Comparative effectiveness of energy dose in critical illness

描述（由申请人提供）：本修订申请是对PA-09-151消化系统疾病和营养的试点和可行性临床研究的回应。危重病人营养支持的有效性比较研究（CER）很少。专门的肠外或肠内（胃肠道）营养是危重患者的常规处方，但不同能量（卡路里）剂量对重要临床结局的比较疗效尚不清楚。在重症监护室（ICU）环境中，缺乏循证数据和迄今为止研究中相互矛盾的信息导致临床医生给予ICU患者的能量剂量范围很广。这项初步研究旨在前瞻性地测试不同能量剂量在危重内科和外科患者中的临床疗效。我们还将产生新的，假设生成系列血浆代谢组学数据。目标患者人群是在内科或外科ICU住院的成人，认为最初需要静脉喂养。我们将在60名需要专门营养支持的重症患者中评估能量剂量对医院获得性感染率和其他重要临床结果的影响。我们假设：1）充足的能量管理，定义为1.3 x测量的静息能量消耗（REE），与接受较低能量剂量的匹配ICU患者相比，将与较低的医院感染率相关; 2）能量摄入的差异将导致与临床结局相关的血浆代谢模式的总体变化。我们的具体目标是：1）进行一项对照、双盲、前瞻性、随机化的28天临床试验，以测试三种能量剂量的影响（分别为0.6、1.0和1.3 x REE），总计28天的医院获得性感染（主要终点）、血流感染和其他重要临床结局; 2）检查累积和平均每日28天能量不足的影响（能量摄入-测量的REE）对Aim 1临床结局终点的影响，以及与估计的REE的关系（通过Harris-Benedict方程）;和3）确定能量剂量和能量缺乏对代谢组学模式的影响以及这些与Aim 1受试者临床结果的关联。

DESCRIPTION (provided by applicant): 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.