SS25 3-3 Inhaled Anesthetics Part 1 (Exam 3) Flashcards
UDME
- Uptake from alveoli into pulm capillary blood
- Distribution
- Metabolism
- Elimination via lungs
What non-modifiable risk factor influences the pharmacokinetics of Volatiles?
- How?
- Age
- ↓ lean body mass
- ↑ fat
- ↑ VD for drugs (esp. fat soluble)
- ↓ CL if pulmonary exchange is impraired
- ↑time constraints d/t low CO
Are volaties lipid soluble or fat soluble?
- Fat/lipid soluble
What is significant about volatiles being delivered via inhalant?
- Respiratory status plays a direct role in uptake and elimination
What is Boyle’s Law?
Clincal significance?
- Pressure and Volume of gas are inversely proportional (↑P = ↓V & vice versa)
- PPV begins → Bellows contract & become more compact → ↑circuit & vent pressure → gasses flow from high pressure circuit to low pressure lungs
In relation to volatiles, what’s Fick’s Diffusion Law?
Once air molecules of vapor & O₂ enter alveoli, they move around freely and begin to diffuse into the pulmonary capillaries to then get to brain
Brain = main effector/ receptor site
Diffusion depends on:
- Partial pressure gradient of the gas (Air, N2O, Sevo, etc.)
- Solubility of the gas (things that are more diffusable get across capillary easier)
- Thickness of the membrane (thicker = hard to cross)
STP
What is Graham’s Law of Effusion?
- Process by which molecules diffuse through pores and channels without colliding
- Process of molecules getting to capillary membrane rlt solubility
Smaller molecules effuse faster depending on (_______).
- Solubility (diffusion)
Which diffuses faster CO₂ or O₂?
- Why?
- Which would you expect to diffuse faster?
- Despite O₂ weighing less, CO₂ diffuses into gas filled spaces 20x faster due to higher solubility
Molecular wt: CO 44 g & O₂ 32 g
Examples of air-filled places
- lungs
- gut
- ear & inner ear
Nitrous can diffuse to these spaces within 15mins
- What gase(s) do we not use alone for anesthesia?
- Why?
- Nitrous gas
- Concentration is 104% for 1 MAC
- Not able to reach effective level without causing hypoxia
- Typically used adjunctly and for analgesia
What does the following equation mean?
PA ⇌ Pa ⇌ PBrain
This is comparing the partial pressure of volatile gas in the alveoli to the arterial blood to the brain
PA and Pa relationship
- Pressure in alveoli can go back and forth from lung capillary (lung artery)
Pa and PBr relationship
Pressure in lung can equilibrate with the brain
How can you determine the Alveolar pressure (PA)?
- Measure end-tidal exhaled gas
Ie: ETDes, ETSevo, etc.
Hard to measure pressure in lung artery or brain
Alveolar pressure (PA) is an indicator of:
- Depth of anesthesia
- Recovery from anesthesia
- able to determine what stage of GA their at
- If PBr > PA then what do we expect to be occurring?
- Why?
- The patient should be waking up
- This means the exhaled gas > than the inhaled gasand the concentration gradient is moving towards the alveoli away from the brain.
- What are the input partial pressure gradient(s)?
- What are the uptake PP gradient(s)?
- Anesthetic machine to the alveoli = Input
- Alveoli to blood = Uptake
- Arterial blood to brain = Uptake
What input factors affect the diffusion of volatile gas getting from the anesthetic machine to the alveoli to the brain?
- Inspired partial pressure (ex: FiO₂ of 70% vs 30%)
- Alveolar ventilation (↑ RR = taking in gas faster)
- Anesthetic system breathing system
- FRC
IAAF =** Input Alveolar Anesthesia Factors**
What anesthetic device has lot of re-breathing? Clinical signifiance?
- What device doesn’t? Why not?
- Re-breathing system = Transport circuits - causes higher uptake of gas
- Breathing system = Anesthesia machines b/c washed out with O2 & then brand new gas.
Which factors affect uptake of anesthetic gas from the alveoli to blood?
- Blood:Gas partition coefficient
- Cardiac output
- A-vpressure difference
ABG-Cardiac
Explain relationship of cardiac output (CO) on the affect of diffusion of anesthetic gas from the alveoli to pulmonary capillary blood?
- ↓CO = Slower onset but more more molecules diffuse across the alveolus at once (more time)
- ↑CO = Faster onset but less molecules diffuse across the alveolus at once (less time)
What factors affect the uptake of anesthetic gas from the arterial blood to the brain?
- Blood:Brain partition coefficient
- Cerebral blood flow
- a-v partial pressure difference.
AB₂C
T/F: You can’t alter uptake for initial distrubution of volatiles.
False: You can adjust uptake factors (by increasing and decreasing) & the initial distrubution of volatile
Gas goes from a ____ gradient to a ____ gradient in order to reach a steady state.
high; low
What are the Induction Methods?
- Concentration effect
- Over pressurization
- Second Gas effect
COS
What does PI mean?
Inspired pressure (of a volatile)
How can gas be “forced” to the brain quicker?
- Concentration Effect
- By increasing PI of volatile
- This creates a higher gradient for the gas to flow from PA → Pa → PBrain
- Offsets uptake into PA
Order of gas flow through ciruit:
FGG= (fresh gas flow) → Inspiratory limb → lungs → pulm vessels → brain → pulm vein → lungs expiratory limb → scavenge system
Reminder VRG: Brain, Heart, Kidney, Liver
What concept is this chart conveying?
- Concentration Effectcs
- As gas ↑ concetration, overtime↑ Fe /Fi increase (1.00)
- ↑PA = increased rate of diffusion
- Higher gas concetration = less breaths needed
This goes for any gas
What is over-pressurization?
-A large increase in PI forces gas from PA → Pa → PBr much faster
- Mainly emergent; not everyday use
- Increase dose get pt to sleep & then decrease dose
- Follows Henry’s Law: ↑ volatile partial pressure in alveoli → ↑ volatile dissolved in blood =↑ uptake and speed of induction
- What’s the normal concentration for Sevo?
- What’s the high concentration for Sevo?
- What can happen during over pressurization of Sevo?
- Normal: 2 - 3%
- High: 7%
- Over pressurizaztion: 1 vital capacity breath of high concetration Sevo can potentiate Stage 2 (loss of eyelash reflex)
What would sustained delivery of over-pressurization result in?
Overdose
What is the second gas effect used for in anesthesia?
- Uptake of a high-volume gas (N₂O) to accelerate a concurrently administered volatile gas
Explain second gas effect between Sevo and Nitrous
- High-volume of 50 % N₂O uptake into pulm capillaires
- Increases concentration of 2nd gas Sevo 50%
- Nitrous diffuses into the pulm artery
- Now alveoli has 100% Sevo - Increased uptake of Sevo d/t to high to low gradient via concentration effect
Nitrous is very easily diffusible
How does N₂O create the second gas effect?
N₂O hyper-concentrates volatiles to create a high concentration gradient by being super-diffusible.
Describe what is being depicted on the graph below.
- This is the concentrating effect of N₂O on halothane.
- Top = concentration effect
- Bottom = 2nd gas effect (FA/FI ↑ w/ 70% N₂O)
What cases would nitrous oxide not be utilized in?
Why?
- Cases with an air-filled cavity
- N₂O will diffuse into the cavity and fill it. (extent of damage dependent on the compliance of the cavity).
How does Nitrous affect Compliant walls?
- Example discussed in class?
- Volume change
- Pressure will not change
- Ex: Open abd, SBO repair - unable to close abdomen
How does Nitrous affect Non-Compliant walls?
- Example discussed in class?
- Pressure change
- Volume will not change
- Ex: Inner ear surgery - unneccesary postop pain d/t lack of distensibility
Per lecture, what specific cases are bad for N₂O use?
- Bonus: Can you think of a cavity not listed?
- Ear & Eye
- Gut/Intestines, Open Belly
- Lung
- Bonus: Paranasal sinuses!
What factors affect the degree of pressure N₂O would exert on a cavity that it filled? “Think PBD”
- What is the rate and volume that Nitrous can diffuse to in air-filled spaces?
- Partial pressure of N₂O
- Blood flow to the cavity
- Duration of N₂O administration
- Up to 10 L in the 1st 10-15 mins
What would nitrous inhalation in a patient with pneumothorax do?
-Explain image:
- shaded shapes = O₂ inhalation;
- open/unfilled shapes= N₂O inhalation
- Severe expansion of pneumo
- Extreme volume changes
- @ 10 mins = 100% ↑ in volume
- @ 20 mins = over 150% ↑ in volume
No major changes with O₂ inhalation
What complications are associated with N₂O on a retinal eye repair?
- How long does it take for this complication to occur?
- Severe ↑ intraocular pressure and cause permanent vision loss d/t retinal artery loss
- 1 hr of nitrous administration
What factors can change the speed of induction?
- Alveolar Ventilation (VA)
- Solubility
At a (__________) PI ,(__________) RR speeds PA toward PI to speed up induction.
- higher
- increasing
What is the concern with high concentrations of volatiles ( high PI ) throughout procedure?
- Risk of cardiopulmonary depression
- ↓VM, ↓CO, ↓ RR
What physiological mechanisms occur with increased anesthesia (deepening sleep) to prevent depression?
- Brain knows when we are in deep sleep b/c the side effects of Volatiles on cardiopulmonary system.
- ↓ PaCO₂ will cause ↓ CBF thus slowing induction speed automatically
Decreased (_________) from hyperventilation will decrease cerebral blood flow and limit induction speed.
- Is this positive or negative feedback?
- PaCO₂
- Negative Feedback loop: the body’s response (vasoconstriction) opposes inhalation of volatiles
T/F: Volatiles have dose-dependent stimulant effects of Alveolar ventilation
False
- dose-dependent depressant effects
D/t decreased ventilation, input decreases. Explain volatile re-distribution.
- As brain concentration ____ , Ventilation ____.
- Volatile redistributed from high concentration tissues of brain to low concentrated fat
- decreases; increases
Based off negative feedback circle discussed in lecture, how does this work in spontaneous ventilation (not intubated)
- Too sleep –> ↓ [drug] to brain & drug still leaving brain –> Volumes ↑ = ↑ LOC –> more gas enter brain –> Volumes ↓ =
↓ LOC .. the cycle continues
Based off negative feedback circle discussed in lecture, how does this work in mechanical ventilation?
- Since Mechanical ventilation has a SET VM, RR, & vaporizer rate, there’s no influence by body’s mechanisms
- Easier to OD
- CRNA is the controller
What is the definition of solubility for anesthetic gasses?
- A RATIO of how inhaled volatile distributes b/w 2 compartments at equilibrium (when partial pressures are equal).
- brain ratio = alveoli ratio = fat ratio
Per lecture, explain volatile maintainance phase.
- Uptake amount = amount body rids of
- No moment to moment changes
Factor(s) that influence the solubility ratio:
- Temperature
Think: If you heat water on stove, when it heats up and start boiling, the water vapor escapes
- If the temp of blood increases, then solubility _________.
- If the temp of blood decreases, then solubility _________.
- decreases = low blood solubility
- increases = high blood solubility
What does a low blood solubility mean for induction?
- It wants to leave blood
- Less gas has to be dissolved = PA → Pa is rapid = rapid induction.
What does a high blood solubility mean for induction?
- It wants to stay in blood
- More gas has to be dissolved = PA → Pa is slow = slow induction.
What is being described in the graph below?
-How quickly the inspired concentration of a gas equals the alveolar concentration of said gas.
- Order: high to low solubility
1. Halothane: #1 Highest solubility = prolonged induction
2. Isoflurane: High
3. Sevoflurane:
4. Desflurane: Low
5. Des + Nitrous: Very low = rapid induction
genereally quick to sleep, quick to wake uo & vice versa but not always
What volatile gasses are intermediately soluble?
- Clinical significance?
- Halothane
- Enflurane
- Isoflurane
- Wants to stay in blood longer, prolonged induction, may need to start early and turn off later
HEI is high to low B:G coefficient
What is the blood:gas partition coefficient of halothane?
Halothane = 2.54
What is the blood:gas partition coefficient of enflurane?
Enflurane = 1.90
What is the blood:gas partition coefficient of Isoflurane?
Isoflurane = 1.46
What volatile gasses are poorly soluble?
- N₂O
- Desflurane
- Sevoflurane
- They want to leave the blood & go to brain
What is the blood:gas partition coefficient of N₂O?
Nitrous = 0.46
What is the blood:gas partition coefficient of Desflurane?
- What is the ratio?
Desflurane = 0.42
- 0.42 in blood to 1.00 in the gas, thus ratio = 0.42 : 1.00
What is the blood:gas partition coefficient of Sevoflurane?
Sevoflurane = 0.69
- 0.69 in blood to 1.00 in the gas, thus ratio = 0.69 : 1.00
Review
- memorize blood:gas partition coefficient and the relationship to fat
Which is the volatile of choice for morbidly obese?
- Clinical significane?
- Bones: What’s the BMI formula?
- Desflurane > Sevo
- Sevo will hold onto more gas & will need to start waking up earlier
- Will affect when you need to turn on oand off gas - BMI = 703 x lbs / ht. (in)2
or kg / ht. (m)2
What occurs (in regards to our partial pressure gradients) during emergence from anesthesia?
Concentration gradient reverses.
PA ← Pa ← PBrain
- Define Emergence:
- What is the first step you do?
- How do volatiles react to this first step?
- Emegence: Rate of decrease in PBr
- Turn the gas off ( FI = 0% )
- Volatiles wash out of brain rapidly b/c they’re not highly soluble in brain and high CO helps
Factor(s) that affect length of volatile/emergence:
- Solubility
- Comes out of brain rapidly but also has to clear from other ALL other compartmemts (same compartments different route)
What helps decrease concentration of volatile in PA and PBr on emergence?
Continued uptake by Muscle/Fat if not already at equilibrium.
Compare emergence from volatiles in image:
- Clinical significance?
-
If I turn my volatile completely off ( FI = 0% ):
1. Des = Fastest
2. sevo = Fast
3. Iso & Halo = slow - Timing; use the volatile to your advantage. Des won’t always be the answer.
Do you need to wake up immediately or is this patient going to ICU and will be better to keep them away from Stage 2… Work on timing with Iso and Sevo as well
Based off 1.6 MAC, which anesthetic would you anticipate as having the quickest recovery?
- Slowest?
- For Iso, what was the recovery time based off 2 hour sleep?
- Fastest recovery = desflurane
- Slowest recovery = halothane
- Isoflurane recovery time = 30 mins
Another trend to consider: Desoflurane has lowest Fat:Blood Par (besides Nitrous) & Halothane has the highest
What is 1 MAC?
- This is the same as ______.
- Why is this not okayy for the patient?
- 1 MAC: Concentration at 1atm that prevents skeletal muscle movement in response to surgical stimulation in 50% of patients.
- Same as ED50
- Not okay b/c we can’t afford a 50% of patient moving
MAC
- Minimum Alveolar Concentration
What is 1.3 MAC?
- Concentration at 1atm that prevents skeletal muscle movement in response to surgical stimulation in 99% of patients.
- Goal = sleep & still
What would ED99 be equivalent to in regards to MAC?
- clinical significance?
- ED99 ≈ 1.3 MAC
- This is the goal: no movement
What is MACawake range?
- When do we use this?
- How do we awake patient from MACawake ?
- 0.3 - 0.5 MAC: partial awakeness and responsiveness but completely still
- MAC value after getting pt to 1.3 MAC or whatever they need for sleep & stillness (“MAC maintanence”
- Will use noxious stimuli to wake them up
What is MACBAR?
- 1.7 - 2.0 MAC: Blunts Autonomic Responses
- No SNS response at all
- Essentially an overdose.
2 Biggest Factors that alter MAC:
- Temp
- Age
Hyperthermia does what to metabolism?
- Increases metabolism
- Eats through gas faster; will need to increase MAC
How does age affect metabolism?
- elder: Low metabolism: decrease MAC
- babies/kids: high metabolism: increase MAC
What patient are standardized MAC values based on?
- 30 - 55 y/o at 37°C at 1atm
- Middle age, normothermic, @ sea-level
- MAC #s are on vaporizer
- Use End-tidal and Inspired to know if you’re at equillbrium
What is 1 MAC of N₂O?
What does this mean?
N₂O MAC = 104%. Can’t be used as sole anesthetic agent.
What is the 1 MAC of Halothane?
0.75%
What is the 1MAC of Enflurane?
1.63%
What is the 1 MAC of Isoflurane?
1.17%
What is the 1 MAC of Desflurane?
6.6
What is the 1 MAC of Sevoflurane?
1.8%
At what age does MAC peak?
- 1 y/o
- The young need more gas and the old needs less
How much does MAC need decrease as one gets older?
- 6% per decade.
What change in MAC would you make for the following ages:
- 60
- 70
- 80
- 20
- 10
- 60 =↓MAC 6%
- 70 =↓MAC 12%
- 80 =↓MAC 18%
- 20 =↑MAC 6%
- 10 =↑MAC 12%
Once surgeon is prepped amd ready. what do you do with the MAC of volatile?
- Start Increase to 1.3 MAC
What factors will increase MAC?
- Hyperthermia (↑ metabolism)
- Excess Pheomelanin (redheads )
- Drug-induced ↑ catecholamines
- Hypernatremia (depolarizes membranes faster)
What factors will decrease MAC?
Extensive list
Essentially anything that SLOWS metabolism
- Hypothermia
- Pre-op meds
- Intra-op opioids
- α-2 agonists (Dex, clonidine) - ↓ SNS
- Acute EtOH
- Pregnancy
- Early post-partum (early - 12-72 hrs)
- Lidocaine
- PaO₂ < 38 mmHg
- MAP < 40mmHg
- Cardiac Bypass
- Hyponatremia
- Age
- Renal Failure: Hypervolemic
- Stroke
- Poor nutrition
What factors will have no effect on MAC?
- Chronic ETOH abuse (New Norm)
- Gender
- Duration of anesthesia
- PaCO₂ 15 - 95 mmHg
- PaO₂ > 38 mmHg
- MAP > 40 mmHg
- Hyper/HypoKalemia
-
Thyroid gland dysfxn
-Exception: Thyroid storm can affect MAC but controlled dysfxn w/ home Synthroid has no effect on MAC
How does spinal immobility occur with the use of volatiles?
(Explain the MOA on what receptors)
- Do volatiles cause paralysis?
- Volatiles depress spinal movement
- Depress excitatory AMPA & NMDA (glutamate-Rs)
- enhance inhibitory glycine- Rs (Strychnine, glycine antagonist)
- Act on Na channels (blocks pre-synap glutamate release
- Volatiles do not 100% paralyze but are synergistic
How does loss of consciousness occur with the use of volatile anesthetics?
- Potentiation/Inhibition of GABAA in the brain (esp. RAS)
- Potentiation of glycine in the brainstem
- No LOC effect of volatiles on AMPA, NMDA, Kainate
Movement and conscioness relate but are different
Partial pressure
- A mixture of gases in a closed container that exert a pressure on the walls
What is Dalton’s law?
- The sum of all partial pressures will equal the total pressure.
- Ptotal = Pgas1 + Pgas2 + Pgas3…
Will never have less than 100%
Define Vapor Pressure.
- Which of these two liquids in the enclosed containers has the higher vapor pressure?
- Vapor pressure is the pressure at which vapor and liquid are at equilibirum
- Evaporation = Condensation
- Liquid B: Contains more gas particles
What color coding does desflurane have?
Blue
What color coding does sevoflurane have?
Yellow
What color coding does isoflurane have?
Purple
Heat will _____ vapor pressure.
increase
Cold temperatures will _____ vapor pressure.
decrease
A lower vapor pressure gas is inherently more volatile. T/F ?
False. ↑ vapor pressure = ↑ volatility
What is the vapor pressure of Halothane?
243 torr
What is the vapor pressure of Enflurane?
175 torr
What is the vapor pressure of Isoflurane (Forane)?
238 torr
What is the vapor pressure of Desflurane (Suprane)?
- Clinical significance of this pressure?
- 669 torr
- Near sea-level; it vaporizes at the same level as sea-level
- So if you pour some on counter, it will evaporate after a few secs
What is the vapor pressure of Sevoflurane (Ultane)?
157 torr (or mmHg)
Functions of Vaporizers
- Change liquud to vapor
- Add an amount of vapor to fresh gas flow
- Partial pressure / total pressue = Volume %
- What information is obtained off the monitor.
- What is the volatile inhalent goal for anesthesia?
- What intervention can I do to reach my goal?
- End-tidal (ET)- Volu % exhaled (88%)
- FI - Volu inspired (93%)
- Nitrous - (0% means it’s off)
- Volatile (Des in this image) - giving 6.8% inspired ~ 93% and exhaling 6%
- Goal: PA = PBr
- Intervention: Still have more space/Des to take up on ET
What is the variable bypass on the anesthetic machine?
- Dilutes saturated vapor gas using a splitting ratio
- Splitting ratio based off splitting valve
Per lecture, what’s Clinical significance of the splitting valve?
- what happens if I increase volatile %?
- what happens if I decrease volatile %?
- Holes in this valve allow fresh O₂ gas to go down into vaporizing chamber & some O₂ goes through bypass pathway
- ↑ hole gets bigger and more O₂ in vaporizing chamber > by pass pathways
- ↓ hole gets smaller: & less fresh O₂ gas in vaporizing chamber < by pass pathway
- Side note: pass pathway is 100% O₂
Per lecture, what’s Clinical significance of the vaporizing chamber?
- Contains anaesthetic agent
- In order to pick up more volatile, send more fresh gas flow by the liquid in vapor chamber (↑ control dial)
How do you get gas from vaporizer to lung
- Flow meter: ↑/↓ flow to control speed of gas
- Changes time
What is the splitting ratio?
How much gas is being sent into the vaporizer
What is the purpose of the wicks found in the vaporizing chamber below?
- Increases gas-liquid interface/surface area
- Improves vaporization efficiency
