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Erschienen in: Journal of Clinical Monitoring and Computing 1/2020

20.02.2019 | Original Research

Pretreatment with glucose–insulin–potassium improves ventricular performances after coronary artery bypass surgery: a randomized controlled trial

verfasst von: Marc Licker, Thomas Reynaud, Najia Garofano, Tornike Sologashvili, John Diaper, Christoph Ellenberger

Erschienen in: Journal of Clinical Monitoring and Computing | Ausgabe 1/2020

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Abstract

Heart failure is the main cause of poor outcome following open heart surgery and experimental studies have demonstrated that glucose–insulin–potassium (GIK) infusion exerts cardioprotective effects by reducing myocardial ischemia–reperfusion injuries. This randomized controlled trial was designed to assess the effects of GIK on left ventricular function in moderate-to-high risk patients undergoing on-pump isolated coronary artery bypass surgery (CABGS), or combined with aortic valve replacement. The primary outcomes were the effects of GIK on two- and three-dimensional left ventricular ejection fraction (2D and 3D-LVEF), and on transmitral flow propagation velocity (Vp), that occurred between the pre- and post-CPB periods. GIK administration was associated with favorable interaction effects (p < 0.001) on 2D-LVEF, 3D-LVEF and Vp changes over the study periods. In GIK pretreated patients (N = 54), 2-D and 3D-LVEF and Vp increased slightly during surgery (mean difference [MD] + 3.5%, 95% confidence interval [95% CI] − 0.2 to 7.1%, MD + 4.0%, 95% CI 0.6–7.4%, and MD + 22.2%, 95% CI 16.0–28.4%, respectively). In contrast, in the Placebo group (N = 46), 2D-and 3D-LVEF, as well as Vp all decreased after CPB (MD − 7.5% [− 11.6 to − 3.4%], MD − 12.0% [− 15.2 to − 8.8%] and MD − 21.3% [− 25.7 to − 16.9%], respectively). In conclusion, the administration of GIK resulted in better preservation of systolic and diastolic ventricular function in the early period following weaning from CPB.
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Literatur
1.
Zurück zum Zitat Writing Group M, Mozaffarian D, Benjamin EJ, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133:e38–60. Writing Group M, Mozaffarian D, Benjamin EJ, et al. Heart disease and stroke statistics-2016 update: a report from the American Heart Association. Circulation. 2016;133:e38–60.
2.
Zurück zum Zitat McNeely C, Markwell S, Vassileva C. Trends in patient characteristics and outcomes of coronary artery bypass grafting in the 2000 to 2012 medicare population. Ann Thorac Surg. 2016;102:132–8.PubMed McNeely C, Markwell S, Vassileva C. Trends in patient characteristics and outcomes of coronary artery bypass grafting in the 2000 to 2012 medicare population. Ann Thorac Surg. 2016;102:132–8.PubMed
3.
Zurück zum Zitat Blumenfeld O, Na’amnih W, Shapira-Daniels A, Lotan C, Shohat T. Shapira OM trends in coronary revascularization and ischemic heart disease-related mortality in Israel. J Am Heart Assoc 2017; 6:e004734.PubMedPubMedCentral Blumenfeld O, Na’amnih W, Shapira-Daniels A, Lotan C, Shohat T. Shapira OM trends in coronary revascularization and ischemic heart disease-related mortality in Israel. J Am Heart Assoc 2017; 6:e004734.PubMedPubMedCentral
4.
Zurück zum Zitat ElBardissi AW, Aranki SF, Sheng S, O’Brien SM, Greenberg CC, Gammie JS. Trends in isolated coronary artery bypass grafting: an analysis of the Society of Thoracic Surgeons adult cardiac surgery database. J Thorac Cardiovasc Surg. 2012;143:273–81.PubMed ElBardissi AW, Aranki SF, Sheng S, O’Brien SM, Greenberg CC, Gammie JS. Trends in isolated coronary artery bypass grafting: an analysis of the Society of Thoracic Surgeons adult cardiac surgery database. J Thorac Cardiovasc Surg. 2012;143:273–81.PubMed
5.
Zurück zum Zitat Likosky DS, Goldberg JB, DiScipio AW, et al. Variability in surgeons’ perioperative practices may influence the incidence of low-output failure after coronary artery bypass grafting surgery. Circ Cardiovasc Qual Outcomes. 2012;5:638–44.PubMed Likosky DS, Goldberg JB, DiScipio AW, et al. Variability in surgeons’ perioperative practices may influence the incidence of low-output failure after coronary artery bypass grafting surgery. Circ Cardiovasc Qual Outcomes. 2012;5:638–44.PubMed
6.
Zurück zum Zitat Nielsen DV, Hansen MK, Johnsen SP, Hansen M, Hindsholm K, Jakobsen CJ. Health outcomes with and without use of inotropic therapy in cardiac surgery: results of a propensity score-matched analysis. Anesthesiology. 2014;120:1098–108.PubMed Nielsen DV, Hansen MK, Johnsen SP, Hansen M, Hindsholm K, Jakobsen CJ. Health outcomes with and without use of inotropic therapy in cardiac surgery: results of a propensity score-matched analysis. Anesthesiology. 2014;120:1098–108.PubMed
7.
Zurück zum Zitat Lomivorotov VV, Efremov SM, Kirov MY, Fominskiy EV, Karaskov AM. Low-cardiac-output syndrome after cardiac surgery. J Cardiothorac Vasc Anesth. 2017;31:291–308.PubMed Lomivorotov VV, Efremov SM, Kirov MY, Fominskiy EV, Karaskov AM. Low-cardiac-output syndrome after cardiac surgery. J Cardiothorac Vasc Anesth. 2017;31:291–308.PubMed
8.
Zurück zum Zitat Hausenloy DJ, Boston-Griffiths E, Yellon DM. Cardioprotection during cardiac surgery. Cardiovasc Res. 2012;94:253–65.PubMedPubMedCentral Hausenloy DJ, Boston-Griffiths E, Yellon DM. Cardioprotection during cardiac surgery. Cardiovasc Res. 2012;94:253–65.PubMedPubMedCentral
9.
Zurück zum Zitat Dobson GP, Faggian G, Onorati F, Vinten-Johansen J. Hyperkalemic cardioplegia for adult and pediatric surgery: end of an era? Front Physiol. 2013;4:228.PubMedPubMedCentral Dobson GP, Faggian G, Onorati F, Vinten-Johansen J. Hyperkalemic cardioplegia for adult and pediatric surgery: end of an era? Front Physiol. 2013;4:228.PubMedPubMedCentral
10.
Zurück zum Zitat Kunst G, Klein AA. Peri-operative anaesthetic myocardial preconditioning and protection—cellular mechanisms and clinical relevance in cardiac anaesthesia. Anaesthesia. 2015;70:467–82.PubMedPubMedCentral Kunst G, Klein AA. Peri-operative anaesthetic myocardial preconditioning and protection—cellular mechanisms and clinical relevance in cardiac anaesthesia. Anaesthesia. 2015;70:467–82.PubMedPubMedCentral
11.
Zurück zum Zitat Cole SP, Gross ER. Happy 53rd birthday GIK: insulin, cake, and presents. Anesthesiology. 2015;123:249–50.PubMed Cole SP, Gross ER. Happy 53rd birthday GIK: insulin, cake, and presents. Anesthesiology. 2015;123:249–50.PubMed
12.
Zurück zum Zitat Ng KW, Allen ML, Desai A, Macrae D, Pathan N. Cardioprotective effects of insulin: how intensive insulin therapy may benefit cardiac surgery patients. Circulation. 2012;125:721–8.PubMed Ng KW, Allen ML, Desai A, Macrae D, Pathan N. Cardioprotective effects of insulin: how intensive insulin therapy may benefit cardiac surgery patients. Circulation. 2012;125:721–8.PubMed
13.
Zurück zum Zitat Fan Y, Zhang AM, Xiao YB, Weng YG. Hetzer R Glucose–insulin–potassium therapy in adult patients undergoing cardiac surgery: a meta-analysis. Eur J Cardiothorac Surg. 2011;40:192–9.PubMed Fan Y, Zhang AM, Xiao YB, Weng YG. Hetzer R Glucose–insulin–potassium therapy in adult patients undergoing cardiac surgery: a meta-analysis. Eur J Cardiothorac Surg. 2011;40:192–9.PubMed
14.
Zurück zum Zitat Ali-Hassan-Sayegh S, Mirhosseini SJ, Zeriouh M, et al. Safety and efficacy of glucose–insulin–potassium treatment in coronary artery bypass graft surgery and percutaneous coronary intervention. Interact Cardiovasc Thorac Surg. 2015;21:667–76.PubMed Ali-Hassan-Sayegh S, Mirhosseini SJ, Zeriouh M, et al. Safety and efficacy of glucose–insulin–potassium treatment in coronary artery bypass graft surgery and percutaneous coronary intervention. Interact Cardiovasc Thorac Surg. 2015;21:667–76.PubMed
15.
Zurück zum Zitat Ellenberger C, Sologashvili T, Kreienbuhl L, Cikirikcioglu M, Diaper J, Licker M. Myocardial protection by glucose–insulin–potassium in moderate- to high-risk patients undergoing elective on-pump cardiac surgery: a randomized controlled trial. Anesth Analg. 2018;126:1133–41.PubMed Ellenberger C, Sologashvili T, Kreienbuhl L, Cikirikcioglu M, Diaper J, Licker M. Myocardial protection by glucose–insulin–potassium in moderate- to high-risk patients undergoing elective on-pump cardiac surgery: a randomized controlled trial. Anesth Analg. 2018;126:1133–41.PubMed
16.
Zurück zum Zitat Ellenberger C, Sologashvili T, Bhaskaran K, Licker M. Impact of intrathecal morphine analgesia on the incidence of pulmonary complications after cardiac surgery: a single center propensity-matched cohort study. BMC Anesthesiol. 2017;17:109.PubMedPubMedCentral Ellenberger C, Sologashvili T, Bhaskaran K, Licker M. Impact of intrathecal morphine analgesia on the incidence of pulmonary complications after cardiac surgery: a single center propensity-matched cohort study. BMC Anesthesiol. 2017;17:109.PubMedPubMedCentral
17.
Zurück zum Zitat Licker M, Diaper J, Cartier V, et al. Clinical review: management of weaning from cardiopulmonary bypass after cardiac surgery. Ann Card Anaesth. 2012;15:206–23.PubMed Licker M, Diaper J, Cartier V, et al. Clinical review: management of weaning from cardiopulmonary bypass after cardiac surgery. Ann Card Anaesth. 2012;15:206–23.PubMed
18.
Zurück zum Zitat Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440–63.PubMed Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440–63.PubMed
19.
Zurück zum Zitat Nagueh SF, Appleton CP, Gillebert TC, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009;22:107–13.PubMed Nagueh SF, Appleton CP, Gillebert TC, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. J Am Soc Echocardiogr. 2009;22:107–13.PubMed
20.
Zurück zum Zitat Nagueh SF, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of cardiovascular imaging. Am Soc Echocardiogr. 2016;29:277–314. Nagueh SF, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of cardiovascular imaging. Am Soc Echocardiogr. 2016;29:277–314.
21.
Zurück zum Zitat Ding W, Ji Q, Shi Y, Ma R. Predictors of low cardiac output syndrome after isolated coronary artery bypass grafting. Int Heart J. 2015;56:144–9.PubMed Ding W, Ji Q, Shi Y, Ma R. Predictors of low cardiac output syndrome after isolated coronary artery bypass grafting. Int Heart J. 2015;56:144–9.PubMed
22.
Zurück zum Zitat Berman M, Stamler A, Sahar G, et al. Validation of the 2000 Bernstein-Parsonnet score versus the EuroSCORE as a prognostic tool in cardiac surgery. Ann Thorac Surg. 2006;81:537–40.PubMed Berman M, Stamler A, Sahar G, et al. Validation of the 2000 Bernstein-Parsonnet score versus the EuroSCORE as a prognostic tool in cardiac surgery. Ann Thorac Surg. 2006;81:537–40.PubMed
23.
Zurück zum Zitat Chakravarthy M. Quality in cardiac anesthesia: is there an alternative to its practice? Ann Card Anaesth. 2015;18:130–2.PubMedPubMedCentral Chakravarthy M. Quality in cardiac anesthesia: is there an alternative to its practice? Ann Card Anaesth. 2015;18:130–2.PubMedPubMedCentral
24.
Zurück zum Zitat Grossgasteiger M, Hien MD, Graser B, et al. Assessment of left ventricular size and function during cardiac surgery. An intraoperative evaluation of six two-dimensional echocardiographic methods with real time three-dimensional echocardiography as a reference. Echocardiography. 2013;30:672–81.PubMed Grossgasteiger M, Hien MD, Graser B, et al. Assessment of left ventricular size and function during cardiac surgery. An intraoperative evaluation of six two-dimensional echocardiographic methods with real time three-dimensional echocardiography as a reference. Echocardiography. 2013;30:672–81.PubMed
25.
Zurück zum Zitat Pouleur AC, le Polain de Waroux JB, Pasquet A, et al. Assessment of left ventricular mass and volumes by three-dimensional echocardiography in patients with or without wall motion abnormalities: comparison against cine magnetic resonance imaging. Heart. 2008;94:1050–7.PubMed Pouleur AC, le Polain de Waroux JB, Pasquet A, et al. Assessment of left ventricular mass and volumes by three-dimensional echocardiography in patients with or without wall motion abnormalities: comparison against cine magnetic resonance imaging. Heart. 2008;94:1050–7.PubMed
26.
Zurück zum Zitat Ma C, Chen J, Yang J, et al. Quantitative assessment of left ventricular function by 3-dimensional speckle-tracking echocardiography in patients with chronic heart failure: a meta-analysis. J Ultrasound Med. 2014;33:287–95.PubMed Ma C, Chen J, Yang J, et al. Quantitative assessment of left ventricular function by 3-dimensional speckle-tracking echocardiography in patients with chronic heart failure: a meta-analysis. J Ultrasound Med. 2014;33:287–95.PubMed
27.
Zurück zum Zitat Yang HS, Song BG, Kim JY, Kim SN, Kim TY. Impact of propofol anesthesia induction on cardiac function in low-risk patients as measured by intraoperative Doppler tissue imaging. J Am Soc Echocardiogr. 2013;26:727–35.PubMed Yang HS, Song BG, Kim JY, Kim SN, Kim TY. Impact of propofol anesthesia induction on cardiac function in low-risk patients as measured by intraoperative Doppler tissue imaging. J Am Soc Echocardiogr. 2013;26:727–35.PubMed
28.
Zurück zum Zitat Nishikawa K, Kanaya N, Kawamata M, Namiki A. Left ventricular mechanical performance in elderly patients after induction of anaesthesia. A comparison of inhalational induction with sevoflurane and intravenous induction with fentanyl and propofol. Anaesthesia. 2004;59:948–53.PubMed Nishikawa K, Kanaya N, Kawamata M, Namiki A. Left ventricular mechanical performance in elderly patients after induction of anaesthesia. A comparison of inhalational induction with sevoflurane and intravenous induction with fentanyl and propofol. Anaesthesia. 2004;59:948–53.PubMed
29.
Zurück zum Zitat Nicolas-Robin A, Amour J, Ibanez-Esteve C, Coriat P, Riou B, Langeron O. Effect of glucose–insulin–potassium in severe acute heart failure after brain death. Crit Care Med. 2008;36:2740–5.PubMed Nicolas-Robin A, Amour J, Ibanez-Esteve C, Coriat P, Riou B, Langeron O. Effect of glucose–insulin–potassium in severe acute heart failure after brain death. Crit Care Med. 2008;36:2740–5.PubMed
30.
Zurück zum Zitat Di Marco S, Boldrini B, Conti U, et al. Effects of GIK (glucose–insulin–potassium) on stress-induced myocardial ischaemia. Clin Sci. 2010;119:37–44. Di Marco S, Boldrini B, Conti U, et al. Effects of GIK (glucose–insulin–potassium) on stress-induced myocardial ischaemia. Clin Sci. 2010;119:37–44.
31.
Zurück zum Zitat Grossman AN, Opie LH, Beshansky JR, Ingwall JS, Rackley CE. Selker HP glucose–insulin–potassium revived: current status in acute coronary syndromes and the energy-depleted heart. Circulation. 2013;127:1040–8.PubMed Grossman AN, Opie LH, Beshansky JR, Ingwall JS, Rackley CE. Selker HP glucose–insulin–potassium revived: current status in acute coronary syndromes and the energy-depleted heart. Circulation. 2013;127:1040–8.PubMed
32.
Zurück zum Zitat Chanda D, Luiken JJ, Glatz JF. Signaling pathways involved in cardiac energy metabolism. FEBS Lett. 2016;590:2364–74.PubMed Chanda D, Luiken JJ, Glatz JF. Signaling pathways involved in cardiac energy metabolism. FEBS Lett. 2016;590:2364–74.PubMed
33.
Zurück zum Zitat Ranasinghe AM, McCabe CJ, Quinn DW, et al. How does glucose insulin potassium improve hemodynamic performance? Evidence for altered expression of beta-adrenoreceptor and calcium handling genes. Circulation. 2006;114:I239-44.PubMed Ranasinghe AM, McCabe CJ, Quinn DW, et al. How does glucose insulin potassium improve hemodynamic performance? Evidence for altered expression of beta-adrenoreceptor and calcium handling genes. Circulation. 2006;114:I239-44.PubMed
34.
Zurück zum Zitat Ferrara N, Abete P, Corbi G, et al. Insulin-induced changes in beta-adrenergic response: an experimental study in the isolated rat papillary muscle. Am J Hypertens. 2005;18:348–53.PubMed Ferrara N, Abete P, Corbi G, et al. Insulin-induced changes in beta-adrenergic response: an experimental study in the isolated rat papillary muscle. Am J Hypertens. 2005;18:348–53.PubMed
35.
Zurück zum Zitat von Lewinski D, Bruns S, Walther S, Kogler H, Pieske B. Insulin causes [Ca2+]i-dependent and [Ca2+]i-independent positive inotropic effects in failing human myocardium. Circulation. 2005;111:2588–95. von Lewinski D, Bruns S, Walther S, Kogler H, Pieske B. Insulin causes [Ca2+]i-dependent and [Ca2+]i-independent positive inotropic effects in failing human myocardium. Circulation. 2005;111:2588–95.
36.
Zurück zum Zitat Albacker T, Carvalho G, Schricker T, Lachapelle K. High-dose insulin therapy attenuates systemic inflammatory response in coronary artery bypass grafting patients. Ann Thorac Surg. 2008;86:20–7.PubMed Albacker T, Carvalho G, Schricker T, Lachapelle K. High-dose insulin therapy attenuates systemic inflammatory response in coronary artery bypass grafting patients. Ann Thorac Surg. 2008;86:20–7.PubMed
37.
Zurück zum Zitat Klein LJ, Visser FC. The effect of insulin on the heart: Part 2: effects on function during and post myocardial ischaemia. Neth Heart J. 2010;18:255–9.PubMedPubMedCentral Klein LJ, Visser FC. The effect of insulin on the heart: Part 2: effects on function during and post myocardial ischaemia. Neth Heart J. 2010;18:255–9.PubMedPubMedCentral
38.
Zurück zum Zitat Cottin Y, Lhuillier I, Gilson L, et al. Glucose insulin potassium infusion improves systolic function in patients with chronic ischemic cardiomyopathy. Eur J Heart Fail. 2002;4:181–4.PubMed Cottin Y, Lhuillier I, Gilson L, et al. Glucose insulin potassium infusion improves systolic function in patients with chronic ischemic cardiomyopathy. Eur J Heart Fail. 2002;4:181–4.PubMed
39.
Zurück zum Zitat Liepinsh E, Makrecka M, Kuka J, et al. The heart is better protected against myocardial infarction in the fed state compared to the fasted state. Metabolism. 2014;63:127–36.PubMed Liepinsh E, Makrecka M, Kuka J, et al. The heart is better protected against myocardial infarction in the fed state compared to the fasted state. Metabolism. 2014;63:127–36.PubMed
40.
Zurück zum Zitat Cross HR, Opie LH, Radda GK, Clarke K. Is a high glycogen content beneficial or detrimental to the ischemic rat heart? A controversy resolved. Circ Res. 1996;78:482–91.PubMed Cross HR, Opie LH, Radda GK, Clarke K. Is a high glycogen content beneficial or detrimental to the ischemic rat heart? A controversy resolved. Circ Res. 1996;78:482–91.PubMed
41.
Zurück zum Zitat Yao H, Han X, Han X. The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway. Am J Cardiovasc Drugs. 2014;14:433–42.PubMed Yao H, Han X, Han X. The cardioprotection of the insulin-mediated PI3K/Akt/mTOR signaling pathway. Am J Cardiovasc Drugs. 2014;14:433–42.PubMed
42.
Zurück zum Zitat Duncan AE, Sessler DI, Sato H, et al. Hyperinsulinemic normoglycemia during cardiac surgery reduces a composite of 30-day mortality and serious in-hospital complications: a randomized clinical trial. Anesthesiology. 2018;128:1125–39.PubMed Duncan AE, Sessler DI, Sato H, et al. Hyperinsulinemic normoglycemia during cardiac surgery reduces a composite of 30-day mortality and serious in-hospital complications: a randomized clinical trial. Anesthesiology. 2018;128:1125–39.PubMed
Metadaten
Titel
Pretreatment with glucose–insulin–potassium improves ventricular performances after coronary artery bypass surgery: a randomized controlled trial
verfasst von
Marc Licker
Thomas Reynaud
Najia Garofano
Tornike Sologashvili
John Diaper
Christoph Ellenberger
Publikationsdatum
20.02.2019
Verlag
Springer Netherlands
Erschienen in
Journal of Clinical Monitoring and Computing / Ausgabe 1/2020
Print ISSN: 1387-1307
Elektronische ISSN: 1573-2614
DOI
https://doi.org/10.1007/s10877-019-00280-5

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