Anesthesia Pharmacology Exam 2 – Uptake & Distribution of IAs by Dr. Welliver

FYI: N?O is inorgainic gas b/c
it doesn’t have Carbon in it

the term “carrier gas” refers to:
oxygen or sometime N?O

Which gas can be a carrier gas and an anesthetic gas?
N?O

volatile anesthetic in the vaporizer b/c
it want to (b?c h?i)

[vapor] pressure is
pressure of molecules sitting on the side (wall) of the container

Pressure of molecules push up & want to come out of the container

If you have infinity (open), you have no pressure

Atmospheric pressure which is composed of:
nitrogen, oxygen, carbon dioxide, and pollution

FYI:
We have atmosphere pressure pushing down with a vapor pressure of 760 mmHg

Each anesthetic agent has its own vapor pressure (for example: Sevo has vapor pressure of 170 mm Hg is pushing up WHILE 760 mmHg is pushing down) ? the % of sevo gas in the vaporizer is 22 %

Isoflurane has the vapor pressure of 240, so there is ____% of vapor in the in its vaporizer

* in other words, it means WHAT % of A MIXTURE is the GAS!

32

Vapor pressure of a volatile gas is depended on
Temperature and it’s own properties

? temperature ? ? molecule movement ? ? vapor pressure

How an anesthetic gas get to our body/tissue?
We give a known concentration of a anesthetic gas via ANESTHETIC CIRCUIT through ventilation to the pt.

Then this Gas ? enter the LUNGS? then passes through the ALVEOLAR MEMBRANE into BLOOD ? Left side of heart ? then out to Rich Muscle Group (which = Brain and liver, kidneys) ? then muscles, skin, fat, & connective tissues

Overpressurization means
give a large concentration of an anesthetic gas (for a quicker onset of anesthetic)

“Delivering a higher FI than the FA actually desired for the patient; similar to IV bolus and thus speed the induction of anesthesia”

For ex: Vapor pressure of Sevo = 170 mm Hg ? 170/760 = 22%

If 170 mm Hg is 23% of 760 mm Hg
then, _____ mm Hg is 2% of 760 mm Hg. (15 mm Hg)

15 mmHg of sevo (it will slowly get diluted to the patient)
If you want to overpressurize the gas –>you ? sevo to 8% = 60 mm Hg

FYI:
What are the only true gas?
& Xenon

(while the other inhaled anesthetics are vapors of volatile liquid – for simplicity- all of them are referred to as gases!)

What is the unique advantage of anesthetic gases ?
the ability to deliver them to the bloodstream via the patient’s lungs

Which inhaled anesthetics are ether derivative?
Which inhaled anesthetics are ether derivative?
, Iso, Des, and Sevo

Which inhaled anesthetics are methyl ethyl ether derivatives?
Which inhaled anesthetics are methyl ethyl ether derivatives?
Enflurane, , and des

Which inhaled anesthetic is a methyl isopropyl ether derivative?
Which inhaled anesthetic is a methyl isopropyl ether derivative?
Sevo

and isoflurane are ___
and isoflurane are ___
Isomers

(Isomer = 2 (or more) compounds that contain the same number of atoms of the same elements but differ in structural arrangement and properties)

How is desflurane differs from isoflurane?
How is desflurane differs from isoflurane?
The substitution of a Fluorine for a Chlorine atom

What are 5 factors of Fick’s law?

= Fick’s Law!!!

5 factors (3 directly proportional & 2 inversely proportional with diffusion )

3 directly proportional with diffusion
1) concentration gradient (or pressure gradient)
2) Surface area (? surace area ? ? diffusion) Lungs surface area = a size of the tennis court
3) Solubility (tissue solubility – how soluble is it in there? Halothane has bld:gas partition coeffiction of 2.4 – highest solubility) ? solubility ? ?diffusion

2 inversely proportional with diffusion
1) membrane thickness (? thickness ? ? diffusion)
2) Molecular weight/size ( The bigger the molecule the slower it diffuses! The smaller the molecule the faster it diffuses)

Does diffusion ever go to Zero Net equilibrium across the semipermeable membrane?
Does diffusion ever go to Zero Net equilibrium across the semipermeable membrane?
No

Think semipermeable membrane as a filter! You need to have a push to get across that semipermeable membrane. Eventually partial pressure on both side almost equal, and there will be no longer enough push from the higher side ? It can’t equilibrate!
(Passive Diffusion: with semipermeable membrane!)

75% of CO goes to ___
Vessel rich group: the BRAIN, liver, kidney

Sevoflurane is really ___
pungent (STINK!)

see 3 charts in pharm A. folder

There 4 tissues compartment:
(what are they?)
There 4 tissues compartment:
(what are they?)
1. Vessel rich (10% of body mass but takes 75% of CO) vital organs -brain, heart, liver, kidneys
2. Muscle (50% of body mass – take about 19-20 % of CO)
3. Fat (19% of body mas – 6% of CO)
4. Vessel poor group (bone/ligament/hair) (1%

Where the Blood goes = where the gas goes

Blood: Gas solubility
Blood: Gas solubility
Lowest to highest

N?O 0.46 (highest due to concentration effect – when we give N?O – we give 70%- a large %-high pressure gradient ? FASTER rate of rise FA/FI )
Des 0.42 (when we give Des. we give 4-6% therefore SLOWER rate of rise FA/FI)
Sevo 0.70
Iso 1.4
Halothane 2.4

Most rapid with least soluble anesthetics (, desflurane, sevo)

What are the 2 gases with more intermediate solubility?
What are the 2 gases with more intermediate solubility?
Iso
Halothane

Therefore, Iso and Halothane: SLOW to go in the brain and SLOW to go out of the brain

After 10 15 min of administration IAs, the slope of the curse decreases - What does it reflect?
After 10 15 min of administration IAs, the slope of the curse decreases – What does it reflect?
saturation of muscle rich group tissues and subsequent ? uptake of the inhaled anesthetic

FYI (but do not need to know for now!)
FYI (but do not need to know for now!)
This table is from Handbook of Clinical Anesthesia (Barash) p. 225

. All volatile anesthetics except Des- all have Fat:Blood solubility of 40:1
. Des Fat: Blood solubility 20:1 (just half of solubility)
. All volatile anesthetic has Muscle: blood solubility of about 3:1 (except: des & 2:1)

If you have 1 hour case, do you worry about anesthetic agent to saturate other muscle group beside the Vessel Rich Group?
No (b/c it doesn’t have time equilibrate!)

The Brain (or Vessel Rich group) = equilibrate very quick (it get 75% of CO)

But the other 20% of CO goes mostly to muscle group. (This will take 4-6 hours for the inhaled anesthetic to equilibrate (base on its solubility ability) ..So, this is Why we are worry for longer case!

Fat group takes about 6% of CO ? it even take longer to equilibrate (about 12+ hours) to equlibrate between fat and blood

Base on blood: gas solubility, Sevo is just as quick as Des (for short case - absolutely right!)So, if I'm going to deliver anesthetic for 12 hours - do I want to go use an anesthetic that is going to saturate the fat twice as much as the other one? (Fat:blood for Des 20:1 and Sevo 40:1) --I shouldn't use Sevo b/c it saturates in Fat twice as much ? longer Wake up
Base on blood: gas solubility, Sevo is just as quick as Des (for short case – absolutely right!)

So, if I’m going to deliver anesthetic for 12 hours – do I want to go use an anesthetic that is going to saturate the fat twice as much as the other one? (Fat:blood for Des 20:1 and Sevo 40:1) –I shouldn’t use Sevo b/c it saturates in Fat twice as much ? longer Wake up

FYI:
Case <2 hours - concern about blood & brain Case 4-6 hours - concern about blood, brain, and muscle Case >6 hours – concern about blood, brain, muscle, and fat compartment (longer cases – use Desflurance -NOT SEVO b/c it has more Fat:Blood solubility)

What are the organs that belong to the Vessel rich group?
The Brain, heart, kidney, liver, digestive tract, and glandular tissues

What are tissues of desired effect?

What are tissues of undesired effects?

The CNS tissues of the VRG

Tissues of undesired effects are heart/kidney/liver/GI Tract (except the Brain tissues in the VRG)

(SG Q. 1)
FD is ...
What are factors affecting F(D)?
(SG Q. 1)
FD is …
What are factors affecting F(D)?
Flow delivered

Factors affect F(D)
. flowmeter settings of carrier gas (O?, air, N?O)
. Vaporizer %

SG Q. 1
FI is…
Fraction Inspired Gas (inspired Gas concentration)

The fractional concentration of anesthetic leaving the circuit is designated as FI

SG Q. 1
FI
What are the factors that effecting FI?
SG Q. 1
FI
What are the factors that effecting FI?
. FD (Fresh gas flow and % of vaporizer)
. breathing-circuit volume ( the bigger = more dilution)
. circuit absorption (not so much an issue with newer machine)

SG Q. 1
FA
Alveolar Gas Concentration

. The fractional concentration of anesthetic present in the alveoli is FA

What are the factors that affecting FA?
. uptake

. Ventilation (the faster/deeper the pt. breaths = the fast he/she loses conciousness = quicker equilibration of AI between alveolar, blood, brain)

. the concentration effect and second gas effect

(3 factors affect uptake are: solubility in the blood, alveolar blood flow (essentially = to CO), and the partial pressure difference between alveolar gas and venous blood)

What is concentration effect?concentration effect (same as overpressurizing)
What is concentration effect?

concentration effect (same as overpressurizing)

is one of the methods to speed the induction of anesthesia

Concentration effect: Giving higher FI of an inhaled anesthetic, the more rapid the rate of increase of the FA/FI

(see top part of the graph! 70% of N?O produces a more rapid increase FI/FA ratio than 10% of N?O

Concentration Effect-The total volume in the lung is decreased by the amount of gas taken up by the blood, this reduction concentrates the remaining gas in the lung.

What is second gas effect?(second gas effect and concentration effect are the essentially the same thing, just looking at a different view
What is second gas effect?

(second gas effect and concentration effect are the essentially the same thing, just looking at a different view

A special case of the concentration effect. Administration of 2 gases simultaneously (nitrous oxide & a potent volatile anesthetic) in which the high volume uptake of nitrous oxide increases the FA concentration of the volatile anesthetic. (the high volume of N?O that moves out of the lungs ? causes the lungs to shrink (ex: 0.2% of sevo in there while the lungs are inflated – when the lungs ? in volume after the N?O diffuses out ? the % of of Sevo ? > 0.2 because of the smaller volume?therefore N?O cause concentration of the 2nd ? speed 2nd gas diffusion

Look at the lower part of the graph!
The FA/FI ratio for halothane ? more rapidly when administered with 70% N?O than 10% N?O

Uptake of large volumes of the first gas (Usually ) increases the rate of rise of a second gas given concomitantly.

Factors affecting inflow are
. Anesthetic concentration (FD)
. Alveolar Ventilation (VA)
. Characteristics of breathing circuit

Anesthetic Concentration (FD)
. Higher FD and thus higher FI increases rate of rase FA

Alveolar Ventilation (VA)
. Hyperventilation ? rate of rise of FA (b/c it delivers more anesthetic to lungs) (rate & depth)
. Hypoventilation ? rate of rise of FA (b/c it delivers less anesthetic to lungs ? ? rate of rise of FA/FI)
. Mechanical hyperventilation that ? venous return ? rise of FA (? venous return ? ? CO)

Characteristics of breathing Circuit
. Volume of circuit acts as buffer to slow rise of FA. (bigger = more dilution =
. Anesthetic solubility in rubber or plastic absorbs anesthetic gas slowing rise of FA.
. High gas in flow from anesthesia machine speeds rise of FA.

What are the 3 factors that affecting uptake?
What are the 3 factors that affecting uptake?
1. Anesthetic Blood Solubility (Most rapid rise of FA/FI with LEAST blood soluble agent; SLOWER with more blood soluble agents)

2. Alveolar to Venous Partial Pressure differences
– PA-PV = reflects tissue uptake of inhaled anesthetics
– Concentration Effect-The total volume in the lung is decreased by the amount of gas taken up by the blood, this reduction concentrates the remaining gas in the lung.
– Second Gas Effect- Uptake of large volumes of the first gas (Usually N2O) increases the rate of rise of a second gas given concomitantly.

3. CO

Ventilation and Affect on FA/FI

Ventilation delivers anesthetic concentrations to the alveoli

1. So, hyperventilation delivers more anesthtic to lungs ? ______ (? or ? rate of rise of FA/FI

2. Hypoventilation delivers less anesthetic to lungs ? ____ (? or ?) rate of rise of FA/FI

3. ? FRC (functional residual capacity) ___ (? or ?) rate of rise of FA/FI (owing to dilution.

4. ? FRC ___ (? or ?) rate of rise of FA/FI

5. Ventilation/Perfusion mismatch tends to ____ (? or ?) rate of rise of FA/FI (high concentration of anesthetic gas toward 1 lung – ? concentration)

1. ?
2. ?
3. ?
4. ?
5. ?

Cardiac Output and Affect on FA? CO ? ? FA (slow induction b/c uptake ? slowing the rise of alveolar partial pressure)Cardiac shunts
- Left to right = no change in FA ? therefore, no change in induction- Right to left (bypass the lungs - not picking up anesthetic) = slower rise of arterial concentration of anesthetic and slower induction
Cardiac Output and Affect on FA

? CO ? ? FA (slow induction b/c uptake ? slowing the rise of alveolar partial pressure)

Cardiac shunts
– Left to right = no change in FA ? therefore, no change in induction

– Right to left (bypass the lungs – not picking up anesthetic) = slower rise of arterial concentration of anesthetic and slower induction

Low CO = fast induction

SLOW train = pick up more anesthetic at time ? 1 CO? more concentration to the brain

FYI: Anesthetic gas induction vs IV induction
here we are talking about induction with anesthetic gas

Because PA = P blood = PCNS
if I know alveolar concentration is (PA) – it’s the same in the PCNS

We want FA/FI close to 1 (equilibrium between alveolar/blood/CNS)

#1 factor that affect PA is DILUTION

# 1 reason for diffusion to occur is:
pressure gradient

? RR ? ? Minute Ventilation ? ? anesthetic uptake
Tell your pt to take deep breath ? to ? minute ventilation ? ? FA

If a crying baby for ex: use 8% – overpressurizing – going to sleep with sevo in 4 breaths!)

30 y.o lady with egg allergy and can’t give propofol ? have her breath 5min on face mask to denitrogenate and fill up her lungs with O? – then start cranking up to the sevo 1%- then 2% – 3% “take another deep breath (just let her breath normal)-next thing you know- you are bagging/breathing for her

FYI:
If you give the pt a volatile anesthetic – you are going to deal with hypotension (b/c volatile anesthetics are potent vasodilators)
. ..

At see level, partial pressure is
760 (also called Barometric pressure)

Sevo has vapor pressure of 170

170/760 =22%

At high elevation, partial pressure is

Know how to calculate partial pressure!

less ( 600 for ex) (like giving anesthesia in Colorado on a mountain

So, Sevo has vapor pressure of 170

170/600 =28%
So, if you have your machine calibrated at 760 mmHg and giving anesthetic at higher elevation ? you OVERDOSE your patient if you don’t recalibrate !

Opposite – machine from Colorado to Jacksonville – we are going to under-dose the patient

What is the goal of elimination?
to lower the brain anesthetic level

What are the ways of elimination for anesthetic agents?
Exhalation (primary)
Biotransformation (0.2-20%)
transcutaneous loss (minimal)

The most important elimination factor is EXHALATION

What are the Factors that speech the elimination process?
Factors which speed elimination are (similar to factors which speed induction):

. High gas flows (turn your flow up to clear anesthetic out of the tubing)
. low anesthetic circuit volume
. low absorption by anesthetic circuit
. low solubility
. ? ventilation

(Ventilate your patient to get the anesthetic gas out 1st – don’t worry to wake the patient up –they will breath when the gas is out!)

Factors which slow elimination are:
. High tissue solubilities
. Longer anesthetic times
. Low gas flows

SG:

FYI: think about the vapor box in the vaporizer – it there to keep each vapor/gas at the right temperature. If the gas in high temperature –? molecule motions ? ? % of gas mixture in that container

Partial pressure is your concentration gradient.

(there always dilution ?there always concentration gradient)

FA/FI ratio the same as
concentration gradient

Q. 2 SG
What is the end-target organ of inhalation anesthesia?
Brain & spinal cord

Q3. SG
..

Q4. SG
Which anesthetic has greatest uptake, why?
Halothane
B/C Halothane has the lowest blood:gas solubility 0.42

Low solubility give you
high FA

High solubility give you
Low FA

Q. 5 SG

MAC is
minimum alveolar concentration of an inhaled anesthetic which prevents movement in 50% of patients in response surgical incision

MAC mirrors
brain partial pressures

What is time constant?
Time constant = capacity/flow

1 time constant = 1/2 min = 63% of oxygen
2 time constant = 1 min = 86% (replacing 86% of oxygen in alveolar)
3 time constant = 1.5 min = 95%
4 time constant = 2 min = 98%

It takes at least 2 min to oxygenate the patient !

Goal of anesthesia is to produce
amnesia
immobility

FYI: Sevo
? Sevo MAC ? every 2 hour to prevent compound A

To prevent changing Sevo – ? fresh gas flow- prevent the pt to re-breath

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