DOI: 10.1097/shk.0000000000002751 ISSN: 1540-0514

Ulinastatin Treatment Associated with Lower Sepsis-Associated Encephalopathy Risk in Sepsis Patients: A Multicenter Observational Study

Tingting Xu, Qin Zhang, Hang Ruan, Xiao Ran, Shusheng Li
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Background:

Ulinastatin, widely used in Asia for sepsis management, lacks a comprehensive evaluation regarding its efficacy in preventing sepsis-associated encephalopathy (SAE). This study investigates ulinastatin’s association with SAE incidence and explores combined biomarkers for early SAE prediction.

Methods:

This study employed a dual-cohort design involving 2,200 sepsis patients from a multicenter retrospective cohort and an independent validation cohort of 534 patients from a single-center prospective study. Using logistic regression and propensity score matching, we assessed the association between ulinastatin treatment and SAE incidence in the retrospective cohort. The findings were subsequently validated in the prospective cohort. We also evaluated clinical outcomes in ulinastatin-treated patients and examined the predictive utility of combining nitric oxide levels with key clinical indicators—including fasting blood glucose/high-density lipoprotein cholesterol ratio, Sequential Organ Failure Assessment score, and lactate levels—for early SAE risk stratification.

Results:

In the retrospective cohort, both univariate (odds ratio [OR] 0.618, 95% confidence interval [CI] 0.472–0.811; P = 0.001) and multivariate analyses (OR 0.603, 95% CI 0.453–0.802; P < 0.001) demonstrated that ulinastatin administration was significantly associated with reduced SAE risk. Propensity score matching confirmed this protective relationship. The prospective validation cohort similarly showed ulinastatin treatment was independently associated with lower SAE incidence (adjusted OR 0.491; 95% CI 0.302–0.800; P = 0.004). While individual biomarkers (nitric oxide, fasting blood glucose/high-density lipoprotein cholesterol, Sequential Organ Failure Assessment, and lactate) showed limited predictive value (all area under the receiver operating characteristic curves <0.70), their combination significantly improved SAE prediction accuracy, achieving a maximum area under the receiver operating characteristic curve of 0.726.

Conclusions:

Ulinastatin treatment is significantly associated with reduced SAE incidence in sepsis patients, offering novel insights and potential therapeutic strategies for preventing SAE and improving neurological outcomes.

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