This revised application is in response to PA-09-151 Pilot and Feasibility Clinical Research Studies in Digestive Diseases and Nutrition. Little rigorous comparative effectiveness research (CER) has been performed in nutrition support of critically ill patients. Specialized parenteral or enteral (gastrointestinal) nutrition is routinely prescribed to critically ill patients, but the comparative efficacy of different energy (calorie) doses with regard to important clinical outcomes are unknown. In intensive care unit (ICU) settings, the lack of evidence-based data and conflicting information from studies to date contribute to the wide range of energy doses given to ICU patients by clinicians. This pilot study is designed to prospectively test the clinical efficacy of different energy doses in critically ill medical and surgical patients. We will also generate novel, hypothesis-generating serial plasma metabolomics data. The target patient population are adults hospitalized in medical or surgical ICUs deemed to initially require intravenous feeding. We will evaluate the impact of energy dose on the rate of hospital-acquired infection and other important clinical outcomes in a group of 60 critically ill patients requiring specialized nutrition support. We hypothesize that: 1) adequate energy administration, defined as 1.3 x measured resting energy expenditure (REE), will be associated with a lower hospital infection rate than in matched ICU patients receiving lower energy doses;and 2) differences in energy intake will result in global changes in plasma metabolic patterns that are associated with clinical outcomes. Our specific aims are: 1) to perform a controlled, double-blind, prospective, randomized 28-day clinical trial to test the impact of three energy doses (0.6, 1.0 and 1.3 x REE, respectively) on total 28-day hospital-acquired infections (primary endpoint), bloodstream infections and other important clinical outcomes in adult medical/surgical ICU patients;2) to examine the effect of cumulative and mean daily 28-day energy deficits (energy intake - measured REE) on Aim 1 clinical outcome endpoints, and relationships with estimated REE (by the Harris-Benedict equation);and 3) to determine the effect of energy dose and energy deficits on metabolomic patterns and the association of these with Aim 1 subject clinical outcomes. PUBLIC HEALTH RELEVANCE: Nutrition support, either by the intravenous or gastrointestinal routes, is commonly given to hospital patients with critical illness, but the doses of energy (calories) that are associated with better clinical outcomes are unknown. This trial is designed to test the clinical effectiveness, especially on hospital infections, of different energy doses in critically ill adults who initially require intravenous feeding as part of their clinical care.