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ANPH 500 - Pharmacology - McCarver > Desflurane > Flashcards

Desflurane Flashcards

1
Q

What is the ONLY inorganic IA?

A

Nitrous (means it does NOT contain carbon)

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2
Q

When did IV inductions begin (approximately)

A

Just before WWII.

Dr Lundy first used thiopental as induction agent? (LM)

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3
Q

1850-1930 Diethyl ether - used for what?

A

Inhalation inductions - historically took a LONG time to induce. This is where the PLANE or STAGE of anesthesia came from.

(was the Queen of anesthesia)

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4
Q

Stage I

A

Analgesia or disorientation - from the beginning of induction of GA to loss of conciousness

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5
Q

Stage II

A

Excitement or delirium

from loss of conciousness to onset of automatic breathing. Eyelash reflex disappears. Coughing, vomitting & struggling may occur; respiration irregular with breath-holding.

(Almost skipped with current IV induction agents, could last 5 minutes with Diethyl ether!)

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6
Q

Stage III

A

Stage of SURGICAL anesthesia

-from onset of automatic respiration to respiratory paralysis, divided into four planes:

(THIS IS WHERE IV INDUCTION PUTS PATIENTS VERY QUICKLY)

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7
Q

Stage III - PLANE 1

A

onset of automatic respiration to cessation of eyeball movements. Eyelid reflex lost, swallowing reflexes disappears, marked eyeball movement may occur, conjunctival reflex is lost at the bottom of the plane.

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8
Q

Stage III - PLANE 2

A

cessation of eyeball movements to beginning paralysis of intercostal muscles. Laryngeal reflex lost, corneal reflex disappears, secretion of tears increases (a good sign of LIGHT anesthesia), respiration automatic and regular, movement & deep breathing as response to skin stimulation disappears.

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9
Q

Stage III - PLANE 3

A

Beginning to completion of intercostal muscle paralysis. Diaphragmatic respiration persists, progressive intercostal paralysis, pupils dilated & light reflex abolished.

  • desired plane when muscle relaxants were not used. ** Typically try to avoid now-a-days**
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10
Q

Stage III - PLANE 4

A

Complete intercostal paralysis to diaphragmatic paralysis

(usually occurs around MAC of 2)

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11
Q

Stage IV

A

Stopping of respiration to death.

  • Anesthesia overdose
  • Medullary paralysis with respiratory arrest and vasomotor collapse
  • Pupils widely dilated and profound muscle relaxation.

MEET BART DURHAM!

-big problem in the 1930’s, as there were no ETTs!

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12
Q

Desflurane was introduced when?

A

1992 (2 years before sevo)

Can be described as LIGHTSWITCH anesthesia…. (by des reps :)

still need to turn up gas flows at the end of a case however to help blow the gas off.

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13
Q

Getting rid of all halogens except for fluorine results in an anesthesitc with??

A
  • Poor lipid solubility
  • Extremely resistant to metabolsim
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14
Q

Insolubility Advantages are what?

A
  • rapid induction
  • Precise control of anesthetic concentrations (can make very quick changes)
  • Prompt recovery independent of length of anesthesia
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15
Q

Disadvantages of Des

A
  • Airway irritation (not suitable for inhalation induction)
  • SNS stimulation (if you increase levels too quickly)
  • CO production (carbon monoxide)
  • Requires New vaporizer technology (can fill des vaporizer while in use)

Vaporizer is warm while in use (like a little campfire in the OR! )

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16
Q

Pharmacoeconomics

A

Des has a high bottle pricetag.

HOWEVER - more than just the pricetag should be a factor.

  • factor in the cost savings of rapid induction and early wake-ups? - could save getting patients out of OR and home sooner.
  • can use lower flow rates

**Could be argued that DES might actually be the cheapest way to go. **

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17
Q

What is the Vapor pressure of Des?

A

669

(close to atmospheric pressure! Ball-spring that pushes ball back and lets vapor out… )

Is why new technology was required…

For every cc you would get into a REGULAR vaporizer, 20 cc would get into the atmosphere…

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18
Q

What is the Odor of Des?

A

Etheral or monkey perfume (but goes away VERY quickly)…. but LM said he doesn’t think he has smelled it..

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19
Q

Which is more insoluble, Des or Nitrous?

A

Des

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20
Q

What is the preservative in Des?

A

There is none!

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21
Q

What is the Blood gas partition of Des?

A

0.42

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22
Q

What is the typical MAC of Des (37 C, 40yo, sea level, 100% 02, blah blah blah)

A

6.6%

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23
Q

Desflurane is Isoflurance with what chemical difference?

A

Clorine atom replaced witha fluorine atom.

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24
Q

Properties of DES

A

Is a Fluorinated methyl ethyl ether

  • Substitution of flourine for chlorine on the ethyl component of the methy-ethyl ether
  • Enhanced molecular STABILITY
  • 3 X Greater vapor pressure than ISO

5 X LESS potent than ISO

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25
Q

Is there a correlation between between anesthetic potency and blood gas partition coefficient?

A

NO

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26
Q

What is the only measurable metabolite in Desflurane?

A

tri-fluoroacetate

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27
Q

Airway properties of Des

A

Airway Irritant (especially if inspired concentrations are increased rapidly - avoided by incremental increases of inspired concentrations 2% every 2-3 breaths. )

Salivation

Breath holding

Coughing

Laryngospasm

Occurs mainly @ concentrations greater than 6% (NOT THE MAC, but the %)

Not for inhilation induction

May be used for LMAs

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28
Q

The FI quickly approximates WHAT?

A

FA

-Rapid achievement of alveolar partial pressures necessary for anesthesia

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29
Q

Des patients usually wake up quickly or slowly (assuming sufficient gas flows)

A

quickly

(Lower blood gas solubility)

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30
Q

Will Desflurane impair the mental function of OR personnel via inhaling trace gases?

A

NO

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31
Q

DES will provide retrograde amnesia. True of False?

A

False (it will not).

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32
Q

Des does what to CMRO2 and cerebral activity?

A

Decreases them.

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33
Q

Des decreases cerebral blood flow. True of False?

A

False!

  • It increases cerebral blood flow (was a typo on his slides)
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34
Q

In regards to EEG, < 0.4 MAC = what?

A

Increased frequency and voltage

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35
Q

EEG - 0.4 MAC ?

A

Begins to reduce CMRO2

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36
Q

EEG - 1 MAC?

A

Decrease in EEG frequency, maximal voltage occurs

37
Q

EEG - 1.5 MAC ?

A

Suppression of BURST activity

38
Q

EEG - 1.5 - 2 MAC

A

Electrical Silence

No S/S of seizure activity

39
Q

Evoked Potential Monitoring

A
  1. Causes dose-depedent large decreases in amplitude.
  2. Causes does-dependent moderate increases in the latency of CORTICAL components.
  3. Decreases amplitude are greater than decreases in latency.
  4. Use of nitrous with desflurane does not abolish these characteristics.
  5. Starting at 0.5 MAC, des INCREASINGLY depresses EVOKE POTENTIALS
40
Q

How would you DECREASE Cerebral blood flow under Des?

A

Hyperventolate to 30 ETCo2.

41
Q

Desflurane produces dose-dependent ____ in Cerebral blood flow?

A

Increases

42
Q

@ Greater than 0.6 MAC, with normocapnia, desflurane produces what??

A

Cerebral vasolidation

reduced cerebral vascular resistance

increased CBF

lowered CMRO2.

These changes occur within MINUTES of des administration.

43
Q

Cerebral Blood flow changes occur independent of ___ and increases in CBF last up to ___ hours.

A

Independent

4

44
Q

Does desflurane abolish cerebral blood flow auto-regulation?

A

No consesus at this time.

45
Q

DES Impact on CMR02

A
  1. Desflurane produces dose depedent decreases in CMRO2
  2. When EEG becomes isoelectric, no further reductions in CMRO2
  3. Desflurane reduces CMRO2 less than iso, but COMPARABLE to sevo.
46
Q

DES and Intracranial pressures?

Raise or lower ICP?

Patients with space occupying intracranial lesions are at ____ risk?

Hyperventilation to what opposes this phenomenon?

What dose is required to increase ICPs?

A

Raise

Increased

30mmHg

0.8-1.1 MAC

47
Q

Circulatory changes of DES? (6)

A
  1. Lower systemic BP
  2. Increased HR
  3. Alterations in CO, SV, and RAP
  4. Reduction of SVR
  5. Alterations in heart rythm
  6. Alterations in coronary blood flow
48
Q

What can be substituted for an equal MAC portion of DES to decrease magnitude of BP drop?

A

Nitrous

49
Q

DES and MAP

A

Dose dependent decreases in MAP

Decreases in BP is due to reduction of systemic vasular resistance, unlike halothane

50
Q

Des and HR

A

Increases HR

(effect is blunted by giving opioids or beta blockers)

Doesn’t alter carotid sinus/SA

HR increases seen LESS with the elderly

Does not cause dysrhythmias

Does NOT alter QT interval

51
Q

DES and Cardiac Output

LV SV is dropped by how much?

A

30%

(dissipates within 5 hours of des anesthesia)

Increases in HR offset decreases in SV

vasodilatory effects of des makes observation of myocardial depressant effects LESS aparent - Yet enough DES can cause stage 4 - Circulatory Collapse!

52
Q

DES and RAP (right atrial pressure)

A

DES raises RAP similar to ISO/SEVO despite vasodilatory effects.

Reduces SVR (due to increased (up to x4) skeletal muscle perfusion)

DOES NOT appreciably alter pulmonary vascular resistance

53
Q

DES and Neurocirculation

A

Abrupt increases in desflurane concentrations INCREASES SNS & renin-angiotensin activities

Transiet Increases in HR & BP

Maximal response is reached at 8% des or higher

Sites mediating this response?

upper airway and lungs

Abated by Fentanyl and Betablockers

54
Q
A
55
Q

DES has what myocardial depressant effects? (4)

A
  1. Inhibition of CNS outflow
  2. Autonomic ganglionic blockade
  3. Decreases catecholamine release
  4. Decreased influx of Calcium Ions
56
Q

Coronary Steal and Des..

A

Robs from the Poor and Gives to the Rich! Robin Hood would be pissed!

Coronary Steal is NOT clinically significant with DES.

-Des induces coronary vasodilation - acts on vessels of 20-50 um.

57
Q

What MAC does des produce increases in RR?

A

Up to 1 MAC

-also produces reductions in Vt, (lizard on a hot rock)

NET Effect:

lower MV, higher PaCO2

58
Q

What is the breathing pattern of DES up to 1 MAC?

A

Rythmic and regular - no sighs

(lizard on a hot rock)

Decreased Ventilatory response to CO2

59
Q

Apnea occurs at what MAC?

A

1.5-2 MAC

60
Q

Increases in PaCO2 more profound in patients that have what?

A

Lung disease

61
Q

Increases in PaCO2 begin to dissipate after how many hours of SPONTANEOUSLY breathing Des anesthesia?

A

5 hours

62
Q

Surgical stimulation under des increases MVV. True or False?

A

True

63
Q

Breathing

Mechanism or action?

Inteferance with intercostal muscle function causes what?

A

Mechanism - direct depressant effects on MEDULLARY VENTILATORY CENTER

Chest wall de-stabilization

64
Q

Assisted ventilation is very effective in significantly reducing PaCO2 under des. True or False?

A

False

it is NOT effective…

65
Q

What is the best way to manage Des mediated ventilatory depression?

A

Controlled Ventilation

(assisted ventilation will only lower PaCO2 3-5 mmHg)

66
Q

DES depresses the ventilatory response to ___?

A

Hypoxemia

67
Q

DES may induce bronchoconstriction in __.

A

Smokers

(not contraindicated in smokers, but you must be sure to use it correctly…

In HIGH enough concentrations DES can actually break status asthmaticus

68
Q

DES and the Liver

A
  • Hepatic blood flow is maintained similar to Iso/Sevo (completely maintained)

Portal vein blood flow may be INCREASED.

There can be transient increases in LFTs following DES administration

69
Q

Hepatotoxicity….

A

Post-op liver dysfunction may occur…

Hepatocyte hypoexmia.

Pre-existing liver disease increases the risk.

Desflurane oxidative metabolized by cytochrome P450 to form acetylated liver protein adducts by mechanisms similar to halothane.

Incidence with desflurane will be markedly lower due to less metabolism.

70
Q

DES produces dose dependent decreases in Renal blood flow, GFR, and U/O. True of False?

A

True

Mechanism is reduced SVR & CO

(preop hydradation helps prevent this)

71
Q

DES produces Compound A.. true or false?

A

FALSE

No compound A or free flouride ion problems

(can used in a closed circuit)

72
Q

Neuromuscular junctions

A

Desflurane relaxes skeletal muscle 2x > than halothane

DES provides dose-dependent enhancement of NM blockers

DES can trigger MH, but less potent than halothane- still avoid DES with pt. hx or family hx of MH.

73
Q

DES produces dose depedent ____ in uterine smooth muscle contractility.

A

Decreases

-also reductions in uterine blood flow.

Modest changes @ 0.5 MAC, significant at 1 MAC

74
Q

Desflurane is both mutagenic and carcinogenic. True or false?

A

False

It is NEITHER.

DES is unlikely to decrease resistance to bacterial infection and does not alter leukocyte phagocytotic function.

75
Q

Overall total body 02 requirements are ___.

Why?

A

reduced

(heart more so than other organs)

Due to metabolic depressant effects and overall decreased functional needs.

76
Q

Where does metabolism of DES occur?

What drug is the metabolic pathway of DES similar to?

What are the results of DES metabolism

A

ether or ether-halogen bonds

Iso

(0.02% undergoes oxidative metaboism via cytochrome P-450)

Results are inorganic fluorides, trifluoroacetic acid, C02, & water

77
Q

Carbon Monoxide - What causes this?

More or less than ISO?

A

Occurs with dry CO2 absorbents, High absorbent temps, prolonged HIGH gas flow rates…

HIGHER Carbon monoxide levels than iso

78
Q

DES requires ___ for production.

A

ISO (will always be more expensive because of this)

79
Q

Boiling point and Vapor pressure (at 20C)

A

23.5 and 664

80
Q

Major Characteristics of DES

(4)

A
  1. DECREASED solubility
  2. DECREASED potency
  3. INCREASED stability
  4. INCREASED vapor pressure
81
Q

Human Tissue: Blood Particion Coefficients

Fat

Brain

Heart

Liver

Kidney

Muscle

A

Fat - 27

Brain 1.3

Heart 1.3

Liver 1.3

Kidney 1.0

Muscle 2.0

82
Q

What are the major implications of LOW solubility?

A
  1. More rapid wash-in
  2. Greater anesthetic control and precision
  3. More rapid emergence
  4. POTENTIAL greater economy
  5. May eliminate N20 without kinetic disadvantage
83
Q

Which is faster for inspired and alveolar concentration equilibration, DES or Nitrous?

A

Nitrous, but a close second id DES…

then sevo, iso, then halothane

84
Q

Metabolic pathway results of both DES and ISO are?

A

Both end up with triflurocetic acid

85
Q

METABOLISM OF INHALED AGENTS

% Uptake recovered as Urinary Metabolites?

A

DES 0.02

ISO 0.2

SEVO 5

Halo 15-20

(the less metabolized = the less metabolites produced! No metabolism would be the best!)

86
Q

Effect of Age on MAC?

A

Younger = Increased MAC %

Age - 100% 02 - 60% N20

<1 - 9.2-10 - 7.5

1-12 - 8.1-9.1 - 6.4

18-30 - 7.3 - 4

31-60 - 6 - 2.8

>60 - 5.2 - 1.7

87
Q

Can a patient have “DES” breath in PACU?

A

Unlikely

88
Q

MAC, make awake, MAC - BAR

A

MAC - 6.0%

MAC-awake 2.42%

MAC-BAR 1.45%

MAC with 60-70% nitrous - 2.83%

ANPH 500 - Pharmacology - McCarver (11 decks)

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