Chest Department, Taipei Veterans General Hospital, Shipai Road, Taipei 112, Taiwan, ROC.
Crit Care. 2011;15(1):R11. doi: 10.1186/cc9412. Epub 2011 Jan 10.
Despite recent advances in the management of septic shock, mortality rates are still unacceptably high. Early identification of the high-mortality risk group for early intervention remains an issue under exploration. Vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR1) and urokinase plasminogen activator (uPA) have diverse effects in the pathogenesis of sepsis, which involve pro-inflammation, anti-inflammation, endothelial cell repair, and vascular permeability change. Their roles in predicting mortality and organ dysfunction remain to be clarified.
Pneumonia-related septic shock patients from medical intensive care units were enrolled for this prospective observational study. We also included 20 patients with pneumonia without organ dysfunction for comparison. Plasma levels of VEGF and sVEGFR1 and uPA activity within 24 hours of shock onset were measured. We compared plasma levels of these biomarkers with APACHE II scores between subgroups of patients, and evaluated their predictive value for 28-day mortality and organ dysfunction.
A total of 101 patients, including 81 with pneumonia-related septic shock and 20 with pneumonia without organ dysfunction, were enrolled. Non-survivors of septic shock had significantly higher plasma sVEGFR1 levels (659.3 ± 1022.8 vs. 221.1 ± 268.9 pg/mL, respectively, P < 0.001) and uPA activity (47.2 ± 40.6 vs. 27.6 ± 17.2 units, respectively, P = 0.001) when compared with those of the survivors. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients with higher levels of sVEGFR1 (P < 0.001) and uPA activity (P = 0.031). In Cox regression analysis, plasma sVEGFR1 level was independently associated with, and best predicted, the 28-day mortality of septic shock (HR: 1.55, 95% CI: 1.05-2.30). Plasma sVEGFR1 level and uPA activity had good correlation with renal dysfunction, metabolic acidosis, and hematologic dysfunction; their levels significantly increased when the number of organ dysfunctions increased. In multivariate analysis, plasma sVEGFR1 level (HR: 2.82, 95% CI: 1.17-6.81) and uPA activity (HR: 2.75, 95% CI: 1.06-7.13) were independent predictors of the presence of concomitant multi-organ dysfunction. The predictive value of VEGF for mortality and organ dysfunction was limited in pneumonia-related septic shock patients.
High plasma sVEGFR1 level in the early stage of pneumonia-related septic shock independently predicted 28-day mortality and multi-organ dysfunction.
尽管在脓毒性休克的治疗方面取得了最近的进展，但死亡率仍然高得令人无法接受。早期识别高死亡率的高危人群并进行早期干预仍然是一个正在探索的问题。血管内皮生长因子（VEGF）、可溶性血管内皮生长因子受体 1（sVEGFR1）和尿激酶型纤溶酶原激活物（uPA）在脓毒症的发病机制中具有不同的作用，涉及促炎、抗炎、内皮细胞修复和血管通透性变化。它们在预测死亡率和器官功能障碍方面的作用仍需阐明。
本前瞻性观察性研究纳入了来自重症监护病房的肺炎相关性脓毒性休克患者。我们还纳入了 20 例无器官功能障碍的肺炎患者作为对照。在休克发生后 24 小时内测量 VEGF 和 sVEGFR1 血浆水平和 uPA 活性。我们比较了这些生物标志物在亚组患者的急性生理与慢性健康状况评分Ⅱ（APACHE II）评分之间的差异，并评估了它们对 28 天死亡率和器官功能障碍的预测价值。
共纳入 101 例患者，其中 81 例为肺炎相关性脓毒性休克，20 例为肺炎无器官功能障碍。脓毒性休克幸存者的 sVEGFR1 水平（659.3 ± 1022.8 vs. 221.1 ± 268.9 pg/mL，P < 0.001）和 uPA 活性（47.2 ± 40.6 vs. 27.6 ± 17.2 单位，P = 0.001）明显高于非幸存者。Kaplan-Meier 生存分析显示，sVEGFR1 水平较高的患者死亡率显著更高（P < 0.001）。Cox 回归分析显示，血浆 sVEGFR1 水平与脓毒性休克 28 天死亡率独立相关，且最佳预测（HR：1.55，95%CI：1.05-2.30）。血浆 sVEGFR1 水平和 uPA 活性与肾功能障碍、代谢性酸中毒和血液学功能障碍有良好的相关性；随着器官功能障碍数量的增加，其水平显著升高。在多变量分析中，血浆 sVEGFR1 水平（HR：2.82，95%CI：1.17-6.81）和 uPA 活性（HR：2.75，95%CI：1.06-7.13）是同时存在多器官功能障碍的独立预测因子。VEGF 对死亡率和器官功能障碍的预测价值在肺炎相关性脓毒性休克患者中有限。
肺炎相关性脓毒性休克早期高血浆 sVEGFR1 水平独立预测 28 天死亡率和多器官功能障碍。
