Iten Manuela, Bachmann Kaspar, Jakob Stephan M, Grandgirard Denis, Leib Stephen L, Cioccari Luca
Department of Intensive Care Medicine, Inselspital, University Hospital Bern, Bern, Switzerland.
University of Bern, Bern, Switzerland.
Crit Care Med. 2025 Jul 1;53(7):e1377-e1388. doi: 10.1097/CCM.0000000000006655. Epub 2025 Mar 31.
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.
Pilot, open-label, randomized controlled clinical trial.
Single-center University Hospital, Switzerland.
Adult patients with sepsis admitted to the ICU, who required intubation and ongoing sedative medication between September 1, 2019, and June 30, 2022.
DEX-based sedation compared with propofol and/or midazolam-based sedation and serum S100-β level at 48 hr after randomization.
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-β 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-β 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).
DEX-based sedation compared to propofol/midazolam-based sedation did not show any significant difference in S100-β or any other markers of SE in critically ill patients with sepsis requiring mechanical ventilation. The finding of lower S100-β levels in DEX-sedated patients with GCS less than 13 warrants further investigation.
脓毒症性脑病（SE）在高达50%的脓毒症重症患者中发生，且与高死亡率和高发病率相关。SE的病理生理学很复杂，涉及炎症介质水平升高。常用的镇静药物，如丙泊酚和咪达唑仑，可能会加重神经元炎症。右美托咪定（DEX）已被证明在脓毒症实验模型中可减少炎症介质的产生。本研究的目的是调查DEX对脓毒症重症患者中与SE相关的生物标志物的影响。
前瞻性、开放标签、随机对照临床试验。
瑞士单中心大学医院。
2019年9月1日至2022年6月30日期间入住重症监护病房（ICU）、需要插管并持续使用镇静药物的成年脓毒症患者。
随机分组后48小时，比较基于DEX的镇静与基于丙泊酚和/或咪达唑仑的镇静以及血清S100-β水平。
该研究纳入70名参与者，34名（48.6%）随机分配至DEX组，36名（51.4%）分配至丙泊酚/咪达唑仑组。DEX组48小时时S100-β水平中位数为0.103（四分位间距0.052 - 0.194）ng/ml，丙泊酚/咪达唑仑组为0.189（0.086 - 0.368）ng/mL（p = 0.064）。其他生物标志物随时间未显示差异。在格拉斯哥昏迷量表（GCS）小于或等于13的患者中，DEX组S100-β水平中位数为0.13 ng/mL（0.06 - 0.18），而丙泊酚/咪达唑仑组为0.91 ng/mL（0.43 - 0.96）（p = 0.033）。
对于需要机械通气的脓毒症重症患者，与基于丙泊酚/咪达唑仑的镇静相比，基于DEX的镇静在S100-β或任何其他SE标志物方面未显示出任何显著差异。在GCS小于13的接受DEX镇静的患者中S100-β水平较低这一发现值得进一步研究。
