Pharmacologic Response to CPB Flashcards
When CPB is employed in cardiac surgery it may profoundly affect
the way drugs are distributed and cleared by the body and how drugs interact with the body to produce their effects.”
Pharmacokinetics
What the body does to the drug
Pharmacodynamics
How a drug interacts with the body to produce its effects
First order kinetics
elimination of a drug occurs at a constant fraction of drug remaining in the body per unit of time
Zero order kinetics:
when drug administration exceeds the body’s ability to clear it, leading to drug accumulation
To prevent drug accumulation,
drug infusion rates should be adjusted according to patient response.
Changes in Pharmacokinetics due to CPB
• Hemodilution • Hypothermia • Perfusion • Acid-BaseStatus • Sequestration
Hemodilution causes
- Reductionincirculatingproteinconcentration
- ReductioninRBCconcentration
- Reduction in concentration of free drug (unless your pump prime matches exactly)
- Alterations in organ blood flow, affecting distribution and clearance
What happens if you add drugs to your prime BEFORE RAP or AFTER RAP??
changes concentration takes some away
Hypothermia fluid shifts
romintravasculartointerstitialspace • Alteredvolumeofdistribution • Increased 3rd spacing
hypothermia vasoconstriction
Changes in organ perfusion
hypothermia and enzymes
Reductionsinenzyme-mediatedbiotransformation
hypothermia and solubility of volatile anesthetics
Increased solubility
altered hepatic flow by these drugs
(Fentanyl, propofol)
lungs excluded from circulation so give these drugs
(Valium,propofol,opioids)
Acid Base Status alters
organ blood flow • pH stat = ↑ cerebral blood flow
• Alteredionizationandproteinbinding
Drugs may be taken up by various components of the CPB circuit
Coated tubing
• Oxygenators
• Hemofilters • Many factors influence the movement of drug across the
membrane • Degree of protein binding is a major determinant
Administering medications ensure that
• you have a physician’s order or standing protocol
authorizing you to administer the medication
• the patient is not allergic to the medication
• you have the correct medication, the correct concentration and the correct dosage
• Inspect the medication for expiration date, precipitates, and sterility
What is in your drug box?
Heparin • Neo-Synephrine • NaHCO3 • Lidocaine • MgSO4 • Calcium • Potassium • Mannitol
Heparin Sodium derived from
bovine lung tissue or porcine mucosa standardized for anticoagulant activity
heparin sodium potency is determined by
biological assay using a USP reference standard based on units of heparin activity per milligram
• 100 units = 1 milligram • Example: 5,000 units = 50mg
heparin sodium action
Action: stops coagulation by potentiating antithrombin III and inhibiting the action of activated Factors IX and XI
Heparin Pharmacokinetics
- Eliminated by kidneys • Half life at CPB doses is 2 or more hours
- Prolonged by hypothermia and renal blood flow alterations
Heparin Side Effects
• Activation of t-PA and platelets • Boluses decrease SVR by 10 to 20% • Anaphylaxisrarelyoccurs • HITandHITT
HLD
300 to 450 units/kg . Rarely need to exceed 35,000 to 40,000 units
Heparin distributes
primarily in plasma, so increasing dose with
increasing body weight is only relevant to a certain point
Priming solution should contain heparin at approximately the same
concentration of the patient’s blood stream
ACT is prolonged by
hypothermia and hemodilution • Target ACT controversial (300 to 480 seconds)
Most vials you will see for adult CPB will be
1000 units/mL Loading dose: 30,000 units
30,000 units x 1mL = 30 mL 1000 units
neo action
syntheticselectiveα1-adranergicagonistthat causes vasoconstriction in arterioles
neo duration
less than 5 minutes
neo other things
Titratedtoeffect • Start with a test dose
Neo-Synephrine Dosing IV bolus
• 100 micrograms/mL • 200 micrograms/mL • 400micrograms/mL
Neo-Synephrine Dosing IV infusion
10 or 15 mg in 250 mL IV fluid (40 to 60 micrograms/mL)
Sodium Bicarbonate
Asterile,nonpyrogenic,hypertonicsolutionofsodium bicarbonate (NaHCO3) in water for injection for administration by the intravenous route as an electrolyte replenisher and system alkalizer
• Also used to treat hyperkalemia
NaHCO3 Dosing
- Dose (mEq) = 0.3 x Weight (kg) x BD (mEq/L) *Or just “1 amp” (50 mEq)
- Hyperkalemia: • Adults:50mEq • Peds: 1-2 mEq/kg
Lidocaine actions
reduces cell membrane permeability for sodium and potassium which increases the stimulation thresholds in ventricles
lidocaine site of action
cellmembrane
lidocaine DOA
15 to 30 minutes post bolus
Lidocaine IV bolus
-2 mg/kg • Usually 100 to 200 mg bolus at XC removal
• Not to exceed 300 mg/hr
Mag sulfate action
controlstransmembraneelectrolytesandenergy metabolism
• Cardiacarrhythmiasmayoccurduringhypomagnesemia
Hypomagnesemia can occur during CPB due to
Poor pre op health • Albuminadministration • Citrated blood product administration
MgSO4 Dosing bolus
2 to 2.5 g initial bolus
MgSO4 infusion
1.75 g/h infusion
mgso4 xc removal
- On CPB, usually given as 2 to 4 grams at XC removal with Lidocaine
- Often 0.5 g/mL concentration
calcium chloride action
Involved in myocardial contractility, blood clotting, neurotransmission and muscle contraction
• May be used for mixing with thrombin for platelet gel
• Levels drop during CPB • May be necessary to replenish before coming off CPB • Especiallyifcitratedbloodproductsgiven
CaCl2 Dosing
200 to 1000 mg slow IV
• Often 100 mg/mL concentration
CaCl2 given
post XC removal and before termination of CPB if levels are low
CaCl2 Hyperkalemia:
Adults:0.5-1gCaCl2 • Peds: 20 mg/kg Calcium Gluconate
Potassium Chloride
- The major intracellular ion • Necessary for normal cardiac contractions
- Hyperkalemia more of an issue than hypokalemia • Cardioplegia
KCL dosing cardioplegia
: 15-30 mmol/L of solution delivered into the heart
• ie. 4 to 1 cdpg requires 5 times the delivery strength in the cardioplegia bag
KCL hypokalemia dose
Dose (mEq) = weight (kg) x 0.3 x K+ deficit
• GIVE IT SLOWLY especially if XC not on • Usually 2 mEq/mL concentration
mannitol action
osmoticdiureticpreventsreabsorptioninthe proximal tubule (also thought to be a free radical scavenger)
mannitol dosing during cpb
0.5 to 1.0 g/kg
mannitol dose during rewarming or in prime
12.5 g
mannitol consideration
Inspect carefully for precipitate or crystals. • Use a filtered needle during administration
What else is in your drug box?
- THAM • Amicar • Trasylol • Thrombate III • Benadryl
- Solu-Medrol • Dextrose • Albumin • Insulin
- Forane
tham action
creates an alkaline environment by combining with hydrogen ions to form bicarbonatecreates an alkaline environment by combining with hydrogen ions to form bicarbonate
THAM Dosing Each 100 mL contains
tromethamine 3.6g (30mEq)
tham dose
Dose (mL) = wt (kg) x Base Deficit (mEq/L) x 1.1
Amicar (ε-aminocaproic acid) action
nhibits plasminogen activators to prevent conversion to plasmin
• Reduces bleeding caused by hyperfibrinolysis
Amicar Dosing loading and infusion
Loading Dose: 5 g IV Infusion: 1-1.25g/hr (30g/day max)
trasylol action
inhibits fibrinolysis and turnover of coagulation factors (serine protease inhibitor)
Trasylol Dosing test loading infusion prime
Test dose: 1 mL at least 10 min before loading • Loading dose: 200 mL (280mg) over 20-30 min • Infusion dose: 50 mL/hr • Pump prime dose: 200 mL
*May artificially prolong ACT results
Thrombate III (antithrombin) action and heparin
- Action: inactivates thrombin and activated forms of clotting factors IX, X, XI, and XII which results in inhibition of coagulation
- The anticoagulant effect of heparin is enhanced with Thrombate III in patients with antithrombin III (AT-III) deficiency
thrombate dosing and vial contents
Dose (IU) = (desired-baseline AT-III level) x kg 1.4
• Each vial will contain approximately 500 IU
thrombate Use within
3 hours of reconstitution
benadryl action
antihistamine,sedative,antiemetic, anticholinergic
• Given on CPB after suspicion of allergic reaction
benadryl dosing
10-50 mg
solumedrol action and side
Action: Intermediate acting glucocorticoid used on bypass to combat inflammation, often during circulatory arrest cases
• May cause hyperglycemia
solumedrol dosing
125mg–1g •
solumedrol consideration
Sterile powder which must be mixed with the
accompanying diluent • Use within 48 hours of mixing
Forane action
thers that modulate the GABAA receptor, used for induction and maintenance of anesthesia
• Potent vasodilators • Pungent odor
forane Bottle must be used with appropriat
appropriate adaptor to fill forane vaporizer on your pump
• Spillage can cause structural degradation of plastic
forane set vaporizer
0.5% to 2% after initiation of gas flow
forane can be temporarily used
increased for blood pressure control
• Scavenge oxygenator gas outflow when using anesthetic gas (recommended by Prof
Gaspar and most people with a conscience)
amsect Standard 6.8
An anesthetic gas scavenge line shall be employed whenever inhalation agents are introduced into the circuit during CPB procedures.
why scavenge short term exposure
Liverandkidneydisease • Headache • Irritability • Fatigue • Nausea • Drowsiness • Compromised performance • Decreased vigilance • Slow reaction time
why scavenge long term exposure
Miscarriage • Geneticdamage • Cancer
• Miscarriage and birth defects in the SPOUSES of exposed workers
three approaches to scavenge
don’t do it, use a passive ventilation,activated charcoal
1 more approach to scavenge
Suctiontubingattachedto oxygenator gas outflow
• With tiny holes cut into it • With a 1⁄4” 1⁄4” 1⁄4” Y connector
on it
• Attachedtowallsuctionor waste suction set at -100mmHg
albumin Concentration of proteins derived
fromhumanblood
albumin used to
Increases plasma volume or serum albumin levels
• May not be consented for by Jehovah’s Witnesses patients
albumin concentrations
5%, 20%, 25% • 25% contains 250g of protein for every 1000mL
albumin will increase CBV
3.5 times the volume injected, in an adequately hydrated individual
Some give when serum albumin
< 3.5 g/dL
ALBUMIN DOSING IN PRIME
12.5 to 25g in prime, or as needed
INSULIN ACTION
stimulates glucose utilization by muscle and fat, and acts on the liver to inhibit glycogenolysis and gluconeogenesis
INSULIN TARGET RANGE
of 110-180 mg/dL during cardiac surgery
• *VERY anesthesia and hospital protocol dependent
INSULIN CONC
100 units/mL
INSULIN DOSING
10-20 units IV on CPB
INSULIN CONSIDERATIONS
Never shake vial, roll in your hands to mix
• Use 1 mL syringe or dedicated insulin syringe
Insulin Dosing for Hyperkalemia ADULTS
Adults: 25g Dextrose + 10 units Insulin
Insulin Dosing for Hyperkalemia PEDS
1-2 g/kg Dextrose + 0.3 units Insulin per gram of
Dextrose
Dextrose “D-50”
Concentrated carbohydrate in the form of dextrose in water used to treat hypoglycemia
Dextrose Dosing
10-25g