Inhaled Anesthetics- Part 1 (3) Flashcards
What are the pharmacokinetics of inhaled agents?
- Uptake from alveoli into pulmonary capillary bed
- Distribution
- Metabolism
- Elimination via lungs
Pharmacokinetics of inhaled anesthetics is influenced by:
Aging
What is Boyles law?
Pressure and volume of a gas are inversely proportional when temperature is constant
How does Boyles Law apply to a ventilator?
What does diffusion of a gas depends on?
- Partial pressure gradient of the gas
- Solubility of gas (diffusion)
- Thickness of the membrane
What is the main effector site for volatile anesthestics?
Brain
Why does membrane thickness matter for gas diffusion?
Thicker membrane= harder for gases to diffuse across
What is Fick’s Diffusion Law?
Once molecules get to the alveoli, they move around randomly and begin to diffuse into the pulmonary capillary
Movement from high to low concentration
What is Graham’s Law of Effusion?
Process by which molecules diffuse through pores and channels without colliding
*Smaller molecules effuse faster dependent on solubility (diffusion)
What is the difference between diffusion and effusion?
Diffusion: Mixing of gas particles
Effusion: Escape of gas molecules through a small opening
If O2 is smaller than CO2, why does CO2 diffuse easier than O2?
- CO2 is VERY soluble compared to O2
Why dont we use nitrous in some gases?
Nitrous has rapid diffusibility (similar to CO2)
CO2 is ___x more diffusible than O2
20x
How do we figure out partial pressure in alveolus?
End tidal of exhaled gas
How does gas pressure equilibrate in the brain?
Alveolar pressure can go back and forth with pressure in pulmonary artery which can equilibrate with the brain
Alveolar pressure is an indicator of:
- Depth of anesthesia
- Recovery of anesthesia
What are the different partial pressure gradients when giving volatile anesthetics?
- Anesthetic machine to Alveoli (gas going in)
- Alveoli to blood
- Arterial blood to brain
What is involved in the partial pressure gradient from anesthetic machine to alveoli?
“INput”
* Inspired partial pressure
* Alveolar ventilation
* Anesthetic breathing system
* FRC
Is there re-breathing from anesthetic circle system?
Not alot of rebreathing in the anesthesia circuit
Some transport machines have more re-breathing
rebreathing helps uptake more gas
What is the purpose of the alveoli to blood pressure gradient?
“Uptake”
* Blood: gas partition coefficient
* Cardiac output
* Alveoli and capillary vein partial pressure difference
Where is the blood:gas partition coefficient?
Alveoli to Blood
Where is the blood:brain partition coefficient?
Arterial blood → brain
What does the arterial blood to brain pressure gradient involve?
*Brain: blood partition coefficient
* CBF
* a-v partial pressure difference
Which partial pressure gradient can we manipulate?
Anesthetic machine to alveoli
* Inspired partial pressure
* Rate of breathing
What happens with distribution of volatiles with low and high cardiac output?
Low CO→ More time for has molecules to hop on board
High CO→ Less time for gas to hop on board
What are factors of aging that affect the uptake, distribution, and metabolism of volatile anesthetics?
- Decrease lean body mass
- Increased body fat
- Increased Vd for drugs (esp. fat soluble drugs)
- Decreased clearance (impaired pulm exchange)
- Increase time constraints (Low CO)
What happens to alveolar pressure with higher inspired pressure of a volatile?
Alveolar pressure will more rapidly approach inspired pressure
Why does a higher concentration of gas get to the alveoli and brain faster?
Due to concentration effect→ the more concentrated the initial breath the faster the gas gets to the alveoli
Takes few breaths
If you are trying to get someone to sleep quickly what would be the best tactic with volatile gas?
Turn the concentration up on vaporizer so they take few breaths to fall asleep (more concentrated so few breaths)
How does gas flow through the circuit to the brain to go to sleep?
Vaporizer→ circuit/ inspiratory limb → lungs → pulmonary vessels → brain
Where goes gas flow once it gets to the brain?
brain →blood→ lungs →expiratory limb and blown off into scavenging system
Goes to vessel poor groups (muscles, fat, skin)
Why do volatiles go to the brain first?
Vessel rich group: goes to brain, heart, kidneys, liver
Brain is where receptors are (effector site)
What percentage of volatile anesthetic would nearly approach where inspiratory and expiratory gas fractions are the same?
85%
What is over pressurization?
Strong intervention (not every day)
A large increase in inspired fraction (very concentrated/ turning vaporizer up as high as it goes)
Momentary thing**
What is the purpose of over pressurization? What is the concern?
Allows us to get pt to sleep in one vital capacity breath and they lose lash reflex→ then need to turn back down to normal dose
If continue to give high dose and dont turn it down there are lots of side effects
What is Second Gas Effect?
Using a high volume of gas (N2O) to accelerate another gas (volatile)
Why is N2O used for second gas effect?
N2O is very diffusible into gas filled spaces so it moved from alveoli quickly into pulm vessels and then to VRG
When N2O moves it leave more volatile (more concentrated) in the alveoli because all of the N2O left
What happens with the second gas effect after N2O diffuses from the alveoli?
Volatile is left more concentrated in the alveoli and it then diffuses to effector site d/t concentration effect
Increases the uptake of the second gas d/t the gradient created
Explain how using 1 gas compares to using 2 gases?
0.5% halothane with 70% N2O showing 2nd gas and concentration effect because it approached a high inspiratory/expiratory ratio
Nitrous oxide can diffuse up to ____L in the 1st 10-15 minutes into air filled spaces.
10L
What are common air filled spaces (air filled spaces) that N2O diffuses into?
- Inner ear
- Lung
- Gut
- Intestine
What happens to volume and pressure if walls of a system are compliant?
Pressure doesnt change even if volume increases
What happens to volume and pressure if walls of a system are noncompliant?
A little volume increases pressure A LOT
What organs/ body parts discussed in lecture were compliant vs noncompliant?
Gut: compliant
Inner ear: non compliant (lacks distensibility)
What factors effect the magnitude of pressure?
- Partial pressure of N2O
- Blood flow to cavity
- Duration of N2O administration
How does N2O inhalation compare to O2 inhalation regarding volume?
O2= no change in volume
N2O= continuous increase in volume with time
What type of surgery discussed in lecture would N2O be no bueno?
Intraocular s/p retinal repair
*1hr of nitrous caused retinal artery vision loss
How can the speed of induction be increased?
- Increase respiratory rate (alveolar vent) →increased inspired pressure vs alveolar pressure
What needs to be increased to speed up induction?
The faster alveolar pressure= arterial pressure= brain then the faster pt is asleep
What is a typical side effect of volatile anesthetics?
Respiratory depression
decrease CO
decrease minute ventilation
How does the body safe guard against prolonged high inspired pressure
CO and RR decrease→ gas isnt leaving to go to brain
Body knows the deeper GA becomes, the more the body slows down the cardiac and pulmonary processes to decreases CBF and get less drug to the brain (decreasing PaCO2)
How would the body attempt to balance anesthetic gas if the patient wasnt intubated and just receiving volatile gas through face mask?
Decreases resp rate Bringing less gas to the brain body starts to wake up→ as pt becomes more awake they breathe faster (more gas going in) and go back to sleep
Would it be easier to OD a patient on a ventilator or a patient who is breathing on their own?
Ventilator→ because we are controlling rate and volume and gas amount regardless what is happening to pts cardiac and respiratory status
non intubated patients play a role in setting their own rate and VT
Decreasing PaCo2 (hyperventilation) decreases ____________ and limits the speed of induction
Cerebral blood flow
Decrease PaCO2 causes cerebral vasoconstriction (CO2 is a potent vasodilator)
Solubility is a _______.
Ratio
What does solubility look at?
Ratio of how the inhaled anesthetic distributes between 2 compartments at equilibrium (when partial pressures are equal)
the relative capacity of each compartment to hold volatile
Ratio of inhaled anesthetics can change depending largely on __________
Temperature
What happens to solubility if blood temperature increases? Why?
blood solubility decreases
* makes volatiles more likely to leave the blood to go to brain/fat
What happens to volatile solubility when the body is cold?
Volatiles are more likely to stay in the blood
*blood solubility is high
How does low blood solubility impact induction?
Small amounts must be dissolved
PA/Pa is rapid→ induction is rapid
How does high blood solubility impact induction?
Large amounts must be dissolved
PA/Pa is slow→induction is prolonged
We want to give anesthesia to patients who are __________.
Normothermic
Which volatile is the most soluble?
Halothane (doesnt want to leave the blood)
Slow to go to sleep
Which volatiles have low solubility? What does this mean?
Desflurane and Nitrous oxide
Means you can go to sleep quicker since they like to leave the blood
Generally if a volatile is quick to go to sleep it is a _______ wake up
Quick
(opposite with slow induction→slow wake up)
What is the blood:gas partition coefficient of Halothane?
2.54
same as saying 2.54 in the blood to 1 in gas
What is the blood:gas partition coefficient of Enflurane?
1.90
What is the blood:gas partition coefficient of Isoflurane?
1.46
What is the blood:gas partition coefficient of Nitrous oxide?
0.46
What is the blood:gas partition coefficient of Desflurane?
0.42
What is the blood:gas partition coefficient of Sevoflurane?
0.69
Why do we want gases with low solubility and low blood:gas partition coefficients?
Quicker onset and offset quick turnovers
If a patient is morbidly obese (with all things being even) what volatile would you prefer to give them?
Desflurane over Sevoflurane
*Fat:blood partition coefficient is less for des than sevo
Can get to sleep at about the same rate
How do we decide when to turn off a volatile to wake someone up at a certain time?
Have to look at Fat:Blood coefficient to know how long it will be around after you turn the vaporizer off
What is the one volatile that isnt as highly sequestered in the fat?
Nitrous Oxide
What is emergence?
Waking up→ how fast the volatile washes from the brain
Why is the rate of volatile decrease in the brain dependent on the length of anesthestic?
When inspired pressure is 0 (inhalation is off) the muscle/fat may not be at equilibrium
Muscle and fat continue to take up anesthetic
What does Fi0 mean?
Inspired fraction of 0= turning vaporizer off
If turning vaporizer off, which volatiles have a slower emergence compared to faster emergence?
Slow: halothane and iso (would need to consider timing)
faster: sevo and des
Which gases (if given the same MAC hours) would have the fastest wake up?
Des and sevo→ by far fastest wake up
Halo and Iso → increased minutes to recovery
What is the definition of 1 MAC?
Minimum alveolar concentration
The concentration at 1 atm that prevents skeletal muscle movement in response to supramaximal painful stimulation in 50% of patients
MAC can be thought of as the _______
Dose
1 MAC is the same as _____
ED50
Why is 1.3 MAC better than 1 MAC?
1.3 MAC prevents skeletal muscle movement in 98% of patients (more ideal)
1.3 MAC is the same as ______
ED98
What concentration is MACawake?
0.3-0.5 MAC (drowsy but can wake up)
What MAC level blunts autonomic reflexes (MACBAR)? Why can this be an issue?
1.7-2.0 MAC→ Wont be able to get BP and HR to go up because they are so deeply asleep
“too asleep”
What is the 1 MAC value of nitrous oxide?
104
What is 1 MAC of Halothane?
0.75
What is 1 MAC of Enflurane?
1.63
What is 1 MAC of isoflurane?
1.17
What is 1 MAC of desflurane?
6.6
What is 1 MAC of sevoflurane?
1.8
What conditions does MAC assume?
30-55 y/o, avg 37 degrees, 1 atm
MAC peaks at __ year old and stays high then starts declining around age _____
1, 55
What are the biggest factors that affect MAC?
Body temp
Age
Where are the MAC % numbers seen?
On the vaporizer dials
How would MAC vary with a patient who is 90 years old and 50 lbs?
Decrease the amount (not full MAC) or might not even turn on
How goes age influence MAC?
Every decade age changes MAC by 6%
20y/o: increase MAC 6%
10y/o: Increase MAC 12%
60y/o: Decrease MAC by 6%
70y/o: decrease MAC by 12%
Why does MAC increase for patients less than 30y/o?
Increased metabolism requires more anesthetic
What increases MAC? (needs more MAC than normal)
INCREAES IN METABOLISM
- Hyperthermia (sepsis)
- Excess pheomelanin production (redhead)
- Drug induced increased in catecholamines (Pheochromocytoma)
- Hypernatremia (faster APs)
- Thyroid storm
What decreases MAC?
- Hypothermia
- Preoperative meds (synergistic meds)
- Intraop opioids
- Alpha 2 agonists (↓ SNS)
- Acute alcohol ingestion
- Pregnancy (hormones)
- Post partum (early 12-72hrs)
- Lidocaine
- PaO2 < 38mmHg
- MAP <40mmHg
- Cardiopulm bipass
- Hyponatremia
- Renal Fx (hypovolemia)
- Debilitated patients
What are some things that do not affect MAC?
- Chronic alcohol abuse
- Gender
- Duration of anesthesia
- PaCO2 15-95 mmHg
- PaO2 >38 mmHg
- MAP >40 mmHg
- Hyperkalemia
- Hypokalemia
- Thyroid gland dysfunction (once on meds and regulated)
How do volatile anesthetics cause spinal immobility?
- Depress excitatory AMPA and NMDA (glutamate receptors)
- Enhance inhibitory glycine receptors
*Act on sodium channels to block presynaptic release of glutamate
_______ is a competitive antagonist of glycine receptors
Strychnine (binds and prevents glycine from activating the receptor)
What MOA of volatile anesthetics causes loss of consciousness?
**Inhibitory transmission of GABA (in brain and RAS)
*Potentiate glycine activation
*No effect of volatiles on AMPA, NMDA, or kainate
What color is associated with des, sevo, and iso?
Des: blue
Sevo: yellow
Iso: purple
What is the safety mechanism to prevent cross filling of different volatiles?
Caps are different shapes and will not fit each other → Doesnt allow for cross filling
What is Daltons Law?
The sum of all partial pressures must = 100
What is vapor pressure?
The pressure at which vapor and liquid are at equilibrium
OR evaporation= condensation
B has higher vapor pressure
How does temperature impact vapor pressure?
Heat increases vapor pressure
Cool decreases vapor pressure
If something has a high vapor pressure, what does that mean?
More likely to evaporate→ considered more volatile
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?
238 torr
What is the vapor pressure of Desflurane?
669 torr → Vaporizes at almost the same pressure as sea level
Other meds stay liquid at sea level
What is the vapor pressure of Sevoflurane?
157 torr
How is volume percent calculated from a vaporizer?
Partial pressure/Total pressure= volumes %
What values on the monitor do we want at equilibrium?
End tidal (exhaled volume percent)
Fi (inspired volume percent)
How does variable bypass method of volatile admin work?
Splitting valve→ holes that allow fresh O2 flow to go down into vapor chamber where liquid is→ comes back up to meet with O2 to travel to airway tubing
Hole leading to vapor chamber gets bigger or smaller based on percent dialed (would cause more or less bypassing O2)
How is MAC increased with variable bypass route?
Need more time and carrier gas= more gas picked up by= higher MAC
What is the flow-over method for volatile anesthetic admin?
- Wick sticks up out of the volatile liquid (absorbs the liquid)
- O2 (carrier gas) goes up and down the wicks= increases surface area and creates more opportunity to get vapor molecules