Corticosteroids in Pediatric Septic Shock Are Not Helpful.
Corticosteroids in Pediatric Septic Shock Are Not Helpful.
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皮质类固醇对小儿感染性休克没有帮助。
DOI：
10.1097/ccm.0000000000002980
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发表时间：
2018
影响因子：
8.8
通讯作者：
Zimmerman,JerryJ
中科院分区：
文献类型：
--
作者：
Zimmerman,JerryJ
齐默尔曼638 www.zimmerman638 ccm杂志。 org 2018 年 4 月• 第 46 卷• 第 4 号结论不一致，并表现出重大的方法论缺陷。另一方面，至少七项高质量的描述性队列研究报告了针对该适应症的这种干预措施要么有害，要么没有益处 (9-15)。例如，对儿童严重败血症和器官功能障碍研究数据库的后续分析：全球视角 (RESOLVE) 试验允许检查辅助皮质类固醇对小儿败血性休克结局的作用 (10)。在这项旨在检查辅助活化蛋白 C（Xigris；礼来公司，印第安纳波利斯，印第安纳州）治疗儿科脓毒症的潜在益处的干预性试验中，RESOLVE 招募了 477 名儿童，其中 193 名接受辅助皮质类固醇（主要被归类为感染性休克的治疗干预），284 名未接受辅助性皮质类固醇治疗。入组时，所有患者均接受机械通气和血管活性肌力支持。皮质类固醇治疗组和未治疗组之间的年龄、性别、儿科死亡风险 III 评分、功能障碍器官的基线数量和基线儿科总体表现类别评分没有差异。同样，研究人员报告说，两个研究组之间的结局（包括死亡率和机械通气持续时间、血管活性肌力支持和 PICU 住院时间）没有差异。一些儿科重症监护医生对出现休克症状的儿童保持偏执的警惕，这也许是可以理解的。事实上，这种临床三联征在当代小儿感染性休克中非常罕见。针对常见儿童细菌病原体（包括脑膜炎奈瑟菌、流感嗜血杆菌和肺炎链球菌）的免疫接种现已广泛应用。因此，自从这项关键的公共卫生措施出台以来，儿科重症监护病房（PICU）的感染性疾病状况已经彻底改变。此外，对 21-羟化酶缺乏症（占先天性肾上腺皮质功能不全病例的 95%）的普遍筛查现在已经很普遍，至少在发达国家是这样。这些儿童肾上腺功能不全的记录应在病历中注明为《国际疾病分类》第 9 版临床修订版 255.41 和《国际疾病分类》第 10 版临床修订版 E27。 40. 对于一些患有血流动力学不稳定或有不稳定风险的儿童，毫无疑问需要开出应激剂量的氢化可的松 (16)。此类患者包括患有急性或慢性皮质类固醇给药、下丘脑-垂体-肾上腺轴疾病、先天性肾上腺增生、多种内分泌病以及接受酮康唑或依托咪酯治疗的儿童。医生常常合理化认为，最好在治疗方面犯错误，但可能会无意中低估治疗的副作用 (17)。认为皮质类固醇治疗脓毒症“不会造成伤害”会低估此类药物的实际风险/效益比。单剂量的皮质类固醇会改变人类基因组 20-30% 的信使 RNA 表达 (18)。高血糖、伤口愈合受损、弥漫性神经肌肉无力（包括膈肌）和医院获得性感染等皮质类固醇副作用可能与危重儿童尤其相关。外源性皮质类固醇可能会放大脓毒症引起的应激反应，增加转化为与宿主抵押相关的代谢窘迫综合征的风险……
Zimmerman638 www. ccmjournal. org April 2018• Volume 46• Number 4 inconsistent conclusions, and demonstrated significant methodological flaws. On the other hand, least seven high-quality descriptive cohort investigations have reported either harm or no benefit with this intervention for this indication (9–15). For example, follow-up analysis of the investigation database for REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective (RESOLVE) trial permitted an examination of the role of adjunctive corticosteroids on outcomes in pediatric septic shock (10). In this interventional trial designed to examine the potential benefit of adjunctive activated protein C (Xigris; Eli Lilly and Co., Indianapolis, IN) in pediatric sepsis, RESOLVE enrolled 477 children, 193 who received adjunctive corticosteroids (mostly classified as therapeutic intervention for septic shock) and 284 who did not. At enrollment, all patients were receiving mechanical ventilation and vasoactive-inotropic support. Age, gender, Pediatric Risk of Mortality III scores, baseline number of dysfunctional organs, and baseline Pediatric Overall Performance Category scores did not differ between corticosteroid-treated and corticosteroid not–treated groups. Similarly, the investigators reported that outcomes including mortality and duration of mechanical ventilation, vasoactive-inotropic support, and PICU stay did not differ between the two study groups. It is perhaps understandable that some pediatric intensivists maintain a paranoid vigilance for Waterhouse-Fredericksen syndrome (that involves purpura fulminans, adrenal hemorrhage, and Addisonian crisis) for any child presenting with shock. In reality, this clinical triad is a very rare event in contemporary pediatric septic shock. Immunizations for common childhood bacterial pathogens including Neisseria meningitides, Hemophilus influenza, and Streptococcus pneumoniae are now widely available. Accordingly, the landscape of infection disease in the PICU has completely changed since the introduction of this key public health measure. Furthermore, universal screening for 21-hydroxylase deficiency, responsible for 95% of cases of congenital adrenal insufficiency, is now commonplace, at least in developed countries. Documentation of adrenal insufficiency for these children should be identifiable in the medical record as International Classification of Diseases, 9th Edition, Clinical Modification 255.41 and International Classification of Diseases, 10th Edition, Clinical Modification E27. 40. For some children presenting with or at-risk for unstable hemodynamics, there is no disagreement that prescription of stress dose hydrocortisone is indicated (16). Such patients include children with acute or chronic corticosteroid dosing, hypothalamic-pituitary-adrenal axis disorders, congenital adrenal hyperplasia, multiple endocrinopathies, and treatment with ketoconazole or etomidate. Often physicians rationalize that it is best to err on the side of treatment but may unintentionally underestimate the adverse effects of treatment (17). Believing that corticosteroids for sepsis “can’t hurt” discounts the real risk/benefit ratio for this drug class. A single dose of corticosteroids alters messenger RNA expression for 20–30% of the human genome (18). Corticosteroid side effects such as hyperglycemia, impaired wound healing, diffuse neuromuscular weakness (including the diaphragm), and hospital acquired infection may be particularly relevant for the critically ill child. Exogenous corticosteroids may amplify aspects of the sepsis-induced stress response, increasing the risk of transition to a metabolic distress syndrome associated with host collateral …