NEONATAL ENCEPHALOPATHY TREATED BY MODERATE HYPOTHERMIA

围产期缺氧缺血（HI）仍然是新生儿护理中的一个严重问题。脑部含氧血供应中断可导致神经元损伤、脑病甚至死亡。新生儿脑病（NE）发生在每1000个足月婴儿中3-9个。低温降低或抑制了许多导致再灌注后神经元损伤的细胞事件，并且在潜在的破坏性疾病过程中提供了早期和相对简单的干预的优势。在接受心脏和神经外科手术的成人和新生儿人群中，短期全身低温治疗的安全性和有效性已经得到证实。长期全身性低温治疗（1-5天）的安全性和有效性已在成人头部外伤患者和17例伴有交界性心动过速的新生儿中得到证实，但在HI新生儿人群中未得到证实。在设计和实施该干预措施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测量。在这项试点研究中，我们将在HI事件发生后6小时内连续招募72名新生儿，并在HI侮辱后48小时内随机将他们分配到低温（33℃）或常温（37.5℃）。本研究将基于对人类婴儿的研究和我们对5个足月新生儿的初步可行性研究，测试一定程度的全身低温可能具有最大的神经保护作用，而且副作用很少。完善疗效和安全性指标，完善治疗方案，完善全面临床试验目标人群。我们将证明，全身低温可以安全、统一地在偏远医院开始，并在新生儿转运到三级护理中心。在这种疾病过程中使用低温可能是开创性的，并深刻地改变了窒息新生儿的治疗方式，即使在大多数农村地区也是如此。在确定的临床试验之前，需要更好地确定有关低温治疗的安全性和有效性措施、在损伤后最初几个小时内识别新生儿的新方法以及这些新生儿的预后预测等问题。

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.