A Prospective Randomized Study in 100 Consecutive Patients Undergoing Major Liver Resection with Versus Without Ischemic Preconditioning

Pierre Alain Clavien, Markus Selzner, Hannes A. Rüdiger, Rolf Graf, Zakiyah Kadry, Valentin Rousson, Wolfram Jochum, D. Jaeck, T. E. Starzl, P. A. Clavien, A. M.M. Eggermont, M. Makuuchi, K. G. Tranberg, P. J. Friend

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Abstract

Objective: To evaluate the protective effects of ischemic preconditioning in a prospective randomized study involving a large population of unselected patients and to identify factors affecting the protective effects. Summary Background Data: Ischemic preconditioning is an effective protective strategy in several animal models. Protection has also been suggested in a small series of patients undergoing a hemihepatectomy with 30 minutes of inflow occlusion. Whether preconditioning confers protection in other types of liver resection and longer periods of ischemia is unknown. Therefore, we conducted a prospective randomized study to evaluate the impact of ischemic preconditioning in liver surgery. Methods: A total of 100 unselected patients undergoing major liver resection (> bisegmentectomy) under inflow occlusion for at least 30 minutes were randomized during surgery to either receive or not receive an ischemic preconditioning protocol (10 minutes of ischemia followed by 10 minutes of reperfusion). Univariate and multivariate analyses were performed to identify independent factors affecting the protective effects of ischemic preconditioning. ATP contents in liver were measured as a possible mechanism of protection. Results: Both groups (n = 50 in each) were comparable regarding age, gender, duration of inflow occlusion, and resected liver volumes. Postoperative serum transaminase levels were significantly lower in preconditioned than in control patients (median peak AST 364 U/L vs. 520 U/L, P = 0.028; ALT 406 vs. 519 U/L, P = 0.049). Regression multivariate analysis revealed an increased benefit of ischemic preconditioning in younger patients, in patients with longer duration of inflow occlusion (up to 60 minutes), and in cases of lower resected liver volume (<50%). Patients with steatosis were also particularly protected by ischemic preconditioning. ATP content in liver tissue was preserved by ischemic preconditioning in young but not older patients. Conclusions: This study establishes ischemic preconditioning as a protective strategy against hepatic ischemia in humans. The strategy is particularly effective in young patients requiring a prolonged period of inflow occlusion, and in the presence of steatosis, and is possibly related to preservation of ATP content in liver tissue. Other strategies are needed in older patients.

Original languageEnglish (US)
Pages (from-to)843-852
Number of pages10
JournalAnnals of surgery
Volume238
Issue number6
DOIs
StatePublished - Dec 2003

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Ischemic Preconditioning
Prospective Studies
Liver
Ischemia
Adenosine Triphosphate
Multivariate Analysis
Transaminases
Reperfusion
Animal Models
Regression Analysis

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

Clavien, Pierre Alain ; Selzner, Markus ; Rüdiger, Hannes A. ; Graf, Rolf ; Kadry, Zakiyah ; Rousson, Valentin ; Jochum, Wolfram ; Jaeck, D. ; Starzl, T. E. ; Clavien, P. A. ; Eggermont, A. M.M. ; Makuuchi, M. ; Tranberg, K. G. ; Friend, P. J. / A Prospective Randomized Study in 100 Consecutive Patients Undergoing Major Liver Resection with Versus Without Ischemic Preconditioning. In: Annals of surgery. 2003 ; Vol. 238, No. 6. pp. 843-852.
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title = "A Prospective Randomized Study in 100 Consecutive Patients Undergoing Major Liver Resection with Versus Without Ischemic Preconditioning",
abstract = "Objective: To evaluate the protective effects of ischemic preconditioning in a prospective randomized study involving a large population of unselected patients and to identify factors affecting the protective effects. Summary Background Data: Ischemic preconditioning is an effective protective strategy in several animal models. Protection has also been suggested in a small series of patients undergoing a hemihepatectomy with 30 minutes of inflow occlusion. Whether preconditioning confers protection in other types of liver resection and longer periods of ischemia is unknown. Therefore, we conducted a prospective randomized study to evaluate the impact of ischemic preconditioning in liver surgery. Methods: A total of 100 unselected patients undergoing major liver resection (> bisegmentectomy) under inflow occlusion for at least 30 minutes were randomized during surgery to either receive or not receive an ischemic preconditioning protocol (10 minutes of ischemia followed by 10 minutes of reperfusion). Univariate and multivariate analyses were performed to identify independent factors affecting the protective effects of ischemic preconditioning. ATP contents in liver were measured as a possible mechanism of protection. Results: Both groups (n = 50 in each) were comparable regarding age, gender, duration of inflow occlusion, and resected liver volumes. Postoperative serum transaminase levels were significantly lower in preconditioned than in control patients (median peak AST 364 U/L vs. 520 U/L, P = 0.028; ALT 406 vs. 519 U/L, P = 0.049). Regression multivariate analysis revealed an increased benefit of ischemic preconditioning in younger patients, in patients with longer duration of inflow occlusion (up to 60 minutes), and in cases of lower resected liver volume (<50{\%}). Patients with steatosis were also particularly protected by ischemic preconditioning. ATP content in liver tissue was preserved by ischemic preconditioning in young but not older patients. Conclusions: This study establishes ischemic preconditioning as a protective strategy against hepatic ischemia in humans. The strategy is particularly effective in young patients requiring a prolonged period of inflow occlusion, and in the presence of steatosis, and is possibly related to preservation of ATP content in liver tissue. Other strategies are needed in older patients.",
author = "Clavien, {Pierre Alain} and Markus Selzner and R{\"u}diger, {Hannes A.} and Rolf Graf and Zakiyah Kadry and Valentin Rousson and Wolfram Jochum and D. Jaeck and Starzl, {T. E.} and Clavien, {P. A.} and Eggermont, {A. M.M.} and M. Makuuchi and Tranberg, {K. G.} and Friend, {P. J.}",
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Clavien, PA, Selzner, M, Rüdiger, HA, Graf, R, Kadry, Z, Rousson, V, Jochum, W, Jaeck, D, Starzl, TE, Clavien, PA, Eggermont, AMM, Makuuchi, M, Tranberg, KG & Friend, PJ 2003, 'A Prospective Randomized Study in 100 Consecutive Patients Undergoing Major Liver Resection with Versus Without Ischemic Preconditioning', Annals of surgery, vol. 238, no. 6, pp. 843-852. https://doi.org/10.1097/01.sla.0000098620.27623.7d

A Prospective Randomized Study in 100 Consecutive Patients Undergoing Major Liver Resection with Versus Without Ischemic Preconditioning. / Clavien, Pierre Alain; Selzner, Markus; Rüdiger, Hannes A.; Graf, Rolf; Kadry, Zakiyah; Rousson, Valentin; Jochum, Wolfram; Jaeck, D.; Starzl, T. E.; Clavien, P. A.; Eggermont, A. M.M.; Makuuchi, M.; Tranberg, K. G.; Friend, P. J.

In: Annals of surgery, Vol. 238, No. 6, 12.2003, p. 843-852.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Prospective Randomized Study in 100 Consecutive Patients Undergoing Major Liver Resection with Versus Without Ischemic Preconditioning

AU - Clavien, Pierre Alain

AU - Selzner, Markus

AU - Rüdiger, Hannes A.

AU - Graf, Rolf

AU - Kadry, Zakiyah

AU - Rousson, Valentin

AU - Jochum, Wolfram

AU - Jaeck, D.

AU - Starzl, T. E.

AU - Clavien, P. A.

AU - Eggermont, A. M.M.

AU - Makuuchi, M.

AU - Tranberg, K. G.

AU - Friend, P. J.

PY - 2003/12

Y1 - 2003/12

N2 - Objective: To evaluate the protective effects of ischemic preconditioning in a prospective randomized study involving a large population of unselected patients and to identify factors affecting the protective effects. Summary Background Data: Ischemic preconditioning is an effective protective strategy in several animal models. Protection has also been suggested in a small series of patients undergoing a hemihepatectomy with 30 minutes of inflow occlusion. Whether preconditioning confers protection in other types of liver resection and longer periods of ischemia is unknown. Therefore, we conducted a prospective randomized study to evaluate the impact of ischemic preconditioning in liver surgery. Methods: A total of 100 unselected patients undergoing major liver resection (> bisegmentectomy) under inflow occlusion for at least 30 minutes were randomized during surgery to either receive or not receive an ischemic preconditioning protocol (10 minutes of ischemia followed by 10 minutes of reperfusion). Univariate and multivariate analyses were performed to identify independent factors affecting the protective effects of ischemic preconditioning. ATP contents in liver were measured as a possible mechanism of protection. Results: Both groups (n = 50 in each) were comparable regarding age, gender, duration of inflow occlusion, and resected liver volumes. Postoperative serum transaminase levels were significantly lower in preconditioned than in control patients (median peak AST 364 U/L vs. 520 U/L, P = 0.028; ALT 406 vs. 519 U/L, P = 0.049). Regression multivariate analysis revealed an increased benefit of ischemic preconditioning in younger patients, in patients with longer duration of inflow occlusion (up to 60 minutes), and in cases of lower resected liver volume (<50%). Patients with steatosis were also particularly protected by ischemic preconditioning. ATP content in liver tissue was preserved by ischemic preconditioning in young but not older patients. Conclusions: This study establishes ischemic preconditioning as a protective strategy against hepatic ischemia in humans. The strategy is particularly effective in young patients requiring a prolonged period of inflow occlusion, and in the presence of steatosis, and is possibly related to preservation of ATP content in liver tissue. Other strategies are needed in older patients.

AB - Objective: To evaluate the protective effects of ischemic preconditioning in a prospective randomized study involving a large population of unselected patients and to identify factors affecting the protective effects. Summary Background Data: Ischemic preconditioning is an effective protective strategy in several animal models. Protection has also been suggested in a small series of patients undergoing a hemihepatectomy with 30 minutes of inflow occlusion. Whether preconditioning confers protection in other types of liver resection and longer periods of ischemia is unknown. Therefore, we conducted a prospective randomized study to evaluate the impact of ischemic preconditioning in liver surgery. Methods: A total of 100 unselected patients undergoing major liver resection (> bisegmentectomy) under inflow occlusion for at least 30 minutes were randomized during surgery to either receive or not receive an ischemic preconditioning protocol (10 minutes of ischemia followed by 10 minutes of reperfusion). Univariate and multivariate analyses were performed to identify independent factors affecting the protective effects of ischemic preconditioning. ATP contents in liver were measured as a possible mechanism of protection. Results: Both groups (n = 50 in each) were comparable regarding age, gender, duration of inflow occlusion, and resected liver volumes. Postoperative serum transaminase levels were significantly lower in preconditioned than in control patients (median peak AST 364 U/L vs. 520 U/L, P = 0.028; ALT 406 vs. 519 U/L, P = 0.049). Regression multivariate analysis revealed an increased benefit of ischemic preconditioning in younger patients, in patients with longer duration of inflow occlusion (up to 60 minutes), and in cases of lower resected liver volume (<50%). Patients with steatosis were also particularly protected by ischemic preconditioning. ATP content in liver tissue was preserved by ischemic preconditioning in young but not older patients. Conclusions: This study establishes ischemic preconditioning as a protective strategy against hepatic ischemia in humans. The strategy is particularly effective in young patients requiring a prolonged period of inflow occlusion, and in the presence of steatosis, and is possibly related to preservation of ATP content in liver tissue. Other strategies are needed in older patients.

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