Comparative effectiveness of energy dose in critical illness

描述(申请人提供)：本修订申请是对PA-09-151消化系统疾病和营养临床研究试点和可行性的回应。在危重病患者的营养支持方面，很少进行严格的比较有效性研究(CER)。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)剂量在重要临床结果方面的比较疗效尚不清楚。在重症监护病房(ICU)环境中，由于缺乏循证数据和迄今研究中相互矛盾的信息，导致临床医生给ICU患者提供了广泛的能量剂量。这项先导性研究旨在前瞻性地测试不同能量剂量对内科和外科危重患者的临床疗效。我们还将生成新的、假设生成的系列血浆代谢组学数据。目标患者人群是在被认为最初需要静脉喂养的内科或外科ICU住院的成年人。我们将评估能量剂量对需要专门营养支持的60名危重患者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倍的静息能量消耗(REE)，将与接受较低能量剂量的匹配ICU患者相比，医院感染率较低相关；以及2)能量摄入的差异将导致与临床结果相关的血浆代谢模式的全球变化。我们的具体目标是：1)进行一项为期28天的对照、双盲、前瞻性、随机临床试验，以测试三种能量剂量(分别为0.6、1.0和1.3×REE)对成人内科/外科ICU患者28天医院感染(主要终点)、血流感染和其他重要临床结局的影响；2)检查累积和平均每天28天能量缺乏(能量摄入量测量的REE)对目标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)；3)确定能量剂量和能量缺乏对代谢模式的影响以及这些影响与目标1受试者临床结果的关系。 公共卫生相关性：通常通过静脉或胃肠途径向危重病人提供营养支持，但与更好的临床结果相关的能量(卡路里)剂量尚不清楚。这项试验旨在测试不同能量剂量对危重成人的临床有效性，特别是对医院感染的疗效，这些危重成年人最初需要静脉喂养作为临床护理的一部分。

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. 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.