MRCPCH, Institute of Child Health, Department of Paediatric Surgery, 30 Guilford St, London WC1N 1EH, UK.
Pediatrics. 2010 Feb;125(2):e300-8. doi: 10.1542/peds.2008-3211. Epub 2010 Jan 25.
Necrotizing enterocolitis (NEC) with multiple organ dysfunction syndrome (MODS) carries significant morbidity and mortality. There is extensive experimental evidence to support investigation of therapeutic hypothermia in infants with these conditions. We aimed to establish the feasibility and safety of mild hypothermia in preterm neonates with NEC and MODS as a prelude to a randomized trial.
This was a prospective, nonrandomized pilot study of 15 preterm infants who were referred for surgical intervention of advanced NEC and failure of at least 3 organs. Whole-body cooling was achieved by ambient temperature adjustment with or without cooling mattress. Three groups (n = 5 per group) were cooled to core temperatures of 35.5 degrees C (+/-0.5 degrees C), 34.5 degrees C, and 33.5 degrees C, respectively, for 48 hours before rewarming to 37 degrees C. Infants were carefully assessed to identify adverse effects that potentially were related to cooling and rewarming. A noncooled group (n = 10) with advanced surgical NEC and MODS was used for comparison. Data are medians (interquartile range).
Gestational age at birth was 27 weeks (26-30), admission weight was 1.1 kg (1.0-1.7), and admission age was 31 days (12-45). Core temperature was maintained within target range for 90% (88%-97%) of the intended time. Statistically significant relationships were identified between core temperature and heart rate (P < .0001), pH (P < .0001), base excess (P = .003), and blood clot dynamics (longer time to initial clot formation, slower rate of clot formation, and decrease in clot strength; all P < .001) as assessed by thromboelastography. No major clinical problems or adverse events were noted during cooling or rewarming. Comparison with the noncooled group revealed no increase in mortality, bleeding, infection, or need for inotropes in infants who were cooled.
Mild hypothermia for 48 hours in preterm neonates with severe NEC seems both feasible and safe. Additional investigation of the efficacy of this therapeutic intervention in this population is warranted.
患有坏死性小肠结肠炎（NEC）合并多器官功能障碍综合征（MODS）的患儿具有较高的发病率和死亡率。大量的实验证据支持对患有这些疾病的婴儿进行治疗性低温治疗的研究。我们旨在研究轻度低温对患有 NEC 和 MODS 的早产儿的可行性和安全性，为随机试验做准备。
这是一项前瞻性、非随机的早产儿试验研究，共纳入 15 例因晚期 NEC 且至少有 3 个器官衰竭而需要手术干预的早产儿。通过调整环境温度和（或）使用冷却床垫来实现全身降温。三组（每组 5 例）分别将核心温度降至 35.5°C（±0.5°C）、34.5°C 和 33.5°C，持续 48 小时，然后再复温至 37°C。仔细评估患儿以确定可能与降温或复温相关的不良反应。同时还设立了一组未进行冷却的晚期外科 NEC 和 MODS 患儿作为对照组（n=10）。数据以中位数（四分位间距）表示。
出生时的胎龄为 27 周（26-30 周），入院体重为 1.1kg（1.0-1.7kg），入院时年龄为 31 天（12-45 天）。核心温度在 90%（88%-97%）的目标范围内维持了 90%（88%-97%）的时间。核心温度与心率（P＜0.0001）、pH 值（P＜0.0001）、碱剩余（P=0.003）和血栓弹性图（TEG）上的血液凝块动力学（初始凝块形成时间延长、凝块形成速度减慢以及凝块强度降低；均 P＜0.001）之间存在显著的相关性。在降温或复温过程中，未出现重大临床问题或不良事件。与未冷却组相比，在接受冷却治疗的患儿中，未增加死亡率、出血、感染或需要使用正性肌力药物的风险。
在患有严重 NEC 的早产儿中进行 48 小时的轻度低温治疗似乎既可行又安全。在该人群中进一步研究这种治疗干预的疗效是必要的。
