Derivation and Validation of Novel Phenotypes of Multiple Organ Dysfunction Syndrome in Critically Ill Children
Derivation and Validation of Novel Phenotypes of Multiple Organ Dysfunction Syndrome in Critically Ill Children
复制标题
危重病患儿多器官功能障碍综合征新表型的建立与验证
DOI：
10.1001/jamanetworkopen.2020.9271
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发表时间：
2020-08-11
影响因子：
13.8
通讯作者：
Luo, Yuan
中科院分区：
文献类型：
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作者：
Sanchez-Pinto, L. Nelson;Stroup, Emily K.;Luo, Yuan
多器官功能障碍综合征（Multiple Organ Dysfunction Syndrome，MODS）是一个动态的、异质性的过程，与危重病患儿的高发病率和死亡率相关。目的探讨基于6种器官功能障碍的数据驱动的MODS表型在危重病患儿中是否具有预后和治疗相关性。这项队列研究包括2010年1月至2016年8月期间在2个大型学术儿科重症监护病房（PICU）住院的14285名儿童中的20827名儿科重症监护患者。如果患者年龄超过21岁或接受过心脏手术，则将其排除。计算前3天的儿科序贯器官衰竭评估（pSOFA）评分的6个分项评分，包括呼吸、心血管、凝血、肝脏、神经和肾功能障碍的分项评分。MODS定义为至少2个器官的pSOFA分项评分至少为2。相遇以80：20的比例分开，分别用于推导和验证。使用6个子评分的轨迹在导出集中使用子图增强的非负矩阵因子分解来导出一组数据驱动的MODS表型。数据分析于2019年3月至10月进行。暴露主要暴露是表型成员。在血管活性物质依赖性休克患者的亚组中，氢化可的松和表型成员之间的相互作用及其与结果的相关性在一个匹配的coherent.Main结局和测量主要结局是住院死亡率。次要结局包括第7天的持续MODS，以及无血管活性物质、无呼吸机和无住院天数。回归分析用于调整年龄、疾病严重程度、免疫功能低下状态和研究地点。结果共有14285例患者，20827次就诊（中位数[四分位数范围]年龄5.2岁[1.5-12.7]岁; 11409例[54.8%; 95%CI，54.1%-55.5%]男性患者）。其中，5297例（25.4%; 95% CI，24.8%-26.0%）为MODS患者，其中5054例（95.4%）符合子图计数阈值并纳入分析。子图增强的非负矩阵因子分解揭示了4种数据驱动的MODS表型，其特征在于神经系统、呼吸系统、凝血系统和心血管功能障碍的组合，如下：表型1，重度持续性脑病（1019例患者[19.2%]）;表型2，中度，低氧血症缓解（1828例患者[34.5%]）;表型3，重度、持续性低氧血症和休克（1012例患者[19.1%]）;表型4，中度、持续性血小板减少和休克（1195例患者[22.6%]）。这些表型在一组验证的遭遇中是可重复的，具有独特的临床特征，并与结局独立相关。例如，使用表型2作为参考，28天时死亡的校正风险比（aHR）如下：表型1，aHR为3.0（IQR，2.1-4.3）;表型3，aHR为2.8（IQR，2.0-4.1）;表型4，aHR为1.8（IQR，1.2-2.6）。在血管活性物质依赖性休克患者的匹配队列中进行的相互作用分析显示，氢化可的松与不同表型的无血管活性物质天数之间存在差异性治疗相关性。例如，接受氢化可的松治疗的表型3患者的无血管活性天数比未接受氢化可的松治疗的患者多（23天vs 18天;相互作用P
IMPORTANCE Multiple organ dysfunction syndrome (MODS) is a dynamic and heterogeneous process associated with high morbidity and mortality in critically ill children.OBJECTIVE To determine whether data-driven phenotypes of MODS based on the trajectories of 6 organ dysfunctions have prognostic and therapeutic relevance in critically ill children.DESIGN, SETTING, AND PARTICIPANTS This cohort study included 20 827 pediatric intensive care encounters among 14 285 children admitted to 2 large academic pediatric intensive care units (PICUs) between January 2010 and August 2016. Patients were excluded if they were older than 21 years or had undergone cardiac surgery. The 6 subscores of the pediatric Sequential Organ Failure Assessment (pSOFA) score were calculated for the first 3 days, including the subscores for respiratory, cardiovascular, coagulation, hepatic, neurologic, and renal dysfunctions. MODS was defined as a pSOFA subscore of at least 2 in at least 2 organs. Encounters were split in a 80:20 ratio for derivation and validation, respectively. The trajectories of the 6 subscores were used to derive a set of data-driven phenotypes of MODS using subgraph-augmented nonnegative matrix factorization in the derivation set. Data analysis was conducted from March to October 2019.EXPOSURES The primary exposure was phenotype membership. In the subset of patients with vasoactive-dependent shock, the interaction between hydrocortisone and phenotype membership and its association with outcomes were examined in a matched cohort.MAIN OUTCOMES AND MEASURES The primary outcome was in-hospital mortality. Secondary outcomes included persistent MODS on day 7, and vasoactive-free, ventilator-free, and hospital-free days. Regression analysis was used to adjust for age, severity of illness, immunocompromised status, and study site.RESULTS There were 14 285 patients with 20 827 encounters (median [interquartile range] age 5.2 years [1.5-12.7] years; 11 409 [54.8%; 95% CI, 54.1%-55.5%] male patients). Of these, 5297 encounters (25.4%; 95% CI, 24.8%-26.0%) were with patients who had MODS, of which 5054 (95.4%) met the subgraph count threshold and were included in the analysis. Subgraph augmented nonnegative matrix factorization uncovered 4 data-driven phenotypes of MODS, characterized by a combination of neurologic, respiratory, coagulation, and cardiovascular dysfunction, as follows: phenotype 1, severe, persistent encephalopathy (1019 patients [19.2%]); phenotype 2, moderate, resolving hypoxemia (1828 patients [34.5%]); phenotype 3, severe, persistent hypoxemia and shock (1012 patients [19.1%]); and phenotype 4, moderate, persistent thrombocytopenia and shock (1195 patients [22.6%]). These phenotypes were reproducible in a validation set of encounters, had distinct clinical characteristics, and were independently associated with outcomes. For example, using phenotype 2 as reference, the adjusted hazard ratios (aHRs) for death by 28 days were as follows: phenotype 1, aHR of 3.0 (IQR, 2.1-4.3); phenotype 3, aHR of 2.8 (IQR, 2.0-4.1); and phenotype 4, aHR of 1.8 (IQR, 1.2-2.6). Interaction analysis in a matched cohort of patients with vasoactive-dependent shock revealed that hydrocortisone had differential treatment association with vasoactive-free days across phenotypes. For example, patients in phenotype 3 who received hydrocortisone had more vasoactive-free days than those who did not (23 days vs 18 days; P for interaction