Medication Summary
Loop diuretics have long been the cornerstone of cardiogenic pulmonary edema (CPE) treatment, with furosemide being the most commonly used of these drugs. Premedication with drugs that decrease preload (eg, nitroglycerin [NTG]) and afterload (eg, angiotensin-converting enzyme [ACE] inhibitors) before the administration of loop diuretics can prevent adverse hemodynamic changes.
Nesiritide is recombinant human brain-type natriuretic peptide (BNP); it reduces pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure, RA pressure, and systemic vascular resistance while increasing the cardiac index and stroke volume index. Therapy with nesiritide has decreased plasma renin, aldosterone, norepinephrine, and endothelin-1 levels and reduced ventricular ectopy and ventricular tachycardia. Heart-rate variability also improves with nesiritide. However, owing to the lack of positive outcomes data (ASCEND-HF) from the use of nesiritide, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure.
Inotropic support is usually used following unsuccessful attempts at preload and afterload reduction or when hypotension precludes the use of these strategies. The two main classes of inotropic agents that are available are catecholamine agents and phosphodiesterase inhibitors (PDIs).
Preload Reducers
Class Summary
Reduced pulmonary venous return decreases pulmonary capillary hydrostatic pressure and reduces fluid transudation into the pulmonary interstitium and alveoli. Preload reducers include NTG (eg, Deponit, Minitran, Nitro-Bid IV, Nitro-Bid ointment, Nitrodisc, Nitro-Dur, Nitrogard, Nitroglyn, Nitrol, Nitrolingual, Nitrong, Nitrostat, Transdermal-NTG, Transderm-Nitro, Tridil) and furosemide (eg, Lasix).
Nitroglycerin IV (Nitro-Bid, Minitran, Nitrostat)
NTG is the drug of choice (DOC) for patients who are not hypotensive. It provides excellent and reliable preload reduction, and high dosages provide mild afterload reduction. NTG has rapid onset and offset (both within minutes), allowing for rapid clinical effects and rapid discontinuation of effects in adverse reactions.
Furosemide (Lasix)
Furosemide is the most commonly used loop diuretic. It increases the excretion of water by interfering with the chloride-binding cotransport system, inhibiting sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. Furosemide reduces preload by diuresis in 20-60 minutes. It may contribute to hastened preload reduction with a direct vasoactive mechanism, but this is controversial.
As many as 50% of patients with CPE have total-body euvolemia. Although furosemide is generally administered to all patients with CPE, it is probably most useful in patients with total-body fluid overload.
The oral form of furosemide has a relatively slow onset of action and, therefore, is generally not appropriate in CPE.
Afterload Reducers
Class Summary
Reduced systemic vascular resistance increases cardiac output and improves renal perfusion, allowing for diuresis.
Captopril
Captopril prevents the conversion of angiotensin I to angiotensin II. It is a potent vasodilator that lowers aldosterone secretion. It is an option in patients who are unable to tolerate NTG (eg, concurrent use of sildenafil). Hemodynamic (improved afterload and cardiac output) and subjective (decreased dyspnea) improvements occur in 10-15 minutes. Although captopril is not specifically formulated for sublingual (SL) use, the tablet can be wetted before it is placed under the patient's tongue to achieve the desired effect.
Enalapril (Vasotec)
Enalapril is a competitive ACE inhibitor. It reduces angiotensin II levels, decreasing aldosterone secretion. The use of IV captopril to treat decompensated heart failure and pulmonary edema not been studied as well as SL captopril has.
In 1993, Varriale evaluated patients with severe CHF and mitral regurgitation; he observed improved preload, afterload, cardiac output, and magnitude of regurgitation. In 1996, Annane evaluated patients with acute CPE and found improvements in preload and afterload. There was no demonstrated effect on cardiac output. Both studies showed an excellent safety profile.
Nitroprusside (Nitropress)
Nitroprusside is a potent, direct smooth muscle–relaxing agent that primarily reduces afterload but can mildly reduce preload. It improves cardiac output but can precipitously decrease blood pressure. Intra-arterial blood pressure monitoring is strongly recommended. Nitroprusside is excellent for use in critically ill patients because of its rapid onset and offset of action (within 1-2 min). It is excellent for use against pulmonary edema associated with severe hypertension that is unresponsive to other agents.
Inotropic Agents
Class Summary
These agents produce vasodilation and increase the inotropic state. At high dosages, they may increase the patient's heart rate, exacerbating myocardial ischemia. Conversely, phosphodiesterase enzyme inhibitors or bipyridine-positive inotropic agents have little chronotropic activity. They differ from digitalis glycosides and catecholamines in their mechanism of action.
Dobutamine
Dobutamine is a synthetic catecholamine that mainly has beta1-receptor activity but also has some beta2- and alpha-receptor activity. It is commonly used in CPE and mild hypotension (systolic blood pressure 90-100 mm Hg). Dobutamine has a combination of beneficial hemodynamic effects (eg, positive inotropism, decreased afterload due to mild vasodilation, increased cardiac output).
Dopamine
Dopamine is a naturally occurring catecholamine that acts as a precursor to norepinephrine. It stimulates adrenergic and dopaminergic receptors. Dopamine's hemodynamic effect is dose dependent. A low dose is associated with dilation in renal and splanchnic vasculature, enhancing diuresis. Moderate doses enhance cardiac contractility and heart rate. High doses increase afterload due to peripheral vasoconstriction. The use of dopamine in CPE is generally reserved for patients with moderate hypotension (eg, systolic blood pressure 70-90 mm Hg). Moderate to high doses are usually used.
Norepinephrine (Levophed)
Norepinephrine is a naturally occurring catecholamine with potent alpha-receptor and mild beta-receptor activity. It stimulates beta1- and alpha-adrenergic receptors, increasing myocardial contractility, heart rate, and vasoconstriction. Norepinephrine increases blood pressure and afterload; it may decrease cardiac output and increase myocardial oxygen demand and cardiac ischemia. This agent is generally reserved for patients with severe hypotension (eg, systolic blood pressure < 70 mm Hg) or hypotension unresponsive to other medication.
Milrinone
Milrinone is a positive inotropic agent and vasodilator. It reduces afterload and preload and increases cardiac output. In several comparisons, milrinone improved preload, afterload, and cardiac output more than dobutamine, without significantly increased myocardial oxygen consumption.
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Radiograph shows acute pulmonary edema in a patient who was admitted with acute anterior myocardial infarction. Findings are vascular redistribution, indistinct hila, and alveolar infiltrates.
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Radiograph shows acute pulmonary edema in a patient known to have ischemic cardiomyopathy. Findings are Kerley B lines (1mm thick and 1cm long) in the lower lobes and Kerley A lines in the upper lobes.
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Radiograph demonstrates cardiomegaly, bilateral pleural effusions, and alveolar opacities in a patient with pulmonary edema.
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Radiograph shows interstitial pulmonary edema, cardiomegaly, and left pleural effusion presenting at an earlier stage of pulmonary edema.
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Lateral chest radiograph shows prominent interstitial edema and pleural effusions.
