P l e u ra l E ff u s i o n S e co n d a ry to D i se a ses

of t h e H e a rt
In this chapter, the pleural effusions that occur after
coronary artery bypass graft (CABG) surgery, those
that occur after cardiac injury (Dressler's syndrome) ,
those that occur concomitantly with pericardia! disease,
and those that occur after heart transplantation
are discussed.
PO ST-CO R O N ARY A RT E RY B Y PA S S
S U R G E RY
More than 500,000 CABG procedures are now performed
annually in the United States ( 1 ) . Because
pleural effusions complicate many of these procedures,
pleural effusions that occur after CABG are
one of the most common types of effusion.
I n c i d e nce
In the period immediately following CABG, there is a
very high incidence of pleural effusion. In one study of
1 52 patients who had undergone CABG surgery, the
incidence of pleural effusion on routine chest radiographs
7 days postoperatively was 42% (2) . In a subsequent
study, patients underwent chest ultrasound
on the 7th, 1 4th, and 30th postoperative day (3) . In
this latter study, the incidence of pleural effusion was
89 .4% on the 7th postoperative day, 76.6% on the
1 4th postoperative day, and 57.4% on the 30th postoperative
day (3) . In a more recent prospective study,
the prevalence of pleural effusions in 349 patients was
63% 30 days postoperatively (4) . The prevalence of
pleural effusion appears similar whether the patient
has valve surgery or not in addition to the CABG (4) .
In patients who have undergone CABG, there
is a substantial incidence of large pleural effusions
although most effusions are small (5) . In a recent
study of 349 patients, the incidence of pleural effusion
that occupied more than 25% of the hemithorax
30 days after CABG was 9.7% (4) . In this study,
the incidence of larger effusions was higher in the
patients who received internal mammary grafts
( 1 0.9%) than it was in patients who received only
saphenous vein grafts (4. 5 %) (4) . Hurlbut et al. (6)
reported that 4% of 1 00 patients who had undergone
CABG developed moderate-to-large effusions.
If 1 0% of all the patients undergoing CABG develop
a moderate-to-large pleural effusion, then the exudative
pleural effusion following CABG is one of the
most common types of exudative pleural effusion.
Pathog e n e s i s a n d Path o l o g i c Featu res
In general the larger pleural effusions, those occupying
more than 2 5 % of the hemithorax, that occur
after CABG surgery can be divided into those that
reach their maximal size within the first 30 days of
surgery and those that reach their maximal size more
than 30 days after surgery (7) . The etiology of the
large early pleural effusion after CABG surgery is
probably related to trauma to the pleura during surgery
(3) . Patients undergoing internal mammary
artery (IMA) grafting are more likely to have a pleural
effusion than those undergoing only saphenous
vein grafting (SVG) (3) . Patients undergoing bilateral
IMA bypasses are more likely to have a pleural effusion
than those undergoing unilateral IMA bypasses
(8) . Patients with a pericardia! effusion postoperatively
are more likely to have a pleural effusion, but
it is likely that both are a result of trauma rather than
one being responsible for the other (3) . The effusions
occurring early in the postoperative period are frequently
bloody. In one series, the mean pleural fluid
red blood cell count in 45 patients with large pleural
effusions within the first 30 days of surgery exceeded
2,000,000/mm3 (7) , which is equivalent to a hematocrit
of 20%.
The etiology of the effusions that occur more than
30 days after CABG is not known. The fluid is an exudate
with predominantly lymphocytes (7) . Because
the fluid is an exudate, the effusion is probably not
due to congestive heart failure. The presence of the
lymphocytes suggests an immunologic basis. Pleural
biopsies obtained within the first few months of surgery
demonstrate an intense lymphocytic pleuritis (9) .
Immunohistochemical staining demonstrates that the
lymphocytes in the pleural tissue are both T lymphocytes
and B lymphocytes with a predominance of
B lymphocytes (9) . The effusions have been attributed
to the post-cardiac injury syndrome (PCIS) ( 1 0) .
This explanation, however, i s unsatisfactory because
patients with PCIS usually have fever, chest pain, pericarditis,
and pneumonitis in addition to the pleural
effusion. Patients with the late pleural effusions after
CABG usually do not have fever, chest pain, pericarditis,
or pneumonitis (4) . Possibly, the late pleural
effusion after CABG is a variant of or a limited variety
of the PCIS (7) .
The administration of topical hypothermia
through iced slush during CABG surgery appears to
be associated with a higher prevalence of pleural effusion.
In one study of patients receiving only saphenous
venous grafts, the prevalence of pleural effusion
was 50% in 50 patients receiving topical hypothermia,
but only 1 8 % in 50 patients not receiving
topical hypothermia ( 1 1 ) . In a second study of 505
nonrandomized, consecutive patients undergoing
CABG surgery, 60% of the 1 9 1 patients who received
topical hypothermia had a pleural effusion, whereas
only 25% of the 3 1 4 patients who did not receive
topical hypothermia had a pleural effusion ( 1 2) . The
explanation for the association between iced slush
and the presence of pleural effusion is not known, but
it has been speculated that cold injury to the phrenic
nerve may cause atelectasis (5) .
It has been hypothesized that the development
of the pleural effusion post-CABG is due, at least
in part, to the patients being on cardiopulmonary
bypass. This is not definitely the case, however,
because in two small series ( 1 3 , 1 4) the prevalence of
pleural effusion was actually higher in patients who
had off-pump coronary artery bypass surgery than in
those who had on-pump surgery. However, in a series
from Nashville, the prevalence of effusion at 30 days
postoperatively that occupied more than 2 5 % of the
hemithorax was only 3% in the off-pump group ( 1 5)
whereas in a previous study from the same hospital it
had been 1 0% in the on-pump group (4) .
C l i n ical M a n ifestations
Dyspnea is the only symptom that most patients with
pleural effusions experience after CABG (4) . Pleuritic
chest pain, chest wall tenderness, fever, pneumonitis,
and pericarditis are all unusual. In one series of
29 patients with large pleural effusions, 7 5 . 9% complained
of dyspnea, 1 0 .3% complained of chest pain,
and only 1 (3.4%) complained of fever (4) .
The pleural effusions that occur after CABG surgery
tend to be unilateral on the left side. In the study
using ultrasound in which 42 of 47 patients had
pleural effusions on the seventh postoperative day,
1 7 ( 40%) of the effusions were unilateral on the left,
24 (57%) were bilateral, and 1 (2%) was unilateral
on the right (3) . By the 30th postoperative day, there
were 27 patients with effusions, and 1 8 (67%) of
these were unilateral left sided, 8 (30%) were bilateral,
and 1 (4%) was unilateral right sided (3) .
In studies of patients who have larger pleural effusions,
the effusions are usually left sided, or if they
are bilateral, they are larger on the left. In the study
by Sadikot et al. (7) of 7 1 patients with post-CABG
pleural effusions who underwent thoracentesis, 42
of the effusions (59%) were unilateral left sided, 1 8
(25%) were bilateral and usually larger on the left,
and 1 1 ( 1 5%) were unilateral on the right.
As mentioned in the preceding text, the larger pleural
effusions that occur after CABG can be divided into
those that occur within the first 30 days of the surgery
and those that occur more than 30 days after surgery
(7, 1 6) . The late effusions do not appear to evolve from
the early effusions. The characteristics of the pleural
fluid in the two situations are quite different. The pleural
fluid with the early effusions is bloody, with a mean
red blood cell count of approximately 2,000,000/mm3
(7, 1 6) . The pleural fluid is frequently eosinophilic,
with a mean eosinophil percentage of greater than
40% (7) . The pleural fluid eosinophilia is probably
due to the blood in the pleural space. Patients with
eosinophilic pleural effusions post-CABG also tend
to have peripheral eosinophilia ( 1 7) . There is a significant
correlation between the percentage of eosinophils
in the pleural fluid and the serum, although the percentage
of eosinophils in the serum is lower ( 1 7) . In
these patients, the eosinophilia is correlated with the
levels of interleukin-5 and eotaxin-3 in the pleural
fluid, which are higher than the corresponding levels
in the serum ( 1 7) . The mean pleural fluid lactate
dehydrogenase (LDH) with the bloody effusions is
approximately twice the upper limit of normal for
serum (7) . It is likely that much of the pleural fluid
LDH is LDH- 1 , which is the LDH from the red
blood cells. The pleural fluid protein is in the exudative
range, and the pleural fluid glucose level is not
reduced (7) .
In contrast to the bloody exudates that were discussed
in the preceding text, the pleural fluid that
occurs more than 30 days after CABG is a clear yellow
lymphocyte-predominant exudate. The mean lymphocyte
percentage for 26 lace effusions in one series
was 61 %, whereas the mean eosinophil percentage
was only 2% (7) . The pleural fluid LDH tends to
be lower with the late effusions than with the early
effusions and averages about the upper limit of normal
for serum (7) . As with the early effusions, the
pleural fluid protein is in the exudative range and
the pleural fluid glucose level is not reduced (7) .
A small percent of patients will develop dyspnea from
a pleural effusion more than 90 days post-CABG
surgery ( 1 8) . Most effusions occurring this long after
surgery are transudates due to heart failure ( 1 8) .
D i a g nosis
The diagnosis of pleural effusion secondary to CABG
is one of exclusion. In the days immediately after
CABG, the main diagnoses to exclude are congestive
heart failure, pulmonary embolus, parapneumonic
effusion, and chylothorax. Congestive heart failure
is excluded if the patient has an exudative pleural
effusion. Chylothorax is excluded if the fluid is clear
yellow or if the triglyceride levels are low. Pulmonary
embolus is more difficult to exclude, and a computed
tomography (CT) angiography is necessary in some
cases (see Chapter 1 7) . However, the pleural effusion
with pulmonary embolus usually occupies less
than 25% of the hemithorax and disappears spontaneously
within a couple of weeks. Patients with
parapneumonic effusions are usually febrile, and the
pleural fluid differential white blood cell (WBC)
count reveals predominantly neutrophils and a very
low percentage of eosinophils.
The differential diagnosis is somewhat different
for the late pleural effusion occurring after CABG,
and the main diagnoses to consider are congestive
heart failure, chylothorax, tuberculosis, malignancy,
constrictive pericarditis, and pulmonary embolus.
As with the early effusion, the diagnosis of congestive
heart failure is eliminated if the patient has an
exudative pleural effusion and the diagnosis of chylothorax
is excluded if the patient's pleural fluid is
clear or has a low triglyceride level. With a lymphocytepredominant
pleural effusion, one must exclude tuberculosis.
Because the adenosine deaminase (ADA) level
is less than 40 IU/L in patients with pleural effusions
after CABG ( 1 9) and is above this level in patients
with tuberculous pleuritis, demonstration of an ADA
below 40 IU/L virtually excludes the diagnosis of
tuberculous pleuritis. Patients with constrictive pericarditis
will usually have other signs and symptoms
such as bilateral pedal edema and ascites.
Treatm e n t
Most patients with smaller pleural effusions postCABG
require no treatment as the effusion gradually
disappears (5). When a patient is identified with a large
pleural effusion after CABG (occupying more than
25% of the hemithorax) , a thoracentesis should be
performed to exclude the other diagnoses in the differential
outlined earlier. Because most of these patients
are dyspneic (4) and the therapy of choice for these
effusions is a therapeutic thoracentesis, it is recommended
that the initial thoracentesis be a therapeutic
thoracentesis (5) .
If the other diagnostic possibilities are excluded
and the fluid recurs, a second and then a third therapeutic
thoracentesis are indicated. Many patients are
also given nonsteroidal anti-inflammatory agents
(NSAIDs) or oral prednisone, but there are no
controlled studies documenting the efficacy of this
approach. There is one study that evaluated the
effectiveness of diclofenac, an NSAID, in preventing
pleural effusion in the immediate postoperative
period (20) . Niva et al. (20) randomized patients to
receive 50 mg diclofenac (22 patients) or placebo
( 1 9 patients) orally every 8 hours in the postoperative
period. They reported chat the control group had a
higher incidence of pleural effusion ( 42. 1 % ) at discharge
than did the diclofenac-treated group (22.7%)
(20) . In a second study, lmazio et al. (20a) studied
whether colchicine would reduce the incidence of
effusions post cardiac surgery in a double-blind randomized
study of 360 patients. They reported that
the incidence of pleural effusion was significantly less
( 1 2.2%) in the group that received colchicine starting
on the third postoperative day and continuing for a
month than it was in the group that received placebo
(22. 8%) (2 1 )

Some patients have been managed successfully

with chemical pleurodesis. Before one becomes too
aggressive in managing this condition, it is important
to realize that most patients will do well with no more
than a couple of thoracenteses. In our prospective
study, we followed 30 patients with pleural effusions
occupying more than 2 5 % of the hemithorax for
12 months. During this period, 8 (27%) received no
invasive treatment for the pleural effusion, 16 (53%)
received a single thoracentesis, 2 (7%) received two
thoracenteses, and 4 ( 1 3%) received three or more
thoracenteses. Only one patient was still receiving
periodic thoracenteses 1 2 months after CABG (4) .
Twenty-two of the 25 patients who underwent thoracentesis
reported that their dyspnea was alleviated
with the thoracentesis (4) .
On occasion, the effusion persists despite several
therapeutic thoracenteses. We have subjected eight
such patients to thoracoscopy in recent years. At thoracoscopy,
several patients had thin sheets of fibrous
tissue that coated the lung and prevented it from
expanding (9) . It is likely that this sheet of fibrous
tissue "trapped" the lung and prevented it from reexpanding.
After the fibrous tissue coating the visceral
pleura was removed, the lung expanded and the effusion
did not recur (9) . However, because most had
a mechanical or a chemical pleurodesis at the same
time, one cannot be certain that the decortication was
responsible for the effusion not recurring. Recurrent
pleural effusions post-CABG surgery have also been
managed successfully with video-assisted thoracic
surgery with talc insuffiation (2 1 ) . No mention was
made in this latter paper about membranes encasing
the visceral pleural (2 1 ) .
I n view o f the series mentioned i n the preceding
text, thoracoscopy is recommended for an effusion
after CABG that continues to recur for several
months despite several therapeutic thoracenteses. At
thoracoscopy, any fibrous tissue coating the visceral
pleura should be removed and the parietal pleura
should be abraded to create a pleurodesis.
P l e u ra l Effu s i o n After Ve ntricu l a r Assi st
Device Placement
Patients who receive ventricular assist devices are
being used more frequently as bridges to cardiac
transplantation or to facilitate patient transfers. It
appears that most placements of this device are associated
with the development of a pleural effusion
(22) . Guha et al. (22) reviewed the placement of
22 of these devices and reported that every patient
had a pleural effusion after placement (22) . Six of
the 22 patients ( 1 8%) had effusions before surgery.
Nine patients required thoracentesis to relieve dyspnea
and the median time from placement to thoracentesis
was 23 days. All the pleural fluids examined
were blood-tinged exudates (22) .
PO ST-CA R D I A C I N J U RY { D R E S S L E R 'S}
S Y N D RO M E { P C I S}
PCIS is characterized by the onset of fever, chest pain,
pleuropericarditis, and parenchymal infiltrates in the
weeks following injury to the pericardium or myocardium
(23,24) . There is no universal agreement on the
definition of the PCIS (22) . Mott et al. (25) defined
noncomplicated PCIS as the presence of a temperature
greater than 1 00. 5F, patient irritability, pericardia!
friction rub, and a small pericardia! effusion with
or without pleural effusion following cardiac trauma
(25 ) . They defined complicated PCIS as a noncomplicated
PCIS plus the need for hospital readmission
with or without the need for pericardiocentesis or
thoracentesis (2 5 ) . I prefer the proposed definition of
Imazio et al. (26) who define the PCIS as the presence
of at least two of the following: fever without alternative
explanation, pleuritic chest pain, pericardia!
friction rub, new or worsening pleural effusion, and
new or worsening pericardia! effusion. This syndrome
has been described following myocardial infarction,
cardiac surgery, blunt chest trauma, percutaneous
left ventricular puncture, pacemaker implantation,
angioplasty, and repair of pectus excavatum (27) .
I n c i d e nce
The incidence of the PCIS was thought by Dressler
to be 3% to 4% after an acute myocardial infarction
(23 ) . Subsequent studies have demonstrated that the
incidence is probably less than 1 % (28), but the incidence
is much higher in patients with large transmural
infarctions in which the pericardium is involved (29) .
In one series, 1 5% of patients with an acute myocardial
infarction and pericarditis developed the postmyocardial
infarction syndrome during the follow-up
period (29) . The incidence of the syndrome is much
higher following surgical procedures involving the
pericardium than after an acute myocardial infarction
(24,30) . Engle et al. (24) reported that 30% of 257
children undergoing cardiac operations developed
the syndrome. Miller et al. (3 1 ) reported an incidence
of 1 7. 8 % in 944 patients undergoing cardiac surgery
at Johns Hopkins Hospital during a 1 -year period. In
a recent study (32), the incidence of PCIS was 1 5 %
in 360 patients undergoing cardiac surgery Etiolog i c Factors
The cause of the syndrome is unknown, but it
appears to have an immunologic basis. The syndrome
is thought to be initiated by a combination of damage
to the pericardium and/or pleura and especially
bleeding into the pericardium (33) . Then this damage
is thought to initiate immunologic events in
susceptible individuals. (33) . In patients undergoing
surgical procedures involving the pericardium,
a close relationship exists between the development
of the syndrome and the presence of antimyocardial
antibodies. Engle et al. (24) prospectively followed
up 257 patients undergoing cardiac operations and
found that 67 (26%) had high titers of antimyocardial
antibodies, and all of these patients developed the
syndrome. None of the 1 02 patients without a rise
in antibody titers developed the syndrome, and only
4 of 93 patients with intermediate titers developed
the syndrome. In a second study conducted by De
Scheerder et al. (34) , antibodies to actin and myosin
were measured preoperatively and postoperatively in
62 patients undergoing CABG. Eight patients ( 1 3%)
developed the PCIS, and all of them had more than
a 60% increase in their antibodies to both actin and
myosin postoperatively. Thirty-eight patients did not
develop the syndrome, and none of these patients
had more than a 50% rise in either of the antibodies.
The remaining patients developed an incomplete syndrome
and had intermediate increases in their antibody
titers. No such clear-cut relationship has been
demonstrated between antimyocardial antibodies and
the syndrome in patients with myocardial infarction.
Liem et al. (28) were unable to find any association
between the development of the syndrome and the
presence of antimyocardial muscle antibodies in
1 36 patients with an acute myocardial infarction.
In postoperative patients, it is unclear whether the
antimyocardial antibodies precipitate or result from
the syndrome.
Other factors also appear to be associated with
the development of PCIS . Epidemiologic studies
indicate that there is a seasonal variation in the PCIS,
with the highest incidence corresponding to the
time of the highest prevalence of viral infection in
the community (3 5 ) . It has been hypothesized that
a concurrent viral infection may trigger the immune
response (34) . In patients undergoing cardiac surgery,
the incidence is approximately the same after
all types of surgery (3 1 ) . Younger patients and those
who are asymptomatic preoperatively are more likely
to develop the syndrome (3 1 ) . There is also a higher
incidence of the syndrome if the patient has a history
of pericarditis or if the patient had taken corticosteroids
previously (3 1 ) .
C l i n ical M a n ifestations
PCIS is characterized by fever, chest pain, pericarditis,
pleuritis, and pneumonitis occurring after cardiac
trauma or an acute myocardial infarction. The symptoms
following myocardial infarction usually develop
in the second or third week; an occasional patient
develops symptoms within the first week (35), and a
larger percentage of patients develops symptoms only
after the third week. The syndrome is seen at an average
of 3 weeks following cardiac operations but can
occur any time between 3 days and 1 year (36) . The
two cardinal symptoms of the syndrome are fever and
chest pain (23,36) . The chest pain often precedes the
onset of fever and varies from crushing and agonizing,
mimicking myocardial ischemia, to a dull ache,
to pleuritic chest pain (23) . Almost all patients have a
pericardia! friction rub, and many of them also have
a pericardia! effusion. As many as 75% of patients
with these syndromes have pulmonary infiltrates,
either linear or in patches, mostly located in the base
of the lungs (37) . Laboratory evaluation reveals a
peripheral leukocytosis ( 1 0,000 to 20,000/mm3) and
an elevated erythrocyte sedimentation rate or CRP in
most patients (23,32,36) .
Pleural involvement is common in the PCIS.
Dressler (23) reported that 68% of 3 5 patients with
the post-myocardial infarction syndrome had pleural
effusions. In another series of 35 patients with PCIS,
29 patients (83%) had a pleural effusion; the effusion
was unilateral in 1 8 and bilateral in 1 1 of the
patients (37) . Imazio et al. (32) reported that 93%
of 54 patients with the PCIS post-cardiac surgery
had a pleural effusion. In general, the pleural effusion
is small, and pericarditis is the dominant feature.
The pleural fluid is an exudate with a normal
pH and a normal glucose level (37) . The pleural fluid
is frankly bloody in approximately 30% of patients,
and the differential WBC may reveal predominantly
polymorphonuclear leukocytes or mononuclear cells,
depending on the acuteness of the process (37) .
D i a g nosis
The diagnosis of the syndrome should be considered
in any patient who develops a pleural effusion following
myocardial infarction, a cardiac operation or other
trauma to the heart, particularly when signs of pericarditis
are present. The diagnosis of the syndrome is
established by the clinical picture and by ruling out congestive heart failure, pulmonary embolism, and
pneumonia. Congestive heart failure as a cause of the
pleural effusion is excluded by the demonstration of
an exudative pleural fluid. A pulmonary CT angiogram
or a perfusion lung scan should be obtained to
exclude the diagnosis of pulmonary embolization.
It is important not to mistakenly diagnose pulmonary
embolism rather than the PCIS because anticoagulation
is contraindicated in the PCIS (23) . Patients
with the syndrome are at risk for developing hemopericardium.
One report suggested that the diagnosis
of the syndrome could be established by demonstrating
a high titer of antimyocardial antibodies and a low
complement level in the pleural fluid (38) . However,
a subsequent publication (39) and our own unpublished
observations have failed to confirm that levels
of antimyocardial antibodies in the pleural fluid are
elevated in patients with the PCIS .
Treatment
This syndrome usually responds to treatment with
antiinflammatory agents such as aspirin or indomethacin
(33) . In the more severe forms of the syndrome,
corticosteroids may be necessary (33 ) . However, the
prophylactic administration of intravenous methylprednisolone
at a standard anti-inflammatory dose
in children after cardiac surgery with cardiopulmonary
bypass neither prevents nor attenuates the PCIS
(25 ) . A recent placebo-controlled double-blind randomized
study (40) of 360 patients reported that the
administration of colchicine on the third postoperative
day and continuing for 30 days was associated
with a reduction in the incidence of pericardia! effusion
from 22.8% to 1 2.8% and a reduction in the
incidence of pleural effusion from 26. 5 % to 1 2 .2%
It is important to establish the diagnosis of the
PCIS in patients who have undergone CAB Gs because
the pericarditis may cause graft occlusion. Urschel
et al. (36) reported that graft occlusion occurred in
1 2 of 1 4 patients (86%) who developed the syndrome
after CABGs and who were treated symptomatically.
When 3 1 subsequent patients were treated with prednisone,
30 mg/day for a week and tapering doses for
5 weeks thereafter, in addition to aspirin 600 mg q.i.d.,
only 5 ( 1 6%) of the grafts became occluded (36) .
P E R I CA R D I A L D I S E A S E
A substantial percentage o f patients with pericardia!
disease develop a pleural effusion, which is usually left
sided. Weiss and Spodick (4 1 ) reviewed the charts of
1 33 consecutively discharged patients with pericardia!
effusion. Thirty-five of the patients (26%) had
a roentgenographically demonstrable pleural effusion
and no other lung disease. Twenty-one of the patients
had inflammatory pericardia! disease without congestive
heart failure, and 1 5 of them had only a left-sided
pleural effusion, 3 had more fluid on the left than on
the right, and in 3, the effusions were of the same size
on both sides. Of the five patients with inflammatory
pericarditis and congestive heart failure, the effusions
were equal bilaterally in two, greater on the right side
in two, and left sided in one. Two of the three patients
with constrictive pericarditis had a unilateral leftsided
effusion. Sun et al. (42) performed CT scans
on 74 patients with pericardia! effusions and reported
that 52 (70%) had a pleural effusion. The incidence
of effusion was comparable whether the patient
had benign or malignant pericardia! disease ( 42) .
Tomaselli et al. (43) reviewed 30 cases of constrictive
pericarditis and found that a pleural effusion was present
in 1 8 (60%) . In 12 of the 1 8 patients, the effusion
was bilateral and approximately symmetric. Three
effusions were left sided, and three were right sided.
We described one patient with constrictive pericarditis
who had a large unilateral right-sided pleural effusion,
which we attributed to the transdiaphragmatic
transfer of his ascitic fluid ( 44) .
The mechanism responsible for the pleural effusion
associated with pericardia! disease is not clear.
The obvious explanation is that the pulmonary and
systemic capillary pressures are elevated secondary
to the pericardia! disease, resulting in a transudative
pleural effusion. However, if this were the sole explanation,
one would not expect most of the effusions to
be left sided in patients with inflammatory pericardia!
disease and also that some patients with constrictive
pericarditis would have exudative pleural effusions
(43 ) . It is probably that in patients with pericardia!
effusions, some of the fluid passes directly from the
pericardia! space into the pleural space. Gibson and
Segal (45) showed that 20% of protein injected into
the pericardium entered the pleural space within
an hour of the injection. The pericardia! inflammation
itself may increase the ease by which fluid passes from
the pericardia! to the pleural space ( 4 1 ) . In addition
the pericardia! inflammation may also cause inflammation
of the pleura covering the pericardium which
could lead to a pleural effusion.
The characteristics of the pleural fluid seen in
conjunction with pericardia! disease are not well
described. Tomaselli et al. (43) reported that the fluid
was exudative in three patients and transudative in one patient with constrictive pericarditis. We described
one patient with a large right-sided pleural effusion
with constrictive pericarditis who had a pleural Buid
protein of 4 g/dL (44) . In another recent report of
two patients with constrictive pericarditis secondary
to bromocriptine therapy, the pleural Buid in one had
a protein level of 4 g/dL (simultaneous serum level of
6.4 g/dL) (46) . I would suspect that the pleural Buid
with inflammatory pericardia! disease is also exudative.
Obviously, the treatment of choice for the pleural
effusion secondary to pericardia! disease is to treat the
pericardia! disease.
PO ST-H EART TRA N S P LA N TAT I O N
Pleural effusions are common after heart transplantation.
Misra et al. (47) retrospectively reviewed the
charts and imaging studies of 72 patients who had
undergone orthotropic heart transplants over a 6-year
period and reported that 6 1 patients (85%) had a
pleural effusion postoperatively while only 1 9 (26%)
had effusions preoperatively. Most of the effusions
were small and bilateral, but 1 6% of the patients
had effusions that occupied more than 2 5 % of the
hemithorax (47) . All of these effusions were attributed
to the transplantation procedure. The effusions
were largest at median hospital day 6 . 5 . Most of
them resolved within the first year after transplantation
(47) . Pleural Buid was examined in four of the
patients and was exudative in two (47) .
A second study (48) reviewed all the pulmonary
complications in 1 57 patients that received 1 5 9
transplants. Ten of the patients (6.3%) developed
pleural effusions that warranted a diagnostic thoracentesis
and/or specific therapeutic intervention
with diuretics, antibiotics, or chest tubes (48) . The
etiology of the effusion was found to be parapneumonic
in four cases, chylothorax in one, hemothorax
secondary to Aspergillus pneumonia in one, sepsis
in one, and probable transudates in three cases (48) .
There was one case report of a pleural effusion due
to post-transplant lymphoproliferative disorder ( 49) .
At autopsy, the patient had pleural-based tumor
nodules compatible with post-transplant lymphoproliferative
disorder (49) .
The management of patients with pleural effusions
depends on the size of the effusion and the patient's
clinical picture. If the effusion occupies more than
2 5 % of the hemithorax, a diagnostic thoracentesis
should be performed immediately in an attempt to
ascertain the etiology of the effusion. The main considerations
are pleural infection, chylothorax, congestive
heart failure, and a pleural effusion post-heart transplant
similar to the effusions post-CABG surgery. If
the effusion is very small, it can probably be ignored
because these effusions are very common (47) . If the
effusion occupies less than 2 5 % of the hemithorax
but represents more than just blunting of the costophrenic
angle, a diagnostic thoracentesis should
be performed if the patient is complaining of shortness
of breath or if the patient is not feeling up to
par. It is important to remember that these patients
are immunosuppressed and accordingly are more
likely to have infections. Moreover, patients with
pleural infections may not be febrile because of the
immunosuppression.
P U L M O N A RY V E I N STE N O S I S A FTE R
CAT H E T E R A B LAT I O N O F AT R I A L
F I B R I L LAT I O N
A procedure that is being used more and more
commonly for the treatment of chronic atrial fibrillation
is circumferential pulmonary-vein ablation (50) .
A known complication of this procedure is pulmonary
vein stenosis (5 1 ) , which occurs in approximately 3%
of patients who undergo this procedure (52) . Presenting
symptoms with pulmonary vein stenosis include
shortness of breath, cough, and hemoptysis (53). In
one series, 5 of 1 8 patients (28%) had a pleural effusion
whereas 7 (39%) had a parenchymal infiltrate
(53) . The pleural Buid was described in one case, and it
was exudative with a pleural Buid protein of 4.7 g/dL
(serum 7. 1 g/dL) and a pleural Buid LDH level of
1 ,308 U/L (serum 302 U/L) (54) . Pathologic examination
of the areas of infiltrate reveal hemorrhagic
infarctions. The pathogenesis of the infiltrates and the
effusion is probably ischemia from the lack of perfusion
of the lung drained by the occluded vein. The
perfusion lung scan shows decreased perfusion to the
areas drained by the stenotic vein. Treatment is stenting
or balloon angioplasty of the stenotic vein (5 5 ) .
F O N TA N P R O C E D U R E
With the Fontan procedure, the right ventricle is
bypassed by an anastomosis between the superior vena
cava and the inferior vena cava and, the right atrium,
or the pulmonary artery (56) . The procedure is typically
performed for tricuspid atresia or univentricular
heart. Pleural effusion is a significant problem after
the Fontan procedure. Persistent pleural drainage is
the primary cause of prolonged postoperative hospital
stay in patients who have had a Fontan procedure (57) Zellers et al. (58) analyzed pleural fluid formation
after this procedure on 46 patients. They reported
that the median amount of pleural drainage was
3 ,220 mL, with a range of 1 5 5 to 3 1 ,000 mL. Most
patients had pleural drainage from both sides. Gupta
et al. (59) reviewed the pleural fluid drainage in 1 00
consecutive patients who underwent the Fontan operation
and reported that the median duration of chest
tube drainage was 1 0 days and the median volume
of drainage was 1 4 . 7 ml/kg/day.
The pathogenesis of the formation of the large
amounts of pleural fluid postoperatively in these
patients is not definitely known. It is probably related
to the increased systemic venous pressure. It is unclear,
however, whether increased pleural fluid transudation
from the parietal pleura, lymphatic leakage into the
pleural space (60) , or hormonal changes are responsible
for the large accumulations of pleural fluid. Spicer
et al. (6 1 ) analyzed the factors that were related to
the development of pleural effusions after the Fontan
procedure in 71 children. They found that patients
with significant aortopulmonary collateral vessels
evidenced by angiographic opacification of the pulmonary
arteries or veins had more prolonged pleural
drainage. They believed that the aortopulmonary collateral
vessels contributed to volume loading of the
systemic ventricle and to elevation of the pulmonary
artery, and right atrial and caval pressures, all of which
increase the rate of formation of the pleural fluid.
When 1 3 patients were subjected to preoperative
embolization of these vessels, the median duration of
the effusion postoperatively was only 6 . 5 days (6 1 ) .
Gupta e t al. (59) performed a multivariate analysis
for significant risk factors for pleural effusions lasting
more than 2 weeks or more than 20 mL/kg/ day
in 1 00 children undergoing the Fontan procedure.
They found that a lower preoperative oxygen saturation,
a smaller conduit size, and a longer duration of
cardiopulmonary bypass were associated with the longer
and larger amounts of fluid drainage. The authors
were unable to demonstrate a relationship between
the presence of aortopulmonary collateral vessels and
the amount of pleural fluid drainage (59) . Yun et
al. (62) studied 85 patients undergoing the Fontan
procedure and reported that prolonged pleural drainage
was associated with a low pulmonary vascular
compliance and cardiopulmonary bypass time. The
Fontan procedure is also performed in adults and persistent
pleural effusion is a problem in adults as it is
in children. Burkhart et al. (62a) reported that 36 of
1 2 1 adults who underwent the Fontan procedure had
pleural effusions that persisted more than 2 weeks.
It appears that creation of a fenestration at the
time of surgery will reduce the amount of pleural
fluid drainage. Lemler et al. (63) randomly assigned
49 patients to receive or not receive a fenestration
at the time of the Fontan procedure. The fenestration
consisted of a single 3- to 6-mm communication
between the Fontan channel and the pulmonary
venous atrium (63) . Performance of the fenestration
was associated with a reduction in the median
chest tube drainage from 4 , 5 8 8 to 1 ,734 mL and
a decreased hospital stay from 23 to 1 2 days (63) .
The disadvantage to the creation of a fenestration
is that it creates a right-to-left shunt which can lead
to increased hypoxemia (63) . Not all studies have
found that fenestration is associated with decreased
amounts of pleural fluid drainage. In a study in which
the patients were not randomized, Atik et al. reported
that pleural drainage was less in patients who did not
receive fenestration (64) .
It has been hypothesized that alterations in the
hormones that regulate fluid and electrolyte homeostasis
may also play a role (65) . Indeed in one study,
patients who developed effusions following surgery
had an elevated serum renin and angiotensin compared
with those who did not (65) . In one study,
patients who were given enalapril 5 ,ug/kg intravenously
within 1 hour of surgery and every 1 2 hours
thereafter until they were able to tolerate enteral feeding
had significantly less total pleural fluid drainage
( 1 0.6 mL/kg) than did patients who did not receive
enalapril ( 1 9.6 mL/kg) (66) . However, the administration
of captopril had no effect on pleural fluid
formation in a subsequent study (57) .
The pleural fluid with the Fontan procedure is an
exudate in almost every case (67) . In one series of 1 5
patients, the mean pleural fluid LDH was 1 , 575 IU/L
suggesting a very inflammatory state (67) . The pleural
fluid triglycerides were elevated in 4 of the 1 5 patients
indicating that these patients had chylothoraces (67) .
The optimal treatment for the patient who has
prolonged pleural drainage after a Fontan procedure
remains to be determined. The intrapleural administration
of tetracycline at the end of the surgical procedure
had no effect on the amount or the duration
of the fluid drainage (58). One study by Cava et al.
demonstrated that the duration of pleural drainage
was shorter and the total volume was less when the
patients postoperatively were placed on a regimen
consisting of diuretics (hydrochlorothiazide and spironolactone)
, fluid restriction, captopril, a low-fat
diet, and a minimum of 0.5 L of supplemental oxygen
by nasal cannula than when they were not placed on such a protocol (68). In patients who have markedly
prolonged pleural fluid drainage, consideration
should be given to the implantation of a pleuroperitoneal
shunt (69), the insertion of an indwelling catheter
such as the Pleurx Pleural Catheter (Care Fusion,
San Diego, California) or an attempt at pleurodesis
with a sclerosing agent such as doxycycline (70) .
Some patients have been managed successfully with
medium-chain triglycerides or with pleurectomy
and ligation of the thoracic duct (60) . Caverly and
coworkers administered octreotide to 1 0 patients
with persistent effusions after the Fontan procedure
and reported resolution of the effusion with octreotide
in 6 of the patients (7 1 ) .