---

Cardiopulmonary Bypass (CPB) - Pathophysiology

MD Anaesthesiology Examination Notes

---

1. DEFINITION AND BASIC PRINCIPLE

• CPB diverts venous blood away from the heart via cannulae in the right atrium/vena cavae, oxygenates it, removes CO2, and returns it via an arterial cannula (usually ascending aorta)
• It replaces both cardiac and pulmonary function simultaneously
• Creates distinctly non-physiological conditions:
  • Non-pulsatile (laminar) flow
  • Mean arterial pressure lower than normal (50-70 mmHg)
  • Hemodilution
  • Systemic hypothermia
  • Blood-foreign surface contact

---

2. COMPONENTS OF THE CPB CIRCUIT

Pump Types:

• Roller pump: Occlusive; produces nonpulsatile flow proportional to RPM; can pump air - risk of air embolism
• Centrifugal pump: Non-occlusive; pressure-sensitive flow (must use flowmeter); less traumatic to blood; cannot pump air

---

3. PRIME VOLUME AND HEMODILUTION

• Prime volume: 1200-1800 mL in adults (typically balanced crystalloid - lactated Ringer's, ± colloid, mannitol, heparin, bicarbonate)
• At onset of CPB in adults, hemodilution decreases hematocrit to ~22-27%
• Formula: HCTr = (BVp × HCT) / (BVp + PVc)
• Blood added to prime for neonates/infants and severely anemic adults to prevent critical hemodilution

Consequences of Hemodilution:

• Reduced oxygen-carrying capacity
• Decreased plasma oncotic pressure - interstitial edema
• Dilution of coagulation factors - coagulopathy
• Dilution of plasma proteins - altered drug binding and pharmacokinetics
• Hypothermia from cold prime

---

4. ANTICOAGULATION DURING CPB

• Heparin is standard: 300-400 units/kg IV (target ACT >400-480 seconds)
• ACT (Activated Clotting Time): Normal <130 s; must be >480 s before initiating CPB
• Note: ACT is influenced by hypothermia, hemodilution, coagulopathy - not purely heparin levels
• Some centers monitor both ACT and circulating heparin levels (1.5-3.0 units/mL target)
• Reversal: Protamine sulfate (1 mg per 100 units heparin given)

---

5. HYPOTHERMIA DURING CPB

Degrees of Hypothermia:

Physiological Effects:

• Beneficial: Reduces metabolic rate (~7% per 1°C), decreases O2 consumption, protects organs (especially brain)
• Harmful:
  • Shifts oxyhemoglobin dissociation curve left (increased Hb-O2 affinity, impaired O2 delivery)
  • Coagulopathy (impairs platelet function and coagulation enzymes)
  • Dysrhythmias (especially <28°C) - VF common at <28°C
  • Increased SVR and viscosity
  • Impaired renal clearance
  • Insulin resistance, hyperglycemia
  • Cold-induced diuresis initially

Deep Hypothermic Circulatory Arrest (DHCA):

• At 15-20°C, up to 60 minutes of complete circulatory arrest is feasible
• Ice packing around head used to prevent rewarming
• Pharmacological brain protection: Methylprednisolone 30 mg/kg + Mannitol 0.5 g/kg
• pH-stat vs α-stat management - pH-stat preferred in pediatric DHCA (more homogeneous cooling, better cerebral metabolic recovery); α-stat preferred in adults with moderate hypothermia (Level A recommendation)

---

6. SYSTEMIC INFLAMMATORY RESPONSE (SIRS) TO CPB

Triggers of Inflammatory Cascade:

1. Blood-foreign surface contact - tubing, oxygenator membrane, reservoir
2. Surgical stress itself
3. Ischemia-reperfusion injury
4. Gaseous and particulate microembolization
5. Endotoxin release from gut ischemia

Molecular Cascade:

• Initiators: Endotoxin, TNF-α, Nuclear factor κB (NF-κB), complement anaphylatoxins (C3a, C5a)
• Complement activation: Both classical and alternative pathways activated; C3a and C5a are potent anaphylatoxins responsible for the "postpump syndrome"
• Effector cells activated: Polymorphonuclear neutrophils (PMNs), platelets, endothelial cells
• Mediators released: Cytokines (IL-1, IL-6, IL-8, TNF), oxygen free radicals, proteases, thromboxane A2, bradykinin

Effects of the Inflammatory Response:

• Upregulation of adhesion molecules (ICAM-1, selectins) → neutrophil adhesion to endothelium
• Cytotoxic oxygen radical and protease release → endothelial damage → capillary leak
• Generalized capillary leak syndrome → interstitial edema, weight gain (3-5 kg)
• Vasoplegia/vasodilatory shock (see below)
• Multi-organ injury (cardiac, pulmonary, renal, neurologic, GI)

Strategies to Reduce SIRS:

1. Surgical/perfusion technique modification: Off-pump CABG (OPCAB), minimally invasive surgery, minimizing aortic manipulation
2. Circuit modifications: Heparin-bonded circuits, biocompatible coatings, ultrafiltration (especially modified ultrafiltration in pediatrics), miniaturized circuits
3. Pharmacological: Corticosteroids (especially in children), aprotinin (withdrawn), tranexamic acid, epsilon-aminocaproic acid

---

7. HEMODYNAMIC EFFECTS OF CPB

Non-Pulsatile (Laminar) Flow:

• Baroreceptors respond to absence of pulse pressure → increased catecholamine, renin-angiotensin release
• Impaired microcirculatory flow and oxygen delivery
• Reduced lymphatic flow
• Increased SVR (organ beds respond to laminar flow with vasoconstriction)

Vasoplegia (Vasoplegic Syndrome):

• Profound vasodilation with high CO, low SVR following CPB
• Mechanism: Excess NO production, impaired vasopressin secretion, cytokine-mediated vasodilation
• Treatment: Norepinephrine, vasopressin, methylene blue (inhibits guanylyl cyclase - interrupts cGMP-mediated vasodilation); phenylephrine

Blood Pressure Management During CPB:

• Target MAP: 50-80 mmHg (higher targets for elderly, hypertensives, diabetics, carotid disease)
• Low MAP: Risk of cerebral, renal, and spinal cord ischemia
• High MAP: Increased risk of aortic dissection, increased surgical bleeding

---

8. COAGULOPATHY ASSOCIATED WITH CPB

Causes (Multifactorial):

1. Hemodilution - dilution of all coagulation factors and platelets
2. Hypothermia - impairs platelet function (releases TXA2 reduced), slows enzymatic coagulation reactions
3. Heparinization - blocks thrombin and factor Xa
4. Platelet dysfunction - activation on foreign surfaces depletes platelet granules; GPIb receptor down-regulation
5. Fibrinolysis - plasminogen activators released from endothelium; tPA released
6. Consumption coagulopathy - subclinical DIC possible during bypass
7. Protamine reactions can cause platelet aggregation, pulmonary hypertension

Post-CPB Bleeding Management:

• TEG/ROTEM - viscoelastic testing to guide targeted factor replacement
• ACT normalization with protamine
• Antifibrinolytics - Tranexamic acid, epsilon-aminocaproic acid (reduces surgical bleeding)
• Desmopressin (DDAVP) - useful if uremic platelet dysfunction or vWF deficiency
• Fresh frozen plasma, cryoprecipitate, platelets as guided by TEG

---

9. ORGAN-SPECIFIC EFFECTS OF CPB

A. Cardiac Effects:

• Myocardial ischemia from aortic cross-clamping → global ischemia
• Myocardial protection: Cardioplegia (hyperkalemic solution - arrests heart in diastole; usually cold, crystalloid or blood-based; delivered antegrade via aortic root or retrograde via coronary sinus)
• Reperfusion injury on unclamping: Calcium overload, free radical burst, mitochondrial dysfunction
• Post-bypass myocardial stunning - transient contractile dysfunction despite restored flow
• Dysrhythmias - VF during hypothermia; post-bypass AF common (30-40%)

B. Pulmonary Effects:

• Lungs are not ventilated during CPB (pulmonary circulation is bypassed) → atelectasis
• Pulmonary ischemia → surfactant depletion
• Complement-activated neutrophils sequester in lungs → ALI/ARDS (post-perfusion lung/pump lung)
• Increased pulmonary vascular resistance post-CPB
• Pulmonary edema from capillary leak
• Management: Low tidal volume ventilation, PEEP, early extubation (fast track)

C. Neurological Effects:

• Type I (focal deficits/stroke): Due to macroembolism (thrombus, atheromatous debris from aorta, air)
• Type II (neurocognitive dysfunction/POCD): Diffuse, multifocal; due to microemboli, hypoperfusion, inflammation, hyperthermia during rewarming
• Emboli sources: Aortic cannulation site, cardiotomy suction, air from open chambers, calcium deposits
• Cerebral monitoring: EEG, NIRS (cerebral oximetry), TCD for emboli detection
• Risk factors: Aortic atherosclerosis, carotid disease, older age, prolonged bypass time, diabetics

D. Renal Effects:

• AKI occurs in 5-30% of patients (severe needing RRT in ~1-3%)
• Mechanisms:
  • Non-pulsatile flow → reduced renal perfusion pressure
  • Hypotension and reduced renal blood flow
  • Hemolysis → free hemoglobin → tubular toxicity
  • Inflammatory mediators
  • Microemboli
  • Longer bypass duration = greater risk
• Monitor: Urine output, color (reddish urine = hemolysis), creatinine
• Fenoldopam and dopamine studied but no clear renal protective benefit proven

E. Gastrointestinal Effects:

• Splanchnic hypoperfusion during CPB → intestinal ischemia
• Gut ischemia → endotoxin release → amplifies SIRS
• Rare but serious: Ischemic colitis, pancreatitis, cholecystitis, hepatic dysfunction
• Mesenteric ischemia - highest mortality complication

F. Endocrine/Metabolic Effects:

• Stress response: Massive catecholamine, cortisol, vasopressin, glucagon release
• Hyperglycemia - insulin resistance; tight glucose control (140-180 mg/dL) recommended
• Hypokalemia during hypothermia (K+ shifts intracellularly)
• Hypocalcemia - from citrate in blood products and hemodilution
• Hypothyroidism-like state - decreased T3 during CPB

---

10. HEMOLYSIS DURING CPB

• Caused by: Roller pump shear stress, cardiotomy suction, cavitation, gas-blood interface in oxygenator
• Free plasma hemoglobin precipitates in renal tubules → AKI
• Centrifugal pumps are less hemolytic than roller pumps
• Reddish urine during CPB = hemolysis; increased urine output (mannitol) recommended

---

11. AIR EMBOLISM

• A catastrophic complication
• Sources: Venous reservoir emptying (air lock), cardiotomy suction, cardiac chambers on deairing, aortic root on unclamping
• Venous air embolism prevented by hard-shell reservoirs with level alarms and roller pump design
• Arterial air embolism: From oxygenator or undetected venous air entering arterial line
• Centrifugal pumps have advantage of not pumping air forward
• Arterial filter traps and vents bubbles

---

12. WEANING FROM CPB

Prerequisites for Weaning:

• Core temperature >36°C (rewarmed)
• Sinus rhythm restored (DC shock if needed)
• Electrolytes corrected (K+, Ca2+, glucose)
• Adequate Hb (>7-8 g/dL, or >8-10 g/dL in high-risk patients)
• Lung re-expansion and ventilation restarted
• ACT reversal with protamine begun
• Adequate MAP and CO on monitoring

Post-Bypass Dysfunction:

• Low CO state: Inotropes required (dopamine, dobutamine, epinephrine, milrinone)
• Right heart failure is common (RV is most vulnerable to ischemia-reperfusion injury)
• IABP (Intra-aortic Balloon Pump) or ECMO/VAD for refractory failure

---

13. PULSATILE vs. NON-PULSATILE FLOW

---

14. pH MANAGEMENT DURING HYPOTHERMIC CPB

---

15. KEY EXAM POINTS (HIGH-YIELD SUMMARY)

1. Non-physiological conditions of CPB: Non-pulsatile flow, hypothermia, hemodilution, blood-foreign surface contact, altered pharmacokinetics
2. SIRS is the most important pathophysiological consequence - triggered by blood-foreign surface contact; mediated by complement, cytokines, PMNs
3. C3a and C5a (complement anaphylatoxins) are key mediators of "postpump syndrome"
4. Hemodilution lowers HCT to 22-27% in adults - reduces O2 carrying capacity, dilutes coagulation factors
5. ACT >480 s required before initiating CPB; normal <130 s
6. Hypothermia protects organs but causes coagulopathy, dysrhythmias (VF at <28°C), and leftward shift of ODC
7. Reperfusion injury on unclamping: Ca2+ overload + ROS burst → myocardial stunning
8. Neurological complications: Type I (stroke - macroemboli) vs Type II (POCD - microemboli + inflammation)
9. Vasoplegia: High CO, low SVR post-CPB - treated with NE, vasopressin, methylene blue
10. pH-stat for pediatric DHCA; α-stat for adult moderate hypothermia (Level A evidence)
11. Centrifugal pumps - cannot pump air forward; less hemolytic; pressure-sensitive
12. Post-bypass coagulopathy - multifactorial: dilution + hypothermia + heparin + platelet dysfunction + fibrinolysis; guide with TEG/ROTEM
13. AKI from non-pulsatile flow, hypotension, free hemoglobin; reddish urine = hemolysis
14. Pump lung (post-perfusion lung) = complement-mediated PMN sequestration in pulmonary vasculature → ALI
15. DHCA at 15°C - up to 60 minutes safe; pH-stat + pharmacological neuroprotection used

---

• SIRS/inflammatory cascade - this is the most tested topic; know the mediators (complement C3a/C5a, TNF, cytokines, NF-κB) and effector cells (PMNs, platelets, endothelium)
• Organ-specific effects - cardiac (stunning, reperfusion), pulmonary (pump lung/ARDS), neurological (Type I vs II), renal (AKI mechanisms)
• Coagulopathy - multifactorial causes and management with TEG/ROTEM
• pH management - α-stat for adults, pH-stat for pediatric DHCA
• Vasoplegia - mechanism and methylene blue treatment
• Hypothermia physiology - degrees, benefits, complications, VF threshold at <28°C