eMedicine Specialties > Cardiology > Myocardial Disease and Cardiomyopathies

Pulmonary Edema, Cardiogenic: Treatment & Medication

Author: Ali A Sovari, MD, Research Fellow, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles (UCLA)
Coauthor(s): Abraham G Kocheril, MD, FACC, FACP, Professor of Medicine, Director of Clinical Electrophysiology, University of Illinois at Chicago; Arnold S Baas, MD, FACC, FACP, Assistant Professor of Medicine, University of California at Los Angeles; Attending Physician, UCLA Santa Monica Hospital and UCLA Westwood Hospital
Contributor Information and Disclosures

Updated: Apr 22, 2008

Treatment

Medical Care

Initial management of patients with CPE should address the ABCs of resuscitation, that is, airway, breathing, and circulation. Oxygen should be administered to all patients to keep oxygen saturation >90%. The method of oxygen delivery varies from use of a face mask to bilevel noninvasive positive-pressure ventilation (NPPV) or continuous positive airway pressure (CPAP) or intubation and mechanical ventilation depending on presence of hypoxemia and acidosis and on the patient's level of consciousness. In case of persistent hypoxemia, acidosis or altered mental status, intubation and mechanical ventilation may become necessary. Any associated arrhythmia or myocardial infarction should be treated appropriately.

Then medical therapy of CPE focuses on 3 main goals: (1) reduction of pulmonary venous return (preload reduction), (2) reduction of systemic vascular resistance (afterload reduction), and (3) inotropic support in some cases. Preload reduction decreases pulmonary capillary hydrostatic pressure and reduces fluid transudation into the pulmonary interstitium and alveoli. Afterload reduction increases cardiac output and improves renal perfusion, which allows for diuresis in the patient with fluid overload. Patients with severe LV dysfunction or acute valvular disorders may present with hypotension. These patients may not tolerate medications to reduce their preload and afterload. Therefore, the third goal in this subset of patients is to provide inotropic support to maintain adequate BP.

Patients who remain hypoxic despite supplemental oxygenation and patients who have severe respiratory distress require ventilatory support in addition to maximal medical therapy.

Ventilatory support

Noninvasive pressure-support ventilation

Consider noninvasive pressure-support ventilation (NPSV) early when treating patients with severe CPE.

In NPSV, the patient breathes through a face mask against a continuous flow of positive airway pressure. NPSV maintains the patency of the fluid-filled alveoli and prevents them from collapsing during exhalation. As a result, the patient saves the energy spent trying to reopen collapsed alveoli. NPSV improves pulmonary air exchange, and it increases intrathoracic pressure with reduction in preload and afterload.

Several studies suggest that NPSV is associated with decreased length of stay in the ICU, decreased need for mechanical ventilation, and decreased hospital costs. A recent small clinical trial showed that in patients with CPE defined as having severe dyspnea, oxygen saturation less than 90%, and basal rales, early and prehospital NPSV treatment by paramedics is safe and associated with faster improvement of oxygen saturation.² However, the mortality and the need for intensive care did not differ between the patients who were treated with NPSV versus Venturi face mask in this small study. A recent randomized trial compared CPAP, NIPPV, and standard oxygen therapy in 1069 patients with acute cardiogenic pulmonary edema demonstrating no mortality benefit from noninvasive ventilation, but improvements in symptomatology and oxygenation.⁴⁴  

Two types of NPSV are continuous positive airway pressure (CPAP) and bilevel positive airway pressure (BiPAP). In CPAP, a single airway pressure is maintained throughout all phases of the respiratory cycle. In BiPAP, high pressures can be applied during inspiration and low pressures, during expiration, increasing the patient's comfort.

In 1 small study, researchers compared the 2 types of NPSV and found that BiPAP was associated with more rapid improvement in vital signs but an increased rate of MIs.³ However, patients who received BiPAP initially had more chest pain than patients who received CPAP. Other randomized clinical trials did not show any increased rate of MI in patients who received CPAP or BiPAP compared with those who received oxygen by means of a face mask. As of now, the data are insufficient to compare the efficacy and safety of BiPAP with CPAP. Therefore, the authors suggest that CPAP is the preferred method when NPSV is used unless the patient has obstructive airway disease.

Mechanical ventilation

In general, use endotracheal intubation and mechanical ventilation when patients with CPE remain hypoxic despite maximal noninvasive supplemental oxygenation, when patients have evidence of impending respiratory failure (eg, lethargy, fatigue, diaphoresis, worsening anxiety), or when the patient is hemodynamically unstable (eg, hypotensive, severely tachycardic).

Mechanical ventilation maximizes myocardial oxygen delivery and ventilation.

Positive end-expiratory pressure is generally recommended to increase alveolar patency and to enhance oxygen delivery and carbon dioxide exchange (see Noninvasive pressure-support ventilation).

Medical therapy

Preload reduction

• Nitroglycerin
  • Nitroglycerin (NTG) is the most effective, predictable, and rapid-acting medication available for preload reduction.
  • Several studies demonstrated greater efficacy and safety and a faster onset of action with NTG than with furosemide or morphine sulfate.
  • Use of sublingual NTG is associated with preload reduction within 5 minutes and some afterload reduction.
  • Topical NTG may be as effective as sublingual NTG in most patients with CPE, but it should be avoided in patients with severe LV failure because of poor skin perfusion (manifesting as skin pallor or mottling) and resultant poor absorption.
  • Intravenous (IV) NTG at high dosages provides rapid and titratable preload and afterload reduction and is excellent mono therapy for patients with severe CPE.
  • IV NTG can be started with 10 mcg/min and then rapidly uptitrated to >100 mcg/min.
  • The other alternative is NTG given as 3-mg IV boluses every 5 minutes.
  • The antianginal dose of NTG of 0.4 mg every 5 minutes has the bioequivalence of an NTG IV infusion of <80 mcg/min. Therefore, the dosage of NTG for patients with CPE is higher than the standard antianginal dosage.
  • Physicians should be comfortable with the high dosage for CPE, especially in most patients with CPE, who present with a hyperadrenergic state and moderately elevated BP, considering short half-life of nitrates. However, nitrates should not be used in hypotensive patients, and they should be used with extreme caution in patients with aortic stenosis and pulmonary hypertension.
• Loop diuretics
  • Loop diuretics have been considered the cornerstone of CPE treatment for many years. Furosemide is used most commonly.
  • Loop diuretics are presumed to decrease preload through 2 mechanisms: diuresis and direct vasoactivity (venodilation).
  • In most patients, diuresis does not occur for at least 20-90 minutes; therefore, the effect is delayed. Loop diuretics affect the ascending loop of Henle; therefore, the diminished renal perfusion in CPE may delay the onset of effects of loop diuretics.
  • Many patients with CPE do not have fluid overload. Continued use of diuretics in these patients after their acute symptoms resolved may be associated with adverse outcomes, including electrolyte derangements, hypotension, and worsening renal function (GFR) as a result of tubuloglomerular feedback.
  • The presumption that these medications have a direct vasoactive (venodilating) effect has been questioned. Some studies demonstrated initial adverse hemodynamic consequences (eg, elevations of PCWP, LV filling pressure, heart rate, and systemic vascular resistance) after the administration of IV furosemide.
  • Premedication with drugs that decrease preload (eg, NTG) and afterload (eg, angiotensin-converting enzyme [ACE] inhibitors) before the administration of loop diuretics can prevent potential adverse hemodynamic changes.
• Morphine sulfate
  • Use of morphine sulfate in CPE for preload reduction has been commonplace for many years.
  • Good evidence supporting a beneficial hemodynamic effect is lacking.
  • Data suggest that morphine sulfate may contribute to a decrease in cardiac output and that it may be associated with an increased need for ICU admission and endotracheal intubation.
  • Adverse effects (eg, nausea and vomiting, local or systemic allergic reactions, respiratory depression) may outweigh any potential benefit, especially given the availability of medications that are more effective than morphine in reducing preload (eg, NTG).
  • Any beneficial hemodynamic effect is probably due to anxiolysis, with a resulting decrease in catecholamine production and decrease in systemic vascular resistance. An alternative can be low-dose benzodiazepines (eg, lorazepam 0.5 mg IV) in patients who are extremely anxious. This alternative reduces the risk of respiratory depression in patients whose condition responded to initial therapy.
• Nesiritide
  • Nesiritide is recombinant human BNP, which decreases PCWP, pulmonary artery pressure, right atrial 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.
  • Most of the beneficial effects of nesiritide was shown in the landmark Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) study. Investigators compared IV nesiritide with IV NTG. IV nesiritide was associated with some hypotension but was otherwise well tolerated. The VMAC study also showed a trend for increased mortality with IV nesiritide group compared with IV NTG, though the difference was not statically significant (90-day mortality, 19% for nesiritide vs 13% for NTG; P = 0.8). The most important limitation of this study was the use of suboptimal dosages of IV NTG (mean 30-40 mcg/min) because the dosage was based on physician's decision and not on a protocol.
  • A later meta-analysis of 3 randomized trials of 485 patients receiving nesiritide and 377 patients not receiving nesiritide showed a 7.2% 30-day mortality with nesiritide versus 4% without nesiritide.
  • Another analysis included 5 randomized trials showed that patients who received nesiritide were more likely than others to have significant renal failure.
  • Finally, length of hospitalization, rate of readmission because of heart failure, and cost-effectiveness of nesiritide compared with NTG therapy is not clear.
  • The evidence is not conclusive whether an increased risk of death or renal failure is present when using nesiritide, and a large (7000 patients) randomized, double-blind, placebo-controlled trial (ASCEND-HF) will provide more precise information in this regard. When NTG is contraindicated (eg, in a patient who has taken sildenafil), nesiritide can be an alternative in the treatment of CPE.

Afterload reduction

• ACE inhibitors
  • These are generally considered the cornerstones for treating chronic CHF, and recent studies have demonstrated excellent results with ACE inhibitors for the treatment of acute decompensated CHF and CPE.
  • Use of ACE inhibitors in CPE is associated with reduced admission rates to ICUs and decreased endotracheal intubation rates and length of ICU stay.
  • Hemodynamic effects of ACE inhibitors include reduced afterload, improved stroke volume and cardiac output, and a slight reduction in preload. The last effects happen when renal perfusion improves after cardiac output improves and diuresis occurs.
  • Enalapril 1.25 mg IV or captopril 25 mg given sublingually result in hemodynamic and subjective improvements within 10 minutes. Improvements occur much more slowly with the oral route.
  • Angiotensin II receptor blockers (ARBs) have comparable beneficial effects in heart failure.
  • Recent studies have proposed a role for ACE inhibitors and ARBs in preventing structural and electrical remodeling of the heart resulting in reducing the incidence of arrhythmias. The Valsartan Heart Failure Trial (Val-HeFT) showed that valsartan reduces the incidence of AF by 37%; BNP level and advanced age were the strongest independent predictors for AF occurrence.⁴ Similarly the Candesartan in Heart Failure: Assessment in Reduction of Mortality and Morbidity (CHARM) trial showed a reduction in the onset of AF in patients who were treated with Candesartan compared with placebo with a median follow-up of 37.7 months.⁵
• Nitroprusside
  • Nitroprusside results in simultaneous preload and afterload reduction by causing direct smooth-muscle relaxation, with an increased effect on afterload.
  • Afterload reduction is associated with increased cardiac output.
  • The potency and rapidity of onset and offset of effect make this an ideal medication for patients who are critically ill.
  • It may induce precipitous falls and labile fluctuations in BP; intra-arterial BP monitoring is often recommended.
  • Nitroprusside should generally be avoided in the setting of acute MI. Its use is associated with shunting of blood away from ischemic myocardium toward healthy myocardium (ie, coronary steal syndrome), which potentiates ischemia.
  • If nitroprusside is used, convert therapy to oral or alternative IV vasodilator therapy as soon as possible because prolonged use is associated with thiocyanate toxicity.
  • Use in pregnancy is associated with fetal thiocyanate toxicity.
  • Prolonged infusion can induce tolerance, and reflex tachycardia may occur.
• Inotropics: Inotropic support is usually used when preload- and afterload-reduction strategies are not successful or when hypotension precludes use of these strategies. Two main classes of inotropic agents are available: catecholamine agents and phosphodiesterase inhibitors (PDIs). Calcium-sensitizer agents are a new class of medications that have notably beneficial effects in acute decompensated heart failure; these drugs are under investigation.  
  • Dobutamine
    • Dobutamine, a catecholamine agent, mainly serves as a beta1-receptor agonist, though it has some beta2-receptor and minimal alpha-receptor activity.
    • IV dobutamine induces significant positive inotropic effects with mild chronotropic effects. It also induces mild peripheral vasodilation (decrease in afterload).
    • The combination effect of increased inotropy with decreased afterload significantly increases cardiac output.
    • Combination use with IV NTG may be ideal for patients with MI and CPE and mild hypotension to simultaneously reduce preload and increase cardiac output.
    • In general, avoid dobutamine in patients with moderate or severe hypotension (eg, systolic BP <80 mm Hg) because of the peripheral vasodilation.
• Dopamine
  • The vascular and myocardial receptor effects of dopamine, a catecholamine agent, are dose dependent.
  • Low dosages of 0.5-5 mcg/kg/min stimulate dopaminergic receptors in the renal and splanchnic vascular beds, causing vasodilation and increasing diuresis.
  • Moderate dosages of 5-10 mcg/kg/min stimulate beta-receptors in the myocardium, increasing cardiac contractility and heart rate.
  • High dosages of 15-20 mcg/kg/min stimulate alpha-receptors, resulting in peripheral vasoconstriction (increased afterload), increased BP, and no further improvement in cardiac output.
  • Moderate and high dosages are arrhythmogenic and increase myocardial oxygen demand (with the potential for myocardial ischemia). Therefore, use these dosages only in patients with CPE who cannot tolerate dobutamine because of severe hypotension (eg, systolic BP 60-80 mm Hg)
• Norepinephrine
  • Norepinephrine, a catecholamine agent, primarily stimulates alpha-receptors, significantly increasing afterload (and the potential for myocardial ischemia) and reducing cardiac output.
  • Norepinephrine is generally reserved for patients with profound hypotension (eg, systolic BP <60 mm Hg). After BP is restored, add other medications to maintain cardiac output.
• Phosphodiesterase inhibitors (PDIs)
  • PDIs increase the level of intracellular cyclic adenosine monophosphate by preventing the breakdown of cAMP to 5'AMP and result in a positive inotropic effect on the myocardium, in peripheral vasodilation (decreased afterload) and in a reduction in pulmonary vascular resistance (decreased preload).
  • Unlike the catecholamine inotropes, PDIs do not depend on adrenoreceptor activity. Therefore, patients are less likely to develop tolerance to PDIs than to other medications. Tolerance to catecholamine inotropes can rapidly develop by means of a downregulation of adrenoreceptors.
  • PDIs are less likely than catecholamine inotropes to cause adverse effects that are typically associated with adrenoreceptor activity (eg, increased myocardial oxygen demand, myocardial ischemia).
  • Several direct comparisons of PDIs (milrinone) to dobutamine in patients with CPE demonstrated that milrinone produced equal or greater improvements in stroke volume, cardiac output, PCWPs (preload), and systemic vascular resistance (afterload). However, milrinone was associated with the same or more tachycardia and with an increased incidence of tachyarrhythmias. Furthermore, use of milrinone, in the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF), did not reduce hospital length of stay and was associated with a significant increase in adverse events compared with placebo.
• All known IV inotropic agents are associated with an increased long-term mortality compared with placebo and therefore should be reserved for patients with heart failure and a markedly depressed cardiac index and stroke volume.
• Calcium sensitizer
  • Levosimendan is a calcium sensitizer that is used in several European countries to manage moderate-to-severe heart failure. It has inotropic, metabolic, and vasodilatory effects.
  • Levosimendan increases contractility by binding to troponin C. It does not increase myocardial oxygen demand, and it is not a proarrhythmogenic agent.
  • Levosimendan opens potassium channels sensitive to adenosine triphosphate (ATP), causing peripheral arterial and venous dilatation. It also increases coronary flow reserve. Recent studies have shown an anti-inflammatory effect of levosimendan.
  • Overall, levosimendan has been an effective and safe alternative to dobutamine. The most common adverse effects of levosimendan treatment are hypotension and headache. A recent randomized clinical trial (SURVIVE trial) demonstrated no mortality benefit of levosimendan as compared with dobutamine in patients with acute decompensated CHF.⁶
• Tolvaptan
  • Tolvaptan is an oral vasopressin V2 receptor antagonist recently evaluated in a large (4133 patients) randomized, double-blind, placebo controlled trial (EVEREST) in patients with acute clinically decompensated CHF. This trial demonstrated no mortality or CHF hospitalization benefit at a median follow-up of 9.9 months. However, patients randomized to tolvaptan demonstrated early (1-7 d) improvements in body weight, dyspnea, serum sodium, and edema as compared with placebo.⁷

Surgical Care

Intra-aortic balloon pumping

Kantrowitz initially described intra-aortic balloon pumping (IABP) in 1953, but IABP was first used clinically in 1969 in a patient with cardiogenic shock. Since the 1980s, IABP has been increasingly applied in various clinical situations as a life-saving intervention to achieve hemodynamic stabilization before definitive therapy. The IABP decreases afterload as the pump deflates, and it inflates during diastole to improve coronary blood flow.

• Procedure  
  • The intra-aortic balloon pump is inserted percutaneously through the femoral artery by using a modified Seldinger technique. The distal end of the pump is placed just distal to the aortic knob and the origin of the left subclavian artery.
  • Fluoroscopy may be used for correct positioning of the balloon, and a subsequent radiograph should be obtained to document satisfactory placement of the balloon.
  • Helium, a low-density gas with minimal water solubility, is used to inflate the balloon.
• Proper timing of IABP for optimal hemodynamic support  
  • Proper timing of counterpulsation is necessary for maximum hemodynamic support. The timing of balloon inflation and deflation are best evaluated and adjusted at a pump ratio of 1:2.
  • Inflation of the balloon should occur in early diastole, just after the aortic valve closes, and it should correspond to the dicrotic notch of the aortic pressure waveform. Balloon deflation should occur in early systole, just before the aortic valve opens.
  • Proper inflation leads to an assisted peak diastolic pressure higher than the unassisted peak systolic arterial pressure. Proper deflation results in assisted aortic end-diastolic pressure of approximately 10 mm Hg lower than the unassisted end-diastolic pressure.
  • Diastolic augmentation enhances perfusion of the coronary circulation and carotid arteries. The reduction in end-diastolic pressure decreases aortic impedance (afterload) and augments systole.
  • IABP reduces aortic impedance and systolic pressure, leading to a 15-25% reduction in LV wall stress. This level of afterload reduction improves LV volume, LV emptying, and myocardial oxygen consumption.
  • Diastolic aortic pressure augmentation improves myocardial perfusion and coronary blood flow. The effects on coronary blood flow may be variable but generally consist of a boost of 10-20% in the ischemic territories.
  • IABP decreases LV filling pressures by 20-25% and improves cardiac output by 20% in patients with cardiogenic shock. Therefore, IABP substantially reduces myocardial oxygen demand, though increased oxygen supply to the myocardium may also be a beneficial effect in some clinical situations.
• Indications for IABP  
  • IABP is effective in providing temporary support to patients in cardiogenic shock and end-stage cardiomyopathy while definite therapies, such as angioplasty or cardiac bypass surgery or cardiac transplantation, are undertaken. In this case, the use of IABP is considered a bridge to a definitive revascularization procedure or implementation of an LV-assist device.
  • IABP is effective in stabilizing patients with unstable angina refractory to medical therapy before a definitive revascularization procedure.
  • IABP may be a life-saving intervention in patients with acute mitral regurgitation secondary to papillary muscle rupture or in patients with ventricular septal defect as a complication of MI. IABP reduces afterload and thereby reduces the severity of mitral regurgitation. It enhances forward cardiac output, reduces left atrial pressure, and improves pulmonary edema. Furthermore, IABP decreases LV afterload and improves cardiac output.
  • IAPB is used to stabilize patients, which allows time to plan definitive surgery in hemodynamically unstable patients.
  • IABP can also provide hemodynamic support in the perioperative and postoperative period in high-risk patients, such as those with severe coronary disease, severe LV dysfunction, or recent MI.
• Contraindications  
  • Absolute contraindications for IABP counterpulsation are a dissecting aortic aneurysm, severe aortic regurgitation, a large arteriovenous shunt, and severe coagulopathy.
  • Relative contraindications are severe peripheral vascular disease, recent thrombolytic therapy, bleeding diathesis, and descending aortic and peripheral vascular grafts.
• Complications
  • IABP can cause several complications, which should be monitored while the patient is receiving IABP support. In general, the platelet counts are mildly reduced; however, the counts usually do not fall below 100 X 10⁹/L.
  • Complications also may occur during cannulation of the femoral artery. These include perforation, laceration, or dissection of the artery (1-6%). Thrombosis of the iliofemoral artery and distal emboli may also occur (1-7%), and limb ischemia is reported in up to 40% of patients. Limb ischemia is reversible by removing the intra-aortic balloon pump unless thrombosis develops; if so, embolectomy is required to save the limb. 
• The other complications are localized bleeding (3-5%), infection (2-4%), thrombocytopenia (<1%), and intestinal ischemia (<1%).

Ultrafiltration

A recent randomized trial of ultrafiltration versus diuresis in patients with acute decompensated systolic heart failure (UNLOAD trial) demonstrated that ultrafiltration was superior in controlling net fluid loss and rehospitalization.⁸  As a result of this trial, UF should be considered in patients with volume overload and acute CHF who have not responded well to moderate to large doses of diuretic treatment or in whom the adverse effects of such treatment (eg, renal dysfunction) did not allow initiation or continuation of the treatment. Broader application of UF needs further investigation with larger clinical trials to determine the efficacy and safety of this method.

Consultations

Consultations with subspecialists depends on the underlying cause of the episode of CPE.

• If the acute episode is attributed to an acute MI, acute cardiac ischemia, or an acute dysrhythmia, consultation with a cardiologist is often warranted.
• If the episode is attributed to fluid overload in patients with renal failure, consultation with a nephrologist is indicated for emergency or urgent hemodialysis.
• If CPE results from acute valvular dysfunction, consultation with a cardiothoracic surgeon (including a cardiologist) for urgent valve replacement may be indicated depending on the integrity of the valve.
• In patients who develop cardiogenic shock, consultation with a cardiologist and/or critical care specialist is generally indicated to assist with titrating inotropic medication and, in some cases, to place an intraaortic balloon pump as a temporizing measure before surgery (eg, valve replacement or coronary revascularization).

Diet

Patients admitted with heart failure or pulmonary edema should be given a low-salt diet to minimize fluid retention. Closely monitor their fluid balance.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Preload reducers

Reduced pulmonary venous return decreases pulmonary capillary hydrostatic pressure and reduces fluid transudation into the pulmonary interstitium and alveoli. Preload reducers include nitroglycerin (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 (Nitro-Bid, Deponit, Nitrol)

Drug of choice (DOC) for patients who are not hypotensive. Provides excellent and reliable preload reduction. High dosages provide mild afterload reduction. Rapid onset and offset (both within min), allowing for rapid clinical effects and rapid discontinuation of effects in adverse reactions.

Furosemide (Lasix)

Most commonly used loop diuretic. Increases excretion of water by interfering with chloride-binding cotransport system, inhibiting sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Reduces preload by diuresis in 20-60 min. May contribute to hastened preload reduction with direct vasoactive mechanism, but controversial. As many as 50% of patients with CPE have total-body euvolemia. Generally administered to all patients with CPE but probably most useful in patients with total-body fluid overload.
PO form has relatively slow onset of action and therefore, generally not appropriate in CPE.

Afterload reducers

Reduced systemic vascular resistance increases cardiac output and improves renal perfusion, allowing for diuresis.

Captopril (Capoten)

Prevents conversion of angiotensin I to angiotensin II. Potent vasodilator that lowers aldosterone secretion. Option in patients unable to tolerate NTG (eg, concurrent use of sildenafil). Hemodynamic (improved afterload and cardiac output) and subjective (decreased dyspnea) improvements in 10-15 min. Although not specifically formulated for SL use, can wet tab before placing under patient's tongue to achieve desired effect.

Enalapril (Vasotec)

Competitive ACE inhibitor. Reduces angiotensin II levels, decreasing aldosterone secretion. Use of IV to treat decompensated heart failure and pulmonary edema not been studied as well as SL captopril. In 1993, Varriale evaluated patients with severe CHF and mitral regurgitation; observed improved preload, afterload, cardiac output, and magnitude of regurgitation. In 1996, Annane evaluated patients with acute CPE; found improvements in preload and afterload. No demonstrated effect on cardiac output. Both studies showed excellent safety profile.

Nitroprusside (Nitropress)

Potent direct smooth-muscle–relaxing agent that primarily reduces afterload but can mildly reduce preload. Improves cardiac output but can precipitously decrease BP. Intra-arterial BP monitoring strongly recommended. Excellent in critically ill patients because of rapid onset and offset of action (within 1-2 min). Excellent in pulmonary edema associated with severe hypertension unresponsive to other agents.

Catecholamines

These agents produce vasodilation and increase inotropic state. At high dosages, they may increase the patient's heart rate, exacerbating myocardial ischemia.

Dobutamine (Dobutrex)

Synthetic catecholamine with mainly beta1-receptor activity but some beta2- and alpha-receptor activity. Commonly used in CPE and mild hypotension (systolic BP 90-100 mm Hg). Combination of beneficial hemodynamic effects (eg, positive inotropism, decreased afterload due to mild vasodilation, increased cardiac output).

Dopamine (Intropin)

Naturally occurring catecholamine that acts as precursor to norepinephrine. Stimulates adrenergic and dopaminergic receptors. Hemodynamic effect dose dependent. Low-dose 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. Use in CPE generally reserved for patients with moderate hypotension (eg, systolic BP 70-90 mm Hg). Moderate-to-high doses usually used.

Norepinephrine (Levophed)

Naturally occurring catecholamine with potent alpha-receptor and mild beta-receptor activity. Stimulates beta1- and alpha-adrenergic receptors, increasing myocardial contractility, heart rate, and vasoconstriction. Increases BP and afterload; may decrease cardiac output, increase myocardial oxygen demand, and cardiac ischemia. Generally reserved for patients with severe hypotension (eg, systolic BP <70 mm Hg) or hypotension unresponsive to other medication.

Phosphodiesterase enzyme inhibitors

These bipyridine-positive inotropic agents and vasodilators have little chronotropic activity. They differ from both digitalis glycosides and catecholamines in their mechanism of action.

Milrinone (Primacor)

Positive inotropic agent and vasodilator. Reduces afterload and preload and increases cardiac output. In several comparisons, improved preload, afterload, cardiac output more than dobutamine, without significantly increased myocardial oxygen consumption.

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