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 (2.0-2.4 LPM/m²) – 70 mL/kg • SvO2 > 65% What is an optimal circulation? • • • • Maintain homeostasis O2 delivery CO2 removal Preserve organ function This is particular important at a microcirculatory level 1 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 2006 2 Grist 2008 Qb=4mL/min/cm³; Lc=0.1cm; Cr=5 µm 100 Blood pO2 Tissue pO2 95 Tissue cylinder = 14 µme cylinder PO2 [mmHg] 90 85 80 75 70 0 0.03 0.06 0.09 0.12 0.15 Axial position in the capillary [cm] pO2 [mmHg] Qb=0.62 mL/min/cm³; Lc=0.1cm; Cr=5 µm 100 95 90 85 80 75 70 65 60 55 50 45 40 35 30 25 20 15 10 5 0 Blood pO2 Tissue pO2 Tissue cylinder = 35 µme cylinder 0 0.03 0.06 0.09 0.12 0.15 axial position in the capillary [cm] 3 What do we know? Pressure - tissue perfusion MAP <50 mmHg vs >50 mmHg Haugen 2006 Hemodilution and functional capillary density Duebener 2001 4 Is transfusion the answer? Tsai 2004 Cabrales 2006 Cabrales 2006 5 Cabrales 2006 Viscosity and tissue perfusion Cabrales 2006 Tsai 2004 1 Relative to baseline Functional Capillary Density Functional Capillary Density 0.8 0.6 LV 0.4 HV 0.2 0 0 0.2 0.4 0.6 0.8 1 Systemic hematocrit Relative to baseline Tsai 1998 6 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 hemoglobin Free plasma Hb [mg/dL] Weight: 80 kg TBV: 5.3 L Damaged blood: 7.3 mL 60 50 40 30 20 10 0 Prae 15 XC end post PO1 Rother 2005 8 Hemolysis and NO Minneci 2005 Activated plts and the microcirculation Activated plts and the microcirculation • 3-4 w old pigs • • • • 10’ normothermic bypass 40’ cooling (Trec = 15°C) 60’ DHCA Rewarming till 37°C Ben Mime 2005 9 Platelet activation and tissue perfusion Ben Mime 2005 Ben Mime 2005 10 11 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 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 Formulas CaO2 =(SaO2 x Hb x 1.34) +(PaO2 x 0.003) CvO2 =(SvO2 x Hb x 1.34) +(PvO2 x 0.003) DO2 = CI x CaO2 x 10 VO2 = CI x (CaO2 - CvO2) x 10 O2ER = VO2/DO2 PCO2 = PvCO2 – PaCO2 Huang 2005 DO2 and VO2 O2ER=40% SvO2=60% 300 O2ER=30% O2ER=25% SvO2=70% SvO2=75% VO2 [mL/min] 250 250 200 150 100 50 0 0 100 200 300 400 500 600 700 800 900 1000 DO2 [mL/min] 14 Hypothesis • If DO2 is a prime variable • If most perfusionists work with a fixed CI Must hemoglobin influence quality of Perfusion Haematocrit during CPB 10 9 8 7 6 5 4 3 2 1 0 Total N/100 % ARF-D <18 19 21 23 25 27 >28 Nadir haematocrit [%] Karkouti 2005 Lowest HCT on CPB is associated to: Reopening Bleeding Perioperative MI Cardiac arrest Stroke Coma Prolonged ventilation IABP Renal failure MOF Habib 2003 15 Conclusions • Evidence based relationship between low Hct and outcome • Most likely due to a low DO2 • The kidney, perfused with a low O2 content, is more vulnerable than other organs Stafford-Smith 2005 Ranucci 2005 16 Conclusions • Scarce information on DO2 during CPB • With a constant pump flow, DO2 is direct related to Hct • Most CPB cases are performed at 32 34°C • Pump flow = 2 - 3 L/min/m² • => Hct = cte => DO2 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 1995 17 Cilley 1991 Cilley 1991 Demers 2000 18 Demers 2000 Mortality Major complications 60 50.9 50 40 35.3 30 20 10 0 Maillet 2003 19.2 14.9 Immediate HL N=67 3.6 1.5 Late HL No HL N=56 N=202 AEROBIC METABOLISM C6H12O6 + 6 02 ----> 6 CO2 + 6 H2O + 36 ATP (RQ = 1.0) (Glucose) C16H32O2 + 23 02 ----> 16 CO2 + 16 H2O + 130 ATP (RQ = 0.71) (Fatty acid) ANAEROBIC METABOLISM Glucose + 2 ADP ----> 2 H+ lactate + 2 ATP (Lactic acid) H+ lactate- + Na+HCO-3 ---> Na+ lactate- + H2CO3 H2CO3 ---> H2O + CO2 19 VCO2 – VO2 1600 Anaerobic threshold VCO2 [mL/min] 1400 1200 RQ: 0.8 1000 800 600 400 200 0 0 200 400 600 800 1000 1200 VO2 [mL/min] Grundler 1986 Ranucci 2006 20 Ranucci 2006 Anaerobic threshold All variables N = 42 1.0 Sensitivity 0.8 0.6 0.4 0.2 0.0 0.0 0.2 0.4 0.6 0.8 1.0 Mekonso-Dessap 2002 Specificity-1 21 Optimal flow and outcome P<0.001 Renal replacement - ARF rate [%] 7 P<0.01 6 5 High Hct N=640 Low Hct N=53 High Hct N=113 Low Hct N=242 4 3 PUMP FLOW 2 1 0 High DO2 Low DO2 Ranucci 2005 Optimal flow and outcome von Heymann 2006 von Heymann 2006 22 Optimal flow and outcome DO2 @ 25% = 356 mL/min/m² DO2 @ 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 DO2i/VCO2i 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 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 O2 and CO2 derived parameters allows dynamic control of blood flow based on metabolic needs 24