04 - Uptake and Distribution of Inhalational Anesthetics Flashcards
T/F Inhalational anesthetics have a extremely slow action?
F. Extremely rapid action.
Fast changes in level of anes. Faster turnover/recovery times. Margin of safety.
What is the system of delivery/
Lungs.
Get 100% of cardiac output.
What are the four spectrum of effects of GA?
- amnesia
- sedation -> unconsciousness
- muscle relaxation/immobility
- analgesia
Where is amnesia accomplished?
hippocampus, amygdala, temporal lobe
Where is sedation/unconsciousness accomplished?
cerebral cortex, thalamus, reticular formation
Where is muscle relaxation/immobility accomplished?
spinal cord, supraspinal effects
Where is analgesia accomplished?
peripheral and central receptors
What can cause GA?
inert elements (Xe) simple inorganic compounds (N2O) halogenated hydrocarbons (halothane) complex organic structures (barbs)
Which hypothesis states that all inhaled agents have a common mechanism of action?
Unitary hypothesis
What is the Meyer-Overton rule?
potency correlates with lipid solubility
Where do the inhalational agents bind to and what do they do?
agents bind to lipid bilayer and make it expand, disturb membrane form, decrease membrane conductance
**Agents may bind to ion channel proteins (GABA receptors, glycine, nicotinic Ach, NMDA)
What is partial pressure?
The pressure a gas exerts - proportional to its fractional mass
T/F Partial pressures are additive.
True
What is Patm?
Patm = PO2 + PN2 = 160mmHg + 600mmHg = 760mmHg
What phase does pressure exist in?
Gas phase
What is concentration?
the amount of gas dissolved in a solution
What is solubility?
Solubility = volume of gas/volume of liquid (at a standard temperature)
how much gas can dissolve in a given solution
SO WHAT DOES “PARTIAL PRESSURE OF GAS” MEAN, IN A SOLUTION???
reflects a “force” of gas to escape out of solution - think of CO2 in a bottle of soda
it’s the pressure of the gas if there were a gas phase in EQ with the solution
Do gases equilibrate based on partial pressures or concentrations?
partial pressures, not based on concentrations
By convention, do we use fractional concentration (F) or partial pressure (P)?
fractional concentration
ex. FO2 = 0.21 instead of PO2 = 160mmHg
T/F F is proportional to P.
True
What is the goal of inhaled anesthetics?
to establish a concentration of anesthetic molecules in CNS
What is Pcns at EQ?
Pcns = Pblood = PA(alveoli)
Is there a slow or rapid transfer of gases from alveoli to blood to CNS?
rapid
What is λ?
solubility coefficient or partition coefficient
What is λB/G?
Blood:Gas partition coefficient
ratio of concentrations of anesthetic gas dissolved in each of the two phases at EQ
partial pressures are equal, concentrations are not
If there is more agent in the blood and less in the gas phase, what is your λB/G? High or low solubility?
λB/G > 1
higher solubility
you need to dissolve MORE gas in order to generate a certain partial pressure
If you have a low solubility, what is your λB/G? What does this mean?
λB/G < 1
less agent in the blood and more in the gas phase
you need to dissolve LESS gas in order to generate a certain partial pressure
What are some other partition coefficients? What are they used for?
Blood:Gas, Brain:Blood, Muscle:Blood, Fat:Blood
describe the movement of a gas from one environment to another
What is induction?
getting agent from the anesthesia machine into the brain so the patient goes to sleep
What is the goal of induction?
to achieve a “steady state” of anesthetic partial pressures throughout the system
What does the vaporizer do?
adds agent to the fresh gas flow at a fixed concentration
T/F Over time the compartments equilibrate and concentration of agent in the circuit falls?
False
Over time the compartments equilibrate and concentrations of agent in the circuit RISES.
What is the fractional concentration of agent leaving the circuit?
Fi (fraction inspired)
What is the fractional concentration of agent in the lungs?
FA (fraction alveolar)
What is initial FA/Fi?
0 because Fa is 0. no agent in the lungs yet
What is FA/Fi at EQ?
you will be at EQ when FA = Fi
FA/Fi = 1
What is fast induction defined as? Why?
FA/Fi approaches 1 quickly
FA is proportion to PA = Pblood = Pcns
T/F Agents passes from alveoli into the blood.
True
Diffusion of agent from alveoli into the blood is dictated by which partition coefficient?
λB/G - the blood:gas partition coefficient
Do soluble agents (high λB/G) leave the lungs slowly or rapidly?
rapidly
Do non-soluble agents (low λB/G) leave the lungs slowly or rapidly?
slowly
What is λB/G of N2O? What does this mean?
0.47
1mL blood contains 0.47 as much N2O as 1 mL of air (at EQ)
What is λB/G of halothane? What does this mean?
2.4
1 mL blood contains 2.4 times as much halothane as 1 mL air (at EQ)
What is uptake?
Agent moving from lungs to blood
What does uptake depend on?
Uptake depends on the agent’s solubility in blood, the rate of pulmonary blood flow (CO), and the difference in the partial pressures of the anesthetic agent in the alveoli and the pulmonary blood.
T/F When agent moves from blood to tissue, the blood that returns to the lungs now has “room” to absorb more agent from the lungs.
True
T/F Soluble agents rapidly dissolve in blood, so uptake is low.
False
Soluble agents rapidly dissolve in blood, so uptake is HIGH.
Insoluble agents do not rapidly dissolve in blood, so uptake is LOW.
How does CO affect uptake?
high CO -> uptake is high
low CO -> uptake is low
CO affects how much blood comes to the lungs to take agent away.
How does the gradient between the Pagent in the blood and in the alveoli affect uptake?
high gradient -> uptake is high
low gradient -> uptake will be low
How does high uptake affect FA?
high uptake causes FA to decrease because agent leaves the lungs
uptake causes FA/Fi to increase more slowly, and FA/Fi approaches 1 more slowly
T/F
THOSE FACTORS THAT MAKE UPTAKE FASTER, MAKE INDUCTION SLOWER
True
Soluble anesthetics have greater uptake. Does it take longer or shorter to become “saturated”?
Longer
Takes longer to reach EQ (PA = Pblood = Pcns)
larger capacity due to higher solubility
**Review examples of uptake of halothane vs desflurane.
More than double the amount of halothane (compared with desflurane) must be transferred from lung to blood before the partial pressures equilibrate.
T/F Changes in blood lipids (post prandial lipidemia) could affect uptake.
True
How does solubility affect the speed of induction?
high solubility have a higher uptake, slower induction
How does alveolar blood flow affect the speed of induction?
Alveolar blood flow ≈ CO (Q)
No CO = no uptake
As CO increases, uptake increases, induction slows
Low CO -> rapid induction -> even lower CO -> etc. (positive feedback loop)
not clinically significant for insoluble agents.
How does ventilation affect the speed of induction?
replace agent taken up by the pulmonary bloodstream - counters the effects of uptake
Higher ventilation speeds induction
high ventilation -> rapid induction -> lower ventilation (negative feedback loop)
How does ventilation affect uptake?
Ventilation does NOT affect uptake.
only solubility, CO, and gradient to blood and alveoli
**Briefly review concentration effect and second gas effect.
“will not be tested”
What is Fa?
arterial concentration
Ideally Fa = FA. Is it? Why?
It isn’t equal due to V/Q mismatch caused by alveolar dead space, non-uniform gas distribution, etc.
slows induction with insoluble gases more than with soluble gases
How are inhaled anesthetics eliminated?
metabolism - mostly with methoxyflurane and halothane
exhalation - similar concepts as with induction, but in reverse
How can you speed elimination?
high FGF, low solubility, high cerebral blood flow, high ventilation
you can’t make Fi less than zero
What is diffusion hypoxia?
elimination of N2O into the alveolus casues N2O to “flood” the alveolus and dilute oxygen.
Only a problem if you use N2O and extubate to room air
What is the “concentration effect” also known as?
overpressurization
What happens with FA when you give a higher Fi?
FA rises quickly
Why does FA/Fi rise more quickly with N2O than desflurane, even though it’s less soluble?
Concentration effect.
You have to use higher concentrations of it.
What happens to alveolar concentrations when you give 5x as much anesthetic?
5x as much anesthetic will lead to a 6.2x increase in alveolar concentrations
What is “augmented gas inflow”?
New gas comes in to replace the absorbed agent
giving 5x as much anesthetic will lead to a 6.8x increase in alveolar concentrations
What is the “Second Gas Effect”? Which anesthetic is usually involved?
concentration effect of one gas on another
when N2O is absorbed, the second gas is concentrated and FA increases