In #WCHAMreport we discussed an approach to pleural effusions. The differential diagnosis and procedural pearls can be found on the blog here. This post is focused on management of specific types of pleural effusions.

1. Pearls on Fluid Analysis Continued

Part I of the blog post (linked above) talks about differentiating between exudative and transudative effusions. Further, based on predominance of white blood cell type, this can give you some clues into the underlying diagnosis. Of course there are exceptions to below and other confirmatory tests to pursue.

• Lymphocytic predominance
  • Malignancy, TB and rheumatoid effusions, sarcoidosis, yellow nail syndrome (which is lymphedema, yellow nails and pulmonary manifestations including pleural effusions and can include bronchiectasis/sinusitis)
  • More than 80% lymphocytes points to TB or lymphoma
• Neutrophilic: Parapneumonic effusions usually
• Eosinophilia > 10%
  • Asbestos related (BAPE), drugs (nitrofurantoin), malignancy (lung), infection (parasites), pulmonary embolism, eosinophilic granulomatosis with polyangiitis

Low glucose can also point you towards specific diagnosis:

• <1 mmol – Rheumatoid arthritis, empyema
• 1-3 mmol – malignancy, TB, systemic lupus erythematosus

The JAMA Rational Clinical Exam on ‘Does This Patient Have an Exudative Effusion?’ (linked below) stated that the diagnosis of an exudate was most accurate if

• Cholesterol in the pleural fluid was greater than 55 mg/dL (+LR 7.1-250)
• Lactate dehydrogenase (LDH) was greater than 200 U/L (LR+ 18)
• Ratio of pleural fluid cholesterol to serum cholesterol was greater than 0.3 (LR+ 14)

A diagnosis of exudative effusion was less likely if all of Light’s criteria were absent. (LR 0.04)

2. Classification of Parapneumonic Effusions

There are a few features that help differentiate uncomplicated versus complicated pleural effusion. Complicated parapneumonic effusions include those with positive gram stain +/- culture, pH < 7.2 (or glucose < 3.4 mmol/L), or LDH > 1000 U/L. Drainage of frank pus or turbid/cloudy fluid is the defining features of an empyema.

3. When Is Drainage of Pleural Space Required?

In the setting of complicated parapneumonic effusion or empyema, drainage of pleural space is required. Any one of the following scenarios require drainage:

• Drainage of frank pus or turbid/cloudy (empyema)
• Gram stain positive
• Aerobic or anaerobic culture positive
• PH < 7.2 (if not available, use glucose < 3.4 mmol/L)
• LDH > 1000 U/L
• > 50% of hemithorax involved in pleural effusion
• Loculations on imaging

Involving chest physician or thoracic surgery is very helpful in these cases to make sure there is appropriate source control. If there is ongoing features of infection such as fever, this may be indication for further surgical interventions.

4. Exudative Effusion Without a Cause?

If someone has a unilateral exudative effusion without an obvious cause, this warrants further investigations:

The British Thoracic Society (BTS) guidelines (Reference #3 below) recommend that computed tomography (CT) the chest should be done. There are some imaging characteristics that can point towards malignant disease but the absence of them does not exclude this. They include: pleural nodularity, pleural thickening of 1 cm or more, mediastinal pleural thickening and circumferential pleural thickening. Whether a CT pulmonary angiography scan is needed to assess for pulmonary embolism is not clear. Positron emission tomography (PET) scan not routinely indicated.

After this point, if there is no clear diagnosis this would be a reason to refer to chest physician such as Respirology as there may be considerations for thoracoscopy, video assisted surgical thorascopic surgery (VATS), or interventional-radiology guided pleural biopsy +/- other interventions for source control.

Remember: Cytology is only 60 to 70% sensitive so if it is negative, it does not exclude malignant disease. The BTS guidelines say that the yield from sending more than two specimens (taken on different occasions) is very low and should be avoided. Similarly, negative sputum cultures cannot rule out tuberculosis.

5. Malignant Pleural Effusions

The reference below (Reference #4) has further details on management of management pleural effusions. As part of the algorithm outlined by the guideline, if it is not clear if the patient’s symptoms are in fact related to the malignant pleural effusions, first ultrasound-guided therapeutic thoracentesis is done to assess for improvement in dyspnea.

If the patient has improvement in symptoms upon drainage of a malignant pleural effusion and there is known or expected re-expandable lung, interventions such as talc pleurodesis or intra-pleural catheters can be considered.

There are various factors that are considered in deciding whether these interventions are offered (and which one) including lung re-expandability, prognosis, among others. The details are not covered here, but feel free to check out the references for more information.

As always, if you have specific questions or comments please email at cmr@wchospital.ca

References:

1. Beaudoin, S., & A. V. Gonzalez. (2018). Evaluation of the patient with pleural effusion. CMAJ. 190:E291-5. doi: 10.1503/cmaj.170420
2. Colice, G. L., Curtis, A., Deslauriers, J., Heffner, J., Light, R., Littenberg, B., Sahn, S., Weinstein, R. A., & Yusen, R. D. (2000). Medical and surgical treatment of parapneumonic effusions : an evidence-based guideline. Chest, 118(4), 1158–1171. https://doi.org/10.1378/chest.118.4.1158
3. Du Rand, I., & Maskell, N. (2010). Introduction and methods: British Thoracic Society Pleural Disease Guideline 2010. Thorax, 65 Suppl 2, ii1–ii3. https://doi.org/10.1136/thx.2010.137042
4. Feller-Kopman, D. J., Reddy, C. B., DeCamp, M. M., Diekemper, R. L., Gould, M. K., Henry, T., Iyer, N. P., Lee, Y., Lewis, S. Z., Maskell, N. A., Rahman, N. M., Sterman, D. H., Wahidi, M. M., & Balekian, A. A. (2018). Management of Malignant Pleural Effusions. An Official ATS/STS/STR Clinical Practice Guideline. American journal of respiratory and critical care medicine, 198(7), 839–849. https://doi.org/10.1164/rccm.201807-1415ST
5. Craig, J. Gold, W. L., & J. A. Leis. (2013). A 44-year-old man with a parapneumonic effusion. CMAJ. 185 (3) 232-234; DOI: 10.1503/cmaj.121051 https://www.cmaj.ca/content/185/3/232
6. Wilcox ME, Chong CAKY, Stanbrook MB, Tricco AC, Wong C, Straus SE. Does This Patient Have an Exudative Pleural Effusion? The Rational Clinical Examination Systematic Review. JAMA. 2014;311(23):2422–2431. doi:10.1001/jama.2014.5552 – linked here https://jamanetwork.com/journals/jama/fullarticle/1881316