感染性休克血管活性藥物進(jìn)展.ppt

感染性休克血管活性藥物進(jìn)展,邱海波ICU,血管活性藥物的應(yīng)用指征,積極充分的液體復(fù)蘇PAWPI518mmHgMAP20ug/kg.min，應(yīng)更換SVRI顯著降低：NESVRI增高：Epi,苯腎上腺素新福林,藥理作用：強(qiáng)烈的受體激動(dòng)劑，受體無(wú)興奮作用表現(xiàn)：強(qiáng)大縮血管作用，無(wú)正性肌力和擴(kuò)血管作用常規(guī)劑量：210ug/kg.min應(yīng)用指征：常規(guī)劑量dopa和NE引起心律失常,去甲腎上腺素(NE),藥理作用:強(qiáng)興奮受體，弱興奮受體臨床效應(yīng)：強(qiáng)烈的縮血管和正性肌力常規(guī)劑量：220ug/min(upto200)應(yīng)用指征：SVRI明顯降低的感染性休克,腎上腺素(Epi),藥理作用:強(qiáng)烈興奮受體和受體臨床效應(yīng)：正性肌力和縮血管常規(guī)劑量：0.052ug/kg.min應(yīng)用指征NE無(wú)效低CO低SVRIdobu(110)+dopa/NE,多巴酚丁胺(Dobu),藥理作用：受體強(qiáng)烈激動(dòng)劑，對(duì)受體無(wú)興奮作用臨床效應(yīng)：正性肌力作用常規(guī)劑量：220ug/kg.min應(yīng)用指征：感染性休克伴低心排,血管活性藥物的進(jìn)展,理想的血管活性藥物,(1)迅速提高血壓，改善心臟和腦灌注(2)改善腎臟和腸道血流灌注糾正組織缺氧防止內(nèi)臟器官衰竭,一、血管活性藥物與腎功能,傳統(tǒng)觀念Dopa30ml/min,UO0.5m1/kg.h分組：5h更換Dopa200ug/minDobu175ug/minPlacebo5GS,Dobu不增加尿量，但明顯增加CcrDopa增加尿量，并不增加CcrConclusion多巴酚丁胺能夠改善腎臟灌注多巴胺僅具有利尿作用,2.Dopa與Epi的比較,實(shí)驗(yàn)對(duì)象：腹腔感染的綿羊分組：Dopa2ug/kg/minEpi40ug/minDopa+Epi/4h,FromBerstenAD，etal，CritCareMed,1995,23,537,EffectofvasoonMAP,EffectofEpiandEpi+DopaonCcr,Epi40ug/min,Epi40ug/min+Dopa2ug/kg.min,Comment,腎上腺素組:腎血流明顯增加Ccr先降低，之后增加多巴胺組多巴胺腎上腺素組：腎血流和Ccr無(wú)明顯增加,3.Dopa與NE比較,試驗(yàn)設(shè)計(jì)：前瞻隨機(jī)雙盲對(duì)照試驗(yàn)病例選擇：低SVRI、高CI的感染性休克患者分組：Dopa2.525ug/kg.minNE0.55ug/kg.min,FromChest，1993，103：1826,預(yù)定的治療目標(biāo)MAP80mmHg,CI4L/min.m2,尿量明顯增加,持續(xù)6h結(jié)果Dopa組31,而NE組93達(dá)到治療目標(biāo)NE能更快、更強(qiáng)的恢復(fù)血流動(dòng)力學(xué),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+小劑量Dopa動(dòng)脈壓、心輸出量明顯增加尿量,尿鈉排泄明顯增加肌酐清除率無(wú)明顯影響,NEvsNE+Dopainvolunters,FromCriticalCareMed,1998,26:260,NormotensivehealthyvolunteersVasoNE:40,80,150ug/minDopa:4ug/kg.minGroupNE+DopaNEaloneBaseline,EffectofNEandNE+DopaonSBP,Conclusion,NE:明顯降低腎臟血漿流量不降低腎小球?yàn)V過(guò)率加小劑量Dopa(4ug/kg.min):腎血漿流量腎排泄分?jǐn)?shù)均明顯增加腎小球?yàn)V過(guò)率無(wú)明顯增加,血管活性藥物對(duì)腎臟功能的影響,DopaDobuEpiNENE+Dopa腎血流量-尿量-Unaex-FEna-Ccr-,感染性休克的腎臟保護(hù)性藥物,去甲腎上腺素多巴酚丁胺,Notice(1),RenaldosedopamineProtectiveeffectonkidneyByreducingoxygendemandBymaintainingtubularflow,Notice(2),21centurystrategiesofARFbyNIHRenaldosedopamineisnotrecommended,二、血管活性藥物與腸系膜血流供應(yīng),1.Dopa與NE比較,試驗(yàn)設(shè)計(jì)：隨機(jī)對(duì)照試驗(yàn)病例選擇：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降低腸道氧債增加,EffectofdopavsNEonDO2ofgut,CriticalCareMed,1993,21:1296,Dopainanimalexp.NetincreasedgutbloodflowButredistributionawayfromgutmucosaDopainhemorrhagicshockdogDopadecreasedtheabilityofguttoextractoxygen,EffectofdopavsNEongut,Comment-Dopamine,IncreaseCI,DO2,VO2IncreaseDO2ofgutIncreasegutmucosaloxygenneed?RedistributionbloodawayfromgutmocosalVO2ofgutdecreasedSplanchnicoxygendebt,2.Epi與NE比較(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與NE比較(2),PorcineendotoxinshockEpiAim:MAP70mmHgNEDopexFromAnnalsofSurgery,1998,228:239,EffectofNEandEpionmucosa,Comment,EpinephrineinducegutdamageInanimalexpriment,Epi與NE比較(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.明顯提高腸系膜血流量腸系膜血流量/心輸出量的比值2.改善腸道缺血？,3.NE+DobuonGut(2),21patientswithsepticsyndromeDobutamine:0,5,10ug/kg.minFromCritCareMed,1994,150:324,Comment,Dobu1.改善腸道缺血2.劑量依賴(lài)關(guān)系機(jī)制增加DO2，同比例增加腸道DO2gut血流重分布:血流從腸壁向粘膜分布,EffectofEpivsNE+Dobu,EffectofEpivsNE+Dobu,Comment-NE+Dobu,IncreaseCI,DO2,VO2IncreaseDO2ofgut(GMP)DecreaselactateIncreasepHi,4.NE+Dopa,11patswithsepticshockNE+Dopa3ug/kg.minEffectofDopaongut腸系膜血流占CO30%:無(wú)明顯影響30%:增加胃腸道血流灌注pHi均無(wú)明顯改善FromIntensiveCareMed,1997,23:31,Comment-NE+Dopa,IncreaseCI,DO2,VO2IncreaseDO2ofgut?(Onlysp30%)不能改善腸道缺氧,5.Comment-Norepinephrine,IncreaseCI,DO2,VO2IncreaseDO2ofgutIncreasegutpHi,去甲腎上腺素對(duì)感染性休克的治療,改善異常的血管擴(kuò)張改善心肌抑制增加或不影響心輸出量增加冠脈血流提高腎臟灌注壓，改善腎臟灌注改善腸系膜血管低灌注狀態(tài),感染性休克的腸道保護(hù)性藥物,DopaEpiNENE+DobuNE+DopaMAPCISVRI-DO2VO2Lactate