PRINCIPLES & evolution OF CARDIO PULMONARY BYPASS

EVOLUTION OF EXTRACORPOREAL CIRCULATION

1812: Le Gallois showed that extracorporeal circulation is Possible, part of the body might be preserved by some sort of external perfusion device. Tissues and organs of apparently dead animals could be brought back temporarily to an apparent living state by restoring the flow of blood to them.

1858: Brown-Sequard arterialized desaturated blood. He used syringes for perfusion and put oxygen into the dark venous blood by beating the blood vigorously. An interesting observation he made was the temporary disappearance of the rigor mortis of muscles of guillotined animals when they were perfused with their own blood, it was evident that supplying an adequate amount of oxygen to the blood is essential for successful perfusion.

1882: first “bubble”-oxygenator by von SchroederBubbling method was based on the supposition that bubbles of a gas, such as air or oxygen passing through blood, would become surrounded by a thin layer of the blood that in turn would absorb oxygen, give off carbon dioxide, and then burst and leave the blood free of gas.Drawback: foaming of the blood and gas embolism

1885: first “film”-type oxygenator Filming MethodIt is best technique for oxygenating the blood, the one that would form the basis of techniques currently in use. Von Frey and Gruber achieved this objective by dispersing the blood as a thin film inside a rotating slanted cylinder filled with oxygen.

1890: Jacob j described an device with a bubble oxygenator & bladder pump in order to provide pulsatile flow

(oxygenating the blood with a mechanical device altogether by accomplishing this objective through the use of the animal's own lungs)

1916: discovery of heparin by McLean significant step in evolution of heart-lung-machine

1928: Dale & Schuster described the prototype pumping mechanism (valved pump)

1934: Debakey modified the twin roller pump

1929: Brukhonenko

He perfusedGuillotined head of a dog. This preparation relied on gas exchange from a second donor dog's lungs. Diaphragm-like pumps pumped blood into the recipient dog's carotid arteries. Dog heads perfused in this manner remained functional for a few hours.

BIRTH OF AN IDEA AND THE DEVELOPMENT OF CARDIOPULMONARY BYPASS

A PATIENT IN DISTRESS

• It was mid afternoon on October 3, 1930 and a patient at the Massachusetts General Hospital in Boston.

• For 2 weeks her convalescence from an uncomplicated cholecystectomy had been uneventful.

• she suddenly developed discomfort in her right chest, and immediately the discomfort gave way to sharp pain.

• Dr. Edward Churchill, who saw her at once in consultation, found her frightened, pale, cyanotic, cold, and moist.

• John H. Gibbon, Jr. was assigned the task of watching the patient and monitoring her vital signs

• He believed that the diagnosis of massive pulmonary embolism.

• she was moved to the operating room where pulmonary embolectomy done.

“Idea naturally occurred to him that if it we continuously remove some of the blue blood from the patient's swollen veins, put oxygen into that blood and allow carbon dioxide to escape from it, and then inject continuously red blood back into the patient's arteries, we might have saved her life. We would have bypassed the obstructing embolus and performed part of the work of the patient's heart and lungs outside the body”

• Gibbon planned to build an apparatus with the oxygenating capacity, which permit safe total CPB in humans.

• Gibbon later estimated that if this objective were achieved using the rotating drum technique.

• Dr.Gibbons, inventor of the cardio-pulmonary bypass machine.

• 1935 –He maintained a cat’s circulation on CPB while closing the pulmonary artery.

1937 :Modified extracorporeal circuit of Gibbon

cannulas were silver coated and thin walled.

A piston-type air pump was being used. The oxygenated blood was delivered into the femoral artery in continuous flow with pulsatileincrements.

Aapparatus was used in later experiments when the pulmonary arteries of cats were occluded for prolonged periods with survival but DeBakey roller pumps are now used to withdraw and return

THE OPEN HEART ERA IS BORN

1952: Dr. John Lewis, after a period of laboratory research on dogs successfully closed a secundum ASD in a 5-year-old girl under direct vision using inflow stasis and moderate total body hypothermia.

• That was the world's first successful operation within the open human heart under direct vision.

1953: Henry Swan, at the University of Colorado, carried out his first open-heart procedure using hypothermia.

1959:Charles Drew, introduced ‘deep hypothermia’

• first successful repair of an atrial and ventricular septaldefect under deep hypothermia.

University of Minnesota Hospital operating room on September 2, 1952 near the end of the first successful open heart operation in medical history.

Dr. F. John Lewis closed an atrial septal defect under direct visualization using inflow stasis and moderate total body hypothermia (26°C).

In a 5-year-old girl who remains alive and well today. Postoperative heart catheterization confirmed a complete closure.

• 1953: John Gibbon

• Cecelia Bavolek First patient to undergo open heart surgery using CPB to repair an atrialseptal defect.

• Just as Gibbon was ready to close the defect, the oxygen saturation of the blood began to rapidly fall, and clots began to form on the oxygenator screens because of inadequate heparinization.

Azygous flow principle

• Morley cohen during some canine experiments in which the cavae were temporarily occluded to test tolerance limits of the brain and heart to ischemia.

• It was discovered that if the azygos vein was not clamped the resulting very small cardiac output (8 to 14 mL/kg body weight/min) was sufficient to sustain the vital organs safely in animals for a minimum of 30 minutes at normothermia.

• Studies agreed that only about 10% of the basal cardiac output was needed to sustain animals unimpaired physiologically for a short period of time at normothermia.

• Reducing the volume of blood necessary to be pumped had immediate and immense benefits.

Autogenous lung for cardiopulmonary bypass

Dodrill experience Autogenous lung bypass

• Dodrill et al. developed a blood pump for animal and clinical use as a right, left, or combined heart bypass with autogenous lung oxygenator.

• In their series of four patients, three had partial heart bypasses (two left sides, one right side).

• All three lived but in only one therapeutic procedure (pulmonary valvuloplasty) carried out

• 1950s: Dodrill had the intention to bypass only the right/left heart (without oxygenation) or to use the patients own

lung as an oxygenator

• William T. Mustard used a monkey lung oxygenator

Cardiopulmonary Bypass• 1954. Lillehei

1st surgical closure of VSD

under controlled cross-

circulation

• Based on placental function

& azygous flow principle

• Used in 45 patients between

1954 to 1955

• VSD

TOF

AVSD

Controlled Cross-circulation

1953:Walton Lillehei’s heart-lung-machine bubble oxygenator (DeWall oxygenator) Sigmamotor pump disposable plastic tubing inexpensive

March 26, 1954:

University of Minnesota Medical Center, during the first controlled cross-circulation operation.

VSD was successfully visualized by ventricular cardiotomy and closed in a 12-month-old infant. The lightly anesthetized donor

( patient's father) with the groin cannulations serving as the extracorporeal oxygenator. The VSD was closed by direct suture during a bypass time of 19 minutes.

first attempts of cardiopulmonary bypass in the 1950s hadseries of disasters:- everyone built his own device - surgeons were inexperience with this new technology poor myocardial protection accidental intra operative air embolism postoperative bleeding

- only the sickest patients were referred to surgeons - error rate in preoperative diagnosis was high

1955: Mayo Clinic-Gibbon heart lung machine (screen oxygenator + rollar pump) . This model was used in first series of open heart operations performed by Dr. John Kirklin and associates

at the Mayo Clinic

More than 30 years of Innovation, Research, and Hard Work

General

Comments• CPB involves an extracorporeal circuit that

provides oxygenated systemic blood flow.

• Is accompanied by normovolemic hemodilution and nonpulsatile flow.

• The contact of blood with the extracorporeal circuit results in the activation of numerous cascades.

• Among the consequences of this contact are thrombin generation, the release of proinflammatory cytokines.

• This systemic inflammatory response may lead to multiple organ system compromise.

• Use of membrane oxygenators, biocompatible circuits, centrifugal pumps, leukocytes filtration and intraoperative steroids may reduce the inflammatory effects of CPB & had a significant impact on clinical outcomes.

• Despite adequate heparinization, the bypass circuit is a potent activator of the coagulation system with generation of factor Xa and thrombin.

• A coagulopathy may develop from activation of platelets and the fibrinolytic system, as well as from dilution of clotting factors and platelets during bypass.

• Circuits coated with the Carmeda BioActive surface, heparin (DurafloII) have been shown to improve biocompatibility, with reduced platelet activation and less release of proinflammatory mediators.

Cardiopulmonary Bypass

Development • 1951. Dodrill. Mitral valve surgery under left heart

bypass

• 1952. Dodrill. Relief of PS under right heart bypass

• 1952. Lewis. ASD closure under surface cooling

• 1953. Gibbon. ASD closure by heart-lung machine

• 1954. Lillihei. VSD closure under controlled cross-circulation

• 1954. Kirklin. Establishment of CPB with

oxygenator in cardiac surgery

Why CPB ?

• To facilitate a surgical intervention

• Provide a motionless field

• Provide a bloodless field

FUNCTIONS OF CPB

• Diversion of blood from heart

• Oxygenation, elimination of CO2

• Systemic cooling and rewarming

• Circulation of blood.

• Non physiological hypothermic hemodilutednon pulsatile circulation.

PRINCIPLES OF CPB

• HYPOTHERMIA

• HEMODILUTION

• ULTRAFILTRATION

• ANTICOAGULATION & NEUTRALIZATION

HYPOTHERMIA

• Mild - 32 –35 degrees

• Moderate - 26-32 degrees

• Deep - 18-26 degrees

• Profound - < 18 degrees

HYPOTHERMIA

• Feasibility and applicability of hypothermia for heart surgery was first suggested by Bigelow and colleagues in(1950)Rationale – provide organ protection and safety margin during CPB

• ↓ metabolic rate and o2 consumption• Preserve high energy po2 store and ↓ excitatory NT release• Lower pump flows suffice- ↓return, improve visibility, less

blood trauma• Better myocardial protection• Safety margin in equipment failure

Flow Rates In Hypothermia:

• 32 c: 2.1 to 2.2 lit / min /m2.

• 30 c: 1.8 to 1.9 lit / min /m2.

• 25 c: 1.6 lit / min /m2.

• 20 c: 1.4 to 1.5 lit / min /m2.

• 15 c: 1 to 1.1 lit / min /m2.

HYPOTHERMIA..

• Concept of Q10

• decrease of metabolic processes in relation of 10 degree c temperature change

• Q10 2-3 in human body

• Freezing – extensive tissue injury

CPB PhysiologyHypothermia

• Q10 (infants) – 3.65

Q10 (adults) – 2.6

• …Higher Q10 suggest a greater metabolic suppression related to hypothermia and hence ability to tolerate longer periods of “imperfect” perfusion on ischemia…

EFFECT OF HYPOTHERMIA ON MYOCARDIUM

• Basal myocardial O2 requirement is 10 ml/100g/min

• In the asystolic state this goes down to 0.1 ml/100g/min

• For every 10 degree drop in temperature there is an additional 50% decrease in O2 requirements

• However there is a potential for myocardial damage below 10 degrees due to damage to the membrane enzymes responsible for cellular integrity

• Therefore target myocardial temperatures are usually 10-15 degrees

HYPOTHERMIA..

• Heart↓HR↑Contractility↑dysarythmiaCoronary b f preserved

• Lungsprogressive↓ in ventilationGas exchange unchanged

• Kidney ↓renal b f↓concentrating ability Glycosuria

• Liver ↓ b f↓ metabolic & excretory function Marked hyperglycemia

• blood vessels- vasoconstriction-skeletal muscles and extremities

• Blood ↑ blood viscosity RBC- aggegationPortal platelet sequestrationComplement activation, catecholamine release Bradykinnin release

• Brain- With a linear decrease in CBF, CMRO2 decreases exponentially.

– At normothermia CBF/CMRO2 of 20:1 changes to 75:1 at deep hypothermia.

ACID BASE MANAGEMENT IN HYPOTHERMIA

ALPHA STAT

• Alpha = unprotonatedhistidine imidazole group/[H+]

• total CO2 content kept constant

• PH & PCO2 is allowed to vary with temperature

PH STAT

• pH kept constant at all temperatures

ALPHA STAT Vs PH STAT

PH STAT

• Increased CBF

• Global cerebral cooling

• Better flow to deep brain structures

• ↑ risk microemboli, cerebral edema, ↑icp, redistribution away from marginally perfused area

• Better in children

ALPHA STAT

• Less but adequate cerebral flow

• Better cerebral recovery

• Cerebral autoregulationpreserved

• Less arrhythmias

• Better in adults

CROSS OVER STRATERGY

• During deep hypothermia or TCA, adopt pH stat during the initial 10 mts of cooling and then cross over to alpha stat .

• Sometimes during TCA, initially go on bypass with alpha stat and change to ph stat a few minutes before TCA is initiated.

HEMODILUTION

• Rationale

– Large volume of homologous banked blood.

– Risk of blood borne infammation

– Severe pulmonary insufficiency

– ↓ immunity – sepsis, MODS

HEMODILUTION

• Blood -- non Newtonian fluid

• As shear rate decreases, viscosity increases.

-Cellular elements and plasma protein aggregate, form rouleaux, intra cellular bridging of fibrinogen.

HEMODILUTION

CPB

↓ flow rate & hypothermia → ↑viscosity

↑ vascular resistance

• Hemodilution

-↓ Hct → shear rate increasebridgesdisintegrate↓viscosity improve microperfusion.

HEMODILUTION..

• Advantages ↓ CPB complications Good tissue perfusionGood oxygen delivery

• Disadvantages ↓plasma colloid oncotic pressure↓plasma protein conc( PK & PD of drugs)↓coagulation factor/ platelet conc↓immunoglobulin conc.

HEMODILUTION

• Extreme hemodilution cause inadequate O2 delivery.

• At 25%- myocardial O2 extraction is complete.

• < 15%- maldistribution of coronary flow from sub endocardium.

• Target HCT- 20-25%

• Prime – crystalloid + colloid

ULTRAFILTRATION

• Reverses the `hemodilution` during CPB initiation and Optimises perfusate Hct

• Raises colloid osmotic pressure

• Decreases post CPB edema and weight gain

• Improved tissue perfusion and oxygenation

• Removes the vasoactive substances eg. C3a, C5a, TNF-α, IL-1b, IL-6, IL-8

• Improves hemostasis - increasing relative conc. of clotting factors

PRINCIPLES OF ULTRAFILTRATION

• Filtration rate –

• …Directly proportional to transmembrane pressure gradient & inversely proportional to Hct…

• …Concentration of all molecules smaller than smallest pores equal on both sides of the membrane…

• …Conc. of molecules larger than the smallest pores, but smaller than the largest pores is dependent on the sieving coefficient of that molecule…

• Conventional ultrafiltration:

done during CPB depending on HCT and venous reservoir level.

No fluid is given to replace that removed-creates negative balance.

ANTICOAGULATION-HEPARIN

N-sulfated-D-Glucosamine L-iduronic acid

• strongest acid,negatively charged

• Heterogenous compound, mol wt. 5000 – 30000

• UFH dose should not be specified by weight but by units.

• 1 USP of heparin activity is the quantity that prevents 1 ml of citrated sheep”s plasma from clotting for 1 hrafter addition of calcium.

• Standard heparin is UNFRACTIONATED HEPARIN (UFH ).

• Abundant in tissues rich in mast cells

liver, lungs, intestines

skin, lymph nodes, thymus lesser sources.

• Two sources for commercial preparation:

Bovine lung ,Porcine intestinal mucosa

• Metabolism:

50%- RES

50%- Renal elimination

• Actions:

Exerts its actions via AT-III which inhibits thrombin, IXa, Xa.

UFH accelerates the formation of thrombin-AT complex 2000 X, Xa-AT complex 1200X

LMWH preferentially inhibits Xa

• Dose:

300-400 u/ kg

given in central vein or directly into RA

always confirm with ACT

• UFH chelates Ca, large bolus- decline in BP due to decrease in SVR & preload.

• Immunologic effects-30-50% pts of cardiac surgery have heparin Abs by the time of hospital discharge

HEPARIN MONITORING- ACT

• Hattersley 1966

• Bull 1975 – use in CPB

• Can be done in OT

• Moderately Sensitive

• Measurable range during CPB

• kaolin tubes

• 3 mts after heparinisation

• >400 s – Target ACT

• Individual anticoagulation response to heparin varies, hence measurement of individual anticoagulation response to heparin for CPB is warranted. Usually heparin effect is measured and not its plasma levels.

• TREATMENT

additional heparin

AT-III concentrate

HEPARIN SUBSTITUTES

PROTAMINE

• Polycationic protein from Salmon sperm

• 67% arginine - Strong alkali

• Mild anticoagulant effect of its own

• Actions:

Formation of complexes with sulfate groups of heparin form the basis for antidote effect

Neutralizes AT effect of heparin far better than anti Xa effect, hence poor ability to neutralize LMWHs

PROTAMINE..

• Anti-coagulation reversal

Fixed dose – 1 mg/100 u heparin

• Sometimes even adequate dosage of protamine fails to normalise ACT

• In such cases the potential reasons are: platelet dysfunction and dilutional/consumption coagulopathy

Protamine reactions

• I – hypotension

• IIa- anaphylaxis

• IIb-immediate anaphylactoid

• IIc- delayed anaphylactoid

• III pulmonary vasoconstriction

PEDIATRIC CPB

• Smaller circulating volume

• Higher oxygen consumption rates

• Intracardiac/extracardiac shunts

• Immature organ systems

• Altered thermoregulation

• Poor tolerance to microemboli

• Reactive pulmonary bed

• Higher Q10

PEDIATRIC CPB- Physiological differences

• Smaller circulating blood volume

• Greater hemodilution on CPB and increased post CPB weight gain

• Dilution of clotting factors and platelets

• Decreased Body surface area to CPB circuit ratio

• More severe SIRS

CPB physiologyHemodilution & Coagulation

• Loss of oncotic activity and increased tissue edema

• Hepatic immaturity -lack of clotting factors.

• Cyanotics - Polycythemia, Abnormalities in platelets,Decrease in Factors 2,5,7,8 & 11, Hypofibrinogenemia, Increased FDP

IN OUR INSTITUTE

• Mild to mod hypothermia• Hemodilution- target min HCT 24%• Adult prime- RL + Mannitol + heparin+HCO3• Blood added to prime in pediatric patients• Alpha stat for mild- mod hypothermia in adults

and pediatric patients.• Cross over strategy in deep hypothermia/ TCA.• UF for redo cases, selected pediatric cases.• Anticoagulation with heparin 300u/ kg & reversal

with protamine 1 mg/100 unit of heparin.

DESIRED PUMP VALUES

ACT >480 seconds>350 seconds for biocompatible circuits

SYSTEMIC FLOW 2–2.5 L/min/m2 at 37 C1.7–2.0 (low flow) or 2.0–2.5 L/min/m2 (high flow) at 30 C

SYSTEMIC BLOOD PRESSURE 50-70 mm Hg

ABG PO2>250 torr, PCO2 40–50 torr with pH 7.40Deep hypothermia:a–stat pH 7.40 measured at 37 CpH–stat pH 7.40 at systemic temperature

HCT 24- 30%

BLOOD GLUCOSE 100-180 mm Hg

Referenc

es• SABISTON & SPENCER SURGERY OF THE CHEST-9th ed.

• MANUAL of PERIOPERATIVE CARE in ADULT CARDIAC SURGERY 5th ed--Robert M. Bojar.

• Evolution of Cardiopulmonary Bypass William S. Stoney, MD Circulation(Circulation. 2009;119:2844 –2853.) © 2009 American Heart Association, Inc

http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.108.830174

• The mid-century revolution in thoracic and cardiovascular surgery: Part 6 A.P. Naef 12 Avenue Villardin, CH-1009 Pully-Lausanne, Switzerland

Interactive CardioVascular and Thoracic Surgery 3 (2004) 535–541