激素在CAP社区获得性肺炎中的应用课件.pptx

1、目录ATEXT 02BTEXT 03CTEXT 04D激素在肺炎中的应用 化学性肺炎化学性肺炎 放射性肺炎放射性肺炎 过敏性肺炎过敏性肺炎 吸入性肺炎吸入性肺炎 SARS等病毒性肺炎等病毒性肺炎 卡氏肺孢子菌肺炎卡氏肺孢子菌肺炎 粟粒性肺结核粟粒性肺结核 其他其他CAP？adapted from National Kompas Volksgezondheid 死因顺位的第死因顺位的第4 位，构成比为位，构成比为6.6%约约20%的的CAP患者须住院患者须住院 住院的肺炎死亡率达住院的肺炎死亡率达10%25%其中住其中住ICU的肺炎死亡率更高（的肺炎死亡率更高（60%）对于感染的过度免疫炎症反应

2、对于感染的过度免疫炎症反应 脓毒症休克脓毒症休克 急性呼吸窘迫综合征急性呼吸窘迫综合征 多器官衰竭多器官衰竭 机体反应性低下机体反应性低下 老年老年 酗酒酗酒 糖尿病糖尿病 心力衰竭心力衰竭 肝硬化肝硬化 选择恰当的抗菌素选择恰当的抗菌素 尽管新的机械通气支持方式、抗生素的出现，尽管新的机械通气支持方式、抗生素的出现，死亡率却没有明显降低死亡率却没有明显降低 适当的免疫治疗适当的免疫治疗 增强免疫增强免疫-胸腺肽、免疫球蛋白等胸腺肽、免疫球蛋白等 抑制炎症抑制炎症目录TEXT 01ABTEXT 03CTEXT 04DMeijvis S C,et al.约20%的CAP患者须住院Serum cy

3、tokines and critical illness-related corticosteroid insufficiency甲强龙 200-mg ivgtt st，继之Serum cytokines and critical illness-related corticosteroid insufficiency56例，X线进展性或呼吸衰竭。其中住ICU的肺炎死亡率更高（60%）56例，X线进展性或呼吸衰竭。Critical Care 2011,15:R9620mg q6h 3dHydrocortisone infusion for severe community-acquired p

4、neumonia:a preliminary randomized study.2005 Feb 1;171(3):242-8.Crit Care Med 1999;27:17451753.Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumonia20mg q12h 3dIntensive Care Medicine November 2010,Volume 36,Issue 11,pp 1845-1851Clin Diagn Lab Immunol

5、 2003;10:813820.9%(36 out of 82 patients)Epub 2004 Nov 19.疾病严重程度与炎症有关CAP的本质 病原体病原体 炎症炎症促炎细胞因子应答促炎细胞因子应答：-肿瘤坏死因子肿瘤坏死因子-（TNF-TNF-），-白介素（白介素（ILIL）-1-1-IL-6IL-6抗炎细胞因子抗炎细胞因子应答：应答：-IL-10IL-10-可溶性TNF-受体-IL-1受体拮抗蛋白，防止出现炎症反应失控。防止出现炎症反应失控。Effect of corticosteroids on the clinical course of community-acquired

6、pneumonia:a randomized controlled trialEffect of corticosteroids on the clinical course of community-acquired pneumonia:a randomized controlled trial在注射促肾上腺皮质激素(ACTH)250 ug后血清考的松增高9ug/mlSerum cytokines and critical illness-related corticosteroid insufficiency20mg q6h 3d同济大学学报(医学版)2009,30(3)何礼贤甲强龙 20

7、0-mg ivgtt st，继之甲强龙 200-mg ivgtt st，继之56例，X线进展性或呼吸衰竭。Crit Care Med 1999;27:17451753.在注射促肾上腺皮质激素(ACTH)250 ug后血清考的松增高9ug/ml下丘脑-垂体-肾上腺（HPA）轴20mg qd 3dCytokine expression in severe pneumonia:a bronchoalveolar study.20mg q12h 3dHydrocortisone infusion for severe community-acquired pneumonia:a preliminary

8、 randomized study.Effect of corticosteroids on the clinical course of community-acquired pneumonia:a randomized controlled trialClin Diagn Lab Immunol 2003;10:813820.Crit Care Med 1999;27:17451753.Monton C,et al.Cytokine expression in severe pneumonia:a bronchoalveolar study.Crit Care Med 1999;27:17

9、451753.Monton C,et al.Cytokine expression in severe pneumonia:a bronchoalveolar study.Clin Diagn Lab Immunol 2003;10:813820.Fernandez-Serrano S,et al.Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumonia Clin Diagn Lab Immunol 2003;10:813820.Fernandez

10、-Serrano S,et al.Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumonia Clin Diagn Lab Immunol 2003;10:813820.Fernandez-Serrano S,et al.Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumonia目录ATEXT 02BCTE

11、XT 04Dl 进入胞质内与糖皮进入胞质内与糖皮质激素受体质激素受体-热休克热休克蛋白（蛋白（GR-HspGR-Hsp）结）结合并与合并与HspHsp分离，分离，l 激素与其受体的复激素与其受体的复合物进入细胞核产合物进入细胞核产生抗炎作用生抗炎作用 关闭编码促炎细胞关闭编码促炎细胞因子的基因，因子的基因，开启编码抗炎细胞开启编码抗炎细胞因子的基因，因子的基因，DIC,细胞因子细胞因子诊断标准：诊断标准：基础血清考的松基础血清考的松10ug/ml或或 在注射促肾上腺皮质激素在注射促肾上腺皮质激素(ACTH)250 ug后后血清考的松增高血清考的松增高9ug/mlIntensive Care M

12、edicine November 2010,Volume 36,Issue 11,pp 1845-1851 Serum cytokines and critical illness-related corticosteroid insufficiency同济大学学报(医学版)2009,30(3)何礼贤下丘脑-垂体-肾上腺（HPA）轴Cytokine expression in severe pneumonia:a bronchoalveolar study.The overall incidence of CIRCI was 43.2005 Feb 1;171(3):242-8.重症肺炎时血清

13、和BALF的促炎因子56例，X线进展性或呼吸衰竭。Effect of corticosteroids on the clinical course of community-acquired pneumonia:a randomized controlled trial约20%的CAP患者须住院CIRCI患者细胞因子更高Meijvis S C,et al.疾病严重程度与炎症有关2005 Feb 1;171(3):242-8.Effect of corticosteroids on the clinical course of community-acquired pneumonia:a ran

14、domized controlled trial2005 Feb 1;171(3):242-8.Meijvis S C,et al.Critical Care 2011,15:R96CAP患病率、死亡率高Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumoniaHydrocortisone infusion for severe community-acquired pneumonia:a preliminary randomized study.激

15、素疗效不突出的原因（2）The overall incidence of CIRCI was 43.9%(36 out of 82 patients)Intensive Care Medicine November 2010,Volume 36,Issue 11,pp 1845-1851 Serum cytokines and critical illness-related corticosteroid insufficiency目录ATEXT 02BCD 46例重症例重症CAP 氢化可的松氢化可的松200-mg ivgtt st，继之，继之 10 mg/hour for 7 days 低剂

16、量低剂量7天疗程可显著减少重症天疗程可显著减少重症CAP患者患者 机械通气时间机械通气时间 住院时间住院时间 死亡率死亡率Am J Respir Crit Care Med.2005 Feb 1;171(3):242-8.Epub 2004 Nov 19.Hydrocortisone infusion for severe community-acquired pneumonia:a preliminary randomized study.CRP氧合指数氧合指数Am J Respir Crit Care Med.2005 Feb 1;171(3):242-8.Epub 2004 Nov 19

17、.Hydrocortisone infusion for severe community-acquired pneumonia:a preliminary randomized study.激素组激素组安慰剂组安慰剂组重症肺炎时血清和BALF的促炎因子激素疗效不突出的原因（2）关闭编码促炎细胞因子的基因，Serum cytokines and critical illness-related corticosteroid insufficiency9%(36 out of 82 patients)CAP时宿主的炎症 文献（1）Cytokine expression in severe pne

18、umonia:a bronchoalveolar study.在注射促肾上腺皮质激素(ACTH)250 ug后血清考的松增高9ug/mlCrit Care Med 1999;27:17451753.COPD等近期接受GC治疗的患者，存在相对性肾上腺皮质功能全的可能性相应增大激素疗效不突出的原因（1）Effect of corticosteroids on the clinical course of community-acquired pneumonia:a randomized controlled trialCritical Care 2011,15:R9656例，X线进展性或呼吸衰竭。

19、（基础皮质醇正常或基础皮质醇升高但变化降低者）20mg q6h 3d在注射促肾上腺皮质激素(ACTH)250 ug后血清考的松增高9ug/ml疾病严重程度与炎症有关在注射促肾上腺皮质激素(ACTH)250 ug后血清考的松增高9ug/ml2005 Feb 1;171(3):242-8.Am J Respir Crit Care Med.2005 Feb 1;171(3):242-8.Epub 2004 Nov 19.Hydrocortisone infusion for severe community-acquired pneumonia:a preliminary randomized s

20、tudy.Dexamethasone and length of hospital stay in patients with community-acquired pneumonia:a randomised,double-blind,placebo-controlled trialJ.激素疗效不突出的原因（1）Crit Care Med 1999;27:17451753.Hydrocortisone infusion for severe community-acquired pneumonia:a preliminary randomized study.Hydrocortisone i

21、nfusion for severe community-acquired pneumonia:a preliminary randomized study.其中住ICU的肺炎死亡率更高（60%）Crit Care Med 1999;27:17451753.Monton C,et al.Cytokine levels(mean+/-SEM)from patients with and without pneumonia in serum and BAL fluid on day 120mg q6h 3d关闭编码促炎细胞因子的基因，Cytokine expression in severe pn

22、eumonia:a bronchoalveolar study.Cytokine expression in severe pneumonia:a bronchoalveolar study.56例，X线进展性或呼吸衰竭。尽管新的机械通气支持方式、抗生素的出现，死亡率却没有明显降低Cytokine expression in severe pneumonia:a bronchoalveolar study.尽管新的机械通气支持方式、抗生素的出现，死亡率却没有明显降低CIRCI患者细胞因子更高2005 Feb 1;171(3):242-8.20mg q6h 3d 56例，例，X线进展性或呼吸衰竭

23、。线进展性或呼吸衰竭。甲强龙甲强龙 200-mg ivgtt st，继之，继之 20mg q6h 3d 20mg q12h 3d 20mg qd 3dCritical Care 2011,15:R96 Effect of corticosteroids on the clinical course of community-acquired pneumonia:a randomized controlled trial 炎症因子炎症因子Critical Care 2011,15:R96 Effect of corticosteroids on the clinical course of co

24、mmunity-acquired pneumonia:a randomized controlled trial氧合指数氧合指数CRPCritical Care 2011,15:R96 Effect of corticosteroids on the clinical course of community-acquired pneumonia:a randomized controlled trialCritical Care 2011,15:R96 Effect of corticosteroids on the clinical course of community-acquired

25、pneumonia:a randomized controlled trialIntensive Care Medicine November 2010,Volume 36,Issue 11,pp 1845-1851CIRCI患者细胞因子更高下丘脑-垂体-肾上腺（HPA）轴20mg qd 3dHydrocortisone infusion for severe community-acquired pneumonia:a preliminary randomized study.在注射促肾上腺皮质激素(ACTH)250 ug后血清考的松增高9ug/ml下丘脑-垂体-肾上腺（HPA）轴关闭编码促

26、炎细胞因子的基因，Dexamethasone and length of hospital stay in patients with community-acquired pneumonia:a randomised,double-blind,placebo-controlled trialJ.Crit Care Med 1999;27:17451753.激素疗效不突出的原因（2）Cytokine levels(mean+/-SEM)from patients with and without pneumonia in serum and BAL fluid on day 120mg q6h

27、 3dCritical Care 2011,15:R96Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumonia尽管新的机械通气支持方式、抗生素的出现，死亡率却没有明显降低Serum cytokines and critical illness-related corticosteroid insufficiencyCytokine expression in severe pneumonia:a bronchoalveolar study.20m

28、g qd 3d进入胞质内与糖皮质激素受体-热休克蛋白（GR-Hsp）结合并与Hsp分离，304例CAP Dexamethasone5 mg for 4 daysLancet,2011,377(9782):2023-2030.Meijvis S C,et al.Dexamethasone and length of hospital stay in patients with community-acquired pneumonia:a randomised,double-blind,placebo-controlled trialJ.C-reactive protein interleukin

29、-6Lancet,2011,377(9782):2023-2030.Meijvis S C,et al.Dexamethasone and length of hospital stay in patients with community-acquired pneumonia:a randomised,double-blind,placebo-controlled trialJ.样本量小样本量小 病例选择病例选择 激素量较小激素量较小危重疾病相关性肾上腺皮质功危重疾病相关性肾上腺皮质功能不全能不全(CIRCI)患者患者COPD等近期接受等近期接受GC治疗的患者，存在治疗的患者，存在相对性肾上

30、腺皮质功能全的可能性相应相对性肾上腺皮质功能全的可能性相应增大增大机械通气患者有机械通气患者有70存在相对性肾上腺存在相对性肾上腺皮质功能不全皮质功能不全不良反应不良反应理论上理论上 消化道出血消化道出血 肌无力肌无力 代谢紊乱代谢紊乱 医院感染医院感染 诱发病毒感染诱发病毒感染 实际上实际上 高血糖高血糖 高钠血症高钠血症 CAP患病率、死亡率高患病率、死亡率高 疾病严重程度与炎症有关疾病严重程度与炎症有关 CIRCI患者细胞因子更高患者细胞因子更高 激素治疗激素治疗CAP的疗效的疗效 降低血清细胞因子降低血清细胞因子 机械通气时间机械通气时间 住院时间住院时间 死亡率死亡率 对于感染的过度

31、免疫炎症反应对于感染的过度免疫炎症反应 脓毒症休克脓毒症休克 急性呼吸窘迫综合征急性呼吸窘迫综合征 多器官衰竭多器官衰竭 机体反应性低下机体反应性低下 老年老年 酗酒酗酒 糖尿病糖尿病 心力衰竭心力衰竭 肝硬化肝硬化Hydrocortisone infusion for severe community-acquired pneumonia:a preliminary randomized study.Cytokine expression in severe pneumonia:a bronchoalveolar study.2005 Feb 1;171(3):242-8.56例，X线进展性

32、或呼吸衰竭。Crit Care Med 1999;27:17451753.重症肺炎时血清和BALF的促炎因子20mg q6h 3d约20%的CAP患者须住院甲强龙 200-mg ivgtt st，继之尽管新的机械通气支持方式、抗生素的出现，死亡率却没有明显降低Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumonia危重疾病相关性肾上腺皮质功能不全(CIRCI)CIRCI患者细胞因子更高20mg q6h 3dCytokine expression i

33、n severe pneumonia:a bronchoalveolar study.在注射促肾上腺皮质激素(ACTH)250 ug后血清考的松增高9ug/ml9%(36 out of 82 patients)激素疗效不突出的原因（1）Dexamethasone5 mg for 4 days56例，X线进展性或呼吸衰竭。选择恰当的抗菌素选择恰当的抗菌素 尽管新的机械通气支持方式、抗生素的出现，尽管新的机械通气支持方式、抗生素的出现，死亡率却没有明显降低死亡率却没有明显降低 适当的免疫治疗适当的免疫治疗 增强免疫增强免疫-胸腺肽、免疫球蛋白等胸腺肽、免疫球蛋白等 抑制炎症抑制炎症Crit Car

34、e Med 1999;27:17451753.Monton C,et al.Cytokine expression in severe pneumonia:a bronchoalveolar study.Crit Care Med 1999;27:17451753.Monton C,et al.Cytokine expression in severe pneumonia:a bronchoalveolar study.Clin Diagn Lab Immunol 2003;10:813820.Fernandez-Serrano S,et al.Molecular inflammatory r

35、esponses measured in blood of patients with severe communityacquired pneumoniaCrit Care Med 1999;27:17451753.CAP时宿主的炎症 文献（1）Hydrocortisone infusion for severe community-acquired pneumonia:a preliminary randomized study.2005 Feb 1;171(3):242-8.Cytokine expression in severe pneumonia:a bronchoalveolar

36、 study.下丘脑-垂体-肾上腺（HPA）轴在注射促肾上腺皮质激素(ACTH)250 ug后血清考的松增高9ug/mlCytokine expression in severe pneumonia:a bronchoalveolar study.增强免疫-胸腺肽、免疫球蛋白等20mg q6h 3d约20%的CAP患者须住院Cytokine expression in severe pneumonia:a bronchoalveolar study.Clin Diagn Lab Immunol 2003;10:813820.Cytokine expression in severe pneum

37、onia:a bronchoalveolar study.机械通气患者有70存在相对性肾上腺皮质功能不全关闭编码促炎细胞因子的基因，Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumonia20mg q12h 3d关闭编码促炎细胞因子的基因，Intensive Care Medicine November 2010,Volume 36,Issue 11,pp 1845-185120mg q6h 3dMonton C,et al.Effect of c

38、orticosteroids on the clinical course of community-acquired pneumonia:a randomized controlled trialCytokine expression in severe pneumonia:a bronchoalveolar study.Serum cytokines and critical illness-related corticosteroid insufficiencyMolecular inflammatory responses measured in blood of patients w

39、ith severe communityacquired pneumonia56例，X线进展性或呼吸衰竭。激素疗效不突出的原因（1）Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumoniaClin Diagn Lab Immunol 2003;10:813820.激素与其受体的复合物进入细胞核产生抗炎作用COPD等近期接受GC治疗的患者，存在相对性肾上腺皮质功能全的可能性相应增大Clin Diagn Lab Immunol 2003;10:8138

40、20.关闭编码促炎细胞因子的基因，Molecular inflammatory responses measured in blood of patients with severe communityacquired pneumonia尽管新的机械通气支持方式、抗生素的出现，死亡率却没有明显降低下丘脑-垂体-肾上腺（HPA）轴Crit Care Med 1999;27:17451753.20mg q12h 3d 56例，例，X线进展性或呼吸衰竭。线进展性或呼吸衰竭。甲强龙甲强龙 200-mg ivgtt st，继之，继之 20mg q6h 3d 20mg q12h 3d 20mg qd 3dCritical Care 2011,15:R96 Effect of corticosteroids on the clinical course of community-acquired pneumonia:a randomized controlled trial