Of interest to the clinicians is that, while appearing minimally responsive to endogenous BNP, heart failure patients will effectively respond to exogenously administered BNP which is nesiritide drip.
In patients with cardiogenic pulmonary edema due to acute decompensated heart failure, plasma brain natriuretic peptide (BNP) measurements can guide the diagnosis, distinguishing this etiology of dyspnea from pulmonary causes.
Plasma BNP concentration is elevated in both asymptomatic and symptomatic heart failure (left ventricular dysfunction) and is useful for both diagnosis and prognosis.
BNP is a hormone abundantly found in the heart (especially the ventricles) but initially identified in the brain. It is released from myocardial cells in response to wall stress, volume expansion, and high filling pressures.
Physiologically, endogenously produced BNP targets the heart, blood vessels, and kidneys to reduce preload and afterload through vasodilatation, diuresis, and natriuresis (sodium excretion).
BNP also counters neurohormones such as endothelin, aldosterone, and angiotensin II. Murine studies further suggest that BNP may protect against the progressive cardiac fibrosis associated with chronic heart failure. In whole, BNP reduces the workload on the heart to improve cardiac performance.
A rapid BNP fluorescence immunoassay was approved in 2000 and can be rapidly performed in 10 to 15 minutes at the bedside. Patients with heart failure have significantly higher levels of plasma BNP than those with dyspnea due to other causes.
Remarkably, plasma BNP is more accurate for predicting heart failure than classic parameters such as rales, cardiomegaly, or the National Health and Nutrition Examination Survey (NHANES) or Framingham criteria. BNP also correlates with the New York Heart Association functional class.
A value >100 pg/mL makes the diagnosis of heart failure with a sensitivity of 90%, specificity of 76%, and a predictive value of 83%. Conversely, low BNP has a strong negative predictive value to rule out heart failure. The rapid assay costs approximately $20 per test.
Despite having elevated levels of cardioprotective BNP, patients with heart failure are generally paradoxically vasoconstricted and sodium avid.
Nesiritide is a recombinant form of human B-type natriuretic peptide (hBNP), approved in 2001 for the intravenous (IV) treatment of patients with acutely decompensated congestive heart failure.
Nesiritide drip is given as an initial IV bolus of 2 mcg/kg, followed by a continuous infusion at 0.01 mcg/kg/min. The dose may be increased to a maximum rate of 0.03 mcg/kg/min.
There is no dose adjustment for renal insufficiency. Nesiritide drip promotes sodium excretion, reduced cardiac filling pressures (reduced pulmonary capillary wedge pressures), and improved cardiac indices and clinical status (e.g., dyspnea, fatigue) in patients with heart failure.
These positive hemodynamic effects are seen within the first hour of administration and are maintained throughout the infusion period and up to 6 to 24 hours after discontinuation.
The most common side effect of nesiritide drip is dose-related hypotension, which may be enhanced when given with other vasodilators, such as angiotensin-converting enzyme (ACE) inhibitors.
While nesiritide drip appears fairly safe and is well tolerated, there are data that have prompted questions about its effects on renal function and survival. For example, one analysis suggested that patients treated with nesiritide drip may have been more likely to develop progressive renal insufficiency, although this may be due to hypoperfusion rather than direct renal toxicity.
Another retrospective analysis suggested a trend (nonsignificant) toward a higher 30-day mortality in patients treated with nesiritide drip.
In summary, nesiritide drip is an effective therapy for patients hospitalized with acute decompensated heart failure, especially those requiring inotropic support.
It may be particularly useful in heart failure patients with tachycardia or arrhythmias, which would otherwise limit the use of traditional agents such as dopamine or dobutamine. nesiritide drip may be used in combination with other heart failure medications (e.g., diuretics, ACE inhibitors, dopamine, dobutamine, or milrinone) when tolerated.
Close monitoring of hemodynamics, urine output, and renal function is essential.
Suggested Readings
Colucci WS, Elkayam U, Horton DP, et al. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group. N Engl J Med 2000;343:246.
Mills RM, Hobbs RE. How to use nesiritide in treating decompensated heart failure. Clev Clin J Med 2002;69:252.
Nesiritide for decompensated congestive heart failure. Med Lett Drugs Ther 2001;43:100.