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Ann Thorac Surg 2003;75:1974-1976
© 2003 The Society of Thoracic Surgeons

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Case report

Nesiritide (BNP) in the management of postoperative cardiac patients

^a Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, Missouri, USA

Accepted for publication November 26, 2002.

^* Address reprint requests to Dr Moazami, Cardiac Transplantation, Washington University School of Medicine, Barnes-Jewish Hospital, Queeny Tower, Suite 3108, One Barnes-Jewish Hospital Plaza, St. Louis, MO 63110-1013, USA
e-mail: moazamin{at}msnotes.wustl.edu

	Abstract

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Recombinant human B-type natriuretic peptide (BNP) is a promising new agent in the management of heart failure. The pharmacologic properties of BNP make it desirable to use in a subset of patients after cardiac surgical operations. Among these therapeutic potentials is the effect on markedly reducing pulmonary vascular resistance and central venous pressure with mild systemic vasodilatation. In addition, BNP directly effects the kidneys to promote natriuresis. We believe this agent to be useful in the treatment of the postcardiac surgery patients with left ventricular dysfunction and mild to moderate renal insufficiency. This report summarizes our experience in 2 patients.

	Introduction

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Recombinant human B-type natriuretic peptide (BNP) is a promising new agent in the management of heart failure. A previous study in patients with acute decompensated heart failure with associated dyspnea has shown improved hemodynamics with intravenous administration related to reduction in pulmonary capillary wedge pressure, pulmonary vascular resistance, and right atrial pressure [1]. The efficacy of BNP administration in patients with poor left ventricular (LV) function undergoing cardiac operations has not been evaluated. We present our experience with 2 patients with preoperative LV dysfunction and renal insufficiency.

	Case reports

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Patient 1
An 87-year-old woman with acute myocardial infarction and moderate left ventricular dysfunction (ejection fraction 30%) underwent emergent coronary artery bypass surgery for unstable angina. Preoperative serum creatinine was 2.1 mg/dL. She required placement of intraaortic balloon pump (IABP) and subsequently had three-vessel coronary artery bypass grafting. Milrinone, dobutamine, and IABP were needed to wean her from cardiopulmonary bypass. Initial hemodynamics included blood pressure (BP) 148/52 mm Hg, pulmonary artery pressure (PAP) 65/24 mm Hg (mean 38), central venous pressure (CVP) 19 mm Hg, and cardiac index (CI) 2.7 l · min^-1 · m^-2. Despite inotropic therapy, filling pressures remained high and she was oliguric.

Nesiritide infusion was started at 0.01 mg · kg^-1 · min^-1. Within 4 hours the hemodynamics were as follows: BP 129/46, CVP 13, PA 54/26 (mean 33), and CI 2.8 (Fig 1, A). Sixteen hours after initiation of nesiritide, IABP had been removed, milrinone had been weaned off, and dobutamine infusion reduced to 2 µg · kg^-1 · min^-1. The following hemodynamics were obtained BP 131/86, CVP 10, PAP 37/10 (mean 19), and CI 2.9. Concomitant with the above improvements in filling pressures there was a significant increase in urine output from less than 200 mL per 8 hours to more than 800 mL per 8 hours, which was sustained over the ensuing days (Fig 2). Serum sodium and creatinine remained stable at 138 mEq/L and 2.7 mg/dL, respectively.

View larger version (14K): [in this window] [in a new window]   Fig 1. Mean pulmonary arterial pressures (mPAP) and central venous pressures (CVP) for patient 1 (A) and patient 2 (B). Circles = mPAP; diamonds = CVP.

View larger version (16K): [in this window] [in a new window]   Fig 2. Urine output at 8-hour intervals after initiation of nesiritide infusion.

	Comment

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The recombinant B-type natriuretic peptide, nesiritide, has been recently approved for use in patients with decompensated heart failure and associated dyspnea at rest or with minimal activity. The Vasodilation in Acute Congestive Heart Failure (VMAC) trial [1] evaluated the efficacy of this treatment in a prospective randomized trial involving 489 patients. The trial involved a comparison between intravenous nesiritide compared to nitroglycerin or placebo and demonstrated significant reduction in pulmonary capillary wedge pressure, pulmonary vascular resistance, and central venous pressure.

To date the use of BNP has not been evaluated as a pharmacologic adjunct for the management of critically ill patients postcardiac operations. This new agent has many therapeutic properties that are desirable in a subset of cardiac surgical patients. We have reported on the effect of BNP in 2 patients who were recently treated at our institution.

Recombinant human B-type natriuretic peptide is a peptide that is normally secreted by ventricular myocardium in response to hemodynamic overload. Elevated levels have been found in conditions of increased preload, afterload, myocardial hypertrophy, myocardial infarction and most cardiomyopathies [2]. Hemodynamic overload induces the expression of BNP from the ventricular myocardium at the transcriptional level. It has been suggested that despite increased circulating levels of BNP in patients with heart failure, there may be a relative deficiency due to inability to upregulate transcription or due to receptor down regulation.

Nesiritide mimics the actions of endogenous BNP by binding to vascular smooth receptors. Activation of the receptors leads to increased synthesis of cyclic guanine monophosphate (cGMP) which mediates the vasodilator actions of this peptide. Clinically this is manifested by decrease in CVP and PVR and systemic arterial vasodilation. In both cases presented here, we observed a reduction in central venous and pulmonary pressures without any clinically significant systemic hypotension. In the VMAC trial [1] the incidence of systemic hypotension was not significantly different between nesiritide and nitroglycerin (4% and .5%, respectively). The drug has a rapid onset of action, with most of its effect seen in the initial 30 minutes of infusion. The drug remains effective throughout the duration of therapy and does not need dose adjustment in patients with renal insufficiency. In addition to its effect on the vascular system BNP also promotes natriuresis [3]. This effect may be ideal in the fluid overloaded post surgical patient with renal insufficiency. In both of our patients there was a dramatic and sustained increase in urine output without any significant change in serum sodium or creatinine.

Finally, other properties of the natriuretic peptides that are theoretically beneficial include attenuation of the sympathetic outflow [4] and inhibition of endothelin, renin and aldosterone production [5]. These neurohormonal pathways clearly play a central role in the pathogenesis of heart failure and down regulation may also be beneficial in the perioperative period.

In conclusion BNP exhibits pharmacologic properties that may be desirable in the post surgical cardiac patient. The exact profile of surgical patients who may benefit from nesiritide has not been clearly defined. Based on knowledge of its pharmacologic action patients who have moderate to severe LV dysfunction, with or without elevated pulmonary artery pressures, may benefit from its vasodilatory properties. In patients with renal insufficiency, unresponsive to standard diuretic therapy, the natriuretic effects may also be beneficial. Whether the counter regulatory neurohormonal effects will also be beneficial remains to be seen. In our brief experience we did not encounter any significant side effects. Ultimately the true potential of this new therapy in the cardiac surgical arena needs to be defined by a well-designed randomized prospective trial. The initial patients for this study can be those with preexisting ventricular dysfunction or the group of heart failure patients after ventricular assist device placement or cardiac transplantation.

	References

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1. Young J.B., Abraham W.T., Stevenson L.W., et al. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure. JAMA 2002;287:1531-1540.[Abstract/Free Full Text]
2. Takahaski T., Allen P.D., Izumo S. Expression of A-, B-, and C-type natriuretic peptide genes in failing and developing human ventricles. Correlation with expression of the Ca²⁺-ATPase gene. Circ Res 1992;71:9-17.[Abstract/Free Full Text]
3. de Zeeuw D., Janssen W.M.T., de Jong P.E. Atrial natriuretic factor: its (patho)physiological significance in humans. Kidney Int 1992;41:1115-1133.[Medline]
4. Abramson B.L., Ando S., Notarius C.F., Rongen G.A., Floras J.S. Effects of atrial natriuretic peptide on muscle sympathetic activity and its reflex control in human heart failure. Circulation 1999;99:1810-1815.[Abstract/Free Full Text]
5. Laragh J.H. Atrial natriuretic hormone, the renin-aldosterone axis, and blood pressure-electrolyte homeostasis. N Engl J Med 1985;313:1330-1340.[Abstract]

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Nader Moazami Ralph J. Damiano Jennifer S. Lawton Marc R. Moon Michael K. Pasque Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moazami, N. Articles by Pasque, M. K. Search for Related Content PubMed PubMed Citation Articles by Moazami, N. Articles by Pasque, M. K.