Inhaled Anesthetics Overview Flashcards
1
Q
What was wrong with the older inhaled anesthetic?
A
Flammable, led to combustion
2
Q
When was diethyl ether made?
A
1842
3
Q
When was chloroform made?
A
1847
4
Q
When was cyclopropane made?
A
1934
5
Q
When was fluroxene made?
A
1951
6
Q
When was halothane made?
A
1956
7
Q
When was methoxyflurane made?
A
1960
8
Q
When was enflurane made?
A
1973
9
Q
When was isoflurane made?
A
1981
10
Q
When was desflurane made?
A
1993
11
Q
When was sevoflurane made?
A
1995
12
Q
Who first used diethyl ether?
A
Crawford Long
13
Q
What is the chemical structure of inhaled anesthetics?
A
Halogenated methyl ethyl ethers
14
Q
What are the components of inhaled anesthetics (2) as a result of their chemical structure?
A
- Non-flammable
- Less toxicity compared to earlier inhaled anesthetics
15
Q
What is the chemical structure of Halothane?
A
Halogenated alkane
16
Q
What is the common structure of inhaled anesthetic?
A
C-O-C (ether bridge)
17
Q
What is halogenated?
A
the addition of Cl, Br, I, Fl influence potency, stability, flammability & arrhythmogenicity
18
Q
What are the goals of general anesthesia (4)?
A
Loss of consciousness, Amnesia, Immobility & Analgesia
19
Q
What is the MOA of inhaled anesthetics?
A
not completely understood
20
Q
What is the meyer-overtone rule?
A
Older theory, predicts the constant increase of anaesthetic potency of n-alkanols with increasing chain length
21
Q
What is the current thinking regarding the MOA of IA?
A
Current thinking: direct binding to ligand-gated ion channels causing spinal and supraspinal effects
- Enhance inhibitory
- Inhibit excitatory signals
22
Q
What receptors enhance inhibitory?
A
GABAa, glycine
23
Q
What receptors inhibit excitatory signals?
A
NMDA receptors
24
Q
What concept relates to MAC? Where is its effects?
A
immobility – likely effect at spinal cord level via glycine, sodium, and NMDA receptor action
25
Where are amnesia and LOC occur stimulated with inhaled anethesias?
Cerebral GABAA receptor stimulation
26
Inhaled anesthetics: where does the unconsciousness occur in the CNS?
Cortex, thalamus, brainstem
27
Inhaled anesthetics: where does the amnesia occur in the CNS?
amygdala, hippocampus
28
Inhaled anesthetics: where does the analgesia occur in the CNS?
spinothalamic tract
29
Inhaled anesthetics: where does the immobility occur in the CNS?
spinal cord central pattern generators
30
What is the definition of Minimal Alveolar Concentration (MAC)?
The MAC of an inhaled anesthetic is the concentration of that inhaled anesthetic at 1 atm (expressed as % of 1 atm) that prevents skeletal muscle movement in response to supramaximal painful stimulus (surgical skin incision) in 50% of patients
31
What do we use to measure MAC?
Expired (end-tidal) concentration (%) of anesthetic agent
32
What is response defined as?
gross, purposeful movement of the head or extremities
33
What does MAC reflect?
required dose of the anesthetic; reflects potency of the inhaled anesthetic agent
34
What is the MAC (Expressed as a % of 1 Atmosphere) of isoflurane?
1.17
35
What is the MAC (Expressed as a % of 1 Atmosphere) of sevoflurane?
2
36
What is the MAC (Expressed as a % of 1 Atmosphere) of desflurane?
6
37
What is the MAC (Expressed as a % of 1 Atmosphere) of nitrous oxide?
104
38
What agent has the most potent MAC?
Isoflurane (MAC 1.17%)
39
What agent has the faster onset?
Desflurane (MAC 6%)
40
What is MAC awake?
The MAC concentration at which 50% of patients will respond to the command “open your eyes”
41
What is the MAC associated with amnesia?
0.3 - 0.4MAC
42
What is MAC bar?
The MAC concentration necessary to block adrenergic response (BP, HR) to skin incision
43
What is the MAC associated with MAC bar?
1.5 – 1.8MAC
44
MAC values for inhaled anesthetics are __________
Additive
45
What are examples of the additive inhaled anesthetics values for inhaled anesthetics?
0.5 MAC of Nitrous Oxide + 0.5 MAC of Isoflurane = clinical effect at the brain as does 1 MAC of either anesthetic alone
46
Understand diagram of MAC?
Slide 14
47
What is the partial pressure of MAC?
Remember MAC is a % of 1atm. (760mmHg at sea level)
48
What is the partial pressure of 1 MAC of desflurane at 1 atm?
- MAC of Desflurane = 6% at 1atm.
| - 0.06 x 760mmHg = 45.6 mmHg
49
What is the partial pressure of 1 MAC of sevoflurane at 1 atm?
- MAC of Sevoflurane = 2% at 1atm.
| - 0.02 x 760mmHg = 15.2 mmHg
50
What is the partial pressure of 1 MAC of isoflurane at 1 atm?
- MAC of Isoflurane = 1.17% at 1atm.
| - 0.0117 x 760mmHg = 8.89 mmHg
51
What drives the inhaled anesthetic into the blood and brain?
the partial pressure of the inhaled anesthetic (not actually the MAC % or concentration)
52
What are the factors that increased MAC (7)?
- Hyperthermia
- Excess pheomelanin production (red hair) in females
- Drug-induced increases in CNS catecholamine levels (cocaine, methamphetamine, amphetamine)
- Cyclosporine
- Hypernatremia
- Chronic alcohol abuse
- Hyperthyroidism
53
What are the factors that decreased MAC (15)?
- Hypothermia
- Increasing age
- Preoperative medication
- Drug-induced decreases in CNS catecholamine levels
- Alpha 2 agonists
- Acute alcohol intoxication
- Pregnancy
- Postpartum
- Lithium
- Lidocaine
- Opioids
- PaO2 < 38 mm Hg
- Mean BP < 40 mm Hg
- Cardiopulmonary bypass
- Hyponatremia
54
What affect does increased age have on MAC?
progressive reduction in MAC of 6% per decade of life
55
How does pregnancy effect MAC?
reduced by 30%
56
When does mac return to normal in the postpartum periods?
Postpartum (returns to normal in 24-72 hours)
57
Review MAC and Age of sevoflurane diagram.
Slide 19
58
Inhaled anesthetics are ______ agents
“volatile”
59
What are volatile liquids?
all liquids that have a high vapor pressure at room temperature
60
What is vapor pressure?
pressure at equilibrium within a closed space exerted by molecules that escape the liquid and enter the gas phase; measured in mmHg, all liquids have a vapor pressure
61
Vapor pressure of water at 20 degrees C = __________
17.5 mmHg
62
Vapor pressure of Isoflurane at 20 degrees C = __________
238 mmHg
63
What is boiling point?
the temperature at which the bulk of a liquid at a given pressure converts to a vapor
64
Boiling point and vapor pressure are _________proportional
inversely
65
What is the boiling point of a liquid?
is the point at which vapor pressure is equal to the atmospheric pressure
66
“Volatile” inhaled anesthetics exist as liquids at _________
room temp
67
What is required of volatiled inhaled anesthetics?
require “vaporizer” that converts the anesthetic liquid poured into the vaporizer into the vapor/gas state which is then inhaled by the patient from the AGM through a face mask, LMA, or ETT
68
What is true about each volatile anesthetics vaporizer?
must be calibrated for each specific agent’s vapor pressure (placing wrong agent into a vaporizer will deliver a greater or lower concentration than dialed)
69
What is the vapor pressure of isoflurance at (standard temp and pressure)?
238 mmHg
70
What is the vapor pressure of sevoflurane at (standard temp and pressure)?
160 mmHg
71
What is the vapor pressure of desflurane at (standard temp and pressure)?
660 mmHg
72
What is the principle objective of inhalation anesthesia?
achieve a constant & optimal brain partial pressure of inhaled anesthetic
73
The pressure exerted by an individual gas in a mixture is known as its ________
partial pressure
74
What is dalton's law of partial pressures?
the total pressure of a mixture of gases is equal to the sum of the partial pressures of the component gases
75
What is the partial pressure of oxygen and nitrogen?
752 mmHg
76
What is the pressure of oxygen?
Pressure 159 mmHg @ 760 mmHg (21%)
77
What is the pressure of nitrogen?
593 mmHg at 760 mmHg
78
Gases dissolve, diffuse, and react according to their partial pressure and reach a state of ___________
EQUILIBRIUM, when a reaction’s forward progress is balanced with the reverse process where the concentrations of all reacting substances remain constant (no change is occurring in concentration)
79
Using Dalton’s Law of PP, we see that each gas in this mixture makes a ________ to the total pressure of the gas mixture
fractional contribution
80
What happens to partial pressure of oxygen when the atmospheric pressure is NOT AT SEA LEVEL > DENVER, CO?
harder to breath because less atmospheric pressure but still breathing 21% oxygen
81
Goal of inhaled anesthetics: to achieve _____________ and _____________
a constant and optimal brain partial pressure of the anesthetic
82
What does the brain and tissues equilibrate with?
The brain and all other tissues in the body EQUILIBRATE with the partial pressure of inhaled anesthetic delivered to them by arterial blood (Pa)
83
What does arterial blood (Pa) equilibrate with?
Arterial blood (Pa) EQUILIBRATES with the alveolar partial pressure (PA) of the inhaled anesthetic agent
84
What happens at steady state to to inhaled anesthetics?
the PA of inhaled anesthetics MIRRORS the partial pressure of the inhaled anesthetic IN THE BRAIN (PBRAIN)
85
What is the goal of inhaled anesthesia?
PA = Pa = PBRAIN
86
What is PA (alveolar partial pressure) indicate?
- Depth of inhalation anesthesia
- Recovery from inhalation anesthesia
- MAC
87
What does equilibration between two phases mean?
Equilibration between the two phases (i.e., blood/gas; tissue/blood) means the same partial pressure of the inhaled anesthetic exists in both phases not equal concentrations
88
What do factors that determine PA also determine? What does it permit?
PBRAIN which permits control of the doses of inhaled anesthetic delivered to the brain to maintain a constant & optimal depth of anesthesia
89
Why can we control inhaled dose delivery?
Because inhaled anesthetics undergo minimal metabolism and are eliminated via the lungs
90
What does end-tidal partial pressure of the inhaled anesthetic reflect?
End-tidal partial pressure of inhaled anesthetic (readout on the anesthesia monitor attached to the patient breathing circuit) reflects the PA of the inhaled anesthetic being delivered) and at equilibrium, reflects the PBRAIN
91
Why id it easier for dose inhaled anesthetic versus IV anesthetic doses?
end tidal partial pressure of inhaled anesthetic makes it easier to determine concentrations of brain and tissues
92
What is true about the vaporizer for desflurane?
Being so close to atm pressure it makes it close to boiling and need a special heater (39C at 2 atm) to prevent it from boiling in the anesthesia vaporizer
93
What affects the site of action for inhaled anesthetics?
Series of partial pressure gradients (barriers) from anesthesia machine to site of action (CNS – BRAIN/sc)
94
What does the PA of inhaled anesthetic (and ultimately the PBRAIN) equals?
input (delivery) into the alveoli – uptake (loss) of inhaled anesthetic from alveoli into arterial blood
95
What effects the input/delivery of the inhaled anesthetic into the alveoli? (3)
Inhaled partial pressure (PI), Alveolar ventilation, Anesthesia breathing circuit
96
What effects the uptake and loss of the inhaled anesthetic from the alveoli into the pulmonary capillary blood? (3)
Solubility of inhaled anesthetic in body tissues (solubility coefficients), Cardiac output, Alveolar-to-venous partial pressure difference
97
When is a high Inhaled Partial Pressure (PI) needed?
A high PI delivered from the anesthesia machine is required during initial administration of an inhaled anesthetic
98
What does high inital output (PI) do?
accelerates induction of anesthesia by increasing the rate of rise in the PA (and ultimately the PBRAIN)
99
What happens if the PI is maintained constant with time?
the PA and PBRAIN will progressively INCREASE as uptake (anesthetic loss) diminishes
100
What the concentration effect?
States that the higher the PI, the more rapidly the PA approaches the PI
101
What does a higher PI provide?
inhaled anesthetic molecule input to offset uptake which then speeds the rate at which the PA approaches the PI
102
What is the second-gas effect?
A high concentration of one gas (first gas) will accelerate the rate of increase of the PA of a concurrently administered second gas
103
What is an example of the second-gas effect?
N2O administered with a volatile agent (Iso, Sevo, Des) will accelerate the rate of increase of the PA of that agent
104
What impact does increased alveolar ventilation have on the inhaled anesthetic?
impacts the speed in which an inhaled anesthetic reaches the alveoli & increases rate of rise of PA to PI
105
What impact does the anesthesia breathing circuit have on IA delivery to the aveoli?
inhaled anesthetic (due to its solubility) can be taken up into components (rubber or plastic components) of the breathing circuit
106
Factors that affect inhaled anesthetic UPTAKE/LOSS from the alveoli into ____________
pulmonary capillary blood
107
What effect do factors that reduce the PA of the inhaled anesthetic from rising within the alveoli causes what?
will REDUCE equilibration of the PA with the Pa and the PBRAIN
108
What are some factors that effect Uptake/Loss of Inhaled Anesthetic from the Alveoli into the Blood? (3)
- Inhaled anesthetic agent solubility
- Cardiac output
- Alveolar-to-venous partial pressure difference
109
What is henry's gas law?
the amount of a given gas dissolved in a given liquid is directly proportional to the partial pressure of the gas in contact with the liquid
110
What is the partial pressure of a gas inversely and proportional to?
The partial pressure of a gas in a solvent is also proportional to the concentration of the gas in the solvent and INVERSELY proportional to their solubility in that solvent
111
If a gas is highly soluble in something, its partial pressure will be __________
Lower
112
More inhaled agent dissolved in blood = ________ in the gas phase
Less
113
What drives diffusion?
The partial pressure of a gas is what drives diffusion
114
What is the relationship of PA to solubility?
The rate of increase of the PA toward the PI (when PI is maintained constant) is inversely related to the solubility of the anesthetic agent in the blood
115
What are the inhaled agents classified as based on their blood: gas solubility coefficients? (3)
soluble, intermediately soluble, & poorly soluble
116
What is blood: gas solubility coefficient?
a ratio that describes how the inhaled anesthetic distributes itself between two phases at equilibrium
117
What is an example of blood: gas solubility?
A blood:gas partition coefficient of 0.5 means that the concentration of the inhaled anesthetic that’s dissolved in the blood is half that present within the alveoli when the partial pressure of the anesthetic in these two phases are identical (equilibrated)
118
***Blood is a ___________for inhaled anesthetic agents
pharmacologically inactive reservoir
119
What must happen before the inhaled anesthetic reaches the brain?
Before the brain reaches the partial pressure of the inhaled anesthetic, the blood and the alveolar partial pressures must equilibrate
120
What determines how fast the equilibration of partial pressures occurs?
the solubility of the inhaled agent determines how fast this equilibration of partial pressures occurs
121
What happens when the Blood:Gas partition coefficient is high?
a large amount of inhaled anesthetic must be dissolved in the blood before the Pa equilibrates with the PA - induction of anesthesia will take longer – (opposite applies)
122
What technique can speed up induction of soluble agents?
Overpressure technique
123
Review the agent solubility.
Slide 37, 38 & 39
124
When might you select a poorly soluble inhaled anesthetic agent for a case?
Morbidly obese because you do not want something to hang out longer in the tissues.
125
What occurs with an insoluble agent?
Quicker onset and offset possible
126
What are examples of tissues?
muscle and fat
127
What is tissue:blood coefficient?
Uptake of agent into tissues and time to equilibrate with the Pa
128
What is true about fat and inhaled anesthetics?
Fat: large depot and accumulation possible
129
What is time constant?
amount of agent that can be dissolved in the tissue divided by tissue blood flow
130
One time constant is _______% equilibration
63%
131
3 time constants = ________% equilibration
95%
132
What does Pa to Pbrain depend on for volatile anesthetics?
Pa to PBRAIN depends on solubility and takes 5-15 minutes (3 time constants)
133
What is the oil:gas partition coefficient?
The potency of an anesthetic is associated with its lipid solubility which is measured by
134
What does Oil:Gas Partition Coefficient parallel?
anesthetic requirement (MAC)
135
What is the MAC concentration refer to?
Concentration of an agent at 1 atmosphere that prevents skeletal muscle movement in response to painful stimulus in 50% of the patients (ED50)
136
MAC is _________ related to the oil:gas partition coefficient
inversely
137
What is the MAC of a higher lipid solubility inhaled anesthetic?
Higher lipid solubility = lower MAC; less needed to achieve anesthetic effect
138
What is the calculation of MAC?
150/oil:gas coefficient
139
How does cardiac output (pulmonary blood flow) influence anesthetic uptake/loss of inhaled anesthetics?
the PA by carrying away more or less anesthetic from the alveoli and reduces the building up of partial pressure of inhaled anesthetic within the alveoli (especially w/more soluble inhaled agents)
140
What impact does increased cardiac output have on influence anesthetic uptake/loss of inhaled anesthetics?
more rapid uptake/loss of inhaled anesthetic from the alveoli = slowing the rate of increase in the PA which slows induction of anesthesia
141
What impact does decreased cardiac output have on influence anesthetic uptake/loss of inhaled anesthetics?
less uptake/loss of inhaled anesthetic from the alveoli = increases the rate the PA rises and speeds induction of anesthesia
142
What does the Alveolar to Venous Partial Pressure Differences (A-vD) reflect?
tissue uptake of inhaled anesthetics
143
What Factors affect the amount of anesthetic removed from the blood and moved into a tissue ? (3)
- Tissue solubility
- Tissue blood flow
- Arterial to tissue partial pressure differences
144
_______ equilibrate rapidly with the Pa
Vessel-rich tissues
145
What effects the time for equlibration among neonates and infants? Why?
Time for equilibration of vessel rich group tissues (brain, heart, kidneys) is more rapid for neonates and infants than adults due to increased CO, decreased solubility of anesthetics in tissues of neonates, and limited quantities of skeletal muscle bulk
146
What effects recovery?
affected by the rate of decrease in the PBRAIN as reflected in the PA
147
What is emergency dependent on?
solubility of the agent and duration of anesthetic
148
Emergence: What is true about the process?
Can't “rush” the process like overpressuring during induction
149
Emergence: What can you do to assist with emergence process?
Can increase fresh gas flows to facilitate washout of inhaled agent in lungs & decrease rebreathing of inhaled agent back into the circuit
150
Emergence: ______ is key as to when to decrease/turn off inhaled anesthetic
Timing
