Pleural Empyema in Spain (2016–2022): A Nationwide Study on Trends in Hospitalizations, Mortality, and Impact of Comorbidities

<b>Background</b>: Pleural empyema (PE) is a major cause of morbidity and mortality worldwide. This study aimed to analyze the epidemiological characteristics of patients hospitalized for PE in Spain between 2016 and 2022. <b>Methods</b>: This retrospective observational study of PE cases was based on the hospital discharge records from the National Health System between 2016 and 2022. The variables analyzed were sex, age, comorbidities, discharge diagnoses and procedures, overall severity, whether empyema was a primary or secondary diagnosis, admission to the intensive care unit (ICU), length of stay (LOS), in-hospital mortality, and healthcare costs. <b>Results</b>: Between 2016 and 2022, 19864 PE cases were diagnosed in Spain, revealing an overall rate of 0.64 per 1000 hospitalizations, with the exception of a slight decline in 2021. The mean age of the patients with PE was 61 years, and 73.85% were men. Most patients had low comorbidities, with a median Charlson comorbidity index (CCI) of 1.7. Most cases (63%) involved secondary diagnoses (pneumonia, pneumococcal pneumonia, sepsis, COVID, or lung cancer). The in-hospital mortality rate was higher in the secondary diagnosis group than in the primary diagnosis group (13.4% vs. 6.2%, respectively, <i>p</i> < 0.001). The factors associated with increased mortality included older age (≥66 years), higher CCI scores, ICU admission, and shorter LOS (<10 days). Conversely, pleural drainage and pneumonia as secondary diagnoses were protective factors. <b>Conclusions</b>: PE is an increasingly common pathology in clinical practice, especially in older and frail patients. It is associated with high morbidity and mortality, and its prognosis worsens with age and comorbidities. Therefore, early and appropriate diagnosis and standardized management strategies are required to mitigate the mortality and healthcare costs.