Lidocaine Toxicity Research Articles

UP-01.068 Intravesical Non-alkalinized Lidocaine Instillation for Interstitial Cystitis/Bladder Pain Syndrome Patients

Purpose: The effectiveness of daily or weekly instillation of non-alkalinized lidocaine for patients suffering interstitial cystitis and/or bladder pain syndrome was evaluated retrospectively. Patients and methods: Five female patients (40 - 71 years old) diagnosed as interstitial cystitis by cystoscopic findings and a 68 year-old bladder pain syndrome patient were enrolled. All patients, having interstitial cystitis, had undergone hydrodistention therapy previously and had not improved their symptoms by empirical therapies. Daily or weekly (upon their severity of symptoms) intravesical instillation of 20 ml of 4% non-alkalinized (pH 6.0 - 7.0) lidocaine solution was performed for several times, and patients were asked to keep them in the bladder as long as two hours each time. Previous medications such as anti-cholinergic drugs and analgesics were continued according to patient's requirements and symptoms. The treatment effect was evaluated comparing O'Leary-Sant Symptom Index for interstitial cystitis patients and visual analog pain scale before and after the series of lidocaine therapies. Results: Instillation was made 6 to 16 times. Patients with interstitial cystitis improved their symptoms from O'Leary-Sant Symptom Index 17.5 to 10, Problem Index from 14.8 to 6 in an average. Crouching pain disappeared in all these patients after the instillation therapy. Severe interstitial cystitis findings on cystoscopy disappeared completely in one patient after the therapy. One patient having bladder pain syndrome reduced her analgesics use, and bladder-filling pain decreased from 7 to 3 as a visual analog scale score. One patient complained palpitation at 11th instillation and abandoned treatment thereafter, otherwise, none of these patients showed side effect concerning lidocaine toxicity. Conclusions: Intravesical non-alkalinized lidocaine instillation therapy for interstitial cystitis/bladder pain syndrome patients were an easy, safe and effective treatment.

Intrauterine lidocaine infusion for pain management during outpatient transcervical tubal sterilization: a randomized controlled trial

BackgroundThe study was conducted to examine the effects of a 4% intrauterine lidocaine infusion on patient-perceived pain during transcervical sterilization. Study DesignThis was a randomized, double-blind, placebo-controlled trial. Subjects received standard premedication with 800 mg ibuprofen, 2 mg lorazepam, a 10-mL 1% lidocaine paracervical block and transcervical instillation of 5 mL of either 4% lidocaine or saline 3 min prior to insertion of the hysteroscope. Subjects completed a series of 100-mm visual analog scales to measure their perceived pain at set time points during and after the procedure. Serum lidocaine levels were obtained in a subset of subjects. ResultsPain scores at all evaluation points did not significantly differ between groups (lidocaine n=29, saline n=29). Mean lidocaine levels did not differ between groups, and no subject demonstrated symptoms of lidocaine toxicity. The highest serum lidocaine level (4022 ng/mL) occurred 20 min after infusion in a lidocaine-treated subject. ConclusionIntrauterine lidocaine prior to outpatient transcervical sterilization does not decrease pain.

Lidocaine (Lignocaine) Dosing Regimen Based upon a Population Pharmacokinetic Model for Preterm and Term Neonates with Seizures

The application of lidocaine (lignocaine) as an anticonvulsant in neonates originated more than 40 years ago in Scandinavia. Lidocaine has been shown to be an effective anticonvulsant for the treatment of neonatal seizures that persist in spite of first-line anticonvulsant therapy. However, lidocaine toxicity, mainly in the form of cardiac arrhythmias, can be life threatening. Therapeutic drug monitoring can be useful to prevent toxicity. In a previous study, a dosing regimen was developed for term neonates, but it was not evaluated for preterm neonates. Extrapolation of the previously developed dosing regimen to premature neonates without accounting for differences in pharmacokinetics because of immaturity of phase I metabolism and body fat/water ratio may result in serious toxicity or therapy failure. The objective of this study was to develop an optimized dosing regimen for lidocaine in preterm as well as term neonates, using population pharmacokinetic modelling and simulation. The requirements for this dosing regimen were simplicity of implementation, equal initial doses for all weight categories and avoidance of plasma concentrations >9 mg/L. After lidocaine administration, blood samples were collected from an arterial line from a total of 46 preterm and term neonates with convulsion, within 10 days after birth. Lidocaine concentrations were measured in plasma using a fluorescence polarization immunoassay. Population pharmacokinetic modelling started with assessment of two important aspects of paediatric pharmacokinetics: relation to body size and the effects of maturation. In the studied neonatal population (term and preterm neonates with gestational ages up to 10 days), gestational age and bodyweight were closely related. Therefore, the effects of allometry and maturation on lidocaine pharmacokinetics could not be described independently and were described by a combined power estimate of bodyweight on clearance and volume of distribution. Based on this pharmacokinetic model, a dosing strategy for lidocaine for neonatal seizure control was developed, which allows rapid and safe administration of lidocaine in this population. When prospective validation confirms our model, routinely performed therapeutic drug monitoring should no longer be necessary and would only be advised in cases of (suspected) clinical symptoms of over- or underdosing. A lidocaine dosing regimen for seizure control in preterm and term neonates has been developed using population pharmacokinetic modelling and simulation. Allometry and maturation exponents were combined into one exponent for each pharmacokinetic parameter and could not be described independently. Based on this model, this regimen allows rapid and safe administration of lidocaine in this population.

Tumescent Liposuction: Partitioning of Lidocaine at a Lower Dose (252 mg/l)

Background: The popularity of large-volume liposuction and the toxicity of lidocaine have led to a reduction of lidocaine dosage in tumescent liposuction. We have gradually reduced the concentration of lidocaine from 500 to 252 mg/l over the past decade. Objective: To evaluate the partitioning and the recovery of lidocaine at a lower concentration in tumescent liposuction. Methods: 10 consecutive patients’ aspirate samples were analysed for the lidocaine concentration in the fat and the fluid component, the percentage of injected lidocaine removed by aspiration and its partition coefficient in fat versus fluid. Results: 7.5% of the injected lidocaine was removed; its partition coefficient was 0.21. Conclusion: 7.5% of the total lidocaine was aspirated in tumescent liposuction. The fat uptake of lidocaine was lower than in previous reports, which was of particular interest for future studies on lidocaine toxicity for the safety of the patients undergoing tumescent liposuction.

Intractable cardiac arrest due to lidocaine toxicity successfully resuscitated with lipid emulsion*

Demonstrate a case report involving successful use of lipid emulsion therapy for intractable cardiac arrest due to lidocaine toxicity. Lipid emulsion therapy has been shown to be effective in treating the cardiotoxic effects of such drugs as bupivacaine, verapamil, propranolol, and clomipramine as mentioned in a 2009 editorial in Critical Care Medicine by Jeffrey Bent. The mechanism of action of lipid emulsion therapy is not well defined and has been postulated to work by both a "lipid sink," decreasing circulating amounts of drugs to the periphery, or through a direct "energy source" to the myocardium. We present a case report of a patient successfully resuscitated with lipid emulsion therapy after prolonged and intractable lidocaine toxicity. Lidocaine is generally considered much less cardiotoxic than other local anesthetics and is used commonly as infusions for intractable ventricular arrhythmias. This case demonstrates the need to consider lipid emulsion therapy in the advanced cardiac life support algorithm for lidocaine toxicity as well as other lipid soluble drug intoxications.

A comparison of the systemic toxicity of lidocaine versus its quaternary derivative QX-314 in mice

We recently showed that the quaternary lidocaine derivative, QX-314, produces long-lasting local anesthesia with a slow onset in animal models in vivo. As quaternary agents do not rapidly penetrate biological membranes or the blood-brain barrier, QX-314 may represent a local anesthetic with decreased systemic toxicity compared with conventional tertiary aminoamines. To test this hypothesis, we conducted an in vivo animal study in mice to compare QX-314 with lidocaine in terms of its relative central nervous system (CNS) and cardiac toxicity. With approval from the institutional Animal Care Committee, we used the "up-and-down" method to determine the relative potencies (ED(50)) of lidocaine and QX-314 for CNS and cardiac toxicity in adult CD-1 mice (weight, 20 to 35g). The animals were administered either intravenous lidocaine or QX-314 (dose range, 7.5 to 30mg·kg(-1)) and were observed for signs of CNS toxicity (convulsions, ataxia, loss of righting reflex, and/or death). We also observed animals for electrocardiographic evidence of toxic effects on cardiac automaticity, conductivity, and rhythmicity. The ED(50) of lidocaine for CNS toxicity as determined by the "up-and-down" method was 19.5mg·kg(-1) (95% confidence interval [CI], 17.7 to 21.3mg·kg(-1); n=6) compared with 10.7mg·kg(-1) for QX-314 (95% CI, 9.1 to 12.3mg·kg(-1); n=6) (potency ratio, 1.8). Similarly, the ED(50) of lidocaine for electrocardiographic evidence of cardiac toxicity was significantly higher than that of QX-314 (ED(50) of lidocaine, 21.2mg·kg(-1); 95% CI, 19.0 to 23.4mg·kg(-1); n=6 vs ED(50) of QX-314, 10.6mg·kg(-1); 95% CI, 8.4 to 12.8mg·kg(-1); n=6) (potency ratio, 2.0). In this in vivo animal study, the relative potencies of QX-314 for systemic CNS and cardiac toxicity were significantly higher than those of lidocaine. These data do not support the hypothesis that QX-314 is a safer local anesthetic compared with lidocaine in terms of systemic toxicity. Whereas our results do not exclude the possibility that QX-314 may represent a clinically useful agent to produce long-lasting local anesthesia and nociceptive blockade after a single shot in humans, its systemic toxicity relative to conventional tertiary aminoamide local anesthetics and the underlying mechanisms warrant further study.

Water-Assisted Liposuction for Body Contouring and Lipoharvesting: Safety and Efficacy in 41 Consecutive Patients

Water-assisted liposuction (WAL) is a new technique for body contouring and fat harvesting that relies on a fan-shaped jet of tumescent solution to anesthetize fatty for liposuction and grafting. As with any new technology, safety and efficacy are paramount. The author evaluates the technique and outcomes for small-to-moderate volume liposuction cases treated with WAL in an office setting. Forty-one consecutive patients were treated with WAL (Body-Jet; Human Med, Eclipse Ltd., Dallas, Texas) in the author's private practice for mild-to-moderate body contouring. Patients were given local anesthesia (standardized tumescent solutions) during all three phases of the surgery. During the latter two phases, irrigation of tumescent solution was accompanied simultaneously by suction aspiration. Fat harvesting was accomplished by collecting and separating the aspirated adipose tissue in a sterile container, without need for washing or centrifugation. Fat grafting by microdroplet technique was performed within two hours of collection. Fat aliquots from five randomly-selected patients were assessed with a trypan blue dye exclusion test within one hour and again six to eight hours after collection. A total of 37 females and four males underwent WAL in this series; average body mass index (BMI) was 25.5. Among the 41 patients, 166 areas involving twelve anatomic sites were treated. Patients were divided into two groups based on the volume of treatment: Group 1 contained 19 patients with small-volume WAL and Group 2 had 22 cases of moderate-volume WAL. All patients experienced uneventful recovery periods with minimal side effects and no significant complications. Although large volumes of tumescent solution were required during the three phases of the technique, the total volume of infiltration almost equaled the final volume of aspiration. The average infiltration-to-aspiration ratio was 1.1 to 1.0 in all cases over both groups. On the other hand, the average infiltration-to-fat ratio was 2.8 to 1.0 in Group l and 2.4 to 1.0 in Group 2. Lidocaine dosage averaged 10.5mg/kg in Group 1 and 20.0mg/kg in Group 2. Patients were monitored for at least 24 hours without adverse signs or symptoms that required fluid resuscitation, blood transfusions, or interventional treatments for lidocaine side effects or toxicity. Twenty-three patients elected to save their fat for autologous fat grafting in nine anatomical sites with thirty-nine procedures. The augmented sites were clinically assessed between three and eight months postoperatively. Trypan blue dye exclusion testing indicated that about 90% of adipocytes expelled the dye after one hour of extraction, while an estimated 10% of cells per patient were observed to be free of dye six to eight hours after removal. The amount of instilled tumescent fluid, lidocaine dosage, and aspiration volumes appeared to be safe, with minimal blood loss in small and moderate volume liposuction cases. The early experience with fat grafting was encouraging, but requires more sophisticated evaluation, longer follow-up, and a larger number of cases.

Efficacy of tumescent local anesthesia with variable lidocaine concentration in 3430 consecutive cases of liposuction

Lidocaine toxicity is a potential complication related to using tumescent local anesthesia (TLA) as the exclusive form of pain management in surgical procedures. We sought to determine the minimum concentration of lidocaine in the tumescent solution required to provide adequate anesthesia in patients undergoing liposuction using TLA exclusively. Liposuction using TLA exclusively was performed in 3430 procedures by the same surgeon. The initial concentration of 1000 mg/L lidocaine in the tumescent solution was gradually reduced to find the minimum required for adequate anesthesia. Adequate anesthesia was achieved using a lidocaine concentration of 500 mg/L saline in all areas treated and 400 mg/L saline for most of the areas treated. Data are based on the specific TLA technique used by the same surgeon. Lidocaine serum levels were not analyzed. For patients undergoing liposuction using TLA exclusively, the concentration of lidocaine in the normal saline solution required for adequate anesthesia is 400 mg/L for most body areas and 500 mg/L for some sensitive areas.

Safety of peak serum lidocaine concentration after Mohs micrographic surgery: A prospective cohort study

Large volumes of dilute local anesthesia are increasingly used not only for liposuction but also for other large cutaneous surgeries, including skin cancer excision. Although the lidocaine serum levels and peaks after injection of tumescent anesthesia in the trunk were shown to be safe even when used in high doses, the levels after use of less dilute (1% lidocaine) solutions for facial cancer surgery have not been described. We sought to ascertain whether perioperative peak lidocaine levels during Mohs micrographic surgery approach thresholds for lidocaine toxicity. In this prospective cohort study, each Mohs micrographic procedure was commenced per routine protocol, with use of injectable 1% lidocaine with 1:200,000 epinephrine and 1:10 8.4% bicarbonate for local anesthesia. Six peripheral blood draws of 5 mL each were performed and sent for serum lidocaine concentration measurement. Blood draws were obtained before and after the first two stages of Mohs micrographic surgery, and before and after the third stage or wound repair, as appropriate. Subjects and investigators reported any symptoms or signs of lidocaine toxicity. The main outcome measures include: (1) number of subjects exhibiting at least one level higher than the threshold for toxicity; and (2) sustained elevated lidocaine levels in one or more subjects. Mean total lidocaine volume per subject was 15 mL (range: 5-48 mL). The highest peak serum lidocaine level detected at any time point (blood draw) for any subject was 0.3 microg/mL. Mean serum lidocaine level for all 6 time points was less than 0.1 microg/mL and was thus not detected. Detectable lidocaine levels were found to be associated with higher mean (P = .028) and median (P = .008) total lidocaine doses. Because no toxic levels were detected, it was not possible to measure sustained high lidocaine levels. Limitations of this study include the lack of use of very concentrated (eg, 2% vs 1%) lidocaine solution. Lidocaine use during Mohs micrographic surgery does not appear to result in serum lidocaine levels approaching toxic levels even when relatively high total lidocaine doses are used. There is an association between higher total lidocaine dose and perioperative peak serum lidocaine level.

Airway topicalisation using atomisation of lidocaine

We read the recent article of Woodruff et al. [1] with interest. A major advantage of the atomisation with lidocaine used in this study is the rapidity with which the airway can be anaesthetised, but this is achieved at the expense of administration of a large dose over a short time (about 5 min). We have concerns over the safety of this topicalisation method in general clinical practice, particularly when the drug is rapidly administered to non-obese patients. The British Thoracic Society has recommended a maximum lidocaine dosage of 8.2 mg.kg−1 for airway topical anaesthesia during bronchoscopy [2], but these drugs are administered in fractional doses at different sites in the airway over a prolonged time period. Compared with a large dose used in a shorter time, fractional doses sprayed over a longer period result in a lower plasma drug level [3]. Moreover, we do not agree that a large dose of lidocaine is safe in routine clinical practice for two reasons. First, lidocaine pharmacokinetics are complex, being affected by many factors, so the plasma lidocaine concentration achieved in a particular patient is often unpredictable. Even with recommended doses, patients may still sometimes achieve an unexpectedly high plasma concentration [4]. After large doses of lidocaine (7.1–14.8 mg.kg−1) administered by a spray-as-you-go technique, 36–92% of subjects report symptoms attributable to lidocaine toxicity [5, 6]. In addition, a healthy volunteer has died from lidocaine toxicity after fibreoptic bronchoscopy [7]. Second, lidocaine toxicity can occur even when the plasma lidocaine levels are in a ‘safe’ range [3, 8]. The authors suggest that airway topicalisation using nebulisation requires a long preparation time and may interfere with rapid turnover of patients. However, this technique can be safely performed in the holding area. We would also like to call the authors’ attention to the two papers in which low doses of nebulised lidocaine (100 or 160 mg) achieved adequate airway anaesthesia in most patients [9, 10]. We appreciate the reference to our recent article [3], but believe that Woodruff et al. have misrepresented our time (> 20 min) for airway topicalisation. As the main aim of our study was to compare the safety and efficacy of 2% and 4% lidocaine to produce airway topical anaesthesia with a spray-as-you-go technique, the repeated lidocaine sprays in the airway were performed at a 3–5 min interval to provide adequate penetration of local anaesthetic into the mucosa for maximal effect, and the whole airway topicalisation protocol required 19.2–28.2 min. The authors think that this prolonged time for airway topicalisation may sometimes be unacceptable. However, we feel that, as with other local anaesthetic methods, ‘tincture of time’ is a useful supplement to the application of airway topical anaesthesia. Inadequate airway topical anaesthesia due to the slow onset of the maximal effect can often result in larger doses' being given or repeated drug delivery in a short time, leading to overdose.

Bupivacaine causes cytotoxicity in mouse C2C12 myoblast cells: involvement of ERK and Akt signaling pathways

The adverse effects of local anesthetics (LAs) on wound healing at surgical sites have been suggested, and may be related to their cytotoxicity. This study was aimed to compare the cellular toxicity of bupivacaine and lidocaine (two well-known LAs), and to explore the molecular mechanism(s). Toxicity of bupivacaine and lidocaine was assessed in cultured mouse C2C12 myoblasts by cell viability and apoptosis assays. Effects of LAs on extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) activation, which are essential for cell proliferation and survival, were evaluated by immunoblotting. Both LAs, especially bupivacaine, prevented cell growth and caused cell death in a dose-dependent manner. The half maximal inhibitory concentrations (IC(50)) for bupivacaine and lidocaine were 0.49+/-0.04 and 3.37+/-0.53 mmol/L, respectively. When applied at the same dilutions of commercially available preparations, the apoptotic effect induced by bupivacaine was more severe than that of lidocaine in C2C12 cells. Furthermore, bupivacaine significantly diminished the ERK activation, which may underlie its anti-proliferative actions. Both LAs suppressed Akt activation, which correlated with their effects on apoptosis. Our study demonstrated that, when used at the same dilutions from clinically relevant concentrations, bupivacaine is more cytotoxic than lidocaine in vitro. Anti-proliferation and cell death with concomitant apoptosis mediated by bupivacaine may offer an explanation for its adverse effects in vivo (eg slowing wound healing at the surgical sites). A less toxic, long-acting anesthetic may be needed.

Tumescent Liposuction: Efficacy of a Lower Lidocaine Dose (400 mg/l)

Background: Local anesthesia has been widely accepted as the standard of care in liposuction. Anesthesia is achieved with a standard tumescent solution, and lidocaine is most often used at a concentration of 500 mg/l. Objective: To evaluate the efficacy of a 400 mg/l lidocaine concentration in tumescent liposuction. Methods: We performed a randomized clinical trial on 200 consecutive patients undergoing lipoaspiration. Patients were divided into two groups: group A (n = 100) received tumescent solution with a lidocaine concentration of 500 mg/l, in group B (n = 100) lidocaine levels were reduced to 400 mg/l. Pain was assessed twice during the procedure, at infiltration and while liposuction was performed. Patients rated their pain level on a numeric rating scale from 0 to 10, with 10 being the worst possible pain. Results: Tumescent solution containing a lidocaine concentration of 400 mg/l provided effective local anesthesia during lipoaspiration. There was no statistically significant difference in the pain level between the two groups. Conclusion: We propose the use of a lower lidocaine concentration of 400 mg/l in the tumescent solution compared to the originally described solution containing 500 mg/l. This is of particular interest when multiple body parts or larger areas are to be treated to avoid lidocaine toxicity.

Acute Auditory and Vestibular Symptoms Associated With Heat and Transdermal Lidocaine

To describe a case of systemic lidocaine toxicity from the simultaneous use of transdermal patches and a heating pad. Case report and discussion. The focus of this case report are the interesting neuro-otologic signs of central lidocaine toxicity that occurred after a patient fell asleep on a heating pad with his Lidoderm patches in place. Hearing improvement, tinnitus reduction, and severe dizziness and ataxia were present for approximately 48 hours before spontaneous resolution. Based upon his symptoms we estimate an 11-fold increase in plasma concentrations of lidocaine. Transdermal delivery of medication affords ease of application, ability to provide continuous pharmacological therapy, and ability to supply medication to the affected site. Due to the superficial application of these medications, external environmental factors may influence the pharmacokinetics of drug delivery. This case highlights the complications that can arise from the combination of heating pads and transdermal pain therapies.

Effect of PaCO2 and PaO2 on Lidocaine and Articaine Toxicity

Alterations in arterial PaCO₂ can influence local anesthetic toxicity. The objective of this study was to evaluate the effect of stress-induced changes in PaCO₂ and PaO₂ on the seizure threshold of lidocaine and articaine. Lidocaine (2% with 1 : 100,000 epinephrine) or articaine (4% with 1 : 100,000 epinephrine) was administered intravenously under rest or stress conditions to 36 rats separated into 4 groups. Propranolol and prazosin were administered preoperatively to minimize cardiovascular effects of epinephrine. Mean arterial pressure (MAP), heart rate (HR), and arterial pH, PaCO₂, and PaO₂ were measured. Results showed no differences in MAP, HR, or pH. Stress significantly increased the latency period for the first tonic-clonic seizure induced by a toxic dose of both lidocaine and articaine (P < .05). Seizures were brought on more rapidly by articaine. No significant difference between toxic doses of lidocaine and articaine was noted. Stress raised the seizure threshold dose for both drugs and significantly (P < .01) increased arterial PaO₂ from 94.0 ± 1.90 mm Hg to 113.0 ± 2.20 mm Hg, and reduced PaCO₂ from 36.0 ± 0.77 mm Hg to 27.0 ± 0.98 mm Hg. In conclusion, reduction in PaCO₂ and/or increase in PaO₂ raised the seizure threshold of lidocaine and articaine. This study also confirmed that lidocaine and articaine have equipotent central nervous system toxicity.

Lidocaine Inhibits Proliferation and Promotes Cluster Formation of Bone Marrow Mesenchymal Stem Cells Cultured in High Glucose Plus Serum Deprivation DMEM.

Abstract 4582 ObjectivesBone marrow mesenchymal stem cells (BMSCs) have multilineage differentiation potential and highly proliferative potential in vitro. Cell therapy with BMSCs has great promise in regenerating the damaged tissues, restoring their function and treating ischemic related failures, but the chief limitation may be the poor viability of BMSCs transplanted into the pre-existing ischemic environment, where massive death of transplanted cells has been detected. The serum deprivation (SD) is a component of ischemia. Lidocaine can be used for relief of pain and has been one of the most widely used local anesthetics. Intravenously, it has been used successfully for emergency treatment of ventricular arrhythmias. It reportedly also showed anti- proliferative, anti-inflammatory and protective effects when administered before or after the ischemic insult. Which effects has it on BMSCs during the BMSCs transplanted in the patient with lidocaine treatment? The experimental objective is to investigate the effects of lidocaine on the proliferation of BMSCs cultured in high glucose plus serum deprivation DMEM. MethodsBMSCs were separated from adult male SD rat bone marrow. The BMSCs were cultured in the high glucose (4.5g/L) DMEM containing 10% fetal bovine serum (FBS). All experiments were performed using BMSCs from the 3rd passage adherent cell fraction. The BMSCs were divided into 10 groups according to the concentrations of lidocaine and FBS: 0μg/ml, 2μg/ml, 20μg/ml, 200μg/ml, 2000μg/ml lidocaine, containing 10% FBS; 0μg/ml, 2μg/ml, 20μg/ml, 200μg/ml, 2000μg/ml lidocaine, containing 0% FBS. Cell proliferation of the BMSCs was assessed by MTT assay at the time points of 24h, 48h and 72h respectively. ResultsAs the MTT colorimetric assay revealed, lidocaine with 2μg/ml, 20μg/ml, 200μg/ml, 2000μg/ml all inhibited the proliferation of the BMSCs at under the condition of 10% FBS and under the condition of 0% FBS. The cells cultured in 0μg/ml lidocaine, 10% FBS displayed a significant proliferation compared to those cultured in 0μg/ml lidocaine,0% FBS (serum deprivation) (P<0.01, n=5) from 24h to 72h. The number of vital cells cultured in 2μg/ml, 20μg/ml, 200μg/ml lidocaine,10% FBS was more significantly compared to that cultured in 2μg/ml, 20μg/ml, 200μg/ml lidocaine, 0% FBS (P<0.01, n=5) at 24 h, 48h, 72 h respectively. But in 2000μg/ml lidocaine, the number of vital cells was similar and nearly zero both the BMSCs cultured in 10% FBS and serum deprivation groups. The number of vital BMSCs of all groups showed having a proliferative potential from 24h to 72h.BMSCs cultured under serum deprivation with 0μg/ml, 2μg/ml, 20μg/ml, 200μg/ml lidocaine gave rise to cell cluster formation, but all groups of BMSCs cultured in the presence of serum did not form the cell clusters. The phenomenon that the number and the size of the cell clusters were more could be observed in the BMSCs cultured under serum deprivation with 20μg/ml, 200μg/ml lidocaine. ConclusionsThe proliferation capacity of the BMSCs cultured in the high glucose DMEM without serum was significantly decreased compared to those cultured in 10% FBS. Lidocaine inhibited the proliferation capacity both of the BMSCs cultured in the high glucose DMEM without serum and with 10% FBS. The results suggest that lidocaine does not exert protective effects on BMSCs in serum deprivation under the high glucose DMEM. Cytotoxicity to lidocaine was maximum at 2000μg/ml. BMSCs cultured under serum deprivation can induce and lidocaine can promote the formation of cell clusters. It is a fascinating point to investigate the relationship between the protective effects and toxicity of lidocaine on BMSCs in high and low glucose microenvironment. It is interested to explore the function and cell characteristics of the cell clusters in a further step of the research work.This research was supported by the grant from Jiangxi Provincial Department of Education, P. R. China (No. GJJ09103). Disclosures:No relevant conflicts of interest to declare.

Reduced Lidocaine Concentration in Tumescent Liposuction: A Report of Efficacy at 400 mg/L

Tumescent liposuction is considered a very safe procedure, but increasing dosages of total lidocaine used in extensive procedures have raised concerns about safety. Multiple cases of fatality probably related to lidocaine toxicity have raised questions about continued performance of liposuction in the office setting; these questions are being evaluated by several state medical boards. We performed a prospective nonblinded evaluation of 100 consecutive tumescent liposuction procedures using the traditional 0.05% lidocaine concentration versus a 0.04% concentration, which theoretically can reduce the total lidocaine dosage by 20% with no evidence of reduced efficacy. We believe that this new dosage could potentially decrease the likelihood of lidocaine-related events, although additional studies are required to confirm our findings.

Viscoanaesthesia in cataract surgery: a prospective, randomized clinical trial

We aimed to compare viscoanaesthesia (VisThesia) with intracameral lidocaine in cataract surgery carried out under topical anaesthesia. In this prospective study 98 patients were randomly assigned to receive VisThesia (group 1, n = 49) or 0.5 cc of 1% unpreserved lidocaine (group 2, n = 49). All surgery was carried out by one surgeon using clear corneal technique. Pachymetry, the status of the cornea and anterior chamber, and intraocular pressure (IOP) were checked pre- and postoperatively. Mean pain scores were 0.12 (maximum: 3) in group 1 and 0.37 in group 2; the difference between the groups was not statistically significant (95% confidence interval [CI] 0.003-0.487; p = 0.05). A total of 48 patients in group 1 (98%) and 49 in group 2 (100%) reported no discomfort or only mild discomfort. No significant differences in flare and cells in the anterior chamber or IOP were found between the two study groups. There was a significantly greater frequency of corneal oedema in group 1 (p = 0.001). Postoperative central corneal thickness values were also significantly higher in group 1 (95% CI 11.64-57.24; p = 0.003). Results suggest that viscoanaesthesia provides a level of comfort during cataract surgery under topical anaesthesia similar to that facilitated by intracameral lidocaine. However, patients who are given viscoanaesthesia may have increased risk for postoperative corneal oedema.

Pharmacokinetics of Anorectal Nifedipine and Lidocaine (Lignocaine) Ointment following Haemorrhoidectomy

This study aimed to assess whether topical anorectal application of an ointment containing nifedipine (0.3% w/w) and lidocaine (lignocaine) [1.5% w/w] to patients undergoing Milligan-Morgan haemorrhoidectomy achieves pharmacologically relevant serum concentrations of the active ingredients and has any haemodynamic effects or adverse effects. A single dose of 3 g of study ointment was circumferentially applied inside the anus to 24 patients (17 males and 7 females) aged 23-71 years (mean +/- SD: 42.9 +/- 4.9 years) during postoperative dressing after Milligan-Morgan haemorrhoidectomy from March 2007 to January 2008. Blood samples for the determination of nifedipine and lidocaine serum concentrations were drawn before surgery and at 20, 40, 60, 90, 120, 240, 360, 480 and 720 minutes after application. Serum concentrations of nifedipine and lidocaine were determined by a high-performance liquid chromatography method in order to calculate pharmacokinetic parameters. Patients' BP, heart rate and ECG readings were monitored during the study. Chromatographic signals of nifedipine were sporadically observed in only five patients (20.8%), consistent with therapeutically negligible concentrations and insufficient to permit calculation of any pharmacokinetic parameters. The serum concentrations of nifedipine in these five patients ranged from 5.9 to 18.8 ng/mL. Lidocaine concentrations were detectable in all patients. The means +/- SD and medians of pharmacokinetic parameters for lidocaine were as follows: maximum serum concentration (C(max)) 245.1 +/- 370.8 ng/mL, 73.6 ng/mL; time to reach C(max) (t(max)) 69.2 +/- 78.3 minutes, 40 minutes; area under the serum concentration-time curve from 0 to 6 hours (AUC(6)) 756.5 +/- 1254.1 ng.h/mL, 238.2 ng.h/mL. Only three patients had maximum serum concentrations above 1000 ng/mL (1037.8, 1044.75 and 1364.1 ng/mL). These outlier concentrations were four to five times lower than the threshold of CNS lidocaine toxicity (5000-6000 ng/mL). No serious local or systemic adverse events were observed throughout the study, and no subjects developed arrhythmias or significant ECG changes. Neither BP nor mean heart rate varied significantly after application of a single dose. This study demonstrates that single-dose topical application of an ointment containing nifedipine (0.3% w/w) and lidocaine (1.5% w/w) to patients undergoing Milligan-Morgan haemorrhoidectomy is safe to use. Following application onto damaged anorectal mucosa, nifedipine and lidocaine are absorbed into the bloodstream in small quantities that do not have any major implications for the safety of the product. Further studies are required to evaluate nifedipine and lidocaine concentrations in serum using a multiple-dose regimen.

Assessment of Local Anesthetic Toxicity Using Cell-Based Assays

Study Objective: Application of local anesthetics (LAs) in minimally invasive gynecology has considerable toxicity. This study was aimed to compare cellular toxicity of bupivacaine (Marcaine®) and lidocaine (Xylocaine®).

Evaluation of Continuous Infusion of Lidocaine on Gastrointestinal Tract Function in Normal Horses

To determine the effect of continuous infusion of lidocaine on fecal transit time in normal horses. Experimental randomized cross-over study. Healthy horses (n=6). Barium-filled microspheres were administered to horses by nasogastric intubation and feces were collected every 2 hours for 4 days. A bolus of 2% lidocaine (1.3 mg/kg) was administered randomly, followed by a continuous infusion of lidocaine (0.05 mg/kg/min) for 3 days or an equivalent volume of saline. The washout period was 10 days. Variables assessed included defecation frequency, weight of feces produced, intestinal transit time (number of microspheres observed on radiographs), fecal moisture content, borborygmus score, heart and respiratory rate, and signs of lidocaine toxicity (e.g., ataxia, CNS depression). During the first 24 hours of lidocaine administration, mean (+/-SD) fecal output (10.8+/-6.9 kg) was decreased compared with controls (15+/-4.9 kg). Mean (+/-SEM) time for passing 50% of the barium-filled microspheres was shorter in controls (42+/-1.13 hours) compared with the lidocaine group (50+/-1.32 hours). Continuous infusion of lidocaine increases the transit time of feces in normal horses. Clinicians need to be aware of the effects of using a continuous infusion of lidocaine on the transit time of feces in normal horses, with a potential for exacerbating those effects when combined with drugs that decrease motility and in horses with medical colic (e.g., impaction) or where a diagnosis has not been made.