（体外膜肺ECMO课件）-Classification-of-microcirculatory-.ppt

1、Classification of microcirculatory abnormalities in distributive shockCan InceClinical PhysiologyAcademic Medical CenterUniversity of AmsterdamDeclared interest:I am CSO of MicroVision Medical an AMC based company Weil MH,Shubin H(1971)Adv Exp Med Biol 23:13-23.Proposed reclassification of shock sta

2、tes with special reference to distributive defects.Hypovolemic,cardiogenic,and obstructive shock occurs as a result of decrease in cardiac output leading to anaerobic tissue metabolism.Septic shock results from distributive alterations in tissue perfusion caused by abnormal control of microvasculatu

3、re with abnormal distribution of a normal or increased cardiac output.Hence end-points have been difficult to define.Vincent JL Hemodynamic support in septic shockIntensive Care Medicine(2001)27:S80-S92“Our understanding of hemodynamic mechanisms(in distributive shock)depends not so much on the tota

4、l volume of blood that flows past the aortic valve or the cardiac output as on the amount of blood delivered to the exchange sites.Even though cardiac output may be substantial,if that blood flow does not arrive at the exchange sites,the ultimate metabolic detriment is no different from low cardiac

5、output without shunt flow.”Weil MH,Shubin H(1971)Adv Exp Med Biol 23:13-23.O2lactateCO2Implication:that active recruitment of the microcirculationis an important component of resuscitation.Ince C&Sinaasappel M(1999)Crit Care Med 27:1369-1377Why the microcirculation is important in shock.It is where

6、oxygen exchange takes place.Every parameter in the microcirculation is different than in the systemic circulation.It plays a central role in the immune system.During sepsis and shock it the first to go and last to recover.Rescue of the microcirculation=resuscitation end-point.Spronk P,Zandstra D,Inc

7、e C(2004)Critical Care 8:462-468Sepsis is a disease of the microcirculationInflammatory activationCoagulatory/RBC dysfunctionEndothelial barrier dysfunctionCapillary fall out Weak microcirculatory units are shuntedHypoxia,apoptosis,organ dysfunctionNot detected by systemic variablesNot responsive to

8、 therapy per se Sepsis is a disease of the microcirculation(vessels 250 m)Spronk P,Zandstra D,Ince C(2004)Critical Care 8:462-468Microcirculatory and Mitochondrial Distress Syndrome(MMDS)MMDS=sepsis+genes+therapy+timeInce C(2005)Critical Care 9:S13-S19Co-morbidityGenesInitial HitResuscitation based

9、oncorrection of systemic hemodynamics+inflammationTimeTherapyRBCDeformability,AggregationO2 transportCoagulation Natural AnticoagulantsMicrovascular ThrombosisLeukocytesAdhesion,Cytokines,ROSEndothelial DysfunctionBarrier,CommunicationCoagulation,RegulationDysfunction AutoregulationMicrocirculatory

10、shunting supply-demand mismatchHypoxiaCellular DistressMitochondriaHibernationApoptosis Organ FailureTimeTherapy.Critical Care(2005)9:S13-S19Sinaasappel&Ince (1996)J.Appl.Physiol.81:2297-2303.Sinaasappel,Donkersloot,vanBommel&Ince(1999)Am.J.Physiol 276:G1515-G1520.Microcirculation is shunted when pO

11、2 becomes less than venous pO2 values remain unchanged.Functional shunting is more severe in septic shock than in blood pressure matched hemorrhagic shock in pig intestinesInce C&Sinaasappel M(1999)Crit Care Medicine 27:1369-1377Gut microcirculatory shunt(pO2 gap)and tissue CO2Po2/Mes Ven.Hem.1.00.1

12、0.730.1Po2/Mes Ven.Sep.1.10.10.570.1p=0.02Pco2 gut(mmHg)Hem 4941.220.1 Pco2 gut.(mmHg)Sep.4831.440.1p=0.002Gut Regional flow and oxygen deliverySMA blood flow.(ml/min)Hem 510690.440.1NSSMA blood flow (ml/min)Sep507380.460.1Do2 gut(mM/min)Hem3.5 0.40.380.1Do2 gut(mM/min)Sep3.20.20.480.1P=0.04pO2 gapt

13、issue CO2Hb based oxygen carriers(DCLHb)resuscitates gut serosa and mucosa equally following hemhorrhage.mucosaserosaheartVan Iterson M,Siegemund M,Burhop K,Ince C(2003)J.of Trauma 55:1111-1124Dopexamin resuscitates the microcirculation of the mucosa but not of the serosa and gut tissue CO2.bllpssho

14、ckt-30t-60t-90t-1202030405060*SIN 1Fluid PserO2 mmHgbllpsshockt-30t-60t-90t-12051015202530*SIN 1Fluid PmucO2 mmHgbllpsshockt-30t-60t-90t-1205101520253035*SIN 1FluidPiCO2-gap mmHgThe NO donor SIN-1 resuscitates gut serosal and mucosal microcirculation as well as gastric CO2 Serosa(pO2)Mucosa(pO2)Gast

15、ric CO2Siegemund M,van Bommel J,Vollebrecht K,Dries J,Ince C(2000)Intensive Care Med 26:S 362Microcirculation Recruitment Manoeuvres Correct pathological flow heterogeneity,microcirculatory shunting and restore autoregulatory dysfunction by control of inflammation,vascular function and coagulation.O

16、pen the microcirculation and keep it open by support of the pump,fluids,vasodilators and restricted use of vasopressor agents.Ince C(2005)Critical Care 9:S13-S19 3 cmMathura et al.(2001)J.Applied Physiology 91:74-78.AnalyzerPolarizerGroner et al.(1999)Nature Med 5:1209 Mathura et al.(2001)The Lancet

17、 58:1698 Mathura et al.(2001)J.Appl Physiol 91:74Spronk et al.(2001)The Lancet 360:1395Pennings et al.(2004)Stroke 35:1284.SAH Brain tumours during hyperventilationBefore HVAfter HVSDF imagingSidestream Dark Field imaging for improved technique for observation of the microcirculationInce C(2005)Crit

18、ical Care 9:S13-S19Calculate velocity(30.49 pixels/s)Flow score:0=no flow1=intermittent2=sluggish3=continuousSmall:10-25 mMedium:26-50 mLarge:51-100 mBoerma et al(2005)Crit Care 9:R601-R606 De Backer,Creteur,Preiser,Dubois,VincentAm J Respir Crit Care Med(2002)166:98-104.Sakr et al.Crit Care Med(200

19、4)32:1825-1831There was no difference in sytemic hemodynamic and oxygenation variables or the amount or type of drugs used between survivors and non-survivors.Microcirculatory dysfunction was the single most sensitive and specific predictor of outcome.Creteur,J.,De Backer,D.Sakr,Y.Koch,M.,Vincent,J.

20、L.(2004)Crit Care Med Suppl Vol.31(12):419Resuscitatation is affective in recruitment of capillaries and correction of sub-lingual CO2Sublingual OPS imaging in a patient with septic shock after pressure guided volume resuscitation.the same patient after subsequent nitroglycerin 0.5 mg ivbolus Spronk

21、,Ince,Gardien,Mathura,Oudemans-van Straaten,Zandstra DF.(2002)The Lancet 360:1395-1396.-0,500,511,522,533,5beforeafter TNTmicrovascular flow indexP=0.01810-25 m-0,500,511,522,533,5beforeafter TNTmicrovascular flow indexP=0.01225-50 m-0,500,511,522,533,5beforeafter TNTmicrovascular flow indexP=0.0125

22、0-100 m.Capillary flow but to a much lesser degree venular flow,is impaired during pressure guided resuscitation from septic shock.NO donor can recruit the microcirculation by promoting flow.Spronk,Ince,Gardien,Mathura,Oudemans-van Straaten,Zandstra DF.The Lancet 2002;360(9343):1395-1396.The effects

23、 of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects.De Backer D et al.(2006)Crit Care Med 2006;34:403408)Thrombolysis in fulminant purpura:observations on changes in microcirculatory perfusion during successful treatment.Spronk PE Romm

24、es JH,Schaar C,Ince C (2006)Thromb Haemost.95(3):576-8MFI stoma3,53,02,52,01,51,0,5MFI sublingual,small vessels3,53,02,52,01,51,0,50,0Microvascular flow index(MFI)of small vessels in the sublingual region versus the MFI in the stoma regionChristian BoermaS Wan,JL LeClerc,JL Vincent.Chest 1997;112Inf

25、lammatory Response to Cardiopulmonary BypassMechanisms Involved and Possible Therapeutic StrategiesAge category7-12 months(n=1)1-6 months(n=21)8-28 days(n=10)0-7 days(n=3)Median FCD 8,58,07,57,06,56,77,37,48,1ECMO reduces FCD in premature infantsJ.E.van Velzen,C Ince,D TibbeauProc.Symp.Micro.Mit.Dys

26、funtion in ICM(2003)Healthy sub lingual microcirculation observed by SDF imaging Cardiogenic ShockClassifying microcirculatory flow abnormalities in distributive shockClassCapillary hemodynamicsObserved in diseased statesIStagnantPressure guided resuscitation from sepsisIIContinuous/capillary fall-o

27、utOn-pump CABG surgery,ECMOIIIContinuous/stagnantResuscitated Sepsis,reperfusion injury,sickle cell crises,malariaIVHyperdynamic/stagnantResuscitated sepsisVHyperdynamicResuscitated sepsis,exerciseFunctionally all classes cause a distributive defect and functional shunting of the microcirculation.Ca

28、pillary hemodynamics underlying distributive defectConclusions1)Distributive shock has a bad prognosis with difficult to define hemodynamics end-points.2)It causes a distributive defect at the capillary level of the microcirculation causing functional shunting of weak microcirculatory units.3)It is

29、the reason why distributive shock cannot be adeqautely monitored by systemic hemodynamic parameters.4)OPS/SDF en tissue capnography provide an integrative evaluation of the functional state of the microcirculation.5)Microcirculatory Recruitment Maneuvres are affective in correcting distributive shoc

30、kTime(sec)Vessel length(m)5020015010014012345230ABA typical space-time diagram of microvascular bloodflow before pump(A)and during pump(B).showing a pulsatile flow and respectively a continuous flow.Ligth bands represent either plasma gaps or white blood cells and dark bands represent red blood cell

31、s.The slope(v)of a band in a space-time diagram is the velocity.The horizontal light and dark bands are indicative of variations in the background light intensity.Panel A shows waivy bands indicating pulsatile flowpattern with a rapid(v1)and a slow(v2)phase.Panel B shows straight linear bands indica

32、ting non-pulsatile continuous flowpattern.The velocities are v1=428 m/s v2=86 m/s v3=327 m/s.132Microcirculation Recruitment Manoeuvres Ince C(2005)Critical Care 9:S13-S19Correct pathological flow heterogeneity,microcirculatory shunting and restore autoregulatory dysfunction by control of inflammati

33、on,vascular function and coagulation.Avontuur(1997)Cardiovas Res 35:368-376.Siegmund M(2005)Inten Care Med 31:985-992.Open the microcirculation and keep it open by support of the pump,fluids,vasodilators and restricted use of vasopressor agents.:Boerma(2005)Acta Anaesthesiol Scand.49(9):1387-90.Spro

34、nk (2001)The Lancet 360:1395-1396 Siegemund(2006)Intensive Care MedGut serosa and mucosaBrain cortexHeart and gut serosaSigns of regional dysoxia in the presence of apparent adequate oxygen delivery.Cytopathic hypoxia:mitochondrial dysfunction in the presence of adequate tissue oxygenation.Fink MP(1997)Acta Anaesth.Scan.110:87-95.Shunting theory of sepsis:microcirculatory shut down of weak microcirculatory units creating hypoxic pockets.Ince C&Sinaasappel M(1999)Crit Care Med.27:1369-1377.