Evaluation of the plasmatic level of mepivacaine in different anatomical regions.

BACKGROUND: To evaluate the serum level of the local anesthetic mepivacaine 3% without vasoconstrictor in patients who underwent procedures performed in the anterior and posterior maxilla, through a method of possible extraction to quantify it in human plasma by high performance liquid chromatography (HPLC). MATERIAL AND METHODS: This was a hybrid study consisting of 18 patients (7 females and 11 males) classified as ASA I, adults and with normal body mass index, submitted to procedures in the anterior region (group I) and posterior region of the maxilla (group II). For 40 minutes, five 6 ml blood samples were collected every 10 minutes after infiltrative injection in each region of the maxilla. Serum levels of the drug were obtained through HPLC. Blood pressure (BP) and heart rate (HR) were measured throughout the procedure. RESULTS: When compared to the general average of the concentrations of each group, significant values (p <0.05) with greater absorption were observed for the anterior region of the maxilla (group I). There was no significant difference when comparing blood pressure (BP) and heart rate (HR) values. CONCLUSIONS: The concentrations found are safe for infiltrative anesthesia in the analyzed patients, there was a higher plasma level of the local anesthetic in the anterior region of the maxilla and there was no change in HR and BP in relation to the anesthetized area.

Chemiluminescence Determination of Local Anaesthetic Mepivacaine in Human Plasma and Pharmaceuticals.

In this study, a new method has been developed for the simple determination of mepivacaine (carbocaine). The method is based on the enhancement effect of mepivacaine in the chemiluminescence (CL) reaction of tris(1,10 phenanthroline) ruthenium(II) with cerium(IV). A mechanism for the CL reaction has been proposed on the basis of UV-Vis, fluorescent and CL spectra. Under optimum conditions, the CL intensity was proportional to the concentration of the drug in solution over the range 0.45-226.25 µg mL-1 (R2 = 0.9996). The LOD was 0.34 µg mL-1 (S/N = 3). LOD was about 10 times lower than the therapeutic concentration of mepivacaine. The percent of relative standard deviation for determination of 11 replicates at level of 9.05 µg mL-1 and 90.50 µg mL-1 of mepivacaine were 1.8 and 3.7%, respectively. The proposed method was applied successfully for the determination of mepivacaine in human plasma and injectable solutions.

Molecularly imprinted polymer in microextraction by packed sorbent for the simultaneous determination of local anesthetics: lidocaine, ropivacaine, mepivacaine and bupivacaine in plasma and urine samples.

This study presents the use of molecularly imprinted polymer (MIP) as packing material for microextraction by packed syringe (MEPS) to achieve higher extraction selectivity. Pentycaine was used as template for MIP. Development and validation of the determination of lidocaine, ropivacaine, mepivacaine and bupivacaine in human plasma and urine samples utilizing MIP-MEPS and liquid chromatography-tandem mass spectrometry (LC-MS/MS) were carried out. The MEPS MIP-cartridge could be used for 100 extractions before it was discarded. The extraction recovery ranged from 60 to 80%. The correlation coefficients values were >0.999 for all assays using lidocaine, ropivacaine, mepivacaine and bupivacaine in the calibration range 5-2000 nmol/L. The accuracy of the studied compounds, given as a percentage variation from the nominal concentration values, ranged from -4.9 to 8.4% using plasma and urine samples. The between-batch precision, given as the relative standard deviation, at three different concentrations (quality control samples) was ranged from -4.7 to 14.0% and from 1.8 to 12.7% in plasma and urine, respectively. The lower limit of quantification and limit of detection of the studied substances were 5.0 and 1.0 nm, respectively.

Intravenous lipid emulsion only minimally influences bupivacaine and mepivacaine distribution in plasma and does not enhance recovery from intoxication in pigs.

BACKGROUND: The reported successful use of IV lipid emulsions in local anesthetic intoxications is thought to be due to lipid sequestration of local anesthetics. However, controlled efficacy studies were lacking, and other mechanisms of action have also been suggested. We investigated the effect of lipid infusion on plasma concentrations and cardiovascular effects of 2 local anesthetics differing in lipophilicity, bupivacaine, and mepivacaine. METHODS: Bupivacaine (n = 20) or mepivacaine (n = 20) was infused into a central vein of anesthetized (isoflurane 1%, Fio(2) 0.21) pigs until mean arterial blood pressure decreased to 50% from baseline. Isoflurane was discontinued and Fio(2) was increased to 1.0. Ten pigs in each local anesthetic group were treated with 20% lipid emulsion (ClinOleic®), and 10 pigs with Ringer's solution: 1.5 mL/kg in 1 minute followed by an infusion of 0.25 mL · kg(-1) · min(-1) for 29 minutes. Five additional pigs were infused bupivacaine and Intralipid®. Total and nonlipid-bound local anesthetic concentrations were determined from repeated blood samples. RESULTS: There were no overall differences in total or nonlipid-bound plasma local anesthetic concentrations between the lipid and Ringer's groups. However, plasma median total bupivacaine concentration was 21% and 23% higher at 20 and 30 minutes, respectively, in the lipid group (P = 0.016 without Holm-Bonferroni correction). There was also no overall difference between lipid and Ringer's groups in the rate of recovery of hemodynamic and electrocardiographic variables. Median mean arterial blood pressure in the lipid group with bupivacaine intoxication was 16 mm Hg and 15 mm Hg higher than in the corresponding Ringer's group at 10 and 15 minutes, respectively (P = 0.016 and P = 0.021, respectively, without Holm-Bonferroni correction). Intralipid® also caused no difference between total plasma and nonlipid-bound concentrations of bupivacaine with no apparent enhancement of recovery. CONCLUSIONS: Lipid emulsion neither had any measurable effect on the disposition of the studied local anesthetics in plasma, nor did it improve the rate of recovery from intoxication by either local anesthetic as measured by hemodynamic variables.

Intravenous lipid infusion in the successful resuscitation of local anesthetic-induced cardiovascular collapse after supraclavicular brachial plexus block.

We describe a case of successful resuscitation with an i.v. lipid infusion of local anesthetic-induced cardiovascular toxicity after supraclavicular brachial plexus block with mepivacaine and bupivacaine. Lipid therapy was initiated after 10 min of unsuccessful resuscitation and resulted in restoration of cardiovascular activity and hemodynamic stability. This case illustrates the utility of i.v. lipid therapy in the treatment of local anesthetic toxicity.

Reversal of central nervous system and cardiac toxicity after local anesthetic intoxication by lipid emulsion injection.

A 91-yr-old man (57 kg, 156 cm, ASA III) received an infraclavicular brachial plexus block for surgery of bursitis of the olecranon. Twenty minutes after infraclavicular injection of 30 mL of mepivacaine 1% (Scandicain) and 5 min after supplementation of 10 mL of prilocaine 1% (Xylonest) using an axillary approach, the patient complained of agitation and dizziness and became unresponsive to verbal commands. In addition, supraventricular extrasystole with bigeminy occurred. Local anesthetic toxicity was suspected and a dose of 200 mL of a 20% lipid emulsion was infused. Symptoms of central nervous system and cardiac toxicity disappeared within 5 and 15 min after the first lipid injection, respectively. Plasma concentrations of local anesthetics were determined before, 20, and 40 min after lipid infusion and were 4.08, 2.30, and 1.73 microg/mL for mepivacaine and 0.92, 0.35, and 0.24 microg/mL for prilocaine. These concentrations are below previously reported thresholds of toxicity above 5 microg/mL for both local anesthetics. Signs of toxicity resolved and the patient underwent the scheduled surgical procedure uneventfully under brachial plexus blockade.

A novel LC-MS/MS method for mepivacaine determination and pharmacokinetic study in a single-dose two-period crossover in healthy subjects.

The objective of this work was to develop a simple, selective, and sensitive LC-MS/MS method for the quantitation of the mepivacaine in Chinese biological matrix. The calibration curve of mepivacaine ranged from 0.5 to 2000 ng/mL with the lower limit of quantitation being 0.5 ng/mL. This sensitivity was high enough to describe the profile of blood mepivacaine level versus time. Thereby it was very desirable for the pharmacokinetic study because of its high sensitivity and accuracy. The study used a single-dose two-period crossover design principle. For the pharmacokinetic analysis of plasma, the mean (SD) values obtained were as follows: t1/2, 1.63 (0.43) h; Cmax, 435.3 (67.4) ng/ml; AUC0-t, 1546.9 (339.7) ng/ml·h; AUC0-∞, 1982.3 (421.4) ng/ml·h; Tmax, 0.62 (0.31) h. The validated method has been successfully applied to assess the pharmacokinetic study of mepivacaine after a single administration to Chinese volunteers.

Simultaneous determination of three local anesthetic drugs from the pipecoloxylidide group in human serum by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous analysis of the local anesthetic amide drugs, bupivacaine, mepivacaine and ropivacaine, belonging to the pipecoloxylidide group using a C(18) reversed-phase column (150 x 4.6 mm I.D.) filled with 5-microm particles and attached to a UV detector. The mobile phase was composed of acetonitrile-methanol-30 mM NaH(2)PO(4) (pH 5.6) (100:100:300, v/v/v) and the flow rate was 1ml/min. The absorbance of the eluate was monitored at 210 nm. The retention times of the three compounds were: 4.6 min (mepivacaine), 9.7min (ropivacaine) and 16.4 min (bupivacaine). With this sample preparation method, good and consistent recoveries of the three compounds were obtained: 88-91% for mepivacaine, 87-89% for ropivacaine and 88-91% for bupivacaine. The limit of quantification for three compounds in human serum was 2 ng/ml for mepivacaine, 5 ng/ml for bupivacaine and ropivacaine. This method may be useful in clinical and forensic applications for the determination or identification of the local anesthetic drugs: bupivacaine, mepivacaine or ropivacaine.

[Systemic toxicity with mepivacaine following axillary block in a patient with terminal kidney failure]. / Toxicité systémique à la mépivacaïne après un bloc axillaire chez un patient insuffisant rénal chronique.

As onset time and duration of sensory block are intermediate, mepivacaine is widely used for regional anaesthesia. Few reports of systemic adverse effects are available following nerve blockade with mepivacaine. We report the case of a 54-year-old patient suffering from terminal renal failure who needs the confection of an arteriovenous shunt under axillary brachial plexus block. At completion of the injection of 25 ml (375 mg) of 1.5% mepivacaine the patient presented dysarthria, mental confusion followed by a loss of verbal contact and agitation, but no convulsion or cardiac dysrythmia. The patient received midazolam and surgery was planned the following day under general anaesthesia. Plasma mepivacaine concentration at time of neurological signs was measured at 5.1 microg/ml. Prevention and treatment of systemic toxic effects after regional anaesthesia are discussed.

Plasma mepivacaine concentrations in patients undergoing third molar surgery.

BACKGROUND: Local anaesthetic-related systemic toxicity mainly results from elevated plasma concentrations of these drugs. We hypothesized that intraoral injection of submaximal doses of mepivacaine does not lead to toxic levels of this drug in blood. This study evaluated the plasma levels of mepivacaine in third molars surgeries. METHODS: Twenty-one patients were randomly assigned into two groups: group I (two unilateral third molars; submaximal dose of mepivacaine 108 mg with epinephrine 54 µg) and group II (four third molars; submaximal dose of mepivacaine 216 mg with epinephrine 108 µg). Blood samples were collected before anaesthesia, and 5, 10, 15, 20, 30, 40, 60, 90 and 120 min after anaesthesia. RESULTS: Individual peak plasma concentrations ranged 0.77-8.31 µg/mL (group I) and from 2.36-7.72 µg/mL (group II). An increase in the average dose of mepivacaine from 1.88 ± 0.12 mg/kg (group I) to 3.35 ± 0.17 mg/kg (group II) increased the mean mepivacaine peak plasma levels from 2.33 ± 0.58 to 4.01 ± 0.69 µg/mL, respectively. Four patients obtained plasma levels of mepivacaine above the threshold for toxicity (5 µg/mL). CONCLUSIONS: Toxic levels of mepivacaine are possible, even when a submaximal dose is used. A twofold increase in the dose of mepivacaine caused the mean peak plasma concentration to increase proportionally, indicating that they may be predicted based on the relation of dose per bodyweight.

Simultaneous determination of bupivacaine, mepivacain, prilocaine and ropivacain in human serum by liquid chromatography-tandem mass spectrometry.

A liquid chromatography-tandem mass spectrometric (LC-MS-MS) method with a rapid and simple sample preparation was developed and validated for the simultaneous determination of the local anesthetics bupivacaine, mepivacaine, prilocaine and ropivacaine in human serum. An external calibration was used. The mass spectrometer was operated in the multiple reaction monitoring mode. A good quadratic response over the range of 1.0-200.0 ng/ml was demonstrated. The accuracy for bupivacaine ranged from 93.2 to 105.7%, for mepivacaine from 96.2 to 104.3%, for prilocaine from 94.6 to 105.7% and for ropivacaine from 94.3 to 104.0%, respectively. The limit of quantification was 1.0 ng/ml for all substances. This method is suitable for pharmacokinetic studies.

Simultaneous determination of mepivacaine, tetracaine, and p-butylaminobenzoic acid by high-performance liquid chromatography.

INTRODUCTION: The purpose of the present study was to develop a simple method for the simultaneous determination of mepivacaine, tetracaine, and p-butylaminobenzoic acid (BABA) in human plasma using high-performance liquid chromatography (HPLC) with a multiwavelength detector. METHODS: Human blood samples containing heparin, as an anticoagulant, and physostigmine (100 microg/ml), as an anticholinesterase, or human plasma containing physostigmine were spiked with various concentrations of mepivacaine, tetracaine and, in some cases, BABA. Blood samples were centrifuged and plasma was deproteinized with trifluoroacetic acid (TFA; 7%). After centrifugation, the pH was adjusted to 4.5 and an aliquot of 20, 50 or 100 microl was injected into the HPLC apparatus. The detection was done simultaneously at wavelengths of 214 and 300 nm. Analytical chromatography was done on a Waters microBondapak C(18) reverse-phase column (3.9 x 300 mm; particle size 10 microm) with a 30-min increasing linear gradient of 20-40% acetonitrile+0.05% TFA in H(2)O+0.05% TFA at a flow rate of 1 ml/min. The Waters HPLC system included two pumps, an automatic injector, a column oven, and a M490 multiwavelength detector. Quantification was done using integration of peak areas with peaks of authentic mepivacaine, tetracaine, and BABA standards. RESULTS: Calibration curves for standards of mepivacaine, tetracaine, and BABA were linear in the concentration ranges from 0.1 to 100 microg/ml, and the correlation coefficients exceeded.99 for all compounds. The lower limits of detection were 100 ng/ml for mepivacaine and 50 ng/ml for tetracaine and BABA. The yields for mepivacaine, tetracaine, and BABA were 91+/-2.1%, 82+/-3.3%, and 88+/-2.0% (mean+/-S.E.M., n=6), respectively. Degradation of tetracaine by human plasma at 37 degrees C was inhibited by physostigmine. DISCUSSION: The method is sensitive enough to allow blood concentration determinations of mepivacaine and tetracaine or its metabolite, BABA, following local anesthesia induced by these two drugs, especially when their toxic effect may be present. This method also may be useful in forensic medicine for determination of the cause of death after local anesthesia with mepivacaine and/or tetracaine.

Brain-to-blood and saliva-to-blood mepivacaine ratios in rats.

Mepivacaine hydrochloride, 25 and 50 mg/kg sc (with sacrifice at 15 min) produced higher (p less than 0.005) drug levels in neonate (24--36-hr-old) rat brain and blood than in adult rat brain and blood; however, there was no significant difference in the brain-to-blood ratio of the drug between neonates and adults at either dose level. Intraarterial infusion of mepivacaine hydrochloride (20 micrograms/min) in adult rats resulted in measurable (GLC) mepivacaine base levels in pilocarpine-induced parotid salivary secretions collected throughout 30- and 45-min infusion periods. The saliva-to-blood ratios (+/- SEM) of mepivacaine base were 0.64 +/- 0.13 after a 30-min infusion and 2.13 +/- 0.48 after a 45-min infusion.

HPCE determination of R(+) and S(-) mepivacaine in human serum using a derivatized cyclodextrin and ultraviolet detection.

A high performance capillary electrophoresis assay for the quantitative determination of R(+) and S(-) mepivacaine in human serum is reported using heptakis (2,6-di-O-methyl) beta-cyclodextrin as the chiral selector for the separation of the enantiomers. The background electrolyte was a 100 mM phosphate buffer (pH 2.5) containing 20 mM heptakis (2,6-di-O-methyl) beta-cyclodextrin and 30 nM hexadecyltrimethylammonium bromide (HTAB). A 72 cm uncoated fused silica capillary was used for the analysis. HTAB was used as the buffer additive to decrease the adsorption of endogenous substances onto the silica wall. To separate the analytes of interest from the endogenous serum substances, a liquid-liquid extraction procedure was used. The extraction recoveries were greater than 70% for both R(+) and S(-) mepivacaine. The detection limits were around 150 ng ml-1 using 1 ml of serum and the limits of quantitation were 200 ng ml-1. The calibration curves were linear over a range of 200-2000 ng ml-1 with R(-) prilocaine as internal standard (IS) and coefficients of determination were greater than 0.999 (n=3). Precision and accuracy of the method were 4.1-7.2 and 2.6-5.9%, respectively, for R(+) mepivacaine and 4.0-7.4 and 3.2-7.4% for respectively, for S(-) mepivacaine. The HPCE method was compared to an existing HPLC method in terms of sensitivity and selectivity for the routine analysis of the drugs.

Blood concentrations of tetracaine and its metabolite following spinal anesthesia.

Blood concentrations of tetracaine and its metabolite, p-butylaminobenzoic acid, were measured after spinal anesthesia with tetracaine which had been administered to patients under going orthopedic surgery. Tetracaine, an ester anesthetic, was given to 10 patients, the dose was 8-14mg, and blood samples were collected 1, 2 and 6h after the injection of tetracaine. We used gas chromatography/mass spectrometry for purposes of analysis. Tetracaine was not detected in any blood sample, but the metabolite was detected in each sample with the mean concentrations of 126.5, 97.9 and 43.3ng/ml at 1, 2 and 6h, respectively. This data will be useful in determination of the cause of death after spinal anesthesia with tetracaine.

Plasma mepivacaine concentrations after caudal epidural and subarachnoid injection in the horse: comparative study.

The venous plasma concentrations of mepivacaine were determined in 7 adult mares (420 +/- 17.1 kg) given an injection of a 2% solution of the hydrochloride at either the sacral (S2-3 to S5-C1) epidural space or the midsacral (S2-3) subarachnoid space. An average dose of 91.4 +/- 15.7 mg (4.6 +/- 0.8 ml) was needed to produce caudal epidural analgesia (CEA) and 26.7 +/- 5.4 mg (1.3 +/- 0.3 ml) to produce caudal subarachnoid analgesia (CSA). Maximal caudal analgesia extended from spinal cord segments S-1 to coccyx during CEA and CSA. The onset of analgesia as measured by response to superficial and deep muscular pinprick stimulations was significantly (P less than 0.05) faster in mares with CSA than with CEA (8.3 +/- 2.4 minutes vs 21.4 +/- 3.8 minutes). The period of analgesia was significantly (P less than 0.05) longer in mares with CEA than with CSA (80.0 +/- 11.5 minutes vs 67.4 +/- 26.3 minutes). The rate of vascular absorption of mepivacaine from the epidural space was significantly (P less than 0.05) faster than from the subarachnoid space. Maximum venous plasma concentrations of mepivacaine were similar (P greater than 0.05) after epidural and subarachnoid injections (0.05 +/- 0.03 micrograms/ml and 0.05 +/- 0.03 micrograms/ml) at the same times after mepivacaine administration (51.4 +/- 33.4 minutes and 53.6 +/- 24.3 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Pediatric caudal block with mepivacaine, bupivacaine or a mixture of both drugs: requirement for postoperative analgesia and plasma concentration of local anesthetics.

STUDY OBJECTIVES: To assess the effects of pediatric caudal block using mepivacaine, bupivacaine, or a mixture of both drugs on postoperative analgesia, and to examine plasma concentrations of the local anesthetics after caudal injection. DESIGN: Prospective, randomized, double-blind study. SETTING: Operating room and pediatric surgical ward. PATIENTS: 60 ASA physical status I children weighing 10 to 20 kg (26 females, 34 males), and scheduled for inguinal herniorrhaphy. INTERVENTIONS: Patients randomly received caudal block with 1 mL/kg of mepivacaine 1% (Group M, n = 20), 1 mL/kg of bupivacaine 0.25% (Group B, n = 20), or a mixture of 0.5 mL/kg of mepivacaine 1% and 0.5 mL/kg of bupivacaine 0.25% (Group MB, n = 20) after induction of anesthesia with sevoflurane in 50% oxygen (O2). Anesthesia was maintained with 66% nitrous oxide in O2 supplemented with sevoflurane at an end-tidal concentration of less than 1%. MEASUREMENTS AND MAIN RESULTS: Postoperative pain scores using a pediatric pain scale and plasma concentration of each local anesthetic were measured. In Group M, four patients required postoperative analgesics within the first 24 hours. However, no patients required postoperative analgesics in Groups B and MB. In Group M, the plasma concentration of mepivacaine of two patients exceeded 5 microg/kg of the level of toxicity. However, these patients did not show any toxic symptoms. Because a mixture of two local anesthetics halves the concentration of each local anesthetic, the plasma concentrations of mepivacaine and bupivacaine in Group MB were significantly lower than those of Groups M and B. CONCLUSIONS: Pediatric caudal block with a mixture of mepivacaine and bupivacaine is effective for intraoperative and postoperative analgesia.

Comparative circulating serum levels of mepivacaine with levo-nordefrin and lidocaine with epinephrien.

Expected blood levels of common local anesthetics have been reported for numerous types of injections. Comparative levels of mepivacaine and lidocaine after dental injection have been only partially evaluated. A study was designed to compare the circulating serum level of 36 mgs. of mepivacaine with 1:20,000 levonordefrin (M) and 36 mgs. of lidocaine with 1:100,000 epinephrine (L) in 1.8 cc dental cartridges after standardized's bilateral maxillary infiltrations. Each of five subjects received 1.8 cc of (L) to the left maxillary second bicuspid and 1.8 cc of (M) to the right maxillary second bicuspid at a rate of one cc per minute. The serum was sampled before the injections and at 5, 15, 30, 60, 90, 120 and 240 minute intervals after the injections and analyzed by gas liquid chromatography. The results indicated that the serum level of (M) peaked at 30 minutes, 0.37 µg/ml of serum and (L) had peaks at 15 and 30 minutes, 0.22 µg/ml of serum. This difference was statistically significant, (p <.01) at all times sampled with (M) always resulting in a higher serum level. Serum levels persisted throughout the four hour test period.

Serum mepivacaine concentrations after intraoral injection in young children.

The authors measured plasma concentrations of mepivacaine in 36 children from the ages of 2 to 5 years who received dental care under light general anesthesia. The subjects were randomly assigned to receive either 2 percent mepivacaine hydrochloride with 1:20,000 levonordefrin or 3 percent mepivacaine hydrochloride without vasoconstrictor. The volume of anesthetic injected depended on the planned procedures for each patient. Blood samples (3 mL) were drawn from an intravenous line before and 5, 10, 20, 30, 45, and 60 minutes after mepivacaine injection. The serum was collected and analyzed by gas-liquid chromatography. Mean serum concentrations, normalized to a dose of 1 mg/kg body weight, reached a peak of 0.67 +/- 0.42 microgram/mL (mean +/- SD) after 3 percent mepivacaine and 0.63 +/- 0.21 microgram/mL after 2 percent mepivacaine with levonordefrin. Levonordefrin had no significant effect on the plasma concentrations. However, because of the higher concentration of mepivacaine in the 3 percent formulation, it was potentially 1.5 times as toxic (P < 0.002) on a volume basis. Statistical analysis also suggested that the maximum recommended dose of 3 mg/lb could result in potentially toxic blood concentrations in a small percentage of pediatric patients. The authors conclude that 3 percent mepivacaine should not be used when relatively large volumes of local anesthetic must be administered to small children and recommend that the maximum dose of mepivacaine not exceed 5 mg/kg.