Schwingshackl Andreas, Kimura Dai, Rovnaghi Cynthia R, Saravia Jordy S, Cormier Stephania A, Teng Bin, West Alina N, Meduri Umberto G, Anand Kanwaljeet J S
Department of Pediatrics, Mattel Children's Hospital at UCLA, Los Angeles, CA, United States.
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States.
Cytokine. 2016 Jan;77:63-71. doi: 10.1016/j.cyto.2015.10.007. Epub 2015 Nov 3.
A double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients.
Double-blind, placebo-controlled randomized trial with blood collection on study entry and day 7.
Tertiary care children's hospital.
Children (0-18years) with ARDS undergoing mechanical ventilation.
35 children were randomized within 72h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2mg/kg loading dose followed by 1mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7.
At study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1α, IFN-γ and IL-10 levels. The glucocorticoid group had lower INF-α, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17α levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson's correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity.
This pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes.
一项双盲随机对照试验表明，小儿急性呼吸窘迫综合征（ARDS）患者采用低剂量糖皮质激素治疗是可行的，且可能改善这些患者的通气和氧合指标。然而，结局潜在变化的分子机制仍不清楚。基于这些临床发现，本研究旨在探讨静脉注射甲泼尼龙对小儿ARDS患者循环炎症生物标志物的影响。
双盲、安慰剂对照随机试验，在研究开始时和第7天采集血液。
三级护理儿童医院。
接受机械通气的ARDS患儿（0 - 18岁）。
35名儿童在机械通气72小时内随机分组。糖皮质激素组接受2mg/kg负荷剂量的甲泼尼龙，随后从第1天至第7天以1mg/kg/天持续输注。两组均按照ARDSnet建议进行通气。在第0天和第7天分析白细胞及分类细胞计数、血浆细胞因子和CRP水平以及凝血参数。
在研究开始时，安慰剂组的IL - 15和嗜碱性粒细胞水平较高。在第7天，与研究开始时相比，安慰剂组的IL - 1α、IFN - γ和IL - 10水平较低。与研究开始时相比，糖皮质激素组在第7天的INF - α、IL - 6、IL - 10、MCP - 1、G - CSF和GM - CSF水平较低，而IL - 17α水平较高。安慰剂组在第0天和第7天之间的总细胞计数和分类细胞计数保持不变，而糖皮质激素组在第7天的白细胞总数和血小板计数增加。安慰剂组和糖皮质激素组内的Pearson相关性研究揭示了细胞因子水平、细胞计数、凝血参数与我们之前研究中确定的疾病严重程度相关临床参数之间的正相关和负相关。多元回归模型确定了几种细胞因子作为疾病严重程度临床参数变化的预测因子。
这项初步研究表明在小儿ARDS患者中同时测量多种炎症细胞因子、细胞计数和凝血参数是可行的。我们报告了可能对未来更大规模试验预测ARDS严重程度和结局有用的统计模型。
