Pediatric Severe Traumatic Brain Injury in Latin America – A Randomized Trial Comparing Two Management Protocols

摘要 在严重创伤性脑损伤(STBI)中幸存下来的儿童生活在严重的损伤中，这些损伤改变了他们的 发展和未来的可能性。在世界范围内，脑外伤是导致儿童死亡和残疾的主要原因 和青少年。在美国，儿童脑损伤的年发病率高于多发性硬化症、艾滋病毒/艾滋病、脊髓 受伤，和乳腺癌加在一起。虽然不是严格意义上的儿科疾病，但这种比较说明了 我们正在处理的儿科全球卫生流行病的规模和重要性。 我们科学研究的首要目标是进行高质量的随机对照试验 解决一个关键的颅脑损伤管理问题：使用带有颅内压信息的方案 与积极治疗相比，监测直接治疗儿童sTBI可改善预后 仅基于影像和临床检查的方案？这是在我们的成人颅内压研究2之后，发现没有 结果差异，并已引起对sTBI患者治疗指南的重新思考&>13.单独的 研究是必要的，因为儿童不是简单的小成年人，一些治疗方法与年龄有关 额外的风险。因此，研究结果将为美国和全球的临床实践提供信息。 这项试验将在7个拉丁美洲儿科ICU进行，这些ICU的基础设施和实践模式 最适合于强大的内部效度和资源，代表着发展中国家的创伤护理。成功者 青少年/成人最佳旅行试验，收集类似环境下的高质量数据(被引用900次) 强调了这一方法的可行性。 具体目的：在一项第三阶段随机优势试验中，对来自7个拉丁美洲儿科的428名sTBI儿童进行研究 创伤中心，测试使用以下信息指导的方案对sTBI治疗结果的影响 使用成像和临床检查来指导治疗的方案的ICP监测仪与管理层。 假设1：患有严重脑外伤的儿童，其急性护理治疗使用基于数据的方案进行管理 在6个月后，通过监测妊娠期肝内胆汁淤积物，死亡率将显著降低，生活质量和全球预后将显著提高 创伤后的患者比那些以影像和临床检查为基础的治疗方案的患者更多。这个 功能恢复的主要指标是6个月时的PedsQL。第二个衡量标准是Gose-Peds。 假设2：将颅内压监测纳入颅脑损伤患者的护理将最大限度地减少继发并发症， 减少在ICU的住院时间，减少脑部特效治疗。 具体目标：在新的研究中心培训如何进行高质量科学研究的人员， 并将延长对与我们合作的人员的培训，巩固以前的能力- 建功立业，开创新局面。

Abstract Children who survive severe traumatic brain injury (sTBI) live with profound impairments that alter their development and future possibilities. Worldwide, TBI is the leading cause of death and disability among children and adolescents. In the US, the annual incidence of pediatric TBI is greater than MS, HIV/AIDS, spinal cord injury, and breast cancer combined1. Although not strictly pediatric diseases, this comparison illustrates the magnitude and importance of the pediatric global health epidemic we are addressing. Our primary focus for scientific investigation is to conduct a high quality randomized controlled trial addressing a critical TBI management question: Does using a protocol with information from intracranial pressure (ICP) monitoring to direct treatment of children with sTBI improve outcomes vs an aggressive management protocol based on imaging and clinical examination alone? This follows on our adult ICP study2 which found no outcome differences and has occasioned re-thinking of treatment guidelines for sTBI patients >13. A separate study is essential because children are not simply small adults and some treatment approaches carry age-related additional risks. Thus, study findings will inform US and global clinical practice. This trial will be conducted in 7 Latin American pediatric ICUs where infrastructures and practice patterns are optimal for strong internal validity and resources represent trauma care in the developing world. The successful adolescent/adult BEST TRIP trial, which collected high-quality data in similar environments (cited > 900 times) underscores the feasibility of this approach. Specific Aim: In a Phase III randomized superiority trial in 428 children with sTBI from 7 Latin American pediatric trauma centers, test the effect on outcomes of management of sTBI guided by a protocol using information from ICP monitors vs. management using a protocol that uses imaging and clinical exams to guide treatment. Hypothesis #1: Children with severe TBI whose acute care treatment is managed using a protocol based on data from ICP monitoring will have significantly lower mortality and better quality of life and global outcome at 6 months post-trauma than those whose treatment is managed with a protocol based on imaging and clinical exam. The primary measure of functional recovery is the PedsQL at 6 months. A secondary measure is GOSE-Peds. Hypothesis #2: Incorporating ICP monitoring into sTBI patient care of will minimize secondary complications, decrease length of stay in ICU and decrease brain-specific treatments. Specific Aim: We will train personnel in centers new to research in how to conduct high-quality scientific studies, and will extend the training for the personnel with whom we have been working, solidifying previous capacity- building efforts, and initiating new efforts.