Inhaled Agents Flashcards
1
Q
N2O synthesized by who?
When?
A
Priestly
1776
2
Q
Diethyl ether effect similar to N2O, noted by who?
When?
A
Faraday
1796
3
Q
Who tested effects on Prime minister noting euphora, analgesia and LOC?
When?
A
Humphrey David
1800
*Mainly used at carnival exhibitions or “ether frolics”, no medical use until mid-nineteenth century.
4
Q
American Dentist ____________ decided to use N2O on his own tooth extraction in ______.
A
Horace Wells
1846
5
Q
Who used Diethyl Ether, first, for cyst removal but did not report findings?
When?
A
Long
1842
6
Q
Familiar with use of nitrous from dental partnership with Wells, _________________ Successfully demonstrated ether as an anesthetic at Mass General on what date?
A
William T.G. Morton (dentist)
OCT 16, 1846
7
Q
\_\_\_\_\_\_\_ first “ideal” anesthetic • Easy to make in pure form • Easy to administer • Liquid at room temp, but readily vaporized • Potent anesthetic, few drops needed, can produce anesthesia without diluting oxygen to hypoxic levels • Supports respiration and circulation • Not toxic to vital organs • Flammable!!
A
Ether
8
Q
In what year did _____________, at Edinburgh University, use chloroform to treat pain during labor? The clergy was highly critical.
A
1846
James Simpson
9
Q
In ____, Queen Victoria gave birth to her seventh child under the influence of chloroform popularizing the technique
A
1853
*procedure became known asanaesthésie à la reine
10
Q
Chloroform • Pleasant odor • Nonflammable • (T or F) hepatotoxin • Severe cardiovascular depressant (T/F) • High incidence of intra and postop deaths associated with its use • Difficult to administer
A
- Pleasant odor
- Nonflammable
- Known hepatotoxin
- Severe cardiovascular depressant
- High incidence of intra and postop deaths associated with its use
- Difficult to administer
11
Q
Advances in fluorine chemistry in ____ allowed incorporation of fluorine into molecules were pivotal in development of modern anesthetics
A
1940
12
Q
First halogenated hydrocarbon anesthetic?
• Withdrawn from market due to organ toxicity
A
Fluroxene
13
Q
Methoxyflurane:
A
Halogenated methyl ethyl ether
Nonexplosive and nonflammable.
Most potent of volatile agents. MAC 0.16
Highly soluble B/G 12
70% metabolized (Oxidative metabolites include fluoride (F-) and oxalic acid, both nephrotoxic.
Flouride
vasopressin-resistant high-output renal failure
14
Q
Theories of Anesthesia
Unitary theory-
Degenerated theory-
Some even suggest different targets for different effects (immobility VS unconsciousness)
•Immobility _________ mediated
•Hypnosis and amnesia ______
________ is the major inhibitory neurotransmitter in the spinal cord and may be the site of action of immobility effect.
2pore potassium channels membrane receptor ion channels that normally help maintain the cells RMP.
A
all GA act same mechanism
different classes = different mechanisms
spinal cord (MAC/GA) brain
Glycine
15
Q
Disproved: _______________ Theory
absorption of anesthetic molecules expands hydrophobic region– expansion of lipid bilayer beyond critical amount and alters membrane function
A
Meyer-Overton
16
Q
Potential sites of action:
A
Pre-synaptic Voltage gated sodium channels
2-pore potassium channels
Ionotropic and metabotropic receptors
• GABAA and glycine
• Glutamate (NMDA, AMPA, Kainate)
17
Q
Stages of Anesthesia- Guedel
A
- Stage I = Amnesia/Analgesia
- Stage II = Delirium/Excitement (troublesome stage ~ laryngospasm)
- Stage III = Surgical Anesthesia 4 planes
- Stage IV = overdose
18
Q
Stages of Anesthesia- Guedel
Stage 1
A
called the stage of analgesia or induction
dizziness
sense of unreality
lessening sensitivity to touch and pain
sense of hearing is increased, and responses to noises are intensified
19
Q
Stages of Anesthesia- Guedel
Stage 2
A
the stage of excitement
reactions involving muscular activity
delirium
vital signs show evidence of physiological stimulation the patient may respond violently to little stimulation
20
Q
Stages of Anesthesia- Guedel
Stage 3
A
the surgical or operative stage
four levels of consciousness (planes)
anesthetist determines which plane is needed
Each successive plane is achieved by increasing the concentration of the anesthetic agent.
21
Q
Stages of Anesthesia- Guedel
Stage 4
A
the toxic or danger stage
never desired
cardiopulmonary failure and death can occur
The fourth level of consciousness of stage 3 is demonstrated by cardiovascular impairment that results from diaphragmatic paralysis. If this plane is not corrected immediately, stage 4 quickly ensues.
22
Q
Nitrous Oxide: MAC
A
104
23
Q
Nitrous Oxide: Vp
A
38800
24
Q
Nitrous Oxide: B/G
A
0.47
25
Nitrous Oxide is how many times more soluble than nitrogen in blood?
34
26
Nitrous Oxide:
Smell =
Color =
sweet/odorless
| none
27
Nitrous Oxide: Flammability
None, but combustible?
28
Reduces MAC for Halothane, Enflurane, Isoflurane, Desflurane, and Sevoflurane by
30-50%
29
Nitrous Oxide: Cardiovascular Effects
• Direct action?
• May unmask what?
myocardial contractility depressant
undiagnosed myocardial depression in CAD, severe hypovolemia
30
Nitrous Oxide: Cardiovascular Effects
| • Arterial BP, SVR, CO, & HR response?
unchanged or modestly elevated secondary to stimulation of catecholamines (sympathomimetic effect)
31
Nitrous Oxide: Cardiovascular Effects
• (Contracts or dilates) pulmonary vascular smooth muscle, and (increases or decreases) PVR and RA
pressure.
• So....dont use if?
Constricts, increases
| PulmHTN, OSA
32
Nitrous Oxide: Cardiovascular Effects
| • Associated with higher incidence of ____________ induced dysrhythmias
epinephrine
33
Nitrous Oxide: Pulmonary Effects
•Increases or decreases respiratory rate?
•Increases or decreases VT?
•Hypoxic drive markedly increased or decreased?
•Diffusion hypoxia!!!!!!!!!!
Increases
Decreases
Decreased
•depression of medullary ventilation center
34
Nitrous Oxide: Pulmonary Effects
| •Change in VE and resting CO2 levels = ?
minimal
35
Nitrous Oxide: Cerebral Effects
•Increases or decreases CBF?
•Produces mild elevation or depression of ICP?
•Increases or decreases CMRO2?
*May increase motor activity – clonus and opisthotonos- a form of spasm in which?
Increases
Elevation
Increases
the head neck and spine are arched backwards
36
Nitrous Oxide: Neuromuscular Effects
•Does or does not provide significant muscle relaxation?
•May cause skeletal muscle rigidity or relaxation at > _ MAC?
•Is or is not an MH trigger according to MHAUS?
* Does not provide significant muscle relaxation.
* May cause skeletal muscle rigidity at >1 MAC (WE ARE NEVER NEAR 1 MAC)
* Not an MH trigger according to MHAUS
37
Nitrous Oxide: Renal Effects
• Increases or decreases renal blood flow by increasing or decreasing renal vascular resistance?
• Increases or decreases GFR and urine output?
* Decreases renal blood flow by increasing renal vascular resistance (sympathetic)
* Decreases GFR and urine output (sympathetic)
38
Nitrous Oxide: Hepatic Effects
| • Hepatic blood flow mildly increased or decreased?
• Hepatic blood flow mildly decreased (sympathetic)
39
Nitrous Oxide: GI Effects
• Meta-analysis 30 studies suggests postoperative nausea and vomiting risk increased or decreased?
• Causes ________ of the bowel
• Meta-analysis 30 studies suggests postoperative nausea and vomiting risk increased (activation of chemoreceptor trigger zone and vomiting centers in medulla and/or middle ear volume changes).
• Causes distention of the bowel
NOT indicated when pt. has bowel obstruction or most bowel surgeries
40
Nitrous Oxide: Biotransformation and Toxicity
| •Almost exclusively eliminated by?
exhalation
41
Nitrous Oxide: Biotransformation and Toxicity
•Biotransformation limited to < ___%
•Irreversibly oxidizes cobalt atom in vitamin B12 and inhibits vitamin B12 dependent enzymes.
•Includes _________________, necessary for _______ formation and __________________, necessary for ______________.
```
0.01
methionine synthetase
myelin
thymidylate synthetase
DNA synthesis
```
42
Nitrous Oxide: Biotransformation and Toxicity
•Almost exclusively eliminated by exhalation. •Biotransformation limited to < 0.01%
•Irreversibly oxidizes cobalt atom in vitamin B12 and inhibits vitamin B12 dependent enzymes.
•Includes methionine synthetase, necessary for myelin formation and thymidylate synthetase, necessary for DNA synthesis.
• Prolonged exposure (>__ hrs) and abuse can result in?
24
bone marrow depression (megaloblastic anemia)
peripheral neuropathies
pernicious anemia
***scavenging = important!!!
43
Nitrous Oxide: Biotransformation and Toxicity
• Avoid use in __________ patients
• May alter immune response to _______
pregnant
| infection
44
Nitrous Oxide: Contraindications
● Diffuses rapidly into air containing cavities
• Air embolism (central line)
• Pneumothorax
• Acute intestinal obstruction
• Intracranial air
• Pulmonary air cysts
• Intraocular air bubbles (detached retina surgery w/ in 10 weeks)
• Tympanic membrane grafting or middle ear surgery
• Diffuses into ETT cuff
45
Nitrous Oxide: Contraindications
● Diffuses rapidly into?
• Avoid in patients with?
• Limited value in patients requiring?
air containing cavities
pulmonary HTN and OSA
high FIO2 (limitw max FiO2)
46
Nitrous Oxide: Drug Interactions
| •Cannot be used as complete anesthetic (high MAC) •Decreases MAC requirements of other agents •Potentiates what?
neuromuscular blockade
47
Diffusion hypoxia:
occurs when inhalation of nitrous is discontinued abruptly, leading to a reversal of partial pressure gradients such that nitrous oxide leaves the blood to enter the alveoli.
High volume can dilute PAO2 = ?
as well as a dilution of PCO2 = ?
***Usually see it in first 5 minutes after dc so common practice to increase PaO2 to 100% as you turn it off.
hypoxia
| reducing the respiratory drive
48
Isomer agents?
Enflurane
F F F
CCOC
ClF F
Isoflurane
F H F
CCOC
F Cl F
49
Volatile Agents
• Halogen substitutions increases or decreases anesthetic potency?
• Lower weight halogens (fluorine a.w.19) increased or decreased potency more than those of higher atomic weight (chlorine a.w.35.5)?
increases
| decreased
50
Volatile Agents
| • ________ substitution leads to most stable cpd. However it leads to?
Chloride
| myocardial depression
51
Volatile Agents
• _____________ reduces flammability, and may produce potential for renal damage (flouride ions inhibit sodium reabsorption in ascending loop)
Fluorination
52
Halothane:
VP =
B/G =
MAC =
Halothane:
VP = 244
B/G = 2.3
MAC = 0.74
53
Enflurane:
VP =
B/G =
MAC =
Enflurane:
VP = 172
B/G = 1.8 (intermediate solubility)
MAC = 1.68 (high potency)
54
Isoflurane:
VP =
B/G =
MAC =
Isoflurane:
VP = 240
B/G = 1.4
MAC = 1.15
55
Desflurane:
VP =
B/G =
MAC =
Desflurane:
VP = 669
B/G = 0.42
MAC = 6
56
Sevoflurane:
VP =
B/G =
MAC =
Sevoflurane:
VP = 160
B/G = 0.69
MAC = 2
57
N2O:
VP =
B/G =
MAC =
N2O:
VP = 38,770
B/G = 0.47
MAC = 104
58
Pt temp:
Hypothermic =
Hyperthermic =
Liquid temp:
Warmer =
Colder =
Pt temp:
Hypothermic = decreases MAC
Hyperthermic = increases MAC
Liquid temp:
Warmer = less gas dissolved
Colder = more gas dissolved
59
Increase Altitude = Increased or decreased Barometric Pressure?
Decreased
60
Decreased Barometric Pressure = Underdosing or overdosing?
Underdosing?
| 240/760 = 1/3 = 33% < 240/500 = ½ = 50%
61
Minimum Alveolar Concentration =
The minimum alveolar concentration @ 1 ATM that produces immobility in 50% of patients exposed to noxious stimuli
• Inhalation equivalent of ED50
62
Factors Decreasing MAC
* Increasing age
* Hypothermia
* Hyponatremia
* Hypotension < 40mmhg
* Pregnancy
* Hypoxemia < 38 mmHg
* Opioids
* Ketamine
* Benzodiazepines
* Clonidine
* A2 agonists
* Local Anesthetics
* ETOH (acute)
* Lithium
63
Factors Increasing MAC
* Hyperthermia
* CNS stimulants
* Youth- under one year of age
* Increased pheomelanin production (red hair)
64
MAC values of different agents are _________
additive
65
To avoid movement when no muscle relaxant is on board in 95% of patients
requires 30% above 1 MAC or 1.3 MAC (similar to ED95)
| Ex: Des ED95 = MAC of 6% x 1.3 MAC = MAC of 8%
66
MAC Awake =
Des/Sevo/Iso =
Halothane =
N2O =
the concentration that prevents consciousness in 50% of patients is approximately 1/2 - 1/3 MAC
1/3 MAC for Des, Sevo, Iso
½ for Halothane
60% for N2O
67
MAC memory =
the concentration of anesthetic associated with amnesia in 50% of of patients is significantly less than MAC Awake, thus NEVER go below MAC awake!
68
EEG burst suppression ~ _ MAC
2
69
Halothane: structure
Halogenated alkane derivative
_FCl
FCCH
_FBr
70
Halothane: VP
244
71
Halothane: B/G
2.3 (int. sol.)
72
Halothane: MAC
0.74 (high pot.)
73
Halothane: Odor
Sweet, Non-pungent (used to be go to for peds)
74
Halothane: Contains Thymol
Sticky, clogs up vaporizer
75
Halothane: Cardiovascular Effects
| Direct =
Direct myocardial depressant = BP decrease
| •Dose dependent decreases in CO (SV decrease 15-30%)
76
Halothane: Cardiovascular Effects
| Does or does not decrease SVR?
Does not decrease SVR (iso, des, sevo do)
77
Halothane: Cardiovascular Effects
| Coronary artery vasoconstrictor or vasodilator?
Coronary artery vasodilator, coronary blood flow decreased from drop in systemic BP, can cause ischemia.
•Yet.....Protection from decreased myocardial oxygen demands?
78
Halothane: Cardiovascular Effects
| Blunts baroreceptor response to hypotension = ?
no increase in HR (iso, des, sevo increase HR)
79
Halothane: Cardiovascular Effects
•Increased or decreased right atrial pressure (CVP)?
•Increase or decrease cutaneous blood flow?
* Increased right atrial pressure (CVP)
| * Increase cutaneous blood flow (increase risk of bleeding and hypothermia)
80
Halothane: Arrhythmias
•Increased or decreased SA node depolarization- prone to?
•Increased or decreased conduction where?
•Caution when ___________ is injected!
* Decreased SA node depolarization- prone to junctional rhythm
* Decreased conduction AV node/His-Purkinje
* Caution when epinephrine is injected!
81
```
Halothane: Respiratory Effects
• Increased or decreased RR?
• Increased or decreased VT?
• Increased or decreased VE?
• Increased or decreased resting PACO2?
• Apneic threshold rises
• Hypoxic drive severely depressed (even at low doses 0.1 MAC)
• Potent bronchodilator can reverse asthma-induced bronchospasm
```
Increased
Decreased
Decreased
Increased
82
Halothane: Respiratory Effects
| • Apneic threshold rises or falls?
rises
83
Halothane: Respiratory Effects
| • Hypoxic drive severely elevated or depressed (even at low doses __ MAC) ?
depressed (even at low doses 0.1 MAC)
84
Halothane: Respiratory Effects
| • Potent broncho___________
dilator
| *can reverse asthma-induced bronchospasm
85
Halothane: Cerebral Effects
• “Uncouples cerebral blood flow and metabolism”
• *Stay well below __ MAC, but ideally avoid use
1/2
86
Halothane: Cerebral Effects
• “Uncouples cerebral blood flow and metabolism”
• Increases or decreases CBF, ICP, IOP?
Increases
87
Halothane: Cerebral Effects
| • Modest increase or decrease in CMRO2?
decrease
88
Halothane: Cerebral Effects
• Autoregulation is ___________
• Can prevent rise in ___ by hyperventilation prior to halothane administration
blunted
| ICP
89
Halothane: Cerebral Effects
| • Cerebral activity increased or decreased?
decreased
90
IA(s) that potentiate nondepolarizing NM blocking meds
Halothane, Sevo
91
IA that evokes skeletal muscle relaxation 2X less than other volatile agents
Halothane (others are better choice)
92
Halothane: Renal Effects
| • Increases or decreases RBF, GFR and urine output?
* Reduces RBF, GFR and urine output.
| * Can limit by pre-op hydration
93
Halothane: Hepatic Effects
• Increased or decreased hepatic blood flow?
• Hepatic artery vaso__________
Decreased
| constriction
94
Halothane: Hepatic Effects
• Anesthetic induced inhibition of ?
• Metabolism of what drugs may be impaired? Meaning they will....?
hepatic drug metabolizing enzymes
| fentanyl, phenytoin, verapamil; stick around longer
95
Halothane: Hepatic Effects
| • Oxidized metabolite = ?, at __%
trifluroracetic acid
| 20%
96
Halothane: Biotransformation and Toxicity
| • Halothane produces _ types of hepatotoxicity in susceptible patients.
2
97
```
Halothane: General Toxicity
• __% of adult patients develop mild, self-limited post-op hepatotoxicity.
• Symptoms = ?
• May be due to ?
*Pts generally recover?
```
20
Nausea, lethargy, fever, minor increases in transaminase enzymes
non-specific drug effect due to changes in hepatic blood flow that impairs hepatic oxygenation
Yes
98
Halothane: Hepatitis
• Occurs in 1 in _0,000 to 1 in _0,000 adults
* 1:______ Extensive hepatic necrosis and death possible
• Most likely ________-mediated hepatotoxicity -__________ antibodies present in 70% of those diagnosed
* Occurs in 1 in 10,000 to 1 in 30,000 adults
* 1:35,000 Extensive hepatic necrosis and death possible
* Most likely immune-mediated hepatotoxicity -Immunoglobulin G antibodies present in 70% of those diagnosed
99
Volatile Agent Induced Hepatitis: National Halothane Study
| •Classic presentation of VA associated hepatitis = ?
fever, anorexia, nausea, chills, myalgias, rash, fever, arthralgia, and eosinophilia followed by jaundice 36 days later
100
Volatile Agent Induced Hepatitis: National Halothane Study
| •Risk factors = ?
```
PRIOR EXPOSURE!
age >40 years old
obesity
female gender
Mexican ethnicity (chromosomal vulnerability)
genetic susceptibility
multiple brief procedures within brief duration of time
enzyme induction
```
101
Volatile Agent Induced Hepatitis: Immune theory
* Cytochrome P450 2EI oxidizes each anesthetic (except for sevoflurane) to yield highly reactive intermediates that bind covalently (acetylation) to a variety of hepatocellular macromolecules
* Altered hepatic proteins may trigger an immunologic response that causes massive hepatic necrosis
102
Volatile Agent Induced Hepatitis:
| All IAs except? Because?
except for sevoflurane
103
Volatile Agent Induced Hepatitis: Metabolism of Volatile Agents
•Halothane _% metabolized
•Halothane 15-20% metabolized
104
Volatile Agent Induced Hepatitis: Metabolism of Volatile Agents
•Enflurane _% metabolized
•Enflurane 2.5-3% metabolized
105
Volatile Agent Induced Hepatitis: Metabolism of Volatile Agents
•Sevoflurane* _% metabolized
*chemical structure of sevoflurane prevents metabolism to a acetyl halide
•Sevoflurane* 2-5% metabolized
| *chemical structure of sevoflurane prevents metabolism to a acetyl halide
106
Volatile Agent Induced Hepatitis: Metabolism of Volatile Agents
•Isoflurane _% metabolized
•Isoflurane 0.2-2% metabolized
107
Volatile Agent Induced Hepatitis: Metabolism of Volatile Agents
•Desflurane _% metabolized
•Desflurane 0.02% metabolized
108
Volatile Agent Induced Hepatitis: Metabolism of Volatile Agents
•N2O _%
•N2O 0.004% (reductive metabolism GI tract)
109
Halothane: Drug Interactions
• Myocardial depression exacerbated by ?
• What may cause BP instability?
Beta-adrenergic blockers and calcium channel blockers
| Tricyclic antidepressants and MAO inhibitors
110
Halothane: Drug Interactions
| • _____________ use has resulted in serious ventricular dysrhythmias.
Aminophylline
| *tx asthma
111
Halothane: Contraindications =?
* Patients with unexplained liver dysfunction, following halothane exposure
* Pre-existing liver disease
* Hypovolemia
* Aortic stenosis
* Patients with pheochromocytoma
* Malignant Hyperthermia – Halothane the most potent trigger of all the volatile agents
112
Most potent MH trigger of all the volatile agents =?
Halothane
113
Mild myocardial depression (dose dependent) in what IAs?
Iso, Des, and Sevo
114
What VAs can overdose result in CV collapse?
ALL
115
Mild Beta Adrenergic stimulation cause by what IAs?
• lowers BP due to decreased SVR
• lowers left stroke volume by 15-30%
Iso, Des, and Sevo
116
IAs causing increased right atrial pressure (CVP)?
Iso, Des, Halothane
117
Rapid increases in concentration in what IAs => transient increase in HR, blood pressure and catecholamine levels?
Iso and Des
118
Isoflurane: Structure
Halogenated methyl ethyl ether
Isoflurane
F H F
CCOC
F Cl F
119
Isoflurane: Odor = ?
Pungent odor-NOT FOR PEDs INDUCTION!!!
120
Isoflurane:
MAC =
BG partition coefficient =
MAC – 1.2 (high potency)
| BG partition coefficient –1.4 (intermediate solubility)
121
Isoflurane: Cardiovascular Effects
| CO is maintained by what response?
Increased HR via partial preservation of baroreceptor reflex
122
Isoflurane: Cardiovascular Effects
| Elderly and neonates may experience what kind of response?
Decrease HR
123
What IA increases cutaneous and skeletal muscle blood flow?
Isoflurane
124
Overpressure results in ?
Initial increased HR and BP, followed by decreased SVR and BP?
125
What IA is NOT recommended during cardiac ablation and why?
Isoflurane, because it increases the refractoriness of accessory pathways and AV conduction so can interfere with interpretation of electrophysiologic studies.
126
Isoflurane: Cardiovascular Effects
| • ________ coronary arteries
Dilates
127
Anesthetic Pre-conditioning
• Brief exposure to what agents?
• Activate KATP channels - effect?
iso/des/sevo
hyperpolarizing effect (negative inotropic/relax vascular smooth muscle) which protects the tissue to subsequent ischemic episode
128
Coronary steal syndrome
• In theory…may cause what and how?
• What IAs can cause this?
ischemia in patients with CAD by taking away from preferential dilation
ALL *any that dilate coronary arteries*
129
Isoflurane: Respiratory Effects
| • Tachypnea more or less pronounced at >1 MAC compared w/other agents
less
130
What IAs blunt response to hypoxia and hypercarbia?
Halothane, Iso, Des, Sevo....well all of them really impact respiratory drive!?!
131
What IAs are a bronchodilator?
Halo, Iso, Sevo
132
What IAs decrease Vt and Mv, increasing PaCO2?
Halothane, Iso, Des, Sevo, En (N2O n/c to resting PaCO2)
133
What IAs result in tachypnea?
N2O, Halothane, Iso, Des, Sevo....all of them really (Hal, Meth, En mostly according to the chart?)
134
Isoflurane: Cerebral Effects
• Increased CBF and ICP at concentrations > _ MAC (effects greater/less than halothane and Enflurane?)
• Effects reversed by _________________
1, less
| hyperventilation
135
Isoflurane: Cerebral Effects
• Increases or decreases CMRO2?
• Electrically silent EEG at _ MAC (thought to provide cerebral protection during ischemic periods)
• Reduces CMRO2, electrically silent EEG at 2 MAC (thought to provide cerebral protection during ischemic periods)
136
Isoflurane: Cerebral Effects
| • Enhances/diminishes CSF reabsorption
• Enhances CSF reabsorption
137
What IAs increase CBF and ICP?
N2O, Halothane, Iso, Des, Sevo, En ..... so all!
138
What IAs increase IOP?
Halothane
139
What IAs decrease CMRO2?
Iso, Des, Sevo the most, but also Halothane & En
140
What IA maintains total hepatic blood flow – vasodilator of hepatic circulation
• Has beneficial effects on hepatic oxygen delivery
• This is a relatively new finding…some texts will still say that portal vein flow is reduced – 2003 study refutes
Isoflurane
141
Renal Effects of IAs?
| How can this be limited?
Decease in RBF, GFR, and urine output (r/t decreased CO and BP)
Can limit by pre-op hydration!
142
Isoflurane-Forane: Metabolism & Toxicity
• Slowly metabolized __%
• Principal end product = ?
```
0.2%
Trifluroacetic acid (very small amount)
```
143
Trifluroacetic acid is the end product of what IAs?
Halothane, Iso, En
144
IAs with a CI of MH?
ALL!
145
Isoflurane-Forane: Hepatotoxicity is common or rare?
| • Does not produce fluoride ion at clinically significant levels
rare
146
Isoflurane-Forane: Does or does not produce fluoride ion at clinically significant levels
does not
147
Desflurane: Structure
Fluorinated methyl ethyl ether (Similar in structure to isoflurane)
Desflurane
F H F
CCOC
F F F
148
Desflurane: Odor
Pungent odor
| *caution with peds and stg II w/ asthmatics
149
```
Desflurane:
• Vapor pressure =
• MAC =
• Blood/gas partition coefficient =
• _______ wash-in (induction) and wash-out (emergence).
```
* Vapor pressure close to atmospheric (669), need special vaporizer.
* MAC 6.0 (low potency)
* Blood/gas partition coefficient 0.42 (low solubility)
* Rapid wash-in (induction) and wash-out (emergence).
150
The TEC 6 Vaporizer:
• Electrically heated to ?
• Pressurized to
```
39 degrees C
1520 mmHg (to keep it in the liquid phase)
```
151
Desflurane: Cardiovascular Effects
• CO remains unchanged or slightly depressed at
_-_MAC
1-2 MAC
152
Desflurane: Cardiovascular Effects
| • Baroreceptor reflex ______, resulting in?
intact
| rise in HR
153
Desflurane: Cardiovascular Effects
• Rapid increases in concentration: transient increase in HR, blood pressure and catecholamine levels (greater or less than with isoflurane?)
greater
154
Desflurane: Cardiovascular Effects
| • Does or does not increase dilate coronary arterial blood flow
does not
155
Desflurane: Respiratory Effects
| Profound apnea at _-_ MAC
1.5-2.0 MAC (i.e. assist)
156
Desflurane: Respiratory Effects
| >_% = Irritating to airways, salivation, breath-holding, coughing, and laryngospasm
6% (1 MAC)
157
Desflurane Cerebral Effects
•Increases CBF and Cerebral oxygen consumption increased or decreased?
•Effect not usually seen until >_ MAC
•Neuro keep less than _ MAC (Can lower ICP with hyperventilation)
decreased
1 MAC
1 MAC
*Carrie -> 1 MAC and hypervent.
158
Desflurane: Neuromuscular Effects
| • Dose dependent decrease in response to ?
TOF and tetanic PNS
159
Desflurane: Hepatic Effects =?
No evidence of hepatic injury following it use.
160
IAs that potentiate NM blocking agents?
Des
161
Desflurane: Biotransformation and Toxicity
• < _% metabolized
• Serum and urine inorganic fluoride levels (, =) preanesthetic levels?
0.1%
| ~=
162
Desflurane: Biotransformation and Toxicity
| • Carbon monoxide results from degradation of Des by ?
dried out CO2 absorbents
| • high flows left on all weekend now 1st case on Monday morning
163
Carbon Monoxide concentrations of all IAs relative to each other =
Des>Enf & Iso> Halo & Sevo
164
Sevoflurane: structure
the only fluorinated methyl isopropyl ether
___C
COC
___C
165
Sevoflurane: Odor
| Good or bad for peds?
Non-pungent, sweet oder
| *idea for peds
166
Sevoflurane = fast on, fast off (T/F)
T
167
Sevoflurane: Cardiovascular Effects
| •SVR, and artBP decline more or less than isoflurane or Desflurane?
•SVR, and artBP decline slightly (less than isoflurane or Desflurane)
168
Sevoflurane: Cardiovascular Effects
| •HR, MAC, &CO?
•Little rise in HR (only significantly increases at >1.5 MAC), CO not as well maintained.
169
Sevoflurane: Cardiovascular Effects
| HR only significantly increases at >_ MAC), __ not as well maintained.
>1.5 MAC
| CO
170
Sevoflurane: Cardiovascular Effects
| •Coronary steal?
•No evidence of coronary steal
171
Only common agent that does not increase CVP is?
Sevoflurane (halothane, des, iso increase)
172
IA that does not cause SNS activation response with increases in concentration?
Sevoflurane
173
IA with minimal airway irritation (best among all current anesthetics)?
Sevoflurane
| *best choice for asthmatics
174
Sevoflurane: Respiratory Effects
| • Profound apnea at _-_ MAC
1.5-2.0 MAC (i.e. assist)
175
IAs causing profound apnea at 1.5-2.0 MAC (i.e. assist)?
Des, Sevo
176
What is the best IA for neuro?
Sevoflurane
177
Sevoflurane: CNS Effects
• Increases or decreases cerebral metabolism O2 consumption?
• Increases or decreases CBF < Halothane
• Inc. ICP
• Effect not usually seen until >1 MAC.
• Response to CO2 & autoregulation maintained at 1.5%
* Dec. cerebral metabolism O2 consumption (> Halothane)
* Inc. CBF (< Halothane)
* Inc. ICP
* Effect not usually seen until >1 MAC.
* Response to CO2 & autoregulation maintained at 1.5%
178
Sevoflurane: CNS Effects
Decrease in cerebral metabolism O2 consumption < or > Halothane?
Increase in CBF < or > Halothane?
Decrease in cerebral metabolism O2 consumption > Halothane
Increase in CBF < Halothane
179
Sevoflurane: CNS Effects
• Effect not usually seen until >_ MAC.
• Response to CO2 & autoregulation maintained at __%
> 1 MAC
| 1.5%
180
COMPOUND A mostly produced by degradation of what IA?
Sevo
181
Sevoflurane: Metabolism & Toxicity
• Compound A is formed when Sevo interacts with?
• Cpd A not nephrotoxic alone but undergoes bioactivation thru glutathione conjugation and metabolism of its conjugates to produce reactive thiol may mediate renal toxicity
soda or baralyme (esp. at low flows) *not a metabolite
182
Sevoflurane: Metabolism & Toxicity
| Is Cpd A a metabolite of Sevo?
NO!
183
Sevoflurane: Metabolism & Toxicity
• Cpd A is or is not nephrotoxic alone
• Undergoes bioactivation thru glutathione conjugation and metabolism of its conjugates to produce reactive _____ that MAY mediate renal toxicity
is not
| thiol
184
Sevoflurane: Metabolism & Toxicity
| • Higher concentrations of compound A in presence of?
```
Baralyme
Soda lyme
Low flow anesthesia
High sevo concentrations
Long duration
```
* No clinical evidence of injury
* Renal injury demonstrated in rats
* Eger et al. demonstrated transient changes in renal function has not been reproduced by subsequent studies
185
Sevoflurane: Metabolism & Toxicity
To minimize exposure to Compound A, sevoflurane exposure should not exceed _ MAC∙hours at flow rates of _ to < _ L/min. Fresh gas flow rates of
2 MAC∙hours
1 to < 2 L/min
<1 L/min
186
Sevoflurane: Metabolism & Toxicity
| As a rule of thumb, Carrie just keeps FGF > _ L/min when using Sevo!
2
187
Sevoflurane: Metabolism & Toxicity
In addition to Cpd A, what is another renal concern?
What is the mechanism of action behind this concern?
* Another concern is production of free fluoride ions = tubular injury and loss of concentrating ability – ARF.
* Fluoride levels can rise close to levels associated with risk – although clinical evidence of injury does not exist
188
Sevoflurane: Metabolism & Toxicity
• metabolized in liver P450
• _-_% undergoes biodegradation
• Can or cannot be metabolized to trifluroacetylated liver proteins? (= ___ risk of “halothane hepatitis”)
Sevoflurane: Metabolism & Toxicity
• metabolized in liver P450
• 3-5% undergoes biodegradation
• Cannot be metabolized to trifluroacetylated liver proteins – 0 risk of “halothane hepatitis”
189
Sevoflurane: Contraindications = ?
* Patients with impaired kidney function (relative contraindication)
* Malignant Hyperthermia (absolute contraindication)
190
Enflurane: structure
| • Isomer of ?
Halogenated methyl ethyl ether
Enflurane
F F F
CCOC
ClF F
Isomer of Isoflurane
191
Enflurane: Odor
• Mild, sweet, ethereal odor
192
Enflurane: Adverse Effects
• Myocardial contractility depression
• Sensitizes heart to dysrhythmic effects of ?
• Hypoxic drive = ?
• Marked respiratory depression, at _ MAC, PACO2 60 mm Hg.
epinephrine
abolished
1 MAC
193
Depressed mucociliary function caused by what IA?
Enflurane
194
Enflurane effects on CSF?
Increases secretion of CSF and resistance to CSF outflow.......DO NOT USE FOR NEURO!
195
Enflurane EEG effects?
* EEG changes, tonic-clonic seizures.
* Exacerbated by high concentration, hypocapnia, and repetitive auditory stim.
* Hyperventilation not recommended.
196
Enflurane: Biotransformation & Toxicity
• High or low metabolism (_-_%)?
• Fluoride production much more or less than Methoxyflurane?
• Detectable renal dysfunction likely or unlikely?
Enflurane: Biotransformation & Toxicity
• Low metabolism (2-5%).
• Fluoride production much less than Methoxyflurane.
• induces defluorination, may be clinically significant in rapid acetylators.
• Detectable renal dysfunction unlikely
197
Enflurane: Contraindications?
* Avoid in patients with preexisting kidney disease or impairment
* Avoid in patients with known or suspected seizure disorders
* Avoid in patients with increased intracranial pressure
* Triggering agent for Malignant Hyperthermia
198
OSHA & Waste Gases:
• No worker should be exposed to more than __ppm Halogenated agents in O2 or air
• No more than __ppm Halogenated agents if used with Nitrous Oxide
• No more than __ppm of N2O
• Highest levels found where?
* No worker should be exposed to more than 2ppm Halogenated agents in O2 or air
* No more than 0.55 ppm Halogenated agents if used with Nitrous Oxide
* No more than 25ppm of N2O
* Highest levels found between anesthesia machine and wall
199
Xenon- FYI
•Inert gas, odorless, nonexplosive
•BG partition coefficient = 0.115
•MAC 63-71%
•Does expand closed air spaces < N2O though
•CV stability, blunt SNS response to pain, analgesia, hypnosis
•Costly
•Limited experience in patients at this time
FYI
