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eMedicine Specialties > Cardiology > Pericardial Disease

Pericardial Effusion
William J Strimel, DO,, Fellow, Cardiovascular Disease, Scott and White Memorial Hospital
Ramin Assadi, MD, Fellow, Department of Cardiology, Loma Linda University; Ali A Sovari, MD, Clinical and
Research Fellow in Cardiovascular Medicine, Section of Cardiology, University of Illinois at Chicago; Abraham G
Kocheril, MD, FACC, FACP,Professor of Medicine, Director of Clinical Electrophysiology, University of Illinois at
Chicago
Updated: Jun 30, 2010

Introduction

Background
Pericardial effusion defines the presence of an abnormal amount and/or character of fluid in the
pericardial space. It can be caused by a variety of local and systemic disorders, or it may be
idiopathic. Pericardial effusions can be acute or chronic, and the time course of development has a
great impact on the patient's symptoms. Treatment varies, and is directed at both removal of the
pericardial fluid and alleviation of the underlying cause, which usually is determined by a combination
of fluid analysis and correlation with comorbid illnesses.

Image is from a patient with malignant pericardial effusion. Note the "water-bottle"
appearance of the cardiac silhouette in the anteroposterior (AP) chest film.

Pathophysiology
Embryology
In the human embryo, the pericardial cavity develops from the intraembryonic celom during the fourth
week. The pericardial cavity initially communicates with the pleural and peritoneal cavities, but during
normal development these are separated by the eighth week. Both the visceral and parietal
pericardium are derived from the mesoderm, albeit from different parts of the embryo. The visceral
pericardium develops from splanchnic mesoderm, as cells originating from the sinus venous spread
out over the myocardium. The parietal pericardium derives from lateral mesoderm that covers and
accompanies the developing pleuropericardial membrane, which will eventually separate the pleural
and pericardial cavities. In healthy subjects, the pericardium covers the heart and great vessels, with
the exception of only partially covering the left atrium.

Congenital absence of the pericardium can occur, and can be either partial or complete. It is often
clinically silent, but can potentially lead to excessive cardiac motion (in the case of complete absence)
causing vague chest pain or dyspnea, or, in case of partial absence with significant defects,
strangulation of heart muscle and possible death.[1 ]

Physiology

The pericardial space normally contains 15-50 mL of fluid, which serves as lubrication for the visceral
and parietal layers of the pericardium. This fluid is thought to originate from the visceral pericardium
and is essentially an ultrafiltrate of plasma. Total protein levels are generally low; however, the
concentration of albumin is increased in pericardial fluid owing to its low molecular weight.

The pericardium and pericardial fluid provide important contributions to cardiac function.

• The parietal pericardium contributes to resting diastolic pressure, and is responsible for most
of this pressure in the right atrium and ventricle.
• Through their ability to evenly distribute force across the heart, the pericardial structures
assist in ensuring uniform contraction of the myocardium.
• The normal pericardium can stretch to accommodate a small amount of fluid without
significant change in intrapericardial pressure. However, once this pericardial reserve volume
is surpassed, the pressure-volume curve becomes steep. With slow increases in volume,
pericardial compliance can increase to lessen the increase in intrapericardial pressure.

Clinical manifestations of pericardial effusion are highly dependent upon the rate of accumulation of
fluid in the pericardial sac. Rapid accumulation of pericardial fluid may cause elevated intrapericardial
pressures with as little as 80 mL of fluid, while slowly progressing effusions can grow to 2 L without
symptoms.

Understanding the properties of the pericardium can help predict changes within the heart under
physiologic stress:

• During hypervolemic states, the pericardium limits acute cardiac cavitary dilatation.
• By distributing forces across the heart, the pericardium plays a significant role in the
physiologic concept of ventricular interdependence, whereby changes in pressure, volume,
and function in one ventricle influence the function of the other.
• The pericardium plays a pivotal role in cardiac changes during inspiration. As the right atrium
and ventricle fill during normal inspiration, the pericardium, by limiting the ability of these
chambers to dilate, contributes to the bowing of the atrial and ventricular septums to the left.
This reduces LV filling volumes, which lead to the drop in cardiac output. As intrapericardial
pressures rise, this effect becomes pronounced, eventually leading to the finding of pulsus
paradoxus (discussed below), heralding the development of pericardial tamponade.
The cause of abnormal fluid production depends on the underlying etiology, but it is usually secondary
to injury or insult to the pericardium (ie, pericarditis). Transudative fluids result from obstruction of fluid
drainage, which occurs through lymphatic channels. Exudative fluids occur secondary to
inflammatory, infectious, malignant, or autoimmune processes within the pericardium.

Frequency
United States

• Few large studies have characterized the epidemiology of pericardial effusion; however, the
available data consistently shows that they are more prevalent than clinically evident.
• A higher incidence of pericardial effusion is associated with certain diseases.
• Small pericardial effusions are often asymptomatic, and pericardial effusion has been found in
3.4% of subjects in general autopsy studies.
• A wide variety of malignant neoplasms and hematologic malignancies can lead to pericardial
effusion. Data on the prevalence varies, with some studies showing the presence of
pericardial effusion as high as 21% in such patients. A large study by Bussani et al showed
cardiac metastases (9.1%) and pericardial metastases (6.3%) in cases of death from all
causes in individuals with an underlying carcinoma at autopsy.[2 ]Malignancies with the highest
prevalence of pericardial effusion include lung (37% of malignant effusions), breast (22%),
and leukemia/lymphoma (17%).
• Patients with HIV, with or without AIDS, are also found to have increased prevalence of
pericardial effusion.[3 ]Studies have shown the prevalence of pericardial effusion in these
patients to range from 5-43%, depending on the inclusion criteria, with 13% having moderate-
to-severe effusion. The incidence of pericardial effusion in patients infected with HIV has been
estimated at 11%; however, whether highly active anti-retroviral therapy (HAART) has
influenced this number is unknown.

Mortality/Morbidity
The mortality and morbidity of pericardial effusion is dependent upon etiology and comorbid
conditions.

• Idiopathic effusions are well tolerated in most patients. As many as 50% of patients with large,
chronic effusions were asymptomatic during long-term follow-up.
• Pericardial effusion is the primary or contributory cause of death in 86% of cancer patients
with symptomatic effusions.
• Survival rate for patients with HIV and symptomatic pericardial effusion is 36% at 6 months,
19% at 1 year.

Race

• No consistent difference among races is reported in the literature.

• AIDS patients with pericardial effusion are more likely to be white.

Sex

• No sexual predilection exists.

Age

• Observed in all age groups

 • Mean occurrence in fourth or fifth decades; earlier in patients with HIV[3 ]

Clinical

History
A patient with pericardial effusion may report the following symptoms:

• Cardiovascular
o Chest pain, pressure, discomfort: Characteristically, pericardial pain may be relieved
by sitting up and leaning forward and is intensified by lying supine.
o Light-headedness, syncope
o Palpitations
• Respiratory
o Cough
o Dyspnea
o Hoarseness
• Gastrointestinal
o Hiccoughs
• Neurologic
o Anxiety
o Confusion

Physical
Upon examination, a patient with pericardial effusion may have the following signs:

• Cardiovascular
o Classic Beck triad of pericardial tamponade (hypotension, muffled heart sounds,
jugular venous distension).
o Pulsus paradoxus: Exaggeration of physiologic respiratory variation in systemic blood
pressure, defined as a decrease in systolic blood pressure of more than 10 mm Hg
with inspiration, signaling falling cardiac output during inspiration.
o Pericardial friction rub: The most important physical sign of acute pericarditis may
have up to 3 components per cardiac cycle and is high-pitched, scratching, and
grating. It can sometimes be elicited only when firm pressure with the diaphragm of
the stethoscope is applied to the chest wall at the left lower sternal border. The
pericardial friction rub is heard most frequently during expiration with the patient
upright and leaning forward.
o Tachycardia
o Hepatojugular reflux: This can be observed by applying pressure to the periumbilical
region. A rise in the jugular venous pressure (JVP) of greater than 3 cm H2 O for
more than 30 seconds suggests elevated central venous pressure. Transient
elevation in JVP may be normal.
• Respiratory
o Tachypnea
o Decreased breath sounds (secondary to pleural effusions)[4 ]
o Ewart sign - Dullness to percussion beneath the angle of left scapula from
compression of the left lung by pericardial fluid
• Gastrointestinal - Hepatosplenomegaly
• Extremities
o Weakened peripheral pulses
 o Edema
o Cyanosis

Causes
In up to 60% of cases, pericardial effusion is related to a known or suspected underlying process.
Therefore, the diagnostic approach should give strong consideration to coexisting medical conditions.

• Idiopathic: In many cases, the underlying cause is not identified. However, this often relates to
the lack of extensive diagnostic evaluation.
• Infectious
o HIV infection can lead to pericardial effusion through several mechanisms, including
the following:
 Secondary bacterial infection
 Opportunistic infection
 Malignancy (Kaposi sarcoma, lymphoma)
 "Capillary leak" syndrome, which is associated with effusions in other body
cavities
o Viral: The most common cause of infectious pericarditis and myocarditis is viral.
Common etiologic organisms include coxsackievirus A and B, and hepatitis viruses.
o Pyogenic (pneumococci, streptococci, staphylococci, Neisseria, Legionella species)
o Tuberculous
o Fungal (histoplasmosis, coccidioidomycosis, Candida)
o Other infections (syphilitic, protozoal, parasitic)
• Neoplasia
o Neoplastic disease can involve the pericardium through the following mechanisms:
 Direct extension from mediastinal structures or the cardiac chamber
 Retrograde extension from the lymphatic system
 Hematologic seeding
 As mentioned previously, the most common cases of malignant effusion are
lung, breast, lymphoma, and leukemia. However, patients with malignant
melanoma or mesothelioma have a high prevalence of associated pericardial
effusions.
• Postoperative/postprocedural
o Pericardial effusions are common after cardiac surgery. In 122 consecutive patients
studied serially before and after cardiac surgery, effusions were present in 103
patients; most appeared by postoperative day 2, reached their maximum size by
postoperative day 10, and usually resolved without sequelae within the first
postoperative month. In a retrospective survey of more than 4,500 postoperative
patients, only 48 were found to have moderate or large effusions by
echocardiography; of those, 36 met diagnostic criteria for tamponade.[5 ]
o Use of preoperative anticoagulants, valve surgery, and female sex were all
associated with a higher prevalence of tamponade. Symptoms and physical findings
of significant postoperative pericardial effusions are frequently nonspecific, and
echocardiographic detection and echo-guided pericardiocentesis, when necessary,
are safe and effective; prolonged catheter drainage reduces the recurrence rate.[6 ]
o Pericardial effusions in cardiac transplant patients are associated with an increased
prevalence of acute rejection.[7 ]
• Other less common causes include the following:
o Uremia
o Myxedema
o Severe pulmonary hypertension
 o Radiation therapy
o Acute myocardial infarction, including the complication of free wall rupture
o Aortic dissection, leading to hemorrhagic effusion in from leakage into pericardial sac
o Trauma
o Hyperlipidemia
o Chylopericardium
o Familial Mediterranean fever
o Whipple disease
o Hypersensitivity or autoimmune related
 Systemic lupus erythematosus [8 ]
 Rheumatoid arthritis
 Ankylosing spondylitis
 Rheumatic fever
 Scleroderma
 Wegener granulomatosis
o Drug-associated (eg, procainamide, hydralazine, isoniazid, minoxidil, phenytoin,
anticoagulants, methysergide)

Differential Diagnoses
Cardiac Tamponade Pericarditis, Constrictive-Effusive
Cardiomyopathy, Dilated Pericarditis, Uremic
Myocardial Infarction Pulmonary Edema, Cardiogenic
Pericarditis, Acute Pulmonary Embolism
Pericarditis, Constrictive
Other Problems to Be Considered
Myocardial ischemia

Workup

Laboratory Studies
The extent to which pericardial effusions should be evaluated with fluid analysis remains an area of
some debate. Initially, in a patient with a new pericardial effusion, the likelihood of myocarditis or
pericarditis should be assessed, and the initial diagnostic evaluation should be directed toward these
conditions. In general, all patients with pericardial tamponade, suspected purulent effusion, or poor
prognostic indicators in the setting of pericarditis should undergo diagnostic pericardiocentesis. Those
with recurrent effusions or large effusions that do not resolve with treatment of the underlying
condition may also warrant fluid analysis.

The following lab studies may be performed in patients with suspected pericardial effusion.

• Electrolytes - Metabolic abnormalities (eg, renal failure)

• CBC count with differential - Leukocytosis for evidence of infection, as well as cytopenias, as
signs of underlying chronic disease (eg, cancer, HIV)
• Cardiac enzymes: Troponin level is frequently minimally elevated in acute pericarditis, usually
in the absence of an elevated total creatine kinase level. Presumably, this is due to some
involvement of the epicardium by the inflammatory process. Although the elevated troponin
may lead to the misdiagnosis of acute pericarditis as a myocardial infarction, most patients
with an elevated troponin and acute pericarditis have normal coronary angiograms. An
 elevated troponin level in acute pericarditis typically returns to normal within 1-2 weeks and is
not associated with a worse prognosis.
• Thyroid-stimulating hormone - Thyroid-stimulating hormone screen for hypothyroidism
• Rickettsial antibodies - If high index of suspicion of tick-borne disease
• Rheumatoid factor, immunoglobulin complexes, antinuclear antibody test (ANA), and
complement levels (which would be diminished) - In suspected rheumatologic causes
• PPD and controls
• Pericardial fluid analysis - Routine tests (these should be considered part of the standard
pericardial fluid analysis)
o Lactic (acid) dehydrogenase (LDH), total protein - The Light criteria (for exudative
pleural effusion) found to be as reliable in distinguishing between exudative and
transudative effusions
 Total protein fluid-to-serum ratio >0.5
 LDH fluid-to-serum ratio >0.6
 LDH fluid level exceeds two thirds of upper-limit of normal serum level
o Other indicators suggestive of exudate - Specific gravity >1.015, total protein >3.0
mg/dL, LDH >300 U/dL, glucose fluid-to-serum ratio <1
o Cell count - Elevated leukocytes (ie, >10,000) with neutrophil predominance suggests
bacterial or rheumatic cause, although unreliable
o Gram stain - Specific but insensitive indicator of bacterial infection
o Cultures - Signals and identifies infectious etiology
o Fluid hematocrit for bloody aspirates - Hemorrhagic fluid hematocrits usually
significantly less than simultaneous peripheral blood hematocrits
• Pericardial fluid - Special tests (these should be considered individually based on the pretest
probability of the coexisting condition under concern)
o Viral cultures
o Adenosine deaminase; polymerase chain reaction (PCR); culture for tuberculosis;
smear for acid-fast bacilli in suspected tuberculosis infection, especially in patients
with HIV
o A definite diagnosis of tuberculous pericarditis is based on the demonstration of
tubercle bacilli in pericardial fluid or on a histological section of the pericardium.
Probable tuberculous pericarditis is based on the proof of tuberculosis elsewhere in a
patient with otherwise unexplained pericarditis, a lymphocytic pericardial exudate with
elevated adenosine deaminase levels, and/or appropriate response to a trial of
antituberculosis chemotherapy.
• Tumor markers: Elevated carcinoembryonic antigen (CEA) levels in pericardial fluid have a
high specificity for malignant effusions.

Imaging Studies
Chest radiography

• Findings include enlarged cardiac silhouette (so-called water-bottle heart) and pericardial fat
stripe.
•
 Image is from a patient with malignant pericardial effusion. Note the "water-
bottle" appearance of the cardiac silhouette in the anteroposterior (AP) chest
film.

• A third of patients have a coexisting pleural effusion.

• Radiography is unreliable in establishing or refuting diagnosis of pericardial effusion.

Echocardiography
Echocardiography is the imaging modality of choice for the diagnosis of pericardial effusion, as the
test can be performed rapidly and in unstable patients. Most importantly, the contribution of pericardial
effusion to overall cardiac enlargement and the relative roles of tamponade and myocardial
dysfunction to altered hemodynamics can be evaluated with echocardiography.[9 ]
Echocardiogram (parasternal, long axis) of a patient with a moderate pericardial
effusion.
Subcostal view of an echocardiogram that shows a moderate-to-large amount of
pericardial effusion.
This echocardiogram shows a large amount of pericardial effusion (identified by the
white arrows).

• 2-D echocardiography
o Pericardial effusion appears as an echo-free space between the visceral and parietal
pericardium. Early effusions tend to accumulate posteriorly owing to expandable
posterior/lateral pericardium. Large effusions are characterized by excessive motion
within the pericardial sac. Small effusions have an echo-free space of less than 10
mm, and are generally seen posteriorly. Moderate-sized effusions range from 10-20
mm and are circumferential, and greater than 20 mm indicates a large effusion. Fluid
adjacent to the right atrium is an early sign of pericardial effusion.[10 ]
o Severe cases may be accompanied by diastolic collapse of the right atrium and right
ventricle (and in hypovolemic patients, the left atrium and left ventricle), signaling the
onset of pericardial tamponade (see Cardiac Tamponade).
o
 This image is from a patient with malignant pericardial effusion. The
effusion is seen as an echo-free region to the right of the left ventricle
(LV).

• M-mode echocardiography
o M-mode is adjunctive to 2D imaging for the detection of pericardial effusion. Effusions
can be classified using M-mode according to a system proposed by Horowitz, et al.[11 ]
 Type A: No effusion
 Type B: Separation of epicardium and pericardium
 Type C1: Systolic and diastolic separation of pericardium
 Type C2: Systolic and diastolic separation of pericardium, attenuated
pericardial motion
 Type D: Pronounced separation of pericardium and epicardium with large
echo-free space
o In the parasternal long-axis view, discordant changes in right and left ventricular
cavity size can suggest pronounced interventricular dependence.
• Doppler echocardiography
o Transmitral and transtricuspid inflow velocities should be interrogated to assess for
respiratory variation. Decreases in flow during inspiration (transmitral) or expiration
(transtricuspid) should raise the suspicion of clinically significant interventricular
dependence and tamponade physiology.
o Pulmonic vein inflow may show a decrease in early diastolic flow with
hemodynamically significant effusions. Hepatic vein diastolic flow reversal may also
be seen.

False-positive echocardiograms can occur in pleural effusions, pericardial thickening, increased

epicardial fat tissue, atelectasis, and mediastinal lesions.

Epicardial fat tissue is more prominent anteriorly but may appear circumferentially, thus mimicking
effusion. Fat is slightly echogenic and tends to move in concert with the heart, 2 characteristics that
help distinguish it from an effusion, which is generally echolucent and motionless.[9 ]
In addition to its mimicry, pericardial fat accumulation is a source of bioactive molecules, is
significantly associated with obesity-related insulin resistance, and may be a coronary risk factor.[12,13 ]

In patients with pericardial effusion, imaging from low to midposterior thorax can provide additional
diagnostic echocardiographic images and should be used in patients in whom conventional images
are technically difficult or require additional information.

Transesophageal echocardiography (TEE)

TEE maintains all of the advantages of transthoracic echocardiography and is useful in characterizing
loculated effusions. However, this may be difficult to perform in patients with symptomatic effusions
due to hemodynamic instability, making the required sedation more difficult.

Intracardiac echocardiography (ICE)

ICE is generally reserved for the assessment of pericardial effusion in the setting of percutaneous
interventional or electrophysiology procedure. Phased array ICE systems can perform both 2-D and
Doppler interrogations.

Computed tomography

• CT can potentially determine composition of fluid and may detect as little as 50 mL of fluid.
• CT can detect pericardial calcifications, which can be indicative of constrictive pericarditis.
• CT results in fewer false-positive results than echocardiography.
• CT can be problematic in patients who are unstable given the time required to transport to
and from the scanner and perform the test.

Magnetic resonance imaging

• MRI can detect as little as 30 mL of pericardial fluid.

• May be able to distinguish hemorrhagic and no hemorrhagic fluids, as hemorrhagic fluids
have a high signal intensity on T-1 weighted images, whereas no hemorrhagic fluids have a
low signal intensity.
• Nodularity or irregularity of the pericardium seen on MRI may be indicative of a malignant
effusion.
• MRI is more difficult to perform than CT scan acutely, given the length of time the patient
must remain in the scanner.

Both MRI and CT scan may be superior to echocardiography in detecting loculated pericardial
effusions, especially when located anteriorly. Also, these modalities allow for greater visualization of
the thoracic cavity and adjacent structures, and therefore may identify other abnormalities relating to
the cause of the effusion.
Other Tests
Electrocardiography

• Early in the course of acute pericarditis, the ECG typically displays diffuse ST elevation in
association with PR depression. The ST elevation is usually present in all leads except for
aVR, but postmyocardial infarction pericarditis, the changes may be more localized.
Classically, the ECG changes of acute pericarditis evolve through 4 progressive stages:
o Stage I - Diffuse ST-segment elevation and PR-segment depression
 o Stage II - Normalization of the ST and PR segments
o Stage III - Widespread T-wave inversions
o Stage IV - Normalization of the T waves
•

This electrocardiogram (ECG) is from a patient with malignant pericardial

effusion. The ECG shows diffuse low voltage, with a suggestion of electrical
alternans in the precordial leads.

• Patients with uremic pericarditis frequently do not have the typical ECG abnormalities.

Procedures

• Pericardiocentesis
o This procedure is used for diagnostic as well as therapeutic purposes. Support for the
use of echocardiographic guidance is increasing, unless emergent treatment is
required.
o Indications include impending hemodynamic compromise (ie, pericardial tamponade),
suspected infectious etiology, and uncertain etiology.
o Use of a needle that is at least 5 cm long, 16-gauge in diameter, and has a short
bevel can minimize the risk of complications and should allow for adequate
pericardial drainage. A system allowing placement of a catheter over the needle is
preferred.
o Contrast echocardiography using agitated saline is useful in cases when bloody fluid
is aspirated to determine if the needle is in the ventricular cavity.
o Attaching an ECG electrode to the pericardiocentesis needle is also useful for
avoiding myocardial puncture. Electrical activity will be seen on the monitor when the
needle comes into contact with atrial or ventricular myocardium. These changes may
be delayed, however, and instill a false sense of security in needle placement; sense
of touch and the findings on aspiration should guide the procedure, with the clinician
ultimately relying on good clinical sense.
o Complications of pericardiocentesis include ventricular rupture, dysrhythmias,
pneumothorax, myocardial and/or coronary artery laceration, and infection.
o Recurrence rates within 90 days may be as high as 90% in patients with cancer.
• Balloon pericardotomy
 o A catheter is placed in the pericardial space under fluoroscopy, which, after inflation
of the balloon, creates a channel for passage of fluid into the pleural space, where
reabsorption occurs more readily.
o This may be useful for recurrent effusions.
• Pericardial sclerosis
o Several pericardial sclerosing agents have been used with varying success rates (eg,
tetracycline, doxycycline, cisplatin, 5-fluorouracil).
o The pericardial catheter may be left in place for repeat instillation if necessary until
the effusion resolves.
o Complications include intense pain, atrial dysrhythmias, fever, and infection.
o Success rates are reported as high as 91% at 30 days.
• Pericardioscopy
o This procedure is not universally available.
o It may increase diagnostic sensitivity in cases of unexplained pericardial effusions. It
allows for visualization of pericardium and for pericardial biopsies.
• CT-guided pericardiostomy
o Patients with effusions after cardiothoracic surgery often have limited
echocardiographic windows, loculated effusions, and may be on continued ventilatory
support, all of which increase the difficulty of echo-guided pericardiocentesis.
o A report by Palmer et al suggests that, in postsurgical cases, CT-guided pericardial
drainage is safe and effective. The authors reported on 36 patients—33 who
underwent major cardiothoracic surgery and 3 who were treated with minimally
invasive procedures—whose symptomatic pericardial effusions were drained using
CT-guided percutaneous placement of an indwelling pericardial catheter. There were
no clinically significant complications associated with any of the placement
procedures. Thirty-three patients experienced no symptom recurrence following
catheter removal, although pericardial effusion did recur in the remaining 3 patients,
requiring a repeat treatment. Comparing procedure costs, the authors determined
that the CT-guided tube pericardiostomies cost 89% less than intraoperative
pericardial window procedures would have. No significant procedure-cost differences
were found between CT-guided and ultrasonographically guided tube
pericardiostomies.[14 ]

Treatment

Medical Care
Initially, medical care of pericardial effusion is focused on determination of the underlying etiology.

• Aspirin/nonsteroidal anti-inflammatory agents (NSAIDs)

o Most acute idiopathic or viral pericarditis occurrences are self-limited and respond to
treatment with aspirin (650 mg q6h) or another NSAID.
o Aspirin may be the preferred nonsteroidal agent to treat pericarditis after myocardial
infarction because other NSAIDs may interfere with myocardial healing.
o Indomethacin should be avoided in patients who may have coronary artery disease.
o Meurin et al performed a multicenter, randomized, double-blind trial on the effect of
the NSAID diclofenac in reducing postoperative pericardial effusion volume.
Diclofenac, 50 mg, or placebo twice daily for 14 days was given to 196 patients at
high risk for tamponade because of pericardial effusion more than 7 days after
cardiac surgery. The authors found that diclofenac was not effective at reducing the
size of the effusion or preventing late cardiac tamponade.[15 ]
• Colchicine: The routine use of colchicine is supported by results from the COlchicine for acute
PEricarditis (COPE) trial. In this trial, 120 patients with a first episode of acute pericarditis
(idiopathic, acute, postpericardiotomy syndrome, and connective tissue disease) entered a
randomized, open-label trial comparing aspirin treatment alone with aspirin plus colchicine (1-
2 mg for the first day followed by 0.5-1 mg/d for 3 mo). Colchicine reduced symptoms at 72
hours (11.7% vs 36.7%; P =0.03) and reduced recurrence at 18 months (10.7% vs
36.7%; P =0.004; 5 needed treatment). Colchicine was discontinued in 5 patients because of
diarrhea. No other adverse events were noted. Importantly, none of the 120 patients
developed cardiac tamponade or progressed to pericardial constriction.[16 ]
• Steroids
o Steroid administration early in the course of acute pericarditis appears to be
associated with an increased incidence of relapse after tapering the steroids.
o In the COPE trial, steroid use was an independent risk factor for recurrence (odds
ratio=4.3). Also, an observational study strongly suggests that the use of steroids
increases the probability of relapse in patients treated with colchicine.[16 ]
o Systemic steroids should be considered only in patients with recurrent pericarditis
unresponsive to NSAIDs and colchicine or as needed for treatment of an underlying
inflammatory disease. If steroids are to be used, an effective dose (1-1.5 mg/kg of
prednisone) should be given, and it should be continued for at least 1 month before
slow tapering.
o The intrapericardial administration of steroids has been reported to be effective in
acute pericarditis without producing the frequent reoccurrence of pericarditis that
complicates the use of systemic steroids, but the invasive nature of this procedure
limits its use.
• Hemodynamic support
o Patients who have effusions with actual or threatened tamponade should be
considered to have a true or potential emergency. Most patients require
pericardiocentesis to treat or prevent tamponade. However, treatment should be
carefully individualized.
o Hemodynamic monitoring with a balloon flotation pulmonary artery catheter is useful,
especially in those with threatened or mild tamponade in whom a decision is made to
defer pericardiocentesis. Hemodynamic monitoring is also helpful after
pericardiocentesis to assess both reaccumulation and the presence of underlying
constrictive disease. However, insertion of a pulmonary artery catheter should not be
allowed to delay definitive therapy in critically ill patients.
o Intravenous fluid resuscitation may be helpful in cases of hemodynamic compromise.
o In patients with tamponade who are critically ill, intravenous positive inotropes
(dobutamine, dopamine) can be used but are of limited use and should not be
allowed to substitute for or delay pericardiocentesis.
• Antibiotics
o In patients with purulent pericarditis, urgent pericardial drainage combined with
intravenous antibacterial therapy (eg, vancomycin 1 g bid, ceftriaxone 1-2 g bid, and
ciprofloxacin 400 mg/d) is mandatory. Irrigation with urokinase or streptokinase, using
large catheters, may liquify the purulent exudate, but open surgical drainage is
preferable.
o The initial treatment of tuberculous pericarditis should include isoniazid 300 mg/day,
rifampin 600 mg/day, pyrazinamide 15-30 mg/kg/day, and ethambutol 15-25
mg/kg/day. Prednisone 1-2 mg/kg/day is given for 5-7 days and progressively
reduced to discontinuation in 6-8 weeks. Drug sensitivity testing is essential.
Uncertainty remains whether adjunctive corticosteroids are effective in reducing
mortality or progression to constriction. Surgical resection of the pericardium remains
 the appropriate treatment for constrictive pericarditis. The timing of surgical
intervention is controversial, but many experts recommend a trial of medical therapy
for noncalcific pericardial constriction and pericardiectomy in nonresponders after 4-8
weeks of antituberculosis chemotherapy.
• Antineoplastic therapy (eg, systemic chemotherapy, radiation) in conjunction with
pericardiocentesis has been shown to be effective in reducing recurrences of malignant
effusions.
• Corticosteroids and NSAIDs are helpful in patients with autoimmune conditions.

Surgical Care
Surgical care of pericardial effusion includes the following:

• Subxiphoid pericardial window with pericardiostomy[17 ]

o This procedure is associated with low morbidity, mortality, and recurrence rates, and
can be considered as a reasonable alternative diagnostic or treatment modality to
pericardiocentesis in selected patients.
o It can be performed under local anesthesia. This is advantageous because general
anesthesia often leads to decreased sympathetic tone, resulting in hemodynamic
collapse in patients with pericardial tamponade and shock.
o It may be less effective when effusion is loculated.
o One study indicated it may be safer and more effective at reducing recurrence rates
than pericardiocentesis. However, only patients who were hemodynamically unstable
underwent pericardiocentesis, and no change in overall survival rate was observed.
• Thoracotomy
o This should be reserved for patients in whom conservative approaches have failed.
o Thoracotomy allows for creation of a pleuropericardial window, which provides
greater visualization of pericardium.
o Thoracotomy requires general anesthesia and thus has higher morbidity and mortality
rates than the subxiphoid approach.
• Video-assisted thoracic surgery[18 ]
o Video-assisted thoracic surgery (VATS) enables resection of a wider area of
pericardium than the subxiphoid approach without the morbidity of thoracotomy.
o The surgeon is able to create a pleuropericardial window and address concomitant
pleural pathology, which is especially common in patients with malignant effusions.
o One disadvantage of VATS is that it requires general anesthesia with single lung
ventilation, which may be difficult in otherwise seriously ill patients.
• Median sternotomy
o This procedure is reserved for patients with constrictive pericarditis.
o Operative mortality rate is high (5-15%).

Consultations

• A cardiologist should be involved in the care of patients with pericardial effusion.

• Cardiothoracic surgery may be required for recurrent or complicated cases (see Surgical
Care).

Medication

Autoimmune pericardial effusions may respond to treatment with anti-inflammatory medications. In

general, selection of an agent depends on the severity of the patient's symptoms and the tolerability
and adverse effect profiles of the medications.
Nonsteroidal anti-inflammatory drugs
Are used mostly for patients with active, nonhemorrhagic pericarditis with or without pericardial
effusion. NSAIDS have analgesic, anti-inflammatory, and antipyretic activities. The mechanism of
action in pericarditis is not known, but NSAIDS may inhibit cyclooxygenase activity and prostaglandin
synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal
enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.

Indomethacin (Indocin, Indometh)

Drug of choice in this class, although other NSAIDs (ie, ibuprofen, naproxen, aspirin) possess some
efficacy. Used as initial therapy for mild-to–moderately severe inflammatory pericardial effusions.

Dosing

Adult
25-50 mg PO bid/tid
75 mg SR PO bid; titrate to effectiveness; not to exceed 200 mg/d

Pediatric
1-2 mg/kg/d PO divided bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d

Interactions

Aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase
concentrations and, possibly, toxicity; may decrease effects of hydralazine, captopril, and beta-
blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct
patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase
phenytoin levels

Contraindications

Documented hypersensitivity; GI bleeding; renal insufficiency

Precautions

Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if
benefits outweigh risk to fetus

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Pregnancy category D in third trimester; acute renal insufficiency, hyperkalemia, hyponatremia,

interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in
patients with preexisting renal disease or compromised renal perfusion; reversible leukopenia may
occur (discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia)
May mask signs and symptoms of infection

Corticosteroids
Have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids
modify the body's immune response to diverse stimuli.
Prednisone (Deltasone, Orasone, Sterapred)

Used for patients with severe inflammatory pericardial effusions or for those in whom initial treatment
with NSAIDs has failed. Other agents may be used if adverse effect profile warrants; dosages should
be determined by prednisone equivalents.

Dosing

Adult

5-60 mg/d PO qd or divided bid/qid; taper over 2 wk, as symptoms resolve, to 5-10 mg PO qd

Pediatric

4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk, as symptoms resolve

Interactions

Estrogens may decrease clearance; may cause digitalis toxicity secondary to hypokalemia;
phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance
dose); diuretics require monitoring for hypokalemia

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective
tissue infections; fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if
benefits outweigh risk to fetus

Precautions

Abrupt discontinuation may cause adrenal crisis; adverse effects may include hyperglycemia, edema,
osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis,
myasthenia gravis, growth suppression, and infections

Anti-inflammatory Agent
These agents inhibit key factors involved in inflammatory reactions.

Colchicine

Alkaloid extract that inhibits microtubule formation. Has unique anti-inflammatory properties.
Concentrates well in leukocytes and reduces neutrophilic chemotaxis and motility. Reduces release of
lactic acid and proinflammatory enzymes. Inhibits release of histamine-containing granules from mast
cells, which may be important in pathogenesis of elastic tissue changes found in anetoderma.

Use in autoimmune disease is primarily empiric, and mechanism of action in decreasing inflammation
is not clear, nor is it truly an immunomodulating agent.

Dosing
Adult

1-2 mg PO to start, then 0.5- 1 mg PO qd

Pediatric

<12 years: Not established

>12 years: Administer as in adults

Interactions

Sympathomimetic agent toxicity and effect of CNS depressants are significantly increased with
colchicine

Contraindications

Documented hypersensitivity; severe renal, hepatic, GI, or cardiac disorders; blood dyscrasias

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if
benefits outweigh risk to fetus

Precautions

Risk of renal failure, hepatic failure, permanent hair loss, bone marrow suppression, numbness or
tingling in hands and feet, disseminated intravascular coagulopathy, and decreased sperm count;
dose-dependent GI upset is common

Follow-up

Further Inpatient Care

• Patients with pericardial effusion who present with significant symptoms or cardiac
tamponade require emergent treatment and admission to ICU.
• The pericardial catheter (if placed) should be removed within 24-48 hours to avoid infection.
• Symptomatic patients should remain hospitalized until definitive treatment is accomplished
and/or symptoms have resolved.

Further Outpatient Care

• Patients should be educated on symptoms of increasing pericardial effusion and should be

evaluated whenever these symptoms begin to occur.
• Indications for echocardiography after diagnosis include the following:
o A follow-up imaging study to evaluate for recurrence/constriction: Repeat studies may
be performed to answer specific clinical questions.
o The presence of large or rapidly accumulating effusions (to detect early signs of
tamponade)

Transfer
Symptomatic patients requiring treatment (who are surgical candidates) should receive care at an
institution with cardiothoracic surgery capabilities.

Complications
 • Pericardial tamponade
o Can lead to severe hemodynamic compromise and death.
o Heralded by equalization of diastolic filling pressures.
o Treat with expansion of intravascular volume (small amounts of crystalloids or
colloids may lead to improvement, especially in hypovolemic patients) and urgent
pericardial drainage. Avoid positive-pressure ventilation if possible, as this decreases
venous return and cardiac output. Vasopressor agents are of little clinical benefit.
• Chronic pericardial effusion
o Effusions lasting longer than 6 months.
o Usually well tolerated.

Prognosis

• Most patients with acute pericarditis recover without sequelae. Predictors of a worse outcome
include the following: fever greater than 38°C, symptoms developing over several weeks in
association with immunosuppressed state, traumatic pericarditis, pericarditis in a patient
receiving oral anticoagulants, a large pericardial effusion (>20 mm echo-free space or
evidence of tamponade), or failure to respond to NSAIDs. In a series of 300 patients with
acute pericarditis, 254 (85%) did not have any of the high-risk characteristics and had no
serious complications. Of these low-risk patients, 221 (87%) were managed as outpatients
and the other 13% were hospitalized when they did not respond to aspirin.
• Patients with symptomatic pericardial effusions from HIV/AIDS or cancer have high short-term
mortality rates.

Miscellaneous

Medicolegal Pitfalls

• Failure to consider pericardial effusion as a principal or secondary diagnosis may lead to

rapid deterioration and death secondary to cardiac tamponade.
• Patients with viral cardiomyopathy, especially in the acute setting, may have a similar
presentation, with an enlarged heart on chest radiographs. Echocardiography readily
distinguishes the difference between enlarged cardiac chambers and a pericardial effusion.

Multimedia
Media file 1: Image is from a patient with malignant pericardial effusion. Note the
"water-bottle" appearance of the cardiac silhouette in the anteroposterior (AP) chest
film.

Media file 2: Echocardiogram (parasternal, long axis) of a patient with a moderate

pericardial effusion.
Media file 3: This image is from a patient with malignant pericardial effusion. The
effusion is seen as an echo-free region to the right of the left ventricle (LV).

Media file 4: This electrocardiogram (ECG) is from a patient with malignant pericardial
effusion. The ECG shows diffuse low voltage, with a suggestion of electrical alternans in
the precordial leads.
Media file 5: Subcostal view of an echocardiogram that shows a moderate-to-large
amount of pericardial effusion.
Media file 6: This echocardiogram shows a large amount of pericardial effusion
(identified by the white arrows).

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