Neurometabolic therapy with Cerebrolysin in patients with sepsis-associated encephalopathy

Sepsis-associated encephalopathy (SAE) presents acute neurological dysfunction following sepsis. Objective. To evaluate the effectiveness of Cerebrolysin in patients with SAE using clinical and laboratory methods. Material and methods. A single-center prospective randomized controlled clinical trial included 40 patients with sepsis or septic shock. Patients were randomized into 2 groups: group 1 — Cerebrolysin therapy, group 2 — no appropriate therapy. We analyzed cerebral biomarkers (S100B, NSE, NR2AT) in 1, 7, 14, 21 and 28 days after diagnosis of sepsis. Neurological status was assessed using the CAM-ICU (Confusion Assessment Method-Intensive Care Unit) scale, the Richmond Agitation-Sedation Scale (RASS), the FOUR (Full Outline of UnResponsiveness) scale and Glasgow Coma Scale (GCS). In both groups, neurovegetative stabilization was used for neuroprotection (haloperidol ± dexmedetomidine for delirium; propofol ± fentanyl ± α2-adrenergic agonist clonidine/dexmedetomidine for impaired consciousness with coma). We chose neurovegetative stabilization (mono- or multicomponent scheme) and depth of blockade in each specific clinical case. Results. In the 1st group, the period of impaired consciousness was significantly shorter according to the CAM-ICU, RASS, FOUR and GCS scales. We revealed a significant decrease in biomarkers of acute cerebral injury, such as NSE and S100B (after 14, 21 and 28 days compared to the 1st and 7th days) in patients with SAE undergoing Cerebrolysin therapy. According to ROC analysis, the likelihood of positive effect after neurometabolic Cerebrolysin therapy is higher in serum S100B protein ≤97 µg/l on the 14th day of sepsis compared concentration >97 µg/l (AUC=0.65±0.17; 95% CI 0.43—0.88; p<0.001). Conclusion. Inclusion of Cerebrolysin in intensive care for sepsis complicated by acute cerebral dysfunction (delirium: CAM-ICU positive) and coma (FOUR ≤12; GCS ≤9) under neurovegetative stabilization accelerates recovery of consciousness in patients with sepsis-associated encephalopathy.