感染性休克血管活性药物.ppt

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,血管活性药物的应用指征,积极充分的液体复苏,PAWP I5,18mmHg,MAP20ug/kg.min,，,应更换,SVRI,显著降低：,NE,SVRI,增高：,Epi,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：,2,10,ug,/kg.min,应用指征：,常规剂量,dopa,和,NE,引起心律失常,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：,220,ug,/min(up to 200),应用指征：,SVRI,明显降低的感染性休克,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：,0.052,ug,/kg.min,应用指征,NE,无效,低,CO,低,SVRI,dobu,(110)+,dopa,/NE,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：,220,ug,/kg.min,应用指征：感染性休克伴低心排,血管活性药物的进展,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,一、血管活性药物与肾功能,传统观念,Dopa,30ml/min,UO0.5m1/kg.h,分组：,5,h,更换,Dopa,200ug/min,Dobu,175ug/min,Placebo 5,GS,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,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,Effect of,vaso,on MAP,Effect of,Epi,and,Epi,+,Dopa,on,Ccr,Epi,40,ug,/min,Epi,40ug/min+,Dopa,2ug/kg.min,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,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,预定的治疗目标,MAP80mmHg,CI4 L/min.m2,尿量明显增加,持续,6,h,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,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,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,Unaex,28.5 15.2,*,32.4,(,mmol,/2h),FEna,(%)5.23.8,*,3.9,Ccr,(ml/min)42.239.456,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,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,Effect of NE and NE+,Dopa,on SBP,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,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,-,-,感染性休克的肾脏保护性药物,去甲肾上腺素,多巴酚丁胺,Notice(1),Renal dose dopamine,Protective effect on kidney,By reducing oxygen demand,By maintaining tubular flow,Notice(2),21,century strategies of ARF by NIH,Renal dose dopamine is not recommended,二、,血管活性药物与肠系膜血流供应,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,Effect of NE,vs Dopa,on MAP,NE,Dopa,Baseline 3hBaseline 3h,MAP 5587*6387*,CI4.24.74.2,5.3,*,PAWP15161516,SVRI1110,1405,*10351221,Effect of NE,vs Dopa,on DO,2,and VO,2,Effect of NE,vs Dopa,on,pHi,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,Effect of,dopa vs,NE on DO,2,of gut,Critical Care Med,1993,21:1296,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,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,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,Effect of,Epi vs,NE on CI and DO,2,NE,Epi,MAP7474,PAWP1514,CI4.45.2*,DO,2,563671*,VO,2,150158,O,2,ext0.280.24,Effect of,Epi vs,NE on,pHi,and GMP,NE,Epi,pHi,7.247.25,deltaPCO,2,1313,GMP256350*,GMP/DO,2,0.520.46,Comment,Gastric,mucosal,perfusion:,Epi,NE,Gut,ischemia,:improved by,Epi,?,Epi,与,NE,比较,(2),Porcine,endotoxin,shock,Epi,Aim:MAP 70mmHg,NE,Dopex,From Annals of Surgery,1998,228:239,Effect of NE and,Epi,on,mucosa,Comment,Epinephrine induce gut damage,In animal,expriment,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,Effect of,Epi vs,NE+,Dobu,Effect of,Epi vs,NE+,Dobu,Effect of,Epi vs,NE+,Dobu,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,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,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,Epi vs,NE on,GMP,NE NE+,Dobu Epi,GMP256419*350*,GMP/DO,2,0.520.61*0.46,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,？,3.,NE+,Dobu,on Gut(2),21,patients with septic syndrome,Dobutamine:0,5,10,ug,/kg.min,From,Crit,Care Med,1994,150324,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,Effect of,Epi vs,NE+,Dobu,Effect of,Epi vs,NE+,Dobu,Comment-NE+,Dobu,Increase CI,DO,2,VO,2,Increase DO,2,of gut (GMP),Decrease lactate,Increase,pHi,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,Comment-NE+,Dopa,Increase CI,DO,2,VO,2,Increase DO,2,of gut,?,(Only sp30%),不能改善肠道缺氧,5.Comment-,Norepinephrine,Increase CI,DO,2,VO,2,Increase DO,2,of gut,Increase gut,pHi,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,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,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,Comment-,Dopexamine,Increase CI,DO,2,VO,2,Decrease SVRI,Increase VO,2,of heart,Increase,pHi,and,mucosal,PtissO,2,Prevent liver injury,Target Is right?,