Topic Editor: Grant E. Fraser, M.D., FRACGP, FACRRM, ASTEM
Review Date: 9/20/2012
Definition 
Cardiogenic Pulmonary Edema (CPE) is the accumulation of fluid in the pulmonary interstitium and alveoli due to increased pulmonary capillary hydrostatic pressure. Cardiac dysfunction, usually left ventricular failure (LVF), with elevated pulmonary venous pressure is the most common cause of this condition.
Description
- Pulmonary edema is the abnormal fluid accumulation in the pulmonary interstitium and alveoli, usually due to elevated pulmonary venous pressure due to cardiac dysfunction
- Pathophysiology: Accumulation of fluid occurs as a result of imbalance of Starling forces (hydrostatic and oncotic pressures) in the pulmonary capillaries and the surrounding tissue
- Left ventricular failure (LVF) and resulting congestion of the pulmonary venous system are the most common etiology
- May be classified into cardiogenic and non-cardiogenic, based on the underlying etiology
- Cardiogenic Pulmonary Edema (CPE) may be classified based on its severity
- Mild: Involves engorgement of pulmonary vasculature
- Moderate: Involves extravasation of fluid into the interstitial space
- Severe: Involves alveolar filling
Epidemiology
Incidence/Prevalance
- Annual incidence of CPE in adults =65 years is 1/100 patients [U.S.]
- Acute CPE results in 1 million annual hospital admissions in the U.S.
- At age 40 years, lifetime risk of developing heart failure (and thus at risk of CPE) is 20% in both genders
Gender- Higher incidence among males
Risk factors
- African Americans have higher incidence
- Cardiac dysrhythmias
- Cardiomyopathy
- Coronary artery disease
- Diabetes
- History of smoking
- Increasing age-much more prevalent as age increases
- Hypertension (SBP>160 doubles risk compared to SBP140)
- Myocardial infarction
- Valvular heart disease
Etiology
- Acute Myocardial Infarction (AMI) or ischemia
- Acute myocarditis
- Acute mitral regurgitation
- Aortic or mitral stenosis
- Atrial fibrillation and flutter
- Congenital heart disease
- Cardiomyopathy
- Endocarditis
- Hypertrophic cardiomyopathy
- Left-ventricular failure (LVF) [most common cause]
- Myocarditis
- Rheumatic heart disease
- Severe systemic hypertension
- Thyrotoxicosis
- Ventricular tachycardia
[Outline]
History
- Acute weight gain
- Cough
- Diaphoresis
- Dyspnea (exertional or at rest)
- Fatigue/weakness
- Orthopnea
- Paroxysmal nocturnal dyspnea
Physical findings on examination
- Ascites
- Cardiac murmur
- Cyanosis
- Hepatojugular reflex
- Hypoxemia
- Hypotension or hypertension
- Jugular venous distension
- Lung examination with wheezes or bibasilar crackles
- Lung percussion with decreased resonance at bases (consistent with effusion)
- S3, S4 or summation gallop
- Peripheral edema
- Pink frothy sputum
- Tachypnea
- Tachycardia
[Outline]
Blood test findings
- Serum cardiac biomarkers
- Elevated troponin is indicative of myocardial injury
- Troponin levels (troponin I and troponin T) should be obtained when Acute Coronary Syndrome (ACS) or AMI is suspected
- Brain natriuretic peptide (BNP) secreted by myocytes in the cardiac ventricles due to volume expansion. This test can be helpful in evaluating CPE. The majority of patients with symptomatic congestive heart failure (CHF) have BNP levels of >500 pg/mL. CHF is not likely if the BNP level is 100 pg/mL. BNP levels between 100 and 500 pg show no clear discrimination, and although being consistent with CHF, is not diagnostic. Values in these ranges require clinical judgment. The predictive value of BNP is unclear in critically ill patients as other etiologies may result in abnormal BNP levels
- Arterial blood gas analysis
- Rarely indicated in most cases, so long as oximetry is generating an adequate wave form and values correlate with clinical impression
- Venous blood gas appropriate in cases where oximetry is adequate for determination of oxygenation, to evaluate for lactate or PCO2
- ABG, in cases where oximetry is not adequately generating reliable waveforms, may be more accurate in accessing oxygenation
- In the early course of CPE, there is a reduction in arterial partial pressures of both oxygen and carbon dioxide. Hypercapnia and metabolic acidosis develop as the disease progresses. The A-a gradient
is an essential item to calculate as it increases with worsening CPE
- Serum electrolyte level
- Serum electrolyte measurements are useful in the assessment of electrolyte abnormalities, such as hypokalemia, hyponatremia, or hypomagnesemia in CHF patients. Additionally, hyperkalemia may be found in renal failure patients
- Hyponatremia is a marker of severe CHF
- Serum creatinine: Elevated serum creatinine is a predictor of all-cause mortality in chronic CHF and also provides evidence of end-organ hypoperfusion
Radiographic findings
- Chest X-ray is often useful in differentiating between cardiogenic and non-cardiogenic pulmonary edema
- CPE cases typically have:
- Bibasilar edema
- Cardiomegaly
- Characteristic 'butterfly appearance'
- Diffuse haziness of lung fields
- Inverted blood flow
- Kerley B lines
- Pleural effusions (often more prominent on the right)
- Chest radiography may have little value in cases of abrupt onset of CPE, as abnormalities are typically delayed by many hours
Other diagnostic test findings
- Pulse oximetry may be helpful in the evaluation of hypoxia and severity of CPE. It can also be helpful in the evaluation of therapeutic response to oxygen supplementation. Its value can be limited by the ability to obtain a satisfactory wave form, as this requires adequate peripheral perfusion. Adequate peripheral perfusion is often absent in the patient presenting in shock
- ECG may also demonstrate evidence of cardiac ischemic changes or ST-elevation myocardial infarction. Evolving Q waves may also be helpful in diagnosing an acute Q-wave MI. ECG is also useful in the detection of arrhythmia, ventricular hypertrophy, and atrial enlargement
- ECG can have some value in the evaluation of diastolic versus systolic LV function and valvular disease; however, echocardiography is more sensitive and specific
- Echocardiography (Echo) to evaluate left ventricular function, measure cardiac output and assess valvular and pericardial pathology
- Pulmonary artery catheterization is only occasionally used to measure pulmonary capillary wedge pressure (PCWP). It can be useful to differentiate between cardiogenic vs non-cardiogenic pulmonary edema. PCWP >18 mmHg with the absence of chronically elevated left atrial pressure is suggestive of a cardiogenic pulmonary edema
[Outline]
General treatment items
- There are immediate treatment goals, which relate to alleviation of increased work of breathing and hypoxia; and long term treatment goals of stabilization and outpatient management of CPE
- Ventilatory support
- Ventilatory support is critical in patients with CPE. It is not unusual for a patient with CPE to have their work of breathing as their greatest physiological stressor. Ventilatory support needs to be emergently addressed in many patient, while appropriate pharmacologic agents are administered
- In patients who have adequate mentation, provision of Positive Pressure Ventilation (PPV) through non-invasive means is a time critical procedure. It is essential that this be applied early before decompensation occurs
- Mechanical ventilation (intubation) can usually be avoided when early Non-invasive PPV (NIPPV) is utilized early. NIPPV includes BiPap or CPAP
- Regardless of whether NIPPV (highly preferred) or invasive ventilation via endotracheal tube is provided; it is critical to decrease the workload of breathing and the stress this places on the heart
- Noninvasive Positive Pressure Ventilation (NIPPV)
- Useful in early treatment of severe CPE, NIPPV involves breathing through a tightly fitting face mask into a continuous flow of positive airway pressure. This intervention significantly reduces intrathoracic pressure during all respiratory phases, along with decreasing preload and afterload
- Two types of NIPPV
- Continuous Positive Airway Pressure (CPAP)
- Bi-level Positive Airway Pressure (BiPAP)
- The efficacy of CPAP and BiPAP may be comparable. Some evidence suggests a greater risk of AMI with BiPAP as compared to CPAP. Evidence of one over the other is not at a high level, with either intervention being acceptable practice
- Mechanical ventilation
- Use of endotracheal intubation and mechanical ventilation provides maximum oxygen delivery and respiratory support
- Use of mechanical ventilation should usually be limited to patients failing NIPPV or those who have hypercapnia with confusion or shock
- Preload reduction
- Nitroglycerin (NTG) is an effective and rapidly-acting nitrate available for preload reduction. Sublingual NTG is the preferred first line therapy for CPE. For ongoing symptoms, an intravenous infusion of NTG may be administered. A limiting issue is hypotension or right heart dysfunction, which contraindicates use of this class of drugs. Nitroprusside can also be used similarly as an IV infusion for afterload and preload reduction
- Loop diuretics (e.g., bumetanide, furosemide, torsemide) reduce preload through their diuretic and direct vasoactive properties, and have been a treatment mainstay. However, patients with renal insufficiency and advanced CHF due to poor renal perfusion may show diuretic resistance
- Morphine is known to reduce preload, along with relieving dyspnea and anxiety. Morphine also reduces ischemic pain. However, use of morphine has not been prospectively studied. The best data, examining the use of morphine on decompensated heart failure (2008 ADHERE analysis) demonstrated the following outcomes as compared to patients who received no morphine:
- >5 fold increase in need for mechanical ventilation
- >5 fold increase in mortality (13% vs. 2.4%)
- Longer time in hospital: 5.6 vs. 4.2 days
- More required ICU: 38.7% vs. 14.4%
- Even after risk adjustment and exclusion of ventilated patients, morphine use independently predicted higher mortality with an odds ratio of 4.84 (p0.001)
- Nesiritide is an intravenous recombinant BNP with vasodilator and diuretic properties and can be considered in refractory cases. However, O'Connor's 2011 prospective randomized trial of 7141 patients showed no benefit, but also little harm to use of this agent. This agent is not justified in most clinical situations
- After-load reduction
- ACE inhibitors (e.g., enalapril and captopril) are known to reduce afterload, and improve stroke volume and cardiac output. Several studies have shown promising results with ACE inhibitors for the treatment of acute decompensated CHF and CPE. ACE inhibitors may reduce ICU admission rates and duration of ICU stay in CPE patients
- Angiotensin II receptor blockers (ARBs) such as valsartan have benefits comparable to ACE inhibitors
- Inotropic agents
- Inotropic agents are used when preload- and afterload-reduction strategies are ineffective, or when hypotension precludes use of these strategies. Catecholamines such as norepinephrine, dobutamine, and dopamine are often preferred, yet adverse effects may include increased myocardial oxygen demand and myocardial ischemia. Phosphodiesterase inhibitors (e.g., milrinone) also show positive inotropic activity but without severe adverse effects. Newer inotropic agents include calcium sensitizers such as levosimendan (available only in few European countries) which increase contractility and may be a safer alternative to catecholamines
- Most evidence indicates worse outcome in patients who require these agents (unclear if this is the effect these medications or whether this is primarily due to patients with hypotension and pulmonary edema being more ill and at increased mortality risk)
- Ultrafiltration
- Ultrafiltration may be an option for patients with renal dysfunction, and diuretic resistance. This procedure may be more effective than IV diuretics in controlling net fluid loss and rehospitalization in hypervolemic patients with CPE
- Intra-Aortic Balloon Pumping (IABP)
- IABP is a lifesaving hemodynamic stabilization technique used in cases with severe mitral regurgitation or ventricular septal rupture causing refractory CPE. IABP reduces afterload and increases coronary blood flow. IABP may be used as a bridging therapy to revascularization or implementation of an LV-assist device. Complications include perforation, laceration, or dissection of femoral artery and thrombosis/embolism
- The use of IABP has not been studied in the setting of a randomized prospective trial until recently. The result published in NEJM in 2012, in the setting of AMI complicated by cardiogenic shock, showed no outcome benefit at 30 days. Although it is likely these results also apply to CPE patients; no trial has been performed specifically in this group
Medications indicated with specific doses
Preload Reduction [Nitrates]
- Nitroglycerin [Sublingual]
- Nitroglycerin [IV]
- Nitroprusside [IV]
Preload Reduction [Loop diuretics]- Bumetanide [IM/IV]
- Furosemide [IM/IV]
- Torsemide [IV]
Preload Reduction [Agents no longer recommended-see text above]- Morphine [Injectable]
- Nesiritide [IV]
Afterload Reduction [ACE-inhibitors]- Benazepril
- Captopril
- Enalapril [IV]
- Enalapril [Oral]
- Fosinopril
- Lisinopril
- Moexipril
- Perindopril
- Quinapril
- Ramipril
- Trandolapril
Afterload Reduction [Angiotensin receptor blockers]- Azilsartan
- Candesartan
- Eprosartan
- Irbesartan
- Losartan
- Olmesartan
- Telmisartan
- Valsartan
Inotropic Agents- Dobutamine [IV]
- Dopamine [IV]
- Inamrinone [IV]
- Milrinone [IV]
- Norepinephrine [IV]
Dietary or Activity restrictions
- A low-sodium diet (2 g/day) is recommended for CPE patients
- Fluid restriction may be beneficial in some patients (e.g. 1500-2000 mL/day)
Disposition
Most cases of CPE are treated in an inpatient CCU or ICU setting
Admission criteria
- Arrhythmias
- Acute coronary syndrome or AMI
- Confusion
- CPE that is of new onset (needs investigation)
- Dyspnea at rest or with minimal exertion
- Hypercapnea
- Hypotension
- Hypoxia (O2 sat 90%)
- Renal dysfunction-acute change in renal function
Discharge criteria- Resolution of issue that met criteria for admission
- Adequate investigation of the underlying cause
- Stabilization of the condition on oral medications
- Stable daily weight
- Adequate family and patient education
- Follow-up as an outpatient arranged
[Outline]
