严重脓毒症治疗药物重组人活化蛋白C

重组人活化蛋白C(recombinanthumanactivatedproteinC ,又名drotrecoginalfa,商品名Xigris)是美国FDA在 2 0 0 1年 11月批准的第一个用于治疗成人严重脓毒症的新一类药物 ,具有抗血栓、抗炎和促纤维蛋白溶解作用。该药由礼莱公司研制开发 ,上市剂型为注射用冻干粉针 ,规格为 5和 2 0mg/ml。在抗击“非典”的特殊时期 ,我国紧急进口本品用于危重病人的救治。蛋白C通路受损在脓毒症的发病机理中起着重要作用 ,给予重组人活化蛋白C可以恢复异常的抗凝血机制 ,抑制凝血酶生成和微血管血栓形成 ,同时调节全身的致炎应答 ,保护器官功能。药理…     

C反应蛋白和降钙素原对早产儿脓毒血症预后分析

目的分析血清C反应蛋白和降钙素水平对早产儿脓毒血症预后的价值。方法选取2012年6月—2014年6月鹿邑县人民医院儿科治疗的182例脓毒血症早产儿为研究对象,监测血清C反应蛋白和降钙素原水平,记录临床资料,并观察预后情况。结果存活组患儿的胎龄大于死亡组,发病日龄长于死亡组,出生体重高于死亡组,两组间比较差异显著（P〈0.05）。存活组患儿随治疗天数增加,血清CRP和PCT水平均逐渐降低且均小于死亡组,差异显著（P〈0.05）;而死亡组患儿的血清CRP和PCT水平均随治疗天数增加基本无变化,差异不显著（P〉0.05）。存活患儿与死亡患儿的NCIS分级差异显著（P〈0.05）。结论血清C反应蛋白和降钙素水平对早产儿脓毒血症预后预测具有重要的临床价值。     

降钙素原检测在脓毒血症急性肾损伤中的意义

目的探讨降钙素原(PCT)检测在脓毒血症导致急性肾损伤(AKI)中的指导意义。方法脓毒血症患者50例作为实验组,再将其分为AKI阳性组(8例)和AKI阴性组(42例),50例健康体检者作为对照组,检测各组人员的PCT、C反应蛋白(CRP)和白细胞(WBC)水平。结果实验组PCT、CRP和WBC结果较对照组均明显增高,差异有统计学意义(P<0.05);AKI阳性组较AKI阴性组PCT明显增高,差异有统计学意义(P<0.05);CRP、WBC结果比较差异无统计学意义(P>0.05)。结论脓毒血症导致急性肾损伤患者,PCT浓度比CRP和WBC敏感,可评估由脓毒血症导致急性肾损伤的风险。     

降钙素原和C反应蛋白在重症病房脓毒血症患者早期诊断中的应用价值

目的 探讨降钙素原(PCT)和C反应蛋白(CRP)在重症病房脓毒血症患者早期诊断中的应用价值。方法 选取2020年1月至2022年2月我院ICU收治的165例脓毒血症患者,分析病原菌的分布,比较革兰阴性菌感染者和革兰阳性菌感染者的临床指标差异,分析各临床指标对区分革兰阴性菌感染者和革兰阳性菌感染者的灵敏度和特异度以及相互间的相关性。数据采用GraphPad软件进行显著性差异和ROC曲线分析,Spearman秩相关法进行相关性分析。结果 165例患者共检出212株病原菌,革兰阴性菌占48.59%,革兰阳性菌占42.45%,真菌占8.96%;绝大部分患者的PCT和CRP水平均高于正常范围,PCT、CRP水平在革兰阴性感染组和革兰阳性感染组间差异有统计学意义(P<0.05),且两者呈正相关(r>0.3),革兰阴性菌感染者的PCT和CRP平均水平显著高于革兰阳性菌感染者;PCT水平高于(28.42±38.87)ng/mL时感染革兰阴性菌概率高,同时,CRP水平高于(148.29±91.45)mg/L时感染菌较可能为常见的肺炎克雷伯菌、大肠埃希菌或鲍曼不动杆菌的其中一种。结论 PCT...     

CRRT治疗严重脓毒血症中的价值分析

目的:评价连续性肾脏替代治疗(CRRT)在严重脓毒血症中的应用价值。方法:选取2016年1月～2018年1月于某院ICU治疗的行CRRT治疗的严重脓毒血症患者46例为观察组,同期常规治疗未选择CRRT的严重脓毒血症患者50例为对照组,动态监测并对比两组患者血流动力学、血清学指标及病死率。结果:治疗后,两组患者中心静脉压(CVP)、平均动脉压(MAP)以及中心静脉血氧饱和度(ScvO_2)均较治疗前显著提高,且观察组显著高于对照组(P0.05);治疗后,两组患者乳酸(Lac)、降钙素原(PCT)、血肌酐(Cr)、C反应蛋白(CRP)均显著降低,且观察组改善显著优于对照组(P0.05);观察组30d病死率显著低于对照组,差别有统计学意义(P0.05)。结论:在严重脓毒血症患者中采用CRRT治疗,能够维持血流动力学平衡,减少炎症介质释放、改善肾脏功能,降低病死率,值得在临床应用中进一步推广。     

小剂量糖皮质激素在脓毒血症患者治疗中的应用

目的：探讨小剂量糖皮质激素在急诊脓毒血症患者治疗中的应用效果。方法急诊脓毒血症患者128例,按治疗方法不同分为观察组72例和对照组56例。两组患者均参照2004国际拯救脓毒症战役（ SSC）指南给予对症支持治疗,观察组在此基础上加用小剂量氢化可的松。比较两组患者治疗前及治疗72 h的急性生理学及慢性健康状况评分Ⅱ（APACHEⅡ）评分、降钙素原（PCT）、CRP、机械通气时间、EICU停留时间、血管活性药物使用时间,28 d内多器官功能不全综合征发生率和病死率。结果两组治疗72 h时APACHEⅡ评分均显著下降（t＝11．12、7．23,均P＜0．05）,观察组显著低于对照组（t＝4．32,P＜0.05）。两组治疗72 h时PCT及CRP水平均较治疗前显著下降（t＝9．45、12．31、5．87、9．10,均P＜0．05）,且观察组较对照组下降更为显著（t＝4．91、5．12,均P＜0．05）。观察组机械通气时间、EICU停留时间、血管活性药物使用时间均明显短于对照组（t＝9．60、5．12、13．60,均P＜0．05）。观察组多器官功能不全综合征发生率、病死率分别为34．72％、26．39％,对照组分别为55．36％、38．29％,差异均有统计学意义（χ2＝4．01、4．22,均P＜0.05）。结论小剂量糖皮质激素用于急诊脓毒血症患者可快速逆转病情,改善预后,降低病死率。     

FDA审查礼来公司重组人活化蛋白C增加出血风险事件

近日美国监管机构宣称,其正在调查由于使用礼来公司的重组人活化蛋白C（drotrecogin alfa,Xigris）导致脓毒血症患者发生严重出血甚至死亡风险增加这一事件。     

重组人活化蛋白C治疗儿童脓毒症休克的临床观察

目的观察重组人活化蛋白C（rhAPC）对儿童脓毒症休克的疗效及安全性。方法选择我院儿科及重症监护病房2011年1月-2014年3月间收治的60例脓毒症休克患儿,随机分为对照组（n=30）和rhAPC组（n=30）。对照组患儿给予对症治疗,rhAPC组患儿在此基础上静脉注射rhAPC 24μg/（kg·h）,连续给药4 d。2组患儿于治疗前及治疗后检测血浆纤维蛋白原和D-二聚体水平及炎症因子IL-6、IL-8、TNF-α、动脉血氧饱和度（SaO2）和中心静脉压（CVP）。结果 rhAPC组患儿治疗后血浆纤维蛋白原和D-二聚体水平及炎症因子IL-6、IL-8和TNF-α均显著低于对照组,而SaO2和CVP高于对照组,其差异均有统计学意义（P〈0.05）。rhAPC组1例患儿发生出血性膀胱炎。结论 rhAPC能有效抑制脓毒症休克患儿的炎症反应,降低血液高凝状态。     

重组人生长激素治疗肝硬变低蛋白血症疗效观察

目的 观察重组人生长激素治疗肝硬变低蛋白血症的疗效。方法 随机选择30例血清蛋白＜30g/L、A／G＜1．0的肝炎后肝硬变（活动期）病人，在常规治疗基础上加用重组人生长激素4IU，皮下注射，每日1次，10d为1个疗程。结果 治疗后，病人临床症状明显改善，腹水明显减少，下肢浮肿消退，血清白蛋白明显增加，球蛋白明显下降，A／G比值升高，停药2周后白蛋白增加更为明显。结论 在综合治疗基础上使用重组人生长激素，能改善肝炎后肝硬变（活动期）病人蛋白合成功能，改善低蛋白血症和营养状况。     

The epidemiology of severe sepsis syndrome and its treatment with recombinant human activated protein C

Severe sepsis syndrome has important consequences to healthcare systems as the incidence is increasing, there is significant attributed morbidity and mortality and there is a substantial cost for in-hospital and post-discharge care. Current treatment includes the use of antimicrobials, local source control and aggressive physiological support, usually in an intensive care unit setting. Drotrecogin-alpha (activated) or recombinant human activated protein C (rhAPC) is the only biological agent approved for use in severe sepsis syndrome that has demonstrated efficacy in reducing 28-day all-cause mortality and new data suggests a trend towards longer term survival. However, given the evidence of a variable effect on survival rates in patient subgroups and its acquisition cost, controversy has arisen concerning its appropriate use. This review discusses the epidemiology of sepsis, preclinical and clinical evidence supporting the use of rhAPC use, controversies about the evidence of efficacy in severe sepsis syndrome and cost-effectiveness data.     

The epidemiology of severe sepsis syndrome and its treatment with recombinant human activated protein C

Severe sepsis syndrome has important consequences to healthcare systems as the incidence is increasing, there is significant attributed morbidity and mortality and there is a substantial cost for in-hospital and post-discharge care. Current treatment includes the use of antimicrobials, local source control and aggressive physiological support, usually in an intensive care unit setting. Drotrecogin-alpha (activated) or recombinant human activated protein C (rhAPC) is the only biological agent approved for use in severe sepsis syndrome that has demonstrated efficacy in reducing 28-day all-cause mortality and new data suggests a trend towards longer term survival. However, given the evidence of a variable effect on survival rates in patient subgroups and its acquisition cost, controversy has arisen concerning its appropriate use. This review discusses the epidemiology of sepsis, preclinical and clinical evidence supporting the use of rhAPC use, controversies about the evidence of efficacy in severe sepsis syndrome and cost-effectiveness data.     

Protective mechanisms of activated protein C in severe inflammatory disorders

The protein C system is an important natural anticoagulant mechanism mediated by activated protein C (APC) that regulates the activity of factors VIIIa and Va. Besides well-defined anticoagulant properties, APC also demonstrates anti-inflammatory, anti-apoptotic and endothelial barrier-stabilizing effects that are collectively referred to as the cytoprotective effects of APC. Many of these beneficial effects are mediated through its co-receptor endothelial protein C receptor, and the protease-activated receptor 1, although exact mechanisms remain unclear and are likely pleiotropic in nature. Increased insight into the structure–function relationships of APC facilitated design of APC variants that conserve cytoprotective effects and reduce anticoagulant features, thereby attenuating the risk of severe bleeding with APC therapy. Impairment of the protein C system plays an important role in acute lung injury/acute respiratory distress syndrome and severe sepsis. The pathophysiology of both diseases states involves uncontrolled inflammation, enhanced coagulation and compromised fibrinolysis. This leads to microvascular thrombosis and organ injury. Administration of recombinant human APC to correct the dysregulated protein C system reduced mortality in severe sepsis patients (PROWESS trial), which stimulated further research into its mechanisms of action. Several other clinical trials evaluating recombinant human APC have been completed, including studies in children and less severely ill adults with sepsis as well as a study in acute lung injury. On the whole, these studies have not supported the use of APC in these populations and challenge the field of APC research to search for additional answers.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Adventure of recombinant human activated protein C in sepsis and new treatment hopes on the horizon

Sepsis continues to be a very important cause of morbidity and mortality despite advances in modern medicine. It is the cause of mortality in approximately 28-50% of the patients, with the risk increasing particularly in patients with multiple organ dysfunctions. Although anti-infective treatment and securing hemostasis form the cornerstone in the management of this condition, studies to develop new drugs are expected to reduce mortality in severely septic patients. Recombinant human activated protein C (rhAPC) was known as an anti-inflammatory agent with proven efficacy in severe sepsis patients and had a critical effect in the reduction of mortality when administered in the right dose and duration so far, but unfortunately current studies indicate that it was unable to show favorable effects of rhAPC on patients with severe sepsis. For this reason, interests are becoming focused on some other new approaches such as antioxidant treatments, stem cells, computer-implemented sepsis alerting systems, endotoxin removal devices. These attempts may reduce the incidence of mortality due to sepsis in the near future. Some patents on sepsis have also been reviewed in this article.     

Recombinant human activated protein C

This review will summarise the relevant pathophysiology of sepsis, the rationale for treatment with recombinant human activated protein C and the evidence for and against its use, and will provide evidence-based recommendations for its administration.     

Coagulopathy and the role of recombinant human activated protein C in sepsis and following polytrauma

Recombinant human activated protein C (rhAPC) also known as drotrecogin alfa (activated) has known antithrombotic, anti-inflammatory, and profibrinolytic properties in severe sepsis. Treatment with rhAPC (Xigris) has been shown to reduce mortality in patients with severe sepsis. The lack of any trials of rhAPC in trauma patients means that a definitive recommendation regarding its use in the polytraumatised patient, in whom severe head trauma or other contraindications for the use of rhAPC have been excluded remains controversial at present. This article describes the current evidence of its efficacy and safety in severe sepsis with relation to surgery and trauma.     

新型严重脓毒症治疗剂--重组人激活蛋白C

通过文献检索综述了用于治疗成人严重脓毒症的药物重组人激活蛋白C的药理作用、药代动力学及临床评价.在1690名患者参加的PROWESS临床试验中,它可以降低严重脓毒症患者28天治疗期内各种原因的死亡率且使用较安全.     

Anti-thrombotic effect of activated protein C

Protein C (PC) is an important anticoagulant protein in blood and converted to its active form, activated protein C (APC), by thrombin bound with thrombomodulin. APC exhibits an anticoagulant effect by the inactivation of FV a and FVIII a. In addition, APC exerts a profibrinolytic effect by inactivation of PAI-1 and inhibition of TAFI activation. APC is strongly anti-thrombotic because of its anticoagulant and profibrinolytic effect. APC has gamma-carboxyglutamic acid residues that bind to acidic phospholipids expressed on activated platelet or injured endothelial cells. Thus APC works only at the site where clots are formed and has a weak effect in primary hemostasis; this means that the use of APC is expected not to have any hemorrhagic risk. In both DIC animal models and clinical studies, we confirmed safer amelioration by APC than heparin. Recently, a specific receptor for PC/APC was found on endothelial cell membrane and anti-inflammatory effects of APC were also reported. Thus APC is thought to play an important regulatory role in blood coagulation, fibrinolysis and inflammation, especially in thrombotic diseases.