Inhaled Anesthetics - Part 1 Flashcards
Pharmacokinetics is:
A_______
D_______
M_______
E_______
What the body does to the drug.
Absorption, Distribution, Metabolism, Elimination
Pharmacokinetics of inhalational anesthetic agents.
The depth of general anesthesia depends on the __________ exerted by the inhalational agent in the patient’s _______.
Partial pressure (or gas fraction)
Brain
Pharmacokinetics of inhalational anesthetic agents.
The brain’s partial pressure depends on ________ blood partial pressure which depends on ________ blood partial pressure which depends on partial pressure of ________ in the inspired gas.
arterial (a); alveolar (A); agent
Capacity/volume of circuit
6 L
What is solubility?
Relative affinity of an anesthetic for two phases and therefore the partitioning of that anesthetic between the two phases at equilibrium.
More soluble the gas is → slower induction/slower emergence
(opposite of IV drug (propofol) which is highly soluble means fast induction)
What is equilibrium for inhaled anesthetics?
No difference in partial pressure exists.
(vs. concentration for IV drugs)
In a mixture of gases, each gas has a _____ ______ which is the pressure which the gas would have if it alone occupied the volume.
partial pressure
P = PN2 + PH2 + PNH3
How can we affect PI (Partial Pressure of inspired agent)
- ↑ concentration (2% - 8%)
- ↑ fresh gas flow (FGF), which ↓ time constant
- ↓ volume of the circuit
- ↓ absorption by the machine (plastic, rubber bag absorb some gas and we cannot affect it)
- Wait it out
What is PA/PI?
The ratio of alveolar pressure relative to inspired pressure. (aka in some texts, FA/FI)
Try to get PA as close to PI as fast as possible, esp during inhalational induction
What is PA and how can we ↑ it?
PA = input into the alveoli - uptake into blood
- ↑ ventilation
- ↑ concentration
How do we measure the PBrain?
Look at endtidal concentration of gas being expired.
Effect of ventialtion on anesthetic uptake. If you change the minute ventilation, what happens to the rate of rise in the alveoli?
↑ minute ventilatoin, ↑ rate of rise of alveolus inspired
Two ways to increase ititial concentration and uptake?
Concentration effect
2nd gas effect
What is the impact of the inspired partial pressure of the agent increases the rate of rise of the partial pressure of the alveolus?
Concentration effect
The more we put in, the more that will be there
Concentration effect
Start with 20ml gas A in total of 100ml (20%)
50% of gas A is taken up by pulmonary circulation
This leaves 10mL of gasA in total of 90ml
What is the alveolar concentration?
Now what if the concentration is 80% and 50% of the anesthetic is taken up by pulmonary circulation?
11%
concentration of gas is larger than original
67% (40ml of gas in 60ml total)
Therefore, a higher inspired concentration results in a disproportionaltely higher alveolar concentration (increasing inspired concentratin 4-fold = 6-fold increase in alveolar concentration)
The concentration effect is more significant with ______ gas than with volatile anestetics because it can be used in much higher concentrations.
Nitrous oxide
2nd gas effect
High concentration of _______ will augment the uptake of a concurrently administerd volatile agent.
Nitrous oxide
High volume uptake of one gas accelerates the rate of increase of the PA of the companion gas.
Concentration effect vs. 2nd gas effect figure
Administration of 65% N2O produces a more rapid rise in the alveolar concentration of anesthetic/concentration of inspired anesthetic (Fa/Fi ratio) for nitrous oxide than administration of 5% (i.e., concentration effect, two solid lines).
The Fa/Fi ratio for 4% desflurane rises more rapidly when given with 65% nitrous oxide than when given with 5% (i.e., second gas effect, two dotted lines)
Gas is continually taken up from the lungs for the bloodstream
PA = PI - uptake (from pulmonary blood flow)
Anesthetic uptake is affected by:
S________
C____O____
A_____V_____ Difference
Solubility
Cardiac Output
Alevolar - Venous Difference (higher # in beginning than 12 hours later)
Anesthetic uptake equation
Uptake = Solubility (x) CO (x) (PA - PV)
What is defined as relative affinity of inhaled anesthtic for two phases at equilibrium?
Solubility
Ex: cup of water + sand vs. cup of water + sugar
The cup of water and sugar wants to dissolve, what sinks to the botom of the cup is what the brain sees.
T/F
↑ solubility of an agent ↓ FA/FI, so induction is slower
True
↑solubility = ↑induction time and ↑ emergence
(brain sees less of what settles at bottom of cup because the sugar dissolves)
Halothane is best example
T/F
↓ Solubility of agent, ↑ FA/FI therefore induction is quicker
True
N2O and Desflurane best examples
↓solubility = ↓induction time & ↓ time to emergence
Put the folowing gases in order (most soluble to least) based on their blood/gas partition coefficients:
Sevo
Des
Iso
N2O
Halothane
- Halothane (2.4)
- Isoflurane (1.4)
- Sevo (0.65)
- N2O (0.47)
- Desflurane (0.42)
For a molecule of desflurane, each liter of blood looks like 0.42 L of gas. For sevoflurane, it looks like 0.65 L of gas, etc
Alveolar ventilation carries anesthetic into the lung, and because this delivery is common to all volatile anesthetics, the anesthetic movement into the lungs is the same. Similarly, the volume of blood passing the lungs (the cardiac output) is the same for all volatile anesthetics. However, the effect of this volume is modified by the capacity of the blood to hold anesthetic: the ______ of the anesthetic as defined by the blood/gas partition coefficient. We can equate this to the volume of gas passing through the lungs.
solubility
If one breathes in a highly soluble anaesthetic vapor, such as _______, as soon as it arrives in the alveoli it dissolves off into the bloodstream and ends up in muscle, fat, bone - everywhere, and so, as you can imagine, very little of this gas arrives where one wants it - in the brain. Consequently it takes “all day” to go to sleep and wake up
Halothane
Use the following in each of the missing word places: N2O and Halothane
The concentration of the anesthetic agent in the brain can rise no faster than the concentration in the blood, the onset of anesthesia will be slower with _______ than with ________.
Halothane; N2O
Increasing CO will (increase/decrease) induction, emergence, and rate of rise of FA/FI.
Decrease induction (slower), decrease emergence (slower), and decrease rate of rise of FA/FI
Greater CO –> greater pulmonary blood flow –> removes more anesthetic and has what affect of PA
lowers PA, which decreases uptake of agent
Low CO = (faster/slower?) rise in FA/FI
faster
Effects of Increased Cardiac Output with fixed ventilation
More pronounced effect when gas is more soluble (halothane)
The ____________ is where the different tissues come into play, if gases were not absorbed by tissues then the difference would be zero and no net flow of gases.
alveolar-venous difference
Which of the following affect tissue uptake of anesthetic gases?
A) Tissue solubility
B) Tissue blood flow
C) Difference between partial pressure of blood and the specific tissue
D) All of the above
D) All of the above
Partition coefficient of inhaled anesthetics and interpretation of their effects
60x amount in fat as in blood to equilibrate, so halothane soaks into fat over time and has to come out of the fat to wake up.
Tissue uptake due to blood flow percentage
Alveolar > Vessel Rich Group (kidney, liver, brain) > Muscle > Fat > Vessle Poor Group
Difference between Fraction of Inspired agent vs. Fraction Expired on monitor is due to…?
Inspired: 3.0 vs. Expired 2.5
Losing 0.5 to other tissue groups
Fraction expired is most closely representative of the partial pressure in the brain
How do we get rid of anesthetic gases?
- Biotransformation - liver does very little
- Transcutaneous loss
- Exhalation - most is through this
Which of the following is most metabolized? Least?
Halothane, and N2O
Halothane is most metabolized
N2O is least metabolized
What changes pharmcokinetics of inhalational agents?
- Age (b/c ↑ CO in young, healthy pts)
- Lean muscle
- Body fat
- Hepatic function
- Pulmonary gas exchange
- CO
