• I.I. Lisnyy National Cancer Institute, Kyiv, Ukraine
  • K.A. Zakalska National Cancer Institute, Kyiv, Ukraine
  • A.A. Burlaka National Cancer Institute, Kyiv, Ukraine
  • S.A. Lysykh National Cancer Institute, Kyiv, Ukraine
  • O.V. Efimenko National Cancer Institute, Kyiv, Ukraine



colorectal cancer, liver metastasis, ischemia-reperfusion injury, sevoflurane preconditioning


Background. The intermittent Pringle maneuver remains the major technique for controlling hemorrhage during liver surgery. Nevertheless, this procedure involves a risk of triggering a cascade of pathological changes resulting in the ischemia-reperfusion injury (I/R) effect. The pharmacological prevention of this I/R injury represents a promising approach. The aim of the study was to compare the effects of pharmacological preconditioning with sevoflurane and propofol-based intravenous anesthesia on the postoperative function of the liver as the primary end-point. Materials and Methods. A prospective cohort study includes the analysis of the data of 73 patients who underwent liver surgery. In the study group (n = 41), preconditioning with sevoflurane inhalation was provided 30 minutes prior to liver resection. In the control group (n = 32), sevoflurane preconditioning was not provided. The primary endpoints were blood lactate concentration shortly after the surgery and one day later; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities on postoperative Days 1, 3, and 5 as markers of hepatocyte damage. Results. On postoperative Day 1, in patients of the study group, lactate decreased to preoperative levels, while in the control group, lactate content increased as compared to both preoperative levels and the levels immediately after liver resection. A significant difference in AST activity levels between the groups was registered on Day 5, although this difference was not clinically relevant. The decrease in the prothrombin index in the study group on Day 3 was superior to that in the control group. The multiple regression analysis demonstrated a moderate positive association between the number of resected liver segments and the markers of the functional state of the liver in the study group while in the control group, such association was not significant. Conclusion. The protective effect of sevoflurane on the postoperative function of the liver is manifested by the lower level of blood lactate and the stable level of transaminase activity.


Jarnagin WR, Gonen M, Fong Y, et al. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg. 2002;236:397-406. doi: 10.1097/01.SLA.0000029003.66466.B3

Man K, Fan ST, Ng IO, et al. Prospective evaluation of Pringle maneuver in hepatectomy for liver tumors by a randomized study. Ann Surg. 1997;226:704-711.

Jiménez-Castro MB, Cornide-Petronio ME, Gracia-Sancho J, Peralta C. Inflammasome-mediated inflammation in liver ischemia-reperfusion injury. Cells. 2019;8(10):1131. doi: 10.3390/cells8101131

Clavien PA, Selzner M, Rüdiger HA, et al. A prospective randomized study in 100 consecutive patients undergo- ing major liver resection with versus without ischemic preconditioning. Ann Surg. 2003;238(6):843-850; discus- sion 851-852. doi: 10.1097/01.sla.0000098620.27623.7d

Hogal RH, Mergental H, Mirza DF, Afford SC. The emerging importance of liver sinusoidal endothelial cells in regulating injury during machine perfusion of deceased liver donors. Semin Liver Dis. 2018;38(3):252-259. doi: 10.1055/s-0038-1661371

Koneru B, Fisher A, He Y, et al. Ischemic preconditioning in deceased donor liver transplantation: a prospective randomized clinical trial of safety and efficacy. Liver Transpl. 2005;11(2):196-202. doi: 10.1002/lt.20315

Koneru B, Shareef A, Dikdan G, et al. The ischemic preconditioning paradox in deceased donor liver transplanta- tion—evidence from a prospective randomized single blind clinical trial. Am J Transplant. 2007;7(12):2788-2796. doi: 10.1111/j.1600-6143.2007.02009.x

Boleslawski E, Vibert E, Pruvot FR, et al. Relevance of postoperative peak transaminase after elective hepatec- tomy. Ann Surg. 2014;260:815-820. doi: 10.1097/SLA.0000000000000942

van de Poll MC, Derikx JP, Buurman WA, et al. Liver manipulation causes hepatocyte injury and precedes sys- temic inflammation in patients undergoing liver resection. World J Surg. 2017; 31:2033-2038. doi: 10.1007/ s00268-007-9182-4

van den Broek MA, Shiri-Sverdlov R, Schreurs JJ, et al. Liver manipulation during liver surgery in humans is as- sociated with hepatocellular damage and hepatic inflammation. Liver Int. 2013;33:633-641. doi: 10.1111/liv.12051

Burlaka A, Paliichuk A, Makhmudov D, et al. Impact of the Pringle manoeuvre on the mitochondrial redox state of hepatocytes in colorectal cancer patients with liver metastases. Contemp Oncol (Pozn). 2021;25:185-190. doi: 10.5114/wo.2021.110050

Dmytriiev D, Dmytriiev K, Stoliarchuk O, Semenenko A. Multiple organ dysfunction syndrome: What do we know about pain management? A narrative review. Anaesth Pain Intensive Care. 2019;23(1):84-91.

Kuchyn IL. Spinal anesthesia with low doses of local anesthetic in patients with multiple trauma. Lik Sprava. 2014;(3-4):95-99 (in Ukrainian).

Müllenheim J, Ebel D, Frässdorf J, et al. Isoflurane preconditions myocardium against infarction via release of free radicals. Anesthesiology. 2002;96:934-940. doi: 10.1097/00000542-200204000-00022

Tanaka K, Ludwig LM, Kersten JR, et al. Mechanisms of cardioprotection by volatile anesthetics. Anesthesiology. 2004;100:707-721. doi: 10.1097/00000542-200403000-00035

Beck-Schimmer B, Breitenstein S, Urech S, et al. A randomized controlled trial on pharmacological pre- conditioning in liver surgery using a volatile anesthetic. Ann Surg. 2008;248:909-918. doi: 10.1097/ SLA.0b013e31818f3dda

Barrier A, Olaya N, Chiappini F, et al. Ischemic preconditioning modulates the expression of several genes, lead- ing to the overproduction of IL-1Ra, iNOS, and Bcl-2 in a human model of liver ischemia-reperfusion. FASEB J. 2005;19:1617–1626. doi: 10.1096/fj.04-3445com

Kunst G, Klein AA. Peri-operative anaesthetic myocardial preconditioning and protection - cellular mechanisms and clinical relevance in cardiac anaesthesia. Anaesthesia. 2015;70(4):467-482. doi: 10.1111/anae.12975

Toda N, Toda H, Hatano Y. Anesthetic modulation of immune reactions mediated by nitric oxide. J Anesth. 2008; 22:155-162. doi: 10.1007/s00540-007-0590-2

Slankamenac K, Breitenstein S, Beck-Schimmer B, et al. Does pharmacological conditioning with the volatile anaesthetic sevoflurane offer protection in liver surgery? HPB (Oxford). 2012;14:854-862. doi: 10.1111/j.1477- 2574.2012.00570.x

Figueira ERR, Rocha-Filho JA, Lanchotte C, et al. Sevoflurane preconditioning plus postconditioning decreases inflammatory response with hemodynamic recovery in experimental liver ischemia reperfusion. Gastroenterol Res Pract. 2019;2019:5758984. doi: 10.1155/2019/5758984

Nguyen TM, Fleyfel M, Boleslawski E. Effect of pharmacological preconditioning with sevoflurane during hepatec- tomy with intermittent portal triad clamping. HPB (Oxford). 2019;21:1194-1202. doi: 10.1016/j.hpb.2019.01.009

Rahbari NN, Garden OJ, Padbury R, et al. Posthepatectomy liver failure: a definition and grading by the interna- tional study group of liver surgery (ISGLS). Surgery. 2011;149:713-724. doi: 10.1016/j.surg.2010.10.001

Mullen JT, Ribero D, Reddy SK, et al. Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergo- ing major hepatectomy. J Am Coll Surg. 2007;204:854-862. doi: 10.1016/j.jamcollsurg.2006.12.032

Riess ML, Kevin LG, Camara AK, et al. Dual exposure to sevoflurane improves anesthetic preconditioning in in- tact hearts. Anesthesiology. 2004;100:569-574. doi: 10.1097/00000542-200403000-00016

Riess ML, Eells JT, Kevin LG, et al. Attenuation of mitochondrial respiration by sevoflurane in isolated car- diac mitochondria is mediated in part by reactive oxygen species. Anesthesiology. 2004;100:498-505. doi: 10.1097/00000542-200403000-00007

Obal D, Preckel B, Scharbatke H, et al. One MAC of sevoflurane provides protection against reperfusion injury in the rat heart in vivo. Br J Anaesth. 2001;87:905-911. doi: 10.1093/bja/87.6.905

Zitta K, Meybohm P, Bein B, et al. Cytoprotective effects of the volatile anesthetic sevoflurane are highly depen- dent on timing and duration of sevoflurane conditioning: findings from a human, in-vitro hypoxia model. Eur J Pharmacol. 2010;645:39-46. doi: 10.1016/j.ejphar.2010.07.017

Lisnyy I, Zakalska K, Melnyk V, et al. Assessment and correction of liver function in liver resection. Lek Obz. 2021;70(9):297-303.

Submitted: February 22, 2023




How to Cite

Lisnyy, I., Zakalska, K., Burlaka, A., Lysykh, S., & Efimenko, O. (2023). PREVENTION OF PATHOLOGICAL EFFECT OF ISCHEMIA-REPERFUSION IN LIVER RESECTION BY SEVOFLURANE PRECONDITIONING. Experimental Oncology, 45(2), 252–262.



Original contributions