Milrinone and the clinical challenge of CHF
Milrinone and the clinical challenge of CHF
Milrinone is an inotropic agent that is indicated for the short-term management of CHF. It inhibits phosphodiesterase III, thereby increasing myocardial contractility.
The drug is typically administered as loading dose of 50 mcg/kg IV over 10 minutes, followed by a continuous infusion of 0.375 mcg/kg/min to 0.75 mcg/kg/min. The infusion rate should be adjusted according to patient response and monitored by improved cardiac output and reduction in pulmonary wedge pressure. Milrinone is available in a concentration of 1 mg/ml and must be diluted prior to administration with 5% dextrose injection and 0.45% or 0.9% sodium chloride injection.
Two different types of positive inotropes have been advocated for use in CHF: beta-adrenergic agonists such as dobutamine and phosphodiesterase inhibitors such as milrinone.1 Both classes of agents work by increasing myocardial contractility.
The American College of Cardiology and the American Heart Association recommend the use of dobutamine and milrinone for patients with severe, refractory CHF. These drugs should only be used in patients who have failed to respond to maximal therapy with established or approved strategies such as ACE inhibitors, diuretics, digoxin, and other agents.
In one study, home parenteral inotropic therapy reduced hospital admission length of stay, and improved functional heart failure classes.2 In some patients, positive inotropic therapy may be necessary as a therapeutic bridge to transplantation.3 Long-term outpatient use of positive inotropic agents has been discouraged due to reported increased mortality rates in some trials and lack of consensus on what agent should be used.
For example, the Vesnarinone Evaluation of Survival Trial (VEST) found an increased mortality with the use of 60 mg/d of vesnarinone.4,5 Another trial evaluating IV dobutamine was terminated because of an increased mortality rate.
When indicated, patients seen and admitted to the hospital through the emergency room can be started on these inotropic agents if their clinical condition has been refractory to other agents. It is recommended that dobutamine be started at a low dose (2-5 mcg/kg/min) to avoid arrhythmias, tachycardia, and exacerbation of myocardial ischemia.
Milrinone may also be used; it should be started using a loading dose of 50 mcm/kg followed by a continuous infusion of 0.375-0.75 mcm/kg/min. Patients who respond to dobutamine or milrinone who are milrinone- or dobutamine-dependent may be transitioned to a chronic long-term basis at home.
There are few data demonstrating the safety and efficacy of using inotropic therapy in decompensated heart failure. The Outcome of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure trial (OPTIME CHF) is a multicenter, randomized, placebo-controlled trial that is ongoing and will evaluate patients with heart failure.
Currently, recommendations of the American College of Cardiology and the American Heart Association are to administer inotropic agents only to patients with severe or refractory heart failure.
Positive inotropic therapy should be used with caution in patients with coronary artery disease and ischemic cardiomyopathy.
(Adapted from Rogers R, Robinson DJ. The clinical challenge of congestive heart failure: Optimizing outcomes in the emergency department and outpatient setting, Part II: Targeted drug therapy, invasive interventions, and patient disposition. Emergency Medicine Reports, June 21, 1999.)
References
1. Packer, Cohn. Consensus recommendations for the management of chronic heart failure. Am J Cardiol 1999; 83:1A-38A.
2. Harjai KJ, et al. Home inotropic therapy in advanced heart failure — Cost analysis and clinical outcomes. Chest 1997; 112:1,298-1,303.
3. Leier CV, et al. Parenteral inotropic support for advanced congestive heart failure. Prog Cardiovasc Dis 1998; 41:207-224.
4. Gheorghiade M, et al. Current medical therapy for advanced heart failure. Am Heart J 1998; 135:S231-S248.
5. Scherrer-Crosbie M, et al. Effect of vesnarinone on cardiac function in patients with severe congestive heart failure. Am Heart J 1998; 136:769-777.
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