Non-anaesthetic effects of modern halogen-containing anaesthetics

Many patients undergo surgery under general anaesthesia each day. One of the high-priority tasks for an anesthesiologist is to protect tissues from a systemic inflammatory reaction or oxidative distress (including ischaemia/reperfusion). This review aims to demonstrate the anti-inflammatory and antioxidant properties of general anaesthesia in experimental and clinical studies. Halogenated anaesthetics lead to the inactivation of glycogen synthase kinase-3β (GSK-3β), a key enzyme in the implementation of cellular damage mechanisms and systemic inflammatory response syndrome (SIRS). These mechanisms are implemented through the transcription factor nuclear factor (NF)-κB. As a result of NF-κB activation, gene expression responsible for proinflammatory cytokine synthesis follows, activating leukocytes and disrupts endothelial cell junctions, leading to a disruption of the endothelial barrier, leukocyte infiltration into tissues, and the development of SIRS. Furthermore, GSK-3β phosphorylation causes an increase in the level in neuronal cells and hepatocytes of transcription factor Nrf2, which is a master regulator of enzyme levels of antioxidant defence in the cell. Thus, halogenated anaesthetics interfere with different elements responsible for the implementation of SIRS and oxidative distress in addition to limiting disturbing factors during the development of multiorgan failure and endothelial dysfunction in experimental sepsis and a model of ischaemia/reperfusion. Understanding these processes can help to reduce many complications during the post-operative period. Received 9 January 2020. Revised 6 April 2020. Accepted 7 April 2020. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Author contributions Conception and study design: O.A. Grebenchikov, Y.V. Skripkin, V.V. Likhvantsev Drafting the article: O.A. Grebenchikov, Y.V. Skripkin, O.N. Gerasimenko, K.K. Kadantseva, A.L. Bachinskiy, L.B. Berikashvili, V.V. Likhvantsev Critical revision of the article: О.А. Grebenchikov, K.K. Kadantseva Final approval of the version to be published: O.A. Grebenchikov, Y.V. Skripkin, O.N. Gerasimenko, K.K. Kadantseva, A.L. Bachinskiy, L.B. Berikashvili, V.V. Likhvantsev