感染性休克患者的血管活性药物应用

感染性休克时血管活性药物的应用浙江省中医院ICU江荣林感染性休克时血管活性药物的应用循环功能支持治疗—目的维持血压以保证重要脏器的灌注和功能保证足够的组织氧合液体复苏治疗纠正低血容量第一个24小时内输注晶体液10–20升或更多液体的选择等张溶液乳酸林格氏液，生理盐水胶体液血液 — 血容量丧失超过30%白蛋白 — 治疗晚期6小时液体复苏治疗晶体液价格低廉增加血管内容量增加血管外间隙〔外周水肿〕胶体液急性复苏后增加胶体渗透压减少血管外间隙6小时血管活性药物目的容量复苏疗效不佳者，以维持或升高血压适应证充分的液体复苏PAWP15–18mmHgMAP<65mmHg血管活性药物争论1：去甲肾上腺素有益抑或有害？Isnorepinephrinethewrongchoice?血管活性药物—去甲肾上腺素From：JAMA1994;272:1354血管活性药物—去甲肾上腺素分组DOPA 263.8g/kg/minNE 0.180.06g/kg/minFrom：JAMA1994;272:1354血管活性药物—去甲肾上腺素NEDOPAbaseline3hrbaseline3hrMAP55876387CI4.24.74.25.3PAWP15161516SVRI1110140510351221DO2498569573703VO2145162183221pHi7.167.237.247.18From：JAMA1994;272:1354血管活性药物—去甲肾上腺素MartinC,etal.Norepinephrineordopamineforthetreatmentofhyperdynamicsepticshock.Chest1993;103:1826-31血管活性药物—去甲肾上腺素分组DOPA (n=16) 2.5–25g/kg/minNE (n=16) 0.5–5.0g/kg/min治疗终点恢复器官灌注持续6hrMAP>80mmHgCI>4.0L/min/m2UOMartinC,etal.Norepinephrineordopamineforthetreatmentofhyperdynamicsepticshock.Chest1993;103:1826-31血管活性药物—去甲肾上腺素NEDOPA剂量(g/kg/min)1.51.210–25有效率93%(15/16)‡31%(5/16)换用药物后有效率0%(0/1)91%(10/11)存活率59%17%出院病人数96MartinC,etal.Norepinephrineordopamineforthetreatmentofhyperdynamicsepticshock.Chest1993;103:1826-31血管活性药物—去甲肾上腺素结论与DOPA相比，NE能够更有效地纠正血流动力学异常对DOPA反响不佳的感染患者，应及时加用NEMartinC,etal.Norepinephrineordopamineforthetreatmentofhyperdynamicsepticshock.Chest1993;103:1826-31去甲肾上腺素与感染性休克的预后变量病死率(%)RR(95%CI)P值NE治疗Yes620.68(0.54–0.87)<.001No82肺炎引发休克Yes821.47(1.07–1.77)<.03No61器官衰竭指数3Yes921.47(1.17–1.82)<.001No60入选时尿量较少Yes881.44(1.06–1.87)<.01No60入院时血乳酸水平Yes911.60(1.27–1.84)<.01No63MartinC,ViviandX,LeoneM,etal.Effectofnorepinephrineontheoutcomeofsepticshock.CritCareMed.2000Aug;28(8):2758-65.输液治疗能否降低NE剂量?输液前输液过程中输液后NE剂量(g/kg/min)0.540.330.21HR(bpm)104139415血容量指数(ml/m2)26506383655885胸腔内血容量指数(ml/m2)8882041050248心脏指数(L/min/m2)3.61.04.00.9内脏血流绝对(ml/m2)0.810.98分数(%)22.323.9粘膜内PCO2(kPa)7.52.59.02.8PCO2差值(kPa)3.12.54.02.9SakkaSG,Meier-HellmannA,ReinhartK.Dofluidadministrationandreductioninnorepinephrinedoseimproveglobalandsplanchnichaemodynamics?BrJAnaesth2000Jun;84(6):758-62.输液治疗能否降低NE剂量?个体反响存在显著差异提示对于病情稳定的感染性休克患者，通过输液治疗降低NE剂量不能增加全身或内脏血流SakkaSG,Meier-HellmannA,ReinhartK.Dofluidadministrationandreductioninnorepinephrinedoseimproveglobalandsplanchnichaemodynamics?BrJAnaesth2000Jun;84(6):758-62.血管活性药物争论2：如何维持肾脏血流？Isdopaminetherightanswer?血管活性药物—肾脏保护血管活性药物—肾脏保护血管活性药物—肾脏保护血管活性药物—肾脏保护血管活性药物—肾脏保护血管活性药物—肾脏保护血管活性药物—肾脏保护时间血管活性药物—肾脏保护健康对照腹腔感染血管活性药物—肾脏保护健康对照腹腔感染血管活性药物—肾脏保护血管活性药物—肾脏保护血管活性药物—肾脏保护KellumJA,DeckerJM.Useofdopamineinacuterenalfailure:ameta-analysis.CritCareMed2001Aug;29:1526-31？血管活性药物—肾脏保护KellumJA,DeckerJM.Useofdopamineinacuterenalfailure:ameta-analysis.CritCareMed2001Aug;29:1526-31血管活性药物—肾脏保护主要研究结果检索到58项研究24项研究报告了至少1项主要预后指标分析包含了17项RCTs(854名患者)KellumJA,DeckerJM.Useofdopamineinacuterenalfailure:ameta-analysis.CritCareMed2001Aug;29:1526-31血管活性药物—肾脏保护事件的加权发生率预后RCT病例数多巴胺对照RRR(95%CI)P值病死率115084.9%5.6%14%(-66to56)0.69ARF发生率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血管活性药物—肾脏保护KellumJA,DeckerJM.Useofdopamineinacuterenalfailure:ameta-analysis.CritCareMed2001Aug;29:1526-31血管活性药物—肾脏保护BellomoR,ChapmanM,FinferS,etal.Low-dosedopamineinpatientswithearlyrenaldysfunction:aplacebo-controlledrandomisedtrial.AustralianandNewZealandIntensiveCareSociety(ANZICS)ClinicalTrialsGroup.Lancet2000Dec23-30;356(9248):2139-43血管活性药物—肾脏保护多巴胺(n=161)安慰剂(n=163)P值Scr峰值245

144249

1470.93Scr差值62

10766

1080.82Scr>300的患者数56560.92需要RRT的患者数35400.55ICU住院日13

1414

150.67总住院日29

2733

390.29死亡人数6966BellomoR,ChapmanM,FinferS,etal.Low-dosedopamineinpatientswithearlyrenaldysfunction:aplacebo-controlledrandomisedtrial.AustralianandNewZealandIntensiveCareSociety(ANZICS)ClinicalTrialsGroup.Lancet2000Dec23-30;356(9248):2139-43血管活性药物争论3：如何评价对内脏灌注的影响？Systemicversusregionaloxygenation血管活性药物—内脏灌注CriticalCareMed1993;21:1296血管活性药物—内脏灌注血管活性药物—内脏灌注血管活性药物—内脏灌注肾上腺素vs去甲肾上腺素临床试验30名感染性休克患者分组EpiNE+Dobu治疗终点MAP>80mmHgIntensiveCareMed1997;23:282血管活性药物—内脏灌注IntensiveCareMed1997;23:282血管活性药物—内脏灌注IntensiveCareMed1997;23:282血管活性药物—内脏灌注IntensiveCareMed1997;23:282血管活性药物—内脏灌注肾上腺素vs去甲肾上腺素感染性休克动物模型〔猪〕分组EpiNE治疗终点MAP>70mmHgAnnSurg1998;228:239血管活性药物—内脏灌注AnnSurg1998;228:239血管活性药物—内脏灌注肾上腺素增加CI,DO2,VO2增加肠道DO2(GMP)增加肠道粘膜和全身氧需增加乳酸降低pHi，导致肠道损害血管活性药物—内脏灌注CritCareMed1999;27:893血管活性药物—内脏灌注NENE+DobuEpiMAP747474PAWP151414CI4.44.75.2DO2563621671VO2150152158O2ER0.280.250.24GMP256419350GMP/DO20.520.610.46CritCareMed1999;27:893血管活性药物—内脏灌注血管活性药物—内脏灌注去甲肾上腺素增加CI,DO2,VO2增加肠道DO2增加pHi腹膜炎时的血管活性药物SunQ,TuZ,LoboS,etal.

Optimaladrenergicsupportinsepticshockduetoperitonitis.Anesthesiology2003Apr;98(4):888-96.腹膜炎时的血管活性药物DB-NE组CO和肠系膜上动脉血流显著增加DO2和VO2明显增加血乳酸水平和PCO2差值较低累计尿量显著增加存活时间DB-NE(24

4h) 联合用药组DA-NE(24

6h) DB-NE和DA-NE(24

5h)NE(20

1h;P<0.05vs.联合用药组)对照组(17

2h;P<0.05vs.其他组)SunQ,TuZ,LoboS,etal.

Optimaladrenergicsupportinsepticshockduetoperitonitis.Anesthesiology2003Apr;98(4):888-96.腹膜炎时的血管活性药物肺活检的组织学检查与对照组和NE组相比，DB-NE组病变较轻肺、肝和小肠的解剖学改变与其他组相比，DB-NE组病变较轻SunQ,TuZ,LoboS,etal.

Optimaladrenergicsupportinsepticshockduetoperitonitis.Anesthesiology2003Apr;98(4):888-96.腹膜炎时的血管活性药物结 论在本研究所采用的长时间感染性休克模型中NE与DA或DB联合应用存活时间最长肺部病变最轻DB+NE心脏功能更好DO2和VO2更高血乳酸水平和PCO2差值更低解剖学病变更轻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(靛氰绿)清除率:血浆清除率(%)12.2(7.6–16.2)NSDünserMW,MayrAJ,UlmerH,etal.TheEffectsofVasopressinonSystemicHemodynamicsinCatecholamine-ResistantSepticandPostcardiotomyShock:ARetrospectiveAnalysis.血管舒张性休克时小剂量血管加压素MalayMB,AshtonRCJr,LandryDW,etal.Low-dosevasopressininthetreatmentofvasodilatorysepticshock.JTrauma1999;47(4):699-703血管舒张性休克时小剂量血管加压素抚慰剂组SBP无改变SVR无改变用药24小时后2名患者因顽固性低血压死亡MalayMB,AshtonRCJr,LandryDW,etal.Low-dosevasopressininthetreatmentofvasodilatorysepticshock.JTrauma1999;47(4):699-703血管加压素与胃粘膜微循环实验设计:前瞻性,抚慰剂对照,随机,单盲试验实验对象:15只雄性Sprague-Dawley大鼠对照组(n=7):CLP模型+NS试验组(n=8)CLP后24小时(M1)持续输注AVP使MAP升高20mmHg(M2)持续输注AVP使MAP升高40mmHg(M3)测定指标:在M1对回肠粘膜的6–10个绒毛进行显微镜检查在M2和M3重复检查血浆AVP和IL-6水平WestphalM,FreiseH,KehrelBE,etal.Argininevasopressincompromisesgutmucosalmicrocirculationinsepticrats.

CritCareMed2004Jan;32(1):194-200.血管加压素与胃粘膜微循环对照组(n=7)实验组(n=8)M2M3粘膜平均血流量下降76%‡81%‡红细胞速度降低45%†47%†绒毛血流中断时间(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.血管加压素与胃粘膜微循环结 论感染大鼠输注AVP胃粘膜血流严重异常感染的炎症反响增强AVP对微血管血流的影响AVP对较大的小动脉(>40microm)的活性心输出量的下降二者兼有WestphalM,FreiseH,KehrelBE,etal.Argininevasopressincompromisesgutmucosalmicrocirculationinsepticrats.

CritCareMed2004Jan;32(1):194-200.感染性休克时血管加压素与去甲肾上腺素KlinzingS,SimonM,ReinhartK,etal.High-dosevasopressinisnotsuperiortonorepinephrineinsepticshock.CritCareMed2003Nov;31(11):2646-50.NE血管加压素剂量(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†内脏血流分数(%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感染性休克时血管加压素与去甲肾上腺素输注AVP导致左心室每搏功减少12

7%门静脉血流减少45

5%小肠粘膜血流减少31

13%内脏氧输送(DO2)下降内脏和肾脏氧摄取增加GuzmanJA,RosadoAE,KruseJA.Vasopressinvsnorepinephrineinendotoxicshock:systemic,renal,andsplanchnichemodynamicandoxygentransporteffects.JApplPhysiol2003Aug;95(2):803-9.血管加压素和皮肤缺血性病变发生率: 19/63(30.2%)肢体远端: 13/19(68%)躯干: 2/19(10.5%)肢体远端和躯干: 4/19(21%)合并舌头缺血: 5/19(26%)AVP治疗中发生ISL的独立危险因素既往外周动脉闭塞性疾病感染性休克DunserMW,MayrAJ,TurA,etal.Ischemicskinlesionsasacomplicationofcontinuousvasopressininfusionincatecholamine-res