The concentration of lidocaine in the blood after intravenous and epidural administration with extensive hepatic resections

Abstract

The aim of the work: to identify the concentration of lidocaine in patients’ blood during an extensive hepatic resection, with its intravenous and epidural administration in dynamics for intra- and postoperative analgesia, to evaluate its analgesic effect and toxicity potential. Materials and methods. The study included 27 patients, who underwent hepatic resection with preservation of 30–60 % of the parenchyma. For all patients, multicomponent intraoperative anesthesia was used. Depending on the adjuvant, patients were divided into two groups: the main group (group 1) consisted of 7 patients who received intravenous (IV) administration of lidocaine, and a comparison group of 20 patients (group 2) whose complex anesthesia was supplemented with thoracic epidural anesthesia (EDA). To solve the tasks was to develop and validate a rapid, sensitive and robust method for the detection and quantification of lidocaine in human plasma using purification by coagulation and ultracentrifugation with cooling followed Liquid chromatography with Orbitrap HRMS method. The method showed a dynamic linear range of 0.1 to 1000 ng/mL with a linearity expressed by the regression coefficient (R2) and a value of 0.9947. The quantitation limit (LOQ) was found to be 1 ng/mL and the detection limit (LOD) 0.3 ng/mL. Recovery accuracy and repeatability were satisfactory. Finally, the method was applied to 54 real human plasma. Results and Discussion. 2 hours after the surgery, there was a tendency (P = 0.29) for a higher concentration of lidocaine in the blood by 28.8 % after epidural administration of lidocaine compared with intravenous administration (1.84 μg/ml in group 1, 2.37 µg/ml – in group 2, p = 0.29), with no fundamental difference 14 hours after surgery (2.62 µg/ml and 2.85 µg/ml, p = 0.76). Epidural administration of the drug was also accompanied by a tendency to increase the frequency of hemodynamic disorders, which was reflected in an increase in the dose of norepinephrine, which was intended to correct blood circulation parameters, by 1.3 times (total dose in group 1 (158.4±58.1) ng, group 2 – (206.9±76.4) ng, p = 0.14). No life-threatening toxic reactions were noticed in any of the cases. The use of lidocaine as an adjuvant for intra- and postoperative analgesia by intravenous and epidural administration with extensive hepatic resections, in most cases, does not lead to an increase of the drug compound in the blood higher than the generally accepted toxic content is. The content of the drug in the blood can be exceeded with epidural administration compared with intravenous administration. The analgesic effect of intravenous lidocaine is not lower than the epidural and may even last longer until the first administration of a narcotic analgesic after surgery for pain relief. However, epidural block is accompanied by intraoperative hemodynamic instability and an increase in the total dose of norepinephrine to correct blood circulation parameters.