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The number of anesthetic body procedures in the United States is rapidly increasing, with many being performed on an outpatient basis. These procedures are advertised as being safe, and many times the serious complications may not be discussed. Although local anesthetic systemic toxicity is a rare complication, it is associated with an increase in morbidity. The emergency department staff should be aware of the possibility of this rare complication, as well as the variety of resulting symptoms (from minor to severe), potential sequelae, and appropriate management for patients who have undergone an outpatient anesthetic body procedure. Multiple factors contribute to the development of local anesthetic systemic toxicity, resulting in life-threatening effects on the neurologic and cardiovascular systems. Also, the site of administration, along with the local anesthetic agent used, can impact the risk of the development of local anesthetic systemic toxicity. To minimize the risk and ensure the best possible outcome for these patients, emergency department staff must be highly aware of the mechanisms, risk factors, prevention, and management/treatment of local anesthetic systemic toxicity. [ABSTRACT FROM AUTHOR]

Lidocaine toxicity is caused by unintended intravascular injection or overdose. Lidocaine is metabolized in the liver by the CYP3A4 isoenzyme. The objective was to investigate if the administration of rifampin could accelerate animal recovery and reduce the symptoms of lidocaine toxicity by induction of the CYP3A4. Thirty-six male rats were divided into control and treatment groups, each containing three subgroups. The treatment group received oral rifampin suspension daily for 1 week. In all rats, 2.00% lidocaine was injected intravenously. The first subgroup was monitored for neurological symptoms. In the second subgroup, data were recorded after the electrode was placed in the right hippocampus. Electrocardiograms were taken from the third subgroup. CYP3A4 was measured using an ELISA kit. Neurological recovery was seen after 22 and 15 min in the control and treatment groups, respectively. Rifampin also caused a significant reduction in amplitude and number of field action potentials compared to the control group. Numerous cardiac arrhythmias were observed in the control group. The mean level of CYP3A4 in the treatment group was significantly higher than in the control group. In conclusion, oral rifampin could increase the synthesis of CYP3A4, therefore, the animal recovery from lidocaine toxicity was accelerated. [ABSTRACT FROM AUTHOR]

Although rare, local anesthetic use has been associated with adverse central nervous system and cardiovascular adverse events. One complication is local anesthetic systemic toxicity (LAST), wherein the anesthetic agent inadvertently enters systemic circulation resulting in widespread inhibition of fast-gated sodium channels. Organs dependent on aerobic metabolism, such as the heart and brain, are especially susceptible to toxic injury resulting in cardiovascular collapse. Lipid emulsion therapy is a mainstay treatment of LAST; however, it may inadvertently cause lipid-induced necrotizing pancreatitis. We present a 71-year-old female with a non-contributory past medical history who presented for elective open reduction and internal fixation (ORIF) of the right wrist after a fall onto the right hand one week prior. A supraclavicular brachial plexus block was planned to deliver regional analgesia for ORIF of the right wrist. Shortly after the introduction of the local anesthetic agent, our patient became bradycardic and hypotensive. The patient's heart rate and systolic blood pressure remained in the low 45s and 50s, respectively, refractory to multiple doses of phenylephrine and ephedrine. Suspicion for LAST syndrome was high and lipid emulsion therapy was started. Once stabilized, the patient was transported to the ICU requiring manual ventilation, where she later reported flank pain. Labs drawn were notable for elevated triglyceride, lipase, and amylase levels of over 3000, 600, and 700, respectively. CT imaging confirmed acute necrotizing pancreatitis. The patient's ICU stay was uncomplicated with stabilization of vitals and discharge 10 days later. A follow-up with gastroenterology (GI) was scheduled after two weeks. Since discharge, the patient noted intermittent abdominal aches. Magnetic resonance cholangiopancreatography (MRCP) and MRI were performed after liver function tests (LFTs) were found to be elevated during her follow-up appointment. MRI showed liquefaction necrosis of 80% of the pancreas, with a 14-centimeter fluid collection pushing on the distal common bile duct, causing extrinsic obstruction. MRCP revealed no stones. Advanced GI performed a transgastric cystogastrostomy with lumen apposing metal stent placement in the common bile duct, and drained the fluid from the obstructing cyst. Cytopathology came back as virtually acellular. Liver enzymes began to downtrend appropriately and the patient was discharged soon after. Follow-up at two and four days post-discharge confirmed resolution of symptoms., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Robles et al.)

Background: The local anaesthetic lidocaine is widely used in the neonatal intensive unit to treat seizures in premature babies. However, other antiepileptics administered during early development in various animal models have shown negative long-term behavioural effects. Since no long-term behavioural data so far exist regarding lidocaine exposure at an early age, we decided to perform this extended follow-up study using a sensitive behavioural test., Methods: Neonatal mice received a subcutaneous administration of saline or one dose of lidocaine (0.5, 4, or 12 mg kg -1 ) on postnatal day 10 (P10; peak of the Brain Growth Spurt). A well-established test to detect long-term behavioural alterations was conducted at 2 and 6 months of age, corresponding to early and late adulthood in humans., Results: All animal survived to later testing. No signs of acute toxicity were observed. Lidocaine exposure did not result in any negative behavioural effects during habituation to a new home environment at any of the two studied time points, compared to saline placebo., Conclusions: Lidocaine does not by itself produce any negative long-term behavioural effects in mice exposed in early life (P10) despite long-term follow-up. This is reassuring regarding the current practice of treating seizures in premature babies with intravenous lidocaine., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Adenosine, lidocaine and Mg 2+ (ALM) solution is an emerging therapy that reduces secondary injury after intravenous administration in experimental models of traumatic brain injury (TBI). Intranasal delivery of ALM may offer an alternative route for rapid, point-of-care management of TBI. As a preliminary safety screen, we evaluated whether ALM exerts cytotoxic or inflammatory effects on primary human nasal epithelial cells (pHNEC) in vitro. Submerged monolayers and air-liquid interface cultures of pHNEC were exposed to media only, normal saline only, therapeutic ALM or supratherapeutic ALM for 15 or 60 min. Safety was measured through viability, cytotoxicity, apoptosis, cellular and mitochondrial stress, and inflammatory mediator secretion assays. No differences were found in viability or cytotoxicity in cultures exposed to saline or ALM for up to 60 min, with no evidence of apoptosis after exposure to supratherapeutic ALM concentrations. Despite comparable inflammatory cytokine secretion profiles and mitochondrial activity, cellular stress responses were significantly lower in cultures exposed to ALM than saline. In summary, data show ALM therapy has neither adverse toxic nor inflammatory effects on human nasal epithelial cells, setting the stage for in vivo toxicity studies and possible clinical translation of intranasal ALM therapy for TBI treatment., (© 2024 The Author(s). Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Lidocaine is a commonly used anesthetic. High doses or intravenous administration of lidocaine, as well as other local anesthetics, may result in systemic effects involving the cardiovascular and neurologic systems. Typically, effects are dependent on the serum concentrations of the offending agent. This is a case where a patient presented with symptoms of systemic lidocaine toxicity despite therapeutic dosage and an undetectable serum lidocaine concentration. A 47-year-old Caucasian male received a lumbar medial branch injection of lidocaine and presented with symptoms of perioral numbness, seizure-like activity, and confusion. The patient had a workup, including a CT head without acute findings and an undetectable serum lidocaine level. Due to symptoms consistent with systemic local anesthetic toxicity, intravenous lipid emulsion (ILE) was administered with resolution and without recurrence of symptoms. There should be a low threshold of suspicion for local anesthetic systemic toxicity when patients have neurologic or cardiovascular symptoms following exposure. Toxicity may be present despite therapeutic dosages and low serum concentrations. ILE may be beneficial and should be considered., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Charleston Area Medical Center issued approval not applicable. Charleston Area Medical Center's IRB does not require approval for case reports. Review has been waived. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Martin et al.)

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., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hematoma blocks are considered a relatively simple, safe, and effective technique in the acute setting to provide sufficient anesthesia and allow for closed reduction of displaced distal radius fractures. Complications associated with the utilization of local anesthetics in this setting are rare. We present the case of a patient who had a hematoma block in the wrist and developed short-term systemic neurologic complications likely secondary to systemic absorption of 20 mL of 1% lidocaine without epinephrine via the cancellous bone channels., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Burch et al.)

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., (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

While the overall incidence of emergencies in dermatologic surgery is low, emergent situations can occasionally pose a risk to patients undergoing such procedures. The clinical importance of several types of emergences related to systemic reactions, high energy systems, and trauma are reviewed, and relevant epidemiology, clinical manifestations, diagnosis, work-up, management, and prevention are discussed. Early detection of surgical emergencies can mitigate any associated adverse outcomes, thereby allowing the outstanding record of safety of dermatologic surgery to continue. [ABSTRACT FROM AUTHOR]

Objectives: Topical lidocaine remains the mainstay for anesthesia in transcutaneous vocal fold injection (VFI). While using topical lidocaine, laryngologists sometimes encounter uncontrolled reflexes or poor compliance. Superior laryngeal nerve block (SLNB) provides deep and rapid anesthesia on the larynx above the vocal folds and abolishes the glottic closure reflex. Herein, we present a pilot study to evaluate the feasibility and safety of SLNB for transcutaneous VFI and explored its usefulness., Methods: Fifty-nine patients were prospectively anesthetized with SLNB during transcutaneous VFI for unilateral vocal fold paralysis. In the SLNB group, 0.5 to 1 mL of 2% lidocaine was infiltrated on bilateral SLNs through the thyrohyoid membrane. As the control group, we included previous 47 patients who underwent VFI with topical lidocaine. In the control group, 10% lidocaine spray was applied to the laryngopharyngeal mucosa. Demographic data, laryngeal exposure, patient compliance, procedural interruption, and complications were investigated. Patient compliance was evaluated based on the frequency of cough and swallowing during VFI procedures., Results: SLNB enabled endoscopic contact on the epiglottis and pharyngeal wall without gag reflex and provided good exposure of the procedure field on the vocal folds. In the SLNB group, the laryngeal exposure is significantly better than in the control (P = 0.005). The frequency of cough and swallowing was significantly lower in the SLNB group than in the control (P < 0.001). The number of procedural interruptions was lower in the SLNB group than in the control (P < 0.001). There was no acute or delayed complication related to SLNB such as bleeding, hematoma, delayed sensory/swallowing problems, or unscheduled hospital visits., Conclusions: SLNB might be safe and effective for anesthesia in transcutaneous VFI. SLNB could be a good anesthetic option for patients with poor compliance despite the sufficient application of topical lidocaine., Competing Interests: Conflict of interest None., (Copyright © 2023 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Tetrodotoxin (TTX) potently inhibits TTX-sensitive voltage-gated sodium (Na V ) 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 Na V 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) Na V 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, IC 20 and IC 50 values were used to determine if pharmacodynamic interactions occur between TTX and these drugs on spontaneous neuronal activity. At IC 20 and IC 50 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., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Remco Westerink reports financial support was provided by NVWA., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: This study evaluated the clinical and biochemical safety profile of infiltration of lidocaine with adrenaline in wide-awake local anesthesia no tourniquet for distal radius plating., Methods: Twenty-four participants were randomly assigned to the therapeutic group (n = 19) (1% lidocaine in 1:100,000 adrenaline) and control group (n = 5) (2% lidocaine alone). Clinical parameters, including skin necrosis, duration of recovery of sensation, and lidocaine toxicity, were monitored. The serum lidocaine level was measured at different time intervals using a high-performance liquid chromatography reagent., Results: No lidocaine toxicity was recorded in any participant. The therapeutic group had a longer time for recovery of sensation. There was a significant difference in the serum lidocaine levels between both the groups at all time intervals up to 6 hours, with all participants exhibiting serum lidocaine levels below the mild toxicity level of 6.0 μg/mL., Conclusions: Lidocaine used within a safe recommended dose in wide-awake local anesthesia no tourniquet for distal radius plating is clinically and biochemically safe., Clinical Relevance: Determining the clinical and biochemical safety profile of lidocaine with adrenaline in wide-awake local anesthesia no tourniquet can promote wider use of this technique., (© 2022 The Authors.)

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., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by Turkish Ophthalmological Association | Turkish Journal of Ophthalmology, published by Galenos Publishing House.)

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., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

This is the case of a 4-year-old girl who presented to the emergency department with acute development of seizures and respiratory failure. The patient had sustained full thickness burns a few days prior covering 20% total body surface area. She was treated with home topical therapies including a lidocaine containing gel. She had resultant lidocaine toxicity and hyponatremic, hypochloremic dehydration. This case report reviews the differential diagnosis of decreased mental status and seizures. The patient's diagnoses of lidocaine toxicity, full thickness burns, dehydration, and child abuse are discussed. Lidocaine toxicity is reviewed including mechanism of action, signs and symptoms, and treatment. [ABSTRACT FROM AUTHOR]

Background: Topical lidocaine is a common form of anesthesia for a wealth of procedures across a large number of disciplines, including laser treatments. Preparations can be purchased over the counter with no prescription necessary. It is considered a safer and more acceptable form of anesthetic than hypodermic injections; however, there have been reports of fatalities following its application. Above certain serum lidocaine concentrations, patients may experience effects of toxicity such as lightheadedness and paraesthesia; these effects can progress to seizures and cardiorespiratory depression, which can ultimately lead to death. The active metabolite of lidocaine, monoethylglycinexylidide (MEGX), can be almost as potent as lidocaine in terms of toxicity. Objectives: The authors examine the levels of both lidocaine and MEGX in blood serum after application of topical lidocaine. Methods: Twenty-five healthy volunteers were assigned to one of four groups (A, B, C, D). Group A had 2.5 g of 4% lidocaine topical anesthetic cream applied to the face for one hour without occlusion, Group B had 5 g applied to the face for one half-hour without occlusion, Group C had 5 g applied to the face for one hour without occlusion, and Group D had 5 g applied to the face for one hour with occlusion. To evaluate serum concentrations, blood was drawn every 30 minutes for four hours. Results: Group D showed the highest serum levels of lidocaine and MEGX, a three-fold increase compared with group C, which received the same dose (5g topical 4% lidocaine) but without occlusion. In group D, peak serum levels occurred at 90 minutes for serum lidocaine, which was also the fastest of the four groups. Serum MEGX levels peaked much later than serum lidocaine levels, at 210 minutes. Individual serum levels did not exceed 0.6 μg/mL. Across the groups, there was significant interindividual variation in both lidocaine and MEGX serum levels (P = .061). Applications of 5 g of 4% lidocaine resulted in higher serum concentration of both lidocaine and MEGX. When comparing group A to group C, doubling the dose of 4% lidocaine from 2.5 g to 5 g resulted in double the serum levels of MEGX and a 50% increase in the serum lidocaine levels (P = .021). When comparing groups C and D, the addition of an occlusive dressing resulted in a tripling of the serum lidocaine levels and a doubling of the serum MEGX levels, both of which were statistically significant (P < .001). When comparing all four groups, there were significant differences between the combined serum concentrations of lidocaine and MEGX (P < .001). Conclusions: Topical lidocaine preparations are increasingly being employed to provide a patient-friendly form of noninvasive analgesia for a multitude of procedures. Some preparations are available over the counter for unsupervised patient application. Our study has demonstrated significant interindividual variability for a given dose, especially when occlusion is applied. There have been fatalities resulting from topical lidocaine application, and our study suggests that this is the result of the unpredictability of lidocaine metabolism between individuals. Therefore, we recommend that caution be exercised with topical lidocaine preparations, in particular when applied in conjunction with occlusive dressings. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The article present a case study of a 52-year-old woman admitted to our inpatient service for intravenous lidocaine infusion to treat intractable hemicrania continua in the setting of Nonsteroidal anti-inflammatory drug (NSAID) intolerance. It mentions the patient was on sertraline and trazodone therapy for her depression; and highlights the need to proceed with caution when using lidocaine infusion.

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., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The article describes the case of a male patient with intractable cardiac arrest who was successfully resuscitated with lipid emulsion. The patient suffered intractable cardiac arrest due to prolonged toxicity with the anesthetic lidocaine. Lidocaine is commonly used as infusions in patients with intractable ventricular arrhythmias.

Oral viscous lidocaine is useful for the treatment of symptoms induced by oral inflamed mucosa, such as radiation- or chemotherapy-induced mucositis. The toxic reactions associated with an accidental overdose have been reported in pediatric cases. We report a case of lidocaine toxicity in a 22-year-old man during frequent viscous lidocaine use for severe painful tongue ulcer. The toxic symptoms developed when the amount of oral viscous lidocaine exceeded 240 ml per day. The serum lidocaine concentration associated with this use was 6.7 μg/ml. The toxic symptoms continued in spite of the serum lidocaine concentration below the toxic level after the start of a diluted preparation, which contained a half-dose lidocaine. It is speculated that lidocaine metabolites might have contributed to the toxic symptoms. Clinicians should consider the risk of lidocaine toxicity in cases of frequent viscous lidocaine use, and determine the serum concentrations of lidocaine and its metabolites. [Copyright &y& Elsevier]

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., (© 2020 John Wiley & Sons, Ltd.)

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.

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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2021 Rosso et al.)

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., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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.

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.

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Epistaxis is a common problem that occurs in up to 60% of the general population, and is a common emergency department (ED) complaint. The use of lidocaine for analgesia is common when cauterization is required for bleeds that are refractory to manual compression. Although the use of lidocaine is generally thought of as a benign intervention, it is not completely without risk.Case Report: We present the case of a 19-year-old man who presented to the ED with persistent anterior epistaxis. He developed severe lidocaine toxicity resulting from topical anesthesia applied prior to intranasal cautery for the epistaxis. This toxicity, which manifested as seizures, bradycardia, hypotension, nausea, and emesis, was rapidly recognized and appropriately treated, with a good clinical outcome for the patient. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We present this case to increase awareness among emergency physicians of the potential complications of the intranasal use of topical lidocaine, something that is generally considered a benign intervention. We also discuss the pathophysiology and management of lidocaine toxicity. [ABSTRACT FROM AUTHOR]

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 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., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Analgesic discoblock is widely used for the diagnosis or treatment of discogenic low back pain by injecting local anesthetics. The purpose of this study was to investigate the deleterious effects of local anesthetics on degenerated rabbit intervertebral disks (IVDs) using an organotypic culture model and in vivo long-term follow-up model. To induce IVD degeneration, a rabbit annular puncture model was used. For the organotypic culture model, degenerated IVDs were harvested 1 month after the initial annular puncture and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine and 0.5% bupivacaine). To perform in vivo analysis, local anesthetics were injected into degenerated IVDs, and IVDs were prepared for histological analysis after 6 or 12 months. In the organotypic model, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive nucleus pulposus (NP) cells were significantly increased in the bupivacaine group compared with the other groups. In the in vivo study, the number of NP cells was significantly decreased in the saline and local anesthetics groups compared with the untreated control and puncture-only groups. However, there was no significant difference among the saline, lidocaine, and bupivacaine groups. In addition, histological analysis showed no significant difference of IVD degeneration among the puncture-only, saline, lidocaine, and bupivacaine groups. Although bupivacaine induced apoptotic NP cell death in the organotypic culture model, in vivo observations did not show any definitive proof to suggest that local anesthetics were capable of promoting degeneration in the degenerated IVD, except for pressurized injection-induced damage. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1963-1971, 2019., (© 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

In equids, it is common to inject lidocaine into the testicles at the time of routine castration to provide analgesia. The effects of lidocaine on equine sperm have not been evaluated in vitro or on epididymal sperm collected following castration. The aims of this study were to determine effects of clinically relevant doses of lidocaine on equine spermatozoa in vitro using freshly collected semen and to compare the characteristics of epididymal spermatozoa after routine castration with or without intra-testicular lidocaine administration. We hypothesized that increasing concentrations of lidocaine would decrease total motility (TM), progressive motility (PM), velocity of the average path (VAP), velocity of the curved line (VCL), linearity (LIN), normal morphology (M) and membrane integrity (MI). We also hypothesized that injection of intra-testicular lidocaine would decrease TM, PM, VAP, VCL, LIN, M, and MI following routine castration, epididymal flushing and cryopreservation. In experiment 1, sperm was collected from four stallions and mixed with lidocaine at concentrations of 1 μg/ml, 10 μg/ml, 100 μg/ml, 1,000 μg/ml and 10,000 μg/ml. M and MI were compared to the control sample at 0 and 48 h. Motility parameters were analyzed at 0, 2, 4, 6, 24, and 48 h. In experiment 2, 12 stallions were castrated under general anesthesia. One testicle was removed without the use of intra-testicular lidocaine and the other testicle was removed 10 min after injection of 10 ml of 2% lidocaine. Results: In experiment 1, fresh sperm showed no significant difference (p < 0.05) compared to control at either 1 μg/ml or 10 μg/ml concentrations of lidocaine. There were significant decreases in PM, VAP, VCL, and LIN at concentrations of 100μg/ml-10,000 μg/ml and for TM at lidocaine concentrations of 1,000-10,000 μg/ml compared to control. Morphology did not change at any lidocaine concentration. Membrane integrity decreased significantly at 10,000 μg/ml lidocaine. In the second experiment 1.03 ± 0.42 μg/ml lidocaine was detected in the epididymal flush of stallions treated with lidocaine. There were no significant differences in any measured parameters between the control and the lidocaine treated testicles. Intra-testicular lidocaine injection at the time of castration did not affect any measured parameters after epididymal flush. Lidocaine concentrations higher than 100 μg/ml in-vitro resulted in decreased motility parameters of the spermatozoa independent of exposure time., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: In orthopedic joint injection, the most frequently used local anesthetics are ropivacaine, bupivacaine, and 1% or 2% lidocaine. The aim of this study was to examine effects of these various anesthetics on the viability of human chondrocytes. Our hypothesis was that all local anesthetics tested damage human chondrocytes in vitro ., Methods: Primary human chondrocytes were isolated and cultured from 6 donated human knee joints (mean age of donors 61.2 years). Local anesthetics were added to these cultures. Toxicity analysis was performed by visualization of cell structure using light microscopy. Determination of vital chondrocytes was performed by use of a Casy cell counter. Chondrocytes' cell death was examined by fluorescence microscopy and an XTT ELISA assay., Results: Light microscope and fluorescence microscope data revealed a defect cell structure and increased number of dead cells after addition of 1% or 2% lidocaine and bupivacaine but not ropivacaine. We were able to show an increased level of XTT activity after treatment with bupivacaine, 2% lidocaine or ropivacaine. The count of vital chondrocytes was significantly decreased after treatment with bupivacaine, 1% or 2% lidocaine, and ropivacaine., Conclusions: The data show that treatment with local anesthetics induces cell damage of human chondrocytes in vitro . Ropivacaine seems to be a local anesthetic with the lowest toxic potential on human chondrocytes, a feature that may favor its preference for use in joint injection.