Serum Lidocaine Concentrations Research Articles

Pharmacokinetics and Safety of Endotracheal Lidocainefor Endotracheal Intubation in Critically Ill Children.

Critically ill pediatric patients are endotracheally intubated in pediatric intensive care units for a variety of illnesses and indications. Management of an endotracheal tube (ETT) requires suctioning to remove patient secretions and prevent occlusion, but this practice can be associated with adverse events, such as hemodynamic deterioration or increases in intracranial pressure. Instillation of lidocaine into the ETT before suctioning may be beneficial in preventing these events. The purpose of this phase I, fixed-dose, open-label pharmacokinetic and safety study, conducted in endotracheally intubated and mechanically ventilated infants and children requiring ETT suctioning, was to determine the serum concentrations and safety of lidocaine after ETT administration. A total of 21 infants and children meeting inclusion criteria received a single dose of ETT lidocaine per institutional protocol. Blood samples were obtained pre-dose and at 5, 10, 30, and 120 minutes after administration for serum concentration analysis. Lidocaine dosing was driven by weight and age, with infants and children aged > 38 weeks' estimated gestational age and <3 years receiving 0.5 mg/kg/dose (maximum: 20 mg/dose) and children aged 3-18 years receiving 1mg/kg/dose (maximum: 100 mg/dose). No subjects aged <3 years had detectable serum lidocaine concentrations. Four subjects in the group aged ≥ 3 years had detectable serum lidocaine concentrations at 5, 10, and/or 30 minutes, but no serum concentrations were within the toxic range. No adverse effects, such as cough, bronchospasm, seizure activity, or clinically significant depression of cardiac or respiratory function, were noted in any subjects. Pharmacokinetic sampling showed that only 4 of 21 subjects had detectable serum lidocaine concentrations and none were within the toxic range. The safety of ETT administration of lidocaine in endotracheally intubated infants and children requiring ETT suctioning was demonstratedat the doses used in this study. The study was conducted at Norton Children's Hospital. The research team confirmed that this study was not registered with clinicaltrials.gov.

A case of a lidocaine intoxication of a 12 week old boy due to a circumcision in a domestic setting - clinical, toxicological and forensic aspects.

Lidocaine is a local anaesthetic commonly used during circumcision for dorsal penile nerve block (DPNB). We describe a case of a 12-week-old infant who presented generalized seizures due to local anesthetic systemic toxicity after Lidocaine administration for circumcision in a non-hospital setting. Serum concentrations of Lidocaine (16.4mg/L) and its main active metabolite monoethylglycinexylidide (MEGX, 1.36mg/L) were determined by HPLC-DAD, in a sample collected shortly after administration, which were higher than in comparable cases reported in literature. The reason for the overdose was assumed to be accidental systemic application. Due to suspicion of an improperly performed circumcision and bodily harm, police was involved and a clinical forensic examination was carried out. Here, we present analytical, clinical and forensic aspects of this case.

Serum Lidocaine Levels in Adult Patients Undergoing Cardiac Surgery With del Nido Cardioplegia

BackgroundLidocaine in del Nido cardioplegia solution prolongs the refractory period of cardiomyocytes, yielding a longer arrest per dose. Serum lidocaine concentrations >8 mg/L are associated with seizure and cardiotoxicity. We evaluated serum lidocaine concentrations in patients receiving del Nido solution during cardiac surgery. MethodsForty consecutive patients undergoing cardiac surgical procedures with del Nido cardioplegia were selected for serum lidocaine concentration measurements determined immediately after aortic cross-clamp removal. Variables included weight, body surface area, operation, cardiopulmonary bypass time, aortic cross-clamp time, and total volume of del Nido solution. The primary outcome was serum lidocaine concentration relative to total volume of del Nido solution. Descriptive statistics and Pearson correlations were computed. ResultsMedian weight was 78.3 kg (range, 43-132.4 kg), and mean body surface area was 1.9 ± 0.2 m2. Operations included coronary artery bypass grafting (n = 26 [65%]), a combination procedure (n = 5 [12.5%]), isolated mitral valve repair or replacement (n = 4 [10%]), isolated aortic valve replacement (n = 3 [7.5%]), and aortic repair or replacement (n = 2 [5%]). Median total volume of del Nido solution was 1870 mL (range, 800-5800 mL). Mean serum lidocaine concentration was 2.2 ± 0.6 mg/L. Serum lidocaine concentration was weakly correlated with del Nido solution volume (R2 = 0.21). The highest total volume of del Nido solution (5800 mL) did not yield the highest serum lidocaine concentration of 3.5 mg/L. ConclusionsSerum lidocaine concentration during cardiac surgical procedures weakly correlates with the volume of del Nido solution used and does not reach toxic levels even at high doses of del Nido solution. The results of this study may help alleviate concerns for lidocaine toxicity with high doses of del Nido solution.

Examination of the Rate and Extent of Drug Released from Commercial Topical Delivery Systems During Wear: An Example with Lidocaine Topical Systems.

This study aimed to determine the extent and rate of lidocaine released in vivo from two bioequivalent topical delivery systems (TDS) by using complementary assessments: pharmacokinetic analysis in healthy human volunteers, and residual lidocaine in TDS following 12h of wear. The goal was to explore a potentially more clinically meaningful strength presentation than percent active pharmaceutical ingredient loaded in topical systems. A three-arm, open-label, crossover clinical study was conducted in 23 human subjects, with 5% lidocaine topical systems from two manufacturers, and intravenous lidocaine administration. Residual drug and LC-MS/MS analyses were performed on worn TDS and serum samples. The rate and extent of drug released from the TDS during wear were determined through (1) calculations of consumed lidocaine via analysis of residual drug in worn TDS, and (2) a pharmacokinetic approach via derivation of the absolute clearance and serum lidocaine concentration at steady state. Overall the pharmacokinetic approach underestimated the amount transferred to the subject and exhibited greater variability, which may relate to natural inter-subject variability in pharmacokinetic parameters. Further, lidocaine TDS are intended for localized, not systemic, delivery and this may also explain some of the variability seen in the systemic serum concentrations. The residual drug and pharmacokinetic approaches align well for transdermal formulations, but the differences in administration route (topical versus transdermal) all but eliminates the potential use of the pharmacokinetic approach unless additional compartmental modeling is explored.

Effectivity of Intravenous Lidocaine in Pain of Neuropathic Origin

Background: In order to accomplish the goals of this research project, lidocaine was administered intravenously (IV) to patients who were experiencing neuropathic pain. The researchers had an interest in gaining a deeper understanding of the connections that exist between effect and concentration, as well as graded and quanta1 dose-response. Study Place: Kulsoom International Hospital Islamabad Study Duration: 6months (Feb 2021 To July 2021) Methods and Materials: Fifteen patients received an intravenous dose of lidocaine at a rate of 8.35 milligrams per minute for a total of one hour. During the course of the study, both venous blood samples and visual analog pain scores were collected at regular intervals of ten minutes for duration of sixty minutes. In addition, blood samples were taken in order to determine the concentrations of lidocaine in the serum as well as the amount of water in the serum both at the start of the analgesia as well as when the patient had reached their maximum level of pain relief. In order to determine the levels of lidocaine, a technique known as gas chromatography was performed. Result: In addition to graded dose-response curves for each participant and the group, a quanta1 dose-response curve was created. Besides graded dose-response curves, this was done. Also done: graded dose-response curves. The dose-response relationship for IV lidocaine showed large pain relief for modest dose changes. Despite moderate dosage increases, this was true. This was when the drug was given. The ED administered 370.0 mg of lidocaine, but the ED administered 415.5 mg (5 min of infusion). Similar to the link between concentration and effect, 0.60 pg/mL of lidocaine significantly reduced pain. It's intriguing that serum lidocaine concentration didn't correlate better with analgesia onset or end than free lidocaine concentration did. Free lidocaine concentration correlated with analgesic effect. Lidocaine concentration in the serum was a stronger predictor of analgesia. Conclusion: This suggests that IV lidocaine's analgesic mechanism may not follow a concentration-effect connection. The evidence shows this. Intravenous lidocaine is significantly stronger than oral. The analgesic response to intravenous lidocaine is a quick "break in pain" over a narrow dosage and concentration range. This was true independent of lidocaine dose. It doesn't matter how much lidocaine is given.

MP37-14 A DOSE-ESCALATING PHASE I STUDY OF AN INJECTION OF LIDOCAINE PASTE FOR PROLONGED SPERMATIC CORD BLOCK IN MEN WITH CHRONIC SCROTAL CONTENT PAIN

You have accessJournal of UrologyCME1 May 2022MP37-14 A DOSE-ESCALATING PHASE I STUDY OF AN INJECTION OF LIDOCAINE PASTE FOR PROLONGED SPERMATIC CORD BLOCK IN MEN WITH CHRONIC SCROTAL CONTENT PAIN Luke Witherspoon, Claudia Kesch, Veronika Schmitt, Graeme Boniface, Colin Lundeen, J. Curtis Nickel, Ryan Paterson, Martin Gleave, and Ryan Flannigan Luke WitherspoonLuke Witherspoon More articles by this author , Claudia KeschClaudia Kesch More articles by this author , Veronika SchmittVeronika Schmitt More articles by this author , Graeme BonifaceGraeme Boniface More articles by this author , Colin LundeenColin Lundeen More articles by this author , J. Curtis NickelJ. Curtis Nickel More articles by this author , Ryan PatersonRyan Paterson More articles by this author , Martin GleaveMartin Gleave More articles by this author , and Ryan FlanniganRyan Flannigan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002591.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Spermatic cord block with local anesthetics provides pain relief in a subset of subjects with chronic scrotal content pain (CSCP), but relief is short-lived due to the rapid elimination of local anesthetics. This Phase I trial assessed the safety, tolerability, pharmacokinetics and efficacy of a long-acting formulation of lidocaine in patients with CSCP. METHODS: This was a prospective, single center, open label, single arm, Phase I dose-escalating trial. Male patients ≥19 years with unilateral scrotal pain lasting ≥3 months who reported an average daily maximum pain score over 7 days of ≥4 on a 0-10 numerical rating scale (NRS) were recruited. The investigational drug ST-01 (sustained-release lidocaine polymer solution for injection) is a long-acting lidocaine injected into the spermatic cord. ST-01 has two inactive ingredients, polyethylene glycol (PEG) and poly(lactic-co-glycolic acid) (PLGA) which slow the release of lidocaine. The study had 3 planned dose-escalating cohorts: cohort I: 2 mL of 140 mg/mL ST-01 (280 mg lidocaine); cohort II: 3 mL of 140 mg/mL ST-01 (420 mg lidocaine); cohort III: 4 mL of 140 mg/mL ST-01 (560 mg lidocaine). Subjects recorded their pain (NRS) three times a day on days 0–14, and once on days 15-27 of the study. The Chronic Epididymitis Symptom Index (CESI) was completed by patients on days 0, 7, 14, and 28 (end of study). RESULTS: Twenty subjects were screened, with 12 subjects being enrolled. NRS (mean, median) was reduced across all cohorts studied. Patients in cohort II (420 mg lidocaine) were identified via the dose escalation protocol. This group reported a baseline mean (median) NRS score of 5.3 (5), compared to an end of study score of 3.3 (3.5). Assessment of CESI score showed reduced scores over the study period with cohort II reporting a baseline mean (median) score of 19.8 (19) and an end of study value of 16.8 (17.5). Serum lidocaine concentrations were measured at 1 hour, 1 day and 7 days. Serum concentrations were similar across all cohorts at day 1 indicating only local release of the medication. There were no serious adverse events (SAE’s) reported in the study. All subjects reported at least one treatment-emergent adverse event (TEAE). Most TEAE’s were mild or moderate and related to bruising or swelling at the injection site. CONCLUSIONS: ST-01 was safely injected in 12 subjects suffering from CSCP with a promising efficacy signal. Source of Funding: This study was conducted with aid from the Vancouver Coastal Health Research Institute Translation and Innovation Award © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e614 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Luke Witherspoon More articles by this author Claudia Kesch More articles by this author Veronika Schmitt More articles by this author Graeme Boniface More articles by this author Colin Lundeen More articles by this author J. Curtis Nickel More articles by this author Ryan Paterson More articles by this author Martin Gleave More articles by this author Ryan Flannigan More articles by this author Expand All Advertisement PDF DownloadLoading ...

Dramatic Response to Lidocaine Infusion for Pain from Brachial Plexus Avulsion Injury

BACKGROUND: Traumatic brachial plexus avulsion injury (tBPI) can cause a severe chronic pain syndrome that is very difficult to treat. Though lidocaine has been shown to be effective for other pain syndromes, effectiveness in tBPI has not previously been reported. CASE REPORT: A 55-year-old man with tBPI had severe pain and minimal relief with numerous analgesic agents. He was able to access intravenous lidocaine as he was being treated at a cancer center, and had a sustained response to 7 mg/kg given over an hour. CONCLUSION: There is potential for a single bolus intravenous lidocaine infusion to provide good pain control sustained over many months in patients with traumatic brachial plexus injury. An adequate serum concentration of lidocaine is required for analgesic effect. If initial doses of lidocaine are tolerated but ineffective, higher doses may still be beneficial. KEY WORDS: Brachial plexus avulsion, lidocaine, lignocaine, pain management, palliative care, therapeutics, trauma

Systemic Absorption of Lidocaine from Continuous Erector Spinae Plane Catheters After Congenital Cardiac Surgery: A Retrospective Study

To examine postoperative serum lidocaine levels in patients with intermittent lidocaine bolus erector spinae plane block (ESPB) catheters after cardiac surgery with or without cardiopulmonary bypass (CPB). A retrospective study. Single-center pediatric quaternary teaching hospital. Patients who received ESPB catheters after congenital cardiac surgery from April 2018 to March 2019. Postoperative serum lidocaine levels were extracted from the record. Twenty-seven of 40 patients were included in the final analyses (19 with CPB and 8 with no CPB, age 1-47 years, undergoing congenital heart repair). Patients who received ropivacaine or were missing data were excluded. The initial intraoperative bolus of lidocaine ranged from 0- to- 3.72 mg/kg, and the range of postoperative intermittent lidocaine boluses ranged from 0.35- to- 0.83 mg/kg, which were administered every hour. Serum lidocaine levels were measured by the hospital laboratory and ranged from <0.05- to- 3.0 μg/mL in the CPB group and from <0.05- to- 3.2 μg/mL in the no- CPB group. CPB was not associated with differences in lidocaine levels when controlling for time (P = 0.529). Lidocaine concentrations ranged from 0.50- to- 1.68 μg/mL in the CPB group and 0.86- to- 2.07 μg/mL in the no- CPB group. There was a normally distributed overall mean peak level of 1.818 ± standard deviation of 0.624 μg/mL, with 95% confidence interval of 0.57- to- 3.06 μg/mL. No patients had clinical signs of toxicity. Postoperative serum lidocaine concentrations did not appreciably differ due to CPB. Serum lidocaine concentrations did not reach near- toxic doses despite the presence of additional lidocaine in the cardioplegia. The results suggested that lidocaine for ESPBs after cardiac surgery is below systemic toxic range at the doses described.

Rectus sheath single-injection blocks: a study to quantify local anaesthetic absorption using serial ultrasound measurements and lidocaine serum concentrations.

Rectus sheath blocks are an established option for analgesia following abdominal surgery, but pharmacokinetic data are limited. This study sought to characterise the absorption of lidocaine injectate and the pharmacokinetics of lidocaine after rectus sheath injection. Bilateral rectus sheath single-injection blocks were given to 10 patients undergoing general or urological surgery. Afterwards, serial lidocaine serum levels and ultrasound measurements of the rectus sheath injectate reservoir were collected. Injectate within the rectus sheath was visible with ultrasound up to 12h after injection. However, the rate of drug absorption exceeded that of injectate disappearance. Peak serum concentration occurred within 30min with average peak concentrations of 1.65μg/ml. Lidocaine clearance was lower than reported in young healthy subjects. The body mass index positively correlated with lidocaine terminal phase half-life, and clearance negatively correlated with age. The study provides the first data describing lidocaine pharmacokinetics after rectus sheath injection. Peak serum concentrations transiently achieved systemic levels associated with pain relief after a single bolus injection. The data from this study could be used to develop a regime using single shot rectus sheath blockade with a bolus of lidocaine followed by infusion using bilateral rectus sheath catheters.

Cardiovasculaire, respiratoire, gastro-intestinale en gedragseffecten van intraveneuze lidocaïnetoediening bij gezonde paarden bij bewustzijn en evaluatie van de relatie met serumconcentraties van lidocaïne en mono-ethylglycinexylidide

Deze studie had als doel de relatie te bepalen tussen de serumconcentraties van lidocaïne/monoethylglycinexylidide (MEGX) en hun effect op de verschillende lichamelijke stelsels bij het paard. Vijf gezonde paarden bij bewustzijn kregen een twee uur durende placebo-intraveneuze infusie gevolgd door een twee uur durende lidocaïne-infusie (bolus van 1,3 mg/kg in tien minuten gevolgd door een constante infusie van 0,05 mg/kg/min). De lidocaïne- en MEGX-serumconcentraties werden om de tien à vijftien minuten gemeten. Het evenwichtsverlies, de spiertrillingen, het ademhalings-, spijsverterings- en cardiovasculaire stelsel werden beoordeeld met behulp van verschillende niet-invasieve methoden. Tijdens de toediening van de lidocaïne-infusie was de gemiddelde (± standaarddeviatie) lidocaïne- en MEGXconcentratie respectievelijk 768,88 ± 93,32 ng/ml en 163,08 ± 108,98 ng/ml. De toediening van een lidocaïne- infusie beïnvloedde significant de aanwezigheid van trillen. Ook veroorzaakte ze een statistisch maar niet-klinisch significante afname van de systolische en diastolische bloeddruk, die beide correleerden met de lidocaïne- en MEGX-serumconcentratie. Verder verhoogde ze eveneens de duodenale contractiefrequentie, die correleerde met de serumlidocaïne-concentratie. In de voorliggende studie werden milde hypotensieve en prokinetische kortetermijneffecten van een lidocaïne-infusie waargenomen.

Usage of Intravenous Lidocaine Infusion with Enhanced Recovery Pathway in Patients Scheduled for Open Radical Cystectomy: A Randomized Trial

Background: Intravenous lidocaine infusion (IVLI) reduces postoperative pain and hastens the return of bowel function. Objectives: We aimed to compare the effects of adding lidocaine infusion to enhanced recovery pathway (ERP) on acute rehabilitation protocol. Study Design: This study uses a double-blind, randomized design with allocation concealment in a 2-armed parallel group format among patients undergoing open radical cystectomy (RC). Setting: The study was conducted at Assiut University Hospital, Asyut, Egypt. The study duration was March 2017 to July 2018. Methods: After ethics committee approval, 111 patients, American Society of Anesthesiologists (ASA) physical status II-III, aged 45-65 years, scheduled for open RC with urinary diversion under an ERP, were randomly selected in a double-blind manner to receive IVLI 2 mg/minute for 4 hours or an equal volume of normal saline solution 0.9%. Postoperative pain scores, rescue analgesic consumption, times to return of bowel sounds, first flatus, first defecation, resuming of regular diet, length of hospital stay, in-hospital complications, and patient satisfaction were recorded. Results: Patients in the lidocaine group experienced significantly lower pain scores after surgery at 6 hours (P = 0.005) and 12 hours (P = 0.001) at rest, and in the first 18 hours during mobilization (P &lt; 0.05), with less paracetamol (P = 0.04) and meperidine (P = 0.02) consumption than in the control group. Between the lidocaine and the control group, mean times to return of bowel sounds (23.7 vs. 26.7 hours; P = 0.001), first flatus (76.5 vs. 86.5 hours; P = 0.001), first defecation (92.7 vs. 106.9 hours; P = 0.001) and resuming of regular diet (80.7 vs. 92.8 days; P = 0.001) were significantly shorter in the lidocaine group. Length of hospital stay, in-hospital complications, and patient satisfaction were similar in both groups. Limitations: Limitations of this study include lack of previous research that compare the additive effects of IVLI to ERP in patients undergoing open RC. Also, the inability to measure the serum lidocaine concentration in our patients. Conclusions: Adding IVLI to ERP improved postoperative analgesia and bowel function after open RC with urinary diversion. Clinical trial registration: NCT03047057. Key words: Lidocaine infusion, ileus, enhanced recovery pathway, acute rehabilitation, open radical cystectomy

Serum Concentrations of Lidocaine During Bariatric Surgery

Lidocaine has been shown to be clinically beneficial during bariatric surgery. However, information about lidocaine serum concentrations in this setting is scarce. This prospective clinical trial included 42 obese patients undergoing laparoscopic bariatric surgery. They received lidocaine based on adjusted body weight. Administration began with a 1.5 mg·kg bolus of intravenous lidocaine followed by a continuous infusion of 2 mg·kg·hour. After skin closure, administration was decreased to 1 mg·kg·hour until discharge from the recovery room. No serum concentrations of lidocaine were outside the usual accepted range (1.5-5 µg·mL).

The Effect of Dexmedetomidine on Oral Mucosal Blood Flow and the Absorption of Lidocaine

Dexmedetomidine (DEX) is a sedative and analgesic agent that acts via the alpha-2 adrenoreceptor and is associated with reduced anesthetic requirements, as well as attenuated blood pressure and heart rate in response to stressful events. A previous study reported that cat gingival blood flow was controlled via sympathetic alpha-adrenergic fibers involved in vasoconstriction. In the present study, experiment 1 focused on the relationship between the effects of DEX on alpha adrenoreceptors and vasoconstriction in the tissues of the oral cavity and compared the palatal mucosal blood flow (PMBF) in rabbits between general anesthesia with sevoflurane and sedation with DEX. We found that the PMBF was decreased by DEX presumably because of the vasoconstriction of oral mucosal vessels following alpha-2 adrenoreceptor stimulation by DEX. To assess if this vasoconstriction would allow decreased use of locally administered epinephrine during DEX infusion, experiment 2 in the present study monitored the serum lidocaine concentration in rabbits to compare the absorption of lidocaine without epinephrine during general anesthesia with sevoflurane and sedation with DEX. The depression of PMBF by DEX did not affect the absorption of lidocaine. We hypothesize that this is because lidocaine dilates the blood vessels, counteracting the effects of DEX. In conclusion, despite decreased palatal blood flow with DEX infusion, local anesthetics with vasoconstrictors should be used in implant and oral surgery even with administered DEX.

Tumescent anaesthesia: its applications and well tolerated use in the out-of-operating room setting.

Tumescent anaesthesia is a method of administering dilute local anaesthetic into the subcutaneous tissue. Many anaesthesiologists are unfamiliar with the technique, its applications and potential risks. The maximum safe dose of lidocaine with epinephrine in tumescent anaesthesia for liposuction is probably between 35 and 55 mg/kg. Without liposuction, the maximum dose of lidocaine with epinephrine should be no more than 28 mg/kg. After tumescent infiltration for liposuction, serum lidocaine concentrations peak between 12 and 16 h after injection. When tumescent lidocaine without epinephrine is used for endovenous laser therapy, peak serum lidocaine concentrations are observed much earlier, between 1 and 2 h after injection. Slow administration of more dilute concentrations of local anaesthetic decreases the risk of local anaesthetic systemic toxicity. Although appealing because of its ability to provide prolonged analgesia, high doses of local anaesthetic are frequently administered using the tumescent technique, and absorption of local anaesthetic from the subcutaneous tissue is variable. When caring for patients having procedures in which tumescent anaesthesia is used, the risk of local anaesthetic toxicity should be acknowledged and lipid emulsion should be available for prompt treatment if needed.

Continuous bilateral thoracic paravertebral blockade for analgesia after cardiac surgery: a randomised, controlled trial.

Continuous bilateral thoracic paravertebral blockade has been used for analgesia after cardiac surgery, but its efficacy has never been formally tested. Fifty adult patients were enrolled in a double-blind, randomised, controlled study of continuous bilateral thoracic paravertebral infusion of 0.5% lidocaine (1 mg.kg-1.hr-1) for analgesia after coronary surgery. Control patients received a subcutaneous infusion of lidocaine at the same rate through catheters inserted at the same locations as the study group. The primary outcome was morphine consumption at 48 hours using patient-controlled analgesia (PCA). Secondary outcomes included pain, respiratory function, nausea and vomiting. Serum lidocaine concentrations were measured on the first two post-operative days. There was no difference in morphine consumption or in any other outcome measure between the groups. Serum lidocaine concentrations increased during the study, with a maximum of 5.9 mg.l-1. There were no adverse events as a consequence of the study. Bilateral paravertebral infusion of lidocaine confers no advantage over systemic lidocaine infusion after cardiac surgery. ISRCTN13424423 ( https://www.isrctn.com ).

The analgesic efficacy of intravenous lidocaine infusion after laparoscopic fundoplication: a prospective, randomized, double-blind, placebo-controlled trial.

This study aimed to determine if intravenous lidocaine infusion reduces postoperative pain intensity following laparoscopic fundoplication surgery and to also validate the safety of intravenous lidocaine at the dose tested. This was an equally randomized, double-blind, placebo-controlled, parallel-group, single center trial. Adult patients undergoing laparoscopic fundoplication were recruited. The intervention group received 1 mg/kg intravenous lidocaine bolus prior to induction of anesthesia, then an intravenous infusion at 2 mg/kg/h for 24 hours. The primary outcome was pain, measured using a numeric rating scale for 30 hours postoperatively. Secondary outcomes were nausea and vomiting, opioid requirements, adverse events, serum lidocaine concentration, and length of hospital stay. The study was terminated after an interim analysis of 24 patients showed evidence of futility. There was no difference in postoperative pain scores (lidocaine versus control, mean ± standard deviation) at rest (2.0 ± 2.7 vs 2.1 ± 2.4, P=0.286) or with movement (2.0 ± 2.6 vs 2.6 ± 2.7, P=0.487). Three adverse events occurred in the lidocaine group (25% of patients). Intravenous lidocaine did not provide clinically significant analgesia to patients undergoing laparoscopic fundoplication. The serum lidocaine concentration of patients who experienced adverse events were within the therapeutic range. This trial cannot confirm the safety of intravenous lidocaine at the dose tested.

Effect of Injection Pressure of Infiltration Anesthesia to the Jawbone.

To obtain effective infiltration anesthesia in the jawbone, high concentrations of local anesthetic are needed. However, to reduce pain experienced by patients during local anesthetic administration, low-pressure injection is recommended for subperiosteal infiltration anesthesia. Currently, there are no studies regarding the effect of injection pressure on infiltration anesthesia, and a standard injection pressure has not been clearly determined. Hence, the effect of injection pressure of subperiosteal infiltration anesthesia on local anesthetic infiltration to the jawbone was considered by directly measuring lidocaine concentration in the jawbone. Japanese white male rabbits were used as test animals. After inducing general anesthesia with oxygen and sevoflurane, cannulation to the femoral artery was performed and arterial pressure was continuously recorded. Subperiosteal infiltration anesthesia was performed by injecting 0.5 mL of 2% lidocaine containing 1/80,000 adrenaline, and injection pressure was monitored by a pressure transducer for 40 seconds. After specified time intervals (10, 20, 30, 40, 50, and 60 minutes), jawbone and blood samples were collected, and the concentration of lidocaine at each time interval was measured. The mean injection pressure was divided into 4 groups (100 ± 50 mm Hg, 200 ± 50 mm Hg, 300 ± 50 mm Hg, and 400 ± 50 mm Hg), and comparison statistical analysis between these 4 groups was performed. No significant change in blood pressure during infiltration anesthesia was observed in any of the 4 groups. Lidocaine concentration in the blood and jawbone were highest 10 minutes after the infiltration anesthesia in all 4 groups and decreased thereafter. Lidocaine concentration in the jawbone increased as injection pressure increased, while serum lidocaine concentration was significantly lower. This suggests that when injection pressure of subperiosteal infiltration anesthesia is low, infiltration of local anesthetic to the jawbone may be reduced, while transfer to oral mucosa and blood may be increased.

Changes of lidocaine concentration and physiological indices in dogs during anaesthesia with lidocaine and isoflurane combined with ketamine or fentanyl

Fentanyl and ketamine are often used as adjuvants in intravenous anaesthesia to prolong analgesia. The aim of this study was to compare changes of the basic physiological variables of intravenous lidocaine administration in combination with ketamine or fentanyl, and to evaluate the impact of addition of fentanyl or ketamine to lidocaine on serum lidocaine concentrations in dogs after intravenous administration. During general anaesthesia, dogs of group L received 2% lidocaine intravenously, dogs of group LF received 2% lidocaine and fentanyl, and dogs of the group LK received 2% lidocaine and ketamine. The heart rate, systolic arterial pressure, diastolic arterial pressure, mean arterial pressure and rectal temperature decreased in all groups, and group LF showed the biggest effect on the basic physiological variables, with the lowest heart rate during the test, significantly decreased rectal temperature, and the most decreased values of arterial pressure. Blood for determination of serum lidocaine concentration was taken before anaesthesia and 5, 30, 60, 90, 120, 150 and 180 min after initial intravenous injection of drugs. Fentanyl and ketamine did not cause significant changes of serum lidocaine concentration in dogs and may be used as adjuvant in intravenous anaesthesia without a significant increase in lidocaine absorption.

Glasgow Coma Scale Improvement after Lidocaine Infusion in Moderate Traumatic Brain Injury

Since the Glasgow Coma Scale was developed 40 years ago it has been accepted throughout the world as a method for assessing impaired consciousness. Fourty moderate TBI patients were simple randomly divided into 2 groups: group A take normal saline infusion without lidocaine as control group (N=20), and group B take normal saline with lidocaine at rate 1 mg/kg/BW infusion as treated groups (N=20). Serum samples were collected at before induction and 2 hours after giving infusion treatment to measure serum IL-6 and PLA2 level, and lidocaine serum concentration. GCS were measured before induction and after 24 hours surgery. Data were analyzed using analytic statistic with paired t test to measure serum IL-6, PLA2, & lidocaine serum level before induction and after 2 hours. The correlation of serum IL-6, PLA2 and GCS was measure with Separman correlation. A P value less than 0.05 were considered significant. The result are both serum IL-6 and PLA2 levels were significantly lower in saline with lidocain infusion group (p<0.005) with Mann Whitney and Dependent t test statistically analyses. The lower serum IL-6 and PLA2 levels, the higher GCS value. GCS measurement was significantly higher in lidocaine infusion group (p<0.05) with dependent t test. The decrese in serum IL-6 and PLA2 was correlated with the dosage of lidocaine. Medium doses of lidocaine achieved the optimum decreases in the serum IL 6 and PLA2 level. Therefore, inhibition of the composition and secretion of IL-6 and PLA2 levels by Lidocaine might be one of the mechanisms involved in decreasing inflammatory reaction and cellular damage in brain cells, and may be responsible for the neuroprotective effect after TBI. Glasgow Coma Scale was improving after infusion with lidocaine 1 mg/ kg/ hr during traumatic brain injury surgery by decreasing IL-6 and PLA2 plasm.

Neurological syndrome with acute dysesthesia and confusion during epidural anesthesia for a caesarian section. Blood concentrations of local anesthetics were considered non-toxic

Introduction Overdoses of local anesthetics (LA) are well-known to induce neurological or cardiologic symptoms such as convulsions, confusion, cardiac arrhythmia and cardiac failure. In most cases, LA diffuse out of a catheter used for loco-regional administration into the bloodstream. Severe side effets are observed when blood concentrations reach toxic levels. We report a case of neurological syndrome after epidural administration of lidocaine and ropivacaine at usual doses for a caesarian section. The symptoms fortunately resolved. A few minutes after the beginning of the incident, a blood sample was taken to assay the LA levels. Case The patient was a 37-year-old woman, primipara, with a history of Crohn's disease and endometriosis. The pregnancy was normal, bit the decision to perform a ceasarian section was made after an episode of fetal bradycardia. Regional anesthesia on D1 at 5:45 pm, with epidural LA: ropivacaine 0.2%, 10 mL and lidocaine 2%, 15 mL. The procedure took place normally without evidence of extravasation. The child was born with normal behavior (Apgar score 10/10 at 1 and 5 min). after the birth, the mother complained of dysarthria, dusfunction of taste and labial dysesthesia. The, she exhibited dizziness and e few upper limb clonic seizures, immediately followed by relative agitation without loss of consciousness. A blood sanple was taken just before the injection of Intralipid ® (soybena oil) and analyzed by GC-MS. Results Serum lidocaine concentration was 1.5 mg/L and ropivacaine 0.10 mg/L. The lidocaine concentration range considered as non-toxic in cardiology is 1.5–6 mg/L. Intralipid ® perfusion accelerated the rapid regression of symptoms. No other cardiac or vascular sign was reported. An MRI was done, which was normal and ruled out a stroke. Discussion The elimination half-life (T1/2 e ) of lidocaine (α = 0.5 h; s = 1–2 h) and ropivacaine (1.8 h) could not explain higher blood concentrations at the time of surgery. Reported toxic blood concentrations for lidocaine are > 6 mg/L. Unfortunately, we did not assay the LA-fractions. There was non-associated medication, including sedatives, morphinomimetics, antibiotics and NSAIDS that could have increased the LA-free fraction after IV injection. Other authors found various cases of LA side effects with the usual dosage and in the absence of extravasation [1] . The LA levels were also within the therapeutic range [2] . Conclusion The acute neurological side effects induced by LA could occur at the therapeutic dosage, with blood concentrations within the usual therapeutic values.