Semenko N. Prevention of systemic toxicity of local anesthetics during the regional anesthesia of peripheral nerves and plexuses

The aim of the study was to increase the level of safety and effectiveness of regional anesthesia of peripheral nerve plexuses. The goal was achieved by retrospectively analyzing cases of systemic toxicity of local anesthetics in hospitals in Ukraine, comparing the incidence of rhythm disturbances in the early perioperative period during surgical interventions of a traumatological profile using general or regional anesthesia, and determining a safer hypnotic in the combination of general and regional anesthesia in the case of the development of systemic toxicity of local anesthetics in an experiment on biological models of domestic rabbits. Three stages of the study were performed in the process of work. At the first stage, a survey was conducted of 287 anesthesiologists working in hospitals in Ukraine. The survey was conducted from October 2021 to February 2022 by anonymously filling out a privately distributed Google form. The survey design was approved by the ethics committee of the O.O. Bogomolets (protocol No. 151 dated October 25, 2021). When filling out the questionnaire, all participants signed a digital informed consent form. The link to the survey was sent to each member of the Association of Anesthesiologists by email (https://aaukr.org/opytuvannya-shhodo-vypadkiv-toksychnosti-mistsevyh-anestetykiv). The questionnaire was designed to ensure sufficient data collection from respondents on demographics, awareness of LAST recommendations, availability of ultrasound navigation, and preparation of fat emulsions in their departments. Special attention was paid to including information on compliance with the safety protocol and use of the checklist during regional anesthesia, as well as on discussing and recording information on LAST cases that occurred in the hospitals where the survey participants work. Only practicing anesthesiologists, heads of departments, practicing postgraduate students, and teachers were invited to participate in the survey. The second part of the study was an experiment on a biological model of domestic rabbits to simulate the systemic toxicity syndrome of local anesthetics (LAST). The essence of the experiment was to determine a safer hypnotic in the context of the development of LAST with a combination of general and regional anesthesia. After the start of prolonged intravenous infusion of bupivacaine to a domestic rabbit already receiving general anesthesia using sevoflurane or propofol as a hypnotic, the plasma concentration of bupivacaine was determined at the time of the appearance of the first rhythm disturbances and at the time of asystole. 2-group randomized experimental study. 10 domestic rabbits (Oryctolagus cuniculus domesticus) were divided into 2 groups depending on the type of general anesthesia (GA): propofol and sevoflurane group. Intramuscular sedation was performed before the procedure. After tracheal intubation, artificial pulmonary ventilation (PV) was started. In group 1, 1% propofol was started at a rate of 1.8 mg/kg/min. In group 2, 4.0% sevoflurane was started by inhalation. 30 minutes after intubation, heart rate and QRS duration were recorded as a “baseline”, after which intravenous bupivacaine solution 0.25% was started at a rate of 1.0 mg/kg/min. Blood samples were obtained when predefined ECG changes were observed and when heart rate reached 75%, 50%, 25% of baseline and 0 beats/min (15 seconds after the last systole). Analysis of bupivacaine in rabbit blood plasma was performed using liquid chromatography-tandem mass spectrometry on Shimadzu LCMS-8050 according to the method developed at the Bogomolets National Medical University. The study compared the plasma concentration of bupivacaine hydrochloride at the time of the first rhythm disturbances and at the time of asystole. In addition, the time to the onset of arrhythmia and asystole was recorded at the same doses of bupivacaine hydrochloride.