Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study): study protocol for a randomized controlled trial.
Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study): study protocol for a randomized controlled trial.
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DOI：
10.1186/1745-6215-13-177
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发表时间：
2012-09-26
期刊：
影响因子：
2.5
通讯作者：
Pandharipande PP
中科院分区：
文献类型：
--
作者：
Patel MB;McKenna JW;Alvarez JM;Sugiura A;Jenkins JM;Guillamondegui OD;Pandharipande PP
重度TBI（定义为格拉斯哥昏迷评分≤ 8）会增加颅内压并激活交感神经系统。TBI后交感神经功能亢进表现为儿茶酚胺过多、高血压、心率变异性异常和激越，并与不良的神经心理学结局相关。普萘洛尔和可乐定是中枢作用药物，可减少交感神经流出、脑水肿和激越。然而，没有前瞻性随机证据证明TBI后肾上腺素能阻滞的可行性、结局获益和安全性。TBI后DASH研究是一项积极累积的、单中心、随机、双盲、安慰剂对照、双臂试验，其中一组在严重TBI后48小时内接受中枢作用的交感神经阻滞药物普萘洛尔（每6小时静脉注射1 mg，持续7天）和可乐定（每12小时每管0.1 mg，持续7天），另一组接受双重安慰剂。该研究采用加权自适应最小化随机化，包括年龄和马歇尔头部CT分类。将通过为随机化提供神经放射学读数的能力、治疗污染和治疗依从性来评估可行性。主要终点是第8天测量的血浆去甲肾上腺素水平降低。次要终点包括综合血浆和尿儿茶酚胺水平、心率变异性、心律失常发生率、感染、使用里士满激动-镇静量表和激动行为量表进行的激动测量、药物使用（抗高血压药、镇静药、镇痛药和抗精神病药）、无昏迷天数、无呼吸机天数、住院时间和死亡率。将在出院时以及3个月和12个月时测量神经心理学结局。测试的领域将包括全球执行功能，记忆，处理速度，视觉空间和行为。其他评估包括扩展格拉斯哥结局量表和脑损伤后生活质量量表。评价的安全性参数将包括心脏并发症。TBI后DASH研究是首个随机、双盲、安慰剂对照试验，旨在确定严重TBI患者肾上腺素能阻滞剂的可行性，并研究其安全性和结局。如果研究结果呈积极趋势，这可能为更大规模的多中心随机临床试验提供初步证据。如果没有治疗效果，该试验仍将提供TBI后交感神经功能亢进的可靠前瞻性描述。ClinicalTrials.gov www.example.com
Severe TBI, defined as a Glasgow Coma Scale ≤ 8, increases intracranial pressure and activates the sympathetic nervous system. Sympathetic hyperactivity after TBI manifests as catecholamine excess, hypertension, abnormal heart rate variability, and agitation, and is associated with poor neuropsychological outcome. Propranolol and clonidine are centrally acting drugs that may decrease sympathetic outflow, brain edema, and agitation. However, there is no prospective randomized evidence available demonstrating the feasibility, outcome benefits, and safety for adrenergic blockade after TBI. The DASH after TBI study is an actively accruing, single-center, randomized, double-blinded, placebo-controlled, two-arm trial, where one group receives centrally acting sympatholytic drugs, propranolol (1 mg intravenously every 6 h for 7 days) and clonidine (0.1 mg per tube every 12 h for 7 days), and the other group, double placebo, within 48 h of severe TBI. The study uses a weighted adaptive minimization randomization with categories of age and Marshall head CT classification. Feasibility will be assessed by ability to provide a neuroradiology read for randomization, by treatment contamination, and by treatment compliance. The primary endpoint is reduction in plasma norepinephrine level as measured on day 8. Secondary endpoints include comprehensive plasma and urine catecholamine levels, heart rate variability, arrhythmia occurrence, infections, agitation measures using the Richmond Agitation-Sedation Scale and Agitated Behavior scale, medication use (anti-hypertensive, sedative, analgesic, and antipsychotic), coma-free days, ventilator-free days, length of stay, and mortality. Neuropsychological outcomes will be measured at hospital discharge and at 3 and 12 months. The domains tested will include global executive function, memory, processing speed, visual-spatial, and behavior. Other assessments include the Extended Glasgow Outcome Scale and Quality of Life after Brain Injury scale. Safety parameters evaluated will include cardiac complications. The DASH After TBI Study is the first randomized, double-blinded, placebo-controlled trial powered to determine feasibility and investigate safety and outcomes associated with adrenergic blockade in patients with severe TBI. If the study results in positive trends, this could provide pilot evidence for a larger multicenter randomized clinical trial. If there is no effect of therapy, this trial would still provide a robust prospective description of sympathetic hyperactivity after TBI. ClinicalTrials.gov NCT01322048
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