ROLE OF EARLY GUT DYSFUNCTION IN LATE POSTINJURY MOF

早期肠道功能障碍在损伤后晚期 MOF 中的作用

• 批准号: 6493984
• 负责人: FREDERICK A MOORE
• 金额: $ 16.87万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6493984
• 关键词: clinical research; disease /disorder proneness /risk; gastrointestinal disorder; human subject; multiple organ failure; outcomes research; prognosis; resuscitation; trauma; tube feeding

Multiple organ failure (MOF) remains the leading cause of late post- injury death. Despite intensive investigation, it's pathogenesis remains elusive. Recently, the gut has been invoke to play a pivotal pathogenic role. In early MOF, the gut appears to be a source of pro-inflammatory mediators that amplify the systemic inflammatory response syndrome (SIRS) which, when severe, causes early MOF. As time proceeds, down- regulation of certain components of severe SIRS results in severe delayed immunosuppression which contributes to late infections. Of note, early enteral nutrition (most recently with immune-enhancing formulas) has been sown to consistently reduce late infections. Unfortunately, patients at high risk for MOF experience intolerance to early EN and as a result, many clinicians will not administer early EN. Rather, they administer total parenteral nutrition (TPN) which promotes further gut dysfunction and further increases in septic morbidity. We believe that early post-injury gut dysfunction can be identified, characterized and improved in high risk patients to improve their outcome. To achieve this goal, patients predicted to be at high risk for MOF will be resuscitated by a standard protocol (this will be refined and computerized) to identify patients who experience early gut hypoperfusion (identified by gastric tonometry). Following resuscitation, gut dysfunction will be further characterized by a newly designed feeding tube that is capable of simultaneously measuring small bowel motility and gut absorption capacity (GAC) Normal human volunteers and a second group of trauma patients not requiring shock resuscitation will serve as controls. The trauma patients will then receive early EN by a standard protocol (this will be refined and computerized) and intolerance to EN will be quantitated. We will then determine how early gut hypoperfusion, small bowel dysmotility, and impaired GAC relate to intolerance to EN. Based on these studies we will then devise strategies to reduce early gut dysfunction. For example, early shock induced gut ischemia/reperfusion injury could be minimized by refining our shock resuscitation protocol. Alternatively, our ability to administer EN could be improved by refining our feeding protocol, treating specific gut dysfunctions, or modifying enteral formula composition. Our ultimate goal is to perform prospective randomized trials of gut specific therapies to document improved patient outcome.

多器官功能衰竭(MOF)仍然是伤后晚期死亡的主要原因。尽管进行了深入的研究，但其发病机制仍不清楚。近年来，肠道被认为起着关键的致病作用。在早期MOF中，肠道似乎是促炎介质的来源，这些促炎介质放大了全身炎症反应综合征(SIRS)，当病情严重时，会导致早期MOF。随着时间的推移，严重SIRS的某些成分的下调会导致严重的延迟免疫抑制，从而导致晚期感染。值得注意的是，早期肠内营养(最近使用的是免疫增强配方)一直被用来持续减少晚期感染。不幸的是，多器官功能衰竭的高危患者对早期肠内营养不耐受，因此，许多临床医生不会使用早期肠内营养。相反，他们实施完全肠外营养(TPN)，这会促进进一步的肠道功能障碍和败血症发病率的进一步增加。我们相信，在高危患者中，可以识别、表征和改善损伤后早期的肠道功能障碍，以改善他们的预后。为了实现这一目标，预计将有MOF高危风险的患者将通过标准方案(这将被改进和计算机化)进行复苏，以识别早期经历肠道低灌流的患者(通过胃压测定来确定)。在复苏后，肠道功能障碍的进一步特征将是新设计的能够同时测量小肠运动和肠道吸收能力(GAC)的喂养管。正常人志愿者和第二组不需要休克复苏的创伤患者将作为对照。然后，创伤患者将通过标准方案接受早期EN(这将被细化和计算机化)，对EN的不耐受程度将被量化。然后，我们将确定早期肠道灌流不足、小肠动力障碍和GAC受损与EN不耐受之间的关系。在这些研究的基础上，我们将制定减少早期肠道功能障碍的策略。例如，早期休克引起的肠缺血/再灌注损伤可以通过完善我们的休克复苏方案来最小化。或者，我们可以通过改进我们的喂养方案、治疗特定的肠道功能障碍或修改肠道配方奶的成分来提高我们管理EN的能力。我们的最终目标是进行肠道特异性治疗的前瞻性随机试验，以记录改善的患者结果。