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Published in: Critical Care 5/2009

Open Access 01-10-2009 | Research

Cardiac effects of induction agents in the septic rat heart

Authors: York A Zausig, Hendrik Busse, Dirk Lunz, Barbara Sinner, Wolfgang Zink, Bernhard M Graf

Published in: Critical Care | Issue 5/2009

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Abstract

Introduction

The current debate about the side effects of induction agents, e.g. possible adrenal suppression through etomidate, emphasizes the relevance of choosing the correct induction agent in septic patients. However, cardiovascular depression is still the most prominent adverse effect of these agents, and might be especially hazardous in septic patients presenting with a biventricular cardiac dysfunction - or so-called septic cardiomyopathy. Therefore, we tested the dose-response direct cardiac effects of clinically available induction agents in an isolated septic rat heart model.

Methods

A polymicrobial sepsis was induced via cecal ligation and single puncture. Hearts (n = 50) were isolated and randomly assigned to five groups, each receiving etomidate, s(+)-ketamine, midazolam, propofol, or methohexitone at concentrations of 1 × 10-8 to 1 × 10-4 M. Left ventricular pressure, contractility and lusitropy, and coronary flow were measured. Cardiac work, myocardial oxygen delivery, oxygen consumption, and percentage of oxygen extraction were calculated.

Results

All of the induction agents tested showed a dose-dependent depression of cardiac work. Maximal cardiac work dysfunction occurred in the rank order of s(+)-ketamine (-6%) <etomidate (-17%) <methohexitone (-31%) <midazolam (-38%) <propofol (-50%). In addition, propofol showed a maximum decrease in contractility of -38%, a reduction in lusitropy of -44%, and a direct vasodilator effect by increasing coronary flow by +29%.

Conclusions

Overall, this study demonstrates that these tested drugs indeed have differential direct cardiac effects in the isolated septic heart. Propofol showed the most pronounced adverse direct cardiac effects. In contrast, S(+)ketamine showed cardiovascular stability over a wide range of concentrations, and might therefore be a beneficial alternative to etomidate.
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Literature
1.
go back to reference Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327.CrossRefPubMed Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med 2008, 36: 296-327.CrossRefPubMed
2.
go back to reference Reinhart K, Brunkhorst F, Bone H, Gerlach H, Grundling M, Kreymann G, Kujath P, Marggraf G, Mayer K, Meier-Hellmann A, Peckelsen C, Putensen C, Quintel M, Ragaller M, Rossaint R, Stuber F, Weiler N, Welte T, Werdan K: [Diagnosis and therapy of sepsis: guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine]. Anaesthesist 2006,55(Suppl 1):43-56.PubMed Reinhart K, Brunkhorst F, Bone H, Gerlach H, Grundling M, Kreymann G, Kujath P, Marggraf G, Mayer K, Meier-Hellmann A, Peckelsen C, Putensen C, Quintel M, Ragaller M, Rossaint R, Stuber F, Weiler N, Welte T, Werdan K: [Diagnosis and therapy of sepsis: guidelines of the German Sepsis Society Inc. and the German Interdisciplinary Society for Intensive and Emergency Medicine]. Anaesthesist 2006,55(Suppl 1):43-56.PubMed
3.
go back to reference Malerba G, Romano-Girard F, Cravoisy A, Dousset B, Nace L, Levy B, Bollaert PE: Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med 2005, 31: 388-392.CrossRefPubMed Malerba G, Romano-Girard F, Cravoisy A, Dousset B, Nace L, Levy B, Bollaert PE: Risk factors of relative adrenocortical deficiency in intensive care patients needing mechanical ventilation. Intensive Care Med 2005, 31: 388-392.CrossRefPubMed
4.
5.
go back to reference McCollum JS, Dundee JW: Comparison of induction characteristics of four intravenous anaesthetic agents. Anaesthesia 1986, 41: 995-1000.CrossRefPubMed McCollum JS, Dundee JW: Comparison of induction characteristics of four intravenous anaesthetic agents. Anaesthesia 1986, 41: 995-1000.CrossRefPubMed
6.
go back to reference Stowe DF, Bosnjak ZJ, Kampine JP: Comparison of etomidate, ketamine, midazolam, propofol, and thiopental on function and metabolism of isolated hearts. Anesth Analg 1992, 74: 547-558.CrossRefPubMed Stowe DF, Bosnjak ZJ, Kampine JP: Comparison of etomidate, ketamine, midazolam, propofol, and thiopental on function and metabolism of isolated hearts. Anesth Analg 1992, 74: 547-558.CrossRefPubMed
7.
go back to reference Parrillo JE: Myocardial depression during septic shock in humans. Crit Care Med 1990, 18: 1183-1184.CrossRefPubMed Parrillo JE: Myocardial depression during septic shock in humans. Crit Care Med 1990, 18: 1183-1184.CrossRefPubMed
8.
go back to reference Muller-Werdan U, Buerke M, Ebelt H, Heinroth KM, Herklotz A, Loppnow H, Russ M, Schlegel F, Schlitt A, Schmidt HB, Schmidt HB, Soffker G, Werdan K: Septic cardiomyopathy - A not yet discovered cardiomyopathy? Exp Clin Cardiol 2006, 11: 226-236.PubMedCentralPubMed Muller-Werdan U, Buerke M, Ebelt H, Heinroth KM, Herklotz A, Loppnow H, Russ M, Schlegel F, Schlitt A, Schmidt HB, Schmidt HB, Soffker G, Werdan K: Septic cardiomyopathy - A not yet discovered cardiomyopathy? Exp Clin Cardiol 2006, 11: 226-236.PubMedCentralPubMed
9.
go back to reference Fernandes CJ Jr, Akamine N, Knobel E: Myocardial depression in sepsis. Shock 2008,30(Suppl 1):14-17.CrossRefPubMed Fernandes CJ Jr, Akamine N, Knobel E: Myocardial depression in sepsis. Shock 2008,30(Suppl 1):14-17.CrossRefPubMed
11.
go back to reference Krishnagopalan S, Kumar A, Parrillo JE: Myocardial dysfunction in the patient with sepsis. Curr Opin Crit Care 2002, 8: 376-388.CrossRefPubMed Krishnagopalan S, Kumar A, Parrillo JE: Myocardial dysfunction in the patient with sepsis. Curr Opin Crit Care 2002, 8: 376-388.CrossRefPubMed
12.
go back to reference Zink W, Kaess M, Hofer S, Plachky J, Zausig YA, Sinner B, Weigand MA, Fink RH, Graf BM: Alterations in intracellular Ca2+-homeostasis of skeletal muscle fibers during sepsis. Crit Care Med 2008, 36: 1559-1563.CrossRefPubMed Zink W, Kaess M, Hofer S, Plachky J, Zausig YA, Sinner B, Weigand MA, Fink RH, Graf BM: Alterations in intracellular Ca2+-homeostasis of skeletal muscle fibers during sepsis. Crit Care Med 2008, 36: 1559-1563.CrossRefPubMed
13.
go back to reference Zausig YA, Stowe DF, Zink W, Grube C, Martin E, Graf BM: A comparison of three phosphodiesterase type III inhibitors on mechanical and metabolic function in guinea pig isolated hearts. Anesth Analg 2006, 102: 1646-1652.CrossRefPubMed Zausig YA, Stowe DF, Zink W, Grube C, Martin E, Graf BM: A comparison of three phosphodiesterase type III inhibitors on mechanical and metabolic function in guinea pig isolated hearts. Anesth Analg 2006, 102: 1646-1652.CrossRefPubMed
14.
go back to reference Stowe DF, Graf BM, Fujita S, Gross GJ: One-day cold perfusion of bimakalim and butanedione monoxime restores ex situ cardiac function. Am J Physiol 1996, 271: H1884-1892.PubMed Stowe DF, Graf BM, Fujita S, Gross GJ: One-day cold perfusion of bimakalim and butanedione monoxime restores ex situ cardiac function. Am J Physiol 1996, 271: H1884-1892.PubMed
15.
go back to reference Heck M, Fresenius M: Repetitorium Anaesthesiologie. 5th edition. Heidelberg: Springer; 2007. Heck M, Fresenius M: Repetitorium Anaesthesiologie. 5th edition. Heidelberg: Springer; 2007.
16.
go back to reference Sinner B, Graf BM: Ketamine. Handb Exp Pharmacol 2008, 313-333. Sinner B, Graf BM: Ketamine. Handb Exp Pharmacol 2008, 313-333.
17.
go back to reference Johnson KB, Egan TD, Kern SE, McJames SW, Cluff ML, Pace NL: Influence of hemorrhagic shock followed by crystalloid resuscitation on propofol: a pharmacokinetic and pharmacodynamic analysis. Anesthesiology 2004, 101: 647-659.CrossRefPubMed Johnson KB, Egan TD, Kern SE, McJames SW, Cluff ML, Pace NL: Influence of hemorrhagic shock followed by crystalloid resuscitation on propofol: a pharmacokinetic and pharmacodynamic analysis. Anesthesiology 2004, 101: 647-659.CrossRefPubMed
18.
go back to reference Annane D: ICU physicians should abandon the use of etomidate! Intensive Care Med 2005, 31: 325-326.CrossRefPubMed Annane D: ICU physicians should abandon the use of etomidate! Intensive Care Med 2005, 31: 325-326.CrossRefPubMed
19.
go back to reference Absalom A, Pledger D, Kong A: Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia 1999, 54: 861-867.CrossRefPubMed Absalom A, Pledger D, Kong A: Adrenocortical function in critically ill patients 24 h after a single dose of etomidate. Anaesthesia 1999, 54: 861-867.CrossRefPubMed
20.
go back to reference Johnson KB, Egan TD, Kern SE, White JL, McJames SW, Syroid N, Whiddon D, Church T: The influence of hemorrhagic shock on propofol: a pharmacokinetic and pharmacodynamic analysis. Anesthesiology 2003, 99: 409-420.CrossRefPubMed Johnson KB, Egan TD, Kern SE, White JL, McJames SW, Syroid N, Whiddon D, Church T: The influence of hemorrhagic shock on propofol: a pharmacokinetic and pharmacodynamic analysis. Anesthesiology 2003, 99: 409-420.CrossRefPubMed
21.
go back to reference Shirozu K, Akata T, Yoshino J, Setoguchi H, Morikawa K, Hoka S: The mechanisms of the direct action of etomidate on vascular reactivity in rat mesenteric resistance arteries. Anesth Analg 2009, 108: 496-507.CrossRefPubMed Shirozu K, Akata T, Yoshino J, Setoguchi H, Morikawa K, Hoka S: The mechanisms of the direct action of etomidate on vascular reactivity in rat mesenteric resistance arteries. Anesth Analg 2009, 108: 496-507.CrossRefPubMed
22.
go back to reference Graf BM, Vicenzi MN, Martin E, Bosnjak ZJ, Stowe DF: Ketamine has stereospecific effects in the isolated perfused guinea pig heart. Anesthesiology 1995, 82: 1426-1437. discussion 1425ACrossRefPubMed Graf BM, Vicenzi MN, Martin E, Bosnjak ZJ, Stowe DF: Ketamine has stereospecific effects in the isolated perfused guinea pig heart. Anesthesiology 1995, 82: 1426-1437. discussion 1425ACrossRefPubMed
23.
go back to reference Sekino N, Endou M, Hajiri E, Okumura F: Nonstereospecific actions of ketamine isomers on the force of contraction, spontaneous beating rate, and Ca2+ current in the guinea pig heart. Anesth Analg 1996, 83: 75-80.PubMed Sekino N, Endou M, Hajiri E, Okumura F: Nonstereospecific actions of ketamine isomers on the force of contraction, spontaneous beating rate, and Ca2+ current in the guinea pig heart. Anesth Analg 1996, 83: 75-80.PubMed
24.
go back to reference Hassoun SM, Marechal X, Montaigne D, Bouazza Y, Decoster B, Lancel S, Neviere R: Prevention of endotoxin-induced sarcoplasmic reticulum calcium leak improves mitochondrial and myocardial dysfunction. Crit Care Med 2008, 36: 2590-2596.CrossRefPubMed Hassoun SM, Marechal X, Montaigne D, Bouazza Y, Decoster B, Lancel S, Neviere R: Prevention of endotoxin-induced sarcoplasmic reticulum calcium leak improves mitochondrial and myocardial dysfunction. Crit Care Med 2008, 36: 2590-2596.CrossRefPubMed
25.
go back to reference Ren J, Ren BH, Sharma AC: Sepsis-induced depressed contractile function of isolated ventricular myocytes is due to altered calcium transient properties. Shock 2002, 18: 285-288.CrossRefPubMed Ren J, Ren BH, Sharma AC: Sepsis-induced depressed contractile function of isolated ventricular myocytes is due to altered calcium transient properties. Shock 2002, 18: 285-288.CrossRefPubMed
26.
27.
go back to reference Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue LW 3rd, Bland KI, Chaudry IH: Cecal ligation and puncture. Shock 2005,24(Suppl 1):52-57.CrossRefPubMed Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue LW 3rd, Bland KI, Chaudry IH: Cecal ligation and puncture. Shock 2005,24(Suppl 1):52-57.CrossRefPubMed
28.
go back to reference Leibowitz AB: Tracheal intubation in the intensive care unit: extremely hazardous even in the best of hands. Crit Care Med 2006, 34: 2497-2498.CrossRefPubMed Leibowitz AB: Tracheal intubation in the intensive care unit: extremely hazardous even in the best of hands. Crit Care Med 2006, 34: 2497-2498.CrossRefPubMed
29.
go back to reference Graf BM, Abraham I, Eberbach N, Kunst G, Stowe DF, Martin E: Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties. Anesthesiology 2002, 96: 1427-1434.CrossRefPubMed Graf BM, Abraham I, Eberbach N, Kunst G, Stowe DF, Martin E: Differences in cardiotoxicity of bupivacaine and ropivacaine are the result of physicochemical and stereoselective properties. Anesthesiology 2002, 96: 1427-1434.CrossRefPubMed
Metadata
Title
Cardiac effects of induction agents in the septic rat heart
Authors
York A Zausig
Hendrik Busse
Dirk Lunz
Barbara Sinner
Wolfgang Zink
Bernhard M Graf
Publication date
01-10-2009
Publisher
BioMed Central
Published in
Critical Care / Issue 5/2009
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/cc8038

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