Cardiopulmonary Bypass Flashcards
When is CO2 extracted from blood?
At the same time that O2 is added back
Process of blood going through CPB stuff
Venous Reservoir
Oxygenator/Heat exchanger (CO2 is extracted from the blood while adding O2 back)
Main pump
Arterial filter (removes fat, thrombi, calcium, and tissue debris)
Patient
Roller vs centrifugal pump:
Roller: non pulsatile flow, constant regardless of pressure generated.
Centrifugal: pressure dependent, less traumatic to RBCS
Which perfusion pressure is recommended to maintain systemic organ function?
50-80 mmHg
Why do we use heparin to anticoagulant patients for CPB?
Consistent in its dose and achievement of adequate AC
Rapid onset time
Easy to monitor
Adequate therapeutic window.
We want it because we don’t want thrombosis to occur in CPB circuit.
How does ACT work? Normal pre-heparin ACT? What do surgeons want before starting? Normal heparin dose?
small aliquot of blood added to a medium which stimulates thrombosis. In a normal, pre-heparinized state, the ACT is 90-150 seconds. Following administration of heparin, 300-400 U/kg, ACT is repeated after 2 minutes. Most surgeons want ACT >400, others want >480
Why is CPB so harmful to the system?
It destroys RBCs, Activates and destructs platelets, stimulates inflammatory and complement system leading to further stimulation of coagulation system after reversal of heparin
How does heparin work?
It enhances the activity of anti-thrombin 3 leading to an enhanced destruction of thrombin and thereby making it difficult to form clots
What situations would make a person be exposed to heparin thereby increasing their chances of having HIIT?
previous MI or STEMI, This could cause decreased levels of heparin and/or decreased activity of antithrombin 3 leading to an inability to reach adequate ACT values
What can you give to patents who have less AT3, or aren’t responding to heparin?
you could give ATIII via 1-2 units of FFP
What makes CPB worse for a person’s system?
Length of time on CPB. So longer surgeries with more parts to it=more time on CPB, and more time for issues of destruction of RBCs, and platelets.
One thing that can affect patients undergoing cardiac surgery as far as getting back to normal after CPB is:
Temperature! if you’re having a problem with coagulation after CPB. Consider their temperature.
How does protamine work? What are 3 potential reactions that can happen with administration of protamine? How do you treat these?
It binds to heparin to form a stable salt
3 reactions: Anaphylactic (profound vasodilation and CV collapse), this can happen in its who have been exposed to protamine before (previous exposure, diabetics using insulin NPH) since protamine is used to prolong effects. Men who have had vasectomies or episodes of orchitis.
tx: support of CV system, admin of diphenhydramine or epinephrine to block histamines and stop degranulation of leukocytes
2. Fulminate pulmonary vasoconstriction-can happen in its with elevated pulmonary pressures. Tx: stop admin of protamine and support CV system. Methylene blue could help counteract increase in pulmonary pressures
3. Giving it too rapidly could cause decrease in intravascular calcium and stimulate release of histamine leading to drop in SVR and hypotension. Rec that no more than 50 mg of protamine be given in a 10 min period.
Tell me about the type 1 HIT:
what happens? why do they think this? what is heparin binding to? What does this binding facilitate?
Heparin induced thrombocytopenia Type 1:
Results in a decrease in the number and function of platelets following admin of heparin-thought to be due to an aggregation of platelets. Heparin binds to the surface of platelets as well as to Platelet factor 4. This binding facilitates platelets clumping together and these aggregates are removed from circulation by the RES
Type 2 HIT: Usually happens in which patient population? What decreases (like in HIT 1), and what else happens? Tell me more about that additional thing and what it leads to. Complications?
Seen in those who have been treated with heparin for a more prolonged time 5-10 years. Decrease in platelet levels due to aggregation and removal from circulation however, there is an additional antibody mediated effect. Antibodies are generated and bind to heparin platelet factor 4 complex-this leads to activation of inflammatory system as well as activation of complement cascade. Thrombotic complications are a thing with HIT 2
So, for type 2 HIT: can you get antibody levels afterwards? Does repeated exposure to heparin always reproduce the HIT type 2 reaction?
Antibody levels in patients who survive a HIT type 2 reaction become undetectable several weeks after cessation of heparin. Repeated exposure does not always reproduce this.
What can you use for AC during CPB in a patient who has a hx of HIT? How does it work? how is it eliminated? half life? is there a reversal agent? how must you administer it for CPB? How to measure its clotting?
Bivalirudin:
Acts by binding to active site on thrombin, preventing its ability to cleave fibrinogen to fibrin. It is itself cleaved by thrombin leading to elimination in the plasma and is not dependent on an organ for removal. Half life of 24 minutes. No reversal agent. You must give a bolus and then an infusion for CPB.
Coagulation system tends to favor___ until ___.
How do endothelial cells play a role in prevention of platelet activation, aggregation, and generation of fibrin clotting? They contain ___, they release ____, they display ____.
Tends to favor AC until endothelial damage occurs
They contain heparin sulphate (which inhibits clotting factors)
Endothelial cells are also responsible for releasing prostacyclin, a molecule that leads to vasodilation, and stabilizes platelet cells preventing their activation and formation of a platelet plug
-endothelial cells, except those present in the cerebral circulation, synthesize and display thrombomodulin on their cell surface. Thrombomodulin greatly decreases activation of clotting cascade .
Once endothelial cells become damaged, ____ becomes expased, and there is activation of _____
Thrombosis occurs when _____.
First phase of clotting: Happens after? decrease in ___ resulting in___
Then what forms?
Following that-what becomes exposed? What is released with that?
sub endothelial matrix becomes exposed and there is an activation of the clotting pathway.
Thromobosis occurs when platelets and fibrin become intertwined, filling area of endothelial damage
First phase (after endothelial damage), occurs with a decrease in prostacyclin and an increase in thromboxane-this results in vasoconstriction
Then-platelet plug forms at area of endothelial damage and this coupled with vasoconstriction limits bleeding, and provides a place where clotting can form
Following platelet plug, Tissue factor becomes exposed when endothelial cells are damaged and is the primary initiator of clotting cascade. From this point, both pro and anti coagulation stuff is released in order to prevent balance from tipping too far in the other direction.
Starting with factor 5, Tell me how we get to fibrin
Factor V turns into Va, which is responsible for transforming prothrombin (2) into thrombin (2a). Thrombin turns fibrinogen into fibrin.
___ is the main initiator of clotting:
Thrombin
The clotting cascade activates which system?
The fibrinolytic system whose role is to remodel and degrade clot formation-allowing for endothelial cell repair
CPB stimulates which two systems?
Fibrinolytic and clotting system
What are the 3 main anti-fibrinolytic drugs used to decrease blood loss and decrease the amount of blood transfusions?
Epsilon aminocaproic acid (amir)
TXA
Aprotinin
MOA of TXA and epsilon aminocaproic acid?
reversibly bind to plasminogen preventing it from being activated to plasmin
How does aprotinin work? why wouldn’t people want to use it?
It decreases activation of fibrinolysis BY INHIBITING PLASMIN. It also binds to kallikrein which initiates the clotting cascade-limiting the activation of the clotting cascade (meaning it puts a limit on coagulation by binding kallikrein) BUT-it can cause renal dysfunction
Tell me the three types of anti-platelet medications:
Aspirin, Gp2b/3a receptor blockers, and ADP receptor blockers
How does ASA work? What happens to platelets afterwards?
It is an anti-platelet that irreversibly inhibits COX1 and COX 2 (which is in the prostaglandin synthesis pathway and leads to production of thromboxane-a platelet ACTIVATING molecule. SO THERE IS LESS THROMBOXANE A2). Due to irreversible inhibition-platelet dysfunction remains for the life of the platelet (10 days)
Gp2b/3a receptor blockers-what are their names, and how do they work?
Doesn’t this word look like a beverage?
TEA
Tirofiban
Eptifibatide
Abciximab
Abciximab, Eptifibatide, Tirofiban
They all work by binding to the Gp2b/3a receptor and decreasing activation and aggregation potential of platelets. (fibrinogen can’t bind and link the platelets)
ADP receptor blockers-how do they work? What are the names?
ADP is a potent stimulator of platelet aggregation. These blockers irreversibly block ADP receptors. They inhibit fibrinogen binding by preventing glycoprotein 2b/3a expression-preventing fibrin from binding toGp2b/3a complex. Clopidogrel and Ticlopidine
MOA of bivalirudin:
Directly inhibit thrombin
So, whats the deal with asthma and NSAIDS?
By blocking anti-inflammatory factors, you could cause people to have an abundance of pro-inflammatory factors
Do any of these anti-platelets have reversal agents? And how does that affect new transfused platelets?
Nope! And those agents can affect new platelets that you’re giving.
So, if you suspect that someone has HIT, what can you do?
Evaluate current platelet count and determine if there is a presence of abs. If pt must have CPB and has a hx of HIT. Get hematologist involved.
How does warfarin work? Which factors does Vit K turn from precursors to main ones
It inhibits epoxide reductase (which turns Vit K into activated Vit K), and turns precursors of 2, 7, 9, 10, C, and S
vWf and factor 8?
vWf protects/carries factor 8
Protein C and Protein S-tell me about what they do/are. Where does Factor V Leiden fit in?
Protein C turns into activitated protein C via protein S. Activated protein C (APC) cleaves and inactivates 5a and 8a. Factor 5 Leiden mutation produces a factor V resistant to APC’s inhibition of factor 5-making a person pro-coagulant.
How does plasminogen get to plasmin? and then what happens?
tPA takes plasminogen to plasmin, and results in the cleavage of a fibrin mesh. Therefore, giving tPA means you are giving a thrombolytic.
Platelet plug formation-what are the steps? detail the steps. Where does ADP play a role-who releases it and what does it do?
Injury
Adhesion
Activation
Aggregation
Injury: vWF binds to exposed collagen upon endothelial damage
Adhesion: platelets bind vWF via Gp1b receptors at site of injury. Platelets release ADP and Ca2+
ADP helps platelets adhere to endothelium.
ADP binding to receptor induces Gp2b/3a on platelet surface.
Aggregation: Fibrinogen binds Gp2b/3a receptors and links platelets.
Explain the anemia of chronic disease:
Iron levels?
TIBC?
Ferritin?
inflammation–>increased hepcidin–> decreased release of iron from macrophages.
Decreased iron
decreased total iron binding capacity
increased ferritin
vW disease: what does it do to BT, PT, and PTT?
What is the basis of the disease? How can you treat it? (most basic)
increases BT
nothing or increases PTT.
Nothing to PT
There is a defect in platelet plug formation.
Treatment: DDAVP which releases vWF stored in endothelium
What exactly is DIC? What does it do to platelet count, BT, PT and PTT. Causes:
Widespread clotting leads to deficiency of clotting factors which creates a bleeding state. Increases BT, Pt, and PTT. Decreases Platelet count. Causes: STOP Making New Thrombi. Causes: Sepsis, trauma, obstetric complications, acute pancreatitis, malignancy, nephrotic syndrome, transfusion.
