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: 7176910
• 负责人: Jeffrey L. Johnson
• 金额: $ 10.46万
• 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 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7176910
• 关键词: 3-methylhistidine; Adrenergic Agents; Amino Acids; Animals; Attenuated; Basic Science; Burn injury; Caring; Catabolism; Clinical; Clinical Research; Complex; Creatinine; Energy Metabolism; Failure; Fatty acid glycerol esters; Functional disorder; Glucose; Hormones; Hospital Mortality; Hydrocortisone; Hyperglycemia; Immune System Diseases; In Vitro; Individual; Infection; Inflammation; Inflammatory; Injury; Insulin; Insulin Resistance; Interleukin-6; Leukocytes; Measurement; Measures; Mediating; Metabolic; Methods; Minor; Molecular; Morbidity - disease rate; Muscle Proteins; Neurosecretory Systems; Nitrogen; Numbers; Nutritional Support; Organ; Organ failure; Outcome; Outcome Measure; Pathway interactions; Patients; Plasma; Population; Production; Propranolol; Proteins; Randomized; Randomized Controlled Trials; Resistance to infection; Rest; Serum; Signal Transduction; Skeletal Muscle; Skeletal system; Standards of Weights and Measures; Stimulus; Supplementation; Survivors; System; Trauma; Upper arm; Ventilator; Wound Healing; adrenergic; cost; cytokine; day; functional outcomes; hemodynamics; injured; mortality; nitrogen balance; protein metabolism; response

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 护理的进步使重伤患者能够最初生存，但幸存者往往会遭受长期发病的困扰。优化对感染的抵抗力、伤口愈合和恢复功能仍然是一个挑战。虽然这些问题的根源很复杂，但提出的一个基础是损伤后分解代谢状态。在重伤患者中观察到的这种代谢亢进期会给个体带来相当大的损失，包括氮损失、胰岛素抵抗、免疫功能障碍和关键合成途径的失败。成功减少这段分解代谢可能对长期结果产生重大影响。事实证明，减少损伤后分解代谢期的影响很困难。补充高水平蛋白质、特定氨基酸或激素的营养支持尚未被证明对创伤患者的净氮损失或功能结果有实质性影响。这些努力的令人失望的结果可能是由于肾上腺素能对这些代谢系统的持续贡献。 β-肾上腺素能系统负责介导炎症引起的许多影响。许多体外和动物研究已经证明，β-肾上腺素能介导高血糖、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传导。创伤人群的一种潜在治疗方法是β-阻断，其结果在 最近的对照烧伤试验。我们建议对严重受伤的创伤患者进行普萘洛尔治疗的随机对照试验。我们的假设是普萘洛尔可降低代谢亢进反应，减弱肾上腺素对炎症的刺激，并降低发病率和死亡率。我们建议在受伤后第三天对严重受伤的 ICU 患者进行随机分组。一只手臂将接受普萘洛尔治疗；另一只手臂将接受普萘洛尔治疗；另一只手臂将接受普萘洛尔治疗；另一只手臂将接受普萘洛尔治疗。 其他人将接受当前标准的护理。结果指标将包括细胞因子水平、静息能量消耗、去脂质量、骨骼肌质量、葡萄糖水平、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对重伤者分解代谢问题的贡献。该信息将为开展基础科学和临床研究提供一个平台 进入（-肾上腺素能系统）及其对炎症、分解代谢和功能结果的影响