etiology and pleural fluid characteristics of large and massive effusions

8/11/2019 Etiology and Pleural Fluid Characteristics of Large and Massive Effusions

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Etiology and Pleural Fluid Characteristics of

Large and Massive Effusions*FREE TO

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Chest. 2003;124(3):978-983. doi:10.1378/chest.124.3.978

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AbstractAbstract |Materials and Methods|Results|Discussion|References

Study objective:To report the etiology of large and massive pleural effusions, and to comparetheir biochemical fluid characteristics with those of smaller size, and between malignant andnonmalignant conditions.

Design:Retrospective chart review of all patients undergoing thoracentesis at an academicmedical center in Lleida, Spain, during a 10-year period.

Patients:Posteroanterior chest radiographs were available in 766 patients during the studyperiod. Large pleural effusions (ie, two thirds or more of the hemithorax without its completeobliteration) were identified in 70 patients (9%), and massive pleural effusions (ie, hemithoraxwas completely opacified) were identified in 93 patients (12%).

Results:A similar etiologic spectrum between large and massive pleural effusions was observed.The most frequent cause of these pleural effusions was malignancy (89 patients; 55%), followedby complicated parapneumonic or empyema (36 patients; 22%), and tuberculosis (19 patients;

12%). Compared with nonmalignant pleural effusions, patients with large or massive malignantpleural effusions were more likely to have pleural fluids with higher RBC counts (18.0 109cells/L vs 2.7 109cells/L, respectively; p < 0.001) and lower adenosine deaminase (ADA)activity (11.5 vs 31.5 U/L, respectively; p < 0.001), which were the two parameters that wereselected by a stepwise logistic-regression model as independent predictors of malignancy. Inaddition, large/massive malignant pleural effusions showed higher median RBC counts (18.0 109cells/L vs 4.3 109cells/L, respectively; p < 0.001), higher lactate dehydrogenase levels(641 vs 409 U/L, respectively; p = 0.001), lower pH (7.39 vs 7.42, respectively; p = 0.006)content, but similar cytologic yield (63% vs 53%, respectively; p = 0.171) than smaller malignantpleural effusions.Conclusions:The presence of a large or massive pleural effusion enables the clinician to narrowthe differential diagnosis of pleurisy, since most effusions are secondary to malignancy or

infections (either bacterial or mycobacterial). Bloody pleural fluid with low ADA content favors amalignant condition.When a pleural effusion is diagnosed in a patient, the need for a timely and systematicevaluation is indicated. The list of etiologies of pleural effusions is extensive, althoughsometimes they can be inferred from the clinical circumstances. Ascertaining the amount ofpleural fluid, as documented by chest radiograph, can be helpful in arriving at a presumptivecause of the pleural effusion. Thus, there is a general agreement that malignancy is the mostcommon cause of pleural effusions occupying the entire hemithorax.1Surprisingly, we have
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identified only two series, one in the English language literature2and the other in the Spanishlanguage literature,3that support this notion (from a MEDLINE search conducted among articlesfrom 1966 to 2002, with the subject heading massive pleural effusion). In addition, the leadingetiology of nonmalignant massive pleural effusions is in dispute.,23In the present study, weintended to evaluate the etiologic spectrum of large and massive pleural effusions in a serieslarger than those previously reported, as well as to compare the biochemical characteristics of

pleural fluid among pleural effusions of different sizes. We next attempted to determine whatfactors from the pleural fluid analysis were predictive of malignancy in patients with large ormassive pleural effusions.

Materials and MethodsAbstract|Materials and Methods |Results|Discussion|References

We reviewed the medical charts of all patients who had undergone a diagnostic thoracentesis atthe University Hospital Arnau de Vilanova (Lleida, Spain) from June 1992 to June 2002. Clinical,radiologic, and pleural fluid data were recorded. The size of the effusion was assessed on theposteroanterior radiograph by visually estimating the area of the hemithorax occupied by pleuralfluid. Pleural effusions were deemed to be nonlarge(ie, slight or of moderate size) if theyoccupied less than two thirds of the hemithorax, largeif they affected two thirds or more of the

hemithorax without reaching its complete length, and massiveif they opacified the entirehemithorax. Only the measurement of the predominant side was considered in patients withbilateral effusions. We examined the following pleural fluid analytes: RBC count; leukocytecount; percentage of neutrophils and lymphocytes; glucose level; protein level; lactatedehydrogenase (LDH) level; adenosine deaminase (ADA) level; pH; fluid/serum protein ratio;and fluid/serum LDH ratio.The causes of pleural effusions were determined by well-established clinical criteria.Specifically, the criteria for pleural effusions of tube cultures of pleural fluid, sputum, or pleural biopsy specimens; (2) thepresence of a granuloma in a pleural biopsy specimen after excluding other causes ofgranulomatous pleuritis; or (3) an exudative lymphocytic effusion with an ADA level of > 40 U/L,along with a positive tuberculin skin test result and the exclusion of any other potential causes of

pleurisy. A pleural effusion was categorized asmalignantif pleural fluid cytology or pleural biopsyfindings were positive for malignancy (ie, true malignant), or if the patient had a known cancerwith no other explanation for the effusion (ie,paramalignant). The term complicated parapneumoniceffusions(PPEs) referred to those non-purulent-appearing effusions that did not resolve withoutchest tube drainage, whereas empyemadescribed the presence of pus within the pleural space.The terms transudateor exudatewere based on the cause of the effusion rather than on thecriteria of Light et al.4Thus, the category transudatesencompasses those effusions that wereclearly due to congestive heart failure, cirrhosis, or nephrosis. Exudative effusions notassociated with neoplasm, tuberculosis, or pneumonia were classified as other exudates.Statistical Analysis

Results are reported as medians (quartiles). Comparisons between groups used the 2andFisher exact tests for categoric variables, and the nonparametric Kruskal-Wallis and Mann-Whitney tests were used for continuous variables. The area under the receiver operating

characteristic curve accurately compared the discriminative properties of pleural fluid analytes.Demographic and pleural fluid data that distinguished malignant from nonmalignantlarge/massive effusions in the bivariate analysis, were entered into a stepwise logisticregression model in order to identify independent predictors of malignancy. All statisticalcomparisons were two-sided and were carried out at the 0.05 significance level. Data wereanalyzed with a statistical software package (SPSS, version 10.0; SPSS, Inc; Chicago, IL).

ResultsAbstract|Materials and Methods|Results |Discussion|References
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Of the 1,051 patients who were evaluated during the study period, 285 were excluded from thestudy because either the radiologic data were unavailable or only an anteroposterior radiographobtained with the patients in the supine position was performed. In the remaining 766 patients, aposteroanterior upright chest radiograph was obtained for review. Among this study group, 231patients had malignant effusions, 150 patients had PPEs (uncomplicated effusion, 52 patients;complicated pleural effusion or empyema, 98 patients), 113 patients had tuberculous effusions,

114 patients had transudative pleural effusions, and 158 patients had other exudative pleuraleffusions.Seventy patients (9%) exhibited large pleural effusions, and 93 patients (12%) exhibitedmassive pleural effusions. Most of these pleural effusions were unilateral (159 of 163 pleuraleffusions; 98%). There were 100 men and 63 women, with a median age of 64 years (quartiles,48 to 75 years). Their underlying diseases are shown inTable 1. Somewhat more than a half oflarge or massive pleural effusions (89 of 163 pleural effusions; 55%) were related tomalignancies. The group of patients with large/massive malignant pleural effusions as a wholeencompassed 58 patients with true malignant effusions and 31 with paramalignant effusions.The following primary tumors were found: lung, 28 tumors; breast, 19 tumors; unknown, 10tumors; gynecologic, 7 tumors; hematologic, 7 tumors; GI, 5 tumors; and miscellaneous, 13tumors (mesothelioma, 4 tumors; head and neck, 4 tumors; kidney, 2 tumors; sarcoma, 1 tumor;

thymoma, 1 tumor; and melanoma, 1 tumor). The second most common cause of large andmassive effusions was PPEs, representing a fifth of the total number of etiologies (36 of 163patients; 22%) and nearly half of nonmalignant etiologies (36 of 74 patients; 49%). Of note, allpatients in this subgroup had complicated PPEs or empyema, whereas none of the 52uncomplicated PPEs extended to two thirds or more of the hemithorax. The third most commoncause was tuberculous pleurisy (19 of 163 patients; 12%), and a variety of miscellaneouscauses completed the list, of which hepatic hydrothorax deserves mention.Overall, 38% of malignant effusions (89 of 231), 37% of complicated PPEs and empyema (36 of98), 27% of hepatic hydrothoraces (4 of 15), and 17% of tuberculous effusions (19 of 113)affected two thirds or more of the hemithorax. These percentages changed to 27%, 23%, 7%,and 8%, respectively, if only a subgroup analysis of massive effusions was considered.Congestive heart failure (2 of 87 patients; 2%) among others, also may cause this condition.

There were significant differences between the groups of patients with large/massive andnonlarge effusions regarding the following pleural fluid parameters: RBC count; pH; glucoselevel; LDH level; pleural fluid/serum protein ratio; and pleural fluid/serum LDH ratio (Table 2).When the 89 patients having large or massive malignant effusions were compared to theremaining 142 patients in the malignant effusion population, the former had fluids with highermedian levels of RBCs (18.0 109cells/L vs 4.3 109cells/L, respectively; p < 0.001), highermedial levels of LDH (641 U/L vs 409 U/L, respectively; p = 0.001), and lower pH (7.39 vs 7.42,respectively; p = 0.006), yet only the subgroup with massive effusions differed in terms ofglucose fluid concentrations (5.55 mmol/L vs 6.27 mmol/L, respectively; p = 0.006). Similarresults were obtained when only true malignant patients were considered for comparisons.However, the sensitivity of cytologic examination did not differ between the large/massive andnonlarge malignant pleural effusion groups (56 of 89 patients [63%] vs 74 of 140 patients [53%];

p = 0.171).On the other hand, the 36 patients with large or massive PPEs showed higher median leukocytecounts (13.38 109cells/L vs 2.72 109cells/L, respectively; p = 0.001), higher median LDHlevels (2,438 U/L vs 996 U/L, respectively; p = 0.002), lower pH (6.97 vs 7.34, respectively; p

etiology and pleural fluid characteristics of large and massive effusions

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