Archan S, Toller W
Journal: Curr Opin Anaesthesiol 21(1):78-84, 2008. 76 References
Reprint: Dept of Anesthesiology and Intensive Care Medicine, University Hospital Graz, Auenbruggerplatz 29, A-8036 Graz, Austria (WG Toller, MD) SO.01 JU0806/156 ©2008
Faculty Disclosure: Abstracted by S. Ouellette, who has nothing to disclose.
Heart failure is a leading cause of hospitalization in patients over 65 years of age and is a progressive disease with a poor prognosis. In patients hospitalized with congestive heart failure the 60-day mortality rate is approximately 10%. Due to epidemiological changes and advancement in treatment the number of patients with congestive heart failure is increasing and the number of these patients presenting for surgery is also increasing.
Patients with congestive heart failure are generally treated with oxygen, diuretics and vasodilators. The most common vasodilators used are nitroglycerin, nitroprusside and nisiritide. Nisiritide, a form of recombinant human B-type natriuretic peptide, improves hemodynamics effectively and has fewer side effects than nitroglycerin. Positive inotropic drugs include catecholamines, phosphodiesterase inhibitors, and, in some countries, calcium-sensitizing agents such as levosimendan. Calcium-sensitizers increase the calcium sensitivity of contractile regulatory proteins, causing an increase in myocardial contractility. These agents are free from the risk of calcium overload and do not require an increase in activation energy. They could improve hemodynamic parameters with a minimum increase in energy expenditure and a low risk of arrhythmias, even under pathophysiologic conditions, such as acidosis and stunned myocardium. Due to its site of action, no antagonistic effects are observed when beta-adrenergic antagonists are used in parallel.
The calcium-sensitizer and vasodilator levosimendan is the most promising agent of this drug group to date. The drug causes dose-dependent increases in stroke volume and cardiac index, and dose-dependent decreases in pulmonary capillary wedge pressure and pulmonary artery pressure. While administration of 6-24 mcg/kg loading dose delivery in 10 min followed by a 24-hr infusion at 0.05-0.2 mcg/kg/min was considered the optimum dose, recent studies suggest omission of the loading dose. The dose should be reduced by half in patients with renal insufficiency since the half-life of levosimendan metabolites was prolonged 1.5-fold in patients with chronic renal failure and patients with end-stage renal disease undergoing hemodialysis. Levosimendan is generally well tolerated in patients with moderate to severe heart failure with an overall frequency of adverse events of 17-29%. The most common side effects reported in clinical trials were hypotension, headache, ventricular tachycardia and atrial fibrillation.
Levosimendan is well established in treatment of acute heart failure with or without ischemia. There are also encouraging preliminary results with levosimendan in patients undergoing cardiac surgery. Effects of levosimendan in patients with right ventricular dysfunction and septic shock are encouraging. |
