NEONATAL ENCEPHALOPATHY TREATED BY MODERATE HYPOTHERMIA

中度低温治疗新生儿脑病

• 批准号: 6188181
• 负责人: DOROTHEA DENISE JENKINS
• 金额: $ 23.32万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6188181
• 关键词: behavior test; blood chemistry; bradycardia; cerebral ischemia /hypoxia; clinical research; clinical trials; health services research tag; hearing tests; heart rate; human subject; human therapy evaluation; hypoxia neonatorum; induced hypothermia; neonatal intensive care; neuroprotectants; neuropsychological tests; newborn human (0-6 weeks); outcomes research; psychometrics; psychomotor function

Perinatal hypoxia-ischemia (HI) remains a serious problem in the care of newborns. Interruption in the supply of oxygenated blood to the brain may result in neuronal injury, encephalopathy and possibly death. Neonatal encephalopathy (NE) occurs in 3-9 of every 1000 term infants. Hypothermia decreases or inhibits many of the cellular events that lead to neuronal damage after reperfusion, and offers the advantage of an early and relatively uncomplicated intervention in a potentially devastating disease process. The safety and efficacy of short-term systemic hypothermia during HI has been established in adult and neonatal populations undergoing cardiac and neurosurgical procedures. The safety and efficacy of longer-term systemic hypothermia (1-5 days) has been substantiated in adult head trauma patients and in 17 newborns with junctional tachyarrhythmias, but not in this population of HI newborns. Before a full-scale clinical trial of this intervention is designed and conducted, we need to validate the uniformity of the intervention protocol and define outcome measures. In this pilot study we will enroll 72 successive newborns within 6 hours of an HI event, and randomly assign them to hypothermia (33 C) or normothermia (37.5 C) for 48 hours after HI insult. This study will test a degree of systemic hypothermia which may have the greatest neuroprotective effect with few adverse effects based on studies in human infants and our preliminary feasibility study of 5 term newborns. We will address measures of efficacy and safety, refine the treatment protocol and the target population for the full-scale clinical trial. We will show that systemic hypothermia can be safely and uniformly begun at outlying hospitals and during transport of newborns to a tertiary care center. The use of hypothermia in this disease process may be groundbreaking and profoundly change the way asphyxiated newborns are treated even in the most rural areas. Questions regarding measures of safety and efficacy of hypothermia, novel methods for identification of neonates in first few hours after the insult, and outcome predictions for these newborns need to be better defined prior to a definitive clinical trial.

围产期缺氧缺血(HI)仍然是新生儿护理中的一个严重问题。脑氧合血液供应中断可能会导致神经元损伤、脑病，甚至可能死亡。每1000名足月婴儿中有3-9名发生新生儿脑病。低温可以减少或抑制再灌注后导致神经元损伤的许多细胞事件，并在潜在的破坏性疾病过程中提供早期和相对简单的干预。在接受心脏和神经外科手术的成人和新生儿群体中，在HI期间进行短期全身低温的安全性和有效性已经得到证实。长期全身低温(1-5天)的安全性和有效性已在成人头部创伤患者和17名患有交界性快速性心律失常的新生儿中得到证实，但在这类HI新生儿中尚未得到证实。在设计和进行这种干预的全面临床试验之前，我们需要验证干预方案的一致性并确定结果衡量标准。在这项先导性研究中，我们将招募72名连续出生的新生儿，在HI事件发生后6小时内，随机将他们分配到低温(33摄氏度)或常温(37.5摄氏度)组，持续48小时。这项研究将基于对人类婴儿的研究和我们对5名足月新生儿的初步可行性研究，测试可能具有最大神经保护效果和最少不良反应的系统低温程度。我们将解决有效性和安全性的措施，完善治疗方案和全面临床试验的目标人群。我们将展示，在边远医院和将新生儿送往三级护理中心的过程中，可以安全和统一地开始全身低温。在这一疾病过程中使用低温可能是开创性的，并深刻改变窒息新生儿的治疗方式，即使在最农村地区也是如此。在进行明确的临床试验之前，需要更好地确定低温安全性和有效性的措施、在侮辱后最初几个小时识别新生儿的新方法，以及对这些新生儿的结果预测。