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Pharm Test 4 > Uptake and Distribution Inhaled Anesthetics > Flashcards

Uptake and Distribution Inhaled Anesthetics Flashcards

1
Q

What determines uptake of volatile agent into blood?

A
  • Solubtility of agent
  • Cardiac output
  • a-v alveolar to venous pressure difference
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2
Q

Where does partial pressure gradient exist between when vaporizer is started at case?

A

Partial Pressure Gradient Exists BETWEEN:

  • Vaporizer and inflow
  • Inflow and Circuit
  • Circuit and alveoli
  • Blood, brain and other tissues
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3
Q

How long does it take to reach equilibrium?

A

24-48 hours for anesthetic to equilibrate with fat compartment.

TAKE HOME POINT: will probably never reach true equilibrium durign case

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4
Q

MAC of halothane?

A

0.74

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5
Q

MAC enflurane

A

1.68

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6
Q

MAC Isoflurane

A

1.15

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7
Q

MAC Desflurane

A

6.0

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8
Q

MAC Sevoflurane

A

2.0

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9
Q

MAC N2O

A

104

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10
Q

What is MAC?

A

Minimum alveolar concentration

  • Concentration that will produce absence of movement in 50% of patient in response to noxious stimuli
  • How we dose our agents
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11
Q

Blood is a pharmacologically ___ ___

A

inactive reservoir

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12
Q

What determines the “size” of the reservoir for inhaled anesthetics?

A

solubility

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13
Q

Equilibrium is achived by state of equal ___ ___

A

partial pressure

NOT concentration!

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14
Q

What determines solubility of an agent?

A

Blood gas partition coefficient

Higher B/G partitian coefficient= higher solubility

Lower B/G partition coefficient= lower solubility

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15
Q

What is the oswaldt solubility coefficient?

A

aka particion coefficient.

  • determines how anesthtic will partition itself between gas phase and blood phase at equilibrium
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16
Q

What is relationship between solubility and onset/offset of inhaled anesthetics?

A

Decreased solubility (lower partition coeff)= quicker onset/offset

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17
Q

B/G coeff @37 for Desflurane

A

0.42 (poorly soluble)

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18
Q

B/G coeff @37 for Nitrous oxide?

A

0.47 (slightly more soluble than des)

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19
Q

B/G coeff @37 for Sevoflurane?

A

0.69

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20
Q

B/G coeff @37 for Isoflurane

A

1.4 (intermediate)

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21
Q

B/G coeff @37 for enflurane?

A

1.8

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22
Q

B/G coeff @37 for halothane?

A

2.4

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23
Q

B/G coeff @37 for diethyl ether?

A

12

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24
Q

Order of b/g solubility coefficients? Poorly–> most soluble?

A
  • Desflurane = 0.42à Poorly soluble (won’t mix with blood, will stay in gas phase – faster onset)
  • Nitrous Oxide = 0.47
  • Sevoflurane = 0.69
  • Isoflurane: 1.4 (intermediate)
  • Enflurane: 1.8
  • Halothane: 2.4
  • Diethy Ether 12 (highly soluble)
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25
Q

What solubility coeffecient favors gas?

A

Less than 1 solubility coeffecient

Think blood/gas. If more in GAS phase (=LESS soluble in blood), then numberator will be less, leading to B/G solubility being <1

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26
Q

Which inhaled agents favor gas phase?

A

Desflurane (0.42)

Nitrous oxide (0.47)

Sevoflurane= 0.69

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27
Q

Wihch inhaled agents favor blood?

A
  • Isoflurane: 1.4 (intermediate)
  • Enflurane: 1.8
  • Halothane: 2.4
  • Diethy Ether 12 (highly soluble)
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28
Q

What is the effect of HCT on blood gas coefficients?

A
  • Lower HCT will alter the B/G coefficient
  • B/G coefficients are 20% less with HCT of 21 vs. 43
  • Less soluble because fewer binding sites for the anesthetic in the blood (means solubility decreases and faster onset/offset!)
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29
Q

The faster FA and FI reach equilibrium, the ____ the uptake to the brain and ___ the induction!

A

Faster, faster

30
Q

What is FA?

A

= alveolar concentration

FA represents the partial pressure of anesthetic going to the brain

-Brain perfusion relatively large—within a VERY short period of time-no gradient between partial pressure between the alveoli and brain. (use this to approximate to what brain is getting)

EQUALS Fe on monitor

31
Q

What is FI?

A

Inspired concentration= FI

inspired %- can be controlled

  • Inflow (Fd) delivered at a high flow rate with no re-breathing allows inflow to equal FI
  • We control FI with our vaporizer setting
32
Q

What determines the concentration of inhaled anesthetics?

A

Relationship of vapor pressure of agent to atmospheric pressure

(Isoflurane 240/760= 32%)

33
Q

Alveolar partial pressure (PA=?=?)

A

PA=Pa=Pbr

Key point- alveoli are window to the brain

34
Q

What do we use PA to estimate?

A
  • Depth of anesthesia
  • Recovery from anesthesia
  • Anesthetic potency or MAC (MAC= like the ED50) MAC reflects potency
35
Q

What determine PA of volatile anesthetic?

A
  • PI: inhaled partial pressure
  • Alveolar ventilation: higher MV = faster onset. Hyperventilate patient as soon as you turn it on to have a quicker onset.
  • Breathing circuit: tubing can have infinity for anesthetic. We overcome this by turning the flow way up at first in the beginning, then back off. Then turn flow up at end as well.
  • FRC (functional residual capacity): 21% O2 & 79% N. (AV:FRC ratio: Adult 1.5:1 and peds 5:1) Large FRC will take longer for anesthetic to have effect
36
Q

How does alveolar ventilation determine onset?

A

More rapid onset of inhaled anesthetic with fast rate and small TV

  • Clinical application: anesthetist takes over and controls the ventilation-hyperventilate for more rapid concentration change
  • We want to increase the alveolar concentration of the agent during induction as this results in more anesthetic agent to the brain
37
Q

What is FA/FI?

A
  • Alveolar concentration will approach inspired, rate varies for each agent
  • Expressed as a ratio of alveolar fraction divided by inspired fraction over time
  • Least soluble agents have fastest rate of the alveolar gas matching the inspired concentration over time
38
Q

What do point 1 and point 2 on this curve represent?

Tail of curve?

What type of agent will reach point 1 quicker?

A

1= Uptake by vessel rich group

Tail= uptake by fat group

  • Less soluble agents will have steeper slope to point 1
  • Higher solubility agents will have a more flat curve to point 1
39
Q

Which FA/FI ratio curve is faster rate of rise, isoflurane or desflurane?

A

Desflurane

40
Q

Why does N2O have a faster rate of rise on FA/FI curve compared to desflurane?

A

Because N2O is much more concentrated than des, so that outcompetes the solubility (concentration effect)

41
Q

Without focusing on numbers, what is difference in FA/FI ratio, when FI 6% is used, if solubility in one scenario was 0.5, and other scenario was 2?

A
  • (FOCUS MORE ON BOLD, reference numbers if needed for clarification)
  • Blood Gas partition coefficient 0.5
    • @ equilibrium 2% in blood
    • 4% remains in lung (MORE IN LUNG)
    • FA/FI 4/6 = 67% of inspired (2/3rds of equilibrium)
      • STEEPER SLOPE ON FA/FI CURVE, quicker onset
  • Blood Gas partition coefficient 2
    • @ equilibrium 4% in blood (MORE IN BLOOD)
    • 2% remains in lung
  • FA/FI 2/6 = 33% of inspired (1/3rd equilibrium)
    • FLATTER SLOPE ON FA/FI CURVE, takes longer for onset
42
Q

What is overpressure?

A
  • Influencing solubility of a gas by increasing concentration used for induction
  • High initial input offsets impact of uptake by blood for highly soluble agents
43
Q

Impact of solubility on emergence?

A
  • The lower the B/G solubility coefficient, the shorter time emergence will take
  • Parallels induction with respect to solubility concepts
  • Higher solubility: slower time to awaken (emergence)
  • Higher solubility: more left in reservoir when gas turned off
  • Clinical application- we turn off the agents sooner. Also begin to decrease the concentration delivered earlier with a very soluble agent compared to one with lower solubility. (Halothane needs to be turned off sooner than Desflurane)
44
Q

Relationship of cardiac output and uptake of inhaled anesthetics?

A
  • Decrease CO = increase speed of induction= faster induction (less in blood)
  • Increase CO = decrease speed of induction= slower induction
  • Increasing CO 4x has same effect as increasing Solubility 4x. It will slow induction
45
Q

Why does CO have inverse relationship on speed of induction?

A

Increased CO means more blood is exposed to VA= more is dissolved in blood if it is a soluble agent and this will increase the time to induction or equilibration (Pa=PA=PBr). A decreased CO speeds induction because there is less uptake to oppose input. Not really an issue with a poorly soluble anesthetic, because the induction is rapid regardless

Unlike the respiratory which is negative feedback there is a positive feedback loop here as CO decreases as the patient gets deeper and then deeper and deeper with reduced CO.

46
Q

The biggest impact of CO on onset is seen with which types of inhaled agents?

A

Highly soluble agents

Less soluble agents have such a fast onset, that it doesn’t really make a clinical impact with changes in CO)

47
Q

The relationship between CO and onset is a ___ ___ ___

A

positive feedback loop

As patient’s CO decreases, patient gets deeper and deeper with decreased CO

Unlike negative feedback loop with Respriatory influence.

48
Q

What is CO effect on FA/FI curve?

A
  • Increase in CO causes decrase in FA/FI curve (slows induction)
    • greatest effect on more soluble agnet
  • Decrease in CO causes increase in FA/FI curve (speeds up induction)
49
Q

What is a time constant?

A

A time constant is the amount of anesthetic that can be dissolved in a tissue divided by the tissue blood flow.

  • One time constant= 63% equilibration. 3 time constants= 95% equilibration.
  • Almost at 1 on FA/FI curve with 3 time constants
50
Q

If no ventilation-perfusion abnormalities, A is reflected by __

A

a (arterial value)

51
Q

Tissue uptake=

A

tissue/blood coeffencitne x flow x (a-t)

52
Q

What are the tissue groups?

A

VRG (vessel rich goup)

MG (Muscle group)

FG (fat group)

VPA (vessel poor group)

53
Q

What consists of vessel rich group?

A
  • Brain, heart, liver, kidney
  • Within 5-15 min, equilibrium reached with FI
  • 75% of CO (9% mass)
54
Q

What consists of muscle group?

A
  • Muscle, skin
  • HIghest % body mass (50%)
  • Only 18% CO
55
Q

What makes vessel poor group?

A
  • Bone, ligaments, tendon
  • 0% CO
56
Q

What is impact of tissue uptake on FA/FI curve?

A
  • Initial steep rise: a-v diff= 0, as no agent occupies the avleoli–> no uptake
  • First knee: uptake by VRG balances input (quasi- equilibrium)
  • Slower 2nd rise: decreased uptake by VRG–> MG uptake
  • Second knee: occurs in 4-8 min, uptake by MRG slows
57
Q

What influences alveolar tension curve shape?

A
  • B/G solubility will influence “knee” height
  • Tissue/gas solubility influences tail
58
Q

The partial pressure in the fat compartent, continues to rise after anesthetic delivery as long as what ?

A

As long as partial pressure in alveolar is greater than fat compartment, the PP in fat will continue to rise

59
Q

What is Fi set to deliver at induction vs maintenance phases?

A
  • For Induction high % given at constant level (overpressure) until target alveolar concentration reached (1-1.3 MAC)
    • To keep FA constant, uptake must be compensated for by delivering a sufficiently high FI
  • The FI will need to be decreased with time as the VRG equilibrates (in 5-10 min) and further decreases when MRG equilibrates
  • For Maintenance-Due to decrease in uptake over time FI needs to be decrease by decreasing % delivered = otherwise overdose
60
Q

Relationship between alveolar ventilation and PA?

A
  • Increased ventilation = increased input of anesthetic to offset uptake = more rapid induction and emergence
  • Decreased ventilation = decreased input to offset uptake = slower induction and emergence
  • A good MV/RR or spontaneous RR pattern will help with faster emergence
    • increase ventilation at end of case to breath off gas
    • robust respiratory rate at end of case increases offset
61
Q

Increase/decrease in ventilation affects what type of drug more so than the other?

A

Increase/decrease ventilation affects highly soluble agents more.

62
Q

There is a ___ ___ ___ in spontaneously ventilating patient

A

negative feedback loop

  • In SPONTANEOUSLY ventilating patient- as % inspired ­increases, ventilation is depressed and FA/FI decreases (the FA does not­ increase because the patient is not ventilating well)
  • Protective against overdose
  • As patient gets deeper, not breathing as much gas, depth of anesthesia gets lighter
63
Q

How does the breathing circuit affect PA?

A
  • Volume of circuit (decreases rate of rise FA/FI) – overcome with high flow rates at induction >5L/min
  • Plastic/rubber components can absorb anesthetic (slow induction) and then re-introduce anesthetic into circuit during wash-out (slow emergence)
64
Q

The greater the alveolar ventilation/FRC ratio, the _____ the induction

A

faster.

  • The greater the alveolar ventilation/FRC ratio = faster the induction
    • (Neonate induction very fast ratio = 5:1), adults 1:1.5
  • Decrease FRC and Increase Alveolar ventilation= Faster induction
  • FRC influences speed of induction
  • Small FRC, Increase AV= faster induction
65
Q

What will happen to FA/FI if both ventilation and CO are increased?

A
  • Will occur in conditions with increased metabolism
  • FA/FI increases slightly
  • 2x ventilation+ 2x CO-doubles both input and removal (in theory no change)
  • Actually- 2 x CO decreases (A-v) by decreasing tissue uptake, thus uptake does not increase ­ in proportion CO and leads to more rapid rise FA/FI
66
Q

What is impact on FA/FI with ventilation/perfusion abnormalities?

A
  • Rise in FA in ventilated lung is higher than if ETT in trachea
  • Rise in arterial blood depressed- increase in ventilation in ventilated lung does not offset unventilated lung (dilutional effect)
  • This dilutional effect causes a slower induction
  • Affects less soluble agents more
67
Q

Why do ventilation/perfusion abnormalities affect less soluble agents more?

A
  • Less soluble agents are reliant on alveoli for induction, you now have unventilated blood mixing with blood that never sees the alveoli, causing a dilutional effect and slowing induction time
68
Q

What is the concentration effect?

A

Results when a large volume of gas is absorbed, 2 results happen:

    1. remaining residual gas in lung is concentrated as volume decreases
    1. Inspired ventilation increases which adds more anesthetic (the negative pressure created by the uptake draws more gas into the lung)

Only applicable if giving agent in high concentration

  • N2O is given in high concentration (80% N2O with 20% O2)
  • Huge gradient for N2O to move out of blood to brain, take huge volume of gas with it
  • This leaves a volume deficit, leaving the gas left in lung to be more concentrated
69
Q

What is the second gas effect?

A
  • Occurs when N2O is used in combination with a second gas (des, iso, sev)
  • Reduction in volume and replacement of N2O causes increase in ­ concentration and amount of any gas given concomitantly with the N2O which was absorbed in a large volume.
  • The increase ­FA of a second gas is greater @ 70% N2O than 50% N2O
  • The FA of a gas ­ increases more rapidly when N2O given as 2nd gas then when given alone
70
Q

What factors affect washout of anesthetics?

A
  • Least soluble washout first
  • Metabolism plays a role- halothane
  • As duration of anesthesia lengthens- washout prolonged
    • more anesthetic in reservoirs
  • Washout will drop precipitously at first, then level off and drop off slowly
71
Q

What are concerns when using N2O?

A
  • N2O is 34 x more soluble than nitrogen. N2O can diffuse into gas spaces quicker than nitrogen can diffuse out
  • this can cause N2O to leave blood and enter the air cavity, causing expansion of air space
    • results in increased pressure/volume in closed space
    • do not use N2O in PE, VAE, GI sx
72
Q

What does emergence and recovery phase from inhaled anesthetics depend on?

A
  • Length of anesthesia
  • depth anesthesia
  • solubility of agent
  • MAC awake (MAC were pt opens eyes)

Pharm Test 4 (4 decks)

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