What is optimal flow?

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1 Perfusing the microcirculation. Did five decades of cardiopulmonary bypass teach us how to achieve optimal perfusion? Filip De Somer, Ph.D. University Hospital Gent Belgium What is optimal flow? Reference value CI ( LPM/m²) 70 ml/kg SvO2 > 65% What is an optimal circulation? Maintain homeostasis O 2 delivery CO 2 removal Preserve organ function This is particular important at a microcirculatory level 1

2 What is optimal microcirculation? Pressure Viscosity Resistance CO DO2 Hematocrit / hemoglobin CO Blood markers Cr, Tr, S100, NAG, lactate, blood gas, etc Microcirculation Lipowsky Tissue cylinder Islam

03 0.06 0.09 0.12 0.15 Axial position in the capillary [cm] Q b =0.62 ml/min/cm³; L c =0.

3 Grist 2008 Q b =4mL/min/cm³; L c =0.1cm; C r =5 µm Tissue cylinder = 14 µme cylinder Blood po2 Tissue po2 90 PO2 [mmhg] Axial position in the capillary [cm] Q b =0.62 ml/min/cm³; L c =0.1cm; C r =5 µm po2 [mmhg] Blood po2 90 Tissue po Tissue cylinder = 35 µme cylinder axial position in the capillary [cm] 3

4 What do we know? Pressure - tissue perfusion MAP <50 mmhg vs >50 mmhg Haugen 2006 Hemodilution and functional capillary density Duebener

5 Is transfusion the answer? Tsai 2004 Cabrales 2006 Cabrales

Density Relative to baseline 1 0.8 0.6 0.

6 Cabrales 2006 Viscosity and tissue perfusion Cabrales 2006 Tsai 2004 Functional Capillary Density Functional Capillary Density Relative to baseline LV HV Systemic hematocrit Relative to baseline Tsai

7 Manduz 2008 Boldt 2008 Summary FCD is as critical for tissue survival as Oxygen supply Increasing plasma viscosity restores FCD up to 75% hemodilution Oxygen delivery is more important than fixed pump flow and absolute Hct values 7

Hemolysis and the microcirculation Free plasma hemoglobin White blood cell activation Cell microparticles Platelet activation Free plasma

8 Hemolysis and the microcirculation Free plasma hemoglobin White blood cell activation Cell microparticles Platelet activation Free plasma hemoglobin Weight: 80 kg TBV: 5.3 L Damaged 60 blood: 7.3 ml Free plasma Hb [mg/dl] Prae 15 XC end post PO1 Rother

9 Hemolysis and NO Minneci 2005 Activated plts and the microcirculation 3-4 w old pigs Activated plts and the microcirculation 10 normothermic bypass 40 cooling (Trec = 15 C) 60 DHCA Rewarming till 37 C Ben Mime

10 Platelet activation and tissue perfusion Ben Mime 2005 Ben Mime

11 11

12 Activation of coagulation and organ dysfunction Dixon 2005 Thrombin activates platelets Pre-op (grade 4) Post-op + aprotinin (grade 4) C Lavee 1992 Post-op (grade 1) 12

13 How can we adapt flow to a patients metabolic needs By retrospective analysis of organ function, blood markers and morbidity What we need is a multivariate online analysis of risk during cardiopulmonary bypass Charles Wildevuur Which parameters? CARDIAC OUTPUT Changes based on metabolic needs Usually in the range of 2.8 to 3.0 L/min/mq May increase up to 15 L/min/m² CO with arterial oxygen content, determines the oxygen delivery (DO2) Guaranty oxygen need (VO2) Pulsatile flow CPB FLOW Adjusted by the perfusionist based on temperature and blood pressure 2.0 to 3.0 L/min/m² Adequacy of the pump flow controlled with SvO2 monitoring Qb with arterial oxygen content, determines the oxygen delivery (DO2) Should guaranty oxygen need (VO2) The role of pump flow is to guarantee an adequate O2 supply to the organs Anesthesia and VO2 37 C: 37 C + anesthesia: 28 C + anesthesia: 4 ml/kg/min 2-3 ml/kg/min 1-2 ml/kg/min O2 consumption decreases with approx. 7% per 1 C 13

14 Formulas CaO 2 =(SaO 2 x Hb x 1.34) +(PaO 2 x 0.003) CvO 2 =(SvO 2 x Hb x 1.34) +(PvO 2 x 0.003) DO 2 = CI x CaO 2 x 10 VO 2 = CI x (CaO 2 - CvO 2 ) x 10 O 2 ER = VO 2 /DO 2 PCO 2 = PvCO 2 PaCO 2 Huang 2005 DO 2 and VO 2 VO2 [ml/min] O 2 ER=40% SvO 2 =60% O 2 ER=30% O 2 ER=25% SvO 2 =70% SvO 2 =75% DO2 [ml/min] 14

15 Hypothesis If DO2 is a prime variable If most perfusionists work with a fixed CI Must hemoglobin influence quality of Perfusion Haematocrit during CPB < >28 Nadir haematocrit [%] Total N/100 % ARF-D Karkouti 2005 Lowest HCT on CPB is associated to: Reopening Bleeding Perioperative MI Cardiac arrest Stroke Coma Prolonged ventilation IABP Renal failure MOF Habib

kidney, perfused with a low O2 content, is more

16 Conclusions Evidence based relationship between low Hct and outcome Most likely due to a low DO 2 The kidney, perfused with a low O2 content, is more vulnerable than other organs Stafford-Smith 2005 Ranucci

17 Conclusions Scarce information on DO 2 during CPB With a constant pump flow, DO 2 is direct related to Hct Most CPB cases are performed at C Pump flow = 2-3 L/min/m² => Hct = cte => DO 2 varies with 50% McDaniel 1995 current guidelines for calculating pump flow during normothermic bypass may be reconciled to better match prebypass systemic oxygen delivery with oxygen delivery during CPB. McDaniel

18 Cilley 1991 Cilley 1991 Demers

19 Demers 2000 Mortality Major complications Maillet Immediate HL Late HL No HL N=67 N=56 N=202 AEROBIC METABOLISM C 6 H 12 O > 6 CO H 2 O + 36 ATP (RQ = 1.0) (Glucose) C 16 H 32 O > 16 CO H 2 O ATP (RQ = 0.71) (Fatty acid) ANAEROBIC METABOLISM Glucose + 2 ADP ----> 2 H + lactate + 2 ATP (Lactic acid) H + lactate - + Na + HCO > Na + lactate - + H 2 CO 3 H 2 CO 3 ---> H 2 O + CO 2 19

20 VCO2 VO2 VCO2 [ml/min] RQ: 0.8 Anaerobic threshold VO2 [ml/min] Grundler 1986 Ranucci

Ranucci 2006 Anaerobic threshold All variables N = 42 1.0 0.

21 Ranucci 2006 Anaerobic threshold All variables N = Sensitivity Mekonso-Dessap 2002 Specificity-1 21

22 Optimal flow and outcome Renal replacement - ARF rate [%] P<0.01 PUMP FLOW P<0.001 High Hct N=640 Low Hct N=53 High Hct N=113 Low Hct N=242 0 High DO2 Low DO2 Ranucci 2005 Optimal flow and outcome von Heymann 2006 von Heymann

23 Optimal flow and outcome 25% = 356 ml/min/m² 20% = 287 ml/min/m² > 270 ml/min/m² von Heymann 2006 Conclusions A minimum DO2 is required during CPB f(qb, Hb, T) CO2 derived parameters are indicators of tissue perfusion Ratio DO 2i /VCO 2i provides online information on the quality of perfusion Conclusions A DO2 of 270 ml/min/m² is enough at 34 C SvO2 > 75% is no guarantee CO2 derived variables are better than O2 derived variables in predicting lactic shock 23

Develop an algorithm DO2/VCO2 ratio <5 Augment pump flow Increase Hb content Decrease T, check anesthesia level Final conclusions Optimal flow is difficult to access due to Pathology (ischemic vs

24 Develop an algorithm DO2/VCO2 ratio <5 Augment pump flow Increase Hb content Decrease T, check anesthesia level Final conclusions Optimal flow is difficult to access due to Pathology (ischemic vs valve) Endothelial dysfunction (diabetes) Perfusion, anesthesia and surgical practice (hemodilution, volatile anesthetics, temperature, etc) Today most analysis is done by postoperative retrospective analysis of morbidity and or blood markers Continuous online analysis of O 2 and CO 2 derived parameters allows dynamic control of blood flow based on metabolic needs 24

PICU Resident Self-Study Tutorial The Basic Physics of Oxygen Transport. I was told that there would be no math!

Physiology of Oxygen Transport PICU Resident Self-Study Tutorial I was told that there would be no math! INTRODUCTION Christopher Carroll, MD Although cells rely on oxygen for aerobic metabolism and viability,