Abstract
BACKGROUND: Encephalopathy is a frequent complication of circulatory shock and is associated with adverse outcomes. Whether encephalopathy is driven primarily by systemic inflammation, endothelial activation or cerebral hypoperfusion remains uncertain. METHODS: We retrospectively studied 198 intensive care unit (ICU) patients with circulatory shock (95 septic shock, 103 non-septic shock). Encephalopathy (coma and delirium) was assessed using the Glasgow Coma Scale, Richmond Agitation-Sedation Scale, and Confusion Assessment Method for the ICU. Neuroinflammation or blood-brain barrier (BBB) dysfunction was evaluated using serum S100B protein. Systemic inflammation and endothelial activation were assessed using serum C-reactive protein (CRP), Matrix metalloproteinase-9 (MMP-9), Intercellular Adhesion Molecule -1 (ICAM-1) and Vascular Endothelial Growth Factor (VEGF). Severe hypotension was defined a priori as mean arterial pressure (MAP) <50 mmHg sustained ≥1 min; we also quantified the number of episodes and cumulative duration of MAP <60 and <50 mmHg across the first 72 h. Multivariable logistic regression and mixed-effect models examined associations with encephalopathy and ICU outcomes. RESULTS: Encephalopathy developed in 140 patients (71%): 31 (23%) with coma and 99 (71%) with delirium. Severe hypotension (OR: 2.56 (1.18, 4.75), p = 0.022), longer sedation duration (OR: 1.09 (1.02, 1.18), p = 0.017), ICU-acquired infections (OR: 1.61(0.73, 3.54), p = 0.021), and elevated S100B (OR: 1.72 (0.66, 3.65), p = 0.03) were associated with encephalopathy. In contrast, systemic inflammation (CRP, MMP-9) and endothelial activation (ICAM-1, VEGF) were not associated with encephalopathy. Despite higher systemic inflammation in septic shock, the prevalence of encephalopathy and structural brain injury was similar to non-septic shock. CONCLUSIONS: In circulatory shock, encephalopathy is most strongly associated with recurrent/severe hypotension (MAP <50 mmHg) and markers of neuroinflammation, not systemic inflammation or endothelial activation.