Levosimendan for the prevention of acute organ dysfunction in sepsis

New England Journal of Medicine

Volumn 375, Issue 17, 2016, Pages 1638-1648

  Gordon, Anthony C ^a   Perkins, Gavin D ^f   Singer, Mervyn ^b   McAuley, Daniel F ^g,h   Orme, Robert M L ⁱ   Santhakumaran, Shalini ^c   Mason, Alexina J ^d   Cross, Mary ^c   Al Beidh, Farah ^a,c   Best Lane, Janis ^a,c   Brealey, David ^e   Nutt, Christopher L ^j   McNamee, James J ^g,h   Reschreiter, Henrik ^k   Breen, Andrew ^l   Liu, Kathleen D ^m   Ashby, Deborah ^c  

^a CHARING CROSS HOSPITAL   (United Kingdom)

^b UNIVERSITY COLLEGE LONDON   (United Kingdom)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

^d LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^e UNIVERSITY COLLEGE LONDON HOSPITALS   (United Kingdom)

^f UNIVERSITY OF WARWICK   (United Kingdom)

^g QUEEN'S UNIVERSITY BELFAST   (United Kingdom)

^h ROYAL VICTORIA HOSPITAL   (United Kingdom)

ⁱ GLOUCESTERSHIRE HOSPITALS NHS FOUNDATION TRUST   (United Kingdom)

^j ANTRIM AREA HOSPITAL   (United Kingdom)

^k POOLE HOSPITAL NHS FOUNDATION TRUST   (United Kingdom)

^l LEEDS TEACHING HOSPITALS NHS TRUST   (United Kingdom)

^m UNIVERSITY OF CALIFORNIA   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

DOBUTAMINE; EPINEPHRINE; LEVOSIMENDAN; NORADRENALIN; PLACEBO; VASOPRESSIN;

ACUTE CORONARY SYNDROME; ADULT; AGED; ARTICLE; ARTIFICIAL VENTILATION; BRADYCARDIA; CONTINUOUS INFUSION; CONTROLLED STUDY; DISEASE SEVERITY; DOUBLE BLIND PROCEDURE; DRUG DOSE INCREASE; FEMALE; HEART INFARCTION; HEART SUPRAVENTRICULAR ARRHYTHMIA; HEART VENTRICLE FIBRILLATION; HUMAN; INTENSIVE CARE UNIT; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; MORTALITY; MULTICENTER STUDY; MULTIPLE ORGAN FAILURE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SEPSIS; SEPTIC SHOCK; SEQUENTIAL ORGAN FAILURE ASSESSMENT SCORE; TACHYCARDIA; TREATMENT OUTCOME; UNITED KINGDOM; VENTILATOR WEANING;

EID: 84992660038     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1609409     Document Type: Article

References (33)

1. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 801-10.
2. Shankar-Hari M, Phillips GS, Levy ML, et al. Developing a new definition and assessing new clinical criteria for septic shock: for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016; 315: 775-87.
3. Vieillard-Baron A, Caille V, Charron C, Belliard G, Page B, Jardin F. Actual incidence of global left ventricular hypokinesia in adult septic shock. Crit Care Med 2008; 36: 1701-6.
4. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med 2013; 41: 580-637.
5. Dünser MW, Ruokonen E, Pettilä V, et al. Association of arterial blood pressure and vasopressor load with septic shock mortality: a post hoc analysis of a multicenter trial. Crit Care 2009; 13: R181.
6. Boldt J, Menges T, Kuhn D, Diridis C, Hempelmann G. Alterations in circulating vasoactive substances in the critically ill-A comparison between survivors and non-survivors. Intensive Care Med 1995; 21: 218-25.
7. Schmittinger CA, Torgersen C, Luckner G, Schröder DC, Lorenz I, Dünser MW. Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study. Intensive Care Med 2012; 38: 950-8.
8. Nieminen MS, Fruhwald S, Heunks LM, et al. Levosimendan: current data, clinical use and future development. Heart Lung Vessel 2013; 5: 227-45.
9. Ukkonen H, Saraste M, Akkila J, et al. Myocardial efficiency during calcium sensitization with levosimendan: a noninvasive study with positron emission tomography and echocardiography in healthy volunteers. Clin Pharmacol Ther 1997; 61: 596-607.
10. Morelli A, De Castro S, Teboul J-L, et al. Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression. Intensive Care Med 2005; 31: 638-44.
11. Morelli A, Donati A, Ertmer C, et al. Levosimendan for resuscitating the microcirculation in patients with septic shock: a randomized controlled study. Crit Care 2010; 14: R232.
12. Memis D, Inal MT, Sut N. The effects of levosimendan vs dobutamine added to dopamine on liver functions assessed with noninvasive liver function monitoring in patients with septic shock. J Crit Care 2012; 27(3): 318.e1-6.
13. Wang Q, Yokoo H, Takashina M, et al. Anti-inflammatory profile of levosimendan in cecal ligation-induced septic mice and in lipopolysaccharide-stimulated macrophages. Crit Care Med 2015; 43(11): e508-e520.
14. Hasslacher J, Bijuklic K, Bertocchi C, et al. Levosimendan inhibits release of reactive oxygen species in polymorphonuclear leukocytes in vitro and in patients with acute heart failure and septic shock: a prospective observational study. Crit Care 2011; 15: R166.
15. Parissis JT, Adamopoulos S, Antoniades C, et al. Effects of levosimendan on circulating pro-inflammatory cytokines and soluble apoptosis mediators in patients with decompensated advanced heart failure. Am J Cardiol 2004; 93: 1309-12.
16. du Toit EF, Genis A, Opie LH, Pollesello P, Lochner A. A role for the RISK pathway and K(ATP) channels in pre-And post-conditioning induced by levosimendan in the isolated guinea pig heart. Br J Pharmacol 2008; 154: 41-50.
17. Zangrillo A, Putzu A, Monaco F, et al. Levosimendan reduces mortality in patients with severe sepsis and septic shock: a meta-Analysis of randomized trials. J Crit Care 2015; 30: 908-13.
18. Orme RM, Perkins GD, McAuley DF, et al. An efficacy and mechanism evaluation study of Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis (LeoPARDS): protocol for a randomized controlled trial. Trials 2014; 15: 199.
19. Ferreira FL, Bota DP, Bross A, Mélot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA 2001; 286: 1754-8.
20. Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA 2016; 316: 509-18.
21. Gordon AC, Mason AJ, Perkins GD, et al. The interaction of vasopressin and corticosteroids in septic shock: a pilot randomized controlled trial. Crit Care Med 2014; 42: 1325-33.
22. Palevsky PM, Molitoris BA, Okusa MD, et al. Design of clinical trials in acute kidney injury: report from an NIDDK workshop on trial methodology. Clin J Am Soc Nephrol 2012; 7: 844-50.
23. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007; 11: R31.
24. Anderson MJ, Ter Braak CJF. Permutation tests for multi-factorial analysis of variance. J Stat Comput Simul 2003; 73: 85-113.
25. R Core Team. R: a language and environment for statistical computing. Vienna: R Foundation for Statistical Computing, 2015.
26. Jörgensen K, Bech-Hanssen O, Houltz E, Ricksten SE. Effects of levosimendan on left ventricular relaxation and early filling at maintained preload and afterload conditions after aortic valve replacement for aortic stenosis. Circulation 2008; 117: 1075-81.
27. Kivikko M, Antila S, Eha J, Lehtonen L, Pentikäinen PJ. Pharmacokinetics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure. Int J Clin Pharmacol Ther 2002; 40: 465-71.
28. Morelli A, Teboul J-L, Maggiore SM, et al. Effects of levosimendan on right ventricular afterload in patients with acute respiratory distress syndrome: a pilot study. Crit Care Med 2006; 34: 2287-93.
29. Shahul S, Gulati G, Hacker MR, et al. Detection of myocardial dysfunction in septic shock: a speckle-tracking echocardiography study. Anesth Analg 2015; 121: 1547-54.
30. Gordon AC, Wang N, Walley KR, Ashby D, Russell JA. The cardiopulmonary effects of vasopressin compared with norepinephrine in septic shock. Chest 2012; 142: 593-605.
31. Morelli A, Ertmer C, Westphal M, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA 2013; 310: 1683-91.
32. Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008; 358: 877-87.
33. Asfar P, Meziani F, Hamel J-F, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014; 370: 1583-93.