CARDIOPULMONARY BYPASS, CARDIOPLEGIA & MYOCARDIAL PROTECTION

A Teaching Session for MD Final Exam Residents

"Anesthetizing patients for cardiac surgery is a dynamic, intellectually challenging, and demanding hands-on experience. The cardiac anesthesiologist must have a thorough understanding of normal and altered cardiac physiology, cardiovascular and anesthetic pharmacology, and be fully cognizant of the physiologic alterations associated with CPB."

• Barash's Clinical Anesthesia, 9e

PART I: CARDIOPULMONARY BYPASS (CPB)

1.1 Historical Background

1.2 Goals and Indications of CPB

• Rewarming in hypothermia
• Resuscitation in severe respiratory failure
• Pulmonary embolectomy (adjunct)
• Single- and double-lung transplantation
• Cardiopulmonary trauma
• Resection of highly vascular tumors invading large vessels (e.g., IVC in renal tumors)

1.3 Components of the CPB Circuit

1.4 The Pump: Roller vs. Centrifugal

• Compresses tubing to propel blood - occlusive, positive displacement
• Provides reliable constant flow
• Risk: if the reservoir empties, air is pumped directly to the patient

• Non-occlusive; uses spinning cone/impeller to create flow
• Cannot generate negative pressure, so air lock in the venous line cannot produce an air embolus
• More physiologic; preferred in many modern circuits
• Flow is preload- and afterload-dependent (not as reliable as roller)

1.5 Priming the Circuit

• Balanced salt solution (e.g., lactated Ringer's)
• Colloid (albumin or starch) - optional
• Mannitol (to promote diuresis)
• Heparin (500-5,000 units)
• Sodium bicarbonate

1.6 Cannulation Strategy

• Standard site: ascending aorta (between aortic cannula and aortic valve)
• Purse-string sutures placed; site inspected manually or by epiaortic scan for calcification/atheromatous plaques
• Alternatives (when ascending aorta is unsafe):
  • Femoral artery - retrograde flow, risk of mobilizing aortic plaques
  • Axillary artery - antegrade flow, preferred in aortic dissection, provides selective cerebral perfusion; increasingly popular

• Single "two-stage" cannula in the right atrial appendage (holes in IVC and RA)
• Alternatively, bicaval cannulation (separate SVC and IVC cannulae) - gives better control, needed for right-sided intracardiac procedures
• Femoral vein - alternative for thoracic aortic or minimally invasive procedures

1.7 Anticoagulation for CPB

• Dose: 300-400 units/kg IV
• Target: Activated Clotting Time (ACT) > 400-480 seconds before initiating CPB
• Monitoring: ACT measured immediately after heparinization, then every 20-30 minutes
• Cooling (hypothermia) increases the half-life of heparin and prolongs its effect
• Heparin dose-response curve can be used to guide dosing and protamine reversal

• Protamine is a highly positively charged protein that binds and inactivates heparin (which is highly negatively charged)
• Heparin-protamine complexes are removed by the reticuloendothelial system
• Dosing: 1-1.3 mg protamine per 100 units heparin administered
• Simpler approach: 3-4 mg/kg then check ACT
• Adverse reactions to protamine:
  • Type 1: Systemic hypotension from histamine release (rapid infusion)
  • Type 2: Anaphylaxis/anaphylactoid reaction (especially in NPH insulin-dependent diabetics, fish allergy)
  • Type 3: Catastrophic pulmonary vasoconstriction (rare, possibly complement-mediated)
• Excess protamine can itself have anticoagulant activity
• ACT must be rechecked 3-5 minutes after completing protamine infusion

1.8 Physiologic Characteristics of CPB

• Non-pulsatile flow (roller pump produces continuous flow)
• Lower-than-normal MAP (typically 50-80 mmHg)
• Hemodilution (hematocrit falls to 22-27%)
• Hypothermia (variable degrees)
• Activation of systemic inflammatory response (contact activation via blood-circuit interface, complement activation, cytokine release, neutrophil activation)

• Mild: > 28°C
• Moderate: 20-28°C
• Tepid: 30-35°C (used increasingly, allowing temperature to drift)
• Deep: < 20°C (used for total circulatory arrest)
• Profound: 15-18°C (for total circulatory arrest in arch surgery, pediatric complex repairs)
• Metabolic oxygen requirement is halved for each 10°C reduction in body temperature
• Adverse effects of hypothermia: platelet dysfunction, coagulopathy, depression of myocardial contractility
• At 28-29°C, VF often occurs spontaneously (hence cardioplegia should be established)
• Osborne wave (J wave) appears on ECG with hypothermia

• Standard: 2.2-2.4 L/min/m² (calculated indexed cardiac output)
• At 20°C: flows as low as 1.2 L/min/m² may be adequate
• Target MAP: 50-80 mmHg (higher MAP preferred in patients with cerebrovascular disease)

1.9 Monitoring During CPB

• ACT - every 20-30 minutes
• Hematocrit - not allowed to fall below 20%
• Blood glucose - even in non-diabetics (hypothermia and stress hyperglycemia)
• Serum potassium - rises due to cardioplegia (treat with furosemide diuresis)
• Arterial blood gas - pH management: alpha-stat vs. pH-stat
  • Alpha-stat: pH maintained at 7.40 at 37°C regardless of actual temperature; preferred for adults (neurological outcomes)
  • pH-stat: CO2 added to maintain pH 7.40 at actual temperature; preferred for pediatric patients and deep hypothermic circulatory arrest (DHCA)
• Temperature - nasopharyngeal, esophageal, bladder, rectal probes
• TEE - assessment of LV volumes, contractility, valvular function, de-airing, residual air

1.10 Ventilation During CPB

1. Adequate pump flows are reached
2. The heart stops ejecting blood

• Stop all gas flow, OR
• Maintain a very reduced O2 flow with CPAP 5 cmH2O to prevent postoperative pulmonary atelectasis/dysfunction

PART II: WEANING FROM CPB

2.1 Prerequisites for Weaning (Checklist)

• Core temperature > 36-37°C (adequate rewarming)
• Heart in sinus rhythm (or paced)
• Ventilation with 100% O2 resumed
• Hematocrit > 25%
• Electrolytes corrected (K+, Mg2+, Ca2+)
• Acid-base normalized
• All monitors rechecked and recalibrated
• Metabolic needs assessed (TEE showing LV volumes and function)

2.2 Weaning Technique

1. Progressively clamp the venous return line - heart fills, ejection resumes
2. Pump flow is gradually decreased as arterial pressure rises
3. Once venous line is completely occluded and systolic BP > 80-90 mmHg, pump flow is stopped
4. Patient is evaluated before decannulation

2.3 Post-CPB Hemodynamic Subgroups (Morgan & Mikhail Table 22-2)

2.4 Post-CPB Period

1. Venous decannulation
2. Heparin reversal with protamine
3. Aortic decannulation
4. Return of residual pump blood
5. Achievement of hemostasis
6. Chest closure
7. Transport to ICU

• Systolic BP kept < 140 mmHg (to minimize bleeding)
• Frequent ventricular ectopy - check electrolytes; treat with amiodarone
• Hypokalemia and hypomagnesemia must be corrected
• A final hematocrit of ≥ 25% is desirable

PART III: CARDIOPLEGIA

3.1 Definition and Purpose

• Provide a motionless, bloodless operative field
• Reduce myocardial oxygen consumption
• Protect the myocardium during the period of aortic cross-clamping

3.2 The Arresting Agent: Potassium

• The resting membrane potential rises from -90 mV toward threshold
• Inactivates fast Na+ channels (phase 0 cannot fire)
• The heart arrests in diastole (not systole)
• Electromechanical arrest reduces myocardial oxygen consumption by ~90%

3.3 Composition of Cardioplegia Solutions

3.4 Types of Cardioplegia Solutions

A. By Temperature

B. By Carrier Fluid

C. By Dosing Strategy

• 1 part blood + 4 parts crystalloid
• Additives: lidocaine, magnesium sulfate, sodium bicarbonate, mannitol, potassium chloride
• Used for adult cardiac surgery with anticipated short aortic cross-clamp times
• Originally developed for pediatric surgery

• Purely crystalloid
• Histidine as buffer, tryptophan as membrane stabilizer, ketoglutarate as energy substrate
• Large volume (up to 2 L) required
• Safe arrest time: up to 90 minutes (used in complex cases, transplantation)

3.5 Routes of Cardioplegia Delivery

A. Antegrade (Anterograde) Cardioplegia

• Most physiological
• Delivered proximal to the aortic cross-clamp into the aortic root
• Pressure: 60-100 mmHg
• Flows down into coronary ostia naturally

• Severe coronary artery stenosis can prevent uniform distribution
• Aortic regurgitation causes solution to pool in LV (not entering coronaries) - LV distension and failure to arrest
• In aortic regurgitation or during aortic valve replacement: cardioplegia must be given directly into the coronary ostia via hand-held cannulae

B. Retrograde Cardioplegia

• Catheter placed in the coronary sinus (with an inflatable balloon to prevent backflow)
• Delivery: 200-400 mL/min to a venous pressure of 30-50 mmHg
• Arrest typically occurs in 2-4 minutes (vs. 30-60 seconds for antegrade)

• Effective in patients with severe CAD (bypasses obstructive plaques)
• Useful when antegrade is contraindicated (significant AI)
• During CABG: individual grafts can deliver cardioplegia after distal anastomoses

• Poor distribution to right ventricle free wall and posterior 1/3 of interventricular septum (RCA territory)
• Microvascular areas less able to sustain energy metabolism
• Placement of coronary sinus catheter requires skill

C. Combined (Antegrade + Retrograde)

• Most complete technique for myocardial protection
• Often administered simultaneously in both directions
• Especially important in patients with severe CAD and/or significant AI

3.6 Timing and Re-Dosing

• Cold cardioplegia: Redosed every 20-30 minutes
• Warm cardioplegia: Must be delivered continuously (washout leads to rapid resumption of electrical activity)
• del Nido: Single dose for anticipated short cross-clamp; re-dose at 60-90 minutes if needed
• HTK: Single large-volume dose

• 30-60 seconds - antegrade delivery
• 2-4 minutes - retrograde delivery

PART IV: MYOCARDIAL PROTECTION DURING CPB

4.1 The Problem: Ischemia During CPB

• Aerobic metabolism stops within seconds
• Anaerobic metabolism becomes the principal energy source
• High-energy phosphate (ATP) stores are rapidly depleted
• Fatty acid oxidation is impaired
• Progressive lactic acidosis develops
• Intracellular calcium begins to rise
• Permanent myocardial damage can develop within 15-20 minutes without protection

4.2 The Triad of Myocardial Protection

1. Hypothermia - reduces metabolic rate
2. Cardioplegia - arrests electromechanical activity (greatest single reduction in O2 consumption)
3. LV decompression - reduces wall tension and O2 demand

"The goal is to minimize myocardial metabolic function." - Barash, 9e

4.3 Hypothermia

• Each 1°C reduction below 37°C decreases cellular metabolism by approximately 8%
• At 28°C, metabolic rate falls to 50%
• Preserves high-energy phosphate substrates
• Inhibits excitatory neurotransmitter release

• Cold (ice) solution poured around the heart ("ice slush")
• Cold cardioplegia solution (10-15°C) directly into coronary vessels
• Myocardial temperature is often monitored (target: < 15°C with cold cardioplegia)

• Reduces myocardial O2 consumption by 97%
• Enables the tissue to withstand complete cessation of blood flow for 20-90 minutes (depending on cardioplegia type)

4.4 LV Decompression (Venting)

• LV distension increases wall tension and therefore oxygen consumption (LaPlace's law: T = P × r / 2h)
• LV vent is a small cannula placed in the LV (via pulmonary veins, pulmonary artery, or aortic root) connected to the CPB circuit
• Critical in aortic regurgitation: regurgitant antegrade cardioplegia fills the LV - the vent prevents distension and ensures arrest
• Monitored with TEE

4.5 Ischemia-Reperfusion Injury

1. Oxygen-derived free radicals (ROS) - generated at the moment of reoxygenation
2. Intracellular calcium overload - begins during ischemia; worsened during reperfusion due to cell membrane damage
3. Abnormal endothelial-leukocyte interactions - neutrophil activation, endothelial adhesion
4. Myocardial cellular edema - osmotic imbalance

• Myocardial "stunning" - reversible systolic and diastolic dysfunction; responds to inotropic drugs; time-dependent recovery
• Myocardial necrosis - irreversible injury
• Inadequate myocardial protection manifests at end of bypass as: reduced cardiac output, worsened ventricular function on TEE, cardiac arrhythmias

4.6 The "Warm Shot" / "Hot Shot" Concept

• After completion of the surgical procedure, warm (37°C) normokalemic blood is infused into the coronary arteries before releasing the cross-clamp
• This "hot shot" or "warm reperfusate" provides:
  • Metabolic substrates (glucose, glutamate, aspartate)
  • Oxygen for aerobic recovery
  • Washes out acidic metabolites
  • Delivered via cardioplegia cannulas
• May also include glutamate/aspartate to replenish depleted energy substrates

4.7 Patients at Highest Risk for Poor Myocardial Protection

• Poor preoperative left ventricular function (EF < 35%)
• Ventricular hypertrophy (increased oxygen demand, impaired subendocardial perfusion)
• Diffuse severe CAD (limits antegrade distribution)
• Aortic regurgitation (antegrade cardioplegia enters LV cavity)
• Combination of the above
• Prolonged aortic cross-clamp time (> 60-90 minutes increases risk)

4.8 Volatile Anesthetic Preconditioning

• Volatile anesthetics (sevoflurane, isoflurane, desflurane) precondition the myocardium against ischemia-reperfusion injury
• Reduce myocardial infarct size
• Mechanism: activation of KATP channels, mitochondrial protection, anti-inflammatory effects
• Volatile agent should be administered before CPB (preconditioning) and ideally also during CPB via vaporizer in the oxygenator

4.9 Total Circulatory Arrest (TCA)

• Complex pediatric cardiac surgery
• Aortic arch surgery
• Pulmonary endarterectomy

• CPB established; core temperature reduced to 15-18°C (profound hypothermia)
• Metabolic rate reduced to ~5-10% of normal at 15°C
• Both heart AND CPB machine are stopped
• Safe duration: up to 20-30 minutes (brain is most vulnerable)
• Additional cerebral protection:
  • Ice packs around the head
  • Pharmacological: thiopental (burst suppression), steroids, mannitol
  • Selective cerebral perfusion techniques for longer arrest times:
    • Antegrade selective cerebral perfusion (via axillary or carotid artery) - allows longer safe arrest
    • Retrograde cerebral perfusion (via SVC) - less effective but widely used

PART V: POST-CPB COMPLICATIONS

PART VI: VIVA QUESTIONS - MD FINAL EXAMINATION

SECTION A: Core Concepts

• Advantages: Reduces metabolic rate through local hypothermia; combined with K+ arrest reduces MVO2 by 97%; allows intermittent delivery; simpler to manage
• Disadvantages: Enzyme depression (impairs metabolic recovery); risk of "stone heart" (calcium paradox) with prolonged ischemia; potential for cold contracture at very low temperatures

• Advantages: Better activation of intramyocardial enzymes; better post-op cardiac indices; provides ongoing aerobic metabolism; better metabolic protection during delivery; avoids hypothermic injury
• Disadvantages: Must be delivered continuously - any interruption allows electrical activity to resume and the heart to resume consuming oxygen; more complex management; temperature of the heart rises between doses; less room for error

1. The right ventricular free wall is poorly perfused retrograde (the coronary veins of the RV drain directly into the RA, bypassing the coronary sinus)
2. The posterior 1/3 of the interventricular septum (RCA territory) is poorly perfused
3. Microvascular areas receiving retrograde perfusion are less able to sustain energy metabolism
4. Slower arrest (2-4 minutes vs. 30-60 seconds antegrade)
5. Requires experience and skill for correct catheter placement
6. Cannot monitor distribution directly

1. Deliver cardioplegia directly into the coronary ostia via hand-held Conney/DLP cannulae inserted directly once the aorta is opened (standard for AVR)
2. Use retrograde cardioplegia via the coronary sinus as an adjunct or alternative
3. Ensure LV venting is adequate and functioning before cross-clamping - monitor with TEE
4. Vigilance for lack of rapid electrical arrest even with direct ostial delivery (the other coronary ostium may be difficult to access)

• Composition: 1 part blood + 4 parts crystalloid, with additives: lidocaine, magnesium sulfate, sodium bicarbonate, mannitol, potassium chloride
• Originally developed for pediatric cardiac surgery; now increasingly used in adults
• Safe arrest time: ~45-60 minutes (single dose for short cross-clamp cases)
• Lidocaine adds membrane stabilization (Na+ channel blockade)

• Purely crystalloid
• Histidine: buffer; Tryptophan: membrane stabilizer; Ketoglutarate: energy substrate
• Safe arrest time: up to 90 minutes
• Large volume required (~1-2 L infused slowly)
• Used in complex procedures, multiorgan donation, heart transplantation
• Crystalloid only (no oxygen carrying capacity)

1. KATP channel activation - both sarcolemmal and mitochondrial; hyperpolarizes mitochondrial inner membrane, reducing calcium entry during ischemia
2. Mitochondrial permeability transition pore (mPTP) inhibition - prevents mPTP opening during reperfusion (the point at which most reperfusion injury occurs)
3. PKC-epsilon activation - intracellular kinase signaling cascade
4. Anti-inflammatory effects - reduce leukocyte adhesion and cytokine release
5. Nitric oxide pathway activation

1. Contact activation of Factor XII (Hageman factor) and the kallikrein-bradykinin system
2. Complement activation (alternative and classical pathways) - C3a, C5a (anaphylatoxins) released
3. Cytokine release - TNF-alpha, IL-1, IL-6, IL-8
4. Neutrophil activation - superoxide generation, elastase release, endothelial adhesion
5. Platelet activation - aggregation, thromboxane release
6. Endothelial dysfunction - increased permeability, reduced NO production

• Post-CPB vasodilation / low SVR (SIRS-like state)
• Capillary leak and fluid shifts
• Pulmonary dysfunction (decreased compliance, ARDS in severe cases)
• Neurological injury (cerebral microemboli, cerebral edema)
• Renal impairment
• Coagulopathy
• Increased risk of infection

• Heparin-coated circuits
• Leukocyte filters
• Cell salvage (avoiding blood exposure to air)
• Steroids (methylprednisolone) - still debated
• Minimizing CPB duration
• "Miniaturized" CPB circuits

1. Confirm hemostasis is judged acceptable and the patient is hemodynamically stable
2. All CPB cannulae removed (venous first, then aortic last - aortic is kept available for rapid volume administration)
3. Protamine administration - via a peripheral venous or central venous line (never the arterial line or directly into the pulmonary artery, as this can precipitate pulmonary hypertensive crisis)
4. Give slowly (over 10-15 minutes) to avoid rapid histamine release and hypotension
5. Dose: 1-1.3 mg protamine per 100 units heparin administered; or 3-4 mg/kg simple adult dose; or based on heparin dose-response curve
6. Recheck ACT 3-5 minutes after completion - target: return to pre-heparin baseline ACT
7. If ACT still elevated: additional protamine doses (25-50 mg increments)

• Type 1 (common): Systemic hypotension, bradycardia (histamine release from too-rapid infusion; treat by slowing infusion rate, fluids, vasopressors)
• Type 2: Anaphylaxis/anaphylactoid reaction (rare; high risk in patients with NPH insulin use - contains protamine, prior protamine exposure, fish allergy)
• Type 3: Catastrophic pulmonary vasoconstriction with RV failure (very rare; complement-mediated; treat with pulmonary vasodilators: inhaled NO, milrinone, epoprostenol)

1. Low arterial pressure (inadequate perfusion pressure to coronary ostia)
2. Obstruction of bypass graft ostium (surgical technical issue)
3. Coronary artery embolism - from thrombi, platelets, air, fat, or atheromatous debris
4. Reperfusion injury (cellular damage during reoxygenation)
5. Coronary artery or bypass graft vasospasm
6. Kinking of excessively long or short bypass grafts
7. Contortion of the heart during surgical manipulation - compresses or kinks coronary vessels
8. Inadequate reversal from cardioplegia (inadequate washout - asystole or poor contractility)
9. Air embolism into the coronary ostia (especially right coronary, which is anterior and most vulnerable)
10. Myocardium distal to high-grade coronary obstruction is at greatest risk

SECTION B: Short Answer / Spot Questions

SECTION C: Scenario-Based Questions

1. Verify the diagnosis - is the LV truly failing or is there a correctable cause? TEE to assess LV function, regional wall motion, RV, valves, any residual air
2. Check and correct electrolytes (K+, Mg2+, Ca2+), acid-base, hematocrit (> 25%), rhythm (pace if bradycardia)
3. Optimize preload (CVP/PCWP)
4. Inotropic support: Start dobutamine 5-15 mcg/kg/min; consider milrinone (especially if elevated PVR) or epinephrine for severe failure
5. IABP insertion - diastolic augmentation increases coronary perfusion, systolic unloading reduces afterload
6. If persists: notify surgeon - consider LVAD (Impella, TandemHeart) or ECMO for severe refractory failure
7. Ongoing: look for reversible causes - graft occlusion, embolism (return to CPB for re-grafting), reperfusion stunning (may recover with time and inotropic support)

1. Stop protamine infusion immediately
2. Surgeon is alerted - may need to return to CPB (leave aortic cannula in place until protamine is reversed/treatment initiated)
3. 100% O2, hyperventilation to reduce PVR
4. Pulmonary vasodilators:
   • Inhaled nitric oxide (iNO) 10-40 ppm - selective pulmonary vasodilator, no systemic effects
   • Milrinone IV - PDE3 inhibitor, reduces PVR and supports RV
   • Prostaglandin E1 / Epoprostenol IV or inhaled
5. Systemic vasopressors to maintain adequate coronary perfusion pressure to the RV (norepinephrine, vasopressin)
6. Epinephrine for RV inotropic support
7. If hemodynamics do not improve: return to CPB - may need ECMO for bridging
8. Heparin for reprotamine reversal does not apply; manage the hemodynamic crisis
9. Alternative anticoagulants for subsequent protamine use (or avoid protamine if possible)

Key Take-Home Points (Summary for Viva Revision)