Protein Metabolism in Critically III Surgical Neonates

描述(由申请人提供)：有史以来报道的外科病人蛋白质分解代谢率最高的是接受体外生命支持(ECLS)的新生儿。尽管蛋白质丢失与外科患者发病率和死亡率的增加密切相关，但限制这一过程的方法研究仍然很少。这项建议旨在验证这样一种假设，即静脉注射胰岛素将改善ECLS新生儿的极端蛋白质分解代谢。这项研究具有重要意义，因为ECLS是一种已被证明的挽救生命的手术疗法，已用于超过16,000名患有呼吸衰竭的婴儿。然而，发病率仍然很高，伴随而来的死亡率在过去十年中一直保持在15%-20%。一项双中心、前瞻性、随机、交叉试验被提出，使用ECLS治疗的新生儿作为新生儿危重疾病的模型，并使用经过验证的、最先进的、稳定的同位素示踪技术来量化蛋白质代谢。该方案旨在确定在使用ECLS的非肠道喂养新生儿中应用高胰岛素正血糖钳是否会改善蛋白质平衡，并阐明这种变化发生的机制。这项基础代谢研究有可能改善对需要ECLS的新生儿的管理，并对确定如何在所有重症外科新生儿中优化净蛋白质平衡非常重要。

DESCRIPTION (provided by applicant): The highest rate of protein catabolism ever reported for surgical patients is found in neonates on extracorporeal life support (ECLS). Methods to limit this process remain sparsely investigated despite the close linkage between protein loss and increased morbidity and mortality in surgical patients. This proposal seeks to test the hypothesis that the intravenous administration of insulin will ameliorate the extreme protein catabolism noted in neonates on ECLS. Such an investigation is of importance as ECLS is a demonstrated lifesaving surgical therapy that has been utilized in over 16,000 babies with respiratory failure. However, morbidity remains high and the attendant mortality has stayed constant at 15-20 % over the past decade. A two-center, prospective, randomized, crossover trial is proposed using neonates on ECLS as a model of neonatal critical illness and employing validated, state of the art, stable isotope tracer techniques to quantify protein metabolism. The protocol is designed to determine if the application of a hyperinsulinemic euglycemic clamp in parenterally fed neonates on ECLS will result in an improvement in protein balance, and to elucidate the mechanisms by which the change occurs. This fundamental metabolic investigation has the potential to improve the management of neonates requiring ECLS and is important in defining how net protein balance may be optimized in all critically ill surgical neonates.