Cardiology

Vasodilator Drugs; Acute Vasodilator Intervention - Nesiritide

General (including evidence of efficacy)

Nesiritide

This is the vasodilator most recently added to the formulary for acute intervention of symptomatic heart failure, and perhaps the most controversial.

Differences between drugs within the class

The hemodynamic effects of nesiritide, at the recommended doses, appear to reside somewhere between those of nitroprusside and nitroglycerin. Nesiritide reduces left ventricular filling pressure less aggressively than nitroprusside and persistently more so than IV nitroglycerin.

Administration

For a more rapid onset of action, nesiritide is administered as a 1.0 to 2.0 mcg/kg bolus followed by a continuous infusion at 0.005 to 0.01 mcg/kg/min. More commonly and in less urgent situations, the bolus is not administered and the continuous infusion of 0.005 to 0.01 mcg/kg/min is used to effectively manage the patient's dyspnea.

Pharmacologic action

Nesiritide is a general vasodilator, acting mostly through the augmentation of vascular cGMP production. Some of the pharmacologic properties may also be rendered by its effects on various circulating hormones, namely a reduction in endothelin and the renin-aldosterone axis.

Nesiritide reduces ventricular diastolic filling pressure, pulmonary capillary wedge pressure, pulmonary artery pressure, and right atrial pressure. Pulmonic and systemic vascular resistance decreases with nesiritide, with a modest rise in cardiac output secondary to some afterload reduction. With prolonged administration and at higher doses, nesiritide can lower systemic blood pressure.

Indications and contraindications

Indications

The indications for nesiritide have changed somewhat over the past 5 years from being a first-line therapy for most cardiogenic dyspnea to that of another option for this problem. If cardiogenic dyspnea is not improved with diuretics, standard heart failure therapy, oral vasodilators, or short-term IV nitroglycerin (< 24 hours), nesiritide may be helpful.

At the recommended doses, nesiritide does not appear to affect mortality out to 30 days and does not alter rehospitalization rates.

Contraindications

Nesiritide is contraindicated in the setting of systemic hypotension.

Undesirable effects

The primary adverse effect is systemic hypotension and as such, it is important to closely monitor blood pressure during administration. The systemic hypotension can develop very gradually during the infusion, and it is not an infrequent event in the middle of the night after hours of what should be an ideal fixed dose.

Hypotension and other undesirable effects will respond to dose reduction (by a half or more) or discontinuation. As a general rule, it is usually not necessary to place a pulmonary artery catheter for nesiritide infusions; following the symptom of dyspnea and avoiding undesirable effects offer an adequate guide to dosing. Other undesirable effects include flushing, headaches, and nausea.

Based on its proposed mechanisms of action, it was felt that nesiritide would be a potential agent to improve renal function. However, several studies have now shown that nesiritide has no net effect on renal performance (glomerular filtration rate, diuresis, and natriuresis), and at higher doses, nesiritide can adversely affect renal function. It does not have a diuretic enhancing or sparing effect.

Alternative approaches

Nitroprusside with diuretics for more severe dyspnea and IV nitroglycerin, diuretics, oral nitrates, and additional heart failure therapies for mild to moderate dyspnea are reasonable alternatives.

Additional vasodilators

Milrinone

Intravenous milrinone has powerful systemic and pulmonary vasodilating properties and is discussed in another section.

Intravenous nicorandil

Intravenous nicorandil has resurfaced again as a potential therapy for acute vasodilatation. Whether it can squeeze out a role among nitroprusside, nitroglycerin, and nesiritide remains to be determined.

Others

Cinaciguat hold some promise as a potential acute vasodilator therapy based on initial studies.

What's the Evidence?

Colucci, WS, Elkayam, U, Horton, DP. " Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure". N Engl J Med. vol. 343. 2000. pp. 246-53.

"Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial". JAMA. vol. 287. 2002. pp. 1531-40.

You must be a registered member of Clinical Advisor to post a comment.
close

Next Article in Cardiology

Sign Up for Free e-newsletters