Association between senna use and outcomes in critically ill patients with hepatic failure: A propensity score-matched real-world cohort study

BACKGROUND: Hepatic failure remains associated with substantial mortality in critically ill patients, with gut-liver axis dysfunction playing an important pathogenic role. Senna, a stimulant laxative with potential pleiotropic effects including gut microbiota modulation and anti-inflammatory properties, and hepatoprotective, may offer therapeutic benefits beyond bowel management. However, its impact on mortality outcomes in this population remains unclear. METHODS: This retrospective cohort study analyzed 1751 critically ill patients with hepatic failure from the MIMIC-IV database (2008-2022). Patients were stratified by senna exposure during Intensive Care Unit (ICU) stay. The primary outcome was 28-day all-cause mortality. Secondary outcomes included ventilator-free days, vasopressor-free days, and ICU-free days within 28 days. Propensity score matching (PSM) and multiple Cox regression models were employed to assess associations. Subgroup analyses explored effect modification, and dose-response relationships were also evaluated. RESULTS: Among 1751 patients (mean age 59.9 ± 15.5 years, 60.4% male), 764 (43.6%) received senna. After PSM (456 pairs), senna use was independently associated with lower 28-day mortality [adjusted: HR (hazard ratio) 0.69, 95%CI 0.58-0.82, p < 0.001]. The E-value is 1.91. This association remained robust in sensitivity analyses including PS-adjusted model (HR 0.81, 95%CI 0.68-0.96, p = 0.017), PSM cohort (HR 0.79, 95%CI 0.64-0.98, p = 0.029), and partial adjustment (HR 0.79, 95%CI 0.64-0.98, p = 0.013). A dose-response relationship was observed, with each 10 mg increase in cumulative senna dose associated with 14% lower mortality (adjusted HR 0.86, 95%CI 0.82-0.90, p < 0.001). Senna administration was associated with an increased number of ventilator-free days (adjusted β=1.38, 95%CI 0.12-2.63, p = 0.031) and vasopressor-free days (adjusted β=1.52, 95%CI 0.26-2.79, p = 0.018). Subgroup analyses revealed stronger mortality benefits in patients aged <65 years, MELD (Model for End-Stage Liver Disease) score ≥24, and APSIII (Acute Physiology Score III) score ≥74 (all p for interaction <0.05). CONCLUSIONS: In this large real-world cohort, senna use was independently associated with lower 28-day mortality with evidence of a dose-response relationship. Prospective randomized controlled trials are warranted to establish causality and inform clinical practice guidelines.