Possibilities for discrimination between chewing of coca leaves and abuse of cocaine by hair analysis including hygrine, cuscohygrine, cinnamoylcocaine and cocaine metabolite/cocaine ratios.

Contrary to the illegal use of any form of manufactured cocaine, chewing of coca leaves and drinking of coca tea are allowed and are very common and socially integrated in several South American countries. Because of this different legal state, an analytical method for discrimination between use of coca leaves and abuse of processed cocaine preparations is required. In this study, the applicability of hair analysis for this purpose was examined. Hair samples from 26 Argentinean coca chewers and 22 German cocaine users were analysed for cocaine (COC), norcocaine (NC), benzoylecgonine (BE), ecgonine methyl ester (EME), cocaethylene (CE), cinnamoylcocaine (CIN), tropacocaine (TRO), cuscohygrine (CUS) and hygrine (HYG) by hydrophilic interaction liquid chromatography (HILIC) in combination with triplequad mass spectrometry (MS/MS) and hybrid quadrupole time-of-flight mass spectrometry (QTOF-MS). The following concentrations (range, median, ng/mg) were determined in hair of the coca chewers: COC 0.085-75.5, 17.0; NC 0.03-1.15, 0.12; BE 0.046-35.5, 6.1; EME 0.014-6.0, 0.66; CE 0.00-13.8, 0.38; CIN 0.005-16.8, 0.79; TRO 0.02-0.16, 0.023; CUS 0.026-26.7, 0.31. In lack of a reference substance, only qualitative data were obtained for HYG, and two metabolites of CUS were detected which were not found in hair of the cocaine users. For interpretation, the concentrations of the metabolites and of the coca alkaloids in relation to cocaine were statistically compared between coca chewers and cocaine users. By analysis of variance (ANOVA) significant differences were found for all analytes (α = 0.000 to 0.030) with the exception of TRO (α = 0.218). The ratios CUS/COC, CIN/COC and EME/COC appeared to be the most suitable criteria for discrimination between both groups with the means and medians 5-fold to 10-fold higher for coca chewers and a low overlap of the ranges between both groups. The same was qualitatively found for HYG. However, these criteria cannot exclude cocaine use in addition to coca chewing. In this regard screening for typical cutting agents can be helpful and led to the detection of levamisole (21×), lidocaine (6×) and paracetamol (3×) in the 22 samples from German cocaine users, whereas no levamisole, lidocaine (3×) and paracetamol (1×) were found in hair from the Argentinean coca chewers. These criteria have to be confirmed for South American cocaine consumers including smokers of coca paste and may be different because of different composition of the drug and other use habits.

Lidocaine concentration in mandibular bone after subperiosteal infiltration anesthesia decreases with elevation of periosteal flap and irrigation with saline.

It has been reported that the action of infiltration anesthesia on the jawbone is attenuated significantly by elevation of the periosteal flap with saline irrigation in clinical studies; however, the reason is unclear. Therefore, the lidocaine concentration in mandibular bone after subperiosteal infiltration anesthesia was measured under several surgical conditions. The subjects were 48 rabbits. Infiltration anesthesia by 0.5 mL of 2% lidocaine with 1 : 80,000 epinephrine (adrenaline) was injected into the right mandibular angle and left mandibular body, respectively. Under several surgical conditions (presence or absence of periosteal flap, and presence or absence of saline irrigation), both mandibular bone samples were removed at a fixed time after subperiosteal infiltration anesthesia. The lidocaine concentration in each mandibular bone sample was measured by high-performance liquid chromatography. As a result, elevation of the periosteal flap with saline irrigation significantly decreased the lidocaine concentration in the mandibular bone. It is suggested that the anesthetic in the bone was washed out by saline irrigation. Therefore, supplemental conduction and/or general anesthesia should be utilized for long operations that include elevation of the periosteal flap with saline irrigation.

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.

Análise comparativa do efeito anestésico da lidocaína 2 por cento e da prilocaína 3 por cento / Comparative analysis of the anesthetic of the boty lidocaine 2 per cents and prilocaine 3 per cents

Uma análise comparativa das soluçöes anestésicas prilocaína a 3 por cento com felipressina 0,03 UI/ml e lidocaína a 2 por cento com noradrenalina 1:50.000 foi realizada com o objetivo de identificar variaçöes do período de latência, duraçäo da anestesia e quantidade de anestésico necessária para a extraçäo de terceiros molares inferiores em inclusäo bilateral semelhante, bem como o comportamento destas soluçöes anestésicas no controle da dor trans e pós-operatória, associada a analgésicos e antiinflamatórios. 20 pacientes jovens, de ambos os sexos, portadores de terceiros molares inferiores retidos foram submetidos a exodontias. Os resultados mostraram semelhança estatística entre as duas soluçöes anestésicas e garantiram eficácia no controle da dor trans-operatória com quantidades mínimas de soluçäo anestésica (médias de 2,125 e 2,025 tubetes para a prilocaína e lidocaína respectivamente). Portanto, a escolha da soluçäo anestésica deve näo estar relacionada à duraçäo do efeito e período de latência e sim aos aspectos sistêmicos do paciente portador de inclusäo dentária, limitantes do uso de sais anestésicos e vasoconstritores

Tumescent anesthesia with a lidocaine dose of 55 mg/kg is safe for liposuction.

BACKGROUND: The safe upper limit of lidocaine dosage in tumescent anesthesia for liposuction has been reported to be 35 mg/kg. OBJECTIVE: This study was undertaken to: 1) evaluate the safety of tumescent anesthesia in liposuction when lidocaine doses greater than 35 mg/kg are required, 2) determine the time interval when the peak plasma lidocaine level occurs following administration of tumescent anesthesia, and 3) assess if the safety of large volume tumescent anesthesia is due to significant lidocaine removed by liposuction. METHODS: Sixty patients who underwent liposuction with a mean lidocaine dose of 57 mg/kg were prospectively evaluated for development of any signs or symptoms of lidocaine toxicity by multiple interviews over a 24-hour period. In addition, another 10 patients who received a mean lidocaine dose of 55 mg/kg had serial plasma lidocaine level measurements over a 24-hour period following liposuction. The lidocaine level of the aspirate was also measured to assess any significant lidocaine removed by liposuction. RESULTS: No evidence of lidocaine toxicity was found based on subjective evaluation of 60 patients as well as determined by plasma sampling of 10 patients. The peak plasma lidocaine concentration occurred at approximately 4 or 8 hours after infusion of tumescent anesthesia. The 24-hour plasma lidocaine level suggests that residual lidocaine is present in the subcutaneous tissue allowing for postoperative analgesia beyond this time. A negligible amount of lidocaine was removed by liposuction as determined by the lidocaine level of the aspirate. CONCLUSION: This study suggests that tumescent anesthesia with a total lidocaine dose of up to 55 mg/kg is safe for use in liposuction.

Liver function tests and lidocaine metabolism (MEGX test) during i.v. CMF therapy in breast cancer.

The measurement of monoethylglycinexylidide (MEGX test) is considered a sensitive method for the evaluation of hepatic metabolic capacity. The multidrug chemotherapy CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/ m2, 5-fluorouracil 600 mg/m2) is widely used in breast cancer patients but very few clinical studies have investigated its possible liver toxicity. We have prospectively evaluated the possible acute liver toxicity after a cycle (i.e. two courses) of CMF by means of the measurement of standard liver function tests and of MEGX, i.e. the main lidocaine (Lid) metabolite after the i.v. injection of Lid. Consecutive patients (n = 15), aged 43-68 years, were radically operated on because of M0 primary breast cancer and candidates for adjuvant CMF because of nodal axillary involvement (pN1) were studied. Tests were performed before the first (given at day 1) and 48 h after the second course (given at day 8) of an i.v. CMF regimen to be repeated every 28 days. Full blood count, serum ALT, AST, gamma-GT, alkaline phosphatase and albumin were measured with standard methods. To investigate the appearance of MEGX, blood samples were taken before, and 5, 10, 15, 20, 25, 30 and 60 min after i.v. Lid injection. MEGX serum concentration was measured by means of a fluorescent polarization immunoassay. We found no significant variation between pre- and post-CMF standard liver function tests with the exception of ALT levels, which, however, decreased (mean 48%, p < 0.05). The MEGX serum concentration was significantly increased over the sampling time period and the 42% mean rise was statistically significant (p < 0.001). Moreover, the post-CMF increase of circulating MEGX was steeper than the basal pre-CMF values. The slopes relating to the curves of MEGX formation over the first 20 min were 3.30 and 2.24, respectively (p < 0.001). In conclusion, no hepatic acute toxicity was observed during the CMF chemotherapy. Further studies are required to understand the meaning of the unexpected MEGX rise.

Concentracao de lidocaina no suco gastrico de recem-nascidos apos anestesia locorregional em partos normais / Concentration of lidocaine in the gastric content of neonates after local anesthesia in vaginal delivery

O objetivo desse estudo foi verificar a transferencia placentaria de lidocaina utilizada em parto normal e a sua possivel presenca no suco gastrico de neonatos, logo apos o nascimento. Foram selecionados 19 recem-nascidos sadios pertencentes a Neonatologia do Hospital Universitario da USP, cujas maes recebem 400mg de lidocaina para anestesia da regiao pudenda. Foram colhidas amostras de sangue para determinar a concentracao plasmatica do anestesico na mae, no cordao umbilical, no neonato e tambem no suco gastrico do recem-nascido...

Excretion of lignocaine and its metabolite monoethylglycinexylidide in breast milk following its use in a dental procedure. A case report.

The excretion of lignocaine in breast milk has been documented in a 34-year-old woman following the injection of 20 mg lignocaine for a dental alloy restoration in the right upper quadrant. Lignocaine and its primary metabolite monoethylglycinexylidide in milk and plasma were quantified by high-performance liquid chromatography. The concentration of lignocaine in milk ranged from 44-66 micrograms l-1 while that for monoethylglycinexylidide ranged from 35-41 micrograms l-1. The milk: plasma ratios for lignocaine and monoethylglycinexylidide were 1.1 and 1.8, respectively. The calculated daily infant doses for the parent drug and metabolite were both less than 0.01 mg kg-1 day-1. With the exception of very rare allergic reactions, these levels of infant exposure are extremely low and of no toxicological significance. Nursing mothers receiving lignocaine for standard dental procedures can be advised that continuation of breast feeding is safe.

The effects of two different local anaesthetic solutions administered for oral surgery on plasma potassium levels in patients taking kaliuretic diuretics.

The effects of two different dental local anaesthetic solutions, administered for oral surgery, on the plasma potassium levels of patients taking non-potassium sparing diuretics has been investigated. There was a significant reduction in plasma potassium concentration in eight subjects who received 4.4 ml of 2% lignocaine with 1:80,000 adrenaline; the mean reduction from baseline being 0.30 mmol.l-1 10 min following intraoral extravascular injection of the local anaesthetic. There was no significant difference from the pre-treatment plasma potassium concentration 10 min following similar injections of 3% prilocaine with 0.03 IU.ml-1 felypressin in 8 patients; the mean change in these subjects being -0.05 mmol.l-1. It is suggested that the use of adrenaline-free local anaesthetics would seem to be appropriate in patients receiving kaliuretic diuretics.

Towards less painful local anesthesia.

Local anesthesia, used for numerous procedures in all fields of medicine, has the drawback of providing significant pain upon injection. Twenty-eight volunteers were asked to compare a subcutaneous injection of plain lidocaine with an injection of lidocaine plus bicarbonate. Twenty-four of the twenty-eight volunteers reported less pain with the buffered lidocaine. The dilution of 1 part bicarbonate to 10 parts plain lidocaine produced a solution that was less painful and better tolerated. The local anesthetic lidocaine is used prior to many minor and major surgical procedures. Although it induces adequate anesthesia, the pain of injection is nearly always of considerable discomfort to the patient. There are numerous factors that have been shown to influence the pain of injection. These include speed of injection, size of needle used, area of the body injected, and simply individual patient characteristics. Since lidocaine comes as an acid solution, local tissue irritation is likely the primary source of pain.

Follicular fluid Lidocaine levels during transvaginal oocyte retrieval.

Lidocaine has been shown to have adverse effects on mouse oocyte fertilization and embryo development. We have demonstrated the presence of pharmacologic levels of lidocaine in human serum and follicular fluid obtained during ultrasound guided transvaginal oocyte retrieval. The significance of this finding is unclear, as four of the eight patients studied became pregnant, including the patient with the highest follicular fluid lidocaine levels. Further evaluation of the effect of lidocaine on human embryos is warranted.

Definitive liquid-chromatographic demonstration that N-ethylglycine is the metabolite of lidocaine that interferes in the Kodak sarcosine oxidase-coupled method for creatinine.

Patients receiving lidocaine may show false increases of serum creatinine as assayed by the single-slide method on the Kodak Ektachem 700. Bissell et al. (Clin Chem 1987;33:951) suggested that this interference was due to oxidation of N-ethylglycine (NEG), a previously uncharacterized metabolite of lidocaine, by the sarcosine oxidase preparation used in the Ektachem creatinine slide. To investigate this possibility, we synthesized NEG, added it to drug-free human serum, and analyzed the NEG-supplemented sera for creatinine with the Ektachem 700. We found the following linear relationships between creatinine bias (y, mg/L) and NEG concentration (x, mg/L) for first (I), third (III), and fourth (IV) generation slides: I: y = 1.70x - 0.8 mg/L (n = 13, r = 1.0) III: y = 0.39x - 0.3 mg/L (n = 3, r = 1.0) IV: y = 0.79x - 1.8 mg/L (n = 13, r = 1.0) Using HPLC, we directly demonstrated the presence of NEG in sera of patients receiving lidocaine and quantified NEG concentrations in sera from four of these patients. The increasing artifactual bias in creatinine with increasing NEG concentration unequivocally confirmed that NEG is responsible for the lidocaine-associated interference in the Kodak Ektachem single-slide creatinine method.