脓毒血症的多学科救治进展-

Fudan UniversityHuashan HospitalDepartment of Infectious Diseases,脓毒症临床多学科救治进展,复旦大学附属华山医院感染科 张文宏2016 7月 青岛,感染病专业覆盖面,抗菌药物治疗血流感染脓毒症FUO 骨关节感染中枢神经系统感染，脑膜炎心内膜炎骨髓炎肺炎移植相关感染免疫低下相关感染（预防与治疗）术后感染病毒感染HIV感染与AIDSHCV感染流感寄生虫感染性传播疾病旅游相关疾病（预防与治疗）结核病院内感染,The main factor in all inflammatory states consists in a lesion of the vessels which are attacked by the irritating cause.,Elias Metchnikoff, 18451916,脓毒血症的病理生理本质,In the old book-1992,Sepsis: a systemic inflammatory response to infection (SIRS), popularly described as a cytokine storm .,Repeatedly criticized as non-specific!,Systemic inflammatory response can be caused by non-microbial irritating causes, such as autoimmune, metabolic or physical insults.,The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. 1992,脓毒血症概念的起源,SIRS: 各种损伤引起的临床反应，符合：,符合2个或2个以上下面的条件：T 38C or 90 beats/minRR20 breaths/min or PaCO212000/L or 10% immature forms,Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. Intensive Care Med (2013) 39:165228,“Sepsis” is bestdefined as the systemic inflammatory response syndrome(SIRS) caused by microbial products.,感染,全身炎症反应综合征,脓毒血症,严重脓毒血症,脓毒症：感染引起的全身炎症反应综合征,老概念：关注体征与症状 （1.0版本）,Sepsis definition 1.0 1992,Sepsis 1.0,SIRS,Infection orTrauma,Severe Sepsis,Septic Shock,MODS,Sepsis induced hypoperfusion 1 organ dysfunction,SepsisHypotensionAdequate fluid resuscitation,T P R W 2,SIRS 2 + infection, 2 organs,Bone et al. Chest. 1992; 101(6):1644-1655.,Sepsis definition 2.0 2003,Sepsis 2.0,Expanded clinical and laboratory variables,Infection orTrauma,Severe Sepsis,Septic Shock,MODS,Sepsis induced hypoperfusion 1 organ dysfunction,SepsisHypotensionAdequate fluid resuscitation,5 items 24 parameters,Some of + infection, 2 organs,Levy MM, et al. Crit Care Med.2003Apr;31(4):1250-6,多脏器功能评分(SOFA) 成为脓毒症的重要诊断和评价标准,Sepsis definition 3.0 2015,Sepsis,SIRS,Infection orTrauma,Severe Sepsis,Septic Shock,MODS,SepsisHypotensionAdequate fluid resuscitation Lactate 2.0mmol/L,T P R W 2,Infecion + SOFA 2, 2 organs,新概念：从微循环障碍到脏器功能受损,Infections that cause a lesion in microcirculation can potentially compromise the function of multiple organs.Leading to hypotension and myocardial dysfunction, thrombocytopenia with- out or with disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and acute brain injury.,从败血症到脓毒症概念的延伸,Zeng M, et al. EID. 2013,19 (7),脓毒血症概念的延伸,脓毒症：感染触发的全身炎症反应综合征,SOFA 概念倡导多学科合作救治,脓毒症生命体征维护救治要点,充分理解脓毒症的疾病阶段,脓毒症死亡率随病程发展而增加,Rangel-Frausto et al, JAMA 1995,器官机能障碍数量:0 to 1 15%2 33 to 50%3 或更多 70%,Angus, Crit.Care Med. 2001Moerer et al., Int.Care Med. 2002,病程的严重性,SIRS,脓毒症,严重脓毒症,脓毒性休克,死亡率,早期ICU介入 改善生存机会: 死亡率出现脓毒症后到ICU 47.5%出现脓毒症前到ICU 37.4%,死亡率,感染ICU 第一时间展开多学科联合救治,为更好的救治重症患者，建立感染ICU病房，这将为重症患者的抢救提供硬件保障。,SSC指南演变,2002年，多位世界知名专家共同发表了巴塞罗那宣言，倡议开展全球拯救全身性感染运动，目标希望5年内使病死率降低25%-surviving sepsis campaign2004年制定了第一版SSC治疗指南-Surviving Sepsis Campaign Guidelines for management of severe sepsis and septic shock.CCM,2004,32(3):858-873. 2008年制定了第二版-Surviving Sepsis Campaign：International guidelines for management of severe sepsis and septic shock.CCM,2008,36(1):296-327.Intensive Care Med,2008,34(1):17-60.2012年2月6日，在美国Houston危重症年会上对上述指南予以了再次更新(目前仍30-70%死亡率)-Update of The Surviving Sepsis Campaign Guidelines. Pre Phil Dellinger.,感染诱发急性ARDS的机械通气,初始复苏治疗,升压药物,多巴胺 vs 去甲肾上腺素,多巴胺和去甲肾上腺素抗休克的总体死亡率无显著差异；发现多巴胺治疗中导致更多不良反应，尤其是房颤；同样也没有证实日渐受到推崇的去甲肾上腺素的“显著疗效”，尤其是在亚组分析中对感染性休克的作用；尤其值得关注的是多巴胺对心源性休克的有害作用这一研究结果，将会对现行ACC/AHA 指南中以多巴胺作为急性心肌梗死低血压患者的首选升压药研究提出强烈挑战，将影响多巴胺作为一线抗休克药物的临床应用。,Backer,Patrick Biston, Jacques Devriendt,et al. Comparison of Dopamine and Norepinephrine in the Treatment of Shock. N Engl J Med，2010,362:779,强心治疗,抗菌药物使用时机,抗菌药物的治疗时机,早期有效抗菌治疗：阻止疾病进展,强化治疗的作用：缩短病程,Kumar A. Virulence. 2014 Jan 1;5(1):80-97,抗生素治疗,多脏器支持：维持脏器功能与康复,抗生素治疗,血液制品输注,抗感染与抗炎治疗,糖皮质激素,糖皮质激素应用的利弊,Annane D, et al. Cochrane Database Syst Rev. 2015 Dec 3;12:CD002243,HDT精准治疗,编码白三烯B4的LTA4H 基因指导下的精准抗炎,ITA4H,促炎通路,抗炎通路,Tobin DM, Roca FJ, Oh SF, et al. Cell 2012; 148: 43446.,糖皮质激素对炎症活动剧烈患者有预后改善作用,未使用糖皮质激素,使用糖皮质激素,T/T基因型，炎症活动水平高，糖皮质激素应用后预后改善最明显,Tobin DM, Roca FJ, Oh SF, et al. Cell 2012; 148: 43446.,总结,重视脓毒症的诊断指标，倡导多学科救治-掌握一般指标、炎症指标、血流动力学指标、器官功能不全指标及组织灌注指标，提高诊断的特