Pleural effusions: exudates could be diagnosed by the albumin gradient or protein ratio.

Clinical bottom line (level 2a)

  1. In patients with pleural effusions, three quarters had exudates.
  2. The albumin gradient (LR+11) and protein effusion: serum ratio (LR+9.9) , were the best tests for diagnosing exudates.
  3. No biochemical test could safely exclude an exudate.
Heffner et al: Chest 1997; 111: 970-980
Expires April 2003

The study

Systematic review of all studies of
  • Patients: pleural effusions
  • Intervention: assessing the diagnostic accuracy of eight biochemical tests
  • Outcome: to distinguish exudative from transudative pleural effusions


    • Articles found in all languages using MEDLINE, 1976 to 1996 (search terms: not given ) and bibliographies were also searched, authors and experts were contacted for unpublished studies or other relevant articles.

    Selection criteria: as above
    Appraisal criteria: selected and appraised by two independent reviewers using set criteria (detailed in text)
    Articles excluded if:

    seven studies were found of 1,448 hospitalised patients
    • ?independent unblinded reference standard applied in all patients from ?appropriate spectrum
    • exudative effusion, defined as any of:
      • absence of clinical disease commonly associated with transudate
      • tissue biopsy, laboratory result or imaging documentation of a disorder commonly associated with exudate
      • three or more months of follow-up to exclude delayed presentation of conditions associated with exudates
    • diagnostic tests:
      • albumin gradient (serum - effusion); positive 1.2 g/dl or less
      • protein effusion: serum ratio; positive if >0.5
      • LDH effusion: serum ratio; positive if >0.6
      • protein; positive if >2.9 g/dl
      • cholesterol effusion: serum ratio; positive if >0.3
      • LDH; positive if >0.45 upper limit of normal
      • cholesterol; positive >45 mg/dl
      • bilirubin effusion: serum ratio; positive if >0.6
    There was no comment on whether the studies were significantly heterogeneous.

    The evidence


    diagnostic test exudate transudate LR+
    (95% CI)    		 post-test probability LR-
    (95% CI)    		 post-test probability
    albumin gradient 11
    ( to )     		97% 0.14
    ( to )     		28%
    protein ratio 9.9
    ( to )     		97% 0.12
    ( to )     		25%
    LDH ratio 6.1
    ( to )     		95% 0.10
    ( to )     		22%
    protein 5.4
    ( to )     		94% 0.10
    ( to )     		22%
    cholesterol ratio 5.0
    ( to )     		93% 0.10
    ( to )     		22%
    LDH 4.8
    ( to )     		93% 0.15
    ( to )     		30%
    cholesterol 4.8
    ( to )     		93% 0.13
    ( to )     		27%
    bilirubin ratio 2.2
    ( to )     		86% 0.26
    ( to )     		42%
    total

    • pre-test probability of exudate: 74% (95% CI: 72% to 76%)
    • cause of effusion:
      • malignancy: 438/1448; 30% (28% to 33%)
      • tuberculosis: 296/1448; 20% (18% to 23%)
      • infection: 185/1448; 13% (11% to 15%)
      • miscellaneous: 73/1448; 5.0% (3.9% to 6.2%)
      • pulmonary embolism: 36/1448; 2.5% (1.7% to 3.3%)
      • collagen vascular disease: 17/1448; 1.2% (0.6% to 1.7%)
      • trauma: 14/1448; 1.0% (0.5% to 1.5%)
      • pancreatitis: 5/1448; 0.3% (0.0% to 0.6%)

    Comments

    1. Cut-off points were based on the costs of false positive results and prevalence of exudates, which was set at 0.5 to achieve maximum uncertainty. This is based on the assumption that the test is being used to screen for exudates.
    2. Data not available to calculate confidence intervals for likelihood ratios.
    3. No combination (doublets, triplets) was found to be clearly better than individual tests (including Light's criteria).
    4. Most of the studies had major methodological flaws such as failing to provide an independent blinded reference standard, thus increasing the risk of bias.

    Citation

    1. Heffner JE, et al: diagnostic value of tests that discriminate between exudative and transudative pleural effusions. Chest 1997; 111: 970-980
    Search Terms: pleural effusion in Cochrane
    Contributor: Donald Stanley and Chris Ball, April 2000
    Reviewer:

    Clinical Question.
    Patient pleural effusions
    Intervention or Exposure biochemical tests
    Outcome diagnosis of exudates