Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-26T04:59:20.971Z Has data issue: false hasContentIssue false

Levosimendan in patients with acute myocardial ischaemia undergoing emergency surgical revascularization

Published online by Cambridge University Press:  01 March 2008

A. Lehmann*
Affiliation:
Klinikum der Stadt Ludwigshafen, Department of Anaesthesiology and Intensive Care Medicine, Ludwigshafen, Germany
A.-H. Kiessling
Affiliation:
Klinikum der Stadt Ludwigshafen, Department of Cardiac Surgery, Ludwigshafen, Germany
F. Isgro
Affiliation:
Klinikum der Stadt Ludwigshafen, Department of Cardiac Surgery, Ludwigshafen, Germany
C. Zeitler
Affiliation:
Klinikum der Stadt Ludwigshafen, Department of Anaesthesiology and Intensive Care Medicine, Ludwigshafen, Germany
E. Thaler
Affiliation:
Klinikum der Stadt Ludwigshafen, Department of Anaesthesiology and Intensive Care Medicine, Ludwigshafen, Germany
J. Boldt
Affiliation:
Klinikum der Stadt Ludwigshafen, Department of Anaesthesiology and Intensive Care Medicine, Ludwigshafen, Germany
*
Correspondence to: Andreas Lehmann, Department of Anaesthesiology and Intensive Care Medicine, Klinikum der Stadt Ludwigshafen, Postfach 21 73 52, D-67073 Ludwigshafen, Germany. E-mail: [email protected]; Tel: +49 621 503 3000; Fax: +49 621 503 3024
Get access

Summary

Background and objective

Levosimendan is a calcium-sensitizing drug that enhances myocardial contractility without increasing intracellular calcium. By activating adenosine triphosphate-dependent potassium channels it exerts cardioprotective and vasodilatory effects.

Methods

A retrospective matched pair analysis was performed in 52 patients undergoing emergency coronary artery bypass grafting for acute myocardial ischaemia with or without cardiogenic shock. A total of 27 patients received levosimendan (bolus 6 μg kg−1; continuous infusion 0.2 μg kg−1 min−1) in addition to catecholamines, while 25 patients were treated with catecholamines only.

Results

Predicted mortality by logistic EuroSCORE was 42% (14–90%) in the levosimendan group and 38% (9–90%) in the control group (median, range). Cardiogenic shock was diagnosed in 52% of the patients in both groups. Compared to the control group, levosimendan-treated patients had fewer intra-aortic balloon pumps inserted (33% vs. 76%, P < 0.05) and were ventilated for a shorter period (39 ± 39 h vs. 106 ± 109 h, P < 0.05). In this limited number of patients, the reduction in mortality at day 30 (26% levosimendan; 44% control, P > 0.05) and need for dialysis (11% levosimendan; 32% control, P > 0.05) did not reach statistical significance. Length of hospital stay did not differ (14 ± 18 days, levosimendan; 13 ± 19 days, control; P > 0.05) between the two groups.

Conclusion

In this retrospective matched pair analysis of 52 patients undergoing emergency coronary artery bypass grafting for acute ischaemia, levosimendan reduced morbidity. The reduced morbidity did not translate into reductions in mortality or length of stay. A larger, prospective randomized trial is warranted to confirm the potentially beneficial effects of levosimendan in patients with acute ischaemia.

Type
Original Article
Copyright
Copyright © European Society of Anaesthesiology 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Khoynezhad, A, Jalali, Z, Tortolani, AJ. Apoptosis: pathophysiology and therapeutic implications for the cardiac surgeon. Ann Thorac Surg 2004; 78: 11091118.CrossRefGoogle ScholarPubMed
2.Lagerqvist, B, Husted, S, Kotny, F et al. Fast Revascularistaion during InStability in Coronary artery disease (FRISC-II) investigators. 5-year outcomes in the FRISC-II randomised trial of an invasive vs. a non-invasive strategy in non-ST-elevation acute coronary syndrome: a follow-up study. Lancet 2006; 368: 9981004.CrossRefGoogle Scholar
3.Fox, KA, Poole-Wilson, P, Clayton, TC et al. . 5-year outcome of an interventional strategy in non-ST-elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial. Lancet 2005; 366: 914920.CrossRefGoogle ScholarPubMed
4.Acute Coronary Syndrome Guidelines Working Group. Guidelines for the management of acute coronary syndromes 2006. Med J Aust 2006; 184 (Suppl 8): S1S32.Google Scholar
5.Maytin, M, Colucci, WS. Cardioprotection: a new paradigm in the management of acute heart failure syndromes. Am J Cardiol 2005; 96: 26G31G.CrossRefGoogle ScholarPubMed
6.Haikala, H, Pollesello, P. Calcium sensitivity enhancers. Idrugs 2000; 3: 11991205.Google ScholarPubMed
7.Sorsa, T, Heikkinen, S, Abbott, MB et al. . Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. J Biol Chem 2001; 276: 93379343.CrossRefGoogle ScholarPubMed
8.Kersten, JR, Montgomery, MW, Pagel, PS, Warltier, DC. Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of KATP channels. Anesth Analg 2000; 90: 511.CrossRefGoogle Scholar
9.Loubani, M, Galinanes, M. Pharmacological and ischemic preconditioning of the human myocardium: mitoKATP channels are upstream and p38MAPK is downstream of PKC. BMC Physiol 2002; 2: 10.CrossRefGoogle ScholarPubMed
10.Roques, F, Nashef, SA, Michel, P et al. . Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients. Eur J Cardiothorac Surg 1999; 15: 816822.CrossRefGoogle ScholarPubMed
11.Roques, F, Michel, P, Goldstone, AR, Nashef, SA. The logistic EuroSCORE. Eur Heart J 2003; 24: 881882.CrossRefGoogle ScholarPubMed
12.Hochman, JS, Sleeper, LA, Webb, JG et al. . Early revascularization in acute myocardial infarction complicated by cardiogenic shock. N Engl J Med 1999; 341: 625634.CrossRefGoogle ScholarPubMed
13.Ducas, J, Grech, ED. ABC of interventional cardiology. Percutaneous coronary intervention: cardiogenic shock. BMJ 2003; 326: 14501452.CrossRefGoogle ScholarPubMed
14.Lehmann, A, Lang, J, Boldt, J, Isgro, F, Kiessling, AH. Levosimendan in patients with cardiogenic shock undergoing surgical revascularization: a case series. Med Sci Monit 2004; 10: MT89MT93.Google ScholarPubMed
15.Pinto, DS, Kirtane, AJ, Nallamothu, BK et al. . Hospital delays in reperfusion for ST-elevation myocardial infarction: implications when selecting a reperfusion strategy. Circulation 2006; 114: 20192025.CrossRefGoogle ScholarPubMed
16.Le May, MR, Davies, RF, Dionne, R et al. . Comparison of early mortality of paramedic-diagnosed ST-segment elevation myocardial infarction with immediate transport to a designated primary percutaneous coronary intervention center to that of similar patients transported to the nearest hospital. Am J Cardiol 2006; 98: 13291333.CrossRefGoogle Scholar
17.Berger, PB, Ellis, SG, Jr.Holmes, DR et al. . Relationship between delay in performing direct coronary angioplasty and early clinical outcome in patients with acute myocardial infarction: results from the global use of strategies to open occluded arteries in acute coronary syndromes (GUSTO-IIb) trial. Circulation 1999; 100: 1420.CrossRefGoogle ScholarPubMed
18.Bassand, JP, Danchin, N, Filippatos, G et al. . Implementation of reperfusion therapy in acute myocardial infarction. A policy statement from the European Society of Cardiology. Eur Heart J 2005; 26: 27332741.CrossRefGoogle ScholarPubMed
19.Pollesello, P, Mebazaa, A. ATP-dependent potassium channels as a key target for the treatment of myocardial and vascular dysfunction. Curr Opin Crit Care 2004; 10: 436441.CrossRefGoogle ScholarPubMed
20.Sugimoto, K, Ito, H, Iwakura, K et al. . Intravenous nicorandil in conjunction with coronary reperfusion therapy is associated with better clinical and functional outcomes in patients with acute myocardial infarction. Circ J 2003; 67: 295300.CrossRefGoogle ScholarPubMed
21.Chinnan, NK, Puri, GD, Thingnam, SK. Myocardial protection by nicorandil during open-heart surgery under cardiopulmonary bypass. Eur J Anaesthesiol 2007; 24: 2632.CrossRefGoogle ScholarPubMed
22.Toller, WG, Stranz, C. Levosimendan, a new inotropic and vasodilator agent. Anesthesiology 2006; 104: 556569.CrossRefGoogle ScholarPubMed
23.Sonntag, S, Sundberg, S, Lehtonen, LA, Kleber, FX. The calcium sensitizer levosimendan improves the function of stunned myocardium after percutaneous transluminal coronary angioplasty in acute myocardial ischemia. J Am Coll Cardiol 2004; 43: 21772182.CrossRefGoogle ScholarPubMed
24.Avgeropoulou, C, Andreadou, I, Markantonis-Kyroudis, S et al. . The Ca2+-sensitizer levosimendan improves oxidative damage, BNP and pro-inflammatory cytokine levels in patients with advanced decompensated heart failure in comparison to dobutamine. Eur J Heart Fail 2005; 7: 882887.CrossRefGoogle ScholarPubMed
25.Adamopoulos, S, Parissis, JT, Iliodromitis, EK et al. . Effects of levosimendan vs. dobutamine on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure. Am J Cardiol 2006; 98: 102106.CrossRefGoogle Scholar
26.Tritapepe, L, De Santis, V, Vitale, D et al. . Preconditioning effects of levosimendan in coronary artery bypass grafting – a pilot study. Br J Anaesth 2006; 96: 694700.CrossRefGoogle ScholarPubMed
27.Ardehali, H, O’Rourke, B. Mitochondrial KATP channels in cell survival and death. J Mol Cell Cardiol 2005; 39: 716.CrossRefGoogle ScholarPubMed
28.Zager, RA, Johnson, AC, Lund, S, Hanson, SY, Abrass, CK. Levosimendan protects against experimental endotoxemic acute renal failure. Am J Physiol Renal Physiol 2006; 290: F1453F1462.CrossRefGoogle ScholarPubMed
29.Feneck, R. Clinical research in anaesthesia; randomized controlled trials or observational studies. Eur J Anaesthesiol 2007; 24: 15.CrossRefGoogle ScholarPubMed