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Protection of Pharmacological Postconditioning in Liver Surgery: Results of a Prospective Randomized Controlled Trial

Beck-Schimmer, Beatrice MD*,†,‡; Breitenstein, Stefan MD*,§; Bonvini, John M. MD*,†; Lesurtel, Mickael MD, PhD*,§; Ganter, Michael MD*,†; Weber, Achim MD*,‖; Puhan, Milo A. MD, PhD¶,**; Clavien, Pierre-Alain MD, PhD, FACS*,§

doi: 10.1097/SLA.0b013e318272df7c
Original Articles From the ESA Proceedings

Objectives: To elucidate the possible organ-protective effect of pharmacological postconditioning in patients undergoing liver resection with inflow occlusion.

Background: Inflow occlusion reduces blood loss during liver transection in selected patients but is potentially harmful due to ischemia-reperfusion injury. Preventive strategies include the use of repetitive short periods of ischemia interrupted by a reperfusion phase (intermittent clamping), application of a short period of ischemia before transection (ischemic preconditioning), or pharmacological preconditioning before transection. Whether intervention after resection (postconditioning) may confer protection is unknown.

Methods: A 3 arm, prospective, randomized trial was designed for patients undergoing liver resection with inflow occlusion to compare the effects of pharmacological postconditioning with the volatile anesthetic agent sevoflurane (n = 48), intermittent clamping (n = 50), or no protective intervention (continuous inflow occlusion, n = 17). Endpoints included peak serum aspartate transaminase level, postoperative complications, and hospital stay. All patients were intravenously anesthetized with propofol. In patients with postconditioning, propofol infusion was stopped upon reperfusion and replaced with sevoflurane for 10 minutes.

Results: Compared with the control group, both postconditioning (P = 0.044) and intermittent clamping (P = 0.015) significantly reduced aspartate transaminase levels. The risk of complications was significantly decreased by postconditioning, odds ratio, 0.08 [95% confidence interval (CI), 0.02–0.36; P = 0.001]) and intermittent clamping, odds ratio, 0.50 [95% CI, 0.26–0.96; P = 0.038], compared with controls. Both interventions reduced length of hospital stay, postconditioning −4 days [95% CI, −6 to −1; P = 0.009], and intermittent clamping −2 days, [95% CI, −4 to 0; P = 0.019].

Conclusions: Pharmacological postconditioning reduces organ injury and postoperative complications. This easily applicable strategy should be used in patients with prolonged continuous inflow occlusion.

Pharmacological postconditioning with the volatile anesthetic agent sevoflurane during liver surgery is protective, reducing both organ injury and postoperative complications. Application of a volatile anesthetic agent is an easy and effective intervention, which in comparison with preconditioning and intermittent clamping, can be used after transection of the parenchyma.

*Swiss HPB (Hepato-Pancreato-Biliary) Center

Institute of Anesthesiology, University Hospital Zurich, Zurich, Switzerland

Institute of Physiology, Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland

§Department of Surgery

Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland

Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

**Horten Centre for Patient-Oriented Research, University of Zurich, Zurich, Switzerland.

Reprints: Pierre-Alain Clavien, MD, PhD, Department of Surgery, University Hospital Zurich, Raemistrasse 100, CH-8091 Zurich, Switzerland. E-mail: clavien@access.uzh.ch.

B.B-S. and S.B. contributed equally as first authors.

M.A.P. and P-A.C. contributed as senior authors.

This study was funded by LGID (Liver and Gastrointestinal Disease Foundation), Zurich, Switzerland.

Disclosure: The authors declare no conflicts of interest.

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© 2012 Lippincott Williams & Wilkins, Inc.