Diagnostik

• Klinik
• Bildgebung: Sonographie, Röntgen-Thorax, CT
• Pleurapunktion: Untersuchung des Punktates auf Eiweiss, LDH, Bakterien, Zytologie
• ggf. Vidio-Thorakoskopie mit makroskopischer Beurteilung, gezielter Biopsie

Körperliche Untersuchung

• Inspektion: Nachschleppen der betroffenen Thoraxhälfte,, ev. Vorwölbung der Interkostalräume
• Stimmfremitus: über grossen Ergüssen aufgehoben
• Perkussion: ab Ergussmenge von 300 ml: absolute Dämpfung, nach lateral ansteigend (Ellis-Damoiseau-Linie)
• Auskultation: abgeschwächtes bis aufgehobenes Atemgeräusch, oberhalb des Ergusses streifenförmige Zone des Bronchialatems (durch Kompression)

Bildgebung

Sonographie: Nachweis ab 50 ml

Röntgen: Nachweis ab 300 ml im Stehen, im Sitzen ab 100 ml: homogene Verschattung, zuerst in den Sinus phrenicocostales (Abflachung der Zwerchfellkuppeln), bei grösseren Ergüssen lateral ansteigende Begrenzung

Weitere Diagnostik

Exsudat vs. Transsudat:

Entität	Transsudat	Exsudat
Spezifisches Gewicht	< 1,016 g/l	> 1,016 g/l
Gesamteiweiß	< 30 g/l	> 30 g/l
Eiweiss Punktat / Serum	< 0,5	> 0, 5
LDH	< 200 U/l	> 200 U/l
LDH Punktat / Serum	< 0,6	> 0, 6

Determining the cause of a pleural effusion is greatly facilitated by the ability to analyze the pleural fluid. Thoracentesis, a simple bedside procedure, permits fluid to be rapidly sampled, visualized, examined microscopically, and quantified. An approach to pleural fluid analysis will be presented here. Pleural imaging, the technique of thoracentesis, and an approach to undiagnosed pleural effusions are discussed separately. (See "Imaging of pleural effusions", see "Diagnostic thoracentesis" and see "The undiagnosed pleural effusion").

A systematic approach to analysis of the fluid in conjunction with the clinical presentation should allow the clinician to diagnose the cause of an effusion in about 75 percent of patients at the first encounter []. A definitive diagnosis, provided by the finding of malignant cells or specific organisms in the pleural fluid, can be established in approximately 25 percent of patients. However, a presumptive diagnosis, based on the pre-thoracentesis clinical impression, can be substantiated by pleural fluid analysis in an additional 50 percent of patients. Even with a nondiagnostic thoracentesis, pleural fluid analysis can be useful in excluding other possible causes, such as infection. Thus, clinical decision-making information can be gained from pleural fluid analysis in over 90 percent of patients [].

INDICATIONS — The indication for diagnostic thoracentesis is the new finding of a pleural effusion. Observation, in lieu of diagnostic thoracentesis, may be warranted in uncomplicated congestive heart failure and viral pleurisy. In the former setting, the clinical diagnosis is usually secure; in the latter, there is typically a small amount of fluid. However, if the clinical situation is atypical or does not progress as anticipated, thoracentesis should be performed [].

Definitive diagnoses — Only a select number of diagnoses can be established definitively by thoracentesis. These include malignancy, empyema, tuberculous pleurisy, fungal infection of the pleural space, lupus pleuritis, chylothorax, urinothorax, esophageal rupture, hemothorax, peritoneal dialysis, and extravascular migration of a central venous catheter (show table 1) [].

OBSERVATION OF THE ASPIRATE — Initial diagnostic clues can be obtained by gross inspection of pleural fluid as it is being aspirated from the patient's chest []. Observations that are helpful for diagnosis are listed (show table 2).

SEPARATION OF TRANSUDATES AND EXUDATES — The pleural fluid is next characterized as either a transudate or an exudate.

Transudates — Transudates are largely due to imbalances in hydrostatic and oncotic pressures in the chest. However, they can also result from movement of fluid from the peritoneal or retroperitoneal spaces, or from iatrogenic causes, such as crystalloid infusion into a central venous catheter that has migrated []. Nevertheless, transudates have a limited number of diagnostic possibilities that can usually be discerned from the patient's clinical presentation (show table 3).

Exudates — In contrast, exudative effusions present more of a diagnostic dilemma. Disease in virtually any organ can cause exudative pleural effusions by a variety of mechanisms, including infection, malignancy, immunologic responses, lymphatic abnormalities, noninfectious inflammation, iatrogenic causes, and movement of fluid from below the diaphragm (show table 4) [].

Exudates result primarily from pleural and lung inflammation (resulting in a capillary protein leak) or from impaired lymphatic drainage of the pleural space (resulting in decreased removal of protein from the pleural space) []. Exudates can also result from movement of fluid from the peritoneal space, as seen with acute or chronic pancreatitis, chylous ascites, and peritoneal carcinomatosis. (See "Mechanisms of pleural liquid accumulation in disease").

Diagnostic criteria — The most practical method of separating transudates and exudates is measurement of serum and pleural fluid protein and LDH. If at least one of the following three criteria is present, the fluid is virtually always an exudate; if none is present, the fluid is virtually always a transudate []:

Pleural fluid protein/serum protein ratio greater than 0.5.

Pleural fluid LDH/serum LDH ratio greater than 0.6.

Pleural fluid LDH greater than two thirds the upper limits of normal of the serum LDH.

A meta-analysis involving 1448 patients in eight studies used receiver operating characteristic (ROC) analysis, and found that three tests on a single pleural fluid sample could each discriminate as well between transudates and exudates as using paired and triplet combinations []. An exudate in this study was best determined by any one of the following:

Pleural fluid protein >2.9 g/dL (29 g/L)

Pleural fluid cholesterol >45 mg/dL (1.16 mmol/L)

Pleural fluid LDH >60 percent of upper limits of normal serum value

CHEMICAL ANALYSIS — The measurement of pleural fluid protein and LDH, glucose, pH, and amylase can provide useful information.

Pleural fluid protein and LDH — Most transudates have absolute total protein concentrations below 3.0 g/dL; however, acute diuresis in congestive heart failure can elevate protein levels into the exudative range [6-8]. Several specific disease associations have been noted with pleural fluid protein and LDH levels:

Tuberculous pleural effusions virtually always have total protein concentrations above 4.0 g/dL [].

When pleural fluid protein concentrations are in the 7.0 to 8.0 g/dL range, Waldenstrom's macroglobulinemia and multiple myeloma should be considered [9,10].

Pleural fluid LDH levels above 1000 IU/L (with upper limit of normal for serum of 200 IU/L) are characteristically found in empyema [], rheumatoid pleurisy [], and pleural paragonimiasis [], and are sometimes observed with malignancy.

Pleural fluid secondary to Pneumocystis carinii pneumonia has the characteristic finding of a pleural fluid/serum LDH ratio greater than 1.0 and a pleural fluid/serum protein ratio of less than 0.5 [].

Pleural fluid glucose — A low pleural fluid glucose concentration (less than 60 mg/dL (3.33 mmol/liter), or a pleural fluid/serum glucose ratio less than 0.5) narrows the differential diagnosis of the exudate to the following possibilities []:

Rheumatoid pleurisy

Complicated parapneumonic effusion or empyema

Malignant effusion

Tuberculous pleurisy

Lupus pleuritis

Esophageal rupture

All transudates and all other exudates have pleural fluid glucose concentration similar to that of blood glucose.

The mechanism responsible for a low pleural fluid glucose depends upon the underlying disease. Specific examples include:

Decreased transport of glucose from blood to pleural fluid with rheumatoid pleurisy [16,17] or malignancy [].

Increased utilization of glucose by constituents of pleural fluid, such as neutrophils, bacteria (empyema), and malignant cells [].

The lowest glucose concentrations are found in rheumatoid pleurisy and empyema, with glucose being undetectable in some cases. In comparison, when the glucose concentration is low in tuberculous pleurisy, lupus pleuritis, and malignancy, it usually falls into the range of 30 to 50 mg/dL (1.66 to 2.78 mmol/liter) [].

Pleural fluid pH — Pleural fluid pH should always be measured in a blood gas machine rather than with a pH meter or pH indicator paper, as the latter will result in inaccurate measurements []. A pleural fluid pH below 7.30 with a normal arterial blood pH is found with the same diagnoses associated with low pleural fluid glucose concentrations []. The pH of normal pleural fluid is approximately 7.60, due to a bicarbonate gradient between pleural fluid and blood []. Thus, a pH below 7.30 represents a substantial accumulation of hydrogen ions. Transudates generally have a pleural fluid pH in the 7.40 to 7.55 range, while the majority of exudates range from 7.30 to 7.45 [].

The mechanisms responsible for pleural fluid acidosis (pH <7.30) include;

Increased acid production by pleural fluid cells and bacteria (empyema) [19,23].

Decreased hydrogen ion efflux from the pleural space, due to pleuritis, tumor, or pleural fibrosis. Specific examples include malignancy [], rheumatoid pleurisy [16,17], and tuberculous pleurisy.

A low pleural fluid pH has diagnostic, prognostic, and therapeutic implications for patients with parapneumonic and malignant effusions []. Patients with a low pleural fluid pH malignant effusion have a high initial positive yield on pleural fluid cytology and tend to have a shorter survival and poorer response to chemical pleurodesis than those with a pH >7.30, although the strength of these associations has been questioned [25-27].

Clinicians should not use the pleural fluid pH as the sole criterion for the decision to recommend pleurodesis. A parapneumonic effusion with a low pleural fluid pH indicates a high likelihood of necessity for pleural space drainage (show figure 1). (See "Pathogenesis and management of parapneumonic effusions and empyema").

Pleural fluid amylase — The finding of an amylase-rich pleural effusion, defined as either a pleural fluid amylase greater than the upper limits of normal for serum amylase or a pleural fluid to serum amylase ratio greater than 1.0, narrows the differential diagnosis of an exudative effusion to the following major possibilities []:

Acute pancreatitis

Chronic pancreatic pleural effusion

Esophageal rupture

Malignancy

Other rare causes of an amylase-rich pleural effusion include pneumonia, ruptured ectopic pregnancy, hydronephrosis, and cirrhosis []. Pancreatic disease is associated with pancreatic isoenzymes, while malignancy and esophageal rupture are characterized by a predominance of salivary isoenzymes [].

PLEURAL FLUID NUCLEATED CELLS — The total pleural fluid nucleated cell count is virtually never diagnostic. There are, however, some settings in which the count may be helpful:

Counts above 50,000/µL are usually found only in complicated parapneumonic effusions, including empyema.

Exudative effusions from bacterial pneumonia, acute pancreatitis, and lupus pleuritis usually have total nucleated cell counts above 10,000/µL [2,29].

Chronic exudates, typified by tuberculous pleurisy and malignancy, typically have nucleated cell counts below 5000/µL [2,29].

The timing of thoracentesis in relation to the acute pleural injury determines the predominant cell type. The early cellular response to pleural injury is neutrophilic. As the time from the acute insult lengthens, the effusion develops a mononuclear predominance if the pleural injury is not ongoing [].

Pleural fluid lymphocytosis — Pleural fluid lymphocytosis, particularly with lymphocyte counts representing 85 to 95 percent of the total nucleated cells, suggests tuberculous pleurisy, lymphoma, sarcoidosis, chronic rheumatoid pleurisy, yellow nail syndrome, or chylothorax however, the percentage of lymphocytes is usually between 50 and 70 percent [. (See "Diagnosis and management of tuberculous pleural effusions in non-HIV infected patients", and see "Diagnosis and management of chylothorax and chyliform effusions").

Pleural fluid eosinophilia — Pleural fluid eosinophilia (defined by pleural fluid eosinophils representing more than 10 percent of the total nucleated cells) usually suggests a benign, self-limited disease, and is commonly associated with air or blood in the pleural space [31,32]. However, two studies have noted that malignancy is as prevalent in eosinophilic as noneosinophilic pleural effusions [33,34]. The differential diagnosis of pleural fluid eosinophilia includes [31,32]:

Pneumothorax

Hemothorax

Pulmonary infarction

Benign asbestos pleural effusion

Parasitic disease

Fungal infection (coccidioidomycosis, cryptococcosis, histoplasmosis)

Drugs

Malignancy (carcinoma, lymphoma)

Pleural fluid eosinophilia appears to be rare with tuberculous pleurisy on the initial thoracentesis [31,32]. (See "Pleural fluid eosinophilia").

Mesothelial cells — Mesothelial cells are found in small numbers in normal pleural fluid, are prominent in transudative pleural effusions, and are variable in exudative effusions. The major clinical significance of mesothelial cells in exudates is that tuberculosis is unlikely if there are more than five percent mesothelial cells [30,32,35,36].