Affiliations: Department of Pediatric Intensive Care Unit, Edmond and Lily Safra Children's Hospital, The Chaim Sheba medical center, Tel Hashomer, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Note:  Corresponding author: Gideon Paret, Pediatric Intensive Care Unit, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer 52621, Israel.
Abstract: We designed this review to examine the mechanism of action of levosimendan (Simdax®, Orion Pharma, Espoo, Finland) and its current clinical application in critically ill adults and children with acutely decompensated severe congestive heart failure and who require inotropic support. We applied Pubmed (primarily) and Google search engines for English-language papers whose main topic was the use of levosimendan in the general population and those that concentrated on pediatric cohorts aged 0 to 18-year-old. Levosimendan increases contractile force of the heart and improves vasodilation. It increases the heart's sensitivity to calcium, thereby increasing cardiac contractility. Its mechanism of action is via the increased calcium sensitivity of myocytes by binding to cardiac troponin C in a calcium-dependent manner. Its opening of adenosine triphosphate-sensitive potassium channels in vascular smooth muscle leads to a vasodilatory effect and smooth muscle relaxation. Levosimendan was shown to be effective in the treatment of acute decompensated heart failure, rescue therapy for septic shock, weaning patients from assisted devices and weaning patients from inotropic therapy. Neonates with hypoplastic left heart syndrome who were treated by levosimendan showed improvement in systemic perfusion following cardiac surgery. Cost-effectiveness of this new drug is discussed.