H. Pleural
Effusion
Introduction
Normally, very small amounts of pleural fluid are
present in the pleural spaces, and fluid is not detectable by routine
methods. When certain disorders occur, excessive pleural fluid may
accumulate and cause pulmonary signs and symptoms. Simply put, pleural
effusions occur when the rate of fluid formation exceeds that of fluid
absorption. Once a symptomatic, unexplained pleural effusion occurs, a
diagnosis needs to be established.
Signs and Symptoms
Pleuritic chest pain, chest pressure, dyspnea, and
cough are the most common symptoms of pleural effusion. Pain may occur with
little fluid formation as the symptom is related to the intense inflammation
of the pleural surfaces. Chest pressure usually does not occur until the
effusion is in the moderate (500-1500 ml) to large (>1500 ml) category.
Dyspnea rarely occurs with small effusions unless significant pleurisy is
present and often the patient will not complain of dyspnea until the
effusion is massive with contralateral mediastinal shift on the chest x-ray.
Cough is usually related to the associated atelectasis, which to some degree
accompanies all pleural effusions. Classic physical findings associated with
pleural effusions may occur when the volume begins to exceed 500 ml and
include diminished breath sounds, dullness to percussion, reduced tactile
and vocal fremitus, and occasionally a pleural friction rub. In contrast to
pneumonia and atelectasis, crackles are not heard with an isolated pleural
effusion.
Noninvasive Diagnostic Techniques
When the presence of a pleural effusion is
suspected by physical examination, confirmation with a chest x-ray is
necessary. With some pleural effusions, especially when subpulmonic in
location (layering below the lung but above the hemidiaphragm), a lateral
decubitus film usually confirms the presence of fluid. Pleural space
ultrasound is extremely helpful to locate small amounts or isolated
loculated pockets of fluid. Thoracentesis can be performed simultaneously
using ultrasound guidance. Chest CT is most helpful to distinguish between
parenchymal and pleural disease and may demonstrate pleural thickening,
pleural calcification, a pleural based mass, or loculated collections of
fluid.
Thoracentesis and Pleural Fluid Analysis
To establish the etiology, a
thoracentesis usually needs to be performed. Fifty to 100 ml
of fluid are usually removed and sent for analysis (See
Table 14).
Not every effusion needs to be tapped, but when the patient has no obvious
clinical cause for the effusion, is febrile, or has pulmonary compromise,
fluid should be removed. The first step is to determine if the fluid is a
transudate or an exudate. Transudative effusions occur when systemic factors
that influence the formation and absorption of pleural fluid are altered
(e.g., low serum proteins and increased pulmonary venous pressure).
Exudative effusions occur when local factors that influence the formation
and absorption of fluid are altered (e.g., infection and malignancy). The
lactate dehydrogenase (LDH), protein levels or specific gravity of the fluid
can distinguish these two. Most agree that exudates must meet one or more of
the following criteria, whereas transudates meet none:
- Pleural fluid/serum protein > 0.5 or absolute
value > 3 g/dl.
- Pleural fluid/serum LDH > 0.6 or absolute value
> 0.45 upper normal serum limit
- Pleural fluid specific gravity > 1.018
Once an effusion is categorized as transudative or
exudative, etiologic considerations narrow. Additional pleural fluid studies
that help to establish a diagnosis include glucose, amylase, white blood
cell counts with differential, and cytologic and microbiologic examination.
Etiology of Pleural Effusions
Transudates: The
causes of transudative pleural effusions are listed in
Table 15.
Congestive Heart Failure:
This is the most common cause of pleural effusion. Frequently the effusions
are bilateral (approximately 75% of the time) but may occur alone on either
side with the right side being more common. Fluid is usually straw colored,
with low white blood cell counts (<500 cells/mm3) and a mononuclear cell
predominance. With severe congestive heart failure, fluid may persist in
spite of vigorous diuresis.
Cirrhosis, Nephrotic Syndrome, and Hepatic
Hydrothorax:
In disorders associated with low serum proteins and ascites, bilateral
effusions are common. Cell counts are low and lymphocytes predominate.
Glucose remains normal (>60 mg/dl). Hepatic hydrothorax occurs in about 5%
of patients with ascites and cirrhosis. The effusion occurs (usually on the
right side) because of direct movement of peritoneal fluid through
communications in the hemidiaphragm.
Exudates: The causes of exudative
pleural effusions are listed in
Table 16.
The most common causes of exudative pleural effusions are parapneumonic
(associated with pneumonia), malignancy, pulmonary embolism, trauma
(including hemothorax and esophageal perforation), collagen vascular disease
(especially rheumatoid arthritis), post-cardiac injury (including surgery),
tuberculosis, trapped lung, and atelectasis. The characteristics of pleural
fluids are listed in
Table 17.
Parapneumonic Effusion:
Bacterial pneumonias are frequently associated with pleural effusions (as
often as 50 % of the time) and when they become complicated, require
drainage. Complicated parapneumonic effusions include empyema (the finding
of gross pus in the pleural space), those with positive pleural fluid
cultures or Gram stains, and those in which the microbiology is negative but
the patient continues to show signs of infection with fever, severe
pleuritic pain and leukocytosis. In this last category the pleural fluid
usually shows high white blood cell counts with polymorphonuclear
predominance, glucose <30 mg/dl, and high LDH (>500 units/dl). Complicated
parapneumonic effusions require drainage by tube thoracoscopy. The patient
who has pneumonia with a small amount of pleural fluid present and is
clinically responding to antibiotic therapy (now afebrile, no pleuritic
pain, normal white blood cell count) does not require thoracentesis. By
contrast, rapid accumulation of pleural fluid in a patient with pneumonia is
an indication for immediate thoracentesis.
Malignant Effusions: Malignancy is the second most
common cause of exudative pleural effusions with lung (36%), breast (25%)
and lymphoma (10%) being the most frequent causes. Typical pleural fluid
characteristics include a mononuclear predominant exudate (average 2500
cells/mm3), with an average red blood cell count of 40,000 cells/mm3, normal
glucose (>60mg/dl) and positive cytology. At the time of diagnosis one-third
of patients have a low pleural fluid glucose (<60mg/dl), which is associated
with more extensive disease and a poorer prognosis.
Effusion Secondary to Pulmonary Embolism: These
exudative effusions are usually bloody, and associated with pleurisy and
dyspnea. The effusion may increase in size the first 24-48 hours after
initial anticoagulation. Unless there is significant pulmonary compromise,
or the effusion continues to increase, these effusions can be observed.
There are reports of transudative effusions associated with pulmonary
embolism, but atelectasis secondary to splinting from pleurisy is a more
likely cause.
Tuberculous Effusion: Typically, this predominantly
lymphocytic exudate is devoid of mesothelial cells and may occur without any
obvious parenchymal involvement. The glucose may be low (<60 mg/dl) and
adenosine deaminase levels are usually elevated (>70 IU/l). Historically, in
the non-immunocompromised host, pleural fluid smears are rarely positive but
pleural fluid cultures are positive in 25%. In contrast, thoracoscopic
pleural biopsy and culture is positive more than 80% of the time. Initially
the tuberculin skin test (TST) may be negative but after a 6 to 8 week
observation time usually converts to positive. Although tuberculous pleurisy
that develops in the course of primary infection is a self-limited disease
that clears without treatment, in as many as 65% of these patients pulmonary
tuberculosis or disease elsewhere will develop within 5 years. If all tests,
including the TST, are negative but tuberculous pleurisy is suspected, a
repeat TST should be done and if positive the patient requires 6 months of
multidrug therapy.
Effusions Secondary to Collagen Vascular Disease:
Effusions secondary to rheumatoid arthritis are predominantly mononuclear
cell exudates, typically with very low glucose levels (<10mg/dl), high
titers of rheumatoid factor (>640) and a cloudy appearance (pseudochylous or
cholesterol effusions). They are usually moderate in size and unilateral. In
systemic lupus erythematosus effusions are usually small, bilateral and are
polymorphonuclear exudates. The finding of an ANA titer that exceeds that of
serum is diagnostic. Severe pleurisy is frequent.
Miscellaneous: Atelectasis is a common cause of
small to moderate effusions. Frequently they are seen postoperatively or
with prolonged bed rest and inactivity. There are no unique diagnostic
features and these effusions usually fit exudative criteria, have normal
glucose levels, and WBC counts of 1000 to 2000 cells/mm3 with mononuclear
cell predominance. Transudates may occur with atelectasis. Since this is a
diagnosis of exclusion, other causes of pleural effusions must be
eliminated. Esophageal rupture and pancreatitis produce polymorphonuclear-predominant
exudative effusions, with high amylase and normal or low glucose (< 30
mg/dl) values. Chylothorax occurs when the thoracic duct is disrupted and is
characterized by the presence of chylomicrons and triglyceride values of
>110 mg/dl in the pleural fluid. Lymphoma, trauma, and thoracic surgery are
the most common causes of chylothorax. Dressler’s syndrome may occur as a
complication of myocardial infarction or open-heart surgery; the resulting
pleural fluid demonstrates a polymorphonuclear-predominant exudate without
specific findings. With a trapped lung (one that cannot fully expand
secondary to a visceral pleural peel), exudative pleural fluid fills the
pleural space and the characteristics of the fluid depend on the etiology
(e.g., malignancy, post-parapneumonic, trauma).
Diagnostic Thoracoscopy and Pleural Biopsy
Thoracoscopy is an excellent technique to determine
the etiology of an undiagnosed exudative pleural effusion. The procedure is
superior to the old closed pleural biopsy techniques because of its higher
diagnostic yield. A rigid thoracoscope with a cold light source is used and
second point of entry is necessary to provide biopsy forceps access to the
pleural space. This technique continues to be most helpful in diagnosing
malignant effusions (including mesothelioma), tuberculosis, and trapped
lung.
When
to Refer
Depending on local medical practice, referral to
determine if thoracentesis is necessary and to perform the thoracentesis may
be most appropriate. Because some imaging techniques including ultrasound
and chest CT may be necessary to coordinate thoracentesis and chest tube
placement, referral to combine these efforts is indicated. In patients with
persistent and undiagnosed pleural effusions, or effusions in severely ill
patients with pneumonia, referral to facilitate prompt diagnostic and
therapeutic measures is recommended. This includes evaluation for
thoracoscopy, chest tube placement and pleurodesis.
Medicolegal Concerns
Most medicolegal issues involving pleural disease
are usually related to complications that occur in the following situations:
1) lack of appropriate follow-up (e.g., complicated parapneumonic effusion
resulting in fibrothorax), 2) system failure where physicians do not receive
critical data (e.g., a positive TB culture at 8 weeks), and 3) missed
diagnosis of a potentially life threatening event such as a pulmonary
embolism. ALWAYS, always follow up on pleural fluid cultures and cytologies.
Summary
Pleural effusions are associated with many systemic
disorders. Thoracentesis to determine if the pleural fluid is a transudate
or an exudate coupled with other appropriate diagnostic studies provides a
diagnosis most of the time. Because pleural fluid findings are often
nonspecific (except for positive cytology and bacteriology), clinical
correlation and response to therapy are critical. Not every pleural fluid
study needs to be ordered on every pleural effusion. Clinical judgement
remains the key |
