Transitions to Comfort Measures Only Among Patients Hospitalized With Sepsis: Clinical Drivers and Implications for Mortality

Background Mortality in sepsis is often considered a direct consequence of infection and organ dysfunction, although many deaths occur after withdrawal of life sustaining treatment. The clinical factors leading to these decisions and their implications for interpreting sepsis mortality are not well characterized. Methods We performed a secondary analysis of a prospective observational cohort of adults with physician adjudicated sepsis at a tertiary academic medical center. Patients who transitioned to comfort measures only (CMO) during the index hospitalization underwent structured chart review to characterize baseline health and functional status, clinical severity, care preferences, anticipated outcomes following survival, and the primary reason for CMO transition. Results Among 239 patients with adjudicated sepsis, 42 (17.6%) transitioned to CMO. These patients had substantial underlying disease, including malignancy in 76% and immunocompromised status in 62%. However, 88% lived at home before hospitalization, 52% were independent in activities of daily living, an additional 26% were partially independent, and 90% were full code on admission. Progressive multi organ failure (19%), refractory septic shock (19%), and irreversible respiratory failure (12%) accounted for half of CMO transitions, while advanced frailty (5%) and poor baseline functional status (2%) were infrequent primary reasons. Median time from admission to CMO was 16 days (IQR 7 to 33), and median time from admission to death was 18 days (IQR 11 to 35). Anticipated ventilator dependence (62%), dialysis dependence (36%), and cognitive impairment frequently influenced goals of care discussions. Overall, 38 patients died during the index hospitalization, and 35 (92%) of these deaths followed transition to CMO. Conclusions Most CMO transitions in this cohort occurred after an evolving course of severe sepsis and were driven primarily by progressive organ dysfunction and failure to recover rather than advanced frailty or poor baseline function. These findings identify failure to recover after the acute septic insult as an important clinical trajectory and highlight the need to account for treatment limitation when interpreting sepsis mortality. Understanding why some patients recover from sepsis associated organ dysfunction while others progress to irreversible organ failure may help identify patients and mechanisms for future therapeutic intervention.