Severe hypotension but not systemic inflammation or endothelial activation predicts encephalopathy in circulatory shock

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. 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. 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. 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.