Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury
Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury
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DOI：
10.1097/01.ccm.0000149854.61192.dc
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发表时间：
2005-01-01
影响因子：
8.8
通讯作者：
Wheeler, AP
中科院分区：
文献类型：
--
作者：
Parsons, PE;Eisner, MD;Wheeler, AP
目的：评估白细胞介素-6、白细胞介素-8和白细胞介素-10与急性肺损伤患者的临床结局（包括死亡率）之间的关系，并确定低潮气量通气是否与急性肺损伤患者血浆细胞因子的降低有关。设计：多中心随机试验。环境：十个大学中心的重症监护病房。患者：该研究纳入了861名患者，他们参加了国家心肺血液研究所急性呼吸窘迫综合征临床网络试验，比较了传统潮气量对急性肺损伤的影响。干预措施：患者随机分为6 mL/kg或12 mL/kg潮气量策略，如前所述。测量结果和主要结果：在控制呼吸机组的logistic回归分析中，白细胞介素-6、白细胞介素-8和白细胞介素-10的基线血浆水平均与死亡风险增加相关，比值比为1.63 / log-10, 95%置信区间为1.33-1.98；优势比为2.33 / log-10, 95%置信区间为1.79-3.03；多因素分析控制了通气策略、急性生理和慢性健康评估III评分、Pao(2)/Fio(2)比、肌酐、血小板计数和血管加压药的使用(比值比为1.63 / log-10, 95%可信区间为0.93-1.49；比值比为1.73 / log-10, 95%可信区间为1.29-2.34；比值比为1.23 / log-10, 95%置信区间分别为0.86 -1.76)。白细胞介素-6和白细胞介素-8水平也与无呼吸机和无器官衰竭天数的显著减少有关。脓毒症患者的细胞因子水平最高，每升高一次细胞因子死亡的风险最大。到第3天，6 mL/kg策略与白细胞介素-6和白细胞介素-8水平的更大下降相关。与12 mL/kg组相比，6 mL/kg组白细胞介素-6减少26%(95%置信区间，12-37%)，白细胞介素-8减少12%（95%置信区间，1-23%）。结论：急性肺损伤患者血浆白细胞介素-6和白细胞介素-8水平与发病率和死亡率相关。炎症的严重程度随临床危险因素的不同而不同，提示在制定和测试治疗干预措施时应考虑临床危险因素。低潮气量通气与炎症反应的更快衰减有关。
Objectives: To evaluate the association between interleukin-6, interleukin-8, and interleukin-10 and clinical outcomes including mortality in patients with acute lung injury and to determine whether lower tidal volume ventilation was associated with a decrease in plasma cytokines in patients with acute lung injury.Design: Multiple-center, randomized trial.Setting: Intensive care units in ten university centers.Patients: The study included 861 patients enrolled in the National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial of lower tidal volumes compared with traditional tidal volumes for acute lung injury.Interventions: Patients were randomized to a 6 mL/kg or a 12 mL/kg tidal volume strategy that has been previously described.Measurements and Main Results: Baseline plasma levels of interleukin-6, interleukin-8, and interleukin-10 were each associated with an increased risk of death in both logistic regression analyses controlling for ventilator group odds ratio 1.63 per log-10 increment, 95% confidence interval 1.33-1.98; odds ratio 2.33 per log-10 increment, 95% confidence interval 1.79-3.03; odds ratio 2.02 per log-10 increment, 95% confidence interval 1.47-2.76, respectively) and multivariate analyses controlling for ventilation strategy, Acute Physiology and Chronic Health Evaluation III score, Pao(2)/Fio(2) ratio, creatinine, platelet count, and vasopressor use (odds ratio 1.63 per log-10 increment, 95% confidence interval 0.93-1.49; odds ratio 1.73 per log-10 increment, 95% confidence interval 1.29-2.34; odds ratio 1.23 per log-10 increment, 95% confidence interval 0.86 -1.76, respectively). Interleukin-6 and interleukin-8 levels were also associated with a significant decrease in ventilator free and organ failure free days. Patients with sepsis had the highest cytokine levels and the greatest risk of death per cytokine elevation. By day 3, the 6 mL/kg strategy was associated with a greater decrease in interleukin-6 and interleukin-8 levels. There was a 26% reduction in interleukin-6 (95% confidence interval, 12-37%) and a 12% reduction in interleukin-8 (95% confidence interval, 1-23%) in the 6 mL/kg group compared with the 12 mL/Kg group.Conclusions: In patients with acute lung injury, plasma interleukin-6 and interleukin-8 levels are associated with morbidity and mortality. The severity of inflammation varies with clinical risk factor, suggesting that clinical risk factor should be considered when both developing and testing therapeutic interventions. Low tidal volume ventilation is associated with a more rapid attenuation of the inflammatory response.