CPB (Heart/Lung/Heme) Flashcards
How does ischemia while on CPB cause myocardial damage?
Ischemia leads to depletion of high energy phosphate bonds leading to lactate, acidosis, cellular edema, impaired Ca handling, and loss of membrane integrity –> myocardial contractile dysfunction
How does the CPB circuit cause myocardial damage?
Systemic inflammatory response from the plastics (cytokines, complement system, O2 free radicals)
What are the causes of myocardial injury from CPB?
Ischemia + CPB circuit itself + reperfusion injury + surgical trauma
How do we decrease myocardial O2 consumption on bypass?
Decompression fo the heart which decreases wall tension (40%) + hypothermia (11%) + asystole via cardioplegia (34%); can also perform ischemic preconditioning
How does cardioplegia protect the heart on CPB?
Hypothermic solution (less O2 demand) + arrest of the heart + pharmacologic agents to reduce ischemia and reperfusion injury is added
Is cardioplegia or a beating but empty and fibrillation heart more protected?
K+ arrested hearts have a 4-fold reduction in O2 consumption compared to a fibrillated, empty heart
What is added to cardioplegia solutions to prevent Ca+ accumulation?
Citrate (CPD), Ca channel blockers, magnesium, and low Na+ (decreases Na/Ca exchange antiport)
What is added to cardioplegia solutions to avoid edema?
Hyperosmolarity additives (i.e. glucose, K+, mannitol, albumin)
What can be added to cardioplegia solutions to avoid O2 radicals?
Allopurinol, nitric oxide, SOD/CAT (superoxide dismutase plus catalase)
What pressure should you not exceed while giving retrograde cardioplegia?
40mmHg (risk of coronary sinus rupture if you are over this)
What are the limitations of retrograde cardioplegia?
RV is not protected well (thebesian veins drain directly into the RV and not via the coronary sinus) + cannual may be distal to the great cardiac vein + if there is a persistent left SVC
What are risk factors for myocardial dysfunction after CPB?
Preop LV dysfunction + acute ischemia + advanced age + cross-clamp time + CPB time + perioperative bleeding + enlarged cardiac chambers
What is the mortality rate if one has prolonged mechanical ventilation (>72 hours) after cardiac surgery?
21-43% mortality rate; prolonged ventilation occurs in 7.5-10% of patients
How does the CPB circuit cause lung injury?
SIRS: CPB causes neutrophil activation and mobilization of other pro-inflammatory mediators that adhere to the pulmonary endothelium which can release proteolytic enzymes and O2 free radicals causing lung injury
How does ischemia and reperfusion cause lung injury?
Decreased pulmonary blood flow during CPB (no blood through PA) causes ischemic injury + reperfusion injury
What are risk factors for post-operative respiratory failure after cardiac surgery per Filsoufi et al?
Preop renal failure + female + EF < 30% + double valve procedures + active endocarditis + >70yo + heart failure + reoperations + emergent procedures + previous MI + prolonged CPB time (>180 min)
What are risk factors for ARDS in isolated valve surgeries per Chen et al?
Age + cirrhosis + massive transfusion + tricuspid valve replacement
What are the most common clinical manifestations of lung injury after CPB?
Atelectasis (from LLL compression during surgical exposure + apnea) and pleural effusions (left is more common, postop bleeding into left thoracic space + pulmonary edema + surgical trauma imparing lymphatic drainage)
Does using CPAP or ventilating the lungs during CPB improve clinical outcomes?
No although CPAP did improve the A-a gradient vs apnea
How do RBCs contribute to clotting?
They expose procoagulants on their surface which contributes to thrombin generation
How does hemodilution from CPB affect coagulation?
Dilution of coagulation factors + reduces RBC’s role in coagulation (clot stability)
How does hypothermia affect the oxyhemoglobin dissociation curve?
It shifts it to the left, impairing O2 offloading at the tissue
Why do we see hemolysis on CPB?
Mechanical sheer stress and turbulence within the CPB circuit + contact with non-endothelial surfaces and air + pressure gradients for venous drainage (vacuum) + cardiotomy suction use
What are other risks of having hemolysis on CPB?
Damage to RBCs can cause release of free Hgb and heme which is a potent scavenger of nitric oxide (vasodilator) -> causes vasoconstriction and reduces microcirculatory function (worsening tissue hypoxia); Free heme can combine with endogenous hydrogen peroxide to form free radicals as well
What % of blood volume is made up of white blood cells?
1% (99% is made up by RBCs)
What happens with white blood cells when on CPB?
Activation of WBCs due to contact with non-endothelial surfaces (mediated by Kallikrein and complement system C5a); C5a causes neutrophil chemotaxis, degranulation and superoxide generation -> ultimately leads to tissue edema
How do monocytes released from WBCs during CPB cause damage?
Releases proinflammatory cytokoines and they express tissue factor which promotes thrombin generation and activates coagulation; they can also conjugate with platelets and cause thrombocytopenia
What is released by leukocytes that degrade and destabilize clots?
Elastase and Cathepsin G
What is a white thrombus?
Platelet plug built up at the site of an endothelial defect, usually starting with a GP1a receptor binding to vWF and subsequent activation of GPIIb/IIIa receptors
What does fibrin do in platelets for clot formation?
Additional platelet activator that recruits more platelets; makes the white thrombus turn into a red thrombus
Why does thrombocytopenia occur with CPB?
Hemodilution + platelet adhesion to circuit surfaces + mechanical disruption, sheer strees + sequestration in pulmonary and splenic tissue + consumptive coagulopathy
Why does thrombocytopathies occur with CPB?
Excessive platelet activation during CPB leads to a blunted response to stimulation (via ADP, collagen, thrombin) + Heparin effects (interferes with platelet-vWF interactions) + protamine (activates platelets as well leading to sequestration) + complement activation leading to more platelet activation
How does heparin affect platelets?
Causes serotonin release + increased ADP-induced/collagen-induced/epi-induced aggregation + decreased thrombin-induced aggregation + opposes prostacyclin-induced aggregation + increased PF4 release + increase in bleeding time + decreased platelet count + P-selectin expression + suppresses alpha granule release (at higher doses)
What is one possible explanation for platelet activation causing dysfunction?
Being on CPB causes platelets to be activated -> produces a population of granule-depleted platelets that cannot contribute to a platelet plug
What can you do to reduce platelet dysfunction after CPB?
Reduce platelet damage and activation (i.e. reducing platelet sheer or coated circuits) + prevent exposure to CPB (i.e. ANH)
How do endothelial cells cause a coagulopathy on CPB?
They upregulate anticoagulant and fibrinolytic pathways, causing thrombin generation and simultaneous fibrinolysis during CPB which sets up for a consumptive coagulopathy
What makes up the contact system in coagulation?
Factor XI + Factor XII + kallikrein + high-molecular weight kininogen
How does the complement system affect coagulation?
The complement system normally amplifies the inflammatory response, C5a (neutrophil activation) and membrane attack complex amplify inflammation, cell lysis, and platelet degranulation causing platelet dysfunction
What factors make up the intrinsic pathway?
Factor XIIa causes Factor XI to become Factor XIa which causes Factor IX to become Factor IXa
What factors make up the extrinsic pathway?
Tissue factor exposed by endothelial cells complexes with Factor VIIa
What factors make up the common pathway?
Factor Xa + Factor Va are activated by both the intrinsic and extrinsic systems; these take prothrombin to thrombin which prevents fibrinogen breakdown into fibrin
What is the predominant method of coagulation that gets activated during CPB?
The intrinsic pathway by the contact system via Factor XII leading to thrombin generation
What is heparin rebound?
Inadequate heparin reversal with protamine caused by protein binding or endothelial sequestration that preserves heparin from neutralization
What are our endogenous anticoagulants?
Antithrombin (neutrolizes thrombin) + Tissue factor pathway inhibitor (binds and inactivates Factor Xa and TF-Factor VIIa complex) + Activated protein C
How does activated protein C work?
Slows down the procoagulant process by inactivating Factor VIIa and Factor Va and also neutralizes plasminogen activator inhibitor-1; it is aided by Protein S
What is the purpose of the fibrinolytic system?
Prevent clot formation in non-injured vessels and maintain blood fluidity
What does plasmin do?
Formed from plasminogen, it breaks down fibrin into soluble fibrin degradation products and inactivates Factor Va and Factor VIIIa
What does t-PA do?
Tissue plasminogen activator = mediates intravascular plasminogen activation, causing dissolution of fibrin in circulation
What happens to the fibrinolytic pathway during CPB?
Profibinolytic activity is increased caused by endothelial cell activation and t-PA release leading to 100-fold increase in plasmin generation (which breaks down fibrin)
How does TXA work?
Protease inhibitor that binds to plasminogen which prevents it from becoming plasmin -> this reduces fibrinolysis
