Inhalation Anesthetic Pharmacokinetics Flashcards
What is the MAC for Des
6%
What is the MAC for Iso
1.2%
What is the MAC for Sevo?
2%
How many fluorine’s does Desflurane have?
6 F
How many fluorine’s does Isoflurane have?
5 F
How many fluorine’s does Sevoflurane have?
7 F
Isoflurane has a chlorine atom, which increases its?
Blood and Tissue Solubility. Has the the highest blood:gas coefficient (1.4) and the most potent oil:gas (99). Making it more lipophilic.
Sevo produces what toxic by-products in soda lime?
Compound A
Des and Iso can become unstable in desiccated soda lime and can produce what toxic byproduct?
Carbon Monoxide
Blood:Gas Coefficient for Sevo
~0.65
Blood:Gas Coefficient for Des
~0.42
Blood:Gas Coefficient for Iso
~1.46
Blood:Gas Coefficient for Nitrous
~0.46
Which inhalation agent is the least soluble and, therefore, the quickest agent, excluding nitrous?
Des. 0.42 B:G Coefficient
Which inhalation agent is the most soluble and, therefore, the slowest agent?
Iso. 1.46 B:G Coefficient
What is the oil:gas coefficient for Sevo
~47
What is the oil:gas coefficient for Des
19
What is the oil:gas coefficient for Iso
91
What is the oil:gas coefficient for Nitrous
1.4
What gas is the most potent, aka most lipid-soluble
Iso
What gas is the least potent aka least lipid soluble
Nitrous (1.4)
If you are using a low solubility agent, will you reach Fa/Fi equilibrium slower or faster?
Faster
an example: Desflurane. 0.42 solubility coefficient
If you are using a higher solubility agent, will you reach Fa/Fi equilibrium slower or faster?
Slower
ex: Iso b:g of 1.4
The concentration of an agent inside the _______ is proportional to its concentration inside the ______
Alveoli (Fa)
Brain
Which volatile gases can trigger Malignant Hyperthermia?
All except, N2O
When you have a V/Q mismatch or poor lung fxn, which agents are more affected, high soluble or low soluble agents? Why?
Low Soluble Agents (ex: Des). Because the high blood:gas coefficient agents (ex: Iso) are more soluble, meaning they have a higher affinity to water (plasma) so, they are less affected by a mismatch, going to cross and diffuse still.
Even though Des has a slightly lower blood:gas coefficient than N20, why is N20 the fastest to reach equilibrium?
Because N2O is given at much higher concentrations (50-70% Fi) vs. Des (3-9%).
If your patient had a V/Q deficit or poor lung function, would increasing ventilation (Fa) help your more or less soluble agents more?
Increasing ventilation (inc TV or RR) would help soluble (slow) agents more (ex: Iso). Your slower agents would be exposed to more blood faster, increasing their concentration and, therefore, increasing the rate of equilibrium.
If your patient had a V/Q deficit or poor lung function, would increasing concentration (Fi) help your more or less soluble agents more?
It would help your Less Soluble agents more (ex, Des) because these agents are more dependent on concentration than solubility. By increasing concentration, you drive the up concentration gradient, forcing more to leave the alveoli and enter the blood. Once in the blood, it reaches equilibrium more quickly than more soluble agents.
Now, if you have normal lung fxn and normal V/Q, will “over-pressuring,” aka higher concentrations at induction, help your high soluble or low soluble agents reach equilibrium faster?
Over-pressuring works for all volatiles. However, it is most effective for the more soluble (slower [Iso]) agents. Bc you reach your state of equilibrium faster. Less soluble agents don’t need as much help reaching equilibrium.
How does Functional Residual Capacity (FRC) influence Volatile Gas equilibrium?
Functional Residual Capacity (FRC) is the volume of air remaining in the lungs after a normal exhalation (~2.5–3.5 L in adults). It acts as a reservoir for inhaled gases and plays a critical role in determining the speed of anesthetic gas uptake and equilibration in the lungs and, subsequently, in the brain.
How would a larger FRC influence the speed of induction? What kinds of patients may have an increased FRC?
Slower induction. More air must be replaced with the anesthetic gas. Takes longer to saturate the alveoli with the anesthetic. Delays equilibrium between alveoli (FA) and Inspired gas (Fi).
- COPD patients
How would a smaller FRC influence the speed of induction? What kinds of patients may have a decreased FRC?
Faster induction. Less dilution of anesthetic gas (aka higher concentration). Faster rise in arterial partial pressure and brain uptake.
-Obese, Pregnant, Supine Position
How would an increased FRC influence volatile anesthetic emergence?
Slower emergence. More anesthetic gas remains in the lung post-exhalation, prolonging elimination.
How would a decrease in FRC influence volatile anesthetic emergence?
Faster emergence. Quicker washout with a reduced FRC.
What are some factors that increase your FA/FI curve aka faster onset
-High FGF
-High Alveolar Ventilation
-Low FRC
-Low anatomic dead space
What are some factors that decrease your Fa/FI curve aka slower onset
Low FGF
Low Alveolar Ventilation
High FRC
High Anatomic Deadspace
After an inhaled anesthetic enters the blood, it is distributed to nearly all the tissues in the body. What are the 4 tissue groups we care about?
Vessel-Rich Group* (brain, heart, kidney, liver)
Muscles (skeletal muscle, skin)
Fat
Vessel-Poor Group (bone, tendon, ligament)
The Vessel Rich group only makes up ____% of total body mass. Yet it receives how much cardiac output?
10% total body mass yet receive 75% of CO. Therefore, these organs receive most of the anesthetic during induction & are the first to
equilibrate with Fa.
The skeletal muscles (and skin) make up ____% of total body mass. They receive how much cardiac output?
50% total body mass but receives only 20% CO
Fat make up about ____% of total body mass. And receives about how much cardiac output?
20% body mass and 5% CO
The vessel-poor group makes up ____% total body mass? And receives how much CO?
20% total body mass but LESS then 1% CO
During induction, an increased CO slows the onset of all agents but affects the more soluble (slow) agents more. Why?
Increased CO means more anesthetic is taken up by the blood and carried away from alveoli before FA can rise significantly. This slows the rise of the FA/Fi ratio, delaying equilibrium.
At atmospheric pressure and room temperature, the ethers and alkanes exist as ______. What are the ethers? What are the alkanes?
Liquid.
Ethers: Des, Iso, Sevo. (less important: enflurane, methoxyflurane, and ether)
Alkanes: Halothane and Chloroform
What gases exist in the gaseous form at atmospheric pressure and room temperature?
Nitrous Oxide (most important)
Cyclopropane
Xenon
Inhaled anesthetics are eliminated from the body in what three ways? Indicate which is the primary, secondary, and not clinically significant.
- Exhaled, eliminated from alveoli (primary)
- Hepatic biotransformation (secondary)
- Percutaneous loss (not clinically significant)
How does nitrous oxide differ in its distribution to the 4 different tissue groups (VRG, Muscle, Fat, VPG)?
Uptake by nitrous in any other of these groups is minimal. However, it will diffuse into gas-containing areas like the GI tract or middle ear. its oil:gas coefficient is only 1.4 (least potent, least lipid soluble)
The halogenated anesthetics undergo metabolism by the ____ system. Carried out by the ______ enzyme.
P450
CYP 2E1 enzyme
What is the metabolism of all 4 inhalation gases?
Sevo: 2-8% (texts vary some say 2-5%)
Iso: <1% (~0.2%)
Des: <1% (~0.02%)
N2O: <1% (~0.004%)
Sevo metabolism produces free fluoride ions, which creates a theoretical risk for which patients?
Renal Failure
Why do we not use Halothane anymore? What byproduct causes the issue?
20% of halothane undergoes hepatic biotransformation. Trifluoroacetic acid (TFA) is a byproduct of halothane metabolism. At high levels, TFA creates hepatic dsfxn.
[Halothane Hepatitis]
What are the FDA guidelines about minimum FGF and Sevo use?
Recommend minimum FGF of 1L/min for up to 2 MAC hours and 2L/min after 2 MAC hours.
FGF rates <1L/min are not recommended at any time.
What is a MAC-hr?
It is 1 x the MAC of whatever gas you’re using (that prevents movement in response to noxious stimulus in 50% of subjects) administered for 1 hour. If you run over 1 hour, multiply by the number of hours.
What is the “Concentration Effect”?
The higher the concentration of inhalation anesthetic delivered to the alveolus (FA), the faster its onset of action. Also called-overpressuring. Works for all the gases, but is probably only clinically relevant to Nitrous Oxide.
Nitrous oxide is how much more soluble than nitrogen in the blood?
34x
Describe the second gas effect
The coadministration of Nitrous oxide and a second volatile gas, such as Isoflurane, shortens the time for the Iso to reach equilibrium.
N20’s rapid uptake causes the alveoli to shrink temporarily, which increases the FA pressure of the Iso. The end result: Alveolar concentration of 2nd gas is greater than if given alone.
Describe diffusion hypoxia via Nitrous Oxide use.
If n2o is used for extended periods of time, on emergence, the n2o absorbed by the body could reduce alveolar oxygen and CO2 concentrations, leading to hypoxia.
To prevent, on emergence, administer higher FiO2 for a few minutes after n2o has been d/c’d.
What are some examples of right-to-left shunts? What does that mean?
Tetralogy of Fallot
Foramen Ovale
Tricuspid Atresia
Eisenmenger’s Symdrome
Ebstein’s Anomaly
Some blood skips getting oxygenated and avoids anesthetic uptake, which mixes with the blood that was oxygenated (and picked up anesthetic gas) in the LV.
How does a right-to-left shunt affect anesthetic gas uptake?
Slows induction of anesthesia.
An agent with a lower solubility will be more affected by the dilution than an agent with higher solubility. (So Des is most affected)
What effect does a Left-to-Right Shunt have on inhalation agent uptake?
Apex: will NOT have a meaningful effect on anesthetic uptake or induction.
Dr. C PowerPoint: A slightly increased rate of anesthetic delivery or uptake into the brain, muscle, and other tissue is a result.
What anesthetic agent undergoes the Greatest degree of elimination from the lungs?
a. Halothane
b. Sevoflurane
c. Desflurance
d. Isoflurance
c. desflurane
What three factors have the most significant impact on anesthetic UPTAKE into the blood?
- Blood:Gas Solubulity
- CO
- Partial pressure difference between the alveolar gas and mixed venous gas
What factors increase MAC requirements? (aka more gas needed)
Young age
Hyperthermia
Drug-induced increases in CNS activity
Hypernatremia
Chronic Alcohol Abuse
Red Hair in Females
Hyperthyroidism
What factors decrease MAC requirements? (aka less gas needed)
*Hypothermia
*Increasing age
*Preop sedatives
Drug-induced decreases in CNS activity
*Alpha-2 Agonists
Pregnancy
Lithium
*Lidocaine
*Hypoxia
*Hypotension
Cardiopulmonary Bypass
Hyponatremia
Why do we no longer use methoxyflurane?
Nephrotoxic
Factors that can create a faster induction
Low Blood Gas Solubility
Low Cardiac Output
High Minute Ventilation
High FGF
High concentration (overpressuring)
Second-gas effect
Factors that can create a slower induction
High blood gas solubility
High CO
Low minute ventilation
Low FGF
Low concentrations
V/Q deficits
Hypothermia
Do Pediatrics have faster or slower uptake compared to adults? Why?
Faster uptake, rapid induction
Children have higher alveolar ventilation rates. Have a higher CO but goes to VRGs, so this offsets.
Anesthetics are ____ blood soluble in children. This _____ MAC requirements.
LESS blood soluble.
Higher MAC requirements.
What age has the highest MAC requirements?
Infants - 6 months old. 1.5-1.8x higher
Emergence agitation usually lasts how long? What inhalation is more likely to cause this?
Lasts 10-15min
More likely with Sevo
What are the high-risk factors for emergence of agitation in pediatrics?
~Preschool Age 2-5 years
~Separation anxiety behavior at baseline
~ General Anxiety
~Post-op pain
Lower Risk Factors
-Male gender
-type of surgery (Tonsillectomy, Strabismus surg, Neuro surg)
What medications can you give for emergence delirium?
Precedex***
Prop
Fent
How does the anesthetic uptake of pregnant patients compare to that of nonpregnant patients?
They are similar. Pregnant pts have higher minute ventilation and higher cardiac output which cancel each other out.
During Cardiopulmonary Bypass, how does the delivery of volatile agents change?
Higher concentrations of volatile agents are given compared to when administering to normal lung inhalation. The bypass machine isn’t as good as the lungs at drug concentrating.
Halogenation of hydrocarbons and ethers influences?
Anesthetic potency
Arrhythmogenic properties
Flammability
Chemical Stability
Factors with no effect on MAC
Duration of anesthesia
gender
hypocapnia and hypercapnia
metabolic alkalosis
hypertension
hyperkalemia or hypokalemia
Volatile anesthetics interact with the main repolarizing cardiac ______ channels. As well as ____ and _____ channels at higher concentrations.
Potassium
Calcium and Sodium
By substituting hydrogen atoms with halogens, _____ is reduced, and ______ stability is enhanced
Flammability reduced and chemical stability enhanced.
What is MAC-BAR ?
MAC necessary to block adrenergic response to skin incision
