这是基于高敏肌钙蛋白状态(BBTBBT)研究的外伤性脑损伤(TBI)中使用β受体阻滞剂(普萘洛尔)的中期分析。BBTBBT是一项正在进行的双盲安慰剂对照随机临床试验,目标样本量为771例TBI患者。我们寻求,在达到50%的样本量后,探讨早期服用β受体阻滞剂(BBs)对肾上腺素能激增的影响,促炎细胞因子,以及与高敏肌钙蛋白T(HsTnT)状态相关的TBI生物标志物。在随机化之前,使用格拉斯哥昏迷量表(GCS)和HsTnT状态(阳性与阴性)根据TBI的严重程度对患者进行分层。HsTnT阳性患者(非随机)接受普萘洛尔(第1组;n=110),试验阴性的患者被随机分配接受普萘洛尔(第2组;n=129)或安慰剂(第3组;n=111).在损伤后24小时内给予普萘洛尔6天,以心率(>60bpm)为导向,收缩压(≥100mmHg),或平均动脉压(>70mmHg)。Luminex和基于ELISA的免疫测定用于定量血清促炎细胞因子(白细胞介素(IL)-1β,IL-6、IL-8和IL-18),TBI生物标志物[S100B,神经元特异性烯醇化酶(NSE),和肾上腺素]。在中期分析中,纳入了年龄(平均34.8±9.9岁)和性别相当的三百五十例患者。第1组有显著较高的基线水平的IL-6,IL-1B,S100B,乳酸,和基差高于随机组(p=0.001)。第1组血清IL-6、IL-1β显著降低,肾上腺素,从基线到受伤后48小时的NSE水平(p=0.001)。严重颅脑损伤患者的基线IL-6、IL-1B水平较高,S100B,HsTnT比轻度和中度TBI高(p=0.01)。HsTnT水平与损伤严重程度评分(ISS)显着相关(r=0.275,p=0.001),GCS(r=-0.125,p=0.02),血清S100B(r=0.205,p=0.001)。普萘洛尔早期给药显示,从基线到损伤后48小时,细胞因子水平和TBI生物标志物显着降低,特别是在HsTnT阳性的患者中,表明在调节TBI后炎症中的潜在作用。试用注册:ClinicalTrials.govNCT04508244。它于2020年11月8日首次注册。招聘于2020年12月29日开始,目前正在进行中。该研究部分发表在第23届欧洲创伤和急诊外科大会(ECTES)上,2024年4月28日至30日,埃斯托里尔,里斯本,葡萄牙。
This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = - 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI.Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28-30, 2024, in Estoril, Lisbon, Portugal.