Multiorgan Drug Action of Levosimendan in Critical Illnesses

Cardiotonic drugs mainly include digitalis, catecholamines, phosphodiesterase inhibitors, and calcium sensitizers, which have been successively discovered and applied in clinical practice. However, there are only a few new drugs available in this field, and the selection is very limited. Digitalis, catecholamines, and phosphodiesterase inhibitors increase myocardial contractility by increasing intracellular concentrations of cyclic adenosine monophosphate (cAMP) and Ca2+, and this increase in intracellular calcium ion concentration enhances myocardial oxygen consumption and causes arrhythmia. For these reasons, the research focus on positive inotropic agents has shifted from calcium mobilization to calcium sensitization. Intracellular calcium sensitizers are more effective and safer drugs because they do not increase the intracellular concentration of calcium ions. However, only three calcium sensitizers have been fully developed and used in the past three decades. One of these drugs, levosimendan, has multiple molecular targets and exerts its pharmacological effects by not only increasing myocardial contractility, but also enhancing respiratory muscle function and liver and kidney protection, and it is useful for patients with severe sepsis and septic shock. Recently, more than 60 randomized controlled clinical trials of levosimendan have been reported; however, these clinical trials have occasionally shown different findings. This article reviews the research progress of levosimendan in critical illnesses in recent years.

Positive inotropes

Inotropic agents are substances used to improve cardiac output and end-organ perfusion in severe forms of acute heart failure. However, inappropriate use of inotropic agents may be associated with severe adverse effects and death. Despite clear indications to restrict their use to acute heart failure patients presenting with signs of end-organ hypoperfusion, the current use of inotropes is very frequent and often unnecessary. This chapter reviews mechanisms of action of current and future inotropes (including catecholamines, phosphodiesterase-III inhibitors, calcium sensitizers, cardiac myosin activators, and istaroxime) and discusses their clinical use in acute heart failure.