TOPLINE:

Full MIST2 dosing of intrapleural enzyme therapy (IET) was infrequent and showed significant facility-level variation across hospitals. The receipt of full dosing was associated with a lower risk for treatment escalation or bleeding and with shorter hospital length of stay.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to evaluate variability in IET dosing across a large integrated healthcare system and assess associations between the MIST2 regimen and patient outcomes.
• They assessed 1730 adults (mean age, 67 years; 64% men) hospitalized with complicated parapneumonic effusion or empyema at 21 hospitals in California between 2015 and 2023.
• Full MIST2 dosing was defined as receiving six standard doses of 10 mg alteplase and 5 mg dornase, with two doses of both drugs given in each 24-hour period for at least 2 consecutive days.
• Primary outcomes were treatment escalation (placement of a second chest tube or thoracic surgery) and bleeding complications (requiring transfusion or surgical evacuation of hematoma). Secondary outcomes included inpatient hospital length of stay and mortality.

TAKEAWAY:

• A significant facility-level variation was observed in full MIST2 dosing implementation across hospitals, with an intraclass correlation coefficient of 0.57.
• Treatment escalation occurred in 28.4% of encounters and bleeding complications in 7.8% of encounters, with full MIST2 dosing showing a protective effect against these outcomes (hazard ratio, 0.61; 95% CI, 0.43-0.88; P = .009).
• Full MIST2 dosing was associated with a 15% reduction in hospital length of stay (95% CI, 5%-23%; P = .003), with a mean length of stay of 11.4 days with full dosing vs 13.4 days without full dosing.
• Full MIST2 dosing was not significantly associated with inpatient mortality.

IN PRACTICE:

“[Our study] results should inform care delivery pathways for patients admitted with parapneumonic pleural effusion and empyema and provide supporting evidence of the need to offer full MIST2 dosing during nighttime and weekend hours when pulmonary specialists might not be available,” the authors of the study wrote. 

SOURCE:

The study was led by Eduardo Solbes, MD, Kaiser Permanente Northern California, Oakland, California. It was published online on December 10, 2025, in Chest.

LIMITATIONS:

Because this was a retrospective cohort study, the results may have been affected by unmeasured factors. Measured factors such as comorbidity burden and illness severity were similar; however, unmeasured differences among patients receiving full MIST2 dosing cannot be ruled out.

DISCLOSURES:

This study was funded by a healthcare delivery science grant from The Permanente Medical Group. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.