Use of and Outcomes Related to Intrapleural Enzyme Therapy for Complicated Parapneumonic Effusion and Empyema in an Integrated Health System.

Abstract

The Second Multicenter Intrapleural Sepsis Trial (MIST2) trial showed that twice-daily dosing of intrapleural enzyme therapy (IET) for 3 days improved outcomes in patients with pleural infection. Many hospitals are unable to administer IET on that schedule. What is the variation in full MIST2 regimen dosing of IET across 21 hospitals in adults hospitalized with complicated parapneumonic effusion or empyema? What are the associations between full MIST2 dosing and outcomes? This study included a retrospective cohort of 1,730 adults hospitalized at Kaiser Permanente Northern California with complicated parapneumonic effusion or empyema who received antibiotics, tube thoracostomy, and at least 1 dose of IET. The primary exposure full MIST2 dosing was defined as receiving 6 doses of alteplase 10 mg and dornase 5 mg, with 2 doses of each medication being given in each 24-hour period for at least 2 consecutive days. Facility-attributable variation in IET dosing was assessed using mixed-effects modeling. The primary outcome of treatment escalation (second concurrent chest tube or surgery) or bleeding (transfusion of blood products or surgical evacuation of hematoma) was evaluated in a time-to-event analysis with death as the competing risk. The secondary outcome was hospital length of stay. Of 1,751 encounters, full MIST2 dosing occurred in 99 encounters (5.7%). High facility-level variation was found in full MIST2 dosing (intraclass correlation coefficient, 0.57). Minimal differences in comorbidity or severity of illness were found between exposed and unexposed patients. Treatment escalation occurred in 498 encounters (28.4%); bleeding occurred in 137 encounters (7.8%). Full MIST2 dosing showed a protective association against treatment escalation or bleeding (hazard ratio, 0.61; 95% CI, 0.43-0.88; P = .009). Full MIST2 dosing was associated with 15% reduction (95% CI, 5%-23% reduction; P = .003) in hospital length of stay (mean, 13.4 days vs 11.4 days). Full MIST2 dosing was infrequent with a high degree of facility-level variation. Given the protective association, hospitals should consider delivering full MIST2 dosing.