感染性休克血管活性药物进展课件

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,感染性休克血管活性药物进展,邱海波,东南大学医学院附属中大医院ICU,东南大学急诊与危重病医学研究所,感染性休克血管活性药物进展邱海波,1,血管活性药物的应用指征,积极充分的液体复苏,PAWP I518mmHg,MAP20ug/kg.min，应更换,SVRI显著降低：NE,SVRI增高：Epi,多巴胺（Dopa）1. 常规剂量：220ug/kg.min,5,苯肾上腺素新福林,药理作用：,强烈的,受体激动剂，,受体无兴奋作用,表现：,强大缩血管作用，无正性肌力和,扩血管作用,常规剂量：210 ug/kg.min,应用指征：,常规剂量dopa和NE引起心律失常,苯肾上腺素新福林药理作用：,6,去甲肾上腺素(NE),药理作用: 强兴奋,受体，弱兴奋,受体,临床效应：强烈的缩血管和正性肌力,常规剂量：220ug/min (up to 200),应用指征：SVRI明显降低的感染性休克,去甲肾上腺素(NE)药理作用: 强兴奋受体，弱兴奋受体,7,肾上腺素(Epi),药理作用: 强烈兴奋,受体和,受体,临床效应：正性肌力和缩血管,常规剂量：0.052ug/kg.min,应用指征,NE无效,低CO低SVRI,dobu (110)+dopa/NE,肾上腺素(Epi)药理作用: 强烈兴奋受体和受体,8,多巴酚丁胺(Dobu,),药理作用：,受体强烈激动剂，对,受体无兴奋作用,临床效应：正性肌力作用,常规剂量：220ug/kg.min,应用指征：感染性休克伴低心排,多巴酚丁胺(Dobu)药理作用：受体强烈激动剂，对受体无,9,血管活性药物的进展,血管活性药物的进展,10,理想的血管活性药物,(1)迅速提高血压，改善心脏和脑灌注,(2)改善肾脏和肠道血流灌注,纠正组织缺氧,防止内脏器官衰竭,理想的血管活性药物(1)迅速提高血压，改善心脏和脑灌注,11,一、血管活性药物与肾功能,传统观念,Dopa30ml/min, UO0.5m1/kg.h,分组： 5h更换,Dopa 200ug/min,Dobu 175ug/min,Placebo 5GS,1. Dopa与Dobu的比较,13,感染性休克血管活性药物进展课件,14,感染性休克血管活性药物进展课件,15,Dobu不增加尿量，但明显增加Ccr,Dopa增加尿量，并不增加Ccr,Conclusion,多巴酚丁胺能够改善肾脏灌注,多巴胺仅具有利尿作用,Dobu不增加尿量，但明显增加Ccr,16,2. Dopa与Epi的比较,实验对象：腹腔感染的绵羊,分组：,Dopa 2 ug/kg/min,Epi 40ug/min,Dopa + Epi / 4h,From Bersten AD，et al，Crit Care Med, 1995, 23,537,2. Dopa与Epi的比较实验对象：腹腔感染的绵羊From,17,Effect of vaso on MAP,Effect of vaso on MAP,18,感染性休克血管活性药物进展课件,19,感染性休克血管活性药物进展课件,20,Effect of Epi and Epi +Dopa on Ccr,Epi 40 ug/min,Epi 40ug/min +,Dopa 2ug/kg.min,Effect of Epi and Epi +Dopa on,21,Comment,肾上腺素组:,肾血流明显增加,Ccr先降低，之后增加,多巴胺组,多巴胺肾上腺素组：,肾血流和Ccr无明显增加,Comment肾上腺素组:,22,3. Dopa与NE比较,试验设计：前瞻随机双盲对照试验,病例选择：低SVRI、高CI的感,染性休克患者,分组：,Dopa 2.525ug/kg.min,NE 0.55ug/kg.min,From Chest，1993，103：1826,3. Dopa与NE比较试验设计：前瞻随机双盲对照试验F,23,预定的治疗目标,MAP80mmHg, CI4 L/min.m2,尿量明显增加, 持续6h,结果,Dopa组31, 而NE组93达到治疗目标,NE能更快、更强的恢复血流动力学,预定的治疗目标,24,4.,NE vs NE+Dopa,Patients with septic shock,Vaso,NE: 0.18 ug/kg.min,Dopa: 2.5 ug/kg.min,Group,NE+Dopa,NE alone,From Intensive Care Med, 1998, 24:564,4. NE vs NE+DopaPatients with,25,NE vs NE+Dopa in septic pts,NE+Dopa NE alone NE+Dopa,MAP89.581.293,CI4.73.9*4.8,PAWP12.813.213.7,Uvol(ml/2h)391234,*,380,Unaex28.5 15.2,*,32.4,(mmol/2h),FEna (%)5.23.8,*,3.9,Ccr (ml/min)42.239.456,NE vs NE+Dopa in septic pts,26,Comment,NE + 小剂量Dopa,动脉压、心输出量明显增加,尿量, 尿钠排泄明显增加,肌酐清除率无明显影响,CommentNE + 小剂量Dopa,27,NE vs NE+Dopa in volunters,From Critical Care Med, 1998,26:260,Normotensive healthy volunteers,Vaso,NE: 40, 80, 150 ug/min,Dopa: 4 ug/kg.min,Group,NE+Dopa,NE alone,Baseline,NE vs NE+Dopa in volunters Fro,28,Effect of NE and NE + Dopa on SBP,Effect of NE and NE + Dopa on,29,Conclusion,NE: 明显降低肾脏血浆流量,不降低肾小球滤过率,加小剂量Dopa(4ug/kg.min):肾血浆流量,肾排泄分数均明显增加,肾小球滤过率无明显增加,ConclusionNE: 明显降低肾脏血浆流量,30,血管活性药物对肾脏功能的影响,Dopa Dobu Epi NE NE+Dopa,肾血流量-, -,尿量,- ,Unaex,-,FEna,-,Ccr,-,-,血管活性药物对肾脏功能的影响 Dopa Dobu,31,感染性休克的肾脏保护性药物,去甲肾上腺素,多巴酚丁胺,感染性休克的肾脏保护性药物去甲肾上腺素,32,Notice (1),Renal dose dopamine,Protective effect on kidney,By reducing oxygen demand,By maintaining tubular flow,Notice (1)Renal dose dopamine,33,Notice (2),21 century strategies of ARF by NIH,Renal dose dopamine is not recommended,Notice (2)21 century strategie,34,二、,血管活性药物与肠系膜血流供应,二、血管活性药物与肠系膜血流供应,35,1. Dopa与NE比较,试验设计：随机对照试验,病例选择：感染性休克20例,高CI低SVRI、MAP75mmHg,Dopa,NE,From：JAMA,1994,272:1354,1. Dopa与NE比较试验设计：随机对照试验From：JA,36,Effect of NE vs Dopa on MAP,NEDopa,Baseline 3hBaseline 3h,MAP 5587*6387*,CI4.24.74.2,5.3,*,PAWP15161516,SVRI1110,1405,*10351221,Effect of NE vs Dopa on MAP,37,Effect of NE vs Dopa on DO,2,and VO,2,Effect of NE vs Dopa on DO2 an,38,Effect of NE vs Dopa on pHi,Effect of NE vs Dopa on pHi,39,Comment,1. NE:,DO,2,、VO,2,、pHi均增加,2. Dopa,DO,2,增加, 但pHi降低,肠道氧债增加,Comment1. NE:,40,Effect of dopa vs NE on DO,2,of gut,Critical Care Med, 1993, 21: 1296,Effect of dopa vs NE on DO2 of,41,Dopa in animal exp.,Net increased gut blood flow,But redistribution away from gut mucosa,Dopa in hemorrhagic shock dog,Dopa decreased the ability of gut to extract oxygen,Effect of dopa vs NE on gut,Dopa in animal exp. Effect of,42,Comment -Dopamine,Increase CI, DO,2, VO,2,Increase DO,2,of gut,Increase gut mucosal oxygen need?,Redistribution blood away from gut mocosal,VO,2,of gut decreased,Splanchnic oxygen debt,Comment -DopamineIncrease C,43,2.,Epi与NE 比较,(1),Prospective, controlled, randomized crossover study,12 patients with septic shock,Patient groups,Epi Aim: MAP 7080mmHg,NE,From Crit Care Med, 1999,27:893,2. Epi与NE 比较 (1)Prospective, c,44,Effect of Epi vs NE on CI and DO,2,NEEpi,MAP7474,PAWP1514,CI4.45.2*,DO,2,563671*,VO,2,150158,O,2,ext0.280.24,Effect of Epi vs NE on CI an,45,Effect of Epi vs NE on pHi and GMP,NEEpi,pHi7.247.25,deltaPCO,2,1313,GMP256350*,GMP/DO,2,0.520.46,Effect of Epi vs NE on pHi a,46,Comment,Gastric mucosal perfusion: Epi NE,Gut ischemia: improved by,Epi,?,CommentGastric mucosal perfusi,47,Epi与NE 比较,(2),Porcine endotoxin shock,Epi Aim: MAP 70mmHg,NE,Dopex,From Annals of Surgery, 1998,228:239,Epi与NE 比较(2)Porcine endotoxin,48,Effect of NE and Epi on mucosa,Effect of NE and Epi on mucosa,49,Comment,Epinephrine induce gut damage,In animal expriment,CommentEpinephrine induce gut,50,Epi与NE 比较,(3),Clinial trial,30 patients with septic shock,Patient groups,Epi Aim: MAP 80mmHg,NE + Dobu,From Intensive Care Med, 1997,23:282,Epi与NE 比较(3)Clinial trial,51,Effect of Epi vs NE +Dobu,Effect of Epi vs NE +Dobu,52,Effect of Epi vs NE +Dobu,Effect of Epi vs NE +Dobu,53,Effect of Epi vs NE +Dobu,Effect of Epi vs NE +Dobu,54,Comment -Epinephrine,Increase CI, DO,2, VO,2,Increase DO,2,of gut (GMP),Increase gut mucosal and whole body oxygen need,Increase lactate,Decrease pHi & induce gut damage,Comment -EpinephrineIncreas,55,3. NE + Dobu on Gut (1),Prospective, controlled, randomized crossover study,12 patients with septic shock,Patient groups,Epi,Aim: MAP 7080mmHg,NE,NE+Dobu 5 ug/kg.min,From Crit Care Med, 1999,27:893,3. NE + Dobu on Gut (1)Prospe,56,Effect of NE+Dobu vs NE,NENE+Dobu Epi,MAP747474,PAWP151414,CI4.44.75.2*,DO,2,563621671*,VO,2,150152158,O,2,ext0.280.250.24,Effect of NE+Dobu vs NENE,57,Effect of Epi vs NE on GMP,NE NE+Dobu Epi,GMP256419*350*,GMP/DO,2,0.520.61*0.46,Effect of Epi vs NE on GMP,58,Comment,NE+Dobu,1.明显提高肠系膜血流量,肠系膜血流量/心输出量的比值,2. 改善肠道缺血,？,CommentNE+Dobu,59,3. NE + Dobu on Gut (2),21 patients with septic syndrome,Dobutamine: 0, 5,10 ug/kg.min,From Crit Care Med, 1994, 150:324,3. NE + Dobu on Gut (2)21 pat,60,感染性休克血管活性药物进展课件,61,Comment,Dobu,1. 改善肠道缺血,2. 剂量依赖关系,机制,增加DO,2,，同比例增加肠道DO,2,gut,血流重分布:血流从肠壁向粘膜分布,CommentDobu,62,Effect of Epi vs NE +Dobu,Effect of Epi vs NE +Dobu,63,Effect of Epi vs NE +Dobu,Effect of Epi vs NE +Dobu,64,Comment - NE + Dobu,Increase CI, DO,2, VO,2,Increase DO,2,of gut (GMP),Decrease lactate,Increase pHi,Comment - NE + DobuIncrease,65,4. NE + Dopa,11 pats with septic shock,NE+ Dopa 3 ug/kg.min,Effect of Dopa on gut,肠系膜血流占CO30%: 无明显影响,30%: 增加胃肠道血流灌注,pHi均无明显改善,From Intensive Care Med, 1997, 23:31,4. NE + Dopa11 pats with septi,66,Comment - NE + Dopa,Increase CI, DO,2, VO,2,Increase DO,2,of gut,?,(Only sp30%),不能改善肠道缺氧,Comment - NE + DopaIncrease,67,5. Comment - Norepinephrine,Increase CI, DO,2, VO,2,Increase DO,2,of gut,Increase gut pHi,5. Comment - Norepinephrine,68,去甲肾上腺素对感染性休克的治疗,改善异常的血管扩张,改善心肌抑制,增加或不影响心输出量,增加冠脉血流,提高肾脏灌注压，改善肾脏灌注,改善肠系膜血管低灌注状态,去甲肾上腺素对感染性休克的治疗改善异常的血管扩张,69,感染性休克的肠道保护性药物,Dopa Epi NE NE+Dobu NE+Dopa,MAP, ,CI, ,SVRI -, ,DO,2, ,VO,2, ,Lactate -, ,Gut血流量, ,DO,2,gut, ,VO,2,gut,-,pHi, ,感染性休克的肠道保护性药物 Dopa,70,新型血管活性药物多培沙明,(Dopexamine, Dopex),药理,2,受体: 强激动剂,DA-1/2受体: 弱激动剂,1受体: 弱激动剂,受体: no effect,强心, 扩血管,舒张内脏血管的作用,新型血管活性药物多培沙明(Dopexamine, Dope,71,Comment-,Dopexamine,Increase CI, DO,2, VO,2,Decrease SVRI,Increase VO,2,of heart,Increase pHi and mucosal PtissO,2,Prevent liver injury,Comment- DopexamineIncrease,72,Target Is right?,Target Is right?,73,