Cardiac failure levosimendan

Levosimendan treatment has generally been well tolerated in patients with acute HP. One of the most common adverse effects is hypotension which occurred more frequently in the group treated with levosimendan than with placebo. However, this effect was not observed in comparison to dobutamine. Other common adverse events are headache, atrial fibrillation, hypokalaemia, and tachycardia. Levosimendan is associated with a higher incidence of atrial fibrillation however, conflicting results have been presented regarding ventricular arrhythmias. Cardiac failure as an adverse effect was less frequent in the levosimendan-treated group compared to placebo [4]. 

The determinants of calcium sensitivity, ie, the curve relating the shortening of cardiac myofibrils to the cytoplasmic calcium concentration, are incompletely understood, but several types of drugs can be shown to affect calcium sensitivity in vitro. Levosimendan is the most recent example of a drug that increases calcium sensitivity (it may also inhibit phosphodiesterase) and reduces symptoms in models of heart failure. 

It has recently become possible to alter the relation between force and [Ca +ji in myocardium, a useful trick in congestive heart failure. Pimobendan modestly increases the affinity of cardiac Tn C (cTn) for Ca +, thereby increasing the activation of contraction at any given [Ca +]i. The more potent levosimendan binds to the N-terminal region of cTn C in a Ca -dependent manner, and amplifies the effect of Ca +, perhaps by increasing the stability of the Ca +-induced conformational change in cTn C or by enhancing cooperativity in the thin filament. 

Levosimendan is a novel inotropic calcium-sensitizing drug. In advanced congestive heart failure, it improves cardiac contractility by sensitizing troponin C to calcium. It has been used recently in a porcine model of endotoxin-induced septic shock, in which pretreatment with levosimendan improved cardiac output and systemic and gut oxygen delivery." There are currently two ongoing clinical trials of levosimendan in septic shock. The role of levosimendan in the supportive management of circulatory failure in sepsis remains to be determined. 

In 12 healthy subjects carvedilol 25 mg twice daily for 7 to 9 days did not alter the effeets of a single 2-mg intravenous dose of levosimendan on cardiac contractility. In addition, the heart rate and diastolic blood pressure responses were not altered, but the systolie blood pressure response was blunted. In a study to eompare levosimendan with dobutamine in patients with severe, low-output heart failure, 33 of the 102 patients receiving levosimendan were also given unnamed beta bloekers. The use of a beta blocker was shown not to reduee the haemodynamie effeets of levosimendan. The authors say this suggests that there may be a place for levosimendan in the management of exaeerbations of heart failure not eontrolled by beta bloekers. ... 

A 38-year-old man was found in his bed deeply comatose and it was suspected that he had taken amlodipine 630 mg, zopiclone 300 mg, and uncertain amounts of citalopram and paracetamol at least 4 hours earlier. He was given activated charcoal, intravenous boluses of glucagon and calcium, and dopamine by infusion, followed by noradrenaline by infusion. Because of persistent hypotension and heart failure he was given levosimendan and the dobutamine was withdrawn. After 90 minutes his cardiac function had improved. The dose of levosimendan was increased and continued for 24 hours, when his lactic acidosis resolved. 

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