Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis
Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis
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DOI：
10.1097/01.shk.0000163802.46355.59
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发表时间：
2005-06-01
期刊：
影响因子：
3.1
通讯作者：
Moldawer, LL
中科院分区：
文献类型：
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作者：
Oberholzer, A;Souza, SM;Moldawer, LL
尽管最近在前瞻性识别可能受益于抗炎或抗血栓治疗的脓毒症患者方面取得了进展，但成功的治疗方案相当有限。我们已经探讨了几种促炎细胞因子或介质浓度的测定是否可以补充生理评分系统，以确定严重脓毒症患者将在28天内生存或死亡。该研究的设计包括一项探索性分析，结合一项前瞻性、随机、双盲、安慰剂对照、多中心临床试验，涉及美国33个学术机构。124例严重脓毒症伴或不伴脓毒性休克的患者纳入本分析。在基线和第1天至第4天采集血样，并评价促炎和抗炎细胞因子浓度以及降钙素原和总蛋白C水平。评价了这些介质的基线浓度和浓度变化与急性生理学和慢性健康评价（APACHE）II和多器官功能障碍（MOD）评分以及28天全因死亡率的关系。使用单变量逻辑回归分析，APACHE II和MOD评分、年龄（但不是性别）以及基线血浆白细胞介素（IL）-6和可溶性肿瘤坏死因子受体（sTNFR）1（log转换）浓度均预测28天全因死亡率的增加（P < 0.01）。基线总蛋白C、IL-8、IL-10、TNF-α和降钙素原浓度以及最初4天内血浆细胞因子浓度较基线的变化对预测结局没有帮助。选定的基线促炎细胞因子浓度与APACHE II评分相关（P < 0.01）。IL-6浓度是预测严重脓毒症患者临床结局的一个强有力的候选指标，或与APACHE II或MOD评分联合使用。应进一步评估细胞因子测量和预后评分相结合对识别可能从抗炎或抗血栓治疗中获益的患者的潜在有用性。
Despite recent advances in the prospective identification of the patient with sepsis who may benefit from anti-inflammatory or antithrombotic therapies, successful treatment regimens have been fairly modest. We have explored whether determination of several proinflammatory cytokine or mediator concentrations can complement physiologic scoring systems to identify patients with severe sepsis who will survive or expire within 28 days. The design of the study included an exploratory analysis performed in conjunction with a prospective, randomized, double-blind, placebo-controlled, multicenter, clinical trial and involved 33 academic institutions in the United States. One hundred twenty-four patients with severe sepsis with or without septic shock were included in this analysis. Blood samples were obtained at baseline and on days 1 through 4, and were evaluated for proinflammatory and anti-inflammatory cytokine concentrations, as well as for procalcitonin and total protein C levels. Baseline concentrations and changes in the concentrations of these mediators were evaluated in relationship to the Acute Physiology and Chronic Health Evaluation (APACHE) II and multiple organ dysfunction (MOD) scores, and 28-day all-cause mortality. Using univariate logistic regression analyses, APACHE II and MOD scores, age (but not gender), and baseline plasma interleukin (IL)-6 and soluble tumor necrosis factor receptor (sTNFR) 1 (log transformed) concentrations were all predictive of increased 28-day all-cause mortality (P < 0.01). Baseline total protein C, IL-8, IL-10, TNF-alpha, and procalcitonin concentrations, and the change in plasma cytokine concentrations from baseline over the initial 4 days were not useful in predicting outcome. Selected baseline proinflammatory cytokine concentrations and APACHE II score were correlated (P < 0.01). IL-6 concentration is a strong candidate for predicting clinical outcome in patients with severe sepsis alone, or when combined with the APACHE II or MOD scores. The potential usefulness of the combination of cytokine measurements and prognostic scores to identify patients who may benefit from treatment with anti-inflammatory or antithrombotic therapies should be further evaluated.