General Considerations

Typical causes of acute cardiogenic pulmonary edema include acute MI or severe ischemia, exacerbation of chronic HF, acute severe hypertension, AKI, acute volume overload of the LV (valvular regurgitation), and mitral stenosis. By far the most common presentation in developed countries is one of acute or subacute deterioration of chronic HF, precipitated by discontinuation of medications, excessive salt intake, myocardial ischemia, tachyarrhythmias (especially rapid atrial fibrillation), or intercurrent infection. Often in the latter group, there is preceding volume overload with worsening edema and progressive shortness of breath for which earlier intervention can usually avoid the need for hospital admission.

Clinical Findings

Acute pulmonary edema presents with a characteristic clinical picture of severe dyspnea, the production of pink, frothy sputum, and diaphoresis and cyanosis. Rales are present in all lung fields, as are generalized wheezing and rhonchi. Pulmonary edema may appear acutely or subacutely in the setting of chronic HF or may be the first manifestation of cardiac disease, usually acute MI, which may be painful or silent. Less severe decompensations usually present with dyspnea at rest, rales, and other evidence of fluid retention but without severe hypoxia.

Noncardiac causes of pulmonary edema include intravenous opioids, increased intracerebral pressure, high altitude, sepsis, medications, inhaled toxins, transfusion reactions, shock, and disseminated intravascular coagulation. These are distinguished from cardiogenic pulmonary edema by the clinical setting, history, and physical examination. Conversely, in most patients with cardiogenic pulmonary edema, an underlying cardiac abnormality can usually be detected clinically or by ECG, CXR, or echocardiogram.

The CXR reveals signs of pulmonary vascular redistribution, blurriness of vascular outlines, increased interstitial markings, and, characteristically, the butterfly pattern of distribution of alveolar edema. The heart may be enlarged or normal in size depending on whether HF was previously present. Assessment of cardiac function by echocardiography is important, since a substantial proportion of patients has normal EFs with elevated atrial pressures due to diastolic dysfunction. In cardiogenic pulmonary edema, BNP is elevated, and the PCWP is invariably elevated, usually over 25 mm Hg. In noncardiogenic pulmonary edema, the wedge pressure may be normal or even low.

Treatment

In full-blown pulmonary edema, the patient should be placed in a sitting position with legs dangling over the side of the bed; this facilitates respiration and reduces venous return. Oxygen is delivered by mask to obtain an arterial PO₂ greater than 60 mm Hg. Noninvasive pressure support ventilation may improve oxygenation and prevent severe CO₂ retention while pharmacologic interventions take effect. However, if respiratory distress remains severe, endotracheal intubation and mechanical ventilation may be necessary.

Morphine is highly effective in pulmonary edema and may be helpful in less severe decompensations when the patient is uncomfortable. The initial dosage is 2-8 mg intravenously (subcutaneous administration is effective in milder cases) and may be repeated after 2-4 hours. Morphine increases venous capacitance, lowering LA pressure, and relieves anxiety, which can reduce the efficiency of ventilation. However, morphine may lead to CO₂ retention by reducing the ventilatory drive. It should be avoided in patients with opioid-induced pulmonary edema, who may improve with opioid antagonists, and in those with neurogenic pulmonary edema.

Intravenous diuretic therapy (furosemide, 40 mg, or bumetanide, 1 mg-or higher doses if the patient has been receiving long-term diuretic therapy) is usually indicated even if the patient has not exhibited prior fluid retention. These agents produce venodilation prior to the onset of diuresis. The DOSE trial has shown that, for acute decompensated HF, bolus doses of furosemide are of similar efficacy as continuous intravenous infusion, and that higher-dose furosemide (2.5 times the prior daily dose) resulted in more rapid fluid removal without a substantially higher risk of kidney impairment.

Nitrate therapy accelerates clinical improvement by reducing both BP and LV filling pressures. Sublingual nitroglycerin or isosorbide dinitrate, topical nitroglycerin, or intravenous nitrates will ameliorate dyspnea rapidly prior to the onset of diuresis, and these agents are particularly valuable in patients with accompanying hypertension.

Intravenous nesiritide, a recombinant form of human BNP, is a potent vasodilator that reduces ventricular filling pressures and improves cardiac output. Its hemodynamic effects resemble those of intravenous nitroglycerin with a more predictable dose-response curve and a longer duration of action. In clinical studies, nesiritide (administered as 2 mcg/kg by intravenous bolus injection followed by an infusion of 0.01 mcg/kg/min, which may be up-titrated if needed) produced a rapid improvement in both dyspnea and hemodynamics. The primary adverse effect is hypotension, which may be symptomatic and sustained. The ASCEND trial randomized nearly 7000 patients with acute decompensated HF to receive either nesiritide or placebo; results showed a reduction in dyspnea, worsening in kidney function, and no effect on death or HF rehospitalization. Because most patients with acute HF respond well to conventional therapy, the role of nesiritide may be primarily in patients who continue to be symptomatic after initial treatment with diuretics and nitrates.

A randomized placebo-controlled trial of 950 patients evaluating intravenous milrinone in patients admitted for decompensated HF who had no definite indications for inotropic therapy showed no benefit in increasing survival, decreasing length of admission, or preventing readmission. In addition, rates of sustained hypotension and atrial fibrillation were significantly increased. Thus, the role of positive inotropic agents appears to be limited to patients with refractory symptoms and signs of low cardiac output, particularly if life-threatening vital organ hypoperfusion (such as deteriorating kidney function) is present. In some cases, dobutamine or milrinone may help maintain patients who are awaiting cardiac transplantation.

Bronchospasm may occur in response to pulmonary edema and may itself exacerbate hypoxemia and dyspnea. Treatment with inhaled beta-adrenergic agonists or intravenous aminophylline may be helpful, but both may also provoke tachycardia and supraventricular arrhythmias.

In most cases, pulmonary edema responds rapidly to therapy. When the patient has improved, the cause or precipitating factor should be ascertained. In patients without prior HF, evaluation should include echocardiography and, in many cases, cardiac catheterization and coronary angiography. Patients with acute decompensation of chronic HF should be treated to achieve an euvolemic state and have their medical regimen optimized. Generally, an oral diuretic and an ACE inhibitor should be initiated, with efficacy and tolerability confirmed prior to discharge. In selected patients, early but careful initiation of beta-blockers in low doses should be considered.