脓毒症的液体治疗

脓毒症的液体治疗

—VISEP试验解读EpidemiologyManagement:guidelinesInitialresuscitationDiagnosisAntibiotictherapySourcecontrolFluidtherapyVasopressorsInotropictherapySteroidsRhAPCBloodproductadministrationk.

Mechanicalventilationl. Sedationm. Glucosecontroln. Renalreplacemento. Bicarbonatetherapyp. Deepveinthrombosisprophylaxisq. StressulcerprophylaxisDellingerRIntCareMed2004;30:536-555早期复苏治疗«

EarlyGoal-DirectedTherapy

»早期目标治疗RiversENEnglJMed2001;345:1368-77单一中心临床研究

263个急诊科收治病人有严重感染或感染性休克随机化:EGDTvs常规治疗结果:医院死亡率(28d)<6HRandomizationEGDTEarlyGoalDirectedTherapy:ResultsEGDT:mortality 16%at28d 12%at60dRiversENEnglJMed2001;345:1368-77Dellinger,et.al.CritCareMed2004,32:858-873.colloidsWholebloodPRBCFFPPlasmaproteinsblood/bloodproductsnaturalcolloidsAlbumin0.9%NaCIRinger`slactatcrystalloidsGelatinDextranHESsyntheticcolloidsVolumereplacement液体复苏

感染性休克>>低容量>>积极液体复苏治疗容量试验:500-1000ml晶体或300-500ml胶体30min内输完，评估病人的反应晶体或胶体??

目前尚无循证医学证据支持哪一类!DellingerCritCareMed2003;31:946-955ShouldwetransfuseRedBloodCells?AMulticenter,Randomized,ControlledClinicalTrial

ofTransfusionRequirementsinCriticalCare

Hebertetal.N.Engl.J.

Med.1999,

340:409-17Acomparisonofalbuminandsaline

forfluidresuscitationintheICUProbabilityofSurvival0,50 28

AlbuminN-Saline1,0

FinferSetal.NEnglJMed2004;350:2247-56RCTstydy6997PatientsControlgroup:N-SalineStudygroup:4%AlbuminMetaAnalysisAlbuminvs.Crystalloids

CochraneStudyGroupBMJ1998;317:235.

Mortality Relativerisk：AlbvsCryst

AlbuminControlHypovolaemia38/256

26/278

1.46(0.97-2.22) Burns

19/81

8/82

2.40(1.11-5.19)Hypoalbumin-41/259

24/248 1.69(1.07-2.57)

aemia

Total

98/596

58/608

1.68(1.26-2.23)

Conclusion:AlbuminincreasedriskofmortalityMulticentertrialAlbuminvs.Crystalloids

SAFEStudyAustralia/NewZealand6997patients:3497albumin,3500normalsalineMortality:726p.albumin,729p.normalsalineSingleorganfailurenodifferenceICUdays:6.5dalbumin,6.2dnormalsalineVent.days:4.5dalbumin,4.3dnormalsalineRenalreplacement:0.5dalbumin,0.4dsalineOutcome:28dmortalitysimilarAUS/NZInt.CareSoc.Clin.TrialGroupNEJM2004;350:2247-56SAFEstudy

任何死亡原因的相对风险度0.51.02.0AlbuminBetterSalineBetter0.99(0.91-1,09)1.36(0.99-1.86)0.96(0.88-1.06)0.87(0.74-1.02)1.05(0.94-1.17)0.93(0.61-1.41)1.00(0.91-1.09)总数 726/3473 729/3460创伤

是 81/596 59/590

否 641/2831 666/2830重度脓毒血症

是 185/603 217/615

否 518/2734 492/2720ARDS

是 24/61 28/66

否 697/3365 697/3354适应症白蛋白

生理盐水风险比值(CI)

死亡例数/总例数NEnglJMed2004;350:2247Preferred

plasmavolumeexpandersforcriticallyillpatients:resultsofaninternationalsurveySchortgenF

etal.IntensiveCareMed2004;30:2222-29CRYCOStudygroup515ICUs75itemquestionairevolumereplacementhemodynamicstabilizationfluid-homeostasiscoagulationsideeffectsSchorgenstudy

328例脓毒血症患者166例不合格162例合格33例未登记:未获同意129例随机分组65例羟乙基淀粉组64例明胶组明胶与羟乙基淀粉对肾功能影响对比SchortgenF.etal.Lancet2001;357:911-916Schorgenstudy没有肾功能衰竭的群体DaysN=64N=65P=0.018ObservationperiodsofHESstudiesw/orenalimpairment1dayLondonetal.(JCardiothoracicAnesth1989)14daysDemanetal.(NephrolDialTransplant1999)6hoursVogtetal.(AnesthAnalg1996)5daysBoldtetal.(IntenseCareMed1998)1dayAllisonetal.(JTrauma1999)3daysKumleetal.(AnesthAnalg1999)perioperative-1dayBoldtetal(JCardiothoracicAnesth2000)perioperativeDehneetal.(JClinAnesth2001)3days(blood);4days(urine)Jungheinrichetal.(AnesthAnalg2002)2daysBoldtetal.(IntensCareMed2003)8days;FU3daysafterinfusion

Neffetal.(AnesthAnalg2003)ObservationperiodAuthor减轻毛细血管渗漏和组织水肿减轻组织的缺血再灌注损伤保持胃粘膜血流和pHi肺水肿发生率低减轻内皮细胞的激活和白细胞与内皮细胞之间的相互作用改善微循环血流，减轻白细胞的黏附羟已基淀粉（HES）的优点VISEPstudyG.Marx,MDDept.ofAnaesthesiologyandIntensiveCareMedicine,Friedrich-Schiller-University,Jena,Germany(德国耶拿大学)30个中心随机对照临床试验最新的评价HES治疗重度脓毒血症和感染性休克病人的多中心试验！Hemohes®10%Fa.B.Braun(HES200/0.5)羟乙基淀粉平均分子量200000分子取代级0.45-0.55C2/C6比值6:1生产商推荐的每日最大用量≤20ml/kgBW/日≈2.0g/kg(75kg的病人≈1,500ml/日)扩容效能130-150%扩容效果:中等(3-4hours)容量治疗用药

DieterichH-J.:JTrauma2003初级观察终点：28天的死亡率降低（10%）平均SOFA评分降低了1.2分次级观察终点：达到血流动力学稳定状态的时间急性肾功能衰竭的频率采用血管加压素治疗的频率(天数)平均SOFA亚评分之间的差异并发症（含出血事件）的发生率机械通气的时间(天)ICU停留时间(天)90-天的死亡率VISEP研究起病24小时之内的重度脓毒血症和感染性休克（发病12小时之内的ICU获得性重度脓毒血症/感染性休克）。纳入标准年龄<18岁怀孕HES过敏史随机化分组前24小时内输注过>1000mlHES严重的急慢性肾功能障碍(既往已知的肌酐水平>320µmol/L或需要透析治疗)颅内出血随机化分组时FiO2>0,7严重头部创伤伴水肿心功能衰竭(NYHAIV)应用免疫抑制剂DNR-order预计生存期<28days排除标准

CVP

12mmHg平均动脉压

70mmHg中心静脉氧饱和度

70%测定点:第1天:1,2,4,6,8,12h第2-4天:Q12h第4天:Q

24h

血流动力学目标600例病人随机分组

297例入HES组

303例入乳酸林格氏液组27例没得到知情同意

34没得到知情同意

1例违反了合法性标准1例违反了合法性标准

262ITT275

ITT研究对象N=53724h12h随机化入选病例晶体容量替代治疗(Sterofundin)胶体容量替代治疗直至用量上限(20mL/kgBW)

(HES)21天ICU前在

ICU研究流程31.78336.4100

病房医源性22.15823.364

ICU医源性44.311639.3108

社区获得性感染源%n%n

HESn=262Ringers´lactaten=275

55.014.456.853.012.954.4SAPS20.06.720.619.06.520.3APACHE67.013.364.468.014.164.9年龄MedianSDMeanMedianSDMean

HESn=262Ringers`lactaten=275

VISEP研究基础值3.8104.412 心脏超声(TTEorTEE)24.16324.467

PICCO5.0136.618

PA导管血流动力学监测24.16326.568ScvO2<70%31.38231.180MAP<70mmHG21.05519.851CVP<8mmHg5.31410.930无需透析的慢性肾衰6.51711.632心衰NYHAII-III30.58030.283糖尿病60.315859.6164性别(男)%n%n

HESn=262Ringers´lactaten=275

VISEP研究

-基础值II-414.538414.640FFP[nos.]226.068221.559RBC[nos.]80014.137100011.331

明胶50016.44350011.632HES10%50034.49050034.294HES6%200069.5182200074.6205

晶体容量负荷(随机分组前12小时内)Median[ml]%nMedian[ml]%nHESn=262Ringers´lactaten=275VISEPTrial(HESvs.乳酸林格氏液)

-基础资料III-20,02413,000max40,56833,507max2,4001463,7875000-24hours3,4001005,9605000-48hours晶体medianminmedianmin

HESn=262晶体n=275

VISEPTrial(HESvs.乳酸林格氏液)

-晶体容量替代治疗(ml)-3,170mlHES16,905mlnon-HESfluids=15.3

RatioofHEStonon-HESfluids

intheHESgroup(day0-4)

平均动脉压中心静脉压中心静脉血氧饱和度10075500%of达到综合目标的病人数25100200300400hours500600乳酸林格氏液n=150HESn=146p=0.024血流动力学目标(CVP,MAP,ScvO2)

24.1%26.7%0%25%50%75%28-day死亡率死亡率(%)n=274n=262乳酸林格氏液HESp=0.48n=274n=26133.9%41.0%0%25%50%75%90-day死亡率p=0.11死亡率Ringers´lactaten=274p=0.141007550250存活率%HESn=261020406080100days

存活率对肾脏的影响75.009.1874.1874.008.7173.44ScvO2(%)75.5013.63

76.2975.00

13.94

77.16MAP(mmHg)12.00

5.3012.1012.00

5.13

11.48CVP(mmHg)126.80

77.90141.99120.0085.72145.90血清肌酐(µmol/L)MedianSDMeanMedianSDMean

HESn=262

Ringers´lactate n=275

VISEPTrial(HESvs.乳酸林格氏液)

-干预开始

-尿量DiuresisRinger’sLactateHESDays01234567891011121314151617181920215000450040003500300025002000150010005000ml肌酐平均SOFA评分7.53MeanRingers`lactaten=2743.62SD6.75Median8.0MeanHESn=2624.05SD7.29Median0.8p0.501.001.301.341.001.191.23CNS肝脏肾脏凝血呼吸心血管SOFA-亚评分0.520.840.552.481.90MeanRingers`lactate0.801.050.820.581.10SD0.110.420.112.571.76Median0.521.120.752.441.83MeanHES0.781.260.860.601.17SD0.090.670.462.501.80Median1.00.02<0.00010.580.51p

并发症发病率0.001<0.0016.09.98.74.07.26.6输RBC(nos.)0.00131.02618118.627251血滤(HF)18.335546509.33471321HF天数0.525.0262133.627510出血事件0.0776.026219968.7275189输血急性肾衰63nRingers´lactate272N23.2%91nHES261N34.9%0.003p

并发症Ringers`lactategroupHESgroupDays0123456789101112131415161718192021100009000800070006000500040003000200010000HESgroupTotalfluids(ml)

Ringers´lactateattributableamountsofHES23618514912410911493938082756768665356