脓毒症休克患者血清Kal、VE-Cad的变化及与预后的关系

目的 探讨脓毒症休克患者血清人源性激肽释放酶结合蛋白（Kal）、血管内皮钙黏蛋白（VE-cad）的变化及与预后的关系。方法 前瞻性选取2016年3月—2018年3月杭州市丁桥医院重症医学科收治的脓毒症休克患者252例，根据纳入和排除标准排除74例，最终纳入研究的脓毒症休克患者为178例。根据患者28 d预后分为存活组120例和死亡组58例。比较两组患者的临床指标及入住重症监护病房（ICU）第1天、第3天、第5天血清Kal和VE-cad水平变化，记录患者急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分和序贯性器官功能衰竭评估（SOFA）评分。采用Pearson相关分析血清Kal、VE-cad与APACHEⅡ评分和SOFA评分的相关性。采用受试者工作特征（ROC）曲线评估血清Kal、VE-cad单独及联合检测对脓毒症休克患者预后的价值。采用二元Logistic回归分析脓毒症休克死亡的影响因素。结果 死亡组的氧合指数和血清白蛋白（ALB）水平低于存活组（P <0.05），机械通气时间、ICU住院时间长于存活组（P <0.05），血清C反应蛋白（CRP）、降钙素原（PCT）水平、血管外肺水指数（EVLWI）、APACHEⅡ评分和SOFA评分高于存活组（P <0.05）。两组入住ICU第1天、第3天、第5天血清Kal、VE-cad水平比较，不同时间点的血清Kal、VE-cad有差异（P <0.05），两组血清Kal、VE-cad有差异（P <0.05），两组血清Kal、VE-cad变化趋势有差异（P <0.05）。血清Kal水平与APACHEⅡ评分和SOFA评分呈负相关（r =-0.397和-0.466，P <0.05）；血清VE-cad与APACHEⅡ评分和SOFA评分呈正相关（r =0.173和0.192，P <0.05）。入院24 h内血清Kal、VE-cad及两者联合检测的曲线下面积（AUC）分别为0.687（95% CI：0.604，0.770）、0.859（95% CI：0.805，0.912）、0.890（95% CI：0.845，0.936），血清Kal检测预测脓毒症休克患者死亡的敏感性为81.0%（95% CI：0.772，0.854），特异性为50.0%（95% CI：0.474，0.531）；VE-cad检测预测脓毒症休克患者死亡的敏感性为69.0%（95% CI：0.649，0.726），特异性为86.7%（95% CI：0.822，0.914）；血清Kal和VE-cad联合检测预测脓毒症休克患者死亡的敏感性为82.2%（95% CI：0.781，0.868），特异性为89.6%（95% CI：0.852，0.954）。CRP［R=1.221（95% CI：1.022，1.459）］、PCT［R=1.195（95% CI：1.035，1.380）］、VE-cad［R=1.373（95% CI：1.055，1.787）］、EVLWI［R=1.846（95% CI：1.178，2.893）］是脓毒症休克患者死亡的危险因素（P <0.05），Kal［R=0.428（95% CI：0.190，0.966）］是脓毒症休克患者死亡的保护因素（P <0.05）。结论 CRP、PCT、Kal、VE-cad、EVLWI是脓毒症休克患者死亡的影响因素，脓毒症休克患者血清VE-cad水平升高，Kal水平降低，两者的联合检测对评估脓毒症休克患者的预后有一定临床价值。

Changes of serum Kallistatin and VE-cad in patients with septic shock and their relationship with prognosis

Objective To investigate the changes of serum human kallikrein-binding protein (Kallistatin, Kal) and vascular endothelial cadherin (VE-cad) in patients with septic shock and their relationship with prognosis.Methods A total of 252 patients with septic shock admitted to the Department of Critical Care Medicine, Hangzhou Hospital of Traditional Chinese Medicine, from March 2016 to March 2018, were prospective selected. 74 patients were excluded according to pre-specified exclusion criteria, and there were 178 patients with septic shock who were eventually included in the study. According to the 28-day prognosis, they were divided into survival group (120 cases) and death group (58 cases). The changes of serum Kal and VE-cad levels on the 1, 3 and 5 days of ICU were observed. The acute physiology and chronic health status scoring system II (APACHE II) score and sequential organ failure assessment (SOFA) score of sepsis patients were recorded. Pearson correlation analysis was used to analyze the correlation of serum Kal and VE-cad with APACHE II score and SOFA score. Evaluation of prognostic value of serum Kal and VE-cad in patients with septic shock was performed with the receiver operating characteristic curve (ROC). Binary logistic regression was used to analyze the influence factors for septic shock death.Results The oxygenation index and serum albumin (ALB) levels in the death group of patients with septic shock were lower than those in the survival group (P < 0.05). Mechanical ventilation time, ICU hospitalization days were longer than those in the survival group (P < 0.05), the levels of serum C-reactive protein (CRP), procalcitonin (PCT), extravascular lung water index (EVLWI), APACHE II score, and SOFA score were higher than those in the survival group (P < 0.05). The serum Kal and VE-cad levels of the death group and the survival group were different at different time points (P < 0.05); the serum Kal and VE-cad levels of the death group and the survival group were different (P < 0.05); the change trend of serum Kal and VE-cad levels of the death group and the survival group were different (P < 0.05), and the serum Kal level in the death group of patients with septic shock (1, 3 and 5d of ICU admission) were lower than those in the survival group (P <0.05). Serum VE-cad level in the death group (1, 3 and 5d of ICU admission) were higher than those in the survival group (P <0.05). There was a negative correlation between serum Kal level and APACHE II score and SOFA score (r = -0.397 and -0.466, both P < 0.05). Serum VE-cad was positively correlated with APACHE II score and SOFA score (r = 0.173 and 0.192, both P < 0.05). Within 24h of admission, the area under curve (AUC) of serum Kal, VE-cad and their combined detection were 0.687 (95% CI: 0.604, 0.770), 0.859 (95% CI: 0.805, 0.912), and 0.890 (95% CI: 0.845, 0.936), respectively; the sensitivity and specificity of serum Kal were 81.0% (95% CI: 77.2%, 85.4%) and 50.0% (95% CI: 47.4%, 53.1%); the sensitivity and specificity of VE-cad were 69.0% (95% CI: 64.9%, 72.6%) and 86.7% (95% CI: 82.2%, 91.4%); the sensitivity and specificity of combined method to predict the death of septic shock patients was 82.2% (95% CI: 78.1%, 86.8%) and 89.6% (95% CI: 85.2%, 95.4%). CRP R = 1.221, (95% CI: 1.022, 1.459)], PCT R = 1.195, (95% CI: 1.035, 1.380)], VE-cad R = 1.373, (95% CI: 1.055, 1.787)], and EVLWI R = 1.846, (95% CI: 1.178, 2.893)] were risk factors for death in patients with septic shock (P < 0.05); Kal R = 0.428, (95% CI: 0.190, 0.966)] was protective factor for death in patients with septic shock (P < 0.05).Conclusion CRP, PCT, VE-cad, Kal, and EVLWI were influence factors for death in patients with septic shock. The serum VE-cad level increased and Kal decreased in patients with septic shock. The combined detection of VE-cad and Kal has certain clinical value in evaluating the prognosis of patients with septic shock.