Pediatric Perfusion Gerald Mikesell, CCP Childrens National Medical Center Washington DC Fundamental Goals of CPB To facilitate a surgical intervention Provide a motionless field Provide a bloodless field Supply adequate substrate for the metabolism of all tissues Remove unwanted byproducts of metabolism Minimize the deleterious effects of bypass The Cardiovascular Perfusionist The perfusionist controls the patients blood flow, blood pressure, and gas exchange as well as monitoring and delivering anticoagulation and protective heart medications Differences Between Adult and Pediatric Cardiopulmonary Bypass Major differences exist between adult and pediatric cardiopulmonary bypass (CPB), stemming from anatomic, metabolic, and physiologic differences in these 2 groups of patients. Cardiopulmonary Bypass Generalized inflammatory reaction Capillary Leak Cardiac dysfunction Organ dysfunction/MSOF Mortality CPB Deleterious Effects Coagulopathy Platelet dysfunction/ consumption Coagulation factor consumption Cellular destruction/Hemolysis Systemic heparinization Hemodilution of factors Mechanical stress Inflammatory Activation Mechanical stress Non-endothelial exposure Complement activation Cytokine and leukocyte activation White cell activation Effects of CPB All the discussed effects of bypass are related to exposure to our circuits and the mechanical devices used to allow bypass to procede Total bypass time continually emerges as a risk factor for morbidity and mortality Optimal outcome is benefited by surgeons operating accurately and rapidly, using efficient sequencing of repair Bypass Management No perfect means to measure level of support Normal monitoring: EKG, NIRS, Saturations and Pressures are designed for non-bypass monitoring With bypass, loss of normal physiologic homeostatic control, loss of pulsatility, change of oxygen supply, hemodilution Venous Saturation Measurement Though looked to as a standard of perfusion adequacy, there are limitations Cooling causes left shift of oxyhemoglobin dissociation curve Cooling causes increase of pH Fetal Hemoglobin in neonates Alkaline blood also causes left shift of oxyhemoglobin curve Left shift of curve Lower levels of 2,3DPG in bank blood also cause left shift Therefore, as temperature of blood drops, venous saturation will rise but brain and tissues are still warm and not receiving the O2 needed to meet metabolic demand Venous Saturation Measurements Left Heart Return and collateral steal Dangerous to assume all flow pumped into patient is going where planned. Colleteral development with some lesions can steal up to 50% of flow and return directly to venous return Collaterals to pulmonary veins to LA across unrepaired ASD,VSD to venous cannula Differental return flow from SVC vs IVC Warm brain uses lots of O2 and SVC with low sat but Systemic blood colder, IVC with higher sat, blood mixes in venous line and sat monitor reading appears fine Bypass Management We do things to exert control of the patient on CPB and work to maintain a margin of safety for the patient even if all parameters aren’t perfectly controlled. The important decisions that we can control: Temperature pH Hematocrit Perfusion flow Temperature Advantage: Reduce Metabolic Rate Tissue preservation Myocardial preservation Allows flow variation to improve surgical access Flexibility in cannulation Decreased inflammatory response to CPB Decreases Complement activation and release of vasoactive substance Decreases white cell activation Temperature Disadvantages: Prolongs bypass Increases probability of post-operative bleeding Possible prolonged post-operative recovery Especially in adults Use of Hypothermia Effect on Central Nervous System The effect of hypothermia on the nervous system is multifactorial. In addition to decreasing the metabolic rate, hypothermia has been demonstrated to decrease the release of glutamate, which is involved in CNS injury during CPB. A negative effect of hypothermia on brain function is the loss of autoregulation at extreme temperatures, which makes the blood flow highly dependent on extracorporal perfusion. Techniques of Hypothermia Currently, two surgical techniques commonly used in congenital heart surgery, namely, Deep hypothermic circulatory arrest (DHCA) Hypothermic low-flow bypass (HLFB) Deep Hypothermic Circulatory Arrest DHCA provides excellent surgical exposure by eliminating the need for multiple cannulas within the surgical field. Normally use arterial cannula and a single venous cannula in the right atrium. Surgical technique Initiate the cooling phase prior to institution of CPB by simple cooling of the operating room environment and begin surface cooling the patient After systemic heparinization and cannulation, initiate CPB. Monitor body temperature via esophageal, tympanic, and rectal routes. Have also seen less edema. Deep Hypothermic Circulatory Arrest Disadvantages: Time constraints on the surgical team. Must be highly organized with the repair and efficient with technique. Precise and accurate repairs must be completed in limited time. Deep Hypothermic Circulatory Arrest Late 1980’s study out of Boston Childrens looking at DHCA vs low flow in arterial switch patients Both groups with deep hypothermia and hematocrit of 20% One group had circulatory arrest, the other group a low flow of 50 mL/kg/min Patients have now been followed for 20+ years CA patients had lower verbal and development scores until age 4. Caught up with developmental scores by age 4 and by age 8 caught up with verbal. Both groups were below mean controls. If longer periods of arrest are anticipated, may be advantageous to apply ancillary procedures such as intermittent reperfusion. Deep Hypothermic Circulatory Arrest Mechanical Problems Arterial cannula misplacement can occur. If the cannula inadvertently slips beyond the takeoff of the right innominate artery, preferential perfusion to the left side of the brain can be observed. Presence of any anomalous systemic-to-pulmonary shunts can lead to shunting of blood away from the systemic circulation, through the pulmonary circuit, and then through the venous cannula returning to the CPB circuit. Thus, the systemic perfusion is shunted away from the body in a futile circuit back to the CPB circuit. Anatomic lesions where such shunting can occur include an unrecognized patent ductus arteriosus and large aortopulmonary collaterals as found in pulmonary atresia. Effect of pH pH and pCO2 have strong systemic and cerebral vasodilatory effects Effects are opposite with pulmonary circulation Shift in pH or pCO2 can cause a marked shift in blood flow between pulmonary and systemic beds A-P collaterals or systemic to pulmonary shunts (B-T shunt for example) need to be considered Effect of pH Perfusionist important to acid-base control during CPB Flow rate Dilution Hypothermia As temperature drops, pH of H2O increases Effect of pH Alpha Stat vs pH Stat: First studies in the 1980s Alpha Stat Maintains optimal intracellular enzyme activity Maintains cerebral auto-regulation and the coupling of flow and metabolism at low temperatures In adults, showed improved cognitive outcome Possibly related to reduced number of micro-emboli pH Stat: Loss of cerebral auto-regulation as temperature drops Cerebral flow is pressure dependent, could cause “luxuriant” flow with the potential for increased micro-emboli Effects of pH Boston Childrens Hospital did multiple studies, both clinical and animal, in the late 1980’s Alpha stat patients had worse developmental outcome during cooling than pH stat. There was strong correlation during cooling of pCO2 and developmental outcome The circulatory attest time of 35-60 minutes had no impact With alpha stat patients, there were 19 cases of choreoathetosis in 4 years/ With pH stat, there were none In lab studies with piglets, found that cerebral microcirculation was better in pH stat piglets vs alpha stat Effect of pH In 1990’s Boston Childrens completed two randomized clinical studies which both showed better outcomes with pH stat pH stat had lower mortality (p=0.058) pH stat, with continuous EEG monitoring during surgery and 48 hours post bypass, show lower rate of post-op seizures pH stat: First EEG activity returned faster after circulatory arrest pH stat: Decreased post-op acidosis (p=0.02) pH stat: Decreased post-op hypotension (p=0.05) Effect of pH Boston pH vs Alpha stat clinical studies (Cont) pH stat: Shorter mechanical ventilation time and ICU stay (p=0.01) pH stat: in d-TGA sub-group, higher cardiac index with lower inotrope requirement pH stat: A trend to better developmental scores at 1 yr of age Effect of pH Boston study: Conclusion was pH stat: Suppresses cerebral metabolism and lengthens safe duration of DHCA for a given temperature and hematocrit Improves oxygen availability by counteracting the oxy-hemoglobin curve’s leftward shift with dropping temperature Very important in early cooling period when blood is cold but brain still warm Improved developmental outcome pO2 and Bypass Historically feeling that hyperoxia was responsible for microemboli associated mobidity post CPB A problem with bubble oxygenators, especially without arterial filters Two studies in piglets at Boston Childrens in 1999 looked at this issue Compared bubble oxygenator vs membrane oxygenator with arterial filter Compared normoxia with hyperoxia and DHCA Compared free radical production Compared histological injury of normoxic vs hyperoxic pO2 and Bypass Study Results: At cold temperatures there was increased microemboli with bubble oxygenator vs membrane oxygenator with filter As temperature was dropping, there were more microemboli with normoxia vs hyperoxia Reasoned that nitrogen was less soluble in the blood than oxygen as the temperature dropped Looking at histological injury, there was significantly more injury in the brains of normoxic animals vs hyperoxic animals after 120 minutes of arrest at 15 deg C An interesting observation was that temperture gradient both cooling and warming had no effect on microemboi Bypass and Optimal Flow The standard bypass flow target has always been 2.4 L/min/m² Must weigh all the options: Normal may be as much as 3.5-4 L/min/m² Hemodilution can add up to 3-4 times greater flow demand to meet O2 demand Add aorto-pulmonary collaterals with 50% of pump flow returning directly to the pump. Leaves an effective flow of 1.2 L/min/m² Potential for hypoxic injury Bypass and Optimal Flow Flow considerations for bypass: What is the metabloic demand for different temperatures Normal thermia Mild hypothermia: temperature greater than 30ºC Moderate hypothermia: temperature 25-28º C Deep hypothermia: temperature less than 18ºC CPB Flows • 2.4 -3.0 at • 1.6 l/ m2 at 28o • 1.2 – 1.6 l/m2 at 25o • 1.0 – 1.6 l/m2 at 20o 2 o • 0.5 – 1.0 l/m at 15 2 l/m o 37 Hemodilution Decreased concentration of cells & solids in the blood RBC’s, WBC’s, Platelets, Plasma Proteins, Clotting factors, Lytes (Ca,Mg) Is hemodilution bad? May allow better perfusion as temperature drops Causes a drop in O2 delivery Prime Volumes Adult 30% of blood volume blood volume prime volume 23% of total volume Hct 35% 27% Pediatric 50% of blood volume blood volume prime volume 33% of total volume Hct 35% 23% Infant 176% of blood volume blood volume prime volume 63% of total volume Hct 40% 14% Hemodilution On bypass and before cooling, O2 demand still high flow not compensated Thought to be related to drop in perfusion pressure Perfusion pressure change in direct proportion to change of viscosity with hemodilution If hemodilution not on bypass, body compensates by increasing cardiac output Hemodilution vs Cerebral Protection 1996 study by Shinoka et al, in JTCVS. Working with piglets looked at 3 levels of hematocrit, 10,20 and 30%; went on bypass and cooled to 15ºC and arrested for 60 minutes. Low hematocrit piglets had worse neurological outcome, both physiologically and histologically. Lowest hematocrit piglets showed hypoxic stress during cooling and before arrest Hemodilution vs Cerebral Protection 2001 Study by Sakamoto et al looked at the interaction of hematocrit (20 and 30%), pH (alpha stat vs pH stat) and temperature on the neurological impact of piglets Lower hematocrit, more alkaline pH and longer circulatory arrest were predictive of neurological damage Hematocrit: 30% showed distinct advantage to neuroprotection vs 20% pH stat was more neuro-protective with lower histological injury vs alpha stat A temperature of 15ºC was more neuro-protective than a temperature of 25ºC Study looked at circulatory arrest times of 60, 80 and 100 min Hemodilution vs Cerebral Protection 2001 a companion study by Duebener et al looked at microcirculation (capillary blood flow) and at tissue oxygenation with hematocrits of 30% vs 10%. 30% was associated with improved re-perfusion (functional capillary density) vs 10% There was no evidence of capillary plugging or white cell activation with the higher viscosity level of the 30% hematocrit Hemodilution vs Cerebral Protection 2002 Study by Jonas et al, JTCVS. The Influence of Hemodilution on Outcome After Hypothermic CPB: Results of a Randomized Trial in Infants 147 patients randomized to a hematocrit of 21 (74) or 27 (73) Hematocrit 21: post-operative serum lactate was higher, cardiac index was lower and had greater total body water at POD1. Blood product usage was the same for both groups Baley Scales of Infant Development: at 1 year the high hematocrit group had higher Psycomotor Development Index (low hct group was 2 SD below normal populations) , there was no difference in Mental Development Index Showed that a hemodilution practice thought to be safe was associated with adverse perioperative and developmental outcomes in infants Hemodilution and Bypass Hemoconcentration During bypass Conventional Modified MUF Ultrafiltration Hemodilution and Hemoconcentration Conventional Removes free water, dissolved ion and small molecules Remove byproducts of bypass and excess volume, i.e. cardioplegia after delivery Maximize hematocrit before termination of bypass We like to come off with hct of 30-35 or even 35-40 with single ventricle repairs Modified Ultra-Filtration (MUF) Hemoconcentration of patients circulating blood volume along with remaining volume in circuit Improvement with CO and blood pressure Disadvantages are the need to maintain heparinization and cannulation for extended time and… Complexity of circuit and risk of air around arterial cannula Myocardial Protection Strategies Myocardial Protection The term "myocardial protection" refers to strategies and methodologies used either to attenuate or to prevent postischemic myocardial dysfunction that occurs during and after heart surgery. Principles of Myocardial Protection The main principles of myocardial protection are the reduction of metabolic activity by hypothermia the therapeutic arrest of the contractile apparatus and all electrical activity of the myocytes by administering cardioplegic solution (e.g. depolarizing of the membrane potential by high potassium crystalloid or blood cardioplegia) CARDIOPLEGIC TECHNIQUES Cardioplegic solutions contain a variety of chemical agents that are designed to arrest the heart rapidly in diastole, create a quiescent operating field, and provide reliable protection against ischemia/reperfusion injury. There are two types of cardioplegic solutions: crystalloid cardioplegia extracellular intracellular blood cardioplegia. These solutions are administered most frequently under hypothermic conditions. CARDIOPLEGIA DELIVERY SYSTEM Purpose = arrest and preservation Two types of delivery crystalloid cardioplegia: no blood added blood cardioplegia: blood is mixed with crystalloid) proposed advantages: oxygen, buffers, proteins Cardioplegia Delivery Antegrade Retrograde Directly to coronary Cases CNMC Cardioplegia Delivery 2-3o C Conducer Recirculation System Plegisol (Oxygenated) First dose 20 ml/kg Following doses 10 ml/kg Above 50 kg 1000 ml With 500 ml second dose Blood Cardioplegia at CNMC Use a modified Plegisol recipe. Potassium is added with a high K and low K formulation. Cardioplegia is delivered 4:1 blood:crystalloid. High K: 20 mEq/L Low K: 10 mEq/L First dose is high K then switch to low K for redosing Hemodilution and Prime 1985 study by Haneda et al, compared crystalloid prime vs blood and plasma prime in pediatrics Crystalloid prime patients had a +63 mL/kg fluid balance vs + 16 mL/kg with blood/plasma Blood/plasma prime group had a lower mortality and 50% reduction in ICU time compared with the crystalloid group There is a general consensus that prime for children should not include lactate or dextrose. Hyperglycemia is associated with a worse neurological outcome. Prime used at Childrens National Medical Center Circuit primed with Plasma-lyte A, excess drained off Packed Cells between 3-7 da old Try to maximize 2,3-DPG and have lower K+ Units are leuco-depleted in the blood bank Primary unit of RBC is divided, half for perfusion for prime and half for anesthesia to use post bypass so donor exposure can be reduced FFP: Same donor as RBC when possible We use some of the unit in the prime, add some to the circuit while rewarming and any remaining goes to anesthesia post CPB. If using clear prime, will add 100-300 mL 25% Albumin CNMC Prime Cefazolin: 25 mg/kg, (1 gm maximum dose) Lasix: 0.25 mg/kg Mannitol 25%: 0.5 gm/kg (12.5 gm maximum dose) Feel a loop diuretic is helpful to maintain renal function Potent osmotic diuretic with free radical scavenger properties Add to prime, some also give a second dose on release of cross clamp Heparin Sodium Bicarbonate 84% Solumedrol: 30 mg/kg Patients ˂ 1 week and DHCA patients CNMC Bypass Magnesium Sulfate: 50 mg/kg (1 gm maximum) Given immediately after cross clamp release Has significantly reduced incidence of junctional ectopic tachycardia ( JET) Calcium Gluconate: 500 mg-1 gm Given 5 minutes after release of cross clamp Current Primes CNMC 250-300 Neonates 300-400Infants 400-600 Toddlers Blood product use for CPB Hemodilution from pump prime Volume expansion Treatment of iatrogenic or concomitant coagulopathies Surgical blood loss Descending order of incidence PRBC Transfusion Hematocrit On CPB < 27% Post CPB < 27% This is patient dependent: size and lesion Oxygenation SVO2 < 65% at maximal flow on bypass Hemodynamics Acute blood loss FFP Transfusion Coagulopathies Obvious non surgical bleeding Long pump runs Hemodilution Preexisting conditions Heparin resistance Inadequate ACT despite 2X normal Heparin Dose “Fast” easy source of ATIII Platelet Transfusion Triggers Coagulopathies Obvious non surgical bleeding Long pump runs Hemodilution Preexisting conditions DHCA patients Low platelet count < 70,000 How do we achieve low prime circuits Get mind set Look at circuit as separate components Be willing to use different venders Must modify perfusion techniques Must be adaptable Constantly update equipment & techniques Our goal with bypass is reduce the surface area of exposure of the patient’s blood to our circuits. We can accomplish this goal through our selection of circuit components and cannulae and the use of techniques such as bio-passive circuit coatings to attenuate the response of our patients to bypass Tubing 2/32" I.D. 0.6ml/ft. 3/32" I.D. 1.8ml/ft. 1/8" I.D. 3.5ml/revolution(2.5 ml/ft.) 5/32" I.D. 5ml/revolution(3.7 ml/ft.) 3/16" I.D. 7ml/revolution(5 ml/ft.) 1/4" I.D. 13ml/revolution(9.65 ml/ft.) 5/16" I.D. 18ml/revolution(13.5 ml/ft.) 3/8" I.D. 27ml/revolution(21.71 ml/ft.) 7/16" I.D. 38ml/revolution(28.5 ml/ft.) 1/2" I.D. 45ml/revolution(38.61 ml/ft.) 5/8" I.D. 65ml/revolution(55.77 ml/ft.) Arterial Lines 3/16” 1200 ml/min 1/4” 2500 ml/min 3/8” 7000 ml/min Venous Lines 3/16” 600 ml/min 1/4” 1500 ml/min 5/16” 2200 ml/min 3/8” 4000 ml/min 1/2” >7000 ml/min A-V LOOPS CNMC Flows 0-1 L/min 3/16 x 1/4 Flows 1 – 1.5 L/min 1/4 x 1/4 Flows 1.5 – 2.5 L/min 1/4 x 3/8 Flows 2.5 – 4.0 L/min 3/8 x 3/8 Flows > 4.0 L/min 3/8 x 1/2 Oxygenators New Oxygenators specific for infants and pediatrics Reduced volume Arterial flilters incorporated in design Improved flow dynamics Reduces prime of circuit (??) Reduced pressure drop Improved reservoir design with improved drainage and volume handling VAVD capable Most common Maquet Terumo Medtronic Sorin Medos VENOUS RESERVOIR Two types of venous reservoirs hardshell venous reservoir “open” system collapsible bag venous reservoir “closed” system VENOUS RESERVOIRS HARDSHELL VS. BAG Arterial Blood Gas Control Blender and Gas Flowmeter Carbon Dioxide Anesthesia - Forane Arterial Blood Gas Control Anesthesia: Forane CDI500 On-line arterial blood gas, hemoglobin/hematocrit, K+ and venous saturation Cannula Selection Arterial Important component of the circuit as it’s a point of narrowing in the pressurized limb of the bypass circuit A point of increased flow velocity and potential high sheer stress and increased hemolysis Want largest cannula possible for expected flow but not large enough to obstruct vessel lumen preventing retrograde flow around the cannula Other factors include: thin wall, tolerate temperature variations without kinking or stressing aorta when cold Ease of insertion VENOUS CANNULA Two types of venous cannulation procedures right atrial cannulation single RA cannula: through the RA appendage; tip in body of the RA cavo-atrial cannula (or two-stage cannula): through the RA appendage; tip in the IVC and “basket” in the body of the RA used when the heart IS NOT going to be opened vena caval cannulation one cannula through the RA appendage into the IVC a second cannula through the RA wall into the SVC used when the heart IS going to be opened a tie encircling the IVC and SVC is secured Cannula Selection Venous Essential for surgeon to have a cannulation plan based on the defect to allow for optimal venous return and perfusion of the entire body throughout the procedure Cannulation must not interfere with appropriate sequencing of operative steps A balance of a size large enough to meet flow demands and small enough to be accommodated with a particular defect Right angle vs straight Develop flow tables for cannulas ( and for each surgeon) Cannulas Venous Drain blood from the body 2 stage Bicaval Femoral Arterial Return blood to the body Aortic Femoral THE SUCTION SYSTEM Purpose = evacuate shed blood Usually ¼” I.D. tubing Requires an occluded roller pump This blood directed to the cardiotomy reservoir filters any fluid to 19-35 microns open system: cardiotomy integral with venous reservoir closed system: cardiotomy is separate from venous reservoir blood, priming fluids, blood components VENT (or sump) SYSTEM Purpose = evacuate LV blood sources of LV blood right atrium escaping the venous cannula bronchial venous blood non-coronary collateral blood Usually ¼” I.D. tubing Usually requires an occluded roller pump requires a negative pressure relief valve This blood directed to the cardiotomy reservoir SAFETY SYSTEMS Reservoir level detection Air bubble detection (arterial line) Arterial line pressure Safety Systems Flow Meter: Distal to all shunts to give more accurate flow delivery to the patient Safety Systems Level and air sensors Safety Systems Pressure Monitoring Cardioplegia delivery pressure Arterial line pressure Cardiopulmonary bypass… Do you ever wonder….How does it affect your patient?