Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome.
Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome.
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DOI：
10.1007/s00134-010-2088-x
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发表时间：
2011-03
影响因子：
38.9
通讯作者：
Carcillo JA
中科院分区：
文献类型：
--
作者：
Hall MW;Knatz NL;Vetterly C;Tomarello S;Wewers MD;Volk HD;Carcillo JA
单核细胞人类白细胞抗原DR长时间抑制定义的免疫麻痹与成人严重脓毒症的不良结局相关，并可被粒细胞巨噬细胞集落刺激因子(GM-CSF)逆转。我们假设，在多器官功能障碍综合征(MODS)的第3天以后，由全血体外脂多糖诱导的肿瘤坏死因子-α(TWF-α)反应和200pg/ml定义的免疫麻痹与儿童的医院感染相似，并且可以用GM-CSF逆转。在研究阶段1，我们对移植和非移植多器官功能障碍综合征(MODS)患者(≥2器官衰竭)进行了多中心队列试验。在第二期研究中，我们对非中性粒细胞减少、非移植、严重的MODS(≥3器官衰竭)患者进行了一项GM-CSF治疗的开放随机试验，患者的肿瘤坏死因子α反应值为160pg/ml。34%的MODS患者(n=70)出现免疫麻痹，并与医院感染(相对风险3.3，95%可信区间[1.8-6.0]p<；0.05)和死亡率(RR 5.8[2.1-16]p<；0.05)增加相关。阳性培养后7天内肿瘤坏死因子α的反应和200pg/mL值与持续医院感染有关，而恢复到200pg/mL值与感染的消退有关(p<；0.05)。在研究2期间，GM-csf治疗促进了肿瘤坏死因子α在7天内迅速恢复对200pg/ml的反应(p<；0.05)，并预防了医院感染(7例患者无感染，7例患者有8例感染)(p<；0.05)。与成人相似，免疫麻痹是儿科MODS发生医院感染的潜在可逆危险因素。全血体外肿瘤坏死因子α反应是一种很有前途的监测这种情况的生物标志物。
Immunoparalysis defined by prolonged monocyte human leukocyte antigen DR depression is associated with adverse outcomes in adult severe sepsis and can be reversed with granulocyte macrophage colony-stimulating factor (GM-CSF). We hypothesized that immunoparalysis defined by whole-blood ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha (TNFα) response <200 pg/mL beyond day 3 of multiple organ dysfunction syndrome (MODS) is similarly associated with nosocomial infection in children and can be reversed with GM-CSF. In study period 1, we performed a multicenter cohort trial of transplant and nontransplant multiple organ dysfunction syndrome (MODS) patients (≥2 organ failure). In study period 2, we performed an open-label randomized trial of GM-CSF therapy for nonneutropenic, nontransplant, severe MODS patients (≥3 organ failure) with TNFα response <160 pg/mL. Immunoparalysis was observed in 34% of MODS patients (n = 70) and was associated with increased nosocomial infection (relative risk [RR] 3.3, 95% confidence interval [1.8–6.0] p < 0.05) and mortality (RR 5.8 [2.1–16] p < 0.05). TNFα response <200 pg/mL throughout 7 days after positive culture was associated with persistent nosocomial infection, whereas recovery above 200 pg/mL was associated with resolution of infection (p < 0.05). In study period 2, GM-CSF therapy facilitated rapid recovery of TNFα response to >200 pg/mL by 7 days (p < 0.05) and prevented nosocomial infection (no infections in seven patients versus eight infections in seven patients) (p < 0.05). Similar to in adults, immunoparalysis is a potentially reversible risk factor for development of nosocomial infection in pediatric MODS. Whole-blood ex vivo TNFα response is a promising biomarker for monitoring this condition.