Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias
Feasibility of adjunct therapeutic hypothermia treatment for hyperammonemia and encephalopathy due to urea cycle disorders and organic acidemias
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DOI：
10.1016/j.ymgme.2013.05.014
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发表时间：
2013-08-01
影响因子：
3.8
通讯作者：
Baumgart, Stephen
中科院分区：
文献类型：
--
作者：
Lichter-Konecki, Uta;Nadkarni, Vinay;Baumgart, Stephen
背景：尿素循环障碍(UCDs)或有机酸中毒(OAS)合并急性高氨血症和脑病的儿童具有神经损伤、发育迟缓、智力残疾和死亡的巨大风险。营养支持、静脉途径替代治疗和透析用于治疗UCDS相关的严重高氨血症，营养支持和透析用于治疗OAS的严重高氨血症。在开始治疗的同时进行脑保护性治疗，可能会在孩子的一生中改善神经和认知功能。急性肝功能衰竭引起的肝性脑病的动物实验和小型临床试验表明，治疗性低温对高氨血症相关性脑病具有神经保护作用。我们报告了一项正在进行的初步研究的结果，该研究评估在抢救新生儿急性高氨血症和脑病期间全身降温是否可行和是否可以安全进行。方法：在标准治疗的基础上，对急性脑病、UCDS和OAS需要透析的急性脑病、高氨血症新生儿进行辅助全身治疗。随着透析准备的进行，使用冷却毯开始治疗低温。与新生儿缺氧缺血性脑病的标准低温治疗相似，将患者维持在33.5℃+/-1℃72 h，然后每隔3 h缓慢复温0.5℃，持续18 h。此外，收集年龄匹配的历史对照数据进行比较。结果：采用先导研究方案对7例患者进行降温，并对7例历史对照的数据进行回顾。所有7名患者均在最初的抢救和降温治疗中存活下来，6名患者在住院2-4周后出院，其中5名患者口服喂养。结论：对接受标准治疗的新生儿UCDS和OAS进行辅助亚低温治疗是可行的，在儿科和新生儿重症监护室应用治疗性亚低温治疗危重新生儿是安全的。然而，在已经涉及的高氨血症和脑病危重患者的治疗方案中包括辅助治疗低温增加了护理的复杂性，除非在随机临床试验中证明是有效的，否则不应该这样做。(C)2013 Elsevier Inc.保留所有权利。
Background: Children with urea cycle disorders (UCDs) or organic acidemias (OAs) and acute hyperammonemia and encephalopathy are at great risk for neurological injury, developmental delay, intellectual disability, and death. Nutritional support, intravenous alternative pathway therapy, and dialysis are used to treat severe hyperammonemia associated with UCDs and nutritional support and dialysis are used to treat severe hyperammonemia in OAs. Brain protective treatment while therapy is initiated may improve neurological and cognitive function for the lifetime of the child. Animal experiments and small clinical trials in hepatic encephalopathy caused by acute liver failure suggest that therapeutic hypothermia provides neuroprotection in hyperammonemia associated encephalopathy. We report results of an ongoing pilot study that assesses if whole body cooling during rescue treatment of neonates with acute hyperammonemia and encephalopathy is feasible and can be conducted safely.Methods: Adjunct whole body therapeutic hypothermia was conducted in addition to standard treatment in acutely encephalopathic, hyperammonemic neonates with UCDs and OAs requiring dialysis. Therapeutic hypothermia was initiated using cooling blankets as preparations for dialysis were underway. Similar to standard therapeutic hypothermia treatment for neonatal hypoxic ischemic encephalopathy, patients were maintained at 33.5 degrees C +/- 1 degrees C for 72 h, they were then slowly rewarmed by 0.5 degrees C every 3 h over 18 h. In addition data of age-matched historic controls were collected for comparison.Results: Seven patients were cooled using the pilot study protocol and data of seven historic controls were reviewed. All seven patients survived the initial rescue and cooling treatment, 6 patients were discharged home 2-4 weeks after hospitalization, five of them feeding orally. The main complication observed in a majority of patients was hypotension.Conclusion: Adjunct therapeutic hypothermia for neonates with UCDs and OAs receiving standard treatment was feasible and could be conducted safely in pediatric and neonatal intensive care units experienced in the application of therapeutic hypothermia in critically ill neonates. However, including adjunct therapeutic hypothermia in the already involved treatment regimen of critically ill patients with hyperammonemia and encephalopathy adds to the complexity of care and should not be done unless it is proven efficacious in a randomized clinical trial. (C) 2013 Elsevier Inc. All rights reserved.