Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery

Troels Dirch Poulsen; Lars Willy Andersen; Daniel Steinbrüchel; Jens Peter Gøtze; Ole Steen Jørgensen; Niels Vidiendal Olsen

doi:10.1053/j.jvca.2008.08.018

Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery

Troels Dirch Poulsen, Lars Willy Andersen, Daniel Steinbrüchel, Jens Peter Gøtze, Ole Steen Jørgensen, Niels Vidiendal Olsen

20 Citations (Scopus)

Abstract

OBJECTIVES: Cardiac surgery and cardiopulmonary bypass (CPB) induce an inflammatory reaction that may lead to tissue injury. Experimental studies suggest that recombinant human erythropoietin (EPO) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug. This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB.

DESIGN AND SETTING: A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital.

PARTICIPANTS: Patients scheduled for coronary artery bypass graft surgery with CPB.

INTERVENTIONS: EPO (epoetin alfa, 500 IU/kg intravenously, n = 22) or placebo (n = 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia.

MEASUREMENTS AND MAIN RESULTS: CPB in both groups greatly increased plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-1beta receptor antagonist, IL-6, IL-10, and N-terminal probrain natriuretic peptide (NT-proBNP). Compared with placebo, EPO at day 3 after CPB augmented the TNF-alpha response (p < 0.05) and at 2 hours after CPB increased NT-proBNP (p < 0.05). Also, EPO tended to enhance the CPB-induced increase in IL-1beta receptor antagonist (p = 0.057). Otherwise, EPO had no effect on pro- and antiinflammatory mediators compared with placebo.

CONCLUSIONS: Two large doses of EPO given shortly before CPB do not reduce perioperative release of inflammatory cytokines. In contrast, EPO may augment the TNF-alpha and NT-proBNP response. Although the long-term clinical impact remains unknown, the findings do not support use of EPO as an anti-inflammatory drug in patients undergoing cardiac surgery.

Original language	English
Journal	Journal of Cardiothoracic and Vascular Anesthesia
Volume	23
Issue number	3
Pages (from-to)	316-23
Number of pages	8
ISSN	1053-0770
DOIs	https://doi.org/10.1053/j.jvca.2008.08.018
Publication status	Published - Jun 2009

Keywords

Aged
Cardiac Surgical Procedures
Double-Blind Method
Erythropoietin
Female
Humans
Inflammation Mediators
Male
Middle Aged
Postoperative Complications
Preoperative Care
Prospective Studies
Recombinant Proteins
Time Factors

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10.1053/j.jvca.2008.08.018

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Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery. / Poulsen, Troels Dirch; Andersen, Lars Willy; Steinbrüchel, Daniel et al.

In: Journal of Cardiothoracic and Vascular Anesthesia, Vol. 23, No. 3, 06.2009, p. 316-23.

Research output: Contribution to journal › Journal article › Research › peer-review

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abstract = "OBJECTIVES: Cardiac surgery and cardiopulmonary bypass (CPB) induce an inflammatory reaction that may lead to tissue injury. Experimental studies suggest that recombinant human erythropoietin (EPO) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug. This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB.DESIGN AND SETTING: A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital.PARTICIPANTS: Patients scheduled for coronary artery bypass graft surgery with CPB.INTERVENTIONS: EPO (epoetin alfa, 500 IU/kg intravenously, n = 22) or placebo (n = 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia.MEASUREMENTS AND MAIN RESULTS: CPB in both groups greatly increased plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-1beta receptor antagonist, IL-6, IL-10, and N-terminal probrain natriuretic peptide (NT-proBNP). Compared with placebo, EPO at day 3 after CPB augmented the TNF-alpha response (p < 0.05) and at 2 hours after CPB increased NT-proBNP (p < 0.05). Also, EPO tended to enhance the CPB-induced increase in IL-1beta receptor antagonist (p = 0.057). Otherwise, EPO had no effect on pro- and antiinflammatory mediators compared with placebo.CONCLUSIONS: Two large doses of EPO given shortly before CPB do not reduce perioperative release of inflammatory cytokines. In contrast, EPO may augment the TNF-alpha and NT-proBNP response. Although the long-term clinical impact remains unknown, the findings do not support use of EPO as an anti-inflammatory drug in patients undergoing cardiac surgery.",

keywords = "Aged, Cardiac Surgical Procedures, Double-Blind Method, Erythropoietin, Female, Humans, Inflammation Mediators, Male, Middle Aged, Postoperative Complications, Preoperative Care, Prospective Studies, Recombinant Proteins, Time Factors",

author = "Poulsen, {Troels Dirch} and Andersen, {Lars Willy} and Daniel Steinbr{\"u}chel and G{\o}tze, {Jens Peter} and J{\o}rgensen, {Ole Steen} and Olsen, {Niels Vidiendal}",

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doi = "10.1053/j.jvca.2008.08.018",

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T1 - Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery

AU - Poulsen, Troels Dirch

AU - Andersen, Lars Willy

AU - Steinbrüchel, Daniel

AU - Gøtze, Jens Peter

AU - Jørgensen, Ole Steen

AU - Olsen, Niels Vidiendal

PY - 2009/6

Y1 - 2009/6

N2 - OBJECTIVES: Cardiac surgery and cardiopulmonary bypass (CPB) induce an inflammatory reaction that may lead to tissue injury. Experimental studies suggest that recombinant human erythropoietin (EPO) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug. This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB.DESIGN AND SETTING: A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital.PARTICIPANTS: Patients scheduled for coronary artery bypass graft surgery with CPB.INTERVENTIONS: EPO (epoetin alfa, 500 IU/kg intravenously, n = 22) or placebo (n = 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia.MEASUREMENTS AND MAIN RESULTS: CPB in both groups greatly increased plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-1beta receptor antagonist, IL-6, IL-10, and N-terminal probrain natriuretic peptide (NT-proBNP). Compared with placebo, EPO at day 3 after CPB augmented the TNF-alpha response (p < 0.05) and at 2 hours after CPB increased NT-proBNP (p < 0.05). Also, EPO tended to enhance the CPB-induced increase in IL-1beta receptor antagonist (p = 0.057). Otherwise, EPO had no effect on pro- and antiinflammatory mediators compared with placebo.CONCLUSIONS: Two large doses of EPO given shortly before CPB do not reduce perioperative release of inflammatory cytokines. In contrast, EPO may augment the TNF-alpha and NT-proBNP response. Although the long-term clinical impact remains unknown, the findings do not support use of EPO as an anti-inflammatory drug in patients undergoing cardiac surgery.

AB - OBJECTIVES: Cardiac surgery and cardiopulmonary bypass (CPB) induce an inflammatory reaction that may lead to tissue injury. Experimental studies suggest that recombinant human erythropoietin (EPO) independent of its erythropoietic effect may be used clinically as an anti-inflammatory drug. This study tested the hypothesis that 2 large doses of EPO administered shortly before CPB ameliorate the systemic inflammatory response to CPB.DESIGN AND SETTING: A prospective, double-blind, placebo-controlled and randomized study at a single tertiary care hospital.PARTICIPANTS: Patients scheduled for coronary artery bypass graft surgery with CPB.INTERVENTIONS: EPO (epoetin alfa, 500 IU/kg intravenously, n = 22) or placebo (n = 21) was administered 12 to 18 hours preoperatively and again at the induction of anesthesia.MEASUREMENTS AND MAIN RESULTS: CPB in both groups greatly increased plasma concentrations of tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, IL-1beta receptor antagonist, IL-6, IL-10, and N-terminal probrain natriuretic peptide (NT-proBNP). Compared with placebo, EPO at day 3 after CPB augmented the TNF-alpha response (p < 0.05) and at 2 hours after CPB increased NT-proBNP (p < 0.05). Also, EPO tended to enhance the CPB-induced increase in IL-1beta receptor antagonist (p = 0.057). Otherwise, EPO had no effect on pro- and antiinflammatory mediators compared with placebo.CONCLUSIONS: Two large doses of EPO given shortly before CPB do not reduce perioperative release of inflammatory cytokines. In contrast, EPO may augment the TNF-alpha and NT-proBNP response. Although the long-term clinical impact remains unknown, the findings do not support use of EPO as an anti-inflammatory drug in patients undergoing cardiac surgery.

KW - Aged

KW - Cardiac Surgical Procedures

KW - Double-Blind Method

KW - Erythropoietin

KW - Female

KW - Humans

KW - Inflammation Mediators

KW - Male

KW - Middle Aged

KW - Postoperative Complications

KW - Preoperative Care

KW - Prospective Studies

KW - Recombinant Proteins

KW - Time Factors

U2 - 10.1053/j.jvca.2008.08.018

DO - 10.1053/j.jvca.2008.08.018

M3 - Journal article

C2 - 18948032

SN - 1053-0770

VL - 23

SP - 316

EP - 323

JO - Journal of Cardiothoracic and Vascular Anesthesia

JF - Journal of Cardiothoracic and Vascular Anesthesia

IS - 3

ER -

Two large preoperative doses of erythropoietin do not reduce the systemic inflammatory response to cardiac surgery

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