Anisodamine hydrobromide exposure and recovery from sepsis-associated encephalopathy: a two-center retrospective cohort study

Background Anisodamine hydrobromide has been used as an adjunctive therapy for circulatory shock and microcirculatory dysfunction; however, its association with recovery from sepsis-associated encephalopathy remains unclear. This study examined the relationship between anisodamine hydrobromide exposure and neurological recovery in patients with sepsis. Methods This two-center retrospective cohort study included adult patients with sepsis admitted to two tertiary hospitals in China between January 2020 and May 2026. Patients who received anisodamine hydrobromide within 24 h of admission were compared with those who did not. The primary outcome was delirium/coma-free days within 7 days of admission. Secondary outcomes included new-onset delirium, delirium duration, time to Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) negativity, Glasgow Coma Scale (GCS) score changes, lactate clearance, capillary refill time (CRT), endothelial injury biomarkers, blood–brain barrier and neural injury biomarkers, and safety outcomes. Results In total, 499 patients were included, of whom 226 received anisodamine hydrobromide and 273 were controls. Anisodamine hydrobromide exposure was associated with more delirium/coma-free days within 7 days than the control group, with negative binomial regression yielding consistent results. The incidence of new-onset delirium did not differ significantly between groups. Among patients who developed delirium, anisodamine hydrobromide exposure was associated with shorter delirium duration. It was also associated with earlier CAM-ICU negativity, greater GCS improvement, higher lactate clearance, shorter CRT, and greater reductions in soluble thrombomodulin, angiopoietin-2, S100β, neuron-specific enolase, and glial fibrillary acidic protein. Anticholinergic-related adverse events were not significantly increased in the anisodamine hydrobromide group. Conclusion Anisodamine hydrobromide exposure was associated with more delirium/coma-free days, shorter delirium duration, earlier CAM-ICU negativity, and greater improvements in neurological, microcirculatory, endothelial, and blood–brain barrier/neural injury markers in patients with sepsis.