Basic Principles of Cardiopulmonary Bypass (CPB)

1. Introduction & Historical Background

• Rewarming in accidental hypothermia
• Resuscitation in severe respiratory failure
• Adjunct in pulmonary embolectomy
• Single- and double-lung transplantation
• Resection of highly vascular tumours invading large vessels (e.g. renal tumour invading the IVC)

2. The CPB Circuit - Basic Components

1. Venous blood drains from patient (via venous cannula in RA/SVC/IVC) by gravity siphon to the venous reservoir
2. Blood flows through the oxygenator - CO₂ removed, O₂ added
3. Heat exchanger adjusts temperature
4. Main pump drives blood forward
5. Arterial line filter removes micro-emboli and air
6. Oxygenated blood returns to patient via arterial cannula (usually ascending aorta)

2.1 Venous Reservoir

• Receives deoxygenated blood from the venous cannula(e)
• Gravity drainage: reservoir positioned 50-70 cm below the level of the heart
• Acts as a buffer against fluctuations in venous return
• Air lock from entrained air can stop venous flow - a critical hazard
• Reservoir level is critical: if a roller pump runs dry, massive air embolism results (lethal)
• If drainage is inadequate (small cannula), assisted venous drainage using regulated vacuum is used

2.2 Mechanical Pumps

2.3 Oxygenators

• Blood flows on one side of a microporous membrane, gas (O₂/CO₂ mixture) on the other
• Diffusion of O₂ into blood and CO₂ out replicates pulmonary gas exchange
• Older bubble oxygenators (blood directly exposed to gas) are now obsolete due to haemolysis and microemboli
• Membrane oxygenators cause far less blood trauma and inflammatory activation

2.4 Heat Exchanger

• Allows active cooling and rewarming of the patient's blood
• Water (at controlled temperature) passes through coils in counter-current to blood
• Used to induce systemic hypothermia and to re-warm before weaning from bypass
• Temperature gradient between water and blood must be kept < 10°C to avoid gas coming out of solution (nitrogen emboli)

2.5 Arterial Line Filter

• Positioned between the pump and the arterial cannula
• Removes micro-emboli, air bubbles, and debris from the circuit
• Contains a 20-40 micron screen filter

2.6 Ancillary Components

• Cardiotomy suction pump: returns blood from the operative field to the venous reservoir after filtering
• LV vent: small cannula placed in the LV to drain blood that accumulates (from bronchial venous return, thebesian veins) - prevents LV distension, which impairs myocardial preservation
• Cardioplegia delivery pump: delivers cardioplegic solution to the coronary arteries

3. Cannulation

3.1 Arterial Cannulation

• Standard site: ascending aorta (most physiological, antegrade flow)
• Alternatives (when ascending aorta not suitable):
  • Femoral artery - retrograde flow, risk of atheroembolism, limb ischaemia
  • Axillary artery - antegrade flow, preferred in aortic dissection, complex aortic surgery; provides selective antegrade cerebral perfusion
• Before cannulation, manual or epiaortic ultrasound inspection rules out severe calcification to reduce stroke risk
• Two purse-string sutures placed, air excluded from cannula before connection

3.2 Venous Cannulation

• Single two-stage cannula (tip in IVC, side holes in RA) - standard for most procedures
• Bicaval cannulation (separate SVC + IVC cannulae) - essential for right heart, tricuspid valve, and atrial surgery
• Alternatively: femoral vein (for minimally invasive or re-do surgery)
• Prerequisite: full systemic heparinisation before cannulation

4. Pump Prime (Priming Solution)

• Volume: 1200-1800 mL for adults
• Standard composition: balanced salt solution (lactated Ringer's) is the base; commonly added components include:
  • Colloid (albumin or starch) - to maintain oncotic pressure
  • Mannitol (0.5 g/kg) - promotes diuresis, free radical scavenger
  • Heparin (500-5000 units) - to anticoagulate circuit
  • Sodium bicarbonate - buffer

5. Anticoagulation

5.1 Heparin

• Mandatory before cannulation and bypass
• Dose: 300-400 units/kg IV (unfractionated heparin)
• Mechanism: Activates antithrombin III → inhibits thrombin and factor Xa → prevents clot formation within the circuit

5.2 Monitoring - Activated Clotting Time (ACT)

• Baseline ACT: 80-130 seconds (normal)
• Target ACT on CPB: ≥ 400-480 seconds (most centres use ≥ 480 sec)
• ACT is checked every 30-60 minutes during bypass; additional heparin given as needed
• Heparin resistance (due to antithrombin III deficiency, prior heparin use) may require fresh frozen plasma or antithrombin III concentrate

5.3 Heparin Reversal - Protamine

• Given at termination of bypass to reverse heparinisation
• Dose: approximately 1 mg protamine per 100 units heparin given (titrated to ACT)
• Adverse reactions to protamine:
  • Hypotension (most common, dose/rate-dependent)
  • Anaphylaxis (especially in patients with fish allergy, prior protamine insulin use, or vasectomy)
  • Catastrophic pulmonary vasoconstriction (rare but fatal)
  • Given slowly (over 10-15 min) via a peripheral vein to minimise reactions

6. Systemic Hypothermia

• Core temp cooled to 15-18°C
• Both heart and CPB machine stopped
• Provides a bloodless, motionless field for complex aortic arch repairs and complex congenital heart defects
• Safe arrest duration: up to 60 minutes with good cerebral protection
• Brain protection adjuncts: ice packing around the head, methylprednisolone 30 mg/kg, mannitol 0.5 g/kg

• Platelet dysfunction and coagulopathy
• Depression of myocardial contractility
• Increased blood viscosity (mitigated by haemodilution)
• Prolonged drug metabolism (hypothermia reduces hepatic/renal drug elimination)

7. Myocardial Protection

7.1 Aortic Cross-Clamping

• Ascending aorta is cross-clamped to completely exclude the coronary arteries
• Heart becomes anoxic - permanent myocardial damage begins within 15-20 minutes
• Cardioplegia arrests the heart and limits ischaemic injury

7.2 Cardioplegia

• Cold (4-10°C): Reduces metabolic requirements; standard approach; requires redosing every 15-20 minutes
• Warm (37°C): May improve myocardial recovery by supporting enzymatic function; used for "hot shot" terminal warm cardioplegia
• Blood cardioplegia: Mixes blood with crystalloid solution (4:1 ratio); provides oxygen and buffering; considered superior for longer cross-clamp times

7.3 Topical Hypothermia

• Ice-slush poured around the heart after cross-clamping
• Provides local epicardial cooling to reinforce cardioplegia

7.4 Intermittent Cross-Clamp Fibrillation (ICXF)

• Intermittent ventricular fibrillation (VF) induced during cross-clamping without cardioplegia
• Used for beating-heart valve surgery and some CABG procedures
• Less metabolic protection than cardioplegia

7.5 Myocardial Injury Despite Protection

• Poor preoperative LV function
• Ventricular hypertrophy
• Diffuse severe coronary artery disease
• Cross-clamp time > 120 minutes
• Total CPB time > 120 minutes

8. Physiological Effects of CPB

8.1 Haemodynamic Changes

• Non-pulsatile flow (steady state, not pulsatile) - affects peripheral organ perfusion and baroreflex responses
• Mean arterial pressure (MAP) is typically lower than normal on CPB (50-80 mmHg acceptable)
• Flow rate: 2.0-2.4 L/min/m² at normothermia; can be reduced at hypothermic temperatures

8.2 Stress Hormone & Inflammatory Response

• Hormone surge: Catecholamines, cortisol, arginine vasopressin (ADH), angiotensin all increase markedly
• Complement activation: Via both the alternate (C3) and classical pathways from blood-artificial surface contact
• Coagulation cascade activated
• Platelet dysfunction: CPB depletes glycoprotein receptors; platelet count falls; platelet function impaired - major cause of post-CPB bleeding
• Leukocyte activation: Neutrophils release proteases and reactive oxygen species
• Kallikrein system and fibrinolysis activated

• Leukocyte-depleted blood cardioplegia
• Haemofiltration/ultrafiltration (removes inflammatory cytokines - particularly valuable in neonates/infants)
• Systemic corticosteroids (methylprednisolone) - modulate but do not eliminate response
• Miniaturised CPB circuits (reduce surface area of blood-artificial surface contact)
• Heparin-bonded circuits

8.3 Effects on Pharmacokinetics

• Volume of distribution: Suddenly increases with haemodilution - plasma concentrations of water-soluble drugs (e.g. muscle relaxants) drop abruptly
• Protein binding: Reduced (haemodilution, hypothermia, altered pH, free fatty acids from heparin-activated lipoprotein lipase)
• Drug elimination: Reduced hepatic and renal perfusion lowers drug clearance
• Hypothermia: Slows drug metabolism
• Net result: Lipid-soluble drugs (fentanyl, sufentanil) are relatively well-maintained; water-soluble drugs show marked concentration changes

8.4 Renal Effects

• Reduced renal perfusion (non-pulsatile flow, hypotension, low cardiac output)
• Acute kidney injury (AKI) is a common complication
• Maintained urine output (target: 0.5-1 mL/kg/hr during bypass) monitored via urinary catheter

8.5 Neurological Effects

• Cerebral autoregulation may be impaired during CPB
• Acid-base management during hypothermic CPB:
  • Alpha-stat: Maintain normal pH/PaCO₂ uncorrected for temperature; preferred in adults (better autoregulation, lower cerebral embolic load)
  • pH-stat: Add CO₂ to maintain temperature-corrected pH 7.4; increases CBF, may improve cerebral cooling; preferred in paediatric patients undergoing circulatory arrest
• Monitoring: EEG, NIRS (cerebral oximetry), transcranial Doppler (TCD) may be used; NIRS is increasingly integrated
• Complications: Stroke, post-operative cognitive dysfunction (POCD), delirium

9. Conducting CPB - Sequence of Events

Step 1: Initiation of Bypass

• Heparin given IV, ACT confirmed ≥ 480 seconds
• Arterial and venous cannulation
• Circuit connected; gradual transition to full CPB flow
• Ventilator stopped once full flow established
• Gradual cooling begins if hypothermia planned

Step 2: Maintenance of Bypass

• Full CPB flow (2.0-2.4 L/min/m²)
• Aortic cross-clamp applied; cardioplegia delivered
• Surgeon performs the cardiac procedure
• Anaesthesiologist maintains: ACT, MAP, temperature, gases, anaesthetic depth, urine output
• Cardioplegia repeated every 15-20 min

Step 3: Preparation for Weaning

• Surgical repair completed
• De-airing of cardiac chambers (critical - air embolism is fatal)
• Aortic cross-clamp released; coronary perfusion restored
• Rewarming to normothermia (nasopharyngeal ≥ 37°C)
• Correction of: acidosis, hypokalaemia, hypocalcaemia, Hb
• Heart rhythm established (spontaneous or by defibrillation/pacing)
• Epicardial pacing wires placed

Step 4: Weaning from CPB

• Ventilation restarted
• Venous inflow to pump reservoir gradually reduced
• Heart gradually takes over circulation
• TEE assessment of ventricular function
• Inotropic/vasopressor support initiated as needed
• When haemodynamics acceptable, CPB discontinued

Step 5: Termination of Bypass

• CPB discontinued
• Protamine given to reverse heparin (ACT returns to baseline)
• Cannulae removed
• Haemostasis achieved

10. Complications of CPB

11. Off-Pump Surgery (OPCAB)

12. Paediatric Considerations

• Circuit prime is 3x the infant's blood volume - blood is added to prevent excessive haemodilution
• Higher flow rates required (up to 200 mL/kg/min in neonates)
• MAP during CPB is lower (20-50 mmHg acceptable)
• pH-stat preferred during hypothermic CPB for better cerebral cooling before DHCA
• Intense inflammatory response due to large surface-area-to-blood-volume ratio; corticosteroids and modified ultrafiltration (after bypass) are used
• DHCA (15°C, up to 60 minutes) necessary for complex congenital repairs
• Calcium supplementation more frequently needed than in adults
• Weaning difficulty should prompt TEE evaluation for residual defects

Summary of Key Points for Exam

1. First successful CPB: Gibbon, 1953
2. Basic components: Venous reservoir → Oxygenator + Heat exchanger → Main pump → Arterial filter → Patient
3. Standard arterial cannulation site: Ascending aorta; alternatives - femoral, axillary artery
4. Priming volume (adults): 1200-1800 mL; causes haemodilution (Hct 22-27%)
5. Heparin dose: 300-400 units/kg; target ACT ≥ 480 sec; reversed with protamine
6. Hypothermia rationale: O₂ requirements halved per 10°C; DHCA at 15-18°C allows 60 min arrest
7. Cardioplegia: Potassium arrests heart in diastole; cold/warm, blood/crystalloid; antegrade/retrograde; repeat every 15-20 min
8. Non-pulsatile flow + hypothermia are major non-physiological aspects of CPB
9. Post-CPB SIRS: Complement, coagulation, kallikrein activation → inflammatory cascade
10. Alpha-stat for adults; pH-stat for paediatric patients undergoing DHCA
11. De-airing before cross-clamp removal is mandatory to prevent air embolism
12. Protamine adverse effects: Hypotension, anaphylaxis, pulmonary vasoconstriction