Attenuating Inflammation via Protein-Calorie Restriction

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DESCRIPTION (provided by applicant): The purpose of this proposal is to cultivate the scientific development and advance the skills of Dr. Todd W. Rice in the design and conduct of clinical trials, so that he may become an independent investigator in conducting clinical research. Vanderbilt University Medical Center, through its several intensive care units, will provide Dr. Rice with the necessary patient population to conduct a prospective, randomized clinical trial comparing the effects of trophic nutrition versus advancement to full-calorie rates in mechanically ventilated, critically ill patients. Laboratory resources are available to investigate changes in biochemical responses, including pro- and anti-inflammatory cytokine responses. Differences in clinical outcomes, including weaning patients from the ventilator, will be assessed. Through collaboration with his clinical mentor, Dr. Arthur P. Wheeler, Dr. Rice will become adept at trial design, biostatistics, epidemiology, patient recruitment, and reporting of results to the scientific community. These skills will provide the foundation for Dr. Rice to pursue an independent academic career in critical care research. Many mechanically ventilated patients, unable to nourish themselves, are provided with nutrition, either enterally or parenterally. Enteral nutrition has been shown to reduce inflammation and improve clinical outcomes by preserving the intestinal mucosa, decreasing bacterial translocation, and reducing systemic infections. Although these improvements have been observed with full enteral feedings, very low rates of enteral feedings show similar protection in animals. We hypothesize that these low-level feedings also preserve the intestinal mucosa in ventilated patients, while reducing the pro- and anti-inflammatory cytokine responses seen in these patients along with the gastrointestinal complications, resulting in improved clinical outcomes compared to full-calorie feeds. The specific aims of this proposal are to demonstrate that low-level as compared to full-calorie enteral feedings will: 1) decrease the early pro-inflammatory and compensatory anti-inflammatory cytokine responses; 2) decrease the incidence of feeding complications, and thus, 3) improve clinical outcomes, such as ventilator-free days and other organ-failure free days. The aging population, increasing immunosuppression, and rising use of invasive procedures will result in the continued growth of critical care. Many mechanically ventilated, critically ill patients are supported with enteral nutrition. Despite widespread use, data on optimal delivery of enteral nutrition to such patients is lacking. This proposal will help weigh the benefits and risks, establish a cost-efficient means of reducing feeding complications, and provide the foundation for future studies of enteral feeds in patients with acute respiratory failure requiring mechanical ventilation.