A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic

Beatrice Beck-Schimmer, Stefan Breitenstein, Severin Urech, Elisena De Conno, Moritz Wittlinger, Milo Puhan, Wolfram Jochum, Donat R. Spahn, Rolf Graf, Pierre Alain Clavien

Research output: Contribution to journalArticle

Abstract

Objective: To evaluate the effects of pharmacological preconditioning with a volatile anesthetic in patients undergoing liver resection with inflow occlusion. Background: In liver surgery, ischemic preconditioning and intermittent clamping are the only established protective strategies to reduce tissue damage due to ischemia during inflow occlusion. Preconditioning with volatile anesthetics has provided protection against cardiac and renal ischemic injury in several animal models through NO and HO-1 pathways. But pharmacological preconditioning has never been tested in patients undergoing liver surgery in a randomized trial. Methods: Sixty-four patients undergoing liver surgery with inflow occlusion were randomized intraoperatively for preconditioning with sevoflurane or not (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with propofol. Thirty minutes before inflow occlusion propofol was replaced by sevoflurane in the preconditioning group. Primary endpoint was postoperative liver injury assessed by peak values of liver transaminases. Postoperative complications were recorded according to an established scoring system. Results: Sevoflurane preconditioning significantly limited the postoperative increase of serum transaminase levels by 261 U/L (95% CI, 65 to 458; P - 0.01) for the ALT and by 239 (95% CI, -2 to 480; P - 0.05) for the AST corresponding to decreases of baseline levels of 35% and 31%, respectively. Patients with steatosis had an even better benefit than patients without steatosis. The rates of any complication (risk ratio 0.46; 95% CI, 0.25 to 0.85; P - 0.006) and of severe complications requiring invasive procedures (risk ratio 0.25; 95% CI, 0.06 to 1.08; P - 0.05) were also lowered by preconditioning. Conclusion: This first randomized trial of pharmacological preconditioning in liver surgery in humans showed a protective effect of preconditioning with volatile anesthetics. This strategy may provide a new and easily applicable therapeutic option to protect the liver and to lower complication rates.

Original languageEnglish (US)
Pages (from-to)909-916
Number of pages8
JournalAnnals of Surgery
Volume248
Issue number6
DOIs
StatePublished - Dec 2008
Externally publishedYes

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Anesthetics
Randomized Controlled Trials
Pharmacology
Liver
Propofol
Transaminases
Odds Ratio
Ischemic Preconditioning
Wounds and Injuries
Constriction
Ischemia
Anesthesia
Animal Models
Kidney
Serum
sevoflurane

ASJC Scopus subject areas

  • Surgery

Cite this

Beck-Schimmer, B., Breitenstein, S., Urech, S., Conno, E. D., Wittlinger, M., Puhan, M., ... Clavien, P. A. (2008). A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic. Annals of Surgery, 248(6), 909-916. https://doi.org/10.1097/SLA.0b013e31818f3dda

A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic. / Beck-Schimmer, Beatrice; Breitenstein, Stefan; Urech, Severin; Conno, Elisena De; Wittlinger, Moritz; Puhan, Milo; Jochum, Wolfram; Spahn, Donat R.; Graf, Rolf; Clavien, Pierre Alain.

In: Annals of Surgery, Vol. 248, No. 6, 12.2008, p. 909-916.

Research output: Contribution to journalArticle

Beck-Schimmer, B, Breitenstein, S, Urech, S, Conno, ED, Wittlinger, M, Puhan, M, Jochum, W, Spahn, DR, Graf, R & Clavien, PA 2008, 'A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic', Annals of Surgery, vol. 248, no. 6, pp. 909-916. https://doi.org/10.1097/SLA.0b013e31818f3dda
Beck-Schimmer, Beatrice ; Breitenstein, Stefan ; Urech, Severin ; Conno, Elisena De ; Wittlinger, Moritz ; Puhan, Milo ; Jochum, Wolfram ; Spahn, Donat R. ; Graf, Rolf ; Clavien, Pierre Alain. / A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic. In: Annals of Surgery. 2008 ; Vol. 248, No. 6. pp. 909-916.
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abstract = "Objective: To evaluate the effects of pharmacological preconditioning with a volatile anesthetic in patients undergoing liver resection with inflow occlusion. Background: In liver surgery, ischemic preconditioning and intermittent clamping are the only established protective strategies to reduce tissue damage due to ischemia during inflow occlusion. Preconditioning with volatile anesthetics has provided protection against cardiac and renal ischemic injury in several animal models through NO and HO-1 pathways. But pharmacological preconditioning has never been tested in patients undergoing liver surgery in a randomized trial. Methods: Sixty-four patients undergoing liver surgery with inflow occlusion were randomized intraoperatively for preconditioning with sevoflurane or not (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with propofol. Thirty minutes before inflow occlusion propofol was replaced by sevoflurane in the preconditioning group. Primary endpoint was postoperative liver injury assessed by peak values of liver transaminases. Postoperative complications were recorded according to an established scoring system. Results: Sevoflurane preconditioning significantly limited the postoperative increase of serum transaminase levels by 261 U/L (95{\%} CI, 65 to 458; P - 0.01) for the ALT and by 239 (95{\%} CI, -2 to 480; P - 0.05) for the AST corresponding to decreases of baseline levels of 35{\%} and 31{\%}, respectively. Patients with steatosis had an even better benefit than patients without steatosis. The rates of any complication (risk ratio 0.46; 95{\%} CI, 0.25 to 0.85; P - 0.006) and of severe complications requiring invasive procedures (risk ratio 0.25; 95{\%} CI, 0.06 to 1.08; P - 0.05) were also lowered by preconditioning. Conclusion: This first randomized trial of pharmacological preconditioning in liver surgery in humans showed a protective effect of preconditioning with volatile anesthetics. This strategy may provide a new and easily applicable therapeutic option to protect the liver and to lower complication rates.",
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AU - Beck-Schimmer, Beatrice

AU - Breitenstein, Stefan

AU - Urech, Severin

AU - Conno, Elisena De

AU - Wittlinger, Moritz

AU - Puhan, Milo

AU - Jochum, Wolfram

AU - Spahn, Donat R.

AU - Graf, Rolf

AU - Clavien, Pierre Alain

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N2 - Objective: To evaluate the effects of pharmacological preconditioning with a volatile anesthetic in patients undergoing liver resection with inflow occlusion. Background: In liver surgery, ischemic preconditioning and intermittent clamping are the only established protective strategies to reduce tissue damage due to ischemia during inflow occlusion. Preconditioning with volatile anesthetics has provided protection against cardiac and renal ischemic injury in several animal models through NO and HO-1 pathways. But pharmacological preconditioning has never been tested in patients undergoing liver surgery in a randomized trial. Methods: Sixty-four patients undergoing liver surgery with inflow occlusion were randomized intraoperatively for preconditioning with sevoflurane or not (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with propofol. Thirty minutes before inflow occlusion propofol was replaced by sevoflurane in the preconditioning group. Primary endpoint was postoperative liver injury assessed by peak values of liver transaminases. Postoperative complications were recorded according to an established scoring system. Results: Sevoflurane preconditioning significantly limited the postoperative increase of serum transaminase levels by 261 U/L (95% CI, 65 to 458; P - 0.01) for the ALT and by 239 (95% CI, -2 to 480; P - 0.05) for the AST corresponding to decreases of baseline levels of 35% and 31%, respectively. Patients with steatosis had an even better benefit than patients without steatosis. The rates of any complication (risk ratio 0.46; 95% CI, 0.25 to 0.85; P - 0.006) and of severe complications requiring invasive procedures (risk ratio 0.25; 95% CI, 0.06 to 1.08; P - 0.05) were also lowered by preconditioning. Conclusion: This first randomized trial of pharmacological preconditioning in liver surgery in humans showed a protective effect of preconditioning with volatile anesthetics. This strategy may provide a new and easily applicable therapeutic option to protect the liver and to lower complication rates.

AB - Objective: To evaluate the effects of pharmacological preconditioning with a volatile anesthetic in patients undergoing liver resection with inflow occlusion. Background: In liver surgery, ischemic preconditioning and intermittent clamping are the only established protective strategies to reduce tissue damage due to ischemia during inflow occlusion. Preconditioning with volatile anesthetics has provided protection against cardiac and renal ischemic injury in several animal models through NO and HO-1 pathways. But pharmacological preconditioning has never been tested in patients undergoing liver surgery in a randomized trial. Methods: Sixty-four patients undergoing liver surgery with inflow occlusion were randomized intraoperatively for preconditioning with sevoflurane or not (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with propofol. Thirty minutes before inflow occlusion propofol was replaced by sevoflurane in the preconditioning group. Primary endpoint was postoperative liver injury assessed by peak values of liver transaminases. Postoperative complications were recorded according to an established scoring system. Results: Sevoflurane preconditioning significantly limited the postoperative increase of serum transaminase levels by 261 U/L (95% CI, 65 to 458; P - 0.01) for the ALT and by 239 (95% CI, -2 to 480; P - 0.05) for the AST corresponding to decreases of baseline levels of 35% and 31%, respectively. Patients with steatosis had an even better benefit than patients without steatosis. The rates of any complication (risk ratio 0.46; 95% CI, 0.25 to 0.85; P - 0.006) and of severe complications requiring invasive procedures (risk ratio 0.25; 95% CI, 0.06 to 1.08; P - 0.05) were also lowered by preconditioning. Conclusion: This first randomized trial of pharmacological preconditioning in liver surgery in humans showed a protective effect of preconditioning with volatile anesthetics. This strategy may provide a new and easily applicable therapeutic option to protect the liver and to lower complication rates.

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