Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper

Abstract

Abstract:Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate–sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. This pharmacological profile identifies levosimendan as a drug that may have applications in a wide range of critical illness situations encountered in intensive care unit medicine: hemodynamic support in cardiogenic or septic shock; weaning from mechanical ventilation or from extracorporeal membrane oxygenation; and in the context of cardiorenal syndrome. This review, authored by experts from 9 European countries (Austria, Belgium, Czech republic, Finland, France, Germany, Italy, Sweden, and Switzerland), examines the clinical and experimental data for levosimendan in these situations and concludes that, in most instances, the evidence is encouraging, which is not the case with other cardioactive and vasoactive drugs routinely used in the intensive care unit. The size of the available studies is, however, limited and the data are in need of verification in larger controlled trials. Some proposals are offered for the aims and designs of these additional studies.

Levosimendan Improves Oxidative Balance in Cardiogenic Shock/Low Cardiac Output Patients

“…Levosimendan is an inotrope used for the treatment of acutely decompensated heart failure patients with low cardiac output or cardiogenic shock [1][2][3][4].…”

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

“…85 Due to the large therapeutic field they encompass, the European guidelines on acute and chronic HF are not as detailed as they could be and, in recommending therapeutic agents, ignore some of the different aetiologies and manifestations of AHF. Supplementary information and recommendations can be found in more than 20 expert consensus papers co-authored by more than 180 clinicians from 30 countries who have discussed when and how to use levosimendan in different therapeutic settings, including AHF and cardiogenic shock, 74,81,[86][87][88] AdHF, [89][90][91][92] perioperative use, [93][94][95] and use in the intensive care unit (ICU), 96 and who have described its cardiorenal effects, 88,97 its effects on quality of life, 98,99 exercise performance, 100 lung function, 101 and pharmaco-economic considerations. 102 In the context of a 20-year retrospective it is worth noting at this point that its complex mode of action might have had the potential to disadvantage levosimendan both in fact and in perception.…”

“…In fact, that plurality of effects has emerged as both an important aspect of the drug's clinical versatility and usefulness and as a stimulant to informed speculation among experts and to medical research. 73,92,94,96,103 Levosimendan in Acute Settings…”

Hypoperfusionssyndrom und kardiogener Schock

“…Phosphodiesteraseinhibitoren spielen in der klinischen Routine derzeit keine wesentliche Rolle mehr. Ein Medikament mit interessanter Pharmakodynamik stellt Levosimendan dar, das ähnlich wie Dobutamin positiv inotrop und vasodilatierend wirkt, aber im Unterschied zu Dobutamin dies ohne Steigerung des myokardialen Sauerstoffbedarfes erreicht [19,20]. Zur reinen Vasodilatation bei kardiogenem Schock mit hohem systemvaskulären Widerstand, aber noch erhaltenem systolischen bzw.…”

“…Dadurch können bei liegenden ECLS-Schleusen Entscheidungshilfen für die antegrade Punktion gegeben werden [38,39]. Nach metaanalytischen Daten unter Einschluss von 1866 Patienten liegt die Rate an Beinischämien bei 16,9 % [ CI 12,[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]6], an Fasziotomien oder Kompartment-Syndromen bei 10,3 % [CI 7,3-14,5] und die Rate an Amputationen bei 4,7 % [CI 2,3-9,3] [40].…”