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The Usefulness of Pericardial Fluid* David G. Meyers, MD, FCCP; Thomas W. Prendergast, MD Diagnostic Tests on Rayma E. Meyers, BA; and Study objectives: To determine the physical, chemical, and cellular characteristics of pericardial fluid in various disease states and to assess their diagnostic accuracies. Setting: A metropolitan university hospital. Design: Consecutive case series. seventy-five hospital patients, aged 1 month to 87 years, who had undergone pericardiocentesis (n=165) or control subjects who had undergone open heart surgery (n=10) between 1984 and 1996. Measurements: The appearance of pericardial fluid and results of chemistry tests, cell counts, and microbial cultures were obtained by chart review. The cytologic studies, Gram's stain, etiology of each pericardial fluid sample was determined using prospective diagnostic criteria. Results: Exudates differed from transudates by higher leukocyte counts and ratios of fluid to serum lactate dehydrogenase levels. Fluid glucose levels were significantly less in exudates. Sensitivity for detecting exudates was high for specific gravity > 1.015 (90%), fluid total protein >3.0 g/dL (97%), fluid to serum protein ratio >0.5 (96%), fluid lactate dehydrogenase ratio >0.6 (94%), and fluid to serum glucose ratio <1.0 (85%). None of these indicators were specific. Fluid total protein and specific gravity were moderately correlated (r=0.56). Fluid cytologic study had a sensitivity of 92% and specificity of 100% for malignant effusion. No other test was diagnostic for a specific etiology. Among infection-associated effusions, culture-positive fluid had more neutrophils, higher lactate dehydrogenase levels, and lower ratios of fluid to serum glucose than culture-negative (parainfective) fluid. Conclusions: Evaluation of pericardial fluid might be limited to cell count, glucose, protein, and lactate dehydrogenase determinations plus bacterial culture and cytology. While not used routinely, other tests that may be highly specific for particular diseases should be ordered only to confirm a high clinical suspicion. (CHEST 1997; 111:1213-21) Patients: One hundred Key words: culture; cytology; diagnosis; glucose; lactate dehydrogenase; protein effusion is present in a variety of pathologic conditions. Often the etiology of the effusion is uncertain and cannot be clearly defined on the basis of clinical assessment or even autopsy. "P ericardial -¦- For editorial comment see page 1156 With few validated tests available, investigators have successfully made correct diagnoses based on peri¬ cardial fluid analysis in 24 to 93% of cases in reported series.1-2 The laboratory analysis of pleural fluid is well Departments of Internal Medicine (Cardiology [Dr. Meyers and Mr. Meyers]) and Surgery (Cardiothoracic [Dr. Kansas University Medical Center, Kansas City. Prendergast]), Manuscript received August 16, 1996; revision accepted Novem¬ ber 1, 1996. Dr. Meyers, Division of Cardiology, Kansas Reprint requests: Medical Center, 3901 Rainbow Blvd., Kansas City, KS University 66160-7378 *From the established. For instance, exudative pleural effusions have protein levels >3.0 g/dL, specific gravity > 1.015, a pleural fluid to serum protein ratio >0.5, and a pleural fluid to serum lactate dehydrogenase ratio >0.6.35 If the pleural fluid has none of these characteristics, it is a transudate. Grossly bloody fluid with an RBC count > 100,000/mm3 is suggestive of trauma, malignancy, or pulmonary embolism. Pleu¬ ral fluid leukocyte counts > 10,000/mm3 are most common with empyema, parapneumonic effusions, pancreatitis, pulmonary infarction, collagen vascular diseases, malignancy, and tuberculosis. Pleural fluid protein level >6.0 g/dL often indicates tuberculosis or parapneumonic effusion. An elevated fluid lactate dehydrogenase with normal fluid protein is most likely due to malignancy. Low pleural fluid glucose level (<60 to 80 mg/dL) may be due to parapneu¬ monic, rheumatoid, tuberculous, or malignant effu¬ sion. CHEST/111 /5/MAY, 1997 Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21747/ on 04/30/2017 1213 In contrast to the well-documented ability of tests identify the cause of pleural pleural effusion, to our knowledge there has been no com¬ parable systematic evaluation of diagnostic test use¬ fulness when applied to pericardial fluid. This report examines the diagnostic and discriminant power of several chemistry, cellular, and microbiological tests on pericardial fluid. on fluid to Materials and Methods The charts of patients admitted to Kansas University Medical Center who underwent pericardiocentesis between January 1, 1984 and January 30, 1992 were identified by a computer search of medical records for pericardiocentesis (International Classifi¬ 37.0). One hundred sixty-seven cases were identified. Two were excluded because no laboratory studies had been obtained. Each hospital discharge summary was reviewed for the cause of the pericardial effusion as originally determined by the patient's attending physician. An investigator (D.G.M.) then reviewed the entire hospital record to confirm the cause of the effusion using the following prospectively defined criteria: ma¬ lignant.a histologically confirmed diagnosis of any type of cancer, known to metastasize or extend to the pericardium, made within 1 year preceding the pericardiocentesis; bacterial.cul¬ ture-proved bacterial infection of blood, lung, or pericardium; viral.clinical presentation suggesting a \iral syndrome; radia¬ tion.prior mediastinal irradiation; uremic.current renal dialy¬ sis or serum creatine value >2.0 mg/dL; rheumatologic.Amer¬ ican Rheumatologic Association criteria6-7 for rheumatoid cation of Diseases code scleroderma, or cur¬ rent exposure to hydralazine or procainamide; postpericardiotomy.pericardiotomy within the previous 3 months; traumat¬ arthritis, systemic lupus erythematosus, or ic.chest trauma within the 7 days preceding pericardiocentesis; and hypothyroid.serum thyroxine value <5 mg/dL and thyroid stimulating hormone value >5 ixIU/mL. If more than one of the above causes of pericardial effusion were present or if the attending physician and the reviewer did not identify the same cause, then the etiology for that patient was classified as undetermined. Diagnoses were confirmed by au¬ topsy in eight cases. Control patients were evaluated by obtaining pericardial fluid artery7 bypass during routine open heart surgery7 (nine coronary one aortic valve replacement) between February procedures and and March 1996 by open pericardial aspiration. None of these patients had diseases or were receiving medications known to cause pericardial effusion. Between 1984 and 1992, virtually all pericardial fluid samples were submitted for the same battery of laboratory7 tests, including the following: appearance; volume; cell count; specific gravity; protein; lactate dehydrogenase; glucose; Gram's stain; culture for bacteria mycobacteria, virus, and fungus; and cytology. Data were abstracted from medical records, entered into a computer database, and analyzed using software (STATA version 4.0 statistical software package; STATA Corporation; College Station, Tex). Because of unequal variance, comparisons of discrete data used the x2 tests, while comparisons of continuous variables used either the Wilcoxon rank-sum test or the KruskalWallis test with Bonferroni post hoc testing. Significance was defined as a two-tailed alpha level <0.10. Sensitivity was defined as true-positives/true-positives + false-negatives. Specificity7 was as true-negatives/true-negatives + false-positives. defined Results The results from 82 male and 93 female subjects aged 46.0±21.6 years (range, 1 month to 87 years) are included. Exudative effusions included those diagnosed as malignant (n=37), viral (n=19), bacte¬ rial (n=9) or associated with infection but with no growth on cultures (parainfective) (n=6), rheumato¬ logic (n=8), or postpericardiotomy (n=8) based on the degree of inflammation inherent in each disease process.3-5 Transudates included those effusions due to radiation (n 15), uremia (n=15), trauma (n=4), hypothyroidism (n=3), and normal controls (n=10). The 41 unclassified cases were analyzed separately. The initial analysis compared exudates with trans¬ udates (Table 1). Neither the volume nor the appear¬ ance of the pericardial fluid differed between exu¬ dates and transudates. While RBC counts were similar, exudates had significantly higher fluid leuko¬ cyte counts (14,116±37,446 vs 2,210± 1,916 cells per milliliter; p=0.0123). The proportions of neutro¬ phils and monocytes did not differ. Few differences between exudates and transudates occurred among the chemistry tests evaluated. The ratio of fluid lactate dehydrogenase to serum lactate dehydroge¬ nase was greater with exudates (11.6± 16.4 vs 2.6±2.8; p=0.0668). Fluid glucose level was lower with exudates (77.9±41.9 vs 96.1±50.7 mg/dL; p 0.0218). Specific gravity and total protein of pericardial fluid are moderately correlated, with specific gravity changing by 0.0025 for each 1.0 g change in total protein (r=0.56, p<0.001) (Fig 1). The ability of each test to correctly classify fluid as exudate or transudate was evaluated using the cut points generally used for pleural fluid.35 Figure 2 shows the individual data points with the horizontal line denoting the cut point and open symbols mark¬ ing correct classifications. Exudate was correctly detected (sensitivity) by specific gravity > 1.015 in 90% of cases. Similarly, a fluid total protein level >3.0 g/dL had a sensitivity of 97%, and a fluid to serum protein ratio >0.5 had a sensitivity of 96%. The most sensitive marker of exudate was fluid lactate dehydrogenase >200 mg/dL, giving a sensi¬ tivity of 98%. The ratio of fluid to serum lactate >0.6 had a sensitivity of 94%. Spec¬ dehydrogenase tests. Conversely, the most ificity wastestslow for these specific (those best<identifying transudate) were fluid leukocyte count 10,000 cells per milliliter (89%) and fluid glucose level >60 mg/dL (76%). Other cut points did not materially improve diagnos¬ tic accuracy for any test. The test that most correctly classified fluids as exudate or transudate was a fluid to serum lactate dehydrogenase ratio >0.6 (diagnos¬ tic accuracy of 87%). While results of fluid-specific = = 1214 Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21747/ on 04/30/2017 Clinical Investigations 5,000,000 pfRBC 140,000 |- pfWBC 1.05 120,000 4,000,000 pfSpGrav pfTP pfTP/sTP 1.04 100,000 3,000,000 80,000 1.03 2,000,000 60,000 1.02 40,000 1.01 1,000,000 20,000 0 Sn=58% Trans. Sn=43% Ex. Trans. Sn=91% Sp=65% Sp=89% Sp=30% pfLDH pfLDH/sLDH pfGluc Ex. Trans. DA=56% 10,000 Ex. DA=52% DA=77% DA=82% pfGluc/sGluc pfPH 8,000 [- Sn=94% Ex. Trans. Sn=25% Ex. Trans. Sn=85% Ex. Trans. Sn=56% Sp=40% Sp=76% Sp=12% Sp=40% Ex. Trans. DA=87% Figure 2. Distributions of DA=36% pericardial fluid characteristics. DA=69% Open triangle=exudate; DA=52% open circle=transudate; open symbols=correct classification; closed symbols=incorrect classification; horizontal line represents the cut point for discriminating exudate from transudate with the numeric value of the cut point to its right; Ex=exudate; Trans=transudate; Sn=sensitivity; Sp=specificity; DA=diagnostic accuracy; pfWBC =pericardial fluid WBC count; pfSpGrav=pericardial fluid pfRBC^pericardial fluid RBC count; fluid total protein; pfTP/sTP== ratio of pericardial to serum total protein; specific gravity; pfTP=pericardial pfLDH/sLDH=ratio of pericardial to serum lactate pfLDH=pericardial fluid lactate dehydrogenase; fluid glucose; pfGluc/sGluc=ratio of pericardial to serum glucose; dehydrogenase; pfGluc=pericardial glucose, pfPH=pericardial fluid pH. high¬ diagnostic groups (Table 3). WBC counts were those among inflammatory diseases, particularly with bacterial (41,410±77,122 cells per milliliter) and rheumatologic (12,100±21,636 cells per millili¬ ter) etiologies. Very low WBC counts were seen in per milliliter). hypothyroid effusions (625±247 cellshad the highest and effusions Hypothyroid malignant and of 74±26%, (79±27% proportions monocytes and bacterial effusions Rheumatoid respectively). had the highest proportions of neutrophils (78±20% and 69±32%, respectively). Two chemistry tests differed among the 11 diag¬ nostic groups (Table 4). The ratio of fluid to serum total protein significantly differed between the 10 control subjects and the 10 patients with bacterial or vs 0.85±0.10, respec¬ parainfective casesAs(0.55±0.07traumatic effusion had tively; p<0.001). expected, est pericardial fluid to serum protein ratio approaching significantly differed between control subjects and subjects with both bacterial-parainfective and malignant fluids (49±18 vs 121±20 and 117±33 mg/dL, respectively; with p=0.09). Lowest pH measurements were noteddiffer infected fluids but this did not statistically from other causes. The overlap between most diag¬ nostic groups is so large with all chemistry tests that discriminating ability is lost. Among the 15 cases clinically classified as having bacterial infection-associated pericardial effusion, nine had positive bacterial cultures of pericardial fluid and six had no growth on aerobic bacterial culture. There were no positive viral, fungal, or mycobacterial cultures in the entire cohort. Based on our clinical definition of bacterial infection-associa 1.0. Pericardial fluid cholesterol levels 1216 Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21747/ on 04/30/2017 Clinical Investigations 5,000,000 pfRBC 140,000 |- pfWBC 1.05 120,000 4,000,000 pfSpGrav pfTP pfTP/sTP 1.04 100,000 3,000,000 80,000 1.03 2,000,000 60,000 1.02 40,000 1.01 1,000,000 20,000 0 Sn=58% Trans. Sn=43% Ex. Trans. Sn=91% Sp=65% Sp=89% Sp=30% pfLDH pfLDH/sLDH pfGluc Ex. Trans. DA=56% 10,000 Ex. DA=52% DA=77% DA=82% pfGluc/sGluc pfPH 8,000 [- Sn=94% Ex. Trans. Sn=25% Ex. Trans. Sn=85% Ex. Trans. Sn=56% Sp=40% Sp=76% Sp=12% Sp=40% Ex. Trans. DA=87% Figure 2. Distributions of DA=36% pericardial fluid characteristics. DA=69% Open triangle=exudate; DA=52% open circle=transudate; open symbols=correct classification; closed symbols=incorrect classification; horizontal line represents the cut point for discriminating exudate from transudate with the numeric value of the cut point to its right; Ex=exudate; Trans=transudate; Sn=sensitivity; Sp=specificity; DA=diagnostic accuracy; pfWBC =pericardial fluid WBC count; pfSpGrav=pericardial fluid pfRBC^pericardial fluid RBC count; fluid total protein; pfTP/sTP== ratio of pericardial to serum total protein; specific gravity; pfTP=pericardial pfLDH/sLDH=ratio of pericardial to serum lactate pfLDH=pericardial fluid lactate dehydrogenase; fluid glucose; pfGluc/sGluc=ratio of pericardial to serum glucose; dehydrogenase; pfGluc=pericardial glucose, pfPH=pericardial fluid pH. high¬ diagnostic groups (Table 3). WBC counts were those among inflammatory diseases, particularly with bacterial (41,410±77,122 cells per milliliter) and rheumatologic (12,100±21,636 cells per millili¬ ter) etiologies. Very low WBC counts were seen in per milliliter). hypothyroid effusions (625±247 cellshad the highest and effusions Hypothyroid malignant and of 74±26%, (79±27% proportions monocytes and bacterial effusions Rheumatoid respectively). had the highest proportions of neutrophils (78±20% and 69±32%, respectively). Two chemistry tests differed among the 11 diag¬ nostic groups (Table 4). The ratio of fluid to serum total protein significantly differed between the 10 control subjects and the 10 patients with bacterial or vs 0.85±0.10, respec¬ parainfective casesAs(0.55±0.07traumatic effusion had tively; p<0.001). expected, est pericardial fluid to serum protein ratio approaching significantly differed between control subjects and subjects with both bacterial-parainfective and malignant fluids (49±18 vs 121±20 and 117±33 mg/dL, respectively; with p=0.09). Lowest pH measurements were noteddiffer infected fluids but this did not statistically from other causes. The overlap between most diag¬ nostic groups is so large with all chemistry tests that discriminating ability is lost. Among the 15 cases clinically classified as having bacterial infection-associated pericardial effusion, nine had positive bacterial cultures of pericardial fluid and six had no growth on aerobic bacterial culture. There were no positive viral, fungal, or mycobacterial cultures in the entire cohort. Based on our clinical definition of bacterial infection-associa 1.0. Pericardial fluid cholesterol levels 1216 Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21747/ on 04/30/2017 Clinical Investigations Type ofEffusion Purulent, % Hemorrhagic, % Table 2.Pericardial Fluid Characteristics by Diagnoses p Value Volume, mL Unclassified Serous, % p Value 666±421 618±565 535 ±649 448±379 429 ±680 365±267 354±263 318±217 217±208 200±100 Uremic Radiation Infection Postpericardiotomy Malignant Viral Rheumatic Trauma Hypothyroid 0.001 Controls Table 3.Cell Counts by Malignant Viral Bacterial RBC WBC Neutrophils, % Monocytes, % 484,446 ±753,594 9,280: ±21,967* 6,999: ±11,276 41,410: ±77,122 2,663: ±2,432 12,100: ±21,636 3,846: ±7,581 2,266: ±1452 3,276: ±3,168 26±26 46±32 69±32 27±20 78±20* 39±36 60±21 32±38 21±27* 32±26 <0.001 74±26 41 ±32 31±32* 70±21 22±20* 61 ±36 38 ±24 68 ±38 79 ±27* 66±28 <0.001 482,691±855,111 766,848±950,206 940,547± 1,044,064 257,840±425,521 617,500± 1,478,254 687,515± 1,186,049 2,107,585± 1,835,324 48,333 ±79,425 5,021±11,190 Postpericardiotomy Rheumatic Radiation Uremic Trauma Hypothyroid Unclassified Kruskal-Wallis p Value Type ofEffusion 625: ±247* 14,690: ±3,605 0. 008 NS *Significant pairwise difference. Table 4.Pericardial Fluid SpGR Bacterial (parainfective) Postpericardiotomy Rheumatologic pfLDH 1.020±.003 3,503±3,281 Chemistry by Type ofEffusion* PfLDH/LDH pfTP PfTP/TP pfGluc PfGlu/Gluc pfChol 8.6±7.6 4.6±0.5 0.85±0.10f 67.1±39.4 0.64±0.50 121±20+ 0.79±0.37 PfCh/Chol 0.98 63.5== 9.3 0.64 j :0.21 63 4.9d 1.4 0.83d 0.20 3.5±3.2 66.4 j 31.9 0.63d :0.34 84 = :35 4.5d 1.0 0.64== 0.14 6.7±4.1 0.98±0.02 126d :58.8 1.03d :0.30 99 4.1d 1.2 0.66d 0.15 2.9±3.4 Radiation 80.8d 37.5 0.69d :0.29 4.8d 1.2 0.80== 0.16 1.3±1.5 Uremic 1.07 43.7== :247 0.43d :0.25 4.5±2.5 0.94±0.29 1.4±1.7 Trauma 164== 83.2 0.83d 0.25 100 1.10 3.5±1.7 0.48±0.39 3.4±5.0 Hypothyroid 4.3±1.5 0.70±0.24 106.2±63.7 0.83±0.26 64±57 0.99±0.03 2.4±2.9 Unclassified *SpGr=specific gravity; PfLDH=pericardial fluid lactate dehydrogenase; PfLDH/LDH=ratio of percardial fluid lactate dehydrogenase to serum lactate dehydrogenase; PfTP.pericardial fluid total protein; PfTP/TP=ratio of pericardial fluid total protein to serum total protein; PfGluc=pericardial fluid glucose; PfGluc/Gluc=ratio of pericardial fluid glucose to serum glucose; PfChol=percardial fluid cholesterol; PfChol/Chol=ratio of percardial fluid cholesterol to serum cholesterol. f Denotes significant pairwise differences. Blank cells had insufficient numbers of tests or no tests performed. 1.021 = :.001 1,552± 1,422 1.019d :.006 3,677±3,631 1.019= :.004 672±1,015 1.021== :.008 2,820 ±2,255 1.019== .008 1,285± 1,330 1.024=^ .003 1,376± 1,937 1.019±.005 2,332± 1,328 ated effusion, which would include septicemia and pneumonitis, the six culture-negative cases could have parainfective pericardial effusions, (similar to parapneumonic effusion). As shown in Table 5, those with infective cases (positive cultures) were signifi¬ cantly younger, trended toward higher fluid WBC counts, had significantly more neutrophils, and higher lactate dehydrogenase levels. They also had significantly lower fluid glucose levels and fluid to serum glucose ratios than those with parainfective cases. The diagnostic accuracy of Gram's stains was evaluated using growth on bacterial cultures of peri¬ cardial fluid as the reference standard. Stained bac¬ teria were noted in three of the eight culture-positive fluid samples and in 1 of 83 culture-negative samples CHEST/111 /5/MAY, 1997 Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21747/ on 04/30/2017 1217 Table 5.Comparison ofInfective and Parainfective Pericardial Effusion* Infective Parainfective 9 Male/female Age, yr 7/2 28.8±20.0 293 ±135.88 Volume, mL Appearance (%) Purulent Hemorrhage Clear RBC WBC Neutrophils, % Monocytes, % LDH, mg/dL Total protein, g/dL pfTP/serum TP Glucose, mg/dL pfGluc/serum glue pH Gram stain 571.67±560.91 2(22) 2(33) 4(45) 3(50) 3(33) 1(17) 345,400±429,645 700,237±943,171 NS 0.05 NS 0.066 31,775±36,092 8,192± 11,216 NS NS 89±5 11±5 52±37 48 ±37 0.015 0.015 7,101 ±3,675 1,704±706 4.15±1.44 4.66±0.63 0.032 NS 0.78±0.28 47.3±25.3 0.28±0.14 7.035±0.445 0.81±0.12 102.5±35.6 0.84±0.23 7.082±0.732 NS 0.014 0.005 NS 2(33) 3(50) 1(17) NS h) 2(25) 3(375) 3(375) Normal WBCs Bacteria * 6 6/0 45.2±24.3 p Value LDH=lactate dehydrogenase; pfTP=pericardial fluid total protein; TP=total protein; pfGlue/serum glue=ratio of pericardial fluid glucose to serum glucose; NS=not significant. (Table 6). Presence of stained bacteria had a sensi¬ tivity of 38% and absence of bacteria had a specificity of 99%. Leukocytes without bacteria were present in the stained pericardial fluid of three culture-positive cases and 42 culture-negative cases. Either bacteria or leukocytes were present in 64% of exudates while no abnormalities on Gram's stain were seen in 58% of samples. Presence of leukocytes on Gram's stains (false-positive) occurred in five transudates: four with uremia and one case with hypothyroidism. Among 110 mycobacterial, 62 viral, and 120 fungal cultures of pericardial fluid, there were no positive results. Viral syndromes had been diagnosed by Table 6.Diagnostic Accuracy of Gram's Stains Bacterial Culture 40 1 42 Exudate 19 4 31 Transudate clinical of these patients. No mycobacterial or fungal diseases had been suspected presentation in 19 clinically. Cytologic tests were obtained in 36 cases with malignancy and 101 cases with no clinical evidence of malignancy at the time of pericardiocentesis. Malignant cells were noted in 33 of 36 cases with malignancy (sensitivity of 92%) and in none of 101 nonmalignant cases (specificity of 100%). Discussion of any other studies that have evaluated the usefulness of laboratory systematically tests performed on pericardial fluid. In the era of outcomes analysis, such critical evaluation is impor¬ tant. Since a battery of tests including microbial cultures, cytology, and chemical tests were obtained almost routinely, selection bias is minimal. The clinical diagnosis was generally not confirmed histo¬ thus allowing some risk of misclassification logically, of diagnoses. To our knowledge, no available literature discrim¬ inates pericardial fluids into transudate, exudate, or complicated exudate, as is done with pleural fluid.35 An article reporting three ill-defined cases with transudative pericardial fluid noted spe¬ purported cific gravities of 1.018 to 1.022, protein level of 4.4 to 5.0 mg/dL, and glucose level of 70 to 90 mg/dL.10 One case series noted that inflammatory pericardial fluid had a pH of 7.06 ±0.07 compared with nonin¬ fluid pH of 7.42±0.06.n The current flammatory series shows that exudate and transudate can be best discriminated by specific gravity > 1.015, fluid pro¬ tein level >3.0 mg/dL, fluid to serum protein ratio >0.5, fluid lactate dehydrogenase value >300 U/dL, and fluid to serum lactate dehydrogenase ratio >0.6. Case reports have described fluid characteristics in several specific diseases. In rheumatoid arthritis, pericardial fluid has been described in 41 cases.1218 The fluid is always serosanguineous and sometimes viscous. A single report noted an RBC count of 30,100 cells per milliliter.13 Leukocyte counts have 300 to 88,100 cells per milliliter.131718 ranged from were the predominant cell type (72 to Neutrophils Total 80%). protein level was 4.2 to 6.4 mg/dL. Fluid level has ranged from 0 to 66 mg/dL, with glucose most reported cases having glucose levels <30 mg/ (JL 1417 Qur series observed similar fluid appear¬ ance, cell counts, and protein levels. But none of our seven cases had fluid glucose levels <75 mg/dL. With pleural fluid, it is believed that a diffusion block of glucose occurs in the inflamed pleura.35 Our cases may have had lower intensities of pericardial inflam¬ mation than those other reported cases that had We are unaware 1218 Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21747/ on 04/30/2017 Clinical Investigations lower glucose levels. Fluid characteristics have been in four patients with systemic lupus ery¬ reported thematosus and three patients with drug-induced colored lupus.19-25wereThree fluid samples wereRBCstraw counts have and two serosanguineous.20-23 from to cells milliliter.2033,750 229,000 per ranged 22,24 Leukocyte counts of 544 to 199,600 cells per milliliter have been reported, with 76 to 96% neu¬ With specific gravity of 1.02821 and trophils.20-2224 of 4.9 to 7.5 mg/dL,20-25 this fluid is an protein exudate. Lactate dehydrogenase levels were 2,085 and 4,688 U/dL in two cases, while glucose level has 20 to 100 mg/dL.21-24 For rheumatoid ranged from the arthritis, most specific tests on pericardial fluid appear to be latex agglutination of rheumatoid anti¬ gen,15 immunoglobin complexes,17 diminished fluid complement,14-26 and cytologic identification of char¬ acteristic "RA cells."13 High pericardial fluid titers of antinuclear antibody have been reported in systemic lupus erythematosus2425 as have "LE cells."19-21'23-25 Our series utilized none of these latter highly specific tests. In one of the only case series published on puru¬ lent pericarditis, detailed analysis was performed on pericardial fluid from five patients.27 Fluid leukocyte counts ranged from 6,100 to 241,000 cells per milli¬ liter and were >50,000 cells per milliliter in four of the five cases with infected fluid. There were >90% in all cases. Fluid glucose level was <35 neutrophils in four mg/dL patients. Protein level ranged from 3.3 to 6.2 g/dL. Lactate dehydrogenase levels were 4,800 and 6,700 U/mL in two patients. Among the cur¬ rently reported culture-positive patients, nearly all test results were similar to these reports. Our ob¬ served fluid glucose levels were not as low (mean of 47.3 mg/dL) as the prior report and two of the five determinations were >60 mg/dL. Similar to rheu¬ matoid diseases, infective pleuritis is believed to to glucose.3-5 To our produce a diffusion block of the stains of pericar¬ Gram's knowledge, accuracy dial fluid has not been evaluated previously. Limited by the fact that only five culture-positive samples in the current series had Gram's stains, we found a sensitivity of 38% and a specificity of 99% for presence of bacteria on the stain. Using either leukocytes or bacteria on Gram's stain as indicators was prohibitively nonspecific for identifying infective pericardial fluid, but was more useful for discrimi¬ nating exudate from transudate. Thus, a fluid to serum glucose ratio <1.0 may be useful in differen¬ tiating exudate from transudate and infective from parainfective effusions. Bacterial culture, but not Gram's stain, is accurate for defining infective effu¬ sions and identifying causative agents. With tuberculous pericarditis, others have re¬ ported a low yield from fluid culture or pericardial biopsy and culture.2829 Fluid cell counts and chem¬ istry have not been described. Recently, adenosine deaminase levels >40 U/L have demonstrated a sensitivity of 93% and a specificity of 97% for tuberculous pericarditis.3031 Nested polymerase chain reaction from as little as 1 jjlL of pericardial fluid can establish the diagnosis.32 Little has been published regarding viral pericar¬ ditis. To our knowledge, no cell counts or chemistry results have been reported. Intranuclear inclusions, multinucleated giant cells, and atypical mesothelial cells have been observed with Papanicolaou-stained pericardial fluid in one case each of cytomegalic and herpes simplex pericarditis.33 We found no distin¬ guishing results of any tests. To our knowledge, no prior reports have described parainfective pericardial effusion. In the cases be¬ lieved associated with bacterial infection, but with negative pericardial fluid cultures, it is likely that the pericardial fluid was an inflammatory response to adjacent infection, eg, parainfective pericarditis. We noted low fluid leukocyte counts (four of six cases had < 10,000 cells per milliliter), a high proportion of monocytes (mean=:48%), lactate dehydrogenase lev¬ els < 1,550 U/dL in four of five cases, and glucose levels always >50 mg/dL. These observations are very similar to those in parapneumonic pleural effu¬ 3-5 sions. The fluid characteristics of one patient with postmyocardial infarction pericarditis34 and nine patients with postpericardiotomy syndrome35 have been re¬ ported. The fluid appears serous or serosanguineous with a mean of 5,628 leukocytes per milliliter, pre¬ dominantly monocytes and lymphocytes, and a mean protein level of 6.1 mg/dL (range, 4.3 to 7.2). Our results closely resemble the results of these re¬ ports.3435 In 15 cases of uremic pericarditis, all had serosan¬ guineous fluid with hematocrits of 1 to 24%.3637 The leukocyte count was 2,580 cells per milliliter, primarily consisting of neutrophils. Mean total protein value has been reported at 4.08 g/dL (80% that of serum levels) and a cholesterol level of 94 mg/dL (50% that of serum levels). In three patients, the mean pericardial fluid pH was 7.08±0.1.37 mean Our results are quite similar for each parameter. In one previously described patient with myxedema, the fluid was amber color with a leukocyte count of 1,800 cells per milliliter, total protein level of 6.0 g/dL (similar to serum), and a cholesterol level of 76 mg/dL.38 The protein levels we observed in two patients were much lower and only half that of serum. Our observed cholesterol levels were higher CHEST/111 /5/MAY, 1997 1219 Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21747/ on 04/30/2017 and similar to serum. These differences are unex¬ Caution is warranted given the few cases plained. examined. To our knowledge, the fluid characteristics of radiation-induced pericardial fluid have not been described previously. We failed to identify any dis¬ tinctive characteristics. Meta-analysis of 113 cases of malignant pericardial effusion demonstrates a sensitivity of 95% for peri¬ cardial fluid cytologic study and a specificity of 100% in 82 samples from patients not having cancer.39-49 Our sensitivity of 92% and specificity of 100% in 36 cancer cases and 101 noncancer cases with agree previous reports. Since our cases, as with many other reports, did not always have histologic confirmation of malignant pericardial involvement, a sensitivity <100% would be expected. Additionally, singlesample cytologic study is known to allow falsenegative results.50 One report has examined normal pericardial fluid, obtained at open heart surgery in 11 patients. These serum: sodium, 138±4 mol/L; samples resembled 4.5±1 mol/L; chloride, 109±5 mol/L; potassium, and bicarbonate, 25 ±6 mol/L.51 Total protein level was 3.1±0.6 g/dL. Fluid pH was 7.57±0.11. We noted a slightly higher protein level in our 10 control patients. The other parameters were not measured. Conclusions evaluation of pericardial fluid should with differentiation between exudate and tran¬ begin sudate. The identification of an exudate is best done with one or more of four tests using the following cut points: fluid total protein level >3.0 g/dL; fluid to serum total protein ratio >0.5; fluid to serum lactate ratio >0.60; and fluid lactate dehy¬ dehydrogenase <300 U/dL. drogenase Two other tests should also be ordered routinely based on their high specificity and the crucial impor¬ tance of detecting a specific disease: bacterial culture and fluid cytology. Other tests either do not have significant discrim¬ inating power, do not identify a prevalent disease, or closely parallel results of another test. Thus, routine testing should be limited to the above six tests. Other tests should be ordered only when a high level of clinical suspicion of a specific disease war¬ rants confirmation. These tests might include the for rheumatoid antigen, following: fluid latex fixation fluid complement levels complexes, andfluid 7-globulin antinuclear antibody for rheumatoid arthritis; titers for systemic lupus erythematosus; and fluid adenosine deaminase and nested polymerase chain reaction for tuberculosis. Diagnostic To our knowledge, no diagnostic tests of pericar¬ dial fluid exist that are specific for effusion associated with postpericardiotomy syndrome, radiation or ure¬ mic pericarditis, hypothyroidism, or trauma. References 1 Kirkorian JG, Hancock EW. Pericardiocentesis. Am J Med 1978; 65:808-14 2 Corey GR, Campbell PT, Van Trigt P, et al. Etiology of large pericardial effusions. Am } Med 1993; 95:209-13 3 Light RW. Pleural effusions. Med Clin North Am. 1977; 61:1339-52 4 5 Jay SJ. Pleural effusions: I. Preliminary evaluation.recogni¬ tion of the transudate. Postgrad Med 1986; 80:164-77 Jay SJ. Pleural effusions: II. 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