Beta-Blockade Reduces Catabolism in Severely Injured Trauma Patients

β-阻断可减少重度创伤患者的分解代谢

• 批准号: 7020943
• 负责人: Jeffrey L. Johnson
• 金额: $ 10.77万
• 依托单位: DENVER HEALTH AND HOSPITAL AUTHORITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-15 至 2008-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7020943
• 关键词: basal metabolism; beta antiadrenergic agent; bioenergetics; biotransformation; chemotherapy; clinical research; clinical trials; cytokine; hormone regulation /control mechanism; human subject; human therapy evaluation; inflammation; intensive care; metabolism; metabolism disorder chemotherapy; multiple organ failure; muscle metabolism; neuroendocrine system; patient oriented research; photon absorptiometry; propranolol; trauma

DESCRIPTION (provided by applicant): Advances in ICU care allow initial survival of critically injured patients, however survivors often suffer from long term morbidity. Optimizing resistance to infection, wound healing, and return to function remains a challenge. While the genesis of these problems is complex, one proposed underpinning is the postinjury catabolic state. This hypermetabolic period observed in the critically injured patient has considerable costs to the individual, including nitrogen loss, insulin resistance, immune dysfunction and failure of pivotal synthetic pathways. A successful reduction of this period of catabolism may have a powerful impact on long term outcome. Reducing the effects of the postinjury catabolic period has proved difficult. Supplementation of nutritional support with high levels of protein, specific amino acids, or hormones has not been shown to have a substantial impact on net nitrogen loss or functional outcomes in trauma patients. The disappointing results of these efforts may be due to the persistent adrenergic contribution to these metabolic systems. The (-adrenergic system is responsible for mediating many of the effects engendered by inflammation. Many in vitro and animal studies have demonstrated (-adrenergic mediated hyperglycemia, insulin resistance, protein catabolism, leukocyte dysfunction, cytokine production and pro-inflammatory intracellular signaling. A potential therapy in the trauma population is (-blockade, results of which have looked promising in recent controlled burn trials. We propose a randomized controlled trial of propranolol treatment in severely injured trauma patients. Our hypothesis is that propranolol reduces the hypermetabolic response, attenuates the (-adrenergic stimulus to inflammation and reduces morbidity and mortality. We propose to randomize severely injured ICU patients on their third postinjury day. One arm will receive treatment with propranolol; the other will receive current standard of care. Outcome measures will include cytokine levels, resting energy expenditure, fat-free mass, skeletal muscle mass, glucose levels, cortisol levels, insulin requirements, infections, organ failure, ICU morbidity and mortality. Results of this study will elucidate the (-adrenergic contribution to the catabolic problems of the severely injured. This information will provide a platform from which to launch both basic science and clinical research into the (-adrenergic system and its effects on inflammation, catabolism, and functional outcome

描述(由申请人提供)： ICU护理的进步使危重患者得以初步存活，但幸存者往往遭受长期发病率的困扰。优化对感染、伤口愈合和恢复功能的抵抗力仍然是一个挑战。虽然这些问题的成因很复杂，但有一种说法是损伤后分解代谢状态。在重伤患者身上观察到的这种高代谢期对个体来说是相当大的代价，包括氮丢失、胰岛素抵抗、免疫功能障碍和关键合成途径的失败。成功地减少这一分解代谢期可能会对长期结果产生强大的影响。事实证明，减少损伤后分解代谢期的影响是困难的。补充高水平的蛋白质、特定氨基酸或激素的营养支持对创伤患者的净氮损失或功能结果没有实质性影响。这些努力的令人失望的结果可能是由于肾上腺素对这些代谢系统的持续贡献。(-肾上腺素能系统负责调节炎症产生的许多效应。许多体外和动物研究表明，肾上腺素能介导的高血糖、胰岛素抵抗、蛋白质分解代谢、白细胞功能障碍、细胞因子产生和促炎细胞内信号转导。在创伤人群中，一种潜在的治疗方法是(-封锁)，其结果在最近的对照烧伤试验中看起来很有希望。我们建议对严重创伤患者进行普奈洛尔治疗的随机对照试验。我们的假设是心得安减少高代谢反应，减弱对炎症的肾上腺素能刺激，降低发病率和死亡率。我们建议将严重损伤的ICU患者在他们受伤后的第三天随机分组。一只手臂将接受心得安治疗；另一只手臂将接受目前标准的护理。结果指标将包括细胞因子水平、静息能量消耗、无脂肪质量、骨骼肌质量、血糖水平、皮质醇水平、胰岛素需求、感染、器官衰竭、ICU发病率和死亡率。这项研究的结果将阐明-肾上腺素能在严重受伤的分解代谢问题中的作用。这些信息将提供一个平台，以启动对肾上腺素能系统及其对炎症、分解代谢和功能结果的影响的基础科学和临床研究