Pulmonary Edema

Definition
Accumulation of fluid in the interstitium and alveoli of the lungs o Classified as cardiogenic or noncardiogenic Cardiogenic pulmonary edema o Due to increased pulmonary capillary pressure, as in severe left ventricular (LV) failure and mitral valve disease Mild: engorgement of pulmonary vasculature Moderate: extravasation into interstitial space due to changes in oncotic pressure Severe: alveolar filling Noncardiogenic pulmonary edema o Increased alveolarcapillary membrane permeability (acute respiratory distress syndrome [ARDS]) o Decreased plasma oncotic pressure o Increased negativity of pulmonary interstitial pressure o Lymphatic insufficiency or obstruction o Other, unknown mechanisms

Epidemiology

Incidence in the U.S. o Heart failure ~0.5 million new cases annually 510% of patients reach stage D, in which pulmonary edema is common. o ARDS Estimated to be 10 per 100,000 persons annually o High-altitude pulmonary edema 12% of persons who ascend above 3000 m (9800 ft) at usual ascent rates May be as high as 10% in people who ascend rapidly to 4500 m (14,800 ft)

Risk Factors Etiology

Cardiogenic

Vary by cause

Basic pathophysiology: A rise in pulmonary venous and pulmonary capillary pressures pushes fluid into the pulmonary alveoli and interstitium. Causes o Acute myocardial infarction (MI)/ischemia LV failure Ventricular septal rupture Papillary muscle/chordal rupture causing severe mitral regurgitation o Refractory sustained tachyarrhythmias o Acute fulminant myocarditis o Advanced, dilated cardiomyopathy o Hypertrophic cardiomyopathy with severe outflow obstruction o Aortic dissection with aortic regurgitation o Severe valvular heart disease Critical aortic or mitral stenosis Acute severe aortic or mitral regurgitation o Toxicmetabolic Beta blocker or calcium-channel blocker overdose

Noncardiogenic Altered alveolarcapillary membrane permeability (ARDS) o Infectious pneumonia: bacterial, viral, parasitic o Sepsis/systemic inflammatory response syndrome o Inhaled toxins (e.g., phosgene, ozone, chlorine, Teflon fumes, nitrogen dioxide, smoke) o Circulating foreign substances (e.g., snake venom, bacterial endotoxins) o Aspiration of acidic gastric contents o Acute radiation pneumonitis o Endogenous vasoactive substances (e.g., histamine, kinins) o Disseminated intravascular coagulation o Immunologic: hypersensitivity pneumonitis, drugs (nitrofurantoin), leukoagglutinins o Shock lung in association with nonthoracic trauma o Acute hemorrhagic pancreatitis Decreased plasma oncotic pressure o Hypoalbuminemia Increased negativity of interstitial pressure o Re-expansion pulmonary edema: rapid removal of pneumothorax with large applied negative pressures (unilateral)

Large negative pleural pressures due to acute airway obstruction with increased end-expiratory volumes (asthma) Lymphatic insufficiency o After lung transplantation o Lymphangitic carcinomatosis o Fibrosing lymphangitis (e.g., silicosis) Unknown or incompletely understood o High-altitude pulmonary edema
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Occurrence depends on altitude, rate of ascent, and individual susceptibility. High intravascular pressures in the lungs appears to lead to stress failures of the pulmonary microvascular endothelium and leakage of fluid into the extravascular space. Susceptible individuals have abnormally accentuated pulmonary vascular responses to hypoxia. Acclimatized high-altitude natives can develop the syndrome upon return to high altitude after a relatively brief sojourn at a lower altitude. More common in persons < 25 years of age Neurogenic pulmonary edema Patients with central nervous system disorders and without apparent preexisting LV dysfunction Narcotic overdose The most frequent cause is use of parenteral heroin. Also associated with parenteral and oral overdoses of legitimate preparations of morphine, methadone, and dextropropoxyphene Eclampsia Cardioversion Anesthesia Cardiopulmonary bypass Transfusion-related acute lung injury

Symptoms & Signs

Acute pulmonary edema usually presents with:
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Rapid onset or aggravation of dyspnea at rest Tachypnea Tachycardia Extreme anxiety Signs of severe hypoxemia

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Hypertension Due to endogenous release of catecholamines Rales Wheezing

Due to airway compression from peribronchial cuffing o Frothy and blood-tinged sputum More commonly associated with cardiogenic cause o Evidence of heart failure S3 gallop Jugular venous distention Unilateral pulmonary edema after rapid evacuation of large pneumothorax o Findings may be apparent only by radiography. o Occasionally, dyspnea with physical findings localized to edematous lung Lymphatic blockade secondary to fibrotic and inflammatory diseases or lymphangitic carcinomatosis Both clinical and radiographic manifestations are dominated by the underlying disease process.
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Differential Diagnosis

Other common causes of acute-onset dyspnea Pulmonary embolism Pneumonia Community acquired Hospital acquired o Aspiration Pneumonia Pneumonitis Foreign body o Pneumothorax o Mucous plug o Exacerbation of chronic obstructive pulmonary disease o Asthma exacerbation
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Diagnostic Approach

Following history and physical examination, it may be difficult to distinguish cardiogenic and noncardiogenic causes. o In patients with coexisting chronic lung disease, the clinical diagnosis of pulmonary edema may not be

clearcut, and the additional steps listed below will also be helpful. The following steps have been proposed to differentiate between cardiogenic and noncardiogenic pulmonary edema.[1] Perform: History and physical Laboratory examination including cardiac enzymes and B-type natriuretic peptide (BNP) measurement Chest radiography o If diagnosis remains uncertain, echocardiography is indicated. o Pulmonary artery catheterization may be necessary when:
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Cause remains uncertain Disease is refractory to therapy Disease is accompanied by hypotension

Laboratory Tests
Arterial blood gas analysis
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Early in the clinical course, arterial partial pressures of both oxygen and carbon dioxide are reduced. o Later, with progressive respiratory failure, hypercapnia develops with progressive acidemia. Serum cardiac biomarkers o If MI is suspected o See Acute ST Elevation Myocardial Infarction for details. BNP measurement Level < 100 pg/mL: heart failure unlikely, negative predictive value 90% o Most patients with symptomatic heart failure have a BNP >400 pg/mL. o 100400 pg/mL: indiscriminate zone; clinical judgment and additional testing required o Elevated levels may be seen in critically ill patients and those with renal failure. Proposed cutoff for diagnosis of heart failure in patients with renal disease is >200 pg/mL.
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May be falsely low in patients with flash pulmonary edema, acute papillary muscle rupture, and obesity (body mass index >30 kg/m2)
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Imaging
Chest radiography o Sometimes difficult to differentiate cardiogenic from noncardiogenic pulmonary edema o A cardiogenic cause is favored with: Cardiomegaly Kerley B lines and loss of distinct vascular margins Cephalization: engorgement of vasculature to the apices In full-blown clinical pulmonary edema, may show diffuse haziness of lung fields with greater density in more proximal hilar regions, "butterfly" appearance Pleural effusion o A noncardiogenic cause is favored with: Cardiomegaly absent Alveolar edema Lack of cephalization Pleural effusion less common Echocardiography with color flow Doppler o May identify systolic and diastolic ventricular dysfunction and valvular lesions suggestive of cardiogenic causes

Diagnostic Procedures

Electrocardiography
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ST elevation and evolving Q waves

Usually diagnostic of acute MI Should prompt immediate institution of MI protocols and coronary artery reperfusion therapy (See Acute ST Elevation Myocardial Infarction.) Pulmonary artery catheterization o Indicated when: Cause (i.e., cardiogenic vs noncardiogenic) remains uncertain o Pulmonary capillary wedge pressure < 18 mmHg is consistent with a noncardiogenic cause. o Pulmonary capillary wedge pressure >20 mmHg favors a cardiogenic cause.

Pulmonary edema refractory to therapy or accompanied by hypotension o Helps to differentiate high-pressure (cardiogenic) and normal-pressure (noncardiogenic) causes

Treatment Approach
Emergency management o Oxygen/intubation as needed o Intravenous furosemide, 0.51.0 mg/kg o Intravenous morphine, 24 mg o Sublingual nitroglycerin Noninvasive positive-pressure ventilation (NIPPV) can: o Rest respiratory muscles o Improve oxygenation and cardiac function o Reduce need for intubation Mechanical ventilation can relieve the work of breathing more completely than NIPPV can, but is associated with more complications. Acute cardiogenic pulmonary edema o Patients often have identifiable cause of acute LV failure, such as:

Arrhythmia Myocardial ischemia MI Myocardial decompensation o Often can be rapidly treated, with improvement in gas exchange o Unless having an acute MI, can sometimes be supported with NIPPV o Further therapeutic considerations Intra-aortic balloon pump (IABP) Reperfusion/revascularization Noncardiogenic edema o Usually resolves much less quickly o Most patients require mechanical ventilation. o NIPPV usually not adequate, as underlying process not readily reversible o See Acute Respiratory Distress Syndrome for therapeutic details of that condition. Conditions that frequently complicate pulmonary edema must be corrected.
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Infection Acidemia Anemia Renal failure

Specific Treatments
Support of oxygenation and ventilation Work of breathing and oxygen requirements are increased in pulmonary edema, which may impose significant physiologic stress on the heart. Oxygen therapy o Essential to ensure adequate oxygen delivery to tissues Positive-pressure ventilation o Should be initiated in patients with inadequate oxygenation or ventilation despite supplemental oxygen o NIPPV Continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPap) An early trial suggested an increased risk of MI associated with CPAP compared with BiPap, but this has not been confirmed in subsequent trials. CPAP, but not BiPap, has been shown to reduce mortality. o Mechanical ventilation Positive end-expiratory pressure can have multiple beneficial effects. o Decreases both preload and afterload, thereby improving cardiac function o Redistributes lung water from intraalveolar to extra-alveolar space, where it does not interfere as much with gas exchange o Increases lung volume to avoid atelectasis

Reduction of preload

Loop diuretics o Effective in most forms of pulmonary edema Even in presence of hypoalbuminemia, hyponatremia, or hypochloremia o Furosemide, 0.31.0 mg/kg IV < 0.5 mg/kg for new-onset acute pulmonary edema without hypervolemia 1 mg/kg for acute or chronic volume overload, renal insufficiency, long-term diuretic use, hypervolemia, or after failure of lower dose

Recommended as combination therapy with nitrates[2] Nitrates o Sublingual nitroglycerin (0.4 mg 3 every 5 minutes) First-line therapy for acute cardiogenic pulmonary edema If pulmonary edema persists and in absence of hypotension, may be followed by intravenous nitroglycerin, commencing at 510 g/min and titrating up to 100 g/min if necessary and systolic blood pressure > 100 mmHg o Intravenous nitroprusside (0.15 g/kg per min) Potent and predominantly arterial vasodilator Useful for patients with pulmonary edema and hypertension and for cautious afterload and preload reduction if systolic blood pressure > 100 mmHg Requires close monitoring and titration, including use of arterial catheter for continuous blood pressure measurement in intensive care unit Limited use owing to cyanide toxicity Morphine o Given in 2- to 4-mg intravenous boluses o Transient venodilator that reduces preload while relieving dyspnea and anxiety o In patients with pulmonary edema and systemic hypertension, can diminish:
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Stress Catecholamine levels Tachycardia Ventricular afterload Angiotensin-converting enzyme inhibitors o Reduce both afterload and preload o Recommended in hypertensive patients o Reduce short- and long-term mortality in acute MI with heart failure Other preload-reducing agents o Intravenous recombinant BNP (nesiritide) Potent vasodilator with diuretic properties Use reserved for refractory patients presenting with acute dyspnea at rest Starting dose is a 2-g/kg IV bolus, followed by 0.01-g/kg per min infusion. Should be used in conjunction with a diuretic

Monitor serum creatinine. Physical methods o Patients without hypotension should be maintained in a sitting position with legs dangling along the side of the bed to reduce venous return and preload.

Inotropic and inodilator drugs Consider in poorly responsive cardiogenic pulmonary edema. Sympathomimetic amines dopamine and dobutamine o Potent inotropic agents o Dobutamine causes vasodilation. o Dopamine causes vasoconstriction. Bipyridine phosphodiesterase-3 inhibitors (inodilators) o Stimulate myocardial contractility while promoting peripheral and pulmonary vasodilation o Indicated in patients with cardiogenic pulmonary edema and severe LV dysfunction and elevated left heart filling pressures[3] o Milrinone: 50 g/kg, followed by 0.250.75 g/kg per min Digoxin: 0.75 g IV loading dose, followed by 0.125 0.25 g daily maintenance dose o Once a mainstay of treatment because of positive inotropic action o May be especially useful for control of ventricular rate in patients with rapid atrial fibrillation or flutter and LV dysfunction Does not have negative inotropic effects of other drugs that inhibit atrioventricular nodal conduction

IABP May help to relieve cardiogenic pulmonary edema Indicated as stabilizing measure when acute severe mitral regurgitation or ventricular septal rupture causes refractory pulmonary edema o Especially in preparation for surgical repair IABP or LV-assist devices

Useful as bridging therapy to cardiac transplantation in patients with refractory pulmonary edema secondary to myocarditis or cardiomyopathy
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Treatment of arrhythmias

Relief of pulmonary congestion will slow sinus rate or ventricular response in atrial fibrillation. Primary tachyarrhythmia may require cardioversion. Patients with reduced LV function and without atrial contraction or with lack of synchronized atrioventricular contraction o Consider placement of an atrioventricular sequential pacemaker.

Treatment of acute coronary syndrome

See Acute ST Elevation Myocardial Infarction for details.

Treatment of ARDS

See Acute Respiratory Distress Syndrome for details.

Unusual types of edema Re-expansion pulmonary edema o Develops after removal of air or fluid that has been in pleural space for some time o Patients may develop hypotension or oliguria resulting from rapid fluid shifts into lung. o Diuretics and preload reduction are contraindicated. o Intravascular volume repletion is often needed while supporting oxygenation and gas exchange. High-altitude pulmonary edema o Oxygen and bed rest o Descent o Inhaled nitric oxide, if feasible o Nifedipine may also be effective. o See High-Altitude Illness. Pulmonary edema resulting from upper-airway obstruction o Recognition of the obstructing cause is key. o Treatment is to relieve or bypass obstruction.

Monitoring
Patients with pulmonary edema need to be in a closely monitored setting, such as telemetry or an intensive care unit, where immediate attention can be given. Monitor oxygenation. o Continuous pulse oximetry is recommended. Monitor urine output. o A Foley catheter is recommended for accurate measurement. Monitor electrolytes.

Monitor BNP. o BNP has a short half-life, and successful therapy is accompanied by a declining BNP. Iatrogenic cardiogenic shock o Vasodilators lower blood pressure, and, particularly when used in combination, their use may lead to:

Complications

Prognosis

Hypotension Coronary artery hypoperfusion Shock o In general, patients with a hypertensive response to pulmonary edema tolerate and are benefited by these medications. o In normotensive patients, low doses of single agents should be instituted sequentially, as needed. Respiratory failure Cardiac arrest End-organ dysfunction Prognosis depends on the underlying cause. Acute ST-segment elevation MI complicated by pulmonary edema o Associated with in-hospital mortality rates of 20 40% ARDS o Mortality estimates: 4065%

Prevention
Compliance with medications related to underlying disease Low-salt diet High-altitude pulmonary edema (See High-Altitude Illness.)
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Acclimatization and slow ascent Medications Calcium-channel blockers Long-acting inhaled 2-adrenergic agonists Tadalafil Dexamethasone

ICD-9-CM
514 Pulmonary congestion and hypostasis (includes pulmonary edema, not otherwise specified) 518.4 Acute edema of lung, unspecified (includes acute pulmonary edema, not otherwise specified)

See Also

Internet Sites
Professionals o Homepage National Heart, Lung, and Blood Institute Patients o Pulmonary edema Mayo Clinic o ARDS U.S. National Heart, Lung, and Blood Institute

Acute ST Elevation Myocardial Infarction Acute Heart Failure Acute Respiratory Distress Syndrome Aortic Dissection Aortic Stenosis Chronic Heart Failure High-Altitude Illness Mitral Stenosis Ventricular Tachycardia

References
1. Ware LB, Matthay MA: Clinical practice. Acute pulmonary edema. N Engl J Med 353:2788, 2005 [PMID:16382065] 2. American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Acute Heart Failure Syndromes et al: Clinical policy: Critical issues in the evaluation and management of adult patients presenting to the emergency department with acute heart failure syndromes. Ann Emerg Med 49:627, 2007 [PMID:17408803] 3. Heart Failure Society Of America : Evaluation and management of patients with acute decompensated heart failure. J Card Fail 12:e86, 2006 [PMID:16500576]

General Bibliography
Cruden NL, Newby DE, Webb DJ: Salmeterol for the prevention of high-altitude pulmonary edema. N Engl J Med 347:1282, 2002 [PMID:12393831] Imray C et al: Acute mountain sickness: pathophysiology, prevention, and treatment. Prog Cardiovasc Dis 52:467, 2010 May-Jun [PMID:20417340] Masip J et al: Non-invasive pressure support ventilation versus conventional oxygen therapy in acute cardiogenic pulmonary oedema: a randomised trial. Lancet 356:2126, 2000 Dec 23-30 [PMID:11191538] Rimoldi SF et al: Flash pulmonary edema. Prog Cardiovasc Dis 52:249, 2009 Nov-Dec [PMID:19917337]

Scherrer U et al: New insights in the pathogenesis of high-altitude pulmonary edema. Prog Cardiovasc Dis 52:485, 2010 May-Jun [PMID:20417341] Schoene RB: Illnesses at high altitude. Chest 134:402, 2008 [PMID:18682459] Terlink JR: Diagnosis and management of acute heart failure, in Libby P et al (eds): Braunwalds Heart Disease, 8th ed. Philadelphia: Saunders, 2008. Weng CL et al: Meta-analysis: Noninvasive ventilation in acute cardiogenic pulmonary edema. Ann Intern Med 152:590, 2010 [PMID:20439577] West JB, American College of Physicians, American Physiological Society: The physiologic basis of highaltitude diseases. Ann Intern Med141:789, 2004 [PMID:15545679] This topic is based on Harrisons Principles of Internal Medicine, 17th edition, chapter 33, Dyspnea and Pulmonary Edema by RM Schwartzstein, and chapter 266, Cardiogenic Shock and Pulmonary Edema by JS Hochman and DH Ingbar.