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When draining a large pleural effusion, the main concern is that excessive fluid removal could lead to re-expansion pulmonary edema.  Clinically significant re-expansion pulmonary edema is very rare, but case reports suggest that it could be dangerous.

Traditional guidelines recommend that the volume of fluid removed during a thoracentesis should be limited to <1.5 liters, to avoid re-expansion pulmonary edema.  However, there is no data to support these arbitrary guidelines.  Over time, the cutoff for the safe volume of fluid which may be removed seems to have gradually been drifting upwards without any specific evidence (from 1 liter, to 1.5 liters, and now 1.8 liters is surfacing more often in the literature).^​1​

Some data suggests that the risk of re-expansion pulmonary edema might correlate with the baseline size of the effusion, rather than the volume of fluid removed.^​2​ This is an extremely difficult distinction to draw, because these two variables are closely correlated (we remove more fluid from larger effusions).  However, this distinction is absolutely essential: 

• Larger effusions may cause more compression injury of lung tissue, leading to a higher risk of re-expansion pulmonary edema. 
• The volume of fluid removed may not impact the risk of re-expansion pulmonary edema.  Specifically, larger effusions may be more likely to cause re-expansion pulmonary edema – regardless of whether a small or large volume of fluid is removed.

The fanciest approach to prevent re-expansion pulmonary edema is pleural manometry.  This involves monitoring pleural pressure during thoracentesis.  Theoretically, avoiding a substantially negative pleural pressure (below -20cm water) might reduce the risk of re-expansion pulmonary edema.  However, there is no persuasive evidence to support this.  The concept that re-expansion pulmonary edema is due to negative pleural pressures depends on an over-simplified model of re-expansion pulmonary edema (based on the concept of Starling forces which suck fluid into the lung tissue).  In reality, re-expansion pulmonary edema probably has more to do with inflammation and endothelial damage than with Starling forces. 

My opinion on large volume thoracentesis was explored in this blog from 2014.  It may be summarized as follows:

1. There is no evidence that re-expansion pulmonary edema can be avoided by limiting the volume of fluid removed to an arbitrary amount (e.g. 1.5 liters) or by the use of pleural manometry.
2. Re-expansion pulmonary edema is rare and generally manageable with supplemental oxygen +/- BiPAP.      
3. The risk of re-expansion pulmonary edema is lower than the risk of other complications associated with thoracentesis (e.g. bleeding, lung laceration).  Therefore, performing multiple small thoracenteses in efforts to avoid re-expansion pulmonary edema doesn’t make sense (multiple procedures may overall increase the risk of a procedural complication).
4. If the patient develops central, vague chest discomfort during a thoracentesis, this does seem to be a sign that excessive negative pressure is developing.  This should be an indication to stop the procedure. 
5. Coughing during thoracentesis is generally an indication of normal lung tissue re-expansion and isn’t an indication to terminate the thoracentesis procedure.
6. Large effusions should be drained dry if this is clinically tolerated by the patient (without the development of central chest discomfort or tightness). 

This post will attempt to evaluate these concepts based on the emergence of two new studies. 

Ault MJ et al.  Thoracentesis outcomes:  a 12-year experience.

This is a cohort study of inpatients who underwent thoracentesis at Cedars-Sinai Medical Center between 2001-2012.^​3​ Data was recorded prospectively during 9320 thoracenteses, providing the largest published series to investigate the rate of rare adverse events.

Thoracentesis was performed without the use of manometry.  Effusions were drained dry unless the patients experienced worsening symptoms or the operator had a subjective sensation of increasingly negative intrapleural pressure (a hand pumping method was used to remove fluid using a syringe with a one-way valve).  799 thoracentesis procedures were performed with removal of >1500 ml fluid.

Overall, there were 10 cases of re-expansion pulmonary edema as shown here:

For patients with removal of >1.5 liters of fluid, the rate of re-expansion pulmonary edema was 6/799 (0.75%).  No patient died due to re-expansion pulmonary edema.  This demonstrates that re-expansion pulmonary edema is generally rare – even in the context of large-volume thoracentesis.  No data is provided about the severity of these episodes, but it is likely that most were mild to moderate in severity.

The rate of bleeding was higher than the rate of re-expansion pulmonary edema (17 vs 10, respectively).  Performing multiple low-volume thoracentesis procedures will further elevate the risk of bleeding, in efforts to reduce the risk of re-expansion pulmonary edema. 

Lentz RJ et al.  Routine monitoring with pleural manometry during therapeutic large-volume thoracentesis to prevent pleural-pressure-related complications:  a multicenter, single-blind randomized controlled trial.

This is a multicenter, single-blind RCT investigating the drainage of large pleural effusions.^​4​ Patients were randomized to two drainage strategies:

• Control group:  Thoracentesis was performed until complete drainage of the effusion, unless there were concerning symptoms (persistent chest discomfort or intractable cough).
• Manometry group:  Pleural pressures were monitored during the thoracentesis procedure.  Fluid removal was terminated if there were concerning symptoms or development of pleural pressures below -20 cm water or if the pressure was falling precipitously (decline by more than 10 cm water between two measurements, to a value below -10 cm). 

124 patients were included in the final analysis, with good matching between groups (table below).  Malignancy was the most common cause of effusion.  Most patients were outpatients, with some inpatients and only a few patients in the ICU.  

The primary endpoint was chest discomfort after the procedure.  This was chosen as a surrogate measurement for the removal of excessive volumes of fluid (leading to negative intrathoracic pressure).  There were no differences in chest discomfort during or after the thoracentesis procedure.

Manometry was able to prevent pneumothorax ex vacuo, a benign and self-limiting condition which occurs when a pleural effusion is drained completely but the lung is unable to expand (table below).  As previously discussed here, pneumothorax ex vacuo isn’t a clinical problem as long as clinicians are aware of its benign nature (specifically, pneumothorax ex vacuo should never be “treated” with a chest tube).  None of the patients in this study with pneumothorax ex vacuo required any treatment for this or had any symptoms – illustrating the benignity of this phenomenon. 

No patient in the study developed re-expansion pulmonary edema.  However, the average volume of fluid removed was only one liter, which may limit the sensitivity to detect this complication. 

This study represents the highest-quality evidence to date regarding the use of manometry to monitor thoracentesis.  Manometry didn’t affect any patient-centered outcome. 

• Large pleural effusions can generally be drained entirely (although the procedure should be stopped if the patient develops vague central chest discomfort). 
• Pleural manometry has not been shown to reduce discomfort or re-expansion pulmonary edema during large volume thoracentesis.    
• The rate of re-expansion pulmonary edema is low, even in large-volume thoracentesis (<1%).  When it occurs, this can generally be treated with conservative measures (e.g. supplemental oxygen or noninvasive ventilation). 
• Using multiple small-volume thoracenteses to avoid large-volume thoracentesis is probably a misguided strategy.  Multiple small-volume thoracenteses may cause an overall increase in the risk of procedural complications (due to increases in the risk of bleeding, infection, or lung laceration with multiple procedures). 

Update: GRAVITAS trial (11/22/19)

The GRAVIAS trial is a prospective multi-center RCT which investigated drainage of large effusions to dryness, if clinically tolerated. The study focused on comparing a hand pump with gravity drainage, with the hypothesis that gravity drainage would be a bit gentler and more comfortable. No differences were observed between the two groups. More importantly, no significant adverse events were noted. This trial is under-powered to evaluate for severe adverse events (e.g. re-expansion pulmonary edema). However, the performance and results of this trial are one more piece of evidence that it's safe and reasonable to drain effusions to dryness (if clinically tolerated).

going further

• Large volume thoracentesis I (PulmCrit, 2014)
• Pneumothorax ex vacuo: Post-thoracentesis pneumothorax in the ultrasonography era (PulmCrit)
• How safe is thoracentesis?  A giant case series sheds light (PulmCCM)

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Josh Farkas

Josh is the creator of PulmCrit.org. He is an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont.

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