Reprinted: Vinas, M.S., Chapter 3 "Extracorporeal Circulation," Kambam, J., Editor, Cardiac Anesthesia for Infants and Children, the C.V. Mosby, Co., St. Louis, MO, 1994

The application of extra-corporeal circulation (ECC) was pioneered by the experiments of Dr. Jack Gibbon in 1934 at Massachusetts General Hospital. However, it was not until 1953 that the first successful human open-heart procedure, closure of an atrial septal defect, was performed by this surgeon on a young female patient (Bone).

It is estimated that there are 750,000 cardiopulmonary bypass (CPB) procedures performed annually in the United States. Of this number approximately 6% involve infant/ pediatric cardiac surgical intervention (AHA).

A 1990 Pediatric Perfusion survey cited a 127 responses from community, government and university medical centers performing infant/ pediatric open-heart surgery. The centers reported performing 14,473 open-heat surgery (OHS) procedures requiring extra-corporeal circulation (Hill). Stammers and Riley compiled data on over 1016 infant/ pediatric treated with cardiopulmonary bypass (CPB) at University of Michigan Hospitals, between 1986-1990, 869 were able to be placed into sixteen categories. The majority of the surgical procedures consisted of the following:

INFANT/ PEDIATRIC SURGICAL PROCEDURES/ PERCENTILE

The application of extracorporeal circulation requires careful assessment of hematologic values and the effects of hemodilution and hypothermia. All attempts should be made to design an accommodating extracorporeal circuit while minimizing, preferrably eliminating, blood product requirements.

HEMOGLOBIN/ HEMATOCRIT

The hemoglobin in infant and pediatric patient's has been surveyed and reported between the ranges of 12.5-22 gm./dL (Hartley-Winkler). Hemodilutional calculations, however, are predicated on hematocrit values.

AGE HEMOGLOBIN VALUES
1 Day 18-22 GM/DL
2 Weeks 17  GM/DL
3 Months 10  GM/DL

3-5 Years 12.5-13 GM/ DL

A non-haemic or asanguinous prime of the heart-lung console circuit may dilute an infant with a standard hematocrit to a calculated value less than 15%, a polycythemic individual not as critical. It is the cardiovascular perfusionist's responsibility to estimate, via calculations, the degree of hemodilution and any blood products requirements needed to adjust the hematocrit to a value of 20-30% or greater during ECC.

Non-haemic primes with circulating hematocrit's of 13-18% have been reported (Berryessa, Conley, Hartley- Winkler, McCormick, Stammers). Our hemodilutional protocol requires a 30% packed cell volume (PCV) during ECC for infants, a 25% PCV for pediatric patients. To augment the hematocrit during ECC, an online ultrafilter may be integrated into the circuit (Han, Molina, Tamari). Ultrafiltration, in the infant/ pediatric circuit, promotes the elimination of excessive extra-cellular solutions less than 17,000 Daltons at a maximum rate of 10-30 ml./min. (Minntech). The hematocrit at the termination of ECC should average 25-30% or greater to enhance available oxygen carrying capacity. 

Plasma normally comprises 55-65% of the estimated blood volume. A 3.0 kilogram infant, for example, may have a plasma volume of 180 ml. A 700 ml. non-plasma prime would dilute the respective clotting factors, fibrinogen and platelets below 20%, which is inadequate for proper hemostasis. The plasma volume in infants/ pediatrics should be calculated to assess hemodilution of these factors, with the possibility of adding fresh frozen plasma (FFP) to the extra-corporeal circuit. 

HEMODILUTION/ TARGET HEMATOCRIT 

Infant and Pediatric patients have a higher blood volume factor than the adult, this value decreases with human development. Institutionally we have adopted the following blood volume factors:

PATIENT AGE BLOOD VOLUME

Several calculations are required to assess hemodilution and blood product requirements. The following depicts a patient with a weight of 10 kilograms, blood volume factor of 85 ml./Kg., hematocrit of 40% (HCT1) and an ECC priming volume of 700 ml. The resultant calculations will estimate the patient's blood volume (PBV), patient red cell volume or mass (RCM1), total system or ECC circulating volume (TSV), hemodilutional hematocrit (HCT2) and hemodilutional or ECC circulating red cell mass (RCM2) required (Vinas):

HEMODILUTIONAL CALCULATIONS

125 ml. RCM is required to be added to the ECC prime to achieve a circulating hematocrit of 30%. The relative body size, compared to the perfusate, required to prime the extra- corporeal circuit, will cause a neonate or infant to be more adversely affected by hemodilution than a pediatric.

FIBRINOGEN

A critical consideration is plasma fibrinogen dilution. Normal plasma fibrinogen levels are 150-400 mg./dL (Ecklund). The infant/ pediatric patient's relative low blood volume with priming requirements of the ECC circuit causes the fibrinogen concentration to be adversely diluted. During CPB, it is desirable to maintain the plasma fibrinogen concentration above 100 mg./dL. in order to prevent impairment of post-ECC hemostasis (Ecklund, Pfefferkorn p. 61, Taylor p.274).

Given an example of a 10 Kilogram patient with a patient blood volume of 850 ml., a pre-bypass hematocrit of 40%, fibrinogen level of 250 mg./dL. and a 700 ml. ECC prime volume, additional fibrinogen via FFP is needed. Given the previous parameters mentioned, the calculation of fibrinogen dilution, and subsequent reconstituting, would be calculated as follows:

The calculated fibrinogen value derives a deficit of 18 mg./dL. x 15.5 = 279 mg. If Fresh Frozen Plasma, diluted with CPD-A contains 200 mg./ 100 ml. (dL) of Fibrinogen, an additional 140 ml. of fresh frozen plasma should be administered to raise the circulating level to 100 mg./dL (Pfefferkorn pp. 61-62).

PLATELETS

Platelet concentration values range from 150,000-400,000/ cu. mm. (Reed and Stafford p.127). The classification of thrombocytopenia is given to levels less than 100,000/ cu. mm.. Levels below this value may result in prolonged bleeding times (Orland p. 273).

Blood exposure to the foreign components of the extracorporeal circuit may deplete platelet concentrations. This phenomenon may be observed in electron photomicrographs of the arterial filter and blood reservoirs. Albumin, added to the ECC prime, reduces platelet aggregation on these foreign surfaces thus minimizing loss to the circuit components (Gurjar, Hedlund). Platelet reconstitution, if indicated, should be reserved until post-bypass in order to optimize the effects of the platelets and their effect on hemostasis.

CRYSTALLOID SOLUTIONS

In the event that crystalloid priming solutions are administered they should be pH balanced and isotonic. The electrolyte composition should approach the values of normal blood chemistries to ensure normal electrolyte levels. Calcium Chloride may be added to solutions that do not contain the electrolyte to a value of 10 mg./ dL or 100 mg./L. Blood chemistries such as Sodium, Potassium, Magnesium, Chloride, Glucose, Total Protein, Total and Ionized Calcium along with hematologic values should be monitored every 20-30 minutes during cardiopulmonary bypass. Patient's with relatively high potassium levels, renal failure for example, should not be administered potassium containing solutions, at least caution is advised. 0.9% Sodium Chloride solutions, buffered to a pH of 7.4, may be substituted. Lactated Ringers solution should not be administered to patients exhibiting clinical signs of lactic acidosis.

ALBUMIN/ PLASMA ONCOTIC PRESSURE

Of the plasma proteins albumin exerts the main influence on oncotic pressure which is 25 mm. Hg. The average albumin molecule has a molecular weight of 69,000 and is half the size of the average globulin molecule (Berne p.147). The colloid osmotic or oncotic properties of protein balances hydrostatic and oncotic pressure gradients across the capillary walls. Normal COP is approximately 20-25 mm. Hg. Values below 17 mm. Hg. may lead to pulmonary edema. COP levels approaching 15 mm. Hg. have been observed without incidence during CPB (Beshere).

"Third spacing", the migration of intravascular fluid into the interstitum causing edema should be realized as a possibility during ECC, especially in the infant and pediatric populations. This phenomenon may be deterred by the use of an isoncotic (protein) priming solution. Reductions of the COP by 30-60% during ECC have been reported without chronic complications in the adult patient (Beshere).

Pediatric patients, not requiring packed red blood cells, or fibrinogen via FFP may be administered an isotonic physiologic solution such as Plasmalyte-A, Normosol, or Lactated Ringer's, however, the protein dilution should be considered (McCormick). Each ml. of 12.5 gms., 25% Albumin is oncotically equivalent to five times its volume of normal human plasma (American Red Cross). 50 ml. of 25% Albumin may be included to reconstitute each 250 ml. of crystalloid perfusate to an isoncotic solution.

Total serum protein levels range between 6.0-7.8 gm./dL, Albumin levels 3.2-4.5 gm./dL (Tilkian). Acceptable total protein levels of 4.0 gm./dL have been reported during cardio-pulmonary bypass. Total serum protein levels should be carefully monitored during I.V. albumin administration to ensure isoncotic levels. The following formula may be used is for correction of an oncotic deficit if the total serum protein (TSP) level, in gm. dL, has been measured and the plasma volume calculated in deciliters (American Red Cross).

(Desired-Actual TSP in gm./dL) x Plasma Volume (dL) x 2

HESPAN

6% Hetastarch, is synthesized by the hydroxethylation of polysaccharides and approximates the behavior of Albumin. It has been used successfully for non-protein primes of the ECC circuit and as an agent to increase the colloid osmotic pressure in patient's exhibiting hypovolemia circulatory shock (Haupt, Palanzo). However, being a non-protein agent; plasma protein, Albumin and/or COP levels should be monitored along with ionized calcium when employing this agent.

CARDIOPULMONARY PRIMING COMPOSITIONS

The compositions of priming volumes are as varied as the institutions performing OHS procedures. In addition to, or in lieu of, banked blood products some institutions may use Lactated Ringer's, Normosol-R or Plasmalyte-A. To these they may add Mannitol or Lasix, 5% Dextrose, 6% Hetastarch, Albumin, Sodium Bicarbonate, Sodium Heparin, the compositions are infinite (Chui, Hartley-Winkler, Molina, Palanzo, Reed and Stafford p.260, Stammers, Taylor pp.229- 236).

BODY SURFACE AREA (B.S.A.)

The DuBois and DuBois Body Surface Area chart is used to establish Body Surface Area predicated on height and weight. The chart is not sex specific. The infant/ pediatric version, as well as the adult, is based one of the following equations:

BSA M2 = [(Kg.) ^ 0.425 x (Cm.) ^ 0.725] x 0.007184
                                        or
BSA M2 = SQR. RT. [(Kg. x Cm.)/ 3500]
The BSA in square meters is essential in calculating extra-corporeal circulation flowrates.

Adopted from The Merck Manual, 15th Edition, 79:900, 1987.

BASAL OXYGEN CONSUMPTION

The basal oxygen consumption (ml./min.) in the infant be 5-7 times the value of an adult, however, the MET levels (ml./min./Kg.) is about twice that of the adult (Galletti).

The Respiratory Quotient (VCO2/VO2) may be reduced by 15-20% due to anesthesia, skeletal muscle paralysis and mechanical ventilation Hypothermia during ECC further reduces this value (Riley and Justison, Mitchell).

 BASAL OXYGEN CONSUMPTION (VO2) vs. BODY WEIGHT

Adopted from: Galletti, P.M. and Brecher, G.A., Heart- Lung Bypass: Principles and Techniques of Extracorporeal Circulation, Grune & Stratton, New York; 1962.

Oxygen consumption is normally derived from the Fick equation. This method calculates the arterial and venous oxygen content difference and multiplies that value by the cardiac output in L/M x 10 (Bolen, Miller).

VO2 (ml./min.) = (CaO2-CvO2) x CO x 10

During ECC, if the Hgb, C.O. and A/V venous saturations are known, oxygen consumption may be calculated without knowing the PO2 values since dissolved oxygen normally contributes less than 0.3 Volumes %. of the arterial O2 content.

VO2 (ml./min.) = Hb. x 1.34 x [(SaO2-SvO2)/100] x CO x 10

The basal oxygen consumption of a neonate may vary due to a variety of factors. Extracorporeal flowrate requirements are predicated on the predicted basal and hypothermic oxygen requirements, level of anesthesia, degree of hemodilution, oxygen carrying capacity, degree of hypothermia etc.

EXTRACORPOREAL PERFUSION FLOWRATES

Pediatric perfusion groups have reported the application of extracorporeal perfusion flowrate ranges between 1.80-3.5 L/Min./M2, others use 70-150 ml/Kg/Min. (Berryessa, Chui, Hartley-Winkler, Mitchell, Molina, Page p.6-1, Pfefferkorn p. 64, Reed and Kuruz p.140, Reed and Stafford p.406). Flowrate guidelines have been adopted from the American Association for Extra-Corporeal Technology's (AmSECT) publication, Pediatric Perfusion, Paul A. Page, PA, CCP. The higher of the two calculations is considered the optimal and the lower value is considered the minimum flowrate.

Extracorporeal perfusion flowrates are adjusted during hypothermia to ensure adequate arterial/ venous oxygen transferability. Oxygen consumption in humans decreases normally at a rate of 7% per degree Celsius . Therefore, decreasing the temperature from 37 C to 30 C would reduce oxygen consumption requirements to 50%, 25% at 23 C. A pediatric patient with a calculated basal VO2 of 84 ml./min. at 37C may experience a reduction to 42 ml./min. at 30 C, 21 ml./min. at 23 C via hemodilution and hypothermia (Reed and Stafford p. 325). Other investigators have reported a 50-60% reduction in total body oxygen consumption at 28 C to 30 C a 80-90% reduction at 18 C to 20 C and 90% between 8 to 10 C (Greeley, Mitchell).

Formulas are subject to estimations and do not consider alterations in cardiopulmonary and hemodynamic pathophysiology. Adequacy of extracorporeal perfusion flowrates and accommodation of oxygen metabolic requirements mandates frequent, if not continuous, arterial and venous blood gas analysis in conjunction with hematology and chemistry values. The assessment of oxygen delivery vs. oxygen consumption is advisable to determine the adequacy of perfusion flowrates and/or assessment of anesthesia levels.

PULSATILE vs. NON-PULSATILE PERFUSION
Pulsatile vs. non-pulsatile perfusion has been debated for several years. The "pulse wave" is generated by a specially designed dual roller pump which may be programed to deliver an intermittent flow that emulates an arterial pressure waveform. Proponents of pulsatile perfusion cite improved perfusion to the vital organs, better distribution to the tissues during warming and cooling, enhanced oxygen utilization by the vital organs, decrease in lactic acid, and systemic vascular resistance, among others (Berryessa, Casper, McCormick, Taylor p.76). Some researchers dispute the value of pulsatile flow and classify it's application as being detrimental (Taylor p.77). It is recommended that pulsatile perfusion should not be performed with a microporous membrane oxygenator that is placed distal to the arterial pump. Gas may be transported across the micropores of the membrane during the negative phase of the pulse wave (Reed and Kuruz p.109).

CEREBRAL FUNCTION
Cerbral function monitors are utilized to monitor the amplitude and frequency of cerebral electrical activity during ECC. Cerebral activity is dependent on the level of anesthesia, arterial pressure as well as the degree of hypothermia. Cerbral electrical activity (EEG waves) is minimized when the arterial pressure during ECC is below 35 mm. Hg. and during circulatory arrest at 18 C core temperature (Greeley, Taylor p. 25). Cerebral function monitoring should be considered as an adjunct to anesthetic, ECC and hypothermic management (Johnson, Kern, Murkin).

Recently, investigators have been able to measure cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) in the neonate, infant and pediatric patients. This has been by direct measurement before, during, and following hypothermic cardiopulmonary bypass, with and without deep hypothermic arrest (DHCA). Brain ischemic tolerance during hypothermia, referred to as hypothermic metabolic index (HMI), has been developed by Greeley et. al. Based on the HMI they have reported a predictable "safe" cerebral ischemic time of 11-19 minutes at 28 C and 39-65 minutes at 18 C.

EXTRACORPOREAL CIRCUITRY
The components selected for the extracorporeal circuit tubing and components are predicated on minimizing hemodilution while being able to accommodate blood flowrate requirements without excessive resistance to perfusion flowrates. The tubing comprising the extracorporeal circuit is manufactured of clear polyvinyl chloride. The cannula, catheter and tubing connectors, as well as the casings of the oxygenators, arterial filters and hemoconcentrators usually consist of clear or opaque Polycarbonate.

The ECC circuit is usually comprised of the arterial line, arterial pump boot, venous line, suction lines, a bubbler or membrane oxygenator. A cardiotomy reservoir is required with certain oxygenators  (Malinaukas). Arterial filters should be incorporated to filter particulate matter between 20-40 microns as well as gaseous microemboli during ECC (Butler, Demierre, Hill, Massimino, Taylor p.369). The cardiotomy allows for the recycling and filtration of blood suctioned from the surgical field.

DUAL ROLLER PUMPHEAD vs. CONSTRAINED VORTEX PUMP
The device which generates forward flow in the extracorporeal circuit is the perfusion pump which may be a DeBakey dual roller, centrifugal pump. Although each of the pumps generate a negative inlet and positive outlet pressure their effect on the blood may be pronounced. Investigators have compared the use of dual roller versus centrifugal

pump and have reported lower levels of hemolysis, serum free hemoglobin, comparatively increased platelet count and activity, increased protaglandin and decreased thromboxane levels when engaging the use of a centrifugal pump (Chi).

ARTERIAL CANNULA/ VENOUS CATHETER SIZES
Aortic or arterial cannula's are usually inserted into the ascending aorta. Alternate routes are the femoral artery, or ductus arteriosus during repair of hypoplastic left heart syndrome (Stammers). The recommended flowrate varies with the manufacturer according to the length and internal diameter of the conduit whic is a function of Poiseuille's Law (Green p.245, Reed and Stafford p. 157). Some cannulas with identical French sizes, but different manufacturer's may vary in flowrates by 40% (Van Meurs). An aortic or arterial cannula is selected which will provide the recommended ECC perfusion flowrate without excessive pressure gradients and resistance approaching Reynold's number, which may lead to increased shear stress with resulting hemolysis. A pressure gradient of < 100 mm. Hg. is preferable(Hope, Molina, Reed and Stafford p.160, Van Meurs).

Venous cannula's may be right-angled or straight at the tip. The body may be wire-wound or non-wired. Venous catheters must be able to provide total right heart drainage (Molina). The average height difference between the tip of the venous cannula, situated approximately at the mid- axillary level to the venous drainage port of the oxygenator is approximately 18-20". This differential will produce an average negative hydrostatic pressure of 34-37 mm. Hg. or 46- 51 centimeters of water (CWP) pressure. The hydrostatic pressure differential may be altered by augmenting the height of the column to enhance or reduce venous return (Frazier, Molina).

The following table should serve as an approximate guide to arterial cannula and venous catheter selections. It is recommended, however, that the performance of the selected conduits are obtained from the manufacturer.

Adopted from K.M. Taylor, Cardiopulmonary Bypass; Principles and Management, Williams and Wilkins, Batimore, MD, p. 117, 1990.

ARTERIAL/ VENOUS CIRCUIT
The arterial/venous circuit is designed to permit the maximum calculated blood flowrate without excessive line pressures from resistance, adequate venous drainage without shunting to the right heart while eliminating the need, or minimizing, blood product requirements (Courtney, Molina).

Accidental reversal of arterial and venous lines to the arterial cannula and venous catheters with tubing of the same caliber has been reported. The practice of selecting identical arterial/ venous tubing calibers is cautioned or discouraged to deter the possibility of this hazard.

The pump boot or "raceway" tubing is the portion of the ECC circuit which comes in contact with the dual roller, or DeBakey, pumphead to provide negative flow at the inlet and positive flow on the outlet ports of the tubing "raceway". Some tubing boots consist of silastic others of polyvinyl chloride.

Provided is a general guide to arterial, venous and pump boot tubing based on flowrate requirements.

Heparin bonded or coated circuits are available from several manufacturer's. These circuits present evidence of increased biocompatability with a corresponding decrease in heparin requirement as well a compliment activation (Bennett, Stenach, von Segesser).

BUBBLER vs. MEMBRANE OXYGENATOR
The debate continues concerning the use of bubbler versus membrane oxygenators. Many authors have reported that there is virtually no difference in the two systems for procedures lasting less than three hours. However, bubbler oxygenators have a direct blood to gas (100% oxygen) interface which is not conducive to extended cardiopulmonary bypass. The FIO2 is not adjustable in bubbler oxygenators which is a concern during ECC of the premature infant. Retrolental Fibroplasia is causes by hyperoxia induced vasoconstriction of the retinal arteries. Permanent retinal damage has been reported when arterial PO'2 are greater than 110 for longer than 1-2 hours.

Semipermeable polypropylene membranes oxygenators, on the other hand, do not have a direct blood to gas interface. These oxygenators may be used exceeding 3 hours of ECC with recommendations of up to 6 hours. The exception is with Extra-corporeal Membrane Oxygenator ECMO applications. The Sci-Med or Kolobow Lung, which is composed of silicone rubber membrane oxygenator is the only alternative for extra- corporeal circulation involving several days.

Listed are the more common polypropylene infant/ pediatric membrane oxygenators. Note that the COBE VPCML is a two compartment folded sheet polypropylene membrane. The first compartment may accommodate infant and the second pediatric perfusion flowrates. The two compartments combined may accommodate a large pediatric or small adult ECC flowrates.

ECC PRIMING VOLUMES
The amount of priming volume for infant and pediatric circuits is dependent on the size of arterial/ venous lines, static prime of the oxygenator and any accessories incorporated such as pre-bypass and arterial filters, hemoconcentrators, ECC arterial line pressure monitoring devices etc. The following are standard priming volumes for average infant and pediatric extracorporeal circuits.

INFANT ECC CIRCUIT
<700 ml. - 3/16 " arterial line, 1/4 " arterial boot, 1/4 " venous line with an integrated membrane oxygenator

PEDIATRIC ECC CIRCUIT
<1000 ml. - 1/4 " arterial line, 1/4-3/8 " arterial boot, 3/8 " venous line with an integrated membrane oxygenator

ADULT ECC CIRCUIT
<1750 ml. - 3/8 " arterial line, 1/2 " arterial boot, 1/2 " venous line with an integrated membrane oxygenator

Extracorporeal circuit priming volumes vary according to the components and accessories used. The values presented are an average depiction of typical infant/ pediatric ECC circuits providing 200-300 ml. residual volume in the perfusate reservoir, 500 ml. in the adult

CENTRAL/ ONLINE PRESSURE MONITORING
An online pressure transducer or manometer with a fluid/ blood barrier should be integrated to monitor the ECC aortic or femoral arterial line pressure. During ECC the delivery pressure should not exceed 200 mm. Hg. (Hope, Taylor p.113). Occasionally the arterial cannula may become displaced and excessive line pressures generated. An online pressure monitoring device would alert the perfusionist to the problem.

During post CPB a peripheral (radial) arterial line pressure may be dampened via vasoconstriction. The ECC arterial line pressure may be used to compare if there is a pressure differential thus avoiding the treatment of pseudo- hypotensive event.

BLOOD PRODUCT REQUIREMENTS
Fresh heparinized, recalcified whole blood, drawn less than 24 hours prior to ECC is the preferred perfusate for the prime of neonatal and infant extracorporeal circuits requiring blood products. Fresh whole blood contains viable elements in the plasma essential for post-ECC hemostasis. These factors deteriorate precipitously after 24 hours and are, in effect, non functional after this period. If citrated fresh whole blood is not available then packed red blood cells may be reconstituted with fresh frozen plasma. However, it must be remembered that reconstituted blood is lacking platelets and may have to be replaced post-bypass depending on blood platelet concentration.

Most packed red blood cells are preserved in Citrate- Phosphate Dextrose (CPD-A) or ADSOL an Adenine Saline (the trademark of Fenwal Laboratories) preservative solution (Miropol). The blood bank preservation solution used to be removed and replaced with either saline or fresh frozen plasma, if the infant is less than 4 months of age. This practice has been recently abandoned.

Irradiated blood posses a special problem. Irradiation destroys leukocytes and lymphocytes which may be responsible for transfusion reactions. Blood units that have been irradiated and stored for over 48 hours will contain excessive levels of potassium which may be sufficient to induce cardiac arrest during the initiation of extra- corporeal circulation. As a precaution, the plasma or preservative solution should be removed from these units to eliminate the possibility of hyperkalemia.

PRIMING CONSIDERATIONS
Once the required perfusion flowrate, blood volume and hemodilutional data has been obtained, the extracorporeal circuit is designed. An updated hematocrit should be obtained in the surgical suite to determine if hemodilution from intravenous fluids have changed the predicted hemodilutional and target hematocrit. On occasion, the reported pre-NPO hematocrit may vary 10-15 % from the updated hematocrit prior to bypass. In this event, all calculations must be refigured and additional blood products may need to be ordered.

PRE-BYPASS RECIRCULATION of the PERFUSATE
Infant circuits will most certainly require blood products. An asanguinous extracorporeal circuit prime would hemodilute the patient to extremely low hematocrit levels approaching 15% and less. The addition of banked blood products will yield an extremely acidotic prime. Once the prime is circulated and vented the pH of the perfusate will approach 7.0 or below depending on the PCO2 value, the base excess is approximately -20. However, the base excess value should be used to calculate the amount of Sodium Bicarbonate required to adjust the pH to 7.40. The following is a calculation for the amount of bicarbonate required to buffer and acidotic prime:

HCO3 (mEq) = Amount of Perfusate (L) x Base Excess (ABS)

It should be remembered that the H+ ions in the acidotic prime will combine with HCO3- to form H2CO3- carbonic acid This further dissociates into CO2 and H2O (Reed and Stafford p. 202-203). Immediate dissociation in ECC primes may produce PCO2 values in excess of 70-80 mm. Hg. (clinical observation). Therefore, a blood prime buffered with sodium bicarbonate should be ventilated for several minutes to reduce the resultant hypercapnea.

HEPARINIZATION
Beef lung sodium heparin is the anticoagulant of choice during extracorporeal circulation. It acts by potentiating the activity of plasma protease inhibitor antithrombin III which inhibits thrombin formation and factors Xa, IXa, XIa. (Orland p.281). A standard average dose is 300 IU/ Kg. to obtain an Activated Clotting Time of over 400 seconds (Berryessa, Bull, Taylor, p.46). However, at Vanderbilt University loading heparin doses for infants, pediatric and adults is 100 IU/ Kg., 200-300 IU/ Kg. and 400 IU/ Kg. respectively.

It is preferable to perform a heparin titration analysis or the Bull protocol to determine Heparin resistance or sensitivity. During ECC an activated clotting time should be performed every 30 minutes to assay the adequacy of anticoagulation, exceeding 400 seconds. Bull concluded that the response to heparin administration is linear . Therefore, once a dose response curve is established addition heparin or reversal with protamine is a matter of plotting the heparin dose response graph (Bull).

Reversal of sodium Heparin with Protamine Sulfate varies from institution to institution. The Bull protocol recommends a reversal of 1: 1.1 mg. of Heparin:Protamine. Many institutions use Heparin to Protamine reversal ratios between 1:1.1 - 1:2.0 (Bull, Friesen, LaDuca). Vanderbilt University reverses the heparin dose with protamine at a 1:2 to 1:3 ratio. Heparin: Protamine analysis systems are designed to provide the most accurate method of determining the amount of protamine required to reverse the heparin in a sample of blood (Harloff and Taraskiewicz). Caution should be used in the administration of Protamine sulfate. Numerous cases involving protamine reactions and hypotension have been reported, therefore, diligent cardiopulmonary and hemodynamic monitoring is in order.

INITIATION of EXTRA-CORPOREAL CIRCULATION
After the administration of sodium heparin, the heart- lung machine arterial pumphead should be increased to the patient's maximum blood flowrate, the lines should be "tapped" to dislodge residual micro/ macro air bubbles. The surgical assistant at the operative filed should do likewise. The extracorporeal circulation should be slowly terminated and the arterial and venous lines clamped. 3-5 minutes after heparin administration, the heart-lung machine pump sucker may be activated to recover mediastinal shed blood. Once aortic and vena cava cannulation has been achieved and the arterial and venous lines connected the patient is prepared for extracorporeal circulation.

Upon initiation of ECC the patient's arterial blood pressure will generally be between 30-40 mm. Hg. with full flowrates (Mitchell). The perfusion pressure should be kept between 50-70 mm. Hg. to maintain adequate cerebral perfusion at normocapnia levels (Taylor p.47).

CARDIOPLEGIA
Cardioplegia solutions administered to induce asystole. These solutions may be composed of crystalloids, blood and crystalloid. There are several cardioplegia solutions available to the surgeon. Some are pre-manufactured, many are mixed in the medical center's pharmacy. Many cardioplegic solutions are modifications of the popular St. Thomas' Hospital cardioplegic solution No. 2 (Plegisol, Abbott Laboratories, Chicago) (Stammers, Taylor p. 381):

St. THOMAS CARDIOPLEGIA SOLUTION 
Na+ 110 mmol/L
K+ 16 mmol/L
Ca++ 1.2 mmol/L .
Mg++ 16 mmol/L .
CL- 160 mmol/L .
NaHCO3 10 mmol/L
pH 7.8 * Contains Sodium 145 mEq/L
Osmolality 32O mOsm/L Potasssium < 2 mEq/L

The principle chemical ingredient is potassium chloride 15-20 mEQ/L. Some institutions use a blood/ crystalloid ratio of 1:1, 1:2 or 1:4 employing an administration set with an integrated cooling coil (McCormick, Stammers). Cardioplegia typically is administered antegrade, sometimes retrograde or both. Cardioplegia is administered at an initial dose of 10- 30 ml./ Kg. at 7-10 C with subsequent doses every 20-30 minutes if desired, myocardial temperatures should be monitored to maintain relatively low temperatures of 15 C or less (Garcia, Reed and Kuruz p.140, Taylor p. 121 and p.384).

HYPOTHERMIA
Bigelow in 1949 suggested the use of hypothermia in conjunction with intracardiac surgery requiring circulatory arrest (Mitchell, Taylor p.7). Today most cardiac surgical cases are performed during hypothermia between 25-30 C. The lower temperatures decreases the basal metabolic rate and provides cerebral and myocardial protection. Cooling and rewarming the patient is accomplished by exposing the perfusate in the oxygenator to an integrated heating/ cooling coil. The regulated water temperature circulates countercurrent to the perfusate for maximum efficiency.

 Many surgeons prefer to cool the patient immediately to the target temperature thus decreasing metabolic rate. If circulatory arrest is the goal an arterial/ venous blood gas sample is obtained after 5 minutes of cardiopulmonary bypass to access oxygenation and acid-base status. Any acidotic pH, PCO2 and Base Excess levels are adjusted immediately and prior to circulatory arrest. If the patient is not to be subjected to circulatory arrest it is advisable to obtain a routine blood gas profile after 5 minutes of ECC or upon obtaining the target temperature.

Hypothermia increases the solubility and affinity of oxygen and carbon dioxide. The pK, thus the pH, is also affected causing the oxyhemoglobin dissociation curve to shift to the left. This leftward shift readily binds the oxygen to the hemoglobin as oxyhemoglobin. This leftward shift is observed while monitoring venous blood oxygen saturation levels during normothermia vs. hypothermia

(Reed and Stafford p.195, Riley, Shoemaker pp.233-234, Taylor p.153, Mitchell).

DEEP HYPOTHERMIC CIRCULATORY ARREST (DHCA)/ PROFOUND HYPOTHERMIA
Infants under twelve months and/or 10 Kilograms body weight who undergo profound hypothermia and circulatory arrest may be pre-cooled by a Subramanian Cooling Chamber. Another alternative is systemic hypothermia via extracorporeal circulation, the patient's head should be packed in ice. The Subramanian device externally cools the patient to 30 C. All patient's scheduled for circulatory arrest are administered Dextran 40 at a dose of 10 ml./ Kg. to prevent aggregation of blood elements at the hypothermic ranges encountered, usually 18-20 C. The following is a classification of the various degrees of hypothermia (Reed and Stafford p.286).

Prior to circulatory arrest the patient's arterial blood gases are corrected for metabolic and/or respiratory acidosis. Safe circulatory arrest, to prevent irreversible cerebral damage and their respective temperatures are depicted.

Adopted from Gordon, et. al. Open heart surgery using deep hypothermia without an oxygenator. Journal of Thoracic and Cardiovascular Surgery, 1960: 40; 787-812.

ALPHA-STAT vs. pH-STAT
There are two methods currently used for analyzing blood gas samples during extra-corporeal circulation; Alpha-Stat and pH-Stat. The Alpha-Stat method measures the blood gas sample at 37 degrees Centigrade regardless of the patient. The pH-Stat method measures the blood gas sample at 37 C degrees then adjusts for the temperature change of the patient. Some authors cite that the increased PCO2 levels caused by the pH Stat method prevents the oxyhemoglobin dissociation curve from shifting too far to the left thus providing better O2 delivery to the tissues. It has also been cited as being responsible for increased cerebral blood flow during ECC. Some investigators dispute this theory and advocate that the Alpha-Stat method is the safer method for monitoring arterial/ venous blood gases during extra- corporeal circulation (Dearing, Hering, Kern, McCormick, Molina, Murkin, Riley and Justison).

ALPHA STAT PERFUSION GOAL: CONSTANT BLOOD CO2 CONTENT
A) Hypothermia will increase CO2 plasma solubility.
B) To maintain constant CO2 content during cooling more carbon dioxide must be removed than with pH-Stat.
C) To maintain constant CO2 content, the gas ventilation rate will be higher than pH-Stat.

ALPHA-STAT
Actual Results

pH STAT PERFUSION GOAL: CONSTANT pH/INCREASING CO2 CONTENT
A) pH stat corrects all blood gases to patient temperature.
(Hypothermia samples not at 37 C)

B) Goal: Maintain PCO2=40 mm.Hg. (pt. temp. corr.)
Maintain pH=7.40 (pt. temp. corr.)

C) Increasing levels of hypothermia and corresponding CO2 plasma solubility will increase total CO2 content in order to maintain temperature corrected PCO's of 40 mm. Hg.

pH STAT
Actual Results

A 1990 pediatric perfusion survey documented that approximately 80% of the reported surgical centers employed to use the Alpha-Stat. Our institution was among the 80%. The remaining 20% use the pH Stat method. Some centers reported blood gas values using both methods (Hill).

On-line or continuous arterial/ venous (A/V) oxygen blood gas monitoring has been available clinically for the past several years. These devices allow for continuous display of pH, PO2, PCO2, Base Excess and Hematocrit (Basha, Bolen, Ferries, Harloff, Molina, Parault, Riley and Burgess, Riley and Fletcher, Rubsamen). Some online monitors analyze Na+, K+ and Ca++ electrolytes (Riley and Burgess). A survey reported that 62% of the infant/pediatric cardiac surgical centers used on-line A/V blood gas monitoring (Hill) Centers not employing on-line blood gas monitoring should elect to at least monitor continuous A/V oxygen saturation to access the adequacy of perfusion and oxygen requirements via the A/V saturation differential (Baraka, Baris, Bolen, Miller, Page and Birenbaum).

ACID-BASE CORRECTION
The conduct of perfusion attempts to maintain normal arterial/venous acid-base physiology with arterial PO2 value less than 200 mm. Hg. Correction of metabolic acidosis via sodium bicarbonate is obtained by recommendation of the American Heart Association standard for administration:

[Body Weight (KG.) x 0.30] x Base Excess divided by 2

A factor that is often dismissed is the addition of the ECC circuit volume to the calculation. This is critical in the neonate. For example a 3 Kilogram patient attached to an 700 ml. ECC circuit would present the following, given a Base Excess of -6 during ECC:

(3.0 Kg. x 0.30 ) x 6 divided by 2 = 2.7 mEq of NaHCO3 to administer.

The addition of a 700 ml. prime to calculate the Total System Volume would alter this figure.

[(3.0 Kg. x 0.30 ) + 0.70] x 6 /2 = 4.8 mEq of NaHCO3 to administer.

Nearly 78% additional sodium bicarbonate is required in comparison to the dose from the previous calculation, not incorporating prime volumes. It is imperative that ECC prime be considered as an adjunct the neonate/ infant and pediatric total body water for correct reversal of acidosis.

The correction of membrane PO2's may be accomplished by the reduction of the FIO2 (O2 %/ 100). A bubbler oxygenator does not allow this feature and PO'2 in excess of 300-400 mm. Hg. may be experienced. PCO2's may be adjusted using the following PCO2 adjustment formula (Camerlengo):

Adjusted Gas Flow = (Measured PCO2/ Target PCO2) x Gas Flow

CONDUCT of PERFUSION
The conduct of perfusion concentrates on regulating medical gas and blood flowrates to ensure adequate perfusion pressure and oxygen delivery to the tissues. Hematologic and

Chemistry values are obtained continuous with in line monitors or serially every 20-30 minutes. Blood products,

pharmacologic and/or electrolyte administration are based on analyzed blood samples and calculations based on deficits. Detailed perfusion record is maintained with entries every 15 minutes or during unscheduled events.

PHARMACOLOGIC DOSEAGE CONSIDERATIONS
The circuit should be considered as an adjunct to the patient during ECC. Therefore, an infant with a blood volume of 700 ml. and a circulating prime of 700 ml. should be considered as having a blood volume of 1,400 ml. since a pharmacologic agent will be diluted to 50% of it's strength predicated on hemodilution. An isoncotic perfusate will have a weight approximating 1 mg./ ml., Therefore, a 700 ml. prime will weigh 700 gms. or 0.70 Kilograms. This is the equivalent blood volume of a 8.2 Kg. patient (700 ml./ 85 ml./ Kg. Blood Volume Factor).

REWARMING DURING EXTRACORPOREAL CIRCULATION
When the surgical procedure is completed or near completion the surgeon will give the command to rewarm the patient. The heating blanket and the heater-cooler are activated. The temperature of the water in the heat exchanger versus the patient's blood temperature should not exceed 42 degrees Celsius and a gradient of 12 C in an adult, 8 C in the pediatric patient (Reed and Stafford p. 327).

As the patient is rewarmed, the solubility of oxygen is decreased and the metabolic oxygen demands of the patient will increase. Therefore, during rewarming, the patient's blood flowrates and FIO2 are increased at incremental rates. CO2 production is not as prevalent during rewarming as during normothermia and cooling therefore caution must be used not to hyperventilate the patient and induce hypocapnia. This is especially prevalent when the anesthesiologist is ventilating the patient while the patient is on partial bypass. Partial bypass is defined when some of the venous return is diverted to the right ventricle and ejected into the pulmonary system.

Rewarming times vary with the size of the patient and the level of hypothermia and may require 25-45 minutes to obtain a 37 C core temperature. Warming the room to 70-75 F enhances rewarming and reduces the possibility of post-bypass hypothermia.

TERMINATION of CARDIOPULMONARY BYPASS
Discontinuation of cardiopulmonary bypass is considered when the surgical procedure has been completed, the esophageal and nasopharyngeal or core temperature has reached 37 C. Likewise when all hematologic and chemistry values have been corrected for any deficits. The anesthesiologist begins ventilating with warm/ humidified gases and the venous return line is partially clamped to permit the patient to eject blood into the right side of the heart and thus through the pulmonary system. Venous saturations should be maintained above 70% while the patient is slowly weaned from bypass. Once the command is given by the surgeon the venous line is clamped, the pumphead rotation terminated and the arterial line clamped proximal to the central line pressure transducer which should emulate the peripheral line pressures. Volume may be infused from the heart-lung machine until a desired filling pressure has been obtained. The remaining perfusate may be processed by draining the venous line and "chasing" the perfusate with physiologic I.V. solution. This technique should yield 300-500 ml. of perfusate with a 25-30% hematocrit. This fluid may be hemoconcentrated and washed as packed cells or given directly to the patient. In the case of the latter, additional protamine sulfate may need to be administered to neutralize the additional heparin in solution.

POST-OPERATIVE COMPLICATIONS
It is obvious that the more complex the surgical procedure the greater the possibility of post-operative complications. Relatively simple procedures such as repair of atrial and/or ventricular septal defects present less cardiovascular and hemodynamic complications than the more complex procedures such as an anomalous left coronary artery, Norwood procedure or arterial switch. The most common challenge is non-mechanical post operative bleeding caused by a coagulopathy, therefore, complete coagulation profiles, including clotting Factor assays, especially Factor's VIII and X should be considered. Ionized calcium levels should not be overlooked in determining hemostasis. Post-operative replacement regimen may include the administration of calcium chloride, fresh frozen plasma, cryoprecipitate and platelets.

SUMMARY
The application of extracorporeal circulation in the neonate, infant and pediatric patient populations is demanding. These patient's present a multitude of variables primarily assessing the effects of hemodilution, hypothermia and flowrate resitrictions of the arterial cannula's, venous catheter's and arterial/venous circuit conduits that are employed.

The cardiovascular perfusionist must be cognizant of the pathophysiology of the defect, the cardiac catheterization values concerning pressure, flow, saturation and intra- cardiac shunts. Cardiopulmonary, hemodynamic, thermal, hematologic and chemistry data must be carefully observed for rapid changes. Much preparation is required to assess and accommodate basal metabolic demands of the anesthetized patient during normo and hypothermia. ECC flowrates, hemodilution, blood product and chemistry reconstitution, hypothermia, oxygen consumption, critical to decreasing morbidity.

Research has been continuous. The priming volumes of the circuits are constantly being reduced, thus the effects of hemodilution. Vital organ, including myocardial and cerebral protection, has been greatly improved. Investigation is continuous for the development of an artificial blood product capable of normal oxygen carrying capacity and gas exchange to the tissues.

The responsibility of neonatal, infant and pediatric cardiopulmonary bypass mandates that we scrutinize the medical literature and adopt the techniques that our peers have discovered to be more valuable than our current methods...if the evidence supports it.

REFERENCES
American Red Cross, Albumin (Human) 25% Solution, Central Laboratory Blood Transfusion Service, Swiss Red Cross, Berne Switzerland, 1991

Baraka A, Baroody M, Haroun S, Nawfal M, El-Khatib R, Taha S, Meshefeddjian G, Baraka H, Prediction of Post-Cardiopulmonary Bypass Cardiac Output by Venous Oximetry, The Journal of Extra-Corporeal Circulation, Volume 24, Number 3, 86-89, 1992

Baris RR, Wilt SL, Schiavo J, Klobus JJ, Mcafee T, Clinical Evaluation of the OxySat 2 Monitoring System, Proceedings of the AmSECT 26th International Conference, 52-55, 1988

Basha JW, Sternlieb JJ, Bjork VO, Bretz PD, Gabrielson TW,

Clinical Evaluation of Cardiomet 4000 Continuous On-Line Blood Gas Analyzer, Proceedings of AmSECT's 26th International Conference, 48-51, 1988

Bennett J, Hill J, Long W, Parsons J, Bruhn P, Starr A, Hiovaguimian H, Okies E, Biocompatible Circuits: An Adjunct to Non-Cardiac Extracorporeal Cardiopulmonary Support, The Journal of Extra-Corporeal Circulation, Volume 24, Number 1, 6-11, 1992

Berne RM, Levy MN, Cardiovascular Physiology, 5th Edition, The C.V. Mosby Company, St. Louis, MO, 1986

Berryessa R, Hydrick D, McCormick J, Tyndal CM, Peterson D, Tornabene M, Tornabene S, Williams W, Pappas G, Campbell, D, Clarke, D, Refinements in Pediatric Perfusion, The Journal of Extra-Corporeal Circulation, Volume 18, Number 2, 140-144, 1986.

Beshere GA, Camerlengo, LJ, Dearing JP, Estimation of Colloid Osmotic Pressure During Hemodilutional Cardiopulmonary Bypass, The Journal of Extra-Corporeal Technology, Volume 14, Number 3, 381-384, 1982

Bolen GZ, Anderson GE, Huddleson, JR, Riley, JB, Sutton R, Bishop DG, Clinical Accuracy of Continuous Hemoglobin Oxygen Saturation Monitoring Devices, The Journal of Extra-Corporeal Technology, Volume 22, Number 2, 61-66, 1990

Bone DK, William WH, Hatcher CR: Techniques of cardiopulmonary bypass and its complications, The Heart, Hurst, JW (ed), New York, McGraw-Hill Book Co., p. 1895, 1982.

Bull B, Huse W, Brauer FS,: Heparin Therapy During Extracorporeal CirculationII:TheUseof a Dose Curve to Individualize Heparinand ProtamineDoseage, The Journal of Thoracic Cardiovascular Surgery, 69: 685-89, 1975Butler BD, Gaseous Micro Emboli: Concepts and Considerations, The Journal of Extra-Corporeal Circulation, Volume 15, Number 6, 148-155, 1983

Cameriengo LJ, Dearing JP, Precise Control of PCO2 During Cardiopulmonary Bypass, The Journal of Extra-Corporeal Technology, Volume 13, Number 2, 183-186, 1981.

Casper M, Pulsatile Flow During Cardiopulmonary Bypass: Is It Beneficial?, The Journal of Extra-Corporeal Circulation, Volume 20, Number 1, 25-31, 1988.

Chui BS, Shapiro JH, Buckley K, Allen EL, Lofland G, Use of the Constrained Vortex Pump in Children Under 20 kg, The Journal of Extra-Corporeal Technology, Volume 23, Number 3, 98-101, 1992

Conley JC, Zografos CA, Bloodless Prime in Pediatric Cardiopulmonary Bloodless Prime in Pediatric Cardiopulmonary Bypass Circuits, The Journal of Extra-Corporeal Technology, Volume 23, Number 4, 80-82, 1991.

Courtney PH, Wansley DE, Heath BJ, Three Sixteenth Inch Perfusion Tubing: A New Concept for the Pediatric Patient, The Journal of Extra-Corporeal Technology, Volume 19, Number 1, 100-102, 1987

Dearing JP, Miller III AR, Linker R, Chaikhouni A,: A Prospective Study of Two pH Management Plans for Hypothermic Cardiopulmonary Bypass, The Proceedings of the American Academy of Cardiovascular Perfusion, 89-93

Demierre D, Maass D, Turina M, ECC Sources of Gaseous Microemboli, The Journal of Extra-Corporeal Technology, Volume 17, Number 1, 20-26, 1985

DuBois D, DuBois EF, Clinical Calorimetry Tenth Paper: A Formula to Estimate the Approximate Surface Area if Height and Weight Be Known, Archives of Internal Medicine, 16, 863, 1916

Ecklund JM, Riley JB, Sutton RG, Crawford FA, Sade RM, Estimation of Fibrinogen Concentration During Extracorporeal Circulation in Pediatric Cardiac Surgery, The Journal of Extra-Corporeal Technology, Volume 23, 3, 72-79, 1992.

Ferries L, Standards of Care in Perfusion: Should Not Continuous In-Line Blood Gas Monitoring Be One?, The Journal of Extra-Corporeal Technology, Volume 24, Number 2, 45-48, 1992.

Frazier, TM, Gravity Drainage Capbailities of Venous Tubing and Catheters, The Journal of Extra-Corporeal Technology, Volume 18, Number 2, pp. 91-94, 1986.

Friesen RH, Hydrick DR, Heparin Reversal in Children Following Cardiopulmonary Bypass, The Journal of Extra- Corporeal Technology, Volume 18, Number 2, 95-97, 1986.

Galletti PM and Brecher GA, Heart-Lung Bypass: Principles and Techniques of Extracorporeal Circulation, Grune & Stratton, New York; 1962

Greeley WJ, Kern FH, Ungerleider RM, Boyd III JL, Quill T, Smith LR, Baldwin B, Reves JG, The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children, The Journal of Thoracic and Cardiovascular Surgery, 101:783-94, 1991.

Green JF, Fundamental CARDIOVASCULAR and PULMONARY PHYSIOLOGY, 2nd Edition, Lea and Febiger, Philadelphia, PA, 1987

Gurjar U, Bowman JM, Prevention of Platelet Adhesion to Extracorporeal Surfaces, The Journal of Extra-Corporeal Circulation, Volume 16, Number 3, 104-107, 1984

Han YQ, Zhu DM, Su ZK, Ding WX, Ultrafiltration in Pediatric Cardiac Surgical Procedures, The Journal of Extra-Corporeal Technology, Volume 23, Number 3, 63-65, 1992.

Harloff M, Taraskiewicz J, Comparison Study of the Hepcon System Four and the Hemostasis Management System, The Journal of Extra-Corporeal Technology, Volume 23, Number 3, 43-46, 1992

Harloff, M, Continuous Blood Gas Monitoring Using the CDI System 300, The Journal of Extra-Corporeal Technology, Volume 23, Number 3, 27-30, 1992

Hartley-Winkler M, Lamberti JJ, Rohrer C, Perfusion Considerations for Infants Weighing Ten Kilograms or Less, The Journal of Extra-Corporeal Technology, Volume 17,

Number 1, 31-36, 1985,

Haupt MT, Rackow EC, Colloid osmotic pressure and fluid resuscitation with hetastarch, albumin and saline solutions, Critical Care Medicine, Volume 10, Number 3, 159-162, 1982

Hedlund KD, Coyne DP, Platelet Function, Faciend, and Fate During Extracorporeal Circulation: A Review, Proceedings of the American Academy of Cardiovascular Perfusion, Volume 9, 90-92, 1988

Hering JP, Schroder T, Singer D, Hellige G, Influence of pH management on hemodynamics and metabolism in moderate hypothermia, The Journal of Thoracic and Cardiovascular Surgery, Volume 104, Number 5, 1388-1395, 1992Hill, AG, Groom RC, Bechara F, Lefrak EA, Krusz, M. 1990 Pediatric Perfusion Survey II: Expanded Multivariate Data Analysis, Proceedings of the American Academy of Cardiovascular Perfusion, Volume 12, 96-102, 1991.

Hope AF, Meyer JM, Verwoerd, The Necessity for Arterial Extra-Corporeal Line Pressure Monitoring for Cardiopulmonary Bypass, The Journal of Extra-Corporeal Circulation, Volume 14, Number 1, 309-311, 1982

Johnson K, Carroll V, Adams D, McInnis RJ, Stafford T, Reed

C, Sabawala PB, EEG Basics for the Clinical Perfusionist, The Proceedings of the American Academy of Cardiovascular Perfusion, Volume 9, 34-36, 1988

Kern FH, Jonas RA, Temperature Monitoring During CPB in Infants: Does it Predict Efficient Brain Cooling? Annals of Thoracic Surgery, 54:749, 1992

LaDuca F, Mills D, Larson K, Neutralization of Heparin Using a Protamine Titration Assay and the Activated Clotting Time Test, The Journal of Extra-Corporeal Technology Volume 19, Number 3, 358-364, 1987

Massimino RJ, Gough JD, Stearns GT, Martin J, Gaseous Emboli Removal Efficiency in Arterial Screen Filters: A Comparative Study, The Journal of Extra-Corporeal Technology, Volume 15, Number 2, 25-34, 1983

MEDTRONIC /HEMOTEC, Inc., Hepcon HMS Operator's Manual, Calculations Section, 1989

(The) Merck Manual, 15th Edition, Berkow R. (Ed.), Merck and Company, Rahway, NJ, 1987

McCormick JS, Berryessa RG, Clark DR, Campbell DN, Tyndal CM, Lactic Acid Generation During Pediatric Cardiopulmonary Bypass: A Comparison of Blood and Crystalloid Primes, The Journal of Extra-Corporeal Technology, 26th Proceedings, 84-88, 1988.

Miller MF, Luckenbach J, Chen C,: Clinical Evaluation of a New Saturation/ Hematocrit Monitor, The Journal of Extra- Corporeal Technology, Volume 24, Number 2, 55-57, 1992

MINNTECH Product Literature, Minntech Corporation, Minneapolis, MN, 1991

Miropol JE, ADSOL Preservative Solution-A New Additive System for the Extended Storage of Red Blood Cells. Fenwall Laboratories, Deerfield, IL 1-4, 1986.
 
 

Mitchell, BA, Optimal Perfusion Flowrates for Cardiopulmonary Bypass, The Journal of Extra-Corporeal Technology, Volume 22, Number 4, 165-183, 1990.

Molina J, Gorney R, Neonate, Infant and Pediatric Perfusion: A Review of Recent Product Selection, Proceedings of the American Academy of Cardiovascular Perfusion, Volume 12, 108-112, 1991.

Murkin JM, Alpha-Stat versus pH-Stat: Implications for the Brain During Cardiopulmonary Bypass, The Journal of Extra- Corporeal Technology, Volume 22, Number 3, 137-139, 1990.

Orland MJ, Saltman RJ (Ed.) Manual of Medical Therapeutics, 25th Edition, Little, Brown and Company, Boston, MA., 1986

Page PA, PEDIATRIC PERFUSION, American Society of Extra- Corporeal Technology, Reston, VA. 1984

Page PA, Birenbaum IB, Thomas L, Baldwin RC, Benak A, Optimizing Cardiopulmonary Bypass Utilizing Continuous Oxygen Saturation Monitoring, The Journal of Extra-Corporeal Technology, Volume 16, Number 2, 62-67, 1984

Palanzo DA, Martin GT, Gough JD, Martin J, Karlson KE, Hetastarch as a Clear Prime for Cardiopulmonary Bypass, The Journal of Extra-Corporeal Technology Volume 16, Number 2, 55-57, 1984

Parault BG, Conrad SA, The Effect of Extracorporeal Circulation Time and Patient Age on Platelet Retention During Cardiopulmonary Bypass: A Comparison of Roller and Centrifugal Pumps, The Journal of Extra-Corporeal Technology Volume 23, Number 2, 34-38, 1991

Pfefferkorn RO, Davis JP, CONGENITAL HEART DISEASE, American Society for Extra-Corporeal Technology (AmSECT), Reston, VA., 1986

Reed CC, Stafford TB, CARDIOPULMONARY BYPASS, 2nd Edition, Surgimedics/TMP, The Woodlands, Texas, 1989

Reed, CC, Kurusz M, SAFETY AND TECHNIQUES IN PERFUSION, Quali-Med, Inc., Stafford, Texas, 1988

Riley JB, Burgess BM, Crowley JC, Soronen SW, In Vitro Measurement of the Accuracy of a New Patient Side Blood Gas, pH, Hematocrit and Electrolyte Monitor, The Journal of Extra-Corporeal Technology Volume 19, Number 3, 322-329, 1987

Riley JB, Justison GA, Alpha-Stat and pH-Stat Management Techniques in Artificial Blood Oxygenators, The Journal of Extra-Corporeal Technology, Volume 16, Number 3, 77-82, 1984

Riley JB, Fletcher RW, Jenusaitis M, Fink S, Hoerr HR, Bell C, Crowley JC, Comparison of the Response Time of Various Sensors for Continuous Monitoring of Blood Gases, pH and O2 Saturation During Cardiopulmonary Bypass, Proceedings of the 26th International Conference of the American Society of Extra-Corporeal Technology, 1-6, 1988

Rubsamen, DS, Continuous Blood Gas Monitoring During Cardiopulmonary Bypass - How Soon Will It Be a Standard of Care?, Journal of Cardiothoracic Anesthesia, Volume 4,

Number 1, 1-4, 1990.

Shoemaker WC, Thompson WL, Holbrook PR, Textbook of Critical Care, W.B. Saunders, Philadelphia, PA, 1984

Stammers AH, Riley JB, Does Cardioplegia Protection of the Pediatric Heart Vary According to the Cardiac Defect?, The Journal of Extra-Corporeal Technology, Volume 23, Number 3, 8-18, 1992.

Stenach N, Korn RL, Fisher CA, Jeevanandam V, Addonizio P, The Effects of Heparin Bound Surface Modification (Carmeda Bioactive Surface) on Human Platelet Alterations During Simulated Extracorporeal Circulation, The Journal of Extra-Corporeal Technology Volume 24, Number 3, 1992

Tamari Y, Nelson R, Levy R, Carolina C, Rea N, Salogub, M, Hall M, Moccio C, Tortolani, Concentration of Blood in the Extracorporeal Circuit Using Ultrafiltration, The Journal of Extra-Corporeal Technology Volume 15, Number 5, 133-142, 1983

Taylor KM, CARDIOPULMONARY BYPASS, Principles and Management, Williams and Wilkins, Baltimore, MD, 1990

Tilkian SM, Conover MB, Tilkian AG, Clinical implications of laboratory tests, The C.V. Mosby Company, St. Louis, p. 13 1979

Tyndal CM, Berryessa RG, Perfusion Error Cause Removal: The Perfusion Case Conference, Proceedings of the 26th International Conference of the American Society of Extra- Corporeal Technology, 103-105, 1988

Van Meurs KP, Mikesell GT, Seale WR, Short BL, Rivera O, Maximum Blood Flow Rates for Arterial Cannula Used in Neontal ECMO, ASAIO TRANSACTIONS, Volume 36, Number 3, M679-M681,July 1990

Vinas MS, The Volume Allowance Formula as a Guide to Non- Haemic Solution Administration, The Journal of Extra-Corporeal Technology, Volume 22, Number 2, 70-72, 1990.

Vinas, MS Chapter 3: Extracorporeal Circulation, J. Kambam, M.D. editor, Anesthesia for Infants and Children, the C.V. Mosby Company, St. Louis, MO, 1995
 
von Segesser LK, Weiss BM, Garcia E, von Felten A, Turina MI, Reduction and elimination of systemic heparinization during cardiopulmonary bypass, The Journal of Thoracic and Cardiovascular Surgery, Volume 103, Number 4, 790-799, 1992