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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Specialized Center (P50)
Project #
5P50GM038529-13
Application #
6493984
Study Section
Special Emphasis Panel (ZGM1)
Project Start
2001-08-01
Project End
2002-07-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
13
Fiscal Year
2001
Total Cost
$168,689
Indirect Cost
City
Houston
State
TX
Country
United States
Zip Code
77225
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