Department of Critical Care Medicine and Department of Public Health Sciences, Queen's University, and the Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada.
Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
JPEN J Parenter Enteral Nutr. 2019 Mar;43(3):326-334. doi: 10.1002/jpen.1449. Epub 2018 Sep 27.
Current randomized trials and observational studies evaluating higher versus lower protein doses in critically ill patients yield inconclusive results. Because of few studies and methodologic limitations, clinical guidelines suggest a wide range of protein intake based on weak evidence. Clinical equipoise about protein dosing exists. The purpose of the current manuscript is to provide the rationale and protocol for a randomized controlled trial (RCT) of 4000 critically ill patients randomly allocated to receive a higher or lower protein dose. We propose a global, volunteer-driven, registry-based RCT involving >100 intensive care units (ICUs). We will enroll mechanically ventilated patients with high nutrition risk, identified by low (≤25) or high (≥35) body mass index, moderate to severe malnutrition, frailty, sarcopenia, or when >96-hour duration of mechanical ventilation is expected. Exclusion criteria include patients who are >96 hours since initiation of mechanical ventilation, moribund, or pregnant, and where the clinician lacks clinical equipoise regarding protein dose. The intervention consists of higher (≥2.2 g/kg/d) or lower (≤1.2 g/kg/d) protein dose, achieved by enteral nutrition, parenteral nutrition, or both. The primary outcome will be 60-day mortality. Key secondary outcomes include time-to-discharge alive from hospital, ICU and hospital survival, and length of stay. As this is research based on existing medical practice, we will apply for a waiver of informed consent, where possible. The large sample size is a reflection of the small signal we expect to see in this large, pragmatic trial.
目前评估危重症患者高蛋白剂量与低蛋白剂量的随机对照试验和观察性研究结果尚无定论。由于研究较少且存在方法学限制，临床指南基于有限的证据建议采用广泛的蛋白质摄入量。对于蛋白质剂量的临床平衡存在争议。本手稿的目的是提供一项针对 4000 名危重症患者的随机对照试验（RCT）的原理和方案，这些患者被随机分配接受高蛋白剂量或低蛋白剂量。我们提出了一项全球性、志愿者驱动、基于注册的 RCT，涉及超过 100 个重症监护病房（ICU）。我们将招募高营养风险的机械通气患者，通过低（≤25）或高（≥35）体重指数、中度至重度营养不良、虚弱、肌少症或预计机械通气持续时间>96 小时来识别。排除标准包括机械通气开始后>96 小时、病危或怀孕的患者，以及临床医生对蛋白质剂量缺乏临床平衡的患者。干预措施包括通过肠内营养、肠外营养或两者联合给予较高（≥2.2 g/kg/d）或较低（≤1.2 g/kg/d）的蛋白质剂量。主要结局将是 60 天死亡率。关键次要结局包括从医院、ICU 和医院存活出院的时间、ICU 和医院存活率以及住院时间。由于这是基于现有医疗实践的研究，我们将在可能的情况下申请免除知情同意。大样本量反映了我们在这项大型实用试验中预期看到的小信号。
