Egar Video #5 Pharmacokinetics Flashcards
Relationship between alveolar and inspired concentration
- FA = alveolar concentration
- FI = inspired concentration
- this curve is what you get when you use a high flow non-rebreathing system
2 things to note in this graph:
- the anesthetics are different in their position
- the shapes of each curve is the same
Why is the inital part of the curve rapid?
This is related to the opposed/unnopposed/partially opposed effect to ventilation to drive the alveolar concentration upwards
- it is unapposed because at time 0 there is no uptake
What is Time Constant?
Time constant = Capacity / flow
- the time it takes to produce a 63% change in the concentration of whatever it is that we’re delivering to the system (the gas)
ex: the lungs have a capacity and flow
- time constant = 2 L (FRC volume) / 4L/min (alveolar ventilation) –> 0.5 min
- time constant for the lungs is 0.5 min
At 0.5 min or 1 time constant we are at ____
63% of the way towards equilibrium
If 1 time constant for the lung is 0.5 min, what is 2 time constants?
86%
What is 3 time constants? 95%
4 time constants? 98% or 2 min
what is the gas for which the time constant applies?
oxygen
What is the time constant and percent change for Oxygen based on this graph?
Time constant is 30 sec
- within 30 sec, there is 63% change
- within 1 min there is 86% change
This graph is the Rate of change of O2 concentration in the lungs
Why is the rise in FA / FI for anesthetics not as rapid as Oxygen?
Uptake
Anesthetic is brought into the lungs, and the concentration should change at the rate it’s being brought into the lungs
we get the rate of change from the time constant
BUT we don’t go to 100% of what we’re delivering, why is that?
something is opposing the effect of ventilation and the upward drive of alveolar concentration –> uptake
What are the 3 factors of uptake?
solubility
cardiac output
arterial venous difference
solubility: Comparison of the ______ between 2 states where you have ____ _____ pressures
concentration; equal partial
What does this relationship represent?
Solubility of Nitrous oxide
Pic represents the equilibrium of NO in the lungs and the blood
We could be using 6% of an anesthetic, and at equilibrium, there is 3% in the blood –> shows us that the anesthetic likes to be in the blood about half as much as it likes to be in the gas phase
Blood/Gas Partition Coefficients for anesthetics
what are the poorly soluble anesthetics?
Desflurane
nitrous oxide
sevoflurane
what are the Moderately soluble anesthetics?
Isoflurane
Enflurane
Halothane
Importance of solubility is in the ____ and ____
blood and tissues
Why are the curves different in position?
solubility
what is the least soluble anesthetic? Most soluble?
Least: desflurane
Most: halothane
Higher the solubility, greater the ____ and therefore greater the opposition to the effect of ventilation to drive the ______ concentration upwards and then ______ the curve
uptake
alveolar
lower
Human Tissue/Gas Partition Coefficients
- Desflurance and Nitrous Oxide are similar in terms of solubility in blood and lean tissue BUT differ in their fat solubility
- sevo on average is 2x more soluble than des
- isoflurane is 2x more soluble than sevo
solubility and blood flow to the tissues determine….
determine how quickly tissues will equilibrate to the anesthetic delievered and it’s reflected in the FA/FI ratio
what are the four tissue groups
know this chart
What organs are in the vessel rich group?
brain, lungs, liver, heart, kidneys
they take up a lot of anesthetic due to receiving the most blood flow.
High blood flow does what to the time constant?
shortens it
ex: vessel rich use 3/4’s of the CO while they make up 9% of the body’s mass. They have high blood flow relative to their capacity. The time constant will be short, 2-4 minutes.
They’ll equilibrate to 98% equilibration in 4 time constants, which is 4 x 2 min = 8 min
muscle group is composed of
muscle and skin
muscle group compared to vessel rich group has ____ blood flow
less
which makes their time constant longer than vessel rich group
why is the fat group separated from the muscle group?
because of solubility
fat has GREATER solubility which makes their capacity to hold anesthetic LARGER
Time constant for fat is ____ for the time constant for muscle
larger
vessel poor group
- bones, ligament, tendon, cartilage
- areas that are poorly perfused
- perfusion is 0 (according to the chart) so their uptake is 0
- This is why we only consider the FG, MG and the VSG
- Which group gets saturated in the first 8 min?
- The slower rise in slope represents?
- vessel rich group
- slower uptake by the muscle group
Why is induction less rapid with desflurane than sevo?
Desflurane is a pungent agent and sevo has a greater advantage in its absence in pungency
Due to it’s low pungency and low solubility it can induce anesthesia to patients in 1-3 breaths
sevoflurane
In One Breath Inhalation Induction:
1. Have the patient inhale and exhale a ___ ____
2. Then have the patient take a ____ ____ breath in and hold it.
3. then when patient breaths normally after they should fall asleep within ____
- large breath
- vital capacity
- 60 seconds
Why isn’t the patient asleep in 1 second with sevo?
uptake, There isn’t enough time to get the anesthetic taken up to the brain.
The VA has to move from the lungs to the brain
Why is the patient still breathing despite 8% sevo?
because the patient isn’t getting the full 8% (it would cause apnea). The sevo has been diluted in the patient’s lungs.
What are other factors that can alter the perception of pungency?
Opioid administration
ex: premedicate with fentanyl (1 mcg/kg)
There was a graph in the video that showed 25% of patients coughed on induction with des + saline, vs 5% coughed on induction with des + fentanyl.
describe this graph
at 1 MAC, 0 patients complained of respiratory irritation with desflurane, isoflurane and sevoflurane
This can also mean that des can also be used to induce anesthesia
What is the equilibration time for Desflurane?
6-8 minutes, before brain is at equilibrium with the concentration at the alveoli
this concludes that desflurance can be used with anesthesia BUT keep in mind the 6% barrier.
what is the 6% barrier with desflurane?
above barrier: irritation of airways
below the barrier: no irritation of airways (no cough or laryngospasm)
Do patient prefer inhaled gases or IV anesthesia?
IV
some patients get claustrophobic
Factors that determine rate of recovery from anesthesia
Solubility/elimination
MACawake
hyperalgesia
is patient able to maintain their airway?
cost (slower room turn over cost money)
why is rapid recovery more desirable?
- hyperalgesia (which occurs at 0.1 MAC) we want to get through this quickly
- patient is able to maintain their airway - safety
- cost (slower room turn over times means less money)
MAC awake ratio for:
N20 ___
Sevo ___
Des ___
Propofol ____
N2O 60%
sevo 33%
Des 33%
prop 19-20%
We have to get rid of more sevo and des compared to N2O to awaken from anesthesia. We have to get rid of even more propofol to reach an awake state.
what determines rate of elimination?
solubility
- this graph describes alveolar concentration during elimination relative to the last alveolar concentration during anesthesia (Fa/Fao)
- most rapid decrease with des, then its sevo and iso
- Conclusion is rate of recovery –> desflurane > sevo > Iso
Describe this Graph
Patients are oriented and ready for discharge within 15 with desflurane compared to isoflurane
Describe this graph
recovery is faster with sevo than halothane
The problem with rapid recovery? is increased agitation on emergence
- this can be helped with narcotics or sedatives like fent or ketorolac
Describe this graph
patients given sevoflurane are oriented soon er than those given isoflurane
Longer procedure means rate of recovery will be ____
longer because washout has to occur from muscle groups (the anesthetic from the muscles goes back to the alveoli if cleared by ventilation)
Anesthetics that are very soluble is ____
Not cleared at the lungs
solubility determines?
clearance
increased solubility means it likes the BLOOD and does NOT want to come to alveolar gas
poor solubility means it gets cleared in the LUNGS and increased duration of anesthesia may have little or no effect on recovery.
Describe this graph
- this is a 5 hour anesthesia with des vs iso
- differance betwen the fit for discharge is 40 min between desflurane and isoflurane
Same thing is seen with another graph comparing sevo and iso, where sevo orients and makes pts fit for discharge faster than iso.
what to expect with obese patients and recovery
2 theorys:
- fat reservoir is larger and can accelerate recovery by extracting anesthetic from the blood because the partial pressure of fat is low –> so they recover faster
or
- fat has a shorter time constant, and it’s connected closer to highly perfused tissues like pericardial fat, perineal fat, or mesenteric fat. This fat layer can have time constants probably around 200 minutes, and can saturate during the prolonged surgery and can contribute to prolonged recovery.
Describe this graph
- this is the recovery of anesthesia in obese patients
- pts wake up in 6 min for des, 2x longer for iso and propofol
Describe this graph
- rapid recovery is important for safety reasons
- patients on des didn’t have desaturation post extubation compared to those given with iso or propofol
Desflurane vs sevoflurane
- Differances are less because the differances in solubility is less compared to des vs iso or iso vs sevo
- the patient recovered faster with desflurane compared to sevoflurane or isoflurane
why is recovery faster in desflurane faster than propofol?
- due to the differance between the MACawake an MAC value
- Other differances between prop and des:
- different in association with N/V
- theres more N/V with des than propofol
why would we combine anesthetics?
- decrease cost
- isoflurane for maintenance (inexpensive anesthetic)
- ## Desflurance for last 30 minutes (rapid recovery)
What was the result of this trial?
Trial test on combining anesthetics
Patients receiving desflurane followed commands and was oriented faster than those given with a combination of iso and des or just iso by itself
Always more rapid recovery with ____ than ____
AND more rapid recovery with ____ than ______
des ; iso
sevo ; iso
How/why does the anesthetic circuit affect anesthesia?
- the volume in the circuit that we have to wash in and wash out is a factor
- certain VA like Halothane can be asborbed in the circuit
- flow in the circuit influences rebreathing
which VA can be absorbed in the circuit?
halothane
Flow through the circuit affects what?
rebreathing
Why is rebreathing important?
when the anesthetic is eliminated from the lungs you want it out of the circuit so it doesn’t return to the patient
why is rebreathing important during induction?
Helps maintain concentration in the circuit. Some anesthetic can be removed in the lungs and get diluted
in a test trial done, the patient’s inspired concentration is far lower than the delivery concentration due to rebreathing
describe this graph
- how rebreathing effects concentration on inspired vs delivered anesthetic
- this is with a soluble anesthetic
- Delivery concentration is 1% and the inspired concentration is only 40% of that
- rebreathing lower inspired concentration and then lowers the alveolar concentration even more (25-30%) of the delievered concentration
inspired concentrations relative to the delievered concentrations is higher with ____ than _____
_____ will accordingly be affected
sevo; iso; alveolar
sevo is more soluble
Inspired and alveolar concentrations vs delivered concentrations of des, sevo and iso
- ## desflurane’s inspired concentration relative to delivered is higher than sevoflurane and isoflurance
which anesthetic has a higher inspired and alveolar concentration relative to delivered concentration using a non rebreathing system?
Desflurane is higher compared to sevoflurane and isoflurane
how do you get better control of anesthesia?
using high flow rates and anesthetics with lower solubility
which type of anesthetic would cost more if we were to raise its concentration?
more soluble the anesthetic the greater you have to raise the delivery concentration
its the delivery concentration that costs money
how does nitrous oxide differ from the potent inhaled anesthetics
Its mac is above 1 atmosphere so its 105% of atmosphere
so we have to deliver it at high concentrations
there are implications to this that are physical in terms of their uptake
The solubility of Nitrous Oxide is ____ than the other gases like nitrogen
greater
it influences the diffusion of nitrous oxide across membranes, such as the membrane of the cuff.
the cuff can become _____ following prolonged used of nitrous oxide during a case, which can cause _____
distended; ischemia
what are other places in the body that can be expanded by continous use of nitrous oxide
inner ear: the pressure is increased
- its considered pressure increase rather than volume increase due to compliance of the space
- the inner ear is a non compliant space which makes it a pressure increase
Other spaces in the body that increase due to pressure
- pneumocephalus and intraocular
what are the spaces in the body that can expand in volume rather than pressure?
lungs (pneumothorax)
intestines
air embolus
diffusion hypoxia
use of nitrous oxide in large volumes can dilute the other gases in the lungs including oxygen
what are the 2 phenomenon that results from the large volume uptake of nitrous oxide?
the concentration effect and the second gas effect
the concentration effect and the second gas effect
the top 2 curves illistrates the concentration effect where the rate of rise of nitrous oxide was greater with a higher concentration of nitrous oxide
the second 2 curves represents the second gas effect
