Pharmacokinetic and clinical effects of two bupivacaine concentrations on axillary brachial plexus block / Efeitos farmacocinéticos e clínicos de duas concentrações de bupivacaína no bloqueio do plexo braquial via axilar

Abstract Introduction: The risk of systemic bupivacaine toxicity is a persistent problem, which makes its pharmacokinetic study fundamental for regional anesthesia safety. There is little evidence of its influence on plasma peak at different concentrations. The present study compares two bupivacaine concentrations to establish how the concentration affects this drug plasma peak in axillary brachial plexus block. Postoperative latency and analgesia were also compared. Methods: 30 patients were randomized. In the 0.25% Group, 0.25% bupivacaine (10 mL) was injected per nerve. In the 0.5% Group, 0.5% bupivacaine (5 mL) was injected per nerve. Peripheral blood samples were collected during the first 2 h after the blockade. For sample analyses, high performance liquid chromatography mass spectrometry was used. Results: Plasma peak occurred 45 min after the blockade, with no difference between groups at the assessed time-points. Plasma peak was 933.97 ± 328.03 ng.mL−1 (mean ± SD) in 0.25% Group and 1022.79 ± 253.81 ng.mL−1 in 0.5% Group (p = 0.414). Latency was lower in 0.5% Group than in 0.25% Group (10.67 ± 3.71 × 17.33 min ± 5.30, respectively, p = 0.004). No patient had pain within the first 4 h after the blockade. Conclusion: For axillary brachial plexus block, there was no difference in bupivacaine plasma peak despite the use of different concentrations with the same local anesthetic mass. The concentration inversely influenced latency.

Resumo Introdução: O risco de intoxicação sistêmica pelo uso da bupivacaína é um problema persistente e torna seu estudo farmacocinético fundamental para a segurança da anestesia regional. São escassas as evidências sobre a influência de diferentes concentrações no pico plasmático desse fármaco. O presente estudo compara duas concentrações de bupivacaína para estabelecer como a concentração afeta o pico plasmático desse fármaco no bloqueio do plexo braquial via axilar. Também se compararam latência e analgesia pós-operatória. Métodos: Foram randomizados 30 pacientes. No Grupo 0,25%, injetaram-se 10 mL de bupivacaína 0,25% por nervo. No Grupo 0,5%, injetaram-se 5 mL de bupivacaína 0,5% por nervo. Amostras de sangue periférico foram colhidas durante as duas primeiras horas após o bloqueio. Para análise das amostras, usou-se a cromatografia líquida de alta frequência acoplada ao espectrômetro de massas. Resultados: O pico plasmático ocorreu 45 minutos após o bloqueio, sem diferença entre os grupos nos tempos avaliados. O pico plasmático (média ± DP) foi 933,97 ± 328,03 ng.mL−1 no Grupo 0,25% e 1.022,79 ± 253,81 ng.mL−1 no Grupo 0,5% (p = 0,414). O Grupo 0,5% apresentou menor latência com relação ao Grupo 0,25% (10,67 ± 3,71 × 17,33 min ± 5,30; respectivamente; p = 0,004). Nenhum paciente apresentou dor nas primeiras quatro horas após o bloqueio. Conclusão: Para o bloqueio do plexo braquial via axilar, não foi detectada diferença no pico plasmático de bupivacaína apesar do uso de diferentes concentrações, com a mesma massa de anestésico local. A concentração influenciou inversamente a latência.

[Pharmacokinetic and clinical effects of two bupivacaine concentrations on axillary brachial plexus block]. / Efeitos farmacocinéticos e clínicos de duas concentrações de bupivacaína no bloqueio do plexo braquial via axilar.

INTRODUCTION: The risk of systemic bupivacaine toxicity is a persistent problem, which makes its pharmacokinetic study fundamental for regional anesthesia safety. There is little evidence of its influence on plasma peak at different concentrations. The present study compares two bupivacaine concentrations to establish how the concentration affects this drug plasma peak in axillary brachial plexus block. Postoperative latency and analgesia were also compared. METHODS: 30 patients were randomized. In the 0.25% Group, 0.25% bupivacaine (10mL) was injected per nerve. In the 0.5% Group, 0.5% bupivacaine (5mL) was injected per nerve. Peripheral blood samples were collected during the first 2hours after the blockade. For sample analyses, high performance liquid chromatography mass spectrometry was used. RESULTS: Plasma peak occurred 45minutes after the blockade, with no difference between groups at the assessed time-points. Plasma peak was 933.97 ± 328.03 ng.mL-1 (mean ± SD) in 0.25% Group and 1022.79 ± 253.81 ng.mL-1 in 0.5% Group (p = 0.414). Latency was lower in 0.5% Group than in 0.25% Group (10.67 ± 3.71 × 17.33min ± 5.30, respectively, p = 0.004). No patient had pain within the first 4hours after the blockade. CONCLUSION: For axillary brachial plexus block, there was no difference in bupivacaine plasma peak despite the use of different concentrations with the same local anesthetic mass. The concentration inversely influenced latency.

Profiles of amino acids and biogenic amines in the plasma of Cri-du-Chat patients.

Cri-du-chat syndrome (CDCS) is a rare innate disease attributed to chromosome 5p deletion characterized by a cat-like cry, craniofacial malformation, and altered behavior of affected children. Metabolomic analysis and a chemometric approach allow description of the metabolic profile of CDCS as compared to normal subjects. In the present work, UHPLC/MS was employed to analyze blood samples withdrawn from CDCS carriers (n=18) and normal parental subjects (n=18), all aged 0-34 years, aiming to set up a representative CDCS profile constructed from 33 targeted amino acids and biogenic amines. Methionine sulfoxide (MetO) was of particular concern with respect to CDCS redox balance. Increased serotonin (3-fold), methionine sulfoxide (2-fold), and Asp levels, and a little lower Orn, citrulline, Leu, Val, Ile, Asn, Gln, Trp, Thr, His, Phe, Met, and creatinine levels were found in the plasma of CDCS patients. Nitrotyrosine and Trp did not differ in normal and CDCS individuals.The accumulated metabolites may reflect, respectively, disturbances in the redox balance, deficient purine biosynthesis, and altered behavior, whereas the amino acid abatement in the latter group may affect the homeostasis of the urea cycle, citric acid cycle, branched chain amino acid synthesis, Tyr and Trp metabolism and amino acid biosynthesis. The identification of enzymatic deficiencies leading to the amino acid burden in CDCS is further required for elucidating its molecular bases and eventually propose specific or mixed amino acid supplementation to newborn patients aiming to balance their metabolism.