[Levosimendan in cardiology and intensive care medicine].
Levosimendan (LS) is a new calcium sensitizer that exerts positive inotropic effects without increasing intracellular cAMP or Ca2+ at therapeutic doses and therefore may avoid major limitations of beta-adrenergic agents. LS also causes arteriolar and venous dilation by opening potassium channels on vascular smooth muscle cells. In addition, LS does not increase myocardial oxygen demand and may exert anti-stunning effects. LS itself has a short elimination half life but has shown to have active metabolites with elimination half lives up to 80 hours. Three hemodynamic studies show that at recommended doses LS increases cardiac output by 8-30% and reduces pulmonary capillary wedge pressure by 11-28% in heart failure patients. Systemic vascular resistance falls significantly and blood pressure tends to decline. The hemodynamic effects are not attenuated by concomitant beta-blocker medication. Two large randomized studies on patients with chronic and acute congestive heart failure found a decrease in mortality with LS. In the LIDO trial there was a 52.9% survival benefit at day 31 when compared with patients receiving dobutamine. In the RUSSLAN trial, the survival benefit approached 40% at day 14 after start of treatment compared to placebo. Experience in the ICU setting is limited but LS therapy in postoperative low output failure and cardiogenic shock seems to be feasible and LS is a promising agent in the inotropic armamentarium. LS has a favourable side effect profile and is approved for 24-hour use in congestive heart failure. It may cause hypotension due to vasodilation, and this effect may be aggravated by inadequate preload conditions. Further morbidity and mortality studies are required to confirm the encouraging data from the LIDO and RUSSLAN trial but already the existing data support LS as the inotropic agent of choice in patients with worsening heart failure and a systolic arterial blood pressure beyond 90 mmHg.
Delle Karth
Georg
G
Abteilung Kardiologie/Intensivstation 13H3, Universitätsklinik für Innere Medizin II, Wien, Osterreich. georg.delle-karth@univie.ac.at
Heinz
Gottfried
G
D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003422:Critical Care; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006835:Hydrazones / Q000009:adverse effects / Q000627:therapeutic use*; D017682:Myocardial Stunning / Q000188:drug therapy* / Q000401:mortality; D011724:Pyridazines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000077464:Simendan; D015996:Survival Rate; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan