1、陈攸涛陈攸涛2012 版儿童严重脓毒症与脓版儿童严重脓毒症与脓毒性休克治疗国际指南解读毒性休克治疗国际指南解读陈攸涛陈攸涛v2012版指南采用GRADE分级系统 vGRADE分级系统由推荐等级与证据强度两部分构成 陈攸涛陈攸涛推荐等级推荐等级v1级推荐(recomment)：指该措施有着良好的预期效果和经济效益。v2级建议(suggest)：指该措施可能有不可预知的不良反应和较低的经济效益陈攸涛陈攸涛证据强度分级证据强度分级A级(强)高质量随机对照研究B级(中等)中等质量随机对照或高质量观察性及队列研究C级(弱)完成良好、设对照的观察性及队列研究D级(极弱)病例总结或专家意见陈攸涛陈攸涛Par
2、t G Protein C and activated protein concentrate vG.Protein C and activated protein concentrate.蛋白C和活化蛋白浓缩物 指南中在儿童及成人均不推荐使用（已退市）vSee“History of recommendations regarding use of recombinant activated protein C”.参照参照“关于重组活化蛋白关于重组活化蛋白C（rhAPC）使用的旧版）使用的旧版推荐推荐”陈攸涛陈攸涛vRecombinant human activated protein C(r
3、hAPC)was approved for use in adult patients in a number of countries in 2001 following the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis(PROWESS)trial,which enrolled 1,690 severe sepsis patients and showed a significant reduction in mortality(24.7%)with rhAPC compared w
4、ith placebo(30.8%,P=0.005).Part G Protein C and activated protein concentrate 陈攸涛陈攸涛v2001年一些国家根据PROWESS研究结果开始批准重组活化蛋白（rhAPC）应用于成人。vPROWESS研究一共收集了1690例严重脓毒症病例，证实rhAPC相对安慰剂可以明显降低严重脓毒症患者死亡率（24.7%vs.30.8%,P=0.005）。Part G Protein C and activated protein concentrate 陈攸涛陈攸涛vThe 2004 SSC guidelines recommen
5、ded use of rhAPC in line with the product labeling instructions required by the US and European regulatory authorities with a grade B quality of evidence 7,8.v2004版SSC指南将rhAPC使用等级定为1B。Part G Protein C and activated protein concentrate 陈攸涛陈攸涛vBy the time of publication of the 2008 SSC guidelines,addi
6、tional studies of rhAPC in severe sepsis(as required by regulatory agencies)had shown it ineffective in less severely ill patients with severe sepsis as well as in children 229,230.v到了2008年，又有一些新的研究表明rhAPC对一些疾病引起的严重脓毒症中是无效的（包括儿童）。Part G Protein C and activated protein concentrate 陈攸涛陈攸涛vThe 2008 SSC
7、 recommendations reflected these findings,and the strength of the rhAPC recommendation was downgraded to a suggestion for use in adult patients with a clinical assessment of high risk of death,most of whom will have Acute Physiology and Chronic Health Evaluation(APACHE)II scores C25 or multiple orga
8、n failure(grade 2C;quality of evidence was also downgraded from 2004,from B to C).Part G Protein C and activated protein concentrate 陈攸涛陈攸涛v2008版SSC指南将rhAPC使用等级下调至2C，仅建议在具有死亡高风险（APACHE II评分C25）或合并多器官衰竭成人患者中使用。Part G Protein C and activated protein concentrate 陈攸涛陈攸涛vThe 2008 guidelines also recommen
9、ded against use of rhAPC in low-risk adult patients,most of whom will have APACHE II scores B20 or single organ failures(grade 1A),and against use in all pediatric patients(grade 1B).v同时2008版指南提出反对rhAPC在低风险（APACHE II 评分B20）及单器官衰竭（1A）和儿童中使用（1B）。Part G Protein C and activated protein concentrate 陈攸涛陈攸
10、涛vThe results of the PROWESS SHOCK trial(1,696 patients)were released in late 2011,showing no benefit of rhAPC in patients with septic shock(mortality 26.4%for rhAPC,24.2%placebo)with a relative risk of 1.09 and a P value of 0.31。v2011年PROWESS SHOCK研究显示严重脓毒症患者并没有从 rhAPC中受益，rhAPC组死亡率26.4%，安慰剂组死亡率24.2
11、%（RR1.09，P0.31）Part G Protein C and activated protein concentrate 陈攸涛陈攸涛vThe drug was withdrawn from the market and is no longer available,negating any need for an SSC recommendation regarding its use。v这个药物从此退出市场Part G Protein C and activated protein concentrate 陈攸涛陈攸涛Part H Blood products and plasm
12、a therapies v1.We suggest similar hemoglobin targets in children as in adults.vDuring resuscitation of low superior vena cava oxygen saturation shock（70%）,hemoglobin levels of 10 g/dL are targeted.vAfter stabilization and recovery from shock and hypoxemia,then a lower target 7.0 g/dL can be consider
13、ed reasonable(grade 1B)陈攸涛陈攸涛Part H Blood products and plasma therapies v建议儿童维持血红蛋白量与成人相似（7.09.0g/dL）。v在低上腔静脉血氧饱和度（70%）的脓毒症休克复苏时，目标血红蛋白量为10 g/dL。v待病情稳定，休克和低氧血症纠正后，目标血红蛋白量可以考虑为7.0g/dL(1B)。陈攸涛陈攸涛Part H Blood products and plasma therapies vThe optimal hemoglobin for a critically ill child with severe s
14、epsis is not known.v儿童脓毒症最佳血红蛋白值尚无定论。v A recent multi-center trial reported no difference in mortality in hemodynamically stable critically ill children managed with a transfusion threshold of 7 g/dL compared with those managed with a transfusion threshold of 9.5 g/dLv一项多中心研究报道在血液动力血稳定的重症患儿HB 7 g/dL
15、（输血阈值）组与 9.5 g/dL在死亡率上无明显差异。陈攸涛陈攸涛Part H Blood products and plasma therapies vhowever,the severe sepsis subgroup had an increase in nosocomial sepsis and lacked clear evidence of equivalence in outcomes with the restrictive strategy陈攸涛陈攸涛Part H Blood products and plasma therapies vBlood transfusion
16、is recommended by the World Health Organization for severe anemia,hemoglobin value 5g/dL,and acidosis.vWHO建议严重贫血（HB5g/dL）及酸中毒时需要输血。陈攸涛陈攸涛Part H Blood products and plasma therapies vA RCT of early goal-directed therapy for pediatric septic shock using the threshold hemoglobin of 10 g/dL for patients
17、with a SvcO2 saturation less than 70%in the first 72h of pediatric ICU admission showed improved survival in the multimodal intervention arm.v一项RCT研究显示，早期目标导向治疗Svc O2 70%的患儿，最初72小时内HB低于10 g/dL时输血可提高生存率。陈攸涛陈攸涛Part H Blood products and plasma therapies v2.We suggest similar platelet transfusion target
18、s in children as in adults(grade 2C).v建议儿童血小板计数目标值与成人相似（2C）。PLT10109L，没有出血表现 PLT 20109L，有严重出血倾向 PLT50109L，但有活动性出血、手术、侵袭性操作时陈攸涛陈攸涛Part H Blood products and plasma therapies v3.We suggest the use of plasma therapies in children to correct sepsis-induced thrombotic purpura disorders,including progressi
19、ve disseminated intravascular coag-ulation,secondary thrombotic microangiopathy,and thrombotic thrombocytopenic purpura(grade 2C).v建议儿童脓毒症导致的血栓性紫癜性疾病，包括DIC、继发性血栓性血管病、血栓性血小板减少性紫癜的患儿给予血浆治疗（2C）陈攸涛陈攸涛Part H Blood products and plasma therapies vWe give plasma to reverse thrombotic micro-angiopathies in c
20、hildren with thrombocytopenia-associated multiple organ failure and progressive purpura because fresh frozen plasma contains protein C,antithrombin III,and other anticoagulant proteins.v新鲜冰冻血浆中含有蛋白C、抗凝血酶和其他抗凝蛋白，可用来逆转血栓性微血管病导致的多脏器功能衰竭和进行性紫癜。陈攸涛陈攸涛Part H Blood products and plasma therapies vRapid resu
21、scitation of shock reverses most disseminated intravascular coagula-tion;however,purpura progresses in some children in part due to critical consumption of antithrombotic proteins(e.g.,protein C,antithrombin III,ADAMTS 13).v脓毒性休克的快速复苏过程中可逆转大部分的弥散性血管内凝血，但一些患儿紫癜进行性增多，部分由于消耗了大量的抗凝蛋白(如蛋白C、抗凝血酶、ADAMTSl3)
22、。陈攸涛陈攸涛Part H Blood products and plasma therapies vPlasma is infused with the goal of correcting prolonged prothrombin/partial thromboplastin times and halting purpura.v血浆的输注可以纠正PT、APTT的延长，并终止紫癜。陈攸涛陈攸涛Part H Blood products and plasma therapies vLarge volumes of plasma require concomitant use of diuretics,continuous renal replacement therapy,or plasma exchange to prevent greater than 10%fluid overload。v大量血浆输注需同时使用利尿剂、持续肾脏透析治疗或血浆置换，以防止液体负荷超过10。陈攸涛陈攸涛
