Chang Enqiang, Wu Lingzhi, Li Xinyi, Zhou Jinpeng, Zhi Hui, Sun Min, Chen Guanyu, Bi Jiaqi, Li Li, Li Tianxiao, Ma Daqing, Zhang Jiaqiang
Department of Anesthesiology and Perioperative Medicine, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, China; Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
Med. 2025 Mar 14;6(3):100523. doi: 10.1016/j.medj.2024.09.012. Epub 2024 Oct 28.
Cerebral hyperperfusion syndrome (CHS) is a severe complication after carotid artery stenting (CAS). Dexmedetomidine (Dex) is an α adrenoceptor agonist with sedative, analgesic, and neuroprotective properties. This randomized, double-blind, placebo-controlled trial (ChiCTR1900024416) aims to investigate whether prophylactic low-dose Dex decreases CH-induced brain injury following CAS.
After obtaining written informed consent, patients aged 18-80 who underwent CAS were enrolled between July 2019 and October 2022. Patients were randomly assigned to receive either intravenous Dex (0.1 μg/kg/h, until post-operative day 3) (n = 80) or placebo (normal saline) (n = 80). The primary endpoint was the incidence of CH and CHS assessed up to the third post-operative day. The secondary endpoints included National Institute of Health Stroke Scale (NIHSS) and Modified Rankin Scale (mRS) scores within 30 days of operation, extubation time, discharge from the hospital within 7 days post-operation, length of hospital stay post-operation, and all-cause 30-day mortality. Blood samples were collected before and after surgery for lipidomics, brain-derived neurotrophic factor (BDNF), and neurofilament light chain (Nfl) measurements. Acceptability, safety, and efficacy were evaluated by Cox model and logistic model.
CH occurred in 30 (37.5%) of 80 patients who received a placebo compared to 9 (11.2%) of 80 patients given Dex (prevalence: odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.088-0.467; p < 0.001; incidence: hazard ratio [HR]: 0.27, 95% CI: 0.14-0.50; p < 0.001). CHS was significantly higher in the placebo group (13.75%) than in the Dex group (2.5%) (prevalence: [OR]: 0.161, 95% CI: 0.024-0.626; p = 0.020; incidence: [HR]: 0.17, 95% CI: 0.06-0.52; p = 0.009). Dex significantly upregulated BDNF, decreased Nfl, and uniquely increased lysophosphatidylethanolamine.
A low prophylactic dose of Dex significantly reduced the incidence of CH and CHS up to 72 h after CAS.
This work was funded by National Natural Science Foundation of China (no. 82271288) and the Henan Provincial Science and Technology Research Project (nos. 242300421192 and JQRC2023004).
脑血流灌注过度综合征(CHS)是颈动脉支架置入术(CAS)后一种严重的并发症。右美托咪定(Dex)是一种α肾上腺素能受体激动剂,具有镇静、镇痛和神经保护特性。这项随机、双盲、安慰剂对照试验(ChiCTR1900024416)旨在研究预防性低剂量Dex是否能减少CAS后CH引起的脑损伤。
在获得书面知情同意后,2019年7月至2022年10月期间纳入了18至80岁接受CAS的患者。患者被随机分配接受静脉注射Dex(0.1μg/kg/h,直至术后第3天)(n = 80)或安慰剂(生理盐水)(n = 80)。主要终点是评估至术后第3天的CH和CHS发生率。次要终点包括术后30天内的美国国立卫生研究院卒中量表(NIHSS)和改良Rankin量表(mRS)评分、拔管时间、术后7天内出院情况、术后住院时间以及30天全因死亡率。手术前后采集血样进行脂质组学、脑源性神经营养因子(BDNF)和神经丝轻链(Nfl)测量。通过Cox模型和逻辑模型评估可接受性、安全性和有效性。
接受安慰剂的80例患者中有30例(37.5%)发生CH,而给予Dex的80例患者中有9例(11.2%)发生CH(患病率:比值比[OR]:0.21,95%置信区间[CI]:0.088 - 0.467;p < 0.001;发生率:风险比[HR]:0.27,95% CI:0.14 - 0.50;p < 0.001)。安慰剂组的CHS显著高于Dex组(13.75%比2.5%)(患病率:[OR]:0.161,95% CI:0.024 - 0.626;p = 0.020;发生率:[HR]:0.17,95% CI:0.06 - 0.52;p = 0.009)。Dex显著上调BDNF,降低Nfl,并独特地增加溶血磷脂酰乙醇胺。
预防性低剂量Dex显著降低了CAS后72小时内CH和CHS的发生率。
本研究由中国国家自然科学基金(项目编号:82271288)和河南省科技攻关项目(项目编号:242300421192和JQRC2023004)资助。