Pattrapun Wongsripuemtet, Tetsu Ohnuma, Nancy Temkin, Jason Barber, Jordan Komisarow, Geoffrey T Manley, Jordan Hatfield, Miriam Treggiari, Katharine Colton, Cina Sasannejad, Nophanan Chaikittisilpa, Ramesh Grandhi, Daniel T Laskowitz, Joseph P Mathew, Adrian Hernandez, Michael L James, Karthik Raghunathan, Joseph B Miller, Monica S Vavilala, Ben Goldstein, Vijay Krishnamoorthy
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Patients ⩾ 17 years with moderate-severe TBI (Glasgow Coma Scale 3-12) admitted to an intensive care unit (ICU) were included. Early beta-blocker exposure was defined as administration within the first 72 h of admission. The primary outcome was blood-based brain injury biomarker levels on day 3 post-injury. Biomarkers included glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and the inflammatory biomarker C-reactive protein (CRP). Propensity-weighted models analyzed the association between beta-blocker exposure and biomarker levels.</p><p><strong>Results: </strong>Among 450 patients, 31 (7%) received beta-blockers (BB+). The mean (SD) age of BB+ patients was 51.4 (16.2) years, compared to 39.5 (17.0) years for unexposed patients (BB-). BB+ group was associated with a decreased NSE level on day 3 (ratio = 0.71, 95% CI 0.52-0.96, <i>p</i> = 0.026), although this was not significant after adjusting for multiple comparisons (<i>p</i> = 0.13). For secondary outcomes, UCH-L1 levels increased on day 5 in the BB+ group (ratio = 1.62, 95% CI 1.12- 2.36, <i>p</i> = 0.011), but this was not significant after adjustment (<i>p</i> = 0.55). The NSE level on day 14 decreased in the BB+ group (ratio 0.45, 95% CI 0.30-0.66, <i>p</i> < 0.001) and remained significant after adjustment (<i>p</i> = 0.005).</p><p><strong>Conclusions: </strong>There was no association between early beta-blocker exposure and the primary outcome which was blood-based brain injury biomarker levels on day 3. In exploratory analysis, we found that early beta-blocker may associated with decreased NSE level on day 14. Due to the retrospective nature of the study and the use of propensity-weighted analysis to identify associations, direct clinical practice changes cannot be recommended. However, the significant association with NSE level warrants further investigation through prospective studies or randomized controlled trials to confirm the potential neuroprotective effect of early beta-blocker exposure on neuronal cellular injury.</p>","PeriodicalId":39161,"journal":{"name":"Journal of the Intensive Care Society","volume":" ","pages":"17511437251349680"},"PeriodicalIF":1.4000,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206746/pdf/","citationCount":"0","resultStr":"{\"title\":\"Early beta-blocker exposure and association with brain injury biomarkers following moderate to severe traumatic brain injury: A TRACK-TBI study.\",\"authors\":\"Pattrapun Wongsripuemtet, Tetsu Ohnuma, Nancy Temkin, Jason Barber, Jordan Komisarow, Geoffrey T Manley, Jordan Hatfield, Miriam Treggiari, Katharine Colton, Cina Sasannejad, Nophanan Chaikittisilpa, Ramesh Grandhi, Daniel T Laskowitz, Joseph P Mathew, Adrian Hernandez, Michael L James, Karthik Raghunathan, Joseph B Miller, Monica S Vavilala, Ben Goldstein, Vijay Krishnamoorthy\",\"doi\":\"10.1177/17511437251349680\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Beta-blockers have been studied for potential benefits in traumatic brain injury (TBI). 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Propensity-weighted models analyzed the association between beta-blocker exposure and biomarker levels.</p><p><strong>Results: </strong>Among 450 patients, 31 (7%) received beta-blockers (BB+). The mean (SD) age of BB+ patients was 51.4 (16.2) years, compared to 39.5 (17.0) years for unexposed patients (BB-). BB+ group was associated with a decreased NSE level on day 3 (ratio = 0.71, 95% CI 0.52-0.96, <i>p</i> = 0.026), although this was not significant after adjusting for multiple comparisons (<i>p</i> = 0.13). For secondary outcomes, UCH-L1 levels increased on day 5 in the BB+ group (ratio = 1.62, 95% CI 1.12- 2.36, <i>p</i> = 0.011), but this was not significant after adjustment (<i>p</i> = 0.55). 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引用次数: 0
摘要
背景:研究了β受体阻滞剂对创伤性脑损伤(TBI)的潜在益处。本研究旨在探讨早期β受体阻滞剂暴露与中重度TBI后脑损伤生物标志物之间的关系。方法:我们进行了一项回顾性队列研究,使用来自TBI临床研究和知识转化(TRACK-TBI)研究的数据。包括住进重症监护病房(ICU)的小于17岁的中重度TBI患者(格拉斯哥昏迷量表3-12)。早期受体阻滞剂暴露被定义为在入院前72小时内给药。主要终点是损伤后第3天基于血液的脑损伤生物标志物水平。生物标志物包括胶质纤维酸性蛋白(GFAP)、泛素c端水解酶- l1 (UCH-L1)、神经元特异性烯醇化酶(NSE)、S100钙结合蛋白B (S100B)和炎症生物标志物c反应蛋白(CRP)。倾向加权模型分析了受体阻滞剂暴露与生物标志物水平之间的关系。结果:在450例患者中,31例(7%)接受了β受体阻滞剂(BB+)治疗。BB+患者的平均(SD)年龄为51.4(16.2)岁,未暴露患者(BB-)的平均(SD)年龄为39.5(17.0)岁。BB+组与第3天NSE水平下降相关(比值= 0.71,95% CI 0.52-0.96, p = 0.026),尽管在调整多重比较后这并不显著(p = 0.13)。对于次要结果,BB+组的UCH-L1水平在第5天升高(比值= 1.62,95% CI 1.12- 2.36, p = 0.011),但调整后无统计学意义(p = 0.55)。BB+组第14天NSE水平下降(比值0.45,95% CI 0.30-0.66, p p = 0.005)。结论:早期β受体阻滞剂暴露与第3天血基脑损伤生物标志物水平的主要结局之间没有关联。在探索性分析中,我们发现早期β受体阻滞剂可能与第14天NSE水平下降有关。由于该研究是回顾性的,并且使用倾向加权分析来确定相关性,因此不建议直接改变临床实践。然而,与NSE水平的显著相关性需要通过前瞻性研究或随机对照试验进一步研究,以证实早期β受体阻滞剂暴露对神经元细胞损伤的潜在神经保护作用。
Early beta-blocker exposure and association with brain injury biomarkers following moderate to severe traumatic brain injury: A TRACK-TBI study.
Background: Beta-blockers have been studied for potential benefits in traumatic brain injury (TBI). This study aimed to investigate the association between early beta-blocker exposure and brain injury biomarkers following moderate-severe TBI.
Methods: We conducted a retrospective cohort study using data from the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. Patients ⩾ 17 years with moderate-severe TBI (Glasgow Coma Scale 3-12) admitted to an intensive care unit (ICU) were included. Early beta-blocker exposure was defined as administration within the first 72 h of admission. The primary outcome was blood-based brain injury biomarker levels on day 3 post-injury. Biomarkers included glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B), and the inflammatory biomarker C-reactive protein (CRP). Propensity-weighted models analyzed the association between beta-blocker exposure and biomarker levels.
Results: Among 450 patients, 31 (7%) received beta-blockers (BB+). The mean (SD) age of BB+ patients was 51.4 (16.2) years, compared to 39.5 (17.0) years for unexposed patients (BB-). BB+ group was associated with a decreased NSE level on day 3 (ratio = 0.71, 95% CI 0.52-0.96, p = 0.026), although this was not significant after adjusting for multiple comparisons (p = 0.13). For secondary outcomes, UCH-L1 levels increased on day 5 in the BB+ group (ratio = 1.62, 95% CI 1.12- 2.36, p = 0.011), but this was not significant after adjustment (p = 0.55). The NSE level on day 14 decreased in the BB+ group (ratio 0.45, 95% CI 0.30-0.66, p < 0.001) and remained significant after adjustment (p = 0.005).
Conclusions: There was no association between early beta-blocker exposure and the primary outcome which was blood-based brain injury biomarker levels on day 3. In exploratory analysis, we found that early beta-blocker may associated with decreased NSE level on day 14. Due to the retrospective nature of the study and the use of propensity-weighted analysis to identify associations, direct clinical practice changes cannot be recommended. However, the significant association with NSE level warrants further investigation through prospective studies or randomized controlled trials to confirm the potential neuroprotective effect of early beta-blocker exposure on neuronal cellular injury.
期刊介绍:
The Journal of the Intensive Care Society (JICS) is an international, peer-reviewed journal that strives to disseminate clinically and scientifically relevant peer-reviewed research, evaluation, experience and opinion to all staff working in the field of intensive care medicine. Our aim is to inform clinicians on the provision of best practice and provide direction for innovative scientific research in what is one of the broadest and most multi-disciplinary healthcare specialties. While original articles and systematic reviews lie at the heart of the Journal, we also value and recognise the need for opinion articles, case reports and correspondence to guide clinically and scientifically important areas in which conclusive evidence is lacking. The style of the Journal is based on its founding mission statement to ‘instruct, inform and entertain by encompassing the best aspects of both tabloid and broadsheet''.