Experimental and Clinical Aspects of Sevoflurane Preconditioning and Postconditioning to Alleviate Hepatic Ischemia-Reperfusion Injury: A Scoping Review

Abstract

Ischemia-reperfusion injury (IRI) is an inflammatory process inherent in organ transplantation procedures. It is associated with tissue damage and, depending on its intensity, can impact early graft function. In liver transplantation (LT), strategies to alleviate IRI are essential in order to increase the use of extended criteria donor (ECD) grafts, which are more susceptible to IRI, as well as to improve postoperative graft and patient outcomes. Sevoflurane, a commonly used volatile anesthetic, has been shown to reduce IRI. This scoping review aims to give a comprehensive overview of the existing experimental and clinical data regarding the potential benefits of sevoflurane for hepatic IRI (HIRI) and to identify any gaps in knowledge to guide further research. We searched Medline and Embase for relevant articles. A total of 380 articles were identified, 45 of which were included in this review. In most experimental studies, the use of sevoflurane was associated with a significant decrease in biomarkers of acute liver damage and oxidative stress. Administration of sevoflurane before hepatic ischemia (preconditioning) or after reperfusion (postconditioning) appears to be protective. However, in the clinical setting, results are conflicting. While some studies showed a reduction of postoperative markers of liver injury, the benefit of sevoflurane on clinical outcomes and graft survival remains unclear. Further prospective clinical trials remain necessary to assess the clinical relevance of the use of sevoflurane as a protective factor against HIRI.

Keywords: anesthesia; ischemia reperfusion injury; liver transplantation; sevoflurane.

Figure 1

Study Flow Chart.

Figure 2

Biological processes involved in sevoflurane protection against HIRI. Akt = protein kinase B; Bax = Bcl-2-associated X protein; Bcl-2 = B-cell lymphoma 2; eIF2α = Eukaryotic Initiation Factor 2 α; Grp-78 = glucose-regulated protein 78; GSK3β = glycogen synthase kinase-3 beta; HGF = hepatocyte growth factor; HIRI = hepatic ischemia-reperfusion injury; HMGB1 = high mobility group box 1; HO-1 = heme oxygenase 1; ICAM-1 = Intercellular Adhesion Molecule 1; IκBα = NF-κB inhibitor alpha; JAK = janus kinase; JNK = c-Jun N-terminal kinase; MET = Met tyrosine kinase receptor; miRNA = microRNA; mPTP = mitochondrial permeability transition pore; mTOR = mechanistic target of rapamycin; NF-κB = Nuclear factor kappa-light-chain-enhancer of activated B cells; PERK = protein kinase R-like endoplasmic reticulum kinase; PI3K = Phosphoinositide 3-kinase; p-p65 = phosphorylated p65; STAT3 = signal transducer and activator of transcription protein 3; TLR4 = toll-like receptor 4; and TRAF-6 = TNF receptor-associated factor 6.