CPB was developed to facilitate open heart surgery by diverting blood from the heart and providing oxygenated blood flow, allowing for a motionless and bloodless surgical field. Early innovations included experiments with external perfusion in animals in the 1800s. The first successful human open heart surgery using surface cooling was performed in 1952. Further developments led to the use of heart-lung machines and controlled cross-circulation techniques in the 1950s. While initial experiences had complications, advances in oxygenators, pumps, circuits and management of coagulation and inflammation improved outcomes and established CPB as essential for cardiac surgery.

1. PRINCIPLES & evolution OF CARDIO
PULMONARY BYPASS

2. 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.

3. 1882: first “bubble”-oxygenator by von Schroeder
Bubbling 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 Method
It 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.

4. 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

5. 1929: Brukhonenko
He perfused
Guillotined 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.

6. 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

7. • He believed that the diagnosis of massive
pulmonary embolism.
• she was moved to the operating room where
pulmonary embolectomy done.

8. “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”

9. • 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.

10. • Dr.Gibbons, inventor of
the cardio-pulmonary
bypass machine.
• 1935 –He maintained a
cat’s circulation on CPB
while closing the
pulmonary artery.

11. 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 pulsatile
increments.
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

12. 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 septal
defect under deep hypothermia.

13. 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.

14. • 1953: John Gibbon
• Cecelia Bavolek First patient to undergo open
heart surgery using CPB to repair an atrial
septal 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.

15. 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.

16. • 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.

17. 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

18. • 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

19. 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

20. 1953:Walton Lillehei’s heart-lung-machine
bubble oxygenator (DeWall oxygenator)
Sigmamotor pump disposable plastic tubing inexpensive

21. 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.

22. first attempts of cardiopulmonary bypass in the 1950s had
series 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

23. 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

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

25. 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.

26. • 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.

27. 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

28. Why CPB ?
• To facilitate a surgical intervention
• Provide a motionless field
• Provide a bloodless field

29. FUNCTIONS OF CPB
• Diversion of blood from heart
• Oxygenation, elimination of CO2
• Systemic cooling and rewarming
• Circulation of blood.
• Non physiological hypothermic hemodiluted
non pulsatile circulation.

30. PRINCIPLES OF CPB
• HYPOTHERMIA
• HEMODILUTION
• ULTRAFILTRATION
• ANTICOAGULATION & NEUTRALIZATION

31. HYPOTHERMIA
• Mild - 32 –35 degrees
• Moderate - 26-32 degrees
• Deep - 18-26 degrees
• Profound - < 18 degrees

32. 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

33. 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.

34. 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

35. CPB Physiology
Hypothermia
• 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…

37. 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

38. HYPOTHERMIA..
• Heart
↓HR
↑Contractility
↑dysarythmia
Coronary b f preserved
• Lungs
progressive↓ in ventilation
Gas exchange unchanged
• Kidney
↓renal b f
↓concentrating ability
Glycosuria

39. • Liver
↓ b f
↓ metabolic & excretory function
Marked hyperglycemia
• blood vessels- vasoconstriction-skeletal muscles and
extremities
• Blood
↑ blood viscosity
RBC- aggegation
Portal platelet sequestration
Complement activation, catecholamine release
Bradykinnin release

40. • Brain- With a linear decrease in CBF, CMRO2
decreases exponentially.
– At normothermia CBF/CMRO2 of 20:1 changes to
75:1 at deep hypothermia.

41. ACID BASE MANAGEMENT IN
HYPOTHERMIA
ALPHA STAT
• Alpha = unprotonated
histidine imidazole
group/[H+]
• total CO2 content kept
constant
• PH & PCO2 is allowed to
vary with temperature
PH STAT
• pH kept constant at all
temperatures

42. 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 autoregulation
preserved
• Less arrhythmias
• Better in adults

43. 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.

44. HEMODILUTION
• Rationale
– Large volume of homologous banked blood.
– Risk of blood borne infammation
– Severe pulmonary insufficiency
– ↓ immunity – sepsis, MODS

45. HEMODILUTION
• Blood -- non Newtonian fluid
• As shear rate decreases, viscosity increases.
-Cellular elements and plasma protein
aggregate, form rouleaux, intra cellular bridging
of fibrinogen.

46. HEMODILUTION
CPB
↓ flow rate & hypothermia → ↑viscosity
↑ vascular resistance
• Hemodilution
-↓ Hct → shear rate increasebridges
disintegrate ↓viscosity  improve
microperfusion.

47. HEMODILUTION..
• Advantages
↓ CPB complications
Good tissue perfusion
Good oxygen delivery
• Disadvantages
↓plasma colloid oncotic pressure
↓plasma protein conc( PK & PD of drugs)
↓coagulation factor/ platelet conc
↓immunoglobulin conc.

48. 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

49. 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

50. 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…

51. • Conventional ultrafiltration:
done during CPB depending on HCT and
venous reservoir level.
No fluid is given to replace that removed-
creates negative balance.

52. 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 hr
after addition of calcium.
• Standard heparin is UNFRACTIONATED HEPARIN (UFH ).

53. • 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

54. • 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

55. • 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

56. 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

57. • 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

58. HEPARIN SUBSTITUTES

59. 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

60. 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

61. Protamine reactions
• I – hypotension
• IIa- anaphylaxis
• IIb-immediate anaphylactoid
• IIc- delayed anaphylactoid
• III pulmonary vasoconstriction

62. 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

63. 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

64. CPB physiology
Hemodilution & 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

65. 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.

66. DESIRED PUMP VALUES
ACT >480 seconds
>350 seconds for biocompatible circuits
SYSTEMIC FLOW 2–2.5 L/min/m2 at 37 C
1.7–2.0 (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
7.40
Deep hypothermia:
a–stat pH 7.40 measured at 37 C
pH–stat pH 7.40 at systemic temperature
HCT 24- 30%
BLOOD GLUCOSE 100-180 mm Hg

67. 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