There are two myths that have persisted about thoracentesis and pleural fluid analysis that must be dispelled. The first myth is that a large volume thoracentesis should not remove more than 1,500 mL fluid due to the risk of re-expansion pulmonary edema (REPE). The second myth is that a pleural effusion is an exudate if any of the three Light’s criteria suggests an exudate.
The exact etiology of REPE is unknown but it is a rare complication of a large volume thoracentesis. The reported incidence of REPE is about 0.75% of all large volume thoracenteses and the risk is independent of the volume of pleural fluid aspirated.[i] Traditional guidelines cap the volume of pleural fluid that can safely be removed at 1,500 mL; however, this is an arbitrary cut-off that is not supported by science. The largest study of large volume thoracenteses included over 9,300 thoracenteses and 799 of these drained more than 1,500 mL pleural fluid. Pleural effusions were “drained dry” in this trial unless the patient started to develop worsening central chest pressure or if the operator detected a subjective sensation of increased negative intrapleural pressure during aspiration.i Some investigators have suggested that pleural fluid can continue to be removed as long as the intrapleural pressure is not less than -20 cmH2O. However, these recommendations require real-time pleural manometry during thoracentesis which is not practical for most clinicians performing a thoracentesis. A recent trial of 124 patients compared pleural manometry vs standard manual aspiration. Pleural manometry did not reduce any complications or patient-centered outcomes. [ii]
Some investigators have theorized that REPE is caused by excessive negative pleural pressures that likely leads to an inflammatory response that induces re-expansion pulmonary edema. That is why aspiration should be aborted if patients develop severe central chest pressure or central chest discomfort during large volume thoracentesis. Coughing and pleuritic chest pain can be common during thoracentesis and these symptoms are not necessarily cause for concern. Even in the rare cases that REPE occurs, it is generally benign, self-limiting and can be managed with supportive care: high-flow oxygen +/- diuretics.
The other myth that I would like to discuss is that abnormal Light’s criteria indicate an exudative effusion. Light’s criteria is about 85% accurate for classifying a transudative vs an exudative pleural effusion. The most common false-positive Light’s criteria is a pleural fluid/serum protein ratio that is greater than 0.5 suggesting an exudate when the pleural fluid LDH is not elevated. This may be related to a transudative pleural effusion in the presence of chronic loop diuretic use. Some additional tests that can be sent that can reclassify a pleural effusion as a transudate when Light’s criteria suggest an exudate are:
- Serum-pleural fluid albumin gradient = serum albumin – PF albumin ³2[iii]
- Pleural fluid NT-pro-BNP>1500 pg/mL suggests transudate from CHF[iv]
To summarize, re-expansion pulmonary edema is an uncommon complication of large volume thoracentesis and there is no absolute volume cap for therapeutic thoracentesis as long as the patient is not experiencing worsening central chest pressure and the operator does not experience a subjective sensation of increased negative intrapleural pressure during aspiration. If REPE develops, it can usually be managed with supportive oxygen therapy and potentially some diuretic therapy. Once pleural fluid is obtained, classify the effusion as a transudate or exudate based on Light’s criteria AND the serum-pleural effusion albumin gradient +/- pleural fluid NT-pro-BNP if chronic CHF is a possibility.
[i] Ault M, Rosen B, Scher J, Feinglass J, Barsuk J. Thoracentesis outcomes: a 12-year experience. Thorax. 2015;70(2):127-132
[ii] Lentz R, Lerner A, Pannu J, et al. Routine monitoring with pleural manometry during therapeutic large-volume thoracentesis to prevent pleural-pressure-related complications: a multicentre, single-blind randomised controlled trial. Lancet Respir Med. 2019;7(5):447-455.
[iii] Sandeesha V, Ravi Kiran CV, Ushakiran P, Sulemani MD, Lakshmanakumar N. A comparative study of serum effusion albumin gradient and Light’s criteria to differentiate exudative and transudative pleural effusion. J Family Med Prim Care. 2020;9(9):4847-4852.
[iv] Janda S, et al. Diagnostic accuracy of pleural fluid NT-pro-BNP for pleural effusions of cardiac origin: a systematic review and meta-analysis. BMC Pulmonary Medicine 2010, 10: 58