It's About Time ….
It's About Time ….
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是时候了……。
DOI：
10.1097/pcc.0000000000000532
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Zimmerman,JerryJ
中科院分区：
文献类型：
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作者：
Zimmerman,JerryJ
编辑794 WWW。PCcmJournal。Org 2015年10月，第16卷·第8名研究人员研究了氢化可的松(2)和非特异性一氧化氮合酶抑制剂(31)作为感染性休克的辅助治疗方法，讨论了感染性休克的缓解不是合适的替代结果衡量标准，因为这与持久的、临床上有意义的结果无关(32)。在儿童严重脓毒症和器官功能障碍的研究中，将完成器官功能障碍的复合时间作为主要结果衡量标准：激活蛋白c治疗儿童严重脓毒症的全球前瞻性(RESOLE)试验(33例)。遗憾的是，这一变量与长期结果的关系尚不清楚。然而，一种量化全球儿科器官功能障碍的工具，儿科后勤器官功能障碍(34)，已经在患有败血症的儿童中得到了专门的验证(35)。此外，个别器官特异性措施现已被证实可用于心血管、肺、肾和凝血功能障碍。Menon和Wong(1)证实，将死亡率作为儿童感染性休克介入试验的主要结果衡量标准是不可行的。然而，有人建议将死亡率和显著的发病率结合起来将构成一种以患者为中心的、具有临床意义的长期结果衡量标准(36)。在临床试验中，功能状态量表被开发为一种易于使用的工具来衡量功能残疾(37)。对RESOLE数据库的分析表明，除了17%的死亡率外，34%的存活受试者的儿科总体表现类别恶化，18%符合功能不良结果的标准(38)。儿科总体表现类别提供了粗略的功能状态评分，并提供了更细粒度的功能状态量化。正在进行的儿科败血症后生活评估(LAPSE)观察性试验(5R01HD0733625)专门设计用于分析与健康相关的生活质量，作为儿科败血症干预试验的结果指标。因此，LOSE将量化儿童感染性休克幸存者在PICU入院后第一年内与健康相关的生活质量恶化的程度和持续时间。儿童脓毒症后的功能状态和与健康相关的生活质量明显受损的发生率似乎比死亡率高得多，如果作为主要结果指标，与使用死亡率相比，需要的登记人数要少得多。试验的纳入和排除标准将需要经过深思熟虑地得出。尽管使用一种现成的生物标志物来确定感染性休克的儿童在辅助性皮质类固醇治疗中获益最多、风险最低是理想的，但这可能是不可能的。感染性休克的皮质类固醇治疗(CORTICUS)试验(临床试验)的一个结论。GOV数字，NCT00147004)是标准促肾上腺皮质激素刺激试验测量基线和刺激的总皮质醇不提供这一功能(2)。Menon和Wong(1)讨论了用于此目的的小剂量促肾上腺皮质激素刺激试验和游离皮质醇测量还没有完全准备好进入黄金时间。事实上，在这个节骨眼上，我们并不真正了解相对肾上腺功能不全或与危重疾病相关的皮质类固醇功能不全的概念和可能的干预措施，特别是在危重儿童中。
Editorials794 www. pccmjournal. org October 2015• Volume 16• Number 8 investigators examining hydrocortisone (2) and a nonspecific nitric oxide synthase inhibitor (31) as adjunctive therapies for septic shock have discussed that resolution of septic shock is not an appropriate surrogate outcome measure because this is not associated with durable, clinically meaningful outcomes (32). Composite time to complete organ dysfunction resolution was used as the primary outcome measure in the REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective (RESOLVE) trial of activated protein c for pediatric severe sepsis (33). Regrettably, the relationship with this variable and longer term outcomes is not known. However, a tool for quantification of global pediatric organ dysfunction, Pediatric Logistic Organ Dysfunction (34), is available and has been specifically validated in children with sepsis (35). In addition, individual organ-specific measures have now been validated for cardiovascular, pulmonary, renal, and coagulation dysfunctions. Menon and Wong (1) ascertain that using mortality as a primary outcome measure for an interventional trial in pediatric septic shock is not feasible. However, it has been suggested that combining mortality and significant morbidity would constitute a patient-centered, clinically meaningful, long-term outcome measure (36). The Functional Status Scale was developed as an easy-to-use instrument to measure functional disability in clinical trials (37). Analysis of the RESOLVE database indicated that in addition to 17% mortality, 34% of surviving subjects exhibited a worsening their Pediatric Overall Performance Category, and 18% met criteria for poor functional outcome (38). Pediatric Overall Performance Category provides a coarse and Functional Status Score provides a more granular quantification of functional status. The ongoing, Life After Pediatric Sepsis Evaluation (LAPSE) observational trial (5R01HD0733625) was specifically designed to analyze health-related quality of life as an outcome measure for pediatric sepsis interventional trials. Accordingly, LAPSE will quantify magnitude and duration of health-related quality of life deterioration among survivors of pediatric septic shock during the first year after PICU admission. Significantly impaired functional status and health-related quality of life following pediatric sepsis appear to occur at a much higher frequency than mortality and if used as primary outcome measures would require much smaller enrollment numbers when compared with using mortality. Inclusion and exclusion criteria for the trial will need to be thoughtfully derived. Although it would be ideal to use a readily available biomarker to identify the group of children with septic shock with the greatest benefit and lowest risk for adjunctive corticosteroid administration, this will likely not be possible. One conclusion of the Corticosteroid Therapy of Septic Shock (CORTICUS) trial (ClinicalTrials. gov number, NCT00147004) was that standard corticotropin stimulation testing measuring baseline and stimulated total cortisol does not serve this function (2). Menon and Wong (1) discuss that low-dose corticotropin stimulation testing and free cortisol measurement for this purpose are not quite ready for prime time. In fact at this juncture, we do not really understand the concept of and potential intervention for relative adrenal insufficiency or critical illness–related corticosteroid insufficiency, particularly among critically ill children.