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Case Report |
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 Top Case Report DiscussionControversy Regarding Nesiritide...SummaryReferences |
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On arrival, the patient had a blood pressure of 158/95 mm Hg, a pulse rate of 86/min, and an oxygen saturation of 91% when breathing room air. An electrocardiogram revealed atrial flutter. Findings on physical examination were consistent with a diagnosis of ADHF, including jugular venous distension, an S3 gallop, rales in the basilar lung fields, soft heart sounds, and 3+ pitting edema in both lower extremities. The patient was directly admitted from the clinic; the diagnosis was ADHF. When he arrived in the telemetry unit, he was given furosemide 80 mg intravenously twice, and the response to furosemide therapy was monitored. When a minimal response was noted, the physicians involved in the patient’s care decided that he might benefit from treatment with nesiritide to improve signs and symptoms and decrease filling pressures. He was given a bolus of nesiritide (2 µg/kg), and then a maintenance infusion (0.01 µg/kg per minute) was started. The bolus dose was administered over 60 seconds through a port in primed tubing and was obtained from the prepared container, which had a concentration of 6 µg/mL.
After approximately 24 hours of nesiritide and diuretic therapy, the patient had a net diuresis of greater than 4 L. His blood pressure during this time ranged from 105 to 167 mm Hg systolic and 55 to 89 mm Hg diastolic. On rounds the next morning, he was feeling better, had less shortness of breath, no longer had a cough, and had no other complaints. Findings on physical examination had improved, he had increased excretion of urine, his signs and symptoms continued to improve, and by day 2 the nesiritide infusion had been discontinued. The patient remained in the hospital for an additional 24 hours for monitoring. At the time of discharge, he was taking his previous medications, albeit at greater doses than at admission (hydralazine and isosorbide mononitrate), and metolazone, a thiazide diuretic, had been added to the regimen. Of note, he was not taking an angiotensin-converting enzyme inhibitor or ß-blocker, which should be standard therapy for all patients with heart failure who can tolerate them.3 Review of previous charts indicated that the patient did not have any allergies, but he may have been told to stop taking the angiotensin-converting enzyme inhibitor because of adverse effects such as increased creatinine levels or cough. The patient did not have any obvious contraindications to ß-blocker therapy.
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Discussion |
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TopCase ReportDiscussionControversy Regarding Nesiritide...SummaryReferences |
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Pathophysiology of Heart Failure and ADHF
The principal function of the heart is to pump oxygenated blood to the peripheral tissues to meet metabolic demands. Heart failure is defined as the inability to meet the metabolic demands of the tissues. The most common causes of heart failure are ischemic heart disease, hypertension, and valvular abnormalities. Two types of heart failure may occur: systolic dysfunction (impaired contracting ability) and diastolic dysfunction (impaired relaxation or filling of the heart).
Patients with systolic dysfunction have decreased ejection fractions (<0.40), and the most common cause of this type of heart failure is ischemic heart disease (coronary artery disease).5 During systole, the heart ejects approximately 50% of its contents into the aorta for distribution to the peripheral tissues; therefore, patients with systolic dysfunction have hearts that do not pump vigorously enough to meet the demands of the tissues.
Patients with diastolic dysfunction have preserved ejection fractions (>0.40), but their ventricles are stiff and often are enlarged (hypertrophied).6 During diastole, the heart relaxes and fills with blood, so patients with diastolic dysfunction have hearts that do not relax normally and cannot completely fill with blood.
ADHF occurs when the heart fails to provide enough cardiac output to meet the metabolic demands of the tissues. Patients with ADHF may have both systolic and diastolic dysfunction, and the drugs that are used to treat ADHF address the 2 types of dysfunction through different mechanisms of action.
When decompensation occurs in a patient with chronic heart failure, an exacerbating factor such as excessive sodium intake, medication non-compliance, or infection causes a shift in cardiovascular homeostasis such that signs and symptoms of heart failure worsen. The patient may have worsening edema, increased shortness of breath, and signs of organ hypoperfusion such as worsening renal function and impaired mentation. These signs reflect fluid retention and poor cardiac output.
Treatment of ADHF
The therapeutic agents used to treat ADHF include intravenous diuretics, inotropic agents, and vasodilators, including nesiritide. These different therapies have different effects on hemodynamic status (see Table
).
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Inotropic Agents
Inotropic agents such as dobutamine or milrinone are also used to treat patients with ADHF. These agents work by increasing contractility of the cardiac myocytes and increasing cardiac output. The safety and efficacy of inotropic agents in the treatment of patients with ADHF have come into question. In a study published in 2002,7 the use of milrinone (vs placebo) in patients with acute heart failure but not cardiogenic shock was associated with a greater risk of adverse effects, namely, arrhythmias and hypotension. Treatment with milrinone did not result in shorter lengths of stay or fewer readmissions. Therefore, inotropic agents should be reserved for patients with systolic dysfunction who have signs or symptoms of current or impending cardiogenic shock, including hypotension and evidence of low cardiac output such as cool extremities and declining renal function.
Vasodilators
Vasodilators such as nitroglycerin or nitroprusside are also commonly used in patients with ADHF to reduce preload (amount of stretch in the left ventricle after diastole) and thereby increase cardiac output. These medications are helpful in unloading the heart during heart failure, but their use may be limited by monitoring and dosing needs. For example, nitroprusside has commonly been used in patients with hypertension and heart failure, but it must be administered in an intensive care setting because it requires monitoring and frequent adjustments in dosage. Use of nitroprusside may also be complicated by toxic effects of cyanide and thiocyanate if renal or liver dysfunction occurs (as in this patient). Nitroglycerin has also been used to reduce preload and provide coronary vasodilatation in patients who require vasodilatation. However, nitroglycerin is usually used in the intensive care unit (ICU) because of the need for monitoring. In addition, the use of nitroglycerin induces physiological tolerance to its effects (tachyphylaxis) after prolonged infusions (about 24 hours) or high doses.
Nesiritide
Nesiritide is the newest drug that has been approved to treat patients with ADHF. Nesiritide is a recombinant formulation of endogenous B-type natriuretic peptide (BNP), which is secreted by ventricular myocytes in response to pressure-volume overloading in the ventricle. BNP has vasodilatory properties and is helpful for relieving signs and symptoms and improving the markedly abnormal hemodynamic changes that occur with ADHF. BNP is secreted by the left ventricle in response to stretching of the myocytes that occurs when left ventricular end-diastolic pressure (preload) is increased.
In addition to its vasodilatory properties, BNP has natriuretic effects and neurohormonal antagonism.8 In fact, in contrast to neurohormones such as norepinephrine, aldosterone, and angiotensin II, which can lead to harmful changes, BNP is a useful counter-regulatory hormone that plays an important role in cardiovascular hemostasis. As the severity of heart failure increases, greater amounts of BNP are secreted by the ventricles in response to greater preload in an attempt to unload the heart and improve function. Unfortunately, the physiological activity of BNP is "overwhelmed" by the vasoconstrictive and fluid-retaining properties of other hormones (angiotensin, aldosterone, nor-epinephrine). This increase in the level of BNP is the basis for the point-of-care test for BNP that has been used to diagnose heart failure in an emergent setting.9
Hemodynamic changes that occur with the use of nesiritide include reduction in pulmonary artery pressures and left ventricular pressures (pulmonary capillary wedge pressure [PCWP], which is a measure of preload). In the patient in the case study, nesiritide was chosen because of its effectiveness in alleviating signs and symptoms and improving hemodynamic status, its ease of administration, its lack of toxicity, and its mild diuretic/natriuretic properties. Inotropic agents were not indicated because the patient’s condition was relatively stable, with a good blood pressure and no indications of hypoperfusion or cardiogenic shock.
The role of nesiritide in the treatment of acute heart failure has been investigated in several trials. In a 2-part trial, Colucci et al10 studied patients with acute heart failure: one part was an efficacy trial (nesiritide vs placebo); the other part was a comparative trial (nesiritide vs standard of care, which could include the administration of dobutamine, milrinone, nitroglycerin, or nitroprusside at the discretion of the investigator). In the efficacy trial, a bolus of 0.3 or 0.6 µg/kg was given and then nesiritide was infused at 2 different doses, either 0.015 µg/kg per minute or 0.03 µg/kg per minute. In the comparative trial, the bolus and maintenance doses of nesiritide were the same; however, nesiritide was compared with standard care as just described. In both trials, the end points were reduction in PCWP and improvement in signs and symptoms of heart failure, as measured by using a global clinical assessment scale. Patients included in the trial had marked hemodynamic dysfunction as indicated by a baseline mean PCWP of 28 mm Hg, a mean cardiac index (calculated as cardiac output in liters per minute divided by body surface area in square meters) of 1.8, and a mean left ventricular ejection fraction of 0.22. In the efficacy trial, compared with placebo, nesiritide improved hemodynamic function and global clinical assessment scores. In the comparative trial, treatment with nesiritide and standard therapy resulted in similar improvements in signs and symptoms. The most common adverse effect of nesiritide was hypotension, both asymptomatic and symptomatic.
The Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial11 was done to compare the effects of nesiritide with the effects of another vasodilator, nitroglycerin. In this large trial, patients with ADHF and resting dyspnea were randomized to receive intravenous nitroglycerin (dosage adjusted by investigator), intravenous nesiritide (either in a fixed dosage of a 2 µg/kg bolus followed by an infusion at 0.01 µg/kg per minute or an adjustable dose), or placebo in addition to standard therapy for heart failure. The investigators decided whether to monitor each patient invasively with a pulmonary artery catheter. This pulmonary artery catheter was used for monitoring in about half of the patients (60 of 143 patients receiving nitroglycerin, 124 of 204 patients receiving nesiritide, and 62 of 142 receiving placebo). This predetermined stratification and the dosing strategy were an attempt to replicate actual common practice in managing patients with heart failure without the aid of hemodynamic monitoring.
Although both nesiritide and nitroglycerin decreased PCWP, nesiritide reduced PCWP significantly more than either standard care plus intravenous nitroglycerin or standard care plus placebo reduced PCWP in the first 3 hours of therapy. The superior reduction of PCWP with nesiritide was largely sustained for 24 hours during the infusion. After 3 hours, patients in the nesiritide groups experienced a significant improvement in dyspneic symptoms compared with the patients who received the placebo but did not show any improvement compared with patients who received nitroglycerin. After 24 hours, both patients treated with nitroglycerin and patients treated with nesiritide had similar improvements in dyspneic symptoms.
Significantly more patients treated with nitroglycerin than patients treated with nesiritide experienced adverse effects during the first 24 hours of drug infusion. The most common adverse effect (in both groups) was headache, which occurred to a greater extent in the nitroglycerin group (20%) than in the nesiritide group (8%). Additionally, more patients treated with nitroglycerin (5%) than patients treated with nesiritide (1%) experienced abdominal and catheter-associated pain. Hypotension occurred in both groups. During the first 24 hours after administration of the drug, 8% of patients receiving nesiritide had asymptomatic hypotension and 4% had symptomatic hypotension. Similarly, among patients treated with nitroglycerin, 8% had asymptomatic hypotension and 5% had symptomatic hypotension, although the duration of the hypotension was longer in the group that received nesiritide therapy. Thirty-day readmission rates and 6-month mortality rates did not differ significantly between the 2 groups.
The VMAC trial provides the evidence to support the currently recommended initial dose of nesiritide, a bolus of 2 µg/kg followed by a maintenance infusion of 0.01 µg/kg per minute. This study indicates a role for nesiritide in the treatment of ADHF.
In the Prospective Randomized Evaluation of Cardiac Ectopy With Dobutamine or Natrecor Therapy (PRECEDENT) study,12 the incidence of ventricular tachycardia was compared between patients with ADHF receiving dobutamine and patients with ADHF receiving nesiritide. In that study, 24-hour Holter monitors were used to detect arrhythmias during infusions of dobutamine and nesiritide. Patients given dobutamine infusions experienced significantly more episodes of ventricular ectopy (tachycardia, premature ventricular contractions, couplets, triplets) than did patients given nesiritide infusions. The occurrence of ventricular arrhythmias can be a problem in patients with acute heart failure because potentially lethal arrhythmias may occur. The commonly used inotropic agents, dobutamine and milrinone, increase the incidence of both atrial and ventricular arrhythmias.7
Nursing Implications
The nursing care of patients hospitalized for treatment of ADHF requires frequent monitoring of vital signs, strict monitoring of fluid intake and output, daily weighing, telemetry monitoring, and administration of appropriate medical therapy. This care does not change markedly when patients are receiving nesiritide therapy. Nesiritide can be given safely outside of an ICU, and its use does not mandate monitoring with a pulmonary artery catheter (50% of the patients who received nesiritide in the VMAC study did not have pulmonary artery catheters in place and were monitored in a telemetry unit).
The most common adverse effect of treatment with nesiritide in the studies reviewed10–12 was hypotension, and the hypotension was usually asymptomatic. The risk for hypotension can be kept low by using the following guidelines. Most important, nesiritide is not indicated in patients with a systolic blood pressure of less than 90 mm Hg or in patients with cardiogenic shock.
When treatment with nesiritide is begun, the most profound effects on blood pressure occur in the first 1 to 2 hours of therapy. Therefore more frequent monitoring is recommended at the beginning of therapy. For example, at the University of Illinois Medical Center at Chicago, nurses check vital signs every 15 minutes for the first hour, then every 30 minutes for 1 hour, and then every 4 hours as dictated by unit policy. When changes in blood pressure are assessed, distinguishing symptomatic hypotension from asymptomatic hypotension is important. Although symptomatic hypotension certainly warrants modifications in therapy, asymptomatic hypotension, in most instances, can be monitored without any immediate changes. In addition, special attention should be given to patients receiving high doses of intravenous diuretics during nesiritide therapy because these patients may be prone to hypotension. It may be necessary to decrease the dose of intravenous diuretics during therapy, depending on the patient’s blood pressure, urine output, renal function, and signs and symptoms.
If a patient experiences marked hypotension while receiving nesiritide, the infusion should be stopped, and the patient can be placed in the Trendelenburg position to increase venous return and improve central perfusion. After the hypotension has resolved, if deemed clinically necessary, the nesiritide infusion may be restarted with a 30% reduction in dosage (no bolus).
In patients who do not respond to nesiritide therapy, the reason for the failure to respond should be determined, and further medical diagnosis (ie, invasive hemodynamic monitoring) and management should ensue.
Nesiritide is physically and/or chemically incompatible with injectable formulations of heparin, insulin, ethacrynate sodium, bumetanide, enalaprilat, hydralazine, and furosemide. These drugs should not be administered as an infusion with nesiritide through the same catheter. The catheter must be flushed between administration of nesiritide and incompatible drugs (eg, furosemide, heparin) when such drugs are being given as a bolus. Nesiritide binds to heparin, so it should not be administered through a central catheter coated with heparin.
Approach to Therapy for ADHF
Because of the various therapeutic options available and the lack of comparative data on efficacy and safety, a careful review of the available literature should guide decision making in the treatment of patients with ADHF. The University of Illinois Medical Center at Chicago has developed an algorithm that takes into account initial signs and symptoms, response to medications, and resolution of signs and symptoms13 (see Figure).
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Controversy Regarding Nesiritide Use |
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TopCase ReportDiscussionControversy Regarding Nesiritide...SummaryReferences |
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Summary |
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TopCase ReportDiscussionControversy Regarding Nesiritide...SummaryReferences |
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Use of nesiritide in patients with ADHF essentially has 4 advantages over use of other therapies. First, nesiritide can be administered outside the ICU, requires minimal monitoring, and does not require the use of a pulmonary artery catheter. Second, the dose does not usually require adjustment, because a standard bolus dose followed by a maintenance infusion rate is effective for most patients. Therefore, nesiritide can be considered fairly easy to use from a practical nursing standpoint. Third, nesiritide is as effective as other vasodilators when added to standard therapy, and it has the additional benefit of fewer adverse effects. Last, nesiritide does not seem to promote arrhythmias, an important characteristic when the frequency of ventricular tachycardia in patients with heart failure is considered. Nesiritide is a relatively new agent that is being used to improve dyspneic symptoms in patients with ADHF, and its use may allow patients to return to their baseline functioning more rapidly. Nesiritide is being used in both academic medical centers and community hospitals, and all critical care and telemetry nurses should be comfortable administering it in the hospital environment.
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References |
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