Abstract
Background: Sepsis-associated encephalopathy (SAE) is a neurological complication of sepsis characterized by acute brain dysfunction in the absence of direct central nervous system infection. Interleukin-1 beta (IL-1β) is a proinflammatory cytokine that may play an important role in this process.
Objective: To evaluate the diagnostic performance of IL-1β in predicting SAE among patients with sepsis admitted to the intensive care unit.
Methods: This observational study included adult patients with sepsis admitted to the intensive care unit (ICU) at Dr. Wahidin Sudirohusodo General Hospital, Makassar. Serum IL-1β was measured at 24 hours, alongside procalcitonin and C-reactive protein. Neurological status and disease severity were assessed using the Glasgow Coma Scale (GCS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis, including area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio, negative likelihood ratio, and diagnostic accuracy.
Results: From a parent cohort of 123 consecutive septic ICU patients, 25 patients who developed SAE and 25 non-SAE controls were included in the final biomarker analysis. At 24 hours, IL-1β levels were significantly higher in patients with SAE than in those without encephalopathy. ROC analysis showed that IL-1β had an AUC of 0.935 (95% confidence interval [CI]: 0.872–0.990; p<0.001). At a cutoff value of >28.5 pg/ml, IL-1β showed 84.0% sensitivity, 80.0% specificity, 80.8% PPV, 83.3% NPV, and 82.0% accuracy. Procalcitonin and C-reactive protein (CRP) showed lower diagnostic performance, with AUC values of 0.827 and 0.782, respectively. In adjusted Firth penalized logistic regression models, 24-hour IL-1β remained associated with SAE after separate adjustment for age, SOFA score, and APACHE II score.
Conclusion: IL-1β measured at 24 hours demonstrated excellent discriminatory performance for predicting SAE in critically ill patients with sepsis and may serve as an adjunctive biomarker to support early neurological risk stratification. Larger multicenter studies with adjusted analyses are required to validate its clinical utility.
Sri Rinia Sari Iswanti, Haizah Nurdin, Andi Adil, Syamsul Hilal Salam, Faisal Muchtar, Charles Wijaya Tan
