical setting.

A weight of evidence assessment of the genotoxicity of 2,6-xylidine based on existing and new data, with relevance to safety of lidocaine exposure.

Lidocaine has not been associated with cancer in humans despite 8 decades of therapeutic use. Its metabolite, 2,6-xylidine, is a rat carcinogen, believed to induce genotoxicity via N-hydroxylation and DNA adduct formation, a non-threshold mechanism of action. To better understand this dichotomy, we review literature pertaining to metabolic activation and genotoxicity of 2,6-xylidine, identifying that it appears resistant to N-hydroxylation and instead metabolises almost exclusively to DMAP (an aminophenol). At high exposures (sufficient to saturate phase 2 metabolism), this may undergo metabolic threshold-dependent activation to a quinone-imine with potential to redox cycle producing ROS, inducing cytotoxicity and genotoxicity. A new rat study found no evidence of genotoxicity in vivo based on micronuclei in bone marrow, comets in nasal tissue or female liver, despite high level exposure to 2,6-xylidine (including metabolites). In male liver, weak dose-related comet increases, within the historical control range, were associated with metabolic overload and acute systemic toxicity. Benchmark dose analysis confirmed a non-linear dose response. The weight of evidence indicates 2,6-xylidine is a non-direct acting (metabolic threshold-dependent) genotoxin, and is not genotoxic in vivo in rats in the absence of acute systemic toxic effects, which occur at levels 35 × beyond lidocaine-related exposure in humans.

The 14-day repeated-dose toxicity study of a fixed-dose combination, QXOH/levobupivacaine, via subcutaneous injection in beagle dogs.

QXOH-Levobupivacaine (LB) is a fixed-dose combination of 35-mM QXOH and 10-mM LB. It was developed for perioperative analgesia because of its long-acting analgesic effect. The purpose of this study was to evaluate the potential toxicity of QXOH-LB in beagle dogs in accordance with the Guidance on the repeated-dose toxicity published by the China Food and Drug Administration. Groups of five male and five female beagle dogs received normal saline, QXOH-LB (2, 4, and 8 mg/kg, calculated as QXOH), QXOH (2, 4, and 8 mg/kg), or LB (2 mg/kg, equals the concentration of LB in 8-mg/kg QXOH-LB group) at the volume of 1 mL/kg once per day for 14 days through subcutaneous injection. No mortality was observed. Dogs in the control group as well as animals treated with 2-mg/kg QXOH or QXOH-LB exhibited normal behaviors. Clinical signs of toxicity in dogs treated with 4 and 8 mg/kg of QXOH or QXOH-LB included decreased activity, unsteady gait, jerks, tremors, vocalization, emesis, ataxia, lateral/sternal recumbency, deep/rapid respiration, and gasping. Additionally, neurological function was found to be affected by QXOH and QXOH-LB at the doses of 4 and 8 mg/kg. All clinical signs were recovered within 24 h. The no-observed-adverse-effect level of QXOH and QXOH-LB was considered to be 2 mg/kg. Toxicokinetic data showed that exposure to QXOH and LB increased as QXOH-LB doses were increased from 4 to 8 mg/kg. There was no evidence of drug accumulation or any effect of gender.

Amitriptyline Protects Against Lidocaine-induced Neurotoxicity in SH-SY5Y Cells via Inhibition of BDNF-mediated Autophagy.

Amitriptyline (AMI) is a traditional tricyclic antidepressant that has been proven to exhibit neuroprotective effects in various neurological disorders. However, the underlying mechanism by which AMI attenuates lidocaine-induced neurotoxicity remains poorly understood. Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin to neuronal development and survival in the brain, and recent studies have suggested that BDNF plays an important role in mediating lidocaine-induced neurotoxicity. The present study was performed to evaluate the protective effect of AMI against the neurotoxicity induced by lidocaine and to explore the role of BDNF-dependent autophagy in this process. The data showed that AMI pretreatment alleviated lidocaine-induced neurotoxicity, as evidenced by the restoration of cell viability, normalization of cell morphology, and reduction in the cell apoptosis index. In addition, autophagy inhibitor 3-methyladenine (3-MA) had a protective effect similar to that of AMI, but autophagy activator rapamycin eliminated the protective effect of AMI by suppressing mTOR activation. Moreover, at the molecular level, we found that AMI-mediated autophagy was involved in the expression of BDNF. The overexpression of BDNF or application of exogenous recombinant BDNF significantly suppressed autophagy and protected SH-SY5Y cells from apoptosis induced by Lido, whereas the neuroprotection of AMI was abolished by either knockdown of BDNF or use of a tropomyosin-related kinase B (TrkB) inhibitor ANA-12 in SH-SY5Y cells. Overall, our findings demonstrated that the protective effect of AMI against lidocaine-induced neurotoxicity correlated with inhibition of autophagy activity through upregulation of BDNF expression.

Pilsicainide Intoxication with Neuropsychiatric Symptoms Treated with Continuous Hemodiafiltration.

A 72-year-old lady with atrial fibrillation and chronic renal failure was hospitalized due to bradycardic shock with electrocardiographic QRS prolongation. She had experienced limb shaking two days before hospitalization, and additionally developed hallucinations one day before admission. Pilsicainide intoxication was diagnosed from a review of her medications and electrocardiographic findings. Consequently, continuous hemodiafiltration was performed resulting in a resolution of the hallucinations and the QRS prolongation. This is a rare case of psychiatric symptoms caused by pilsicainide intoxication. It is important to know the mode of excretion of a drug and to adjust its dose, so that such drug-related incidents can be avoided.

Dexmedetomidine protects against lidocaine-induced neurotoxicity through SIRT1 downregulation-mediated activation of FOXO3a.

Lidocaine, a typical local anesthetic, has been shown to directly induce neurotoxicity in clinical settings. Dexmedetomidine (DEX) is an alpha-2-adrenoreceptor agonist that has been used as anxiolytic, sedative, and analgesic agent which has recently found to protect against lidocaine-induced neurotoxicity. Nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-1 (SIRT1)/forkhead box O3 (FOXO3a) signaling is critical for maintaining neuronal function and regulation of the apoptotic pathway. In the present study, we designed in vitro and in vivo models to investigate the potential effects of lidocaine and DEX on SIRT1 and FOXO3a and to verify whether SIRT1/FOXO3a-mediated regulation of apoptosis is involved in DEX-induced neuroprotective effects against lidocaine. We found that in both PC12 cells and brains of mice, lidocaine decreased SIRT1 level through promoting the degradation of SIRT1 protein. Lidocaine also increased FOXO3a protein level and increased the acetylation of SIRT1 through inhibiting SIRT1. Upregulation of SIRT1 or downregulation of FOXO3a significantly inhibited lidocaine-induced changes in both cell viability and apoptosis. DEX significantly inhibited the lidocaine-induced decrease of SIRT1 protein level and increase of FOXO3a protein level and acetylation of FOXO3a. Downregulation of SIRT1 or upregulation of FOXO3a suppressed DEX-induced neuroprotective effects against lidocaine. The data suggest that SIRT1/FOXO3a is a potential novel target for alleviating lidocaine-induced neurotoxicity and provide more theoretical support for the use of DEX as an effective adjunct to alleviate chronic neurotoxicity induced by lidocaine.

Comparisons of Monopolar Lesion Volumes with Hypertonic Saline Solution in Radiofrequency Ablation: A Randomized, Double-Blind, Ex Vivo Study.

BACKGROUND: Chronic degeneration of the zygapophyseal joints in the cervical or lumbar spine are common causes of axial back pain. Radiofrequency (RF) ablation is a treatment modality in the denervation of facet joint-related pain. Although multiple factors have been theorized to contribute to the size of the optimal RF lesion, the addition of hypertonic saline solution has been posited to create larger RF lesion sizes. OBJECTIVES: This study compares lesion of 20-gauge RF monopolar probe using 2% lidocaine, 0.9% normal saline solution, and 3% saline solution administered through the RF needle prior to ablation, with subsequent lesion sizes recorded. STUDY DESIGN: Randomized, double-blinded, ex vivo study using clinically relevant conditions. SETTING: Procedural laboratory in an academic institution. METHODS: RF ablation lesions were reproduced in room temperature (21°C ± 2°C) chicken breast specimens with 20-gauge monopolar RF probes inserted. RF was applied for 90 seconds at 80°C after injection of 1 mL of either 2% lidocaine, 2% lidocaine and 0.9% normal saline solution in a 1:1 ratio, or 2% lidocaine and 3% saline solution in a 1:1 ratio. Tissues were dissected, measured, and ellipsoid volumes of burn calculated. Homogeneity of variances was assessed via the Bartlett's test, and heteroskedasticity with the studentized Breusch-Pagan test. One-way analysis of variance (ANOVA) (alpha of 0.05) was used to evaluate statistical significance between volume means across groups. When the null hypothesis of no difference in burn volume between samples could not be rejected, a predefined equivalence volume of ± 0.05 cm3 was used with Welch's 2 one-sided t-tests (TOST) with a Bonferroni adjusted alpha of 0.0167 to evaluate for null acceptance. RESULTS: The mean lesion volume for monopolar RF with 1 mL 2% lidocaine was 0.16 cm3. Monopolar RF with 1 mL 2% lidocaine + 0.9% normal saline solution had a mean lesion volume of 0.15 cm3, and treatment with 1 mL 2% lidocaine + 3% saline solution measured 0.17 cm3. ANOVA failed to reject the null, and TOST accepted as equivalent all 3 comparisons. LIMITATIONS: In vivo anatomy and physiology of a human organism was not used for this study. Samples were not warmed to physiologic temperature. Randomization resulted in slightly unequal sample sizes, although all groups were of sufficient size that the central limit theorem should apply. CONCLUSIONS: Three commonly used solutions were found to have equivalent lesion sizes from monopolar probe RF ablation. KEY WORDS: Radiofrequency, ablation, lesion shape, lesion size, monopolar RF, hypertonic saline solution.

A novel dual action monolithic thermosetting hydrogel loaded with lidocaine and metronidazole as a potential treatment for alveolar osteitis.

Alveolar osteitis is a complication that can occur after tooth extraction, whereby exposed bone results in severe throbbing pain for the patient and can be prone to infection. The current treatment options are widely regarded as sub-optimal. The aim of this project was to investigate in vitro the plausibility of a dual-action monolithic drug-loaded thermosensitive hydrogel that undergoes thermal gelation within the tooth socket and releases both anaesthetic and antimicrobial agents. Hydrogels containing different levels of lidocaine HCl and metronidazole were prepared based upon Carbopol 934P NF and Pluronic F-127 blends. Membrane-less drug release was determined from the set hydrogels into phosphate buffered saline (PBS) at 37 °C as a function of time, following analysis by HPLC. Gelation characteristics and hydrogel dissolution characteristics were also determined. At 23.38% Pluronic F-127, sol-gel transition commenced at 23 °C and gelation was completely at 37 °C (physiological temperature). Setting times varied with Pluronic content and there was an inverse relationship between drug release and Pluronic content. Sustained and dose dependent release of both drugs was observed at therapeutically relevant levels over 24 h, via a combination of diffusion, dissolution and surface erosion processes. Based on the amounts of drugs released, it was determined that hydrogels containing up to 0.5% lidocaine and 0.1% metronidazole exhibited low risk of cytotoxicity to primary human gingival fibroblasts. In an in vivo scenario, the sol-phase formulation would make contact with all inner surfaces of a tooth socket prior to transitioning to monolithic gel-phase and provide sustained release of lidocaine and metronidazole at sub-toxic levels, thereby providing simultaneous pain relief, protection from ingress of debris and pathological bacteria.

Infant with status epilepticus secondary to systemic lidocaine toxicity from topical application.

A previously healthy 11-month-old infant presented to the emergency department in status epilepticus. There was no clear trigger of her seizure activity which resolved with benzodiazepines and fosphenytoin. On further review, her parents disclosed that she had been prescribed topical 4% lidocaine cream for a groin rash and was ultimately diagnosed with lidocaine toxicity in the emergency department. She was monitored in the intensive care unit without cardiovascular abnormalities or recurrence of seizure activity. Emergency medicine providers must maintain a broader differential of status epileptics and be able to recognise and manage potential complications from systemic lidocaine toxicity.

Lidocaine Use in Vaginal Surgery and Risk of Toxicity.

OBJECTIVES: The primary objective of this study was to compare the amount of lidocaine administered for vaginal reconstruction with versus without hysterectomy. The secondary objective was to assess the risk of lidocaine toxicity. METHODS: This retrospective cohort study compares lidocaine dose in 2 cohorts: women who underwent vaginal hysterectomy with additional vaginal reconstruction (VH + VR) versus those who underwent vaginal reconstruction without hysterectomy (VR only). Total intraoperative lidocaine dose included the intravenous dose from anesthesia and the vaginally injected dose from the surgeon. The risk of toxicity was defined as total dose greater than 7 mg/kg. The primary outcome was the difference in total lidocaine dose for VH + VR versus VR only. RESULTS: Among 372 women included, 140 (37.6%) were in the VH + VR group, and 232 (62.4%) in the VR-only group. For the primary outcome of total lidocaine dose between groups, VH + VR received more total lidocaine than did VR only (228 ± 105 vs 168 ± 78 mg, P < 0.001). This difference was due to the vaginal lidocaine dose (P < 0.001), with no significant difference in the intravenous lidocaine dose (P = 0.68). In a logistic regression model controlling for age, anesthesia type, sling, and anterior repair, posterior repair, and anesthesia type, VH remained an independent risk factor for increased lidocaine dose (P < 0.001). Two women received a toxic dose of lidocaine, and both were in the VH + VR group. CONCLUSIONS: Women undergoing vaginal hysterectomy with additional vaginal reconstructive procedures are more likely to receive a higher dose of lidocaine compared with women undergoing vaginal reconstruction alone. The risk of lidocaine toxicity is increased with concomitant procedures.