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Flashcards in Pharmacology 4 Volatile Agents Deck (125):
1

Why worry about Anesthesia?

BC we give muscle relaxants, which abolish pt's ability to let us know if they are light - possibility of pt being immobile w normal VS and fully aware but unable to let you know

2

Ideal VA

Rapid onset, rapid and predictable recovery, no residual effects on organs, easy to administer, high safety margin

3

Woodbridge's definition of Anesthesia 1950

GA is depression of sensory, motor, reflex, and mental fxn.
Analgesia, skeletal muscle relaxation, freedom from reflexes, unconsciousness (hypnosis and amnesia)

4

Prys-Roberts' definition of Anesthesia 1970

As a result of drug-induced unconsciousness, a state in which the pt neither perceives nor recalls unpleasant stimuli. Increasing dose produces pattern of suppression of responses (somatic easier than autonomic)
Pain - mvmt - breathing - bp/hr - sweating - stress response

5

Eger's definition 2002

2 qualities apply to VA:
Immobility - what surgeon wants
Amnesia - what pt wants
(reflex suppression and MR are useful, but have nothing to do with anesthetic state, pt can't tell us anything if amnesia is present)

6

Stage 1

Analgesia and sedation
-eyes open to command, breathe normally, tolerate mild pain (suturing)
-airway protective and other reflexes intact

7

Stage 2

Excitement
-rarely see (induction masked d/t IV agents, emergence quick d/t low solubility of VA)
-Muscle mvmt, retching, heightened laryngeal reflexes, disconjugate pupils, increased HR/BP and VE
-Associated w MACawake and amnesia
MACawake = responds to commands but won't remember

8

Stage 3

Surgical anesthesia
-associated w MAC
-no mvmt in response to surgical stimuli
-no behavioral pain response
-amnesia
-reflex depression
-skeletal muscle relaxation

9

Stage 4

Medullary depression (OD)
-CV collapse (decreased BP/CO
-Respiratory collapse (apnea)

10

Gauging depth - clinical signs - Respiratory

-increased depth of VA = increased RR, decreased tidal volume "pant like puppies"
-Changes in character of spontaneous breathing
~excessive depth = rocking boat d/t diaphragmatic breathing only, loss of ICM
-Hard to use in controlled ventilation, NDMR, and opioids

11

Gauging depth - clinical signs - Eyes

-Lacrimation, eye mvmt, disconjugate = light
-Pupils have no direct relationship: opioids = miosis, except meperidine causes mydriasis
mydriasis = increased paCO2 or cerebral hypoxia
all abolished by anti-Ach

12

Gauging depth - clinical signs - Motor

Active expiration = light
Soft abdomen = deep

13

Gauging depth - electronically - BIS

Bispectral Index Monitoring
-scale of 0 - 100
-at 60 return to responsiveness
-Doesn't work w KETAMINE or N2O
-NOT a standard of care per ASA or AANA

14

ASA Practice Advisory on assessing for increased risk of awareness 2005 - Pre-op Eval

*review medical records:
-substance abuse
-previous hx of awareness
-hx or anticipated difficult intubation
-chronic pain pts on high doses of opioids
-ASA status of IV or V
-limited hemodynamic reserve
*Interview pt:
-level of anxiety
-other potential risk factors
>cardiac, c/s, trauma, ER, paralysis, use of
MR, N2O, opioids

15

ASA Practice Advisory on assessing for increased risk of awareness 2005 - Pre-induction phase

Adhere to checklist protocol for anesthesia machines and equipment, verify fxn of IV access, pumps, connections
use benzo pre-op

16

" " " - Intra-op monitoring

-Clinical techniques
-Conventional monitoring
-Brain fxn monitoring

17

Gauging depth - electronically - Gas analysis

End-tidal agent - monitoring standard
-dial setting
-inspired VA
-expired VA

18

T or F: Accuracy is most difficult and critical after induction and before incision?

True : why?
Too much VA = hypotension d/t lack of stimulus (incision) and vasodilatory effect of VA
Too little VA = salivate, tachycardia, HTN and mvmt on incision

19

When is inspired amt of VA more than expired?

Beginning of the case

20

What does halogenation do to an agent?

Decreases flammability

21

Using only Fluorine yields what kind of agent?

Non-flammable, low solubility, and extreme resistance to metabolism

22

What current VA degrades in soda lime?

Sevo

23

What VA has the fastest onset?

Des < N20 < Sevo < Iso

24

Lower solubility in blood yields:

-rapid induction
-more precise control
-favor prompt recovery

25

What VA is the cheapest?

Iso at 10 cents per ml

26

What VA is the most expensive?

Sevo at 61 cents per ml

27

N2O

Vapor pressure: its a gas, there isn't one
BGPC: 0.46 (fast onset)
MAC: 104

28

Iso

VP: 240
BGPC: 1.46 (longest next to enflurane)
MAC: 1.17 % (most potent next to N2O)

29

Des

VP: 669
BGPC: 0.42 (fastest onset)
MAC: 6.6 % (least potent)

30

Sevo

VP: 170
BGPC: 0.69
MAC: 1.8 %

31

Which VA needs a heated vaporizer? Why?

Des bc Vapor pressure is 669

32

What structures do Iso, Des, and Sevo have?

Iso - halogenated methyl ethyl ether w Cl-
Des - Completely fluorinated methyl ethyl ether, replacing Cl- on Iso w Fl-
Sevo - Completely fluorinated methyl isopropyl ether

33

If the VA has a low MAC value...

the more potent the agent

34

Which agent is not stable in soda lime?

Sevo, degrades into Compound A

35

Which agent is the only inorganic compound?

Nitrous oxide (N2O)

36

In what 2 ways is nitrous oxide used?

Alone for sedation or in combination w opioids and VA to enhance GA

37

Is N2O flammable?

No, but supports combustion

38

What are advantages of N2O?

*low solubility so rapid on/off
*doesn't depress BP
*analgesic (10mg of morphine)
*additive MAC w VA

39

What are disadvantages of N2O?

*supports combustion
*minimal skeletal muscle relaxation
*causes PONV
*high volume of absorption
*decreases immunity r/t ↓ in PMNs
*causes miscarriages r/t ↓ methionine synthetase
*causes polyneuropathy and B12 inactivation =
pernicious anemia

40

N2O is contraindicated in what surgeries?

Some eye surgeries, pneumothorax, belly cases

41

What VA is an organic alkane?

Halothane

42

Why was is taken off of the market?

20% metabolized by the liver = halothane hepatitis

43

What agents are Ethers?

Iso, Des, and Sevo

44

Iso characteristics

*gold standard
*most potent w MAC of 1.17%
*longest onset/offset w solubility of 1.46
*pungent, so no inhaled induction
*extreme physical stability

45

Des characteristics

*Least potent w MAC of 6.6%
*need heated vaporizer d/t vapor pressure of 669
*boils near room temp
*more stable and resistant to metabolism than iso
*the most rapid onset/offset w solubility of 0.42
*expensive
*pungent
*carbon monoxide generation in soda lime

46

Sevo characteristics

*MAC of 1.8%
*solubility of 0.69
*non pungent
*most expensive
*metabolism 5% potential nephrotoxicity
*degrades in soda lime to compound A =
No FGF < 1 L/min and no 2 MAC hours a low flow

47

Name brand names for agents

Iso = Forane
Des = Suprane
Sevo = Ultane

48

MAC values for VA's are additive

True

49

What are the factors that decrease (modify) MAC?

Opioids - decrease MAC significantly
Age - decrease MAC with age
Hypothermia, hyponatremia
Pregnancy, Lidocaine, Alpha-2 agonist

50

What are some factors that increase MAC?

Hyperthermia, Drugs that ↑ CNS (cocaine, MAIOs, anxiety), hyperthermia, hypernatremia

51

What is VA MOA?

unknown
mediated at cord, supraspinally, RAS likely

52

What is the Meyer-Overton theory?

correlation btw lipid solubility (oil:gas partition coefficient) and VA potency
causes distortion of ion channels, AP blocked

53

Unlikely that voltage-gated channels plan a role in production of anesthetic state

True

54

What is the effect on ligand-gated channels?

Glutamate, glycine, and GABA may be important site (role)

55

What are the effects of VA's on CNS?

*No retrograde amnesia
*No prolonged effects
*Luxury perfusion - ↑ CBF and ↓ CMRO2 (risk of ↑
ICP w tumors so hyperventilate, ↓ CO2 to ↓
vasodilation

56

What are the effects on EEG?

< 0.4 MAC = VA ↑ freq + voltage
0.4 MAC = shift post to ant, ↓ CMRO2, + amnesia
1 MAC = freq ↓ + max voltage
1.5 MAC = burst suppression
2 MAC = silence/isoelectric
No sz activity (fast freq + high voltage = spikes

57

How does VA effect EP's?

↓ amplitude + ↑ latency
*Don't go above 1 MAC
*Don't go up and down
*Usually asked to avoid N2O

58

At what MAC does cerebral vasodilation occur?

> 0.6 MAC

59

At what MAC is cerebral autoregulation best preserved?

at 1 MAC

60

Do VA's including N2O enhance CSF production?

No, they ↑ reabsorption and ↑ CSF pressure

61

What are the effects of VA's on MAP and how are they produced?

current VA's ↓ MAP by ↓ SVR (vasodilate)
*not N2O*
so use some N2O w VA to ↓ drop in MAP

62

What are the effects of VA's on HR from greatest to least?

They ↑ HR - Iso > des > sevo
The more rapid the rise on conc, the more rapid the increase in HR

63

What are the effects of VA's on RAP?

Des, Iso, and N2O ↑ RAP while sevo ↓ RAP

64

What are the effects of N2O on PVR?

↑, more pronounced if pre-existing pulm HTN and neonates, congenital heart dz R to L shunt

65

Describe a spontaneously breathing pt w VA's

Higher HR, Lower CO, SVR, BP d/t higher levels of CO2 (vasodilator) and SNS stimulation

66

What is coronary steal, what VA does this, and what must be done in CAD pts?

coronary vasodilation and blood is diverted away from ischemic areas, Iso does this
In CAD pt, no ↑ HR or drop in BP

67

How do you control Des and Iso neurocirculatory responses?

Don't stomp on the gas! slower increase in VA, use fentanyl, esmolol, precedex or clonidine

68

List cardiac coexisting dz's and choices of VA:

CHF - no VA, use N2O and fent
CAD - Sevo and fent
Valvular HD - VA good for regurg (full, fast, forward)
VA contraindicated in stenosis!!! Use N2O

69

What are the 3 prominent effects of VA's on ventilation?

1. Pattern of breathing (↑ RR, ↓ VT) = rapid shallow
2. ↓ Ventilatory response to CO2 and hypoxemia
(quality of each breath ↓, so dead space ↑)
3. ↑ Airway resistance
(bronchodilator once alseep)

70

Why does pt on vent need great VT?

VT augmented bc VQ mismatch, ↓ FRC, ↑ dead
space (d/t lack of diaphragmatic vent)
So assist spontaneous breathers... LMA's

71

What is the response to hypoxemia in VA?

0.1 MAC depresses this by 50-70%
1.1 MAC abolishes response completely

72

All VA's including N2O ↓ FRC

True

73

What are VA hepatic effects?

Maintain hepatic BF and venous O2 saturation

74

What agents have metabolites?

Iso and des have trifluoroacteic acid but remember, des has almost NO metabolism
Sevo produces hepatotoxic compound A

75

VA produce dose-related decreases in:

*Renal blood flow
*GFR
*Urine output (d/t ↓ BF)

76

How do you abolish or lesson these effects?

Pre-op hydration

77

How is Compound A formed?

When Sevo degrades in CO2 absorbent

78

What makes the degradation of sevo worse?

Dry granules, higher absorbent temps

79

What is important to remember about the flow of Sevo?

Never use with FGF < 1 L/min, do not exceed 2 MAC hours at 1-2 L/min FGF

80

What are the effects of VA's on skeletal muscles?

Produce some skeletal muscle relaxation
Potentiate MR's
N2O does not do either!

81

What about MH?

All VA's and Succs can trigger MH, but NOT N2O

82

What are the obstetric effects of VA's?

↓ in uterine BF and uterine smooth muscle tone
modest at 0.5 MAC, substantial at 1 MAC
N2O does NOT do this

83

What is a good cocktail for C/S?

0.5 MAC VA + 0.5 MAC N2O

84

Do VA's cross the placenta?

Yes, but rapidly exhaled after birth

85

What do VA's do to the resistance of infection?

All but N2O > VA's inhibit WBC chemotaxis

86

What are the genetic effects of VA's?

*Not mutagens or carcinogens (-Ames test)
*N2O ↑ abortion/miscarriage (B12 enzyme
methionine synthetase decreased)

87

How do VA's work w bone marrow fxn?

N2O > 24 h = megaloblastic changes
N2O > 4 d = agranulocytosis
Can still give to bone marrow recipients
Avoid in burns/immune depressed = repeated exposure have cumulative effects

88

N2O and peripheral neuropathy

Long exposure = nerve degeneration
sensorimotor polyneuropathy
pernicious anemia

89

What do VA's do to total body O2 needs?

VA decrease VO2

90

What makes VA's resistant to metabolism?

Fluorine-carbon bond

91

What is the % of Iso metabolism?

0.2%

92

What is the % of Des metabolism?

0.02%

93

What is the type of metabolism that they undergo and what metabolite do they have in common?

Oxidation by cytochrome P450
Trifluoroacetic acid

94

Carbon monoxide toxicity:

Des >> Iso DEGRADATION
Caused by strong bases (KOH and NaOH)
Can not detect intraop
Cause CNS disturbances

95

What factors favor carbon monoxide?

Dry absorbent (prolonged high FGF)
High absorbent temp (low FGF)
baralyme > sodasorb

96

Metabolism of Sevo:

2-5% oxidation by cytochrome P450

97

Degradation of Sevo and causes:

produces compound A
*high absorbent temps
*dry absorbent
*baralyme >> soda lime

98

Des compensation is used on the Fabius GS bc:

Des has characteristics that affect the sensitivity of the Fabius GS flow sensor

99

If this is not done, what will happen?

VT readings will be higher than set VT (up to 25%)

100

List physical signs of adequate ventilation in an anesthetized pt:

*chest mvmt * BBS * mvmt of bag/bellow * mvmt of unidirectional valves * sounds of vent * moisture in ETT w exhalation

101

List monitors that display signs of adequate ventilation in an anesthetized pt:

*Oxygen analyzer * spirometry * airway pressure * exhaled volume on monitor * gas analysis * capnography

102

What are common problems w spirometry?

weight/bulk close to face
tubing disconnections/damaged
peds vs adult D Lite sensor

103

List common problems w mechanical ventilation:

*Failure to resume or failure to initiate
***Disconnection*** most common - Y piece -

104

How to prevent these problems from occurring:

*Pre-anesthesia checklist
*Precordial
*If you turn off vent, keep your finger on the switch
*Use apnea alarms and DON'T silence them

105

List the umpteen mechanisms of circulatory effects of VA -

*direct myocardial depression
*decreased SNS
*peripheral autonomic ganglionic block
*decreased carotid sinus baroreceptor activity
*decreased cAMP
*decreased release of catecholamines
*decreased calcium ion influx thru slow channels

106

N2O alone or w VA produces mild SNS stim:

increased, plasma catecholamines, mydriasis, increased body temp, diaphoresis, increased RAP, systemic and pulmonary vasoconstriction

107

N2O w opiates:

more circ depression
decreased bp, co, increased lvedp and svr

108

High risk factors for PONV:

3 pts; hx, gyn, breast

109

Medium risk factors for PONV:

2 pts: face, ear, neuro, obesity, cross eyed

110

Low risk factors for PONV:

1 pt: young, female, anxiety, lap chole, opioids given, case > 1 hr

111

What determines FGF:

the vaporizer and flow meter settings

112

What determines FI

FGF, circuit vol, circuit absorption

113

what determines FA

uptake, ventilation, and conc and second gas effects

114

what determines Fa

V/Q mismatch

115

Why do we use PA as a measure of depth?

bc Pbr = Pa = FA

116

Why is solubility important?

The more poorly blood soluble agent has a faster speed of induction

117

What is a time constant and what are the %?

Capacity / flow
1 = 63%
2 = 86%
3 = 95%
There is circuit, lungs, and brain

118

Uptake =

BGSC x Content (A-V) x Q (CO)

119

The higher the uptake....

the slower the induction

120

High FA/FI ratio =

less difference btw inhaled and exhaled VA

121

The VRG is how much % of body wt and how much % of CO?

10 % body wt and 75% CO

122

What organs are in the VRG?

Brain, heart, liver, kidneys

123

The greater the VAlv / FRC ratio...

the faster induction
5:1 in neonates as compared to 1.5/1 in adults

124

What cases would it be wise to avoid N2O?

abdominal, bowel, craniotomies, sitting positions, anytime the wound is higher than the heart

125

The greater the A-V difference of VA...

the slower the rate of rise/slower induction