Early Redox Biomarker Changes After Stellate Ganglion Block in Traumatic Brain Injury: A Paired Arterial-Jugular Pilot Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in Oxidative Stress Index in Paired Arterial and Jugular Venous Blood Samples
研究概览
简要总结
Oxidative stress is a key mediator of secondary brain injury after traumatic brain injury (TBI). The stellate ganglion block (SGB) has been shown to modulate cerebral hemodynamics and neuroinflammation in brain-injured patients, but its effect on circulating redox biomarkers in human TBI has not been studied.
This is a post hoc secondary analysis of stored paired arterial and internal jugular venous blood samples from a prospective, single-center, before-and-after pilot study conducted at the University Medical Centre Ljubljana (parent trial: NCT04208477). Twenty adult patients with moderate-to-severe TBI (Glasgow Coma Scale score 12 or lower before intubation) who received a single ultrasound-guided SGB were included.
Paired blood samples collected at baseline and at 12 and 24 hours after SGB were assayed for derivatives of reactive oxygen metabolites (d-ROMs), plasma antioxidant capacity (PAT), the composite oxidative stress index (OSI = d-ROMs/PAT), the early lipid-peroxidation marker hexanoyl-lysine (HEL), and the oxidative DNA-damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG). No new intervention was administered, no additional patients were enrolled, and no additional biological samples were collected.
The primary outcome is the within-participant change in jugular venous OSI from baseline to 12 hours after SGB. Secondary outcomes include temporal changes in d-ROMs, HEL, and 8-OHdG in both arterial and jugular venous compartments, and the interaction between blood compartment and time. The statistical analysis plan for the oxidative-stress endpoints was documented before the biomarker assays were performed.
This pilot study provides variability estimates and preliminary data to inform the design of future controlled trials evaluating SGB as a potential modulator of post-traumatic oxidative stress.
详细描述
Background and Rationale_____ Traumatic brain injury triggers a cascade of secondary injury mechanisms, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress. Reactive oxygen and nitrogen species overwhelm endogenous antioxidant defenses in the hours to days following injury, contributing to lipid peroxidation, protein oxidation, and DNA damage that exacerbate neuronal loss beyond the initial mechanical insult.
The stellate ganglion, located at the C7-T1 vertebral level, provides sympathetic innervation to the head, neck, and upper extremities. Blockade of this ganglion with local anesthetic has been used clinically for decades in the management of complex regional pain syndrome and other sympathetically mediated conditions. In cerebrovascular pathology, SGB has been associated with increased cerebral blood flow velocity, improved brain tissue oxygenation, and attenuation of neuroinflammatory markers. The parent study (NCT04208477) demonstrated favorable hemodynamic and oxygenation changes after SGB in TBI patients. Whether these hemodynamic effects are accompanied by measurable changes in the systemic and cerebral redox environment has not been investigated in humans.
The present post hoc analysis was designed to characterize the early temporal profile of circulating oxidative-stress biomarkers in paired arterial and internal jugular venous blood after SGB in moderate-to-severe TBI. The paired sampling strategy enables estimation of trans-cerebral gradients (jugular minus arterial concentration), providing indirect information about the balance of cerebral production and clearance of redox metabolites._____
Study Design_____
This is a secondary biomarker analysis embedded within a prospective, single-center, uncontrolled, before-and-after pilot study conducted at the surgical intensive care unit of the University Medical Centre Ljubljana, Slovenia (November 2021 to December 2023). The study was approved by the National Medical Ethics Committee of the Republic of Slovenia (approval KME RS 0120-537/2019/15) and conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from the legally authorized representative of each patient, as participants were unable to consent due to their clinical condition.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients with moderate or severe traumatic brain injury who participated in the original stellate ganglion block study (NCT04208477).
- •Glasgow Coma Scale score of 12 or lower before tracheal intubation.
- •Receipt of a single ultrasound-guided stellate ganglion block during the original study.
- •Availability of stored paired arterial and jugular venous blood samples collected at baseline and at the required post-block time points.
- •Availability of sufficient clinical and laboratory data to link the paired samples and determine their collection time relative to the stellate ganglion block.
- •Original informed consent provided by the participant's legally authorized representative permitted storage and subsequent scientific analysis of the collected samples.
排除标准
- •Absence of a baseline paired arterial and jugular venous blood sample.
- •Absence of suitable post-block samples required for the longitudinal analysis. Insufficient sample volume or sample quality for the planned redox biomarker analyses.
- •Samples failing prespecified laboratory quality-control criteria.
- •Incomplete or inconsistent sample identification or collection-time data preventing reliable pairing of arterial and jugular venous samples.
- •Withdrawal of consent or absence of authorization for secondary analysis of stored samples.
研究组 & 干预措施
Patients With Traumatic Brain Injury Previously Treated With Stellate Ganglion Block
A cohort of adult patients with moderate or severe traumatic brain injury who received an ultrasound-guided stellate ganglion block as part of a previously conducted clinical study. This post hoc study retrospectively analyzes stored paired arterial and jugular venous blood samples collected before and at 12 and 24 hours after the block. No intervention was assigned and no additional samples were collected specifically for the present analysis.
干预措施: Ultrasound-guided stellate ganglion block (parent study) (Other)
结局指标
主要结局
Change in Oxidative Stress Index in Paired Arterial and Jugular Venous Blood Samples
时间窗: Baseline, 12 hours, and 24 hours after stellate ganglion block
Within-participant change from baseline in the oxidative stress index (OSI) measured in paired arterial and jugular venous blood samples at 12 and 24 hours after stellate ganglion block. OSI is a derived measure combining reactive oxygen metabolite levels assessed by the derivatives of reactive oxygen metabolites test (d-ROMs) and antioxidant capacity assessed by the plasma antioxidant test (PAT). Higher OSI values indicate a greater imbalance toward oxidative stress. The analysis evaluates changes over time, differences between arterial and jugular venous compartments, and the interaction between sampling time and blood compartment.
次要结局
- Change in Derivatives of Reactive Oxygen Metabolites(Baseline, 12 hours, and 24 hours after stellate ganglion block)
- Change in Hexanoyl-Lysine Concentration(Baseline, 12 hours, and 24 hours after stellate ganglion block)
- Change in 8-Hydroxy-2'-Deoxyguanosine Concentration(Baseline, 12 hours, and 24 hours after stellate ganglion block)
- Change in plasma antioxidant capacity(Baseline, 12 hours, and 24 hours after stellate ganglion block)
研究者
Ivan Kostadinov
Consultant Anesthesiologist
University Medical Centre Ljubljana