感染性休克患者的血管活性藥物應(yīng)用

感染性休克時(shí)血管活性藥物的應(yīng)用浙江省中醫(yī)院ICU江榮林感染性休克時(shí)血管活性藥物的應(yīng)用循環(huán)功能支持治療—目的維持血壓以保證重要臟器的灌注和功能保證足夠的組織氧合液體復(fù)蘇治療糾正低血容量第一個(gè)24小時(shí)內(nèi)輸注晶體液10–20升或更多液體的選擇等張溶液乳酸林格氏液，生理鹽水膠體液血液 — 血容量喪失超過30%白蛋白 — 治療晚期6小時(shí)液體復(fù)蘇治療晶體液價(jià)格低廉增加血管內(nèi)容量增加血管外間隙〔外周水腫〕膠體液急性復(fù)蘇后增加膠體滲透壓減少血管外間隙6小時(shí)血管活性藥物目的容量復(fù)蘇療效不佳者，以維持或升高血壓適應(yīng)證充分的液體復(fù)蘇PAWP15–18mmHgMAP<65mmHg血管活性藥物爭(zhēng)論1：去甲腎上腺素有益抑或有害？Isnorepinephrinethewrongchoice?血管活性藥物—去甲腎上腺素From：JAMA1994;272:1354血管活性藥物—去甲腎上腺素分組DOPA 263.8g/kg/minNE 0.180.06g/kg/minFrom：JAMA1994;272:1354血管活性藥物—去甲腎上腺素NEDOPAbaseline3hrbaseline3hrMAP55876387CI4.24.74.25.3PAWP15161516SVRI1110140510351221DO2498569573703VO2145162183221pHi7.167.237.247.18From：JAMA1994;272:1354血管活性藥物—去甲腎上腺素MartinC,etal.Norepinephrineordopamineforthetreatmentofhyperdynamicsepticshock.Chest1993;103:1826-31血管活性藥物—去甲腎上腺素分組DOPA (n=16) 2.5–25g/kg/minNE (n=16) 0.5–5.0g/kg/min治療終點(diǎn)恢復(fù)器官灌注持續(xù)6hrMAP>80mmHgCI>4.0L/min/m2UOMartinC,etal.Norepinephrineordopamineforthetreatmentofhyperdynamicsepticshock.Chest1993;103:1826-31血管活性藥物—去甲腎上腺素NEDOPA劑量(g/kg/min)1.51.210–25有效率93%(15/16)?31%(5/16)換用藥物后有效率0%(0/1)91%(10/11)存活率59%17%出院病人數(shù)96MartinC,etal.Norepinephrineordopamineforthetreatmentofhyperdynamicsepticshock.Chest1993;103:1826-31血管活性藥物—去甲腎上腺素結(jié)論與DOPA相比，NE能夠更有效地糾正血流動(dòng)力學(xué)異常對(duì)DOPA反響不佳的感染患者，應(yīng)及時(shí)加用NEMartinC,etal.Norepinephrineordopamineforthetreatmentofhyperdynamicsepticshock.Chest1993;103:1826-31去甲腎上腺素與感染性休克的預(yù)后變量病死率(%)RR(95%CI)P值NE治療Yes620.68(0.54–0.87)<.001No82肺炎引發(fā)休克Yes821.47(1.07–1.77)<.03No61器官衰竭指數(shù)3Yes921.47(1.17–1.82)<.001No60入選時(shí)尿量較少Yes881.44(1.06–1.87)<.01No60入院時(shí)血乳酸水平Y(jié)es911.60(1.27–1.84)<.01No63MartinC,ViviandX,LeoneM,etal.Effectofnorepinephrineontheoutcomeofsepticshock.CritCareMed.2000Aug;28(8):2758-65.輸液治療能否降低NE劑量?輸液前輸液過程中輸液后NE劑量(g/kg/min)0.540.330.21HR(bpm)104139415血容量指數(shù)(ml/m2)26506383655885胸腔內(nèi)血容量指數(shù)(ml/m2)8882041050248心臟指數(shù)(L/min/m2)3.61.04.00.9內(nèi)臟血流絕對(duì)(ml/m2)0.810.98分?jǐn)?shù)(%)22.323.9粘膜內(nèi)PCO2(kPa)7.52.59.02.8PCO2差值(kPa)3.12.54.02.9SakkaSG,Meier-HellmannA,ReinhartK.Dofluidadministrationandreductioninnorepinephrinedoseimproveglobalandsplanchnichaemodynamics?BrJAnaesth2000Jun;84(6):758-62.輸液治療能否降低NE劑量?個(gè)體反響存在顯著差異提示對(duì)于病情穩(wěn)定的感染性休克患者，通過輸液治療降低NE劑量不能增加全身或內(nèi)臟血流SakkaSG,Meier-HellmannA,ReinhartK.Dofluidadministrationandreductioninnorepinephrinedoseimproveglobalandsplanchnichaemodynamics?BrJAnaesth2000Jun;84(6):758-62.血管活性藥物爭(zhēng)論2：如何維持腎臟血流？Isdopaminetherightanswer?血管活性藥物—腎臟保護(hù)血管活性藥物—腎臟保護(hù)血管活性藥物—腎臟保護(hù)血管活性藥物—腎臟保護(hù)血管活性藥物—腎臟保護(hù)血管活性藥物—腎臟保護(hù)血管活性藥物—腎臟保護(hù)時(shí)間血管活性藥物—腎臟保護(hù)健康對(duì)照腹腔感染血管活性藥物—腎臟保護(hù)健康對(duì)照腹腔感染血管活性藥物—腎臟保護(hù)血管活性藥物—腎臟保護(hù)血管活性藥物—腎臟保護(hù)KellumJA,DeckerJM.Useofdopamineinacuterenalfailure:ameta-analysis.CritCareMed2001Aug;29:1526-31？血管活性藥物—腎臟保護(hù)KellumJA,DeckerJM.Useofdopamineinacuterenalfailure:ameta-analysis.CritCareMed2001Aug;29:1526-31血管活性藥物—腎臟保護(hù)主要研究結(jié)果檢索到58項(xiàng)研究24項(xiàng)研究報(bào)告了至少1項(xiàng)主要預(yù)后指標(biāo)分析包含了17項(xiàng)RCTs(854名患者)KellumJA,DeckerJM.Useofdopamineinacuterenalfailure:ameta-analysis.CritCareMed2001Aug;29:1526-31血管活性藥物—腎臟保護(hù)事件的加權(quán)發(fā)生率預(yù)后RCT病例數(shù)多巴胺對(duì)照RRR(95%CI)P值病死率115084.9%5.6%14%(-66to56)0.69ARF發(fā)生率1151117.9%19.5%20%(-14to44)0.50需要透析1061816.2%16.5%10%(-21to34)0.86KellumJA,DeckerJM.Useofdopamineinacuterenalfailure:ameta-analysis.CritCareMed2001Aug;29:1526-31血管活性藥物—腎臟保護(hù)KellumJA,DeckerJM.Useofdopamineinacuterenalfailure:ameta-analysis.CritCareMed2001Aug;29:1526-31血管活性藥物—腎臟保護(hù)BellomoR,ChapmanM,FinferS,etal.Low-dosedopamineinpatientswithearlyrenaldysfunction:aplacebo-controlledrandomisedtrial.AustralianandNewZealandIntensiveCareSociety(ANZICS)ClinicalTrialsGroup.Lancet2000Dec23-30;356(9248):2139-43血管活性藥物—腎臟保護(hù)多巴胺(n=161)安慰劑(n=163)P值Scr峰值245

144249

1470.93Scr差值62

10766

1080.82Scr>300的患者數(shù)56560.92需要RRT的患者數(shù)35400.55ICU住院日13

1414

150.67總住院日29

2733

390.29死亡人數(shù)6966BellomoR,ChapmanM,FinferS,etal.Low-dosedopamineinpatientswithearlyrenaldysfunction:aplacebo-controlledrandomisedtrial.AustralianandNewZealandIntensiveCareSociety(ANZICS)ClinicalTrialsGroup.Lancet2000Dec23-30;356(9248):2139-43血管活性藥物爭(zhēng)論3：如何評(píng)價(jià)對(duì)內(nèi)臟灌注的影響？Systemicversusregionaloxygenation血管活性藥物—內(nèi)臟灌注CriticalCareMed1993;21:1296血管活性藥物—內(nèi)臟灌注血管活性藥物—內(nèi)臟灌注血管活性藥物—內(nèi)臟灌注腎上腺素vs去甲腎上腺素臨床試驗(yàn)30名感染性休克患者分組EpiNE+Dobu治療終點(diǎn)MAP>80mmHgIntensiveCareMed1997;23:282血管活性藥物—內(nèi)臟灌注IntensiveCareMed1997;23:282血管活性藥物—內(nèi)臟灌注IntensiveCareMed1997;23:282血管活性藥物—內(nèi)臟灌注IntensiveCareMed1997;23:282血管活性藥物—內(nèi)臟灌注腎上腺素vs去甲腎上腺素感染性休克動(dòng)物模型〔豬〕分組EpiNE治療終點(diǎn)MAP>70mmHgAnnSurg1998;228:239血管活性藥物—內(nèi)臟灌注AnnSurg1998;228:239血管活性藥物—內(nèi)臟灌注腎上腺素增加CI,DO2,VO2增加腸道DO2(GMP)增加腸道粘膜和全身氧需增加乳酸降低pHi，導(dǎo)致腸道損害血管活性藥物—內(nèi)臟灌注CritCareMed1999;27:893血管活性藥物—內(nèi)臟灌注NENE+DobuEpiMAP747474PAWP151414CI4.44.75.2DO2563621671VO2150152158O2ER0.280.250.24GMP256419350GMP/DO20.520.610.46CritCareMed1999;27:893血管活性藥物—內(nèi)臟灌注血管活性藥物—內(nèi)臟灌注去甲腎上腺素增加CI,DO2,VO2增加腸道DO2增加pHi腹膜炎時(shí)的血管活性藥物SunQ,TuZ,LoboS,etal.

Optimaladrenergicsupportinsepticshockduetoperitonitis.Anesthesiology2003Apr;98(4):888-96.腹膜炎時(shí)的血管活性藥物DB-NE組CO和腸系膜上動(dòng)脈血流顯著增加DO2和VO2明顯增加血乳酸水平和PCO2差值較低累計(jì)尿量顯著增加存活時(shí)間DB-NE(24

4h) 聯(lián)合用藥組DA-NE(24

6h) DB-NE和DA-NE(24

5h)NE(20

1h;P<0.05vs.聯(lián)合用藥組)對(duì)照組(17

2h;P<0.05vs.其他組)SunQ,TuZ,LoboS,etal.

Optimaladrenergicsupportinsepticshockduetoperitonitis.Anesthesiology2003Apr;98(4):888-96.腹膜炎時(shí)的血管活性藥物肺活檢的組織學(xué)檢查與對(duì)照組和NE組相比，DB-NE組病變較輕肺、肝和小腸的解剖學(xué)改變與其他組相比，DB-NE組病變較輕SunQ,TuZ,LoboS,etal.

Optimaladrenergicsupportinsepticshockduetoperitonitis.Anesthesiology2003Apr;98(4):888-96.腹膜炎時(shí)的血管活性藥物結(jié) 論在本研究所采用的長(zhǎng)時(shí)間感染性休克模型中NE與DA或DB聯(lián)合應(yīng)用存活時(shí)間最長(zhǎng)肺部病變最輕DB+NE心臟功能更好DO2和VO2更高血乳酸水平和PCO2差值更低解剖學(xué)病變更輕SunQ,TuZ,LoboS,etal.

Optimaladrenergicsupportinsepticshockduetoperitonitis.Anesthesiology2003Apr;98(4):888-96.JolyLM,MonchiM,CariouA,etal.Effectsofdobutamineongastricmucosalperfusionandhepaticmetabolisminpatientswithsepticshock.AmJRespirCritCareMed.1999Dec;160(6):1983-6多巴酚丁胺前多巴酚丁胺后1hP值CO(L/min)4.0(1.7–7.4)5.0(3.5–8.9)0.004PCO2差值(mmHg)13(5–54)7(5–48)0.005ICG(靛氰綠)清除率:血漿清除率(%)12.2(7.6–16.2)NSDünserMW,MayrAJ,UlmerH,etal.TheEffectsofVasopressinonSystemicHemodynamicsinCatecholamine-ResistantSepticandPostcardiotomyShock:ARetrospectiveAnalysis.血管舒張性休克時(shí)小劑量血管加壓素MalayMB,AshtonRCJr,LandryDW,etal.Low-dosevasopressininthetreatmentofvasodilatorysepticshock.JTrauma1999;47(4):699-703血管舒張性休克時(shí)小劑量血管加壓素?fù)嵛縿┙MSBP無改變SVR無改變用藥24小時(shí)后2名患者因頑固性低血壓死亡MalayMB,AshtonRCJr,LandryDW,etal.Low-dosevasopressininthetreatmentofvasodilatorysepticshock.JTrauma1999;47(4):699-703血管加壓素與胃粘膜微循環(huán)實(shí)驗(yàn)設(shè)計(jì):前瞻性,撫慰劑對(duì)照,隨機(jī),單盲試驗(yàn)實(shí)驗(yàn)對(duì)象:15只雄性Sprague-Dawley大鼠對(duì)照組(n=7):CLP模型+NS試驗(yàn)組(n=8)CLP后24小時(shí)(M1)持續(xù)輸注AVP使MAP升高20mmHg(M2)持續(xù)輸注AVP使MAP升高40mmHg(M3)測(cè)定指標(biāo):在M1對(duì)回腸粘膜的6–10個(gè)絨毛進(jìn)行顯微鏡檢查在M2和M3重復(fù)檢查血漿AVP和IL-6水平WestphalM,FreiseH,KehrelBE,etal.Argininevasopressincompromisesgutmucosalmicrocirculationinsepticrats.

CritCareMed2004Jan;32(1):194-200.血管加壓素與胃粘膜微循環(huán)對(duì)照組(n=7)實(shí)驗(yàn)組(n=8)M2M3粘膜平均血流量下降76%?81%?紅細(xì)胞速度降低45%?47%?絨毛血流中斷時(shí)間(sec/min)8.12.643.85.2?47.06.2?IL-6水平(pg/mL)63855905160??:p<0.05vs.control;?:p<0.001vs.controlWestphalM,FreiseH,KehrelBE,etal.Argininevasopressincompromisesgutmucosalmicrocirculationinsepticrats.

CritCareMed2004Jan;32(1):194-200.血管加壓素與胃粘膜微循環(huán)結(jié) 論感染大鼠輸注AVP胃粘膜血流嚴(yán)重異常感染的炎癥反響增強(qiáng)AVP對(duì)微血管血流的影響AVP對(duì)較大的小動(dòng)脈(>40microm)的活性心輸出量的下降二者兼有WestphalM,FreiseH,KehrelBE,etal.Argininevasopressincompromisesgutmucosalmicrocirculationinsepticrats.

CritCareMed2004Jan;32(1):194-200.感染性休克時(shí)血管加壓素與去甲腎上腺素KlinzingS,SimonM,ReinhartK,etal.High-dosevasopressinisnotsuperiortonorepinephrineinsepticshock.CritCareMed2003Nov;31(11):2646-50.NE血管加壓素劑量(g/kg/minorIU/min)0.56(0.18–1.1)0.47(0.06–1.8)CI(L/min/m2)3.81.33.01.1HR(bpm)96148016?VO2(mL/min)2486721875?內(nèi)臟血流分?jǐn)?shù)(%ofCO)10.87.625.916.6?胃局部PCO2差值(mmHg)17.526.636.526.6??:p<0.01;?:p<0.05vs.NE感染性休克時(shí)血管加壓素與去甲腎上腺素輸注AVP導(dǎo)致左心室每搏功減少12

7%門靜脈血流減少45

5%小腸粘膜血流減少31

13%內(nèi)臟氧輸送(DO2)下降內(nèi)臟和腎臟氧攝取增加GuzmanJA,RosadoAE,KruseJA.Vasopressinvsnorepinephrineinendotoxicshock:systemic,renal,andsplanchnichemodynamicandoxygentransporteffects.JApplPhysiol2003Aug;95(2):803-9.血管加壓素和皮膚缺血性病變發(fā)生率: 19/63(30.2%)肢體遠(yuǎn)端: 13/19(68%)軀干: 2/19(10.5%)肢體遠(yuǎn)端和軀干: 4/19(21%)合并舌頭缺血: 5/19(26%)AVP治療中發(fā)生ISL的獨(dú)立危險(xiǎn)因素既往外周動(dòng)脈閉塞性疾病感染性休克DunserMW,MayrAJ,TurA,etal.Ischemicskinlesionsasacomplicationofcontinuousvasopressininfusionincatecholamine-res