感染性休克血管活性药物.ppt

感染性休克血管活性药物进展,邱海波ICU,血管活性药物的应用指征,积极充分的液体复苏PAWPI518mmHgMAP20ug/kg.min，应更换SVRI显著降低：NESVRI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：210ug/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：220ug/min(upto200)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：0.052ug/kg.min应用指征NE无效低CO低SVRIdobu(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：220ug/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Dopa30ml/min,UO0.5m1/kg.h分组：5h更换Dopa200ug/minDobu175ug/minPlacebo5GS,Dobu不增加尿量，但明显增加CcrDopa增加尿量，并不增加CcrConclusion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：Dopa2ug/kg/minEpi40ug/minDopa+Epi/4h,FromBerstenAD，etal，CritCareMed,1995,23,537,EffectofvasoonMAP,EffectofEpiandEpi+DopaonCcr,Epi40ug/min,Epi40ug/min+Dopa2ug/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：Dopa2.525ug/kg.minNE0.55ug/kg.min,FromChest，1993，103：1826,预定的治疗目标MAP80mmHg,CI4L/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,4.NEvsNE+Dopa,PatientswithsepticshockVasoNE:0.18ug/kg.minDopa:2.5ug/kg.minGroupNE+DopaNEalone,FromIntensiveCareMed,1998,24:564,NEvsNE+Dopainsepticpts,NE+DopaNEaloneNE+DopaMAP89.581.293CI4.73.9*4.8PAWP12.813.213.7Uvol(ml/2h)391234*380Unaex28.515.2*32.4(mmol/2h)FEna(%)5.23.8*3.9Ccr(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,NEvsNE+Dopainvolunters,FromCriticalCareMed,1998,26:260,NormotensivehealthyvolunteersVasoNE:40,80,150ug/minDopa:4ug/kg.minGroupNE+DopaNEaloneBaseline,EffectofNEandNE+DopaonSBP,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,DopaDobuEpiNENE+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),RenaldosedopamineProtectiveeffectonkidneyByreducingoxygendemandBymaintainingtubularflow,Notice(2),21centurystrategiesofARFbyNIHRenaldosedopamineisnotrecommended,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、MAP75mmHgDopaNE,From：JAMA,1994,272:1354,EffectofNEvsDopaonMAP,NEDopaBaseline3hBaseline3hMAP5587*6387*CI5.3*PAWP15161516SVRI11101405*10351221,EffectofNEvsDopaonDO2andVO2,EffectofNEvsDopaonpHi,Comment,1.NE:DO2、VO2、pHi均增加2.DopaDO2增加,但pHi降低肠道氧债增加,EffectofdopavsNEonDO2ofgut,CriticalCareMed,1993,21:1296,Dopainanimalexp.NetincreasedgutbloodflowButredistributionawayfromgutmucosaDopainhemorrhagicshockdogDopadecreasedtheabilityofguttoextractoxygen,EffectofdopavsNEongut,Comment-Dopamine,IncreaseCI,DO2,VO2IncreaseDO2ofgutIncreasegutmucosaloxygenneed?RedistributionbloodawayfromgutmocosalVO2ofgutdecreasedSplanchnicoxygendebt,2.Epi与NE比较(1),Prospective,controlled,randomizedcrossoverstudy12patientswithsepticshockPatientgroupsEpiAim:MAP7080mmHgNEFromCritCareMed,1999,27:893,EffectofEpivsNEonCIandDO2,NEEpiMAP7474PAWP1514CI4.45.2*DO2563671*VO2150158O2ext0.280.24,EffectofEpivsNEonpHiandGMP,NEEpipHi7.247.25deltaPCO21313GMP256350*GMP/DO20.520.46,Comment,Gastricmucosalperfusion:EpiNEGutischemia:improvedbyEpi?,Epi与NE比较(2),PorcineendotoxinshockEpiAim:MAP70mmHgNEDopexFromAnnalsofSurgery,1998,228:239,EffectofNEandEpionmucosa,Comment,EpinephrineinducegutdamageInanimalexpriment,Epi与NE比较(3),Clinialtrial30patientswithsepticshockPatientgroupsEpiAim:MAP80mmHgNE+DobuFromIntensiveCareMed,1997,23:282,EffectofEpivsNE+Dobu,EffectofEpivsNE+Dobu,EffectofEpivsNE+Dobu,Comment-Epinephrine,IncreaseCI,DO2,VO2IncreaseDO2ofgut(GMP)IncreasegutmucosalandwholebodyoxygenneedIncreaselactateDecreasepHi&inducegutdamage,3.NE+DobuonGut(1),Prospective,controlled,randomizedcrossoverstudy12patientswithsepticshockPatientgroupsEpiAim:MAP7080mmHgNENE+Dobu5ug/kg.minFromCritCareMed,1999,27:893,EffectofNE+DobuvsNE,NENE+DobuEpiMAP747474PAWP151414CI*DO2563621671*VO2150152158O2ext0.280.250.24,EffectofEpivsNEonGMP,NENE+DobuEpiGMP256419*350*GMP/DO20.520.61*0.46,Comment,NE+Dobu1.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+DobuonGut(2),21patientswithsepticsyndromeDobutamine:0,5,10ug/kg.minFromCritCareMed,1994,150:324,Comment,Dobu1.改善肠道缺血2.剂量依赖关系机制增加DO2，同比例增加肠道DO2gut血流重分布:血流从肠壁向粘膜分布,EffectofEpivsNE+Dobu,EffectofEpivsNE+Dobu,Comment-NE+Dobu,IncreaseCI,DO2,VO2IncreaseDO2ofgut(GMP)DecreaselactateIncreasepHi,4.NE+Dopa,11patswithsepticshockNE+Dopa3ug/kg.minEffectofDopaongut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FromIntensiveCareMed,1997,23:31,Comment-NE+Dopa,IncreaseCI,DO2,VO2IncreaseDO2ofgut?(Onlysp30%)不能改善肠道缺氧,5.Comment-Norepinephrine,IncreaseCI,DO2,VO2IncreaseDO2ofgutIncreasegutpHi,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,DopaEpiNENE+DobuNE+DopaMAPCISVRI-DO2VO2Lactate