Textbook of Pleural Diseases, Third Edition by Richard W. Light

Author:Richard W. Light
Language: eng
Format: epub
Publisher: CRC Press
Published: 2018-03-14T04:00:00+00:00

Figure 23.14 Primary result of the MIST2 study11 showing relative change in chest radiograph pleural opacity by treatment arm, measured at day 7 and expressed as percentage of hemithorax occupied.

(From Rahman NM et al., N Engl J Med, 365(6), 518–526, 2011. With permission.)

The MIST2 trial results11 reaffirm the findings of the MIST1 trial10 that fibrinolytics alone—be it tPA or streptokinase—have no clinical benefit in adult pleural infection, but also identify a potential role for the novel combination of intrapleural tPA and DNase while providing clues toward their modes of action. DNase may reduce fluid viscosity and release bacteria into the pleural space, potentially causing the sepsis response (increased odds of fever at day 7) and increased surgical referral rate seen in MIST2 patients on this agent alone,11 but cannot improve drainage alone. Fibrinolytics (tPA) break down septations but in isolation cannot alter fluid viscosity to enhance clearance of infected material. Instead, it is only through combining these two modes of action—reduction in both septations (tPA) and fluid viscosity (DNase)—that drainage of infected material from within the pleural space can be successfully achieved.

In terms of everyday clinical practice, the results of the MIST2 trial11 while promising require replication on a larger scale before the routine use of combination intrapleural therapy (tPA and DNase) can be widely recommended. There are strong signals toward benefit in key clinical outcomes such as surgical referral rate and hospital stay,11 but these measures have wide confidence intervals and do not provide robust enough evidence. The limited number of patients (n = 52) in the combination therapy arm also means a full description of the drugs’ safety profile is not possible. Instead, further and larger trials of this combination intrapleural therapy assessing nonradiological primary outcomes of clinical importance are both necessary and planned before widespread use in pleural infection becomes commonplace. For now, in the authors’ view, combination of tPA and DNase should be limited to those cases where conventional tube thoracostomy has failed and patients are not suitable for more established methods (i.e., thoracic surgery) of clearing infected material from the pleural space.

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