Impact of Urokinase Shortage on Empyema Management and Clinical Outcomes in Japan.

INTRODUCTION: Urokinase is an important fibrinolytic therapy for empyema. In February 2022, a nationwide shortage occurred, but its impact remains unclear. PATIENTS AND METHODS: We conducted a retrospective cohort study using a nationwide Japanese administrative database. Adults with empyema who underwent pleural drainage or surgery from January 2020 to December 2023 were identified. Treatment changes were evaluated using interrupted time-series (ITS) analysis and visualized with an alluvial plot. Clinical outcomes were evaluated using multivariable logistic regression. The primary outcome was in-hospital mortality, and the secondary outcome was prolonged hospitalization (≥60 days). RESULTS: Among 9,104 patients, urokinase use declined from 27.1% to 9.2%, whereas surgery increased from 18.9% to 23.0% after February 2022. ITS analysis demonstrated significant post-restriction slope changes in urokinase use (odds ratio [OR] = 0.87, 95% confidence interval [CI] = 0.86-0.88) and surgery (OR = 1.03, 95% CI = 1.01-1.04). The alluvial plot showed reduced urokinase use and increased surgical and conservative management. In-hospital mortality was 13.8% before and 14.5% after the shortage, and the shortage period was not associated with increased in-hospital mortality (adjusted OR: 1.05, 95% CI: 0.92-1.20). No clear increase in prolonged hospitalization was observed. CONCLUSIONS: The urokinase shortage substantially altered empyema management, although no clear worsening of short-term clinical outcomes was detected.