OBJECTIVES: Septic encephalopathy (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. Commonly used sedative drugs, such as propofol and midazolam, may worsen neuronal inflammation. Dexmedetomidine (DEX) has been shown to decrease the production of inflammatory mediators in experimental models of sepsis. The aim of this study was to investigate the effect of DEX on biomarkers associated with SE in critically ill patients with sepsis.
DESIGN: Pilot, open-label, randomized controlled clinical trial.
SETTING: Single-center University Hospital, Switzerland.
PATIENTS: Adult patients with sepsis admitted to the ICU, who required intubation and ongoing sedative medication between September 1, 2019, and June 30, 2022.
INTERVENTIONS: DEX-based sedation compared with propofol and/or midazolam-based sedation and serum S100-ß level at 48 hr after randomization.
MEASUREMENTS AND MAIN RESULTS: The study included 70 participants with 34 (48.6%) randomized to the DEX group and 36 (51.4%) to the propofol/midazolam group. Median S100-ß levels in the DEX group at 48 hr were 0.103 (interquartile range 0.052-0.194) ng/ml, and in the propofol/midazolam group 0.189 (0.086-0.368) ng/mL (p = 0.064). Other biomarker showed no differences over time. In patients with a Glasgow Coma Scale less than or equal to 13, the median S100-ß level in the DEX group was 0.13 ng/mL (0.06-0.18) compared to 0.91 ng/mL (0.43-0.96) in the propofol/midazolam group (p = 0.033).
CONCLUSIONS: DEX-based sedation compared to propofol/midazolam-based sedation did not show any significant difference in S100-ß or any other markers of SE in critically ill patients with sepsis requiring mechanical ventilation. The finding of lower S100-ß levels in DEX-sedated patients with GCS less than 13 warrants further investigation.
| Discipline Area | Score |
|---|---|
| Infectious Disease |  |
| Intensivist/Critical Care |  |
The authors present a interesting study of dexmedetomidine vs propofol/midazolam infusion. Like almost all studies of this nature, it fails to find a clinically significant difference between them, but the biomarker aspect to their study makes for a potential promising direction for a follow-up study.
If prior large RCTs did not demonstrate that dexmedetomidine was superior to propofol/midazolam in reducing delirium, coma-free or ventilator-free days, or mortality in ICU patients with sepsis. Also, the role of S100-ß levels as a biomarker of sepsis encephalopathy is yet uncertain. It is unclear what this relatively small single-center RCT with S100-ß levels as the primary outcome measure hoped to prove in applicable clinical value.