Plasma Lidocaine Research Articles

Capillary gas chromatographic method for the determination of n-butyl- p-aminobenzoate and lidocaine in plasma samples

A fast capillary gas chromatographic method with nitrogen-selective detection is described that allows selective and reproducible quantification of n-butyl- p-aminobenzoate (BAB) and lidocaine in plasma. The sampling and sample storage conditions are critical for the quantification of BAB. Diisopropyl fluorophosphate, an organophosphorus pesticide, has to be added during sampling to prevent the rapid decomposition of BAB by cholinesterases.

Low plasma lidocaine concentration does not affect oxygen uptake at awakening from isoflurane anesthesia.

To clarify the effects of lidocaine in plasma after epidural administration on oxygen uptake (VO2) at awakening from isoflurane anesthesia, we measured VO2 in 45 patients undergoing abdominal hysterectomy under four conditions: control group, intravenous normal saline; epidural group, 3 mg/kg of 1.5% lidocaine epidurally as a bolus; and groups CIV-A and CIV-B, continuous intravenous infusion of 2% lidocaine, 0.5 and 1 mg/kg, respectively, for 5 min followed by 30 micrograms.kg-1 x min-1. VO2 at both periods of steady state during anesthesia before lidocaine administration and awakening from anesthesia were measured using a mass spectrometer system during spontaneous breathing. At awakening, VO2 in the control, CIV-A, and CIV-B groups increased significantly (P < 0.02) from 142 to 262-328 mL.min-1 x m-2 which as more (P < 0.01) than that in the epidural group which increased from 166 to 159 mL.min-1 x m-2. These results indicate that epidural lidocaine prevents the increase in VO2 associated with arousal from isoflurane anesthesia. This effect is not due to the absorbed plasma lidocaine but due to the epidural neural block.

Plasma protein binding of lidocaine during hypothermic conditions

The effect of hypothermia on the protein binding of lidocaine in plasma from six healthy volunteers was studied in vitro. A significant increase (p &lt;0.001) in the unbound fraction of lidocaine was found at 24°C (38.3 [SD 7.0] %) compared to 37°C (30.7 [SD 6.0] %). A further reduction in temperature to 10°C resulted in a slight but not statistically significant increase in the free fraction of the drug (39.9 [SD 10.2] %). As a conclusion, hypothermia enhances the transfer of lidocaine over the blood-brain barrier. In order to avoid unwanted side effects or frank toxicity, caution is recommended when administering highly protein-bound drugs during hypothermic conditions.

Lontophoretic Transdermal Delivery of Salicylic Acid and Lidocaine to Local Subcutaneous Structures

The depth of penetration of solutes into underlying tissues after transdermal iontophoresis has been evaluated with salicylic acid and lidocaine as model compounds. Concentrations of salicylic acid and lidocaine were measured in plasma and tissues below the donor electrode after iontophoresis in rats. The concentrations obtained were then compared with those obtained after passive delivery (without iontophoresis) of the drugs applied either to intact epidermis or to the exposed dermis (epidermis removed) of rats. Iontophoresis yielded high concentrations of lidocaine in each underlying tissue when compared with passive application to rat epidermis or dermis. Negligible concentrations of lidocaine in plasma were found for each mode of delivery. Similar concentrations of salicylic acid were found in each of the underlying tissues after delivery of salicylic acid either by iontophoresis through intact epidermis or after passive application to the exposed dermis. Negligible concentrations of salicylic acid in underlying tissues were obtained after passive application to intact epidermis. The plasma salicylic acid concentrations observed after both iontophoretic epidermal and passive dermal (epidermis removed) treatments were approximately the same as the tissue salicylic acid concentrations observed at —3-4 mm below the application site. It is concluded that transdermal ionto-phoresis allows salicylic acid and lidocaine to be effectively delivered across the stratum corneum. Local direct deep tissue penetration of lidocaine is facilitated by iontophoresis. The concentrations of salicylic acid in deeper underlying tissues (>3-4 mm) tend to be similar to the concentrations in plasma after either iontophoresis or passive dermal application, a result indicating that direct penetration of salicylic acid occurs only to a depth of 3-4 mm.

Intravenous Lidocaine in the Treatment of Convulsions in the Neonatal Period

Thirteen newborn infants (five premature, eight full term) with severe seizures and not responding to phenobarbital and diazepam received a lidocaine (LD) infusion. The schedule was 4 mg/kg/h on the 1st day, 3 mg/kg/h on the 2nd day, 2 mg/kg/h on the 3rd day, and 1 mg/kg/h on the 4th day. The LD plasma levels were measured every 24 h just before decreasing the dose. The control of seizures was achieved in 11 of 13 patients, with plasma LD concentration ranging from 2.8 to 10.5 mg/L. The LD concentration was linearly correlated with the dose in each group. In the premature group, LD clearance was always smaller than in the full-term group. Although no side effects were observed on heart rate and blood pressure, it is suggested that the dose of LD be adjusted to maintain the LD concentrations between 3-6 mg/L.

Summation and Inhibition by Ultrarapid Train Pulses in Dogs: Effects of Frequency and Duration of Trains, Lidocaine, and Beta Blockade

To test whether summation and inhibition of excitation by ultrarapid train pulses were modified by frequency and duration of trains, using lidocaine and beta blockade, the strength-interval relationship was determined with a single extrastimulus and train pulses (100 and 200 Hz) in 28 anesthetized, open-chest dogs. The effective refractory period (ERP) determined at greater than or equal to 5 mA was shorter for trains than for single stimulus (summation). Summation determined at 15 mA increased progressively as the duration of trains was increased to 50 msec after which it reached a plateau. ERP determined at less than or equal to 2 mA was longer with train pulses than with single stimulus (inhibition). Inhibition for 200 Hz trains increased linearly with train duration up to 200 msec, while for 100 Hz trains it became constant when the duration was greater than or equal to 80 msec. Lidocaine (plasma concentration: 2.6 +/- 1.0 micrograms/mL) did not affect inhibition and summation in 11 dogs. Propranolol (1 mg/kg, iv) increased summation at 15 mA (n = 7, 30 +/- 10 vs 46 +/- 11 msec with 100 Hz trains, P less than 0.01), but did not affect inhibition (37 +/- 26 vs 29 +/- 17 msec, NS). In conclusion, (1) effect of frequency of train pulses was more on inhibition than on summation; (2) lidocaine did not affect inhibition and summation; and (3) propranolol increased summation but not inhibition.

Simple alternative method for capillary gas chromatographic determination of lidocaine in plasma

Simple alternative method for capillary gas chromatographic determination of lidocaine in plasma

Sensitive high-performance liquid chromatographic assay using 9-fluorenylmethylchloroformate for monitoring controlled-release lidocaine in plasma.

A sensitive high-performance liquid chromatographic (HPLC) assay using fluorescence detection for quantifying lidocaine levels in plasma (in the ng/ml range) was developed. This novel HPLC assay has made possible the simultaneous monitoring of lidocaine levels in coronary and peripheral plasma obtained after myocardial controlled-release matrix administration (0.92 mg/kg during 4 h) in the arrhythmic dog. The method employed extracts the drug from plasma using 1-chlorobutane and a subsequent derivatization with 9-fluorenylmethylchloroformate in acetonitrile at 110 degrees C. The derivative was chromatographed on a C18 reversed-phase column and measured with fluorescence detection (excitation 254 nm, emission 313 nm). N-Methylephedrine was found to be suitable as an internal standard, post-derivatization. The derivatization product of lidocaine was identified and characterized by mass spectral analysis. It was found to have a unique and reproducible dicarbamate structure, which was stable for at least three days at room temperature. The method was tested with human plasma as well as on dog plasma. Analytical recoveries were 88.6 +/- 3.6 and 77.4 +/- 3.0% (mean +/- S.E.), respectively, at levels ranging from 25 to 200 ng/ml. The lower detection limit was 1 ng/ml lidocaine. In conclusion, this rapid and convenient analysis was found to be suitable for the bioavailability pharmacokinetic assessment of lidocaine following low-dose regional drug administration.

Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia.

Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were studied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320-400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35-55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 +/- 0.46 (mean +/- SD) microgram/ml following the first injection and 3.34 +/- 0.76 microgram/ml after the second, to 4.11 +/- 0.72 microgram/ml following the third. The maximum concentrations of MEGX and GX were 0.66 +/- 0.22 and 0.28 +/- 0.08 microgram/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2 = 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 +/- 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 +/- 0.61 l/kg), and clearance divided by bioavailability (Cl/F, 11.65 +/- 1.21 ml X kg-1 X min-1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (approximately equal to 6 microgram/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous determination of lidocaine, mexiletine, disopyramide, and quinidine in plasma by high performance liquid chromatography.

A high performance liquid chromatographic method is described for the simultaneous quantitation of four commonly prescribed antiarrhythmic drugs: lidocaine, mexiletine, disopyramide, and quinidine. An isocratic system using a reverse phase column was used to separate these compounds. Coefficients of variation were less than 4%.

Gas chromatographic analysis of lidocaine in blood and tissues.

A rapid, sensitive, and specific gas chromatographic assay for lidocaine in plasma and blood is reported. The procedure involves a single step extraction of the drug and internal standard, and analysis without derivatization. The method can be modified to include the analysis of lidocaine in tissues.

A rapid and simple microassay for lidocaine in human blood plasma using gas-liquid chromatography with nitrogen detection.

Lidocaine is widely used in antiarrhythmic therapy, and the need to monitor the drug concentration in the blood of patients receiving lidocaine is well established. We have developed a new assay for lidocaine designed for the routine clinical therapeutic drug monitoring laboratory. A 100-microliter aliquot of blood plasma is treated with 50 microliters of internal standard solution and the mixture alkalinized. The drug and internal standard are extracted with toluene and analyzed by nitrogen-detection gas-liquid chromatography. A single extraction is used, and no solvent evaporation is required, resulting in a simple and rapid procedure. Using the single-point standard, the within-day coefficient of variation (CV) was 6.4%, while the between-day CV was 7.4%. Monoethylglycinexylidide, the major plasma metabolite of lidocaine, and several drugs potentially present in patients receiving lidocaine were shown not to interfere. The procedure has significant advantages over previously published similar methods.

Simplified GLC Assay for Lidocaine in Plasma

A simple, rapid GLC method for the determination of lidocaine in plasma is described. After addition of mepivacaine as an internal standard, the plasma sample is deproteinated and centrifuged. The supernate is alkalinized, and the lidocaine and internal standard are extracted into a microvolume of carbon disulfide. By using GLC with a flame-ionization detector, linear concentration-response curves were obtained in the 1–6-μg/ml range. The method can easily determine plasma concentrations at the 250-ng/ml level when a 1-ml plasma sample is analyzed.

Simultaneous Determination of Lidocaine (Lignocaine) and Thiopental in Plasma Using High Pressure-Liquid Chromatography

Abstract A sensitive and precise high-pressure liquid chromatographic method for the simultaneous quantitation of lidocaine (lignocaine) and thiopental in 0.5 ml samples of plasma is described. Extraction was conducted at pH 7.0 using ethyl acetate, and bupivicaine was employed as an internal standard. The drugs were eluted from a reversed-phase column using a mobile phase consisting of aceton-itrile/0.2 M phosphate buffer pH 4.0 (1:9) at a flow rate of 1.0 ml/min. The drugs were detected and quantified by their UV absorption at 205 nm. The sensitivity limits of detection for lidocaine and thiopental were 1 ug/ml and 5 ug/ml, respectively. Atropine, caffeine and meperidine were found to have interfering retention times.

GLC analysis of lidocaine in plasma using a novel nitrogen-sensitive detector

AbstractA simple, rapid GLC method for the determination of therapeutic levels of lidocaine in plasma or blood is described. After extraction with benzene from alkalinized plasma, the compound is analyzed by GLC using a nitrogen-sensitive detector. Quantitation is accomplished using an internal standard and a standard curve, which was linear over the 0.1–10-μg range. The limit of detection was approximately 10 ng/ml. Recovery of the parent compound was essentially quantitative. Plasma data are presented to demonstrate the utility of the method.

CARDIAC RHYTHM IN MEN DURING CYSTOSCOPY

AbstractCardiac rhythm was monitored prospectively in 69 men during 191 cystoscopies. Ectopic beats from ventricular and supraventricular foci occurred in a significantly greater proportion of procedures in men with (76 per cent) compared to men without (16 per cent) heart disease. Other arrhythmias occurred to a lesser extent but there was no significant difference between men with and without heart disease. Plasma lidocaine was detected in significant amounts following intraurethral injection used for local anesthesia. Comparison of the types of arrhythmias that occurred during cytoscopy and the type of anesthetic used showed that significantly fewer ventricular ectopic beats occurred with general (8 per cent) or epidural anesthesia (13.8 per cent) as opposed to local lidocaine anesthesia (48.7 per cent). Among the 3 anesthetic groups there was no difference with respect to frequency of supraventricular ectopic beats. No permanent cardiovascular complications occurred although several potentially seriou...

Cardiac Rhythm in Men During Cystoscopy

Cardiac rhythm was monitored prospectively in 69 men during 191 cystoscopies. Ectopic beats from ventricular and supraventricular foci occurred in a significantly greater proportion of procedures in men with (76 per cent) compared to men without (16 per cent) heart disease. Other arrhythmias occurred to a lesser extent but there was no significant difference between men with and without heart disease. Plasma lidocaine was detected in significant amounts following intraurethral injection used for local anesthesia. Comparison of the types of arrhythmias that occurred during cytoscopy and the type of anesthetic used showed that significantly fewer ventricular ectopic beats occurred with general (8 per cent) or epidural anesthesia (13.8 per cent) as opposed to local lidocaine anesthesia (48.7 per cent). Among the 3 anesthetic groups there was no difference with respect to frequency of supraventricular ectopic beats. No permanent cardiovascular complications occurred although several potentially serious dysrhythmias were seen.