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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL081431-05
Application #
7913067
Study Section
Special Emphasis Panel (ZHL1-CSR-R (M1))
Program Officer
Scott, Jane
Project Start
2006-09-30
Project End
2012-07-31
Budget Start
2010-08-01
Budget End
2012-07-31
Support Year
5
Fiscal Year
2010
Total Cost
$151,929
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Janz, David R; Bastarache, Julie A; Rice, Todd W et al. (2015) Randomized, placebo-controlled trial of acetaminophen for the reduction of oxidative injury in severe sepsis: the Acetaminophen for the Reduction of Oxidative Injury in Severe Sepsis trial. Crit Care Med 43:534-41
Fremont, Richard D; Rice, Todd W (2014) How soon should we start interventional feeding in the ICU? Curr Opin Gastroenterol 30:178-81
Rice, Todd W; Rubinson, Lewis; Uyeki, Timothy M et al. (2012) Critical illness from 2009 pandemic influenza A virus and bacterial coinfection in the United States. Crit Care Med 40:1487-98
Hooper, Michael H; Weavind, Lisa; Wheeler, Arthur P et al. (2012) Randomized trial of automated, electronic monitoring to facilitate early detection of sepsis in the intensive care unit*. Crit Care Med 40:2096-101
Rice, Todd W (2012) Can we stomach gastric feeding in critically ill patients with gastrointestinal intolerance? Crit Care Med 40:2508-9
Janz, David R; Hollenbeck, Ryan D; Pollock, Jeremy S et al. (2012) Hyperoxia is associated with increased mortality in patients treated with mild therapeutic hypothermia after sudden cardiac arrest. Crit Care Med 40:3135-9
Bastarache, Julie A; Ware, Lorraine B; Girard, Timothy D et al. (2012) Markers of inflammation and coagulation may be modulated by enteral feeding strategy. JPEN J Parenter Enteral Nutr 36:732-40
Rice, Todd W; Mogan, Susan; Hays, Margaret A et al. (2011) Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med 39:967-74
Walkey, Allan J; Rice, Todd W; Konter, Jason et al. (2010) Plasma adiponectin and mortality in critically ill subjects with acute respiratory failure. Crit Care Med 38:2329-34
Lancaster, Lisa H; Mason, Wendi R; Parnell, James A et al. (2009) Obstructive sleep apnea is common in idiopathic pulmonary fibrosis. Chest 136:772-778

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