Adjunctive Sedation With Dexmedetomidine for the Prevention of Severe Inflammation and Septic Encephalopathy
Summary
Septic encephalopathy (SE) is defined as acute cerebral dysfunction in patients with sepsis or septic shock. SE occurs in up to 50% of critically ill patients with sepsis and is associated with a high mortality and morbidity. The pathophysiology of SE is complex and involves increased levels of inflammatory mediators such as tumor necrosis factor (TNF)-α, Interleukin (IL)-1 and IL-6, leading to blood brain barrier dysfunction and neuronal inflammation. Several biomarkers of neuronal injury have been proposed to identify patients with SE. Of these biomarkers, S100-β has the highest sensitivity and specificity. Sedation with Dexmedetomidine (DEX) is a promising strategy for the management of these patients, as DEX has been shown to decrease the production of inflammatory mediators in experimental models of sepsis. In clinical studies, DEX lowers the incidence of delirium and critical illness polyneuropathy. However, its effectiveness in treatment and prevention of SE remains unclear. The aim of the present study is to investigate the effect of two standard sedation protocols (Dexmedetomidine sedation vs. Propofol / Midazolam) on serum markers of SE in critically ill patients with sepsis who require sedation and mechanical ventilation.
Timeline
- Start
- 2019-09-01
- Primary completion
- 2022-06-17
- Completion
- 2022-07-08
Outcome
Missed primary endpoint
paper DEX-based sedation compared to propofol/midazolam-based sedation did not show any significant difference in S100-β or any other markers of SE PMID 40162868 ↗
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Dexmedetomidine | Other / unclassified | — | — |
| Comparator | Midazolam | Small molecule | — | — |
| Comparator | Propofol | Small molecule | — | — |