adequacy of perfusion during cardiopulmonary bypass

Adequacy of Perfusion duringCardiopulmonary Bypass:Empiric or ScientificDouglas F. Larson, Ph.D.,CCPProfessor of SurgeryProgram Director, Circulatory SciencesThe University of Arizona

IntroductionCardiopulmonary bypass has been used since 1953.In 2003 (50 years later), we are still trying to determine the correct parameters for conducting CPB.As the CPB systems and anesthesia techniques improve, we must re-evaluate our methods. Also, we must adapt our perfusion techniques to meet the patients age and pathology.

IntroductionWe have seen that there is a significant morbidity and mortality associated with CPB (6 percent to 10 percent with neurologic sequeli). What we dont know is what is related:To patient diseaseTo CPBThis appears to be the proper time to re-evaluate our perfusion techniques with the recent reports of adverse neurological outcomes with CPB.

ISSUES: What we can controlFlowsTissue perfusionPressuresPressuresViscosity Vascular compliance

HematocritOxygen carrying capacityGas exchangeOptimal PaO2sOptimal PaCO2s

Arterial Flow ratesComputation:By body weight (kg)By body surface area (m2)Body WeightAdults 30-70 ml/kgBody Surface Area1.6 -3.2 L/m2

With this wide range how do we select a flow rate?Many of the standards of perfusion were established in the 1980s what do we do today?

Arterial Flow ratesAt 37oC 2.2 L/m2 was recommended by Kirklin (Cardiac Surgery 1993, pg 80)

Increased lactate formation is seen with flow rates < 1.6 L/m2Clowes, Surgery 44;200-225:1958Diesh, Surgery 42;67-72:1957

Arterial Flow Rates It is apparent that CPB flow rates were based on unanesthetized human values that is 2.4 3.2 L/m2/min.

It is logical that under flow anesthesia that CBP flow rates could be markedly reduced.

Arterial Flow Rates Historically in the 1950s was established as the standard flow rate of 2.4 L/m2/min.

Currently, the standard of practice is 2.0 2.4 L/m2/min.

However, Stanford University used low-flow technique, without obvious neurologic complications of 1.0 1.2 L/m2/min.

Arterial Flow Rates - IssuesOxygen delivery (Hgb/Hct)Patients oxygen consumption (VO2)Patient temperatureLevel of anesthesiaPressuresPerfusion of critical organs:Heart, Kidneys, BrainBlood traumaThird spacingBronchial blood flow into surgical field

Oxygen Consumption is related to AgeInfants VO21 -3 weeks old7.6 ml O2/kg/min2 months9.0 ml O2/kg/min

Adults 4.0 ml O2/kg/min 250 ml O2/min 100-130 ml O2/min/m2* However these values are unanesthetizedCasthely, Cardiopulmonary Bypass 1991, p 85-86

Oxygen Consumption (VO2) : Anesthesia and Temperature Condition (VO2) 37oC Unanesthetized = 4 ml/kg/min37oC Anesthetized = 2-3 ml/kg/min28oC Anesthetized* = 1-2 ml/kg/min

*Patient oxygen consumption decreases 7% per 1oC.

Dinardo, Cardiac Anesthesia 1998

DO2 versus VO2VO2 = 2 ml/kg DO2 VO2:80 kgHCT 24% VO2 = 3 ml/kg

Chart3

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HCT

Flow Rate (L/min)

Oxygen Transfer (ml/min)

Relationhsip between Flow Rate and Oxygen Transfer by Capiox SX 18 (HCT 24%, SvO2 =65%)

Sheet1

3.23.62.4

HCTHGBCaO2CvO2diffFlowFlowFlowHGBConsumpt

6231.316.9814.323.23.62.4245.82451.55234.368

9344.725.0219.683.23.62.4362.97670.84847.232

12458.133.0625.043.23.62.4480.12890.14460.096

15571.541.130.43.23.62.4597.28109.4472.96

18684.949.1435.763.23.62.46114.432128.73685.824

21798.357.1841.123.23.62.47131.584148.03298.688

248111.765.2246.483.23.62.48148.736167.328111.552

279125.173.2651.843.23.62.49165.888186.624124.416

3010138.581.357.23.23.62.410183.04205.92137.28

3311151.989.3462.563.23.62.411200.192225.216150.144

3612165.397.3867.923.23.62.412217.344244.512163.008

3913178.7105.4273.283.23.62.413234.496263.808175.872

4214192.1113.4678.643.23.62.414251.648283.104188.736

Transfer

HCTHGBA-VFlowO2 TransFlowO2

620.43.225.6432

930.43.238.4448

1240.43.251.2464

1550.43.264480

1860.43.276.8496

2170.43.289.64112

2480.43.2102.44128

2790.43.2115.24144

30100.43.21284160

33110.43.2140.84176

36120.43.2153.64192

39130.43.2166.44208

42140.43.2179.24224

awakeAnesth28oC Anes

20804020

401608040

6024012060

8032016080

100400200100

120480240120

1286

362418

0000

1604530

21209060

318013590

4240180120

5300225150

6360270180

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Hemoglobin (gm/dl)

Oxygen Censumption (ml/min)

Oxygen Consumption related to HGB and Flow Rate

Sheet2

2 ml/kg/min

3 ml/kg/mn

1 ml/kg/min

HGB 6

HGB 8

HGB 12

Flow Rate (l/min)


Relationship: Oxygen Transfer and Hemoglobin and Flow rate (Capiox 18)

Sheet2

51.55245.82434.368

70.84862.97647.232

90.14480.12860.096

109.4497.2872.96

128.736114.43285.824

148.032131.58498.688

167.328148.736111.552

186.624165.888124.416

205.92183.04137.28

225.216200.192150.144

244.512217.344163.008

263.808234.496175.872

283.104251.648188.736

3.6

3.2

2.4

Hemoglobin (gm/dl)

Oxygen Censumption (ml/min)

Oxygen Consumption related to HGB and Flow Rate

Sheet3

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Flow Rate (l/min)


Oxygen Transfer of SX18 (HGB=12 gm/dl, SvO2=65%)

HCTHGBCaO2CvO2diffFlowFlowFlowHGBConsumpt

6231.316.9814.323.23.62.4245.82451.55234.368

9344.725.0219.683.23.62.4362.97670.84847.232

12458.133.0625.043.23.62.4480.12890.14460.096

15571.541.130.43.23.62.4597.28109.4472.96

18684.949.1435.763.23.62.46114.432128.73685.824

21798.357.1841.123.23.62.47131.584148.03298.688

248111.765.2246.483.23.62.48148.736167.328111.552

279125.173.2651.843.23.62.49165.888186.624124.416

3010138.581.357.23.23.62.410183.04205.92137.28

3311151.989.3462.563.23.62.411200.192225.216150.144

3612165.397.3867.923.23.62.412217.344244.512163.008

3913178.7105.4273.283.23.62.413234.496263.808175.872

4214192.1113.4678.643.23.62.414251.648283.104188.736

8612

241836

FLOWHCT

0000

1453060

29060120

313590180

4180120240

5225150300

6270180360

HCT 18

HGB 6

HGB 8

HGB 12

Flow Rate (l/min)


Relationship: Oxygen Transfer and Hemoglobin and Flow rate (Capiox 18)

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HCT 36

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Relationhsip between Flow Rate and Oxygen Transfer by Capiox SX 18 (HCT 24%, SvO2 =65%)

Arterial Flow RatesWhat can we measure to determine the adequacy of arterial flow rates?Venous PvO2 and SvO2Lactates DPCO2Arterial pressures

Venous PvO2 and SvO2Are PvO2 and SvO2 good markers of adequacy of perfusion?

Oxygen Consumption (VO2)Fick Equation VO2 = Q(CaO2 CvO2) = mL/min

Since 1971 it has been suggested that measuring venous saturations (SvO2) with a constant oxygen consumption(VO2), one can estimate the adequacy of CPB arterial flows (Q). Harris, Br. J. Anaesth. 43;1113:1971

Venous Saturation (SvO2)However, PvO2 or SvO2 does not mean that cellular oxygenation is satisfactory.If distant capillaries are not equally perfused, tissues may not get blood flow and as a result the PvO2 or SvO2 may actually increase mimicking a vascular shunt.Therefore PvO2 or SvO2 are useful and easy markers to measure but may NOT always related to adequate tissue perfusion.(Kirklin. Cardiac Surgery 1993, pg 81)

LactateIs serum Lactate a good marker of adequacy of perfusion?

LactateElevated blood lactate levels associated with metabolic acidosis are common among critically ill patients with systemic hypoperfusion and tissue hypoxia. This situation represents type A lactic acidosis, resulting from an imbalance between tissue oxygen supply and demand.

LactateLactate production results from cellular metabolism of pyruvate into lactate under anaerobic condition.

Therefore, blood lactate level in type A lactic acidosis is related to the total oxygen debt and the magnitude of tissue hypoperfusion.

Lactate and OutcomesAdult PatientsDemmers Ann Thorac Surg 70:2082-6:2000A peak blood lactate level of >4.0 mmol/L during CPB was identified as a strong independent predictor of mortality and morbidity and suggests that occult tissue hypoperfusion occurred during CPB.

Serum lactates vs Peds OutcomesPost-CPB (ICU) in ChildrenLactate (mmol/l)Mean (range)Status n 2.8 (0.6-19.6)Survived21510.6 (2.1-22.4)Died 18 9.8 (2.1-19.6)Multiorgan failure 10 9.0 (1.0-22.4)Neurological 23 complications

CONCLUSIONS: Postoperative morbidity and mortality is increased with higher lactate concentrations.Bernhardt Crit Care 5(Suppl B)13: 2001.

LactateProblemsLactate release into the blood does require blood flow. Therefore, the elevated levels may typically be identified later - post-operatively. (Perfusion 17;167-173:2002).Additional instrumentation is required for intra-operative measurements of lactate levels.The lactate/pyruvate (LA/PVA) ratios may be a superior method but requires additional analytical instrumentation

A-V PCO2 Gradient (DPCO2)Can the PCO2 gradient between arterial and venous blood gas samples (DPCO2) represent adequacy of perfusion?

A-V PCO2 Gradient (DPCO2)DPCO2 = PvCO2 PaCO2

The DPCO2 is an index to identify the critical oxygen delivery point (VO2/DO2).

The critical oxygen delivery point is when consumption (VO2) is dependent on delivery (DO2).

A-V PCO2 Gradient (DPCO2) It is now well established in experimental and clinical studies that critical oxygen delivery point is associated with an abrupt increase of blood lactate levels and a significant widening in DPCO2.

Since CO2 is 20x more soluble in aqueous solutions than O2, it is logical that DPCO2 may serve as an excellent measurement of adequacy of perfusion.

A-V PCO2 Gradient (DPCO2)Teboul. Crit Care Med 26;1007-1010:1998 Increasing cardiac output with dobutamine decreases DPCO2

ComparisonofDPCO2versusSvO2Warm1.7 L/m21.9 L/m2HGB = 9 g/dlArt. Press = 70 mmHg

Comparison of DPCO2versusTemperature and Flow Rate1.7 L/m21.9 L/m2HGB = 8 g/dlArt. Press = 60-70 mmHgn= 50 Adult CABG

Comparison of SvO2versusTemperature and Flow Rate1.7 L/m21.9 L/m2HGB = 8 g/dlArt. Press = 60-70 mmHgn = 50 Adult CABG

DPCO2 DPCO2 is a valuable parameter for determining the adequacy of CPB to a given metabolic condition. DPCO2 can help to detect changes in oxygen demand (e.g., the metabolic changes that accompany temperature changes, flow rates, and drug administration) DPCO2, together with SvO2, can help to assess the adequacy of DO2 to global oxygen demand and thus may help to assess perfusion adequacy.

Comparison of DPCO2 and SvO2CONCLUSIONS

SvO2 may reflect the metabolic rate of the patient during CPB.

DPCO2 may reflect the adequacy of tissue perfusion during CPB.

Adequacy of PerfusionFlowsPressuresTissue perfusionPressuresViscosity Vascular compliance


Arterial PressuresThe arterial pressures are a very important determinant of adequacy of perfusion during cardiopulmonary bypass.

However, what are the optimal perfusion pressures? (30, 40, 50, 60, 70, 80, 100 mm Hg)

Arterial Pressures - FactorsVascular toneAnesthetic agentsHemodilution (Hgb/Hct)Prime composition (viscosity)TemperaturePathological conditions (diabetes)Anatomic features: Bronchial blood flowPatent ductus arteriosus

Arterial Pressures

Flow Pressures = ResistanceWe have discussed the issues about arterial flow and now will discuss the factors related to vascular resistance.

Vascular ResistancePoiseuilles Law

Q = flow rate (cm3/s, ml/s)

P = pressure difference (dyn/cm2)

r = radius of the vessel (cm)

h = coefficient of blood viscosity (dyn-s/cm2)

L = length of vessel (cm)

Q = p DPr4 8 h lTherefore:Vascular resistance is related to: vascular tone, blood viscosity (HCT) at a given flow rate.

Vascular ResistanceAutoregulation of vascular resistance.Different organs display varying degrees of autoregulatory behavior. The renal, cerebral, and coronary circulations show excellent autoregulation. The skeletal muscle and splanchnic circulations show moderate autoregulation. The cutaneous circulation shows little or no autoregulatory capacity.

Normal AutoregulationDrop in arterial pressuredue to institution of CPBRestoration of blood flow

AutoregulationAt normothermic conditions in normal individuals, autoregulation is preserved at pressures between 50 150 mm Hg.

Under profound hypothermia in normal individuals conditions autoregulation threshold may be as low as 30 mm Hg. Govier Ann Thorac Surg 38;592-600:1989

AutoregulationAutoregulation of blood flow for the heart, kidney, and brain can be uncoupled by vascular disease and diabetes. In the diabetic, cerebral artery perfusion flow is completely dependent upon perfusion pressures!Therefore, perfusion pressures need to be maintained at 65-80 mm Hg to provide adequate cerebral blood flow.Pallas, Larson Perfusion.11;363-370:1996

Normal VasorelaxationNOSRelaxationPaCO2AcetylcholineHypoxiaADPNOVascularEndothelial CellVascularSmoothMuscle Cell

NO is nitric oxide

Diabetic VasorelaxationNOSRelaxationPaCO2AcetylcholineHypoxiaADPNOVascularEndothelial CellVascularSmoothMuscle Cell

ThickenedBasementMembraneReduced NOSynthesisUncoupledautoregulation in diabetic vasculaturePallas, Larson Perfusion.11;363-370:1996

Arterial PressuresTherefore, arterial pressures are coupled to arterial flows.More importantly arterial pressures need to be managed independently to assure adequacy of perfusion of critical organs such as the brain especially in the patient with vascular pathology.

DO2 (Oxygen delivery) versus Hct3 ml/kg 2 ml/kg Through increasingDO2 withflow rateorhematocrit-the VO2 demandcan be achieved.VO21 ml/kg

HematocritTherefore, the coupling between hematocrit and arterial flow rate has been established to provide adequate DO2.The optimal hematocrit is 27% however with a lower hematocrit the flow rate must be increased to provide adequate DO2 to meet the patients VO2.

Oxygenation (PaO2)What are optimal PaO2sOxygen content in the blood is mainly dependent upon the hematocrit and the percentage of saturation of the hemoglobin. Once the hemoglobin is 100% saturated, normally at a PO2 of 120 mm Hg, increasing the PO2 provides minimal increases in oxygen content of the blood.What hasnt been proven is if high PaO2s induce pathological changes during CPB.

PaCO2PaCO2s have a marked effect on the pH, HCO3-, hemoglobin saturation and most importantly cerebral circulation.

All data suggests that it is justifiable to keep the PaCO2s within a physiological range of 35-40 mm Hg during normal CPB procedures.

ConclusionFlow rates1.8 L/min/m2 adult2.4 L/min/m2 in the pediatrics?? In the agedPressures> 50 mm Hg except higher in the diabeticHematocrit 24-28%, may be higher in the agedPaO2 >120 mm HgPaCO2 35- 40 mm Hg

Systems PatientVenous blood gasesVO2Vascular resistanceAnesthesiaPatient disease

Heart-lung MachineArterial blood gasesDO2Arterial flowsVentingTemperature Hematocrit AnticoagulationShared

New IssuesPatient disease: diabetes, peripheral or carotid vascular diseasePatient age (senescent)We have no protocols for perfusion of the aged patient. It is known that their physiology is as different as infants are compared to adults.

New IssuesPatient age (senescent) The risk of major complications is 14% to 24% in 80 to 90 yo.

Neurological ProblemsThe neurological problems associated with bypass surgery have been widely reported. As much as 6 percent to 10 percent of bypass patients will experience memory loss, visual changes, or even stroke. These outcomes are partly due to "debris" lining the aorta that may break off during surgery.

Neurological ProblemsThe most important risk factors for brain injury after cardiopulmonary bypass surgery are aortic atheromatosis and cardiac lesions that pose a risk for brain embolism.Aortotomy, or cross clamping of the aorta to anastomose vein grafts, discharges cholesterol crystals and calcific plaque debris.The frequency of aortic atheromas increases dramatically with age, from 20% in the fifth decade at necropsy to 80% in patients older than 75 years. Archives in Neurology.58; April 2001

Neurological ProblemsCorrespondingly, the stroke rate after coronary artery bypass graft (CABG) also increases sharply with age from 1% in patients aged 51 to 60 years to 9% in patients older than 80 years. Barbut D, Caplan LR. Brain complications of cardiac surgery. Curr Probl Cardiol. 22:447-476:1997.

Neurological ProblemsPlacement of the arterial cannula into the axillary artery, a branch of the aortic arch provides direct blood flow to the the brain. This innovative approach significantly reduced the flow of emboli (debris) to the brain. University Hospitals of Cleveland, Dec-2002

MIXED VENOUS OXYGEN SATURATION (SvO2)Fick's equation: SvO2 = SaO2 -VO2 / 13.9 x Q x [Hb]The normal SVO2 is 75%, which indicates that under normal conditions, tissues extract 25% of the oxygen delivered. An increase tissue oxygen extraction (VO2) or a decrease in arterial oxygen content (SaO2 x Hb) can be compensated by increasing arterial flow rates .

MIXED VENOUS OXYGEN SATURATIONFick's equation: SvO2 = SaO2 -VO2 / 13.9 x Q x [Hb]When the SVO2 is less than 30%, tissue oxygen balance is compromised, and anaerobic metabolism ensues. A normal SVO2 does not ensure a normal metabolic state but suggests that oxygen kinetics are either normal or compensated.

DefinitionsCaO2 =(SaO2 x Hgb x 1.34) +(PaO2 x 0.003)CvO2 =(SvO2 x Hgb x 1.34) +(PvO2 x 0.003)DO2 = CI x CaO2 x 10VO2 = CI x (CaO2 - CvO2) x 10DPCO2 = PvCO2 PaCO2

LactateTissue hypoperfusion with lactic acidosis during CPB may occur despite normal blood gas concentrations. High blood lactate levels during CPB may be used as a marker of inadequate tissue oxygen delivery. Therefore, lactate is a sensible marker of the magnitude of anaerobic metabolism and tissue oxygen deficit.

LactateUnder anaerobic condition, oxidative phosphorylation is not possible and ATP is produced from pyruvate metabolized into lactate. Anaerobic glycolysis results when there is an imbalance between systemic oxygen delivery and tissue oxygen consumption, producing a type A lactic acidosis. The normal lactate/pyruvate ratio (10:1) and under anaerobic conditions this ratio increases.

LactateSystemic microvascular control may become disordered in non-pulsatile CPB resulting in peripheral arteriovenous shunting and a rise in lactate levels despite an apparently adequate oxygen supply. Extreme hemodilution, hypothermia, low-flow CPB, and excessive neurohormonal activation have also been linked to lactic acidosis during CPB

adequacy of perfusion during cardiopulmonary bypass

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