DIAGNOSTIC VALUE OF SERUM–EFFUSION ALBUMIN GRADIENT IN DIAGNOSING EXUDATIVE FROM TRANSUDATIVE PLEURAL EFFUSIONS
E. Razi MD, * GH. Mossavi MD**
Departments of
Internal Medicine*, and Hygiene**, Kashan University of
Medical Sciences, Kashan, Iran
Background-Differentiation of exudates from
transudates is the first step in the approach to a
patient with pleural effusion. The predictive value of
the relevant tests are a matter of debate.
Objective-To determine the diagnostic
value of serum-effusion albumin gradient to discriminate
effusions into exudate and transudate.
Methods-Eighty-nine effusion samples
taken from patients with pleural effusion who were
undergoing diagnostic or therapeutic thoracenthesis.
Based on their clinical diagnosis, they were classified
as either transdate or exudate. In a previous study, a
cutoff value of 1.2 g/dl was taken for serum-pleural
effusion albumin gradient to differentiate between
exudate and transudate. A serum-pleural effusion albumin
gradient of >1.2 g/dl was interpreted as transudate
while a gradient =1.2 g/dl was interpreted as exudate.
Results-Based on final clinical
diagnosis, of 89 pleural effusions, 47 were transudates,
and 42 were exudates. Based on serum-effusion albumin
gradient with a cut off value of 1.2 g/dl, 4 patients
with transudates, and three with exudates, were
misclassified, which gives an overall accuracy of 91.5% .
Conclusions-Determination of serum-effusion
albumin gradient is of great value for distinguishing
between transudative and exudative pleural effusions.
Keywords • Pleural fluid • albumin gradient • exudates • transudates
Introduction
Distinguishing an exudate from a transudate is the first step in the diagnostic approach of a patient with pleural effusions.1,2 Currently, the criteria proposed by Light et al.3 in 1972, is the standard method for this discrimination. However, in recent years, several reports indicated that these criteria misclassified a number of effusions, and that was why several parameters such as the pleural fluid cholesterol level and the pleural fluid
to serum cholesterol ratio,4,5 the pleural fluid to serum bilirubin concentration ratio,6 the alkaline phosphatase value,7 and pleural fluid to serum cholinestrase ratio,8 have been proposed in segregating the transudates from exudateds more reliably than those of Light’s criteria. Nevertheless, all these alternative parameters falsely classified some effusions, and their superiority with respect to the Light’s criteria is therefore insignificant if not dubious.
In 1990, Roth et al.9 assessed the diagnostic value of serum-pleural effusion albumin gradient and found that this gradient was significantly higher in patients with transudative than exudative pleural effusions. To identify exudative from transudative ascitic fluids, it is now well-accepted that a serum-ascitic fluid gradient of <1.1 g/dl can be interpreted as an exudate.10-12
To re-assess in our patient group, what was shown previously by Roth,9 we conducted a prospective study to determine the diagnostic value of the measured serum-pleural effusion albumin gradient to discriminate transudative from exudative pleural effusions.
Materials and Methods
During a one-year period, we prospectively studied all patients with pleural effusion who were referred to the Internal Medicine Wards of Shahid Beheshti Hospital, Tehran.
Only diagnostic thoracenteses were considered, and whenever more than one pleural effusion sample was taken, the data from the first one were used. All pleural fluid samples were tested for glucose, albumin, protein, lactate dehydrogenase (LDH), cholesterol, cell count, differential cell count, Gram stain and bacterial culture, acid-fast bacilli smear and culture, and cytology. A concomitant blood sample was taken and tested for the same biochemical parameters. Further investigations, such as pleural biopsy, were performed in patients in whom the etiology had not been decisive.
Pleural effusion samples were categorized according to the diagnoses of patients. The diagnosis of patients were made according to the following predetermined criteria:
Student t test for unpaired data were used to compare means of parameters measured in two patient groups with transudative and exudative pleural effusions.
Results
Eighty-nine patients with pleural effusion were evaluated. Table 1 shows the various causes of pleural effusion in the sample.
Based on the study of Roth et al,9 a cut-off value for serum-fluid albumin gradient of 1.2 g/dl was used in differentiating transudates from exudates. The mean of the serum-effusion albumin gradient was 1.94±0.67 g/dl for transudates, significantly higher (p<0.0001) than that of 0.690±0.39 g/dl observed in exudates. Using this cut-off value, 43 of 47 effusion (91.5%) were correctly classified. Using an albumin gradient >1.2 g/dl for transudate, four patients were misclassified; two had hypoalbuminemia with albumin gradients of 1.1, and 0.6 g/dl. Another two patients had congestive heart failure both with albumin gradients of 1.2 g/dl.
Discussion
By using the serum-effusion albumin gradient, we correctly classified 92% of pleural effusions. The initial step in determining the cause of a pleural effusion is to categorize effusion as transudate or exudate. The classic criteria given for differentiation of exudates from transudate was provided by Light, et al.1 However, several reports have shown that this criteria misclassified a large number of effusions, especially transudates.4-6, 13
Thereafter a number of alternative parameters have been proposed to improve the results of the classic criteria.These newely developed methods include the pleural fluid cholesterol level and the pleural fluid/serum cholesterol ratio.4,5,13-16
In addition to cholesterol, other parameters have been proposed for separating pleural transudates from exudates. In a study of 46 pleural effusions, Mesiel et al,6 evaluated the usefulness of the pleural fluid/serum bilirubin ratio. Using this criterion, 3 of 23 transudates and 6 of 23 exudates were misclassified, a finding not too different, and thus not superior to, that obtained with the classical Light’s ceriteria.3
Roth et al,9 in a series of 59 patients, used the serum-effusion albumin gradient for the classification of pleural effusions. With a cut-off value of 1.2 g/dl, all the transudates and 39 of the 41 exudates were classified correctly. However, other authors were not fortunate enough to attain such good results.17,18 In the study of Roth et al,9 the serum-effusion albumin gradient had a sensitivity and specificity of 87%, and 92%, respectivity. However, another study obtained a sensitivity of only 63% and a specificity of 81%.19
In the study of Burgess et al,20 the gradient had a sensitivity and specificity of 87%, and 92%, respectively. In the present study, this method resulted in a sensitivity of 91.5%, and a specificity of 92.86%.
Recently, for evaluation of pleural effusion, Light recommended that a decision be made on the serum-effusion albumin gradient when the patient’s pleural fluid meets the exudative criteria, but the patient appears classically to have a transudative effusion.21 Burgess et al,20 advocated that measurment of the gradient is useful when patients are receiving concurrent diuretic therapy.
Both albumin and the globulin fraction in the pleural fluid are believed to originate from the serum via diffusion22-24, However, some protein can form within the pleural space, such as LDH from pleural fluid leukocytes25.
In abnormal states, pleural fluid can be collected for a number of reasons which leads to either increased fluid formation, or decreased fluid absorption, or both. Causes for production of a transudative effusion usually occur in association with an intact microvascular endothelium, and thus, the gradient between serum and fluid protein is maintained.1,2
Etiologies for production of an exudative effusion, on the other hand, usually involve some type of inflammation that results in a compromised pulmonary or pleural micro-vasculture, which in turn, leads to an increased fluid leakage, a higher protein concentration, and hence, a lower albumin gradient.1,2
Regarding the good results obtained, we suggest the use of albumin gradient as an effective means of discriminating exudative from transudative pleural effusions. Since this method only relies on measurments of effusion and serum albumin concentrations, it can be very helpful when other measurements are not available.
Nevertheless, the results should be treated cautiously when the patient is suspected of having degrees of hypoalbuminemia. On account of the very high discrepancy among the results obtained by several researchers, further study is necessary to make a final decision on the efficacy of this method.
References