Flashcards in Pharmacology 4 Volatile Agents Deck (125):
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
Rapid onset, rapid and predictable recovery, no residual effects on organs, easy to administer, high safety margin
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)
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
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)
Analgesia and sedation
-eyes open to command, breathe normally, tolerate mild pain (suturing)
-airway protective and other reflexes intact
-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
-associated w MAC
-no mvmt in response to surgical stimuli
-no behavioral pain response
-skeletal muscle relaxation
Medullary depression (OD)
-CV collapse (decreased BP/CO
-Respiratory collapse (apnea)
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
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
Gauging depth - clinical signs - Motor
Active expiration = light
Soft abdomen = deep
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
ASA Practice Advisory on assessing for increased risk of awareness 2005 - Pre-op Eval
*review medical records:
-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
-level of anxiety
-other potential risk factors
>cardiac, c/s, trauma, ER, paralysis, use of
MR, N2O, opioids
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
" " " - Intra-op monitoring
-Brain fxn monitoring
Gauging depth - electronically - Gas analysis
End-tidal agent - monitoring standard
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
When is inspired amt of VA more than expired?
Beginning of the case
What does halogenation do to an agent?
Using only Fluorine yields what kind of agent?
Non-flammable, low solubility, and extreme resistance to metabolism
What current VA degrades in soda lime?
What VA has the fastest onset?
Des < N20 < Sevo < Iso
Lower solubility in blood yields:
-more precise control
-favor prompt recovery
What VA is the cheapest?
Iso at 10 cents per ml
What VA is the most expensive?
Sevo at 61 cents per ml
Vapor pressure: its a gas, there isn't one
BGPC: 0.46 (fast onset)
BGPC: 1.46 (longest next to enflurane)
MAC: 1.17 % (most potent next to N2O)
BGPC: 0.42 (fastest onset)
MAC: 6.6 % (least potent)
MAC: 1.8 %
Which VA needs a heated vaporizer? Why?
Des bc Vapor pressure is 669
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
If the VA has a low MAC value...
the more potent the agent
Which agent is not stable in soda lime?
Sevo, degrades into Compound A
Which agent is the only inorganic compound?
Nitrous oxide (N2O)
In what 2 ways is nitrous oxide used?
Alone for sedation or in combination w opioids and VA to enhance GA
Is N2O flammable?
No, but supports combustion
What are advantages of N2O?
*low solubility so rapid on/off
*doesn't depress BP
*analgesic (10mg of morphine)
*additive MAC w VA
What are disadvantages of N2O?
*minimal skeletal muscle relaxation
*high volume of absorption
*decreases immunity r/t ↓ in PMNs
*causes miscarriages r/t ↓ methionine synthetase
*causes polyneuropathy and B12 inactivation =
N2O is contraindicated in what surgeries?
Some eye surgeries, pneumothorax, belly cases
What VA is an organic alkane?
Why was is taken off of the market?
20% metabolized by the liver = halothane hepatitis
What agents are Ethers?
Iso, Des, and Sevo
*most potent w MAC of 1.17%
*longest onset/offset w solubility of 1.46
*pungent, so no inhaled induction
*extreme physical stability
*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
*carbon monoxide generation in soda lime
*MAC of 1.8%
*solubility of 0.69
*metabolism 5% potential nephrotoxicity
*degrades in soda lime to compound A =
No FGF < 1 L/min and no 2 MAC hours a low flow
Name brand names for agents
Iso = Forane
Des = Suprane
Sevo = Ultane
MAC values for VA's are additive
What are the factors that decrease (modify) MAC?
Opioids - decrease MAC significantly
Age - decrease MAC with age
Pregnancy, Lidocaine, Alpha-2 agonist
What are some factors that increase MAC?
Hyperthermia, Drugs that ↑ CNS (cocaine, MAIOs, anxiety), hyperthermia, hypernatremia
What is VA MOA?
mediated at cord, supraspinally, RAS likely
What is the Meyer-Overton theory?
correlation btw lipid solubility (oil:gas partition coefficient) and VA potency
causes distortion of ion channels, AP blocked
Unlikely that voltage-gated channels plan a role in production of anesthetic state
What is the effect on ligand-gated channels?
Glutamate, glycine, and GABA may be important site (role)
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 ↓
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
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
At what MAC does cerebral vasodilation occur?
> 0.6 MAC
At what MAC is cerebral autoregulation best preserved?
at 1 MAC
Do VA's including N2O enhance CSF production?
No, they ↑ reabsorption and ↑ CSF pressure
What are the effects of VA's on MAP and how are they produced?
current VA's ↓ MAP by ↓ SVR (vasodilate)
so use some N2O w VA to ↓ drop in MAP
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
What are the effects of VA's on RAP?
Des, Iso, and N2O ↑ RAP while sevo ↓ RAP
What are the effects of N2O on PVR?
↑, more pronounced if pre-existing pulm HTN and neonates, congenital heart dz R to L shunt
Describe a spontaneously breathing pt w VA's
Higher HR, Lower CO, SVR, BP d/t higher levels of CO2 (vasodilator) and SNS stimulation
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
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
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
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)
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
What is the response to hypoxemia in VA?
0.1 MAC depresses this by 50-70%
1.1 MAC abolishes response completely
All VA's including N2O ↓ FRC
What are VA hepatic effects?
Maintain hepatic BF and venous O2 saturation
What agents have metabolites?
Iso and des have trifluoroacteic acid but remember, des has almost NO metabolism
Sevo produces hepatotoxic compound A
VA produce dose-related decreases in:
*Renal blood flow
*Urine output (d/t ↓ BF)
How do you abolish or lesson these effects?
How is Compound A formed?
When Sevo degrades in CO2 absorbent
What makes the degradation of sevo worse?
Dry granules, higher absorbent temps
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
What are the effects of VA's on skeletal muscles?
Produce some skeletal muscle relaxation
N2O does not do either!
What about MH?
All VA's and Succs can trigger MH, but NOT N2O
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
What is a good cocktail for C/S?
0.5 MAC VA + 0.5 MAC N2O
Do VA's cross the placenta?
Yes, but rapidly exhaled after birth
What do VA's do to the resistance of infection?
All but N2O > VA's inhibit WBC chemotaxis
What are the genetic effects of VA's?
*Not mutagens or carcinogens (-Ames test)
*N2O ↑ abortion/miscarriage (B12 enzyme
methionine synthetase decreased)
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
N2O and peripheral neuropathy
Long exposure = nerve degeneration
What do VA's do to total body O2 needs?
VA decrease VO2
What makes VA's resistant to metabolism?
What is the % of Iso metabolism?
What is the % of Des metabolism?
What is the type of metabolism that they undergo and what metabolite do they have in common?
Oxidation by cytochrome P450
Carbon monoxide toxicity:
Des >> Iso DEGRADATION
Caused by strong bases (KOH and NaOH)
Can not detect intraop
Cause CNS disturbances
What factors favor carbon monoxide?
Dry absorbent (prolonged high FGF)
High absorbent temp (low FGF)
baralyme > sodasorb
Metabolism of Sevo:
2-5% oxidation by cytochrome P450
Degradation of Sevo and causes:
produces compound A
*high absorbent temps
*baralyme >> soda lime
Des compensation is used on the Fabius GS bc:
Des has characteristics that affect the sensitivity of the Fabius GS flow sensor
If this is not done, what will happen?
VT readings will be higher than set VT (up to 25%)
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
List monitors that display signs of adequate ventilation in an anesthetized pt:
*Oxygen analyzer * spirometry * airway pressure * exhaled volume on monitor * gas analysis * capnography
What are common problems w spirometry?
weight/bulk close to face
peds vs adult D Lite sensor
List common problems w mechanical ventilation:
*Failure to resume or failure to initiate
***Disconnection*** most common - Y piece -
How to prevent these problems from occurring:
*If you turn off vent, keep your finger on the switch
*Use apnea alarms and DON'T silence them
List the umpteen mechanisms of circulatory effects of VA -
*direct myocardial depression
*peripheral autonomic ganglionic block
*decreased carotid sinus baroreceptor activity
*decreased release of catecholamines
*decreased calcium ion influx thru slow channels
N2O alone or w VA produces mild SNS stim:
increased, plasma catecholamines, mydriasis, increased body temp, diaphoresis, increased RAP, systemic and pulmonary vasoconstriction
N2O w opiates:
more circ depression
decreased bp, co, increased lvedp and svr
High risk factors for PONV:
3 pts; hx, gyn, breast
Medium risk factors for PONV:
2 pts: face, ear, neuro, obesity, cross eyed
Low risk factors for PONV:
1 pt: young, female, anxiety, lap chole, opioids given, case > 1 hr
What determines FGF:
the vaporizer and flow meter settings
What determines FI
FGF, circuit vol, circuit absorption
what determines FA
uptake, ventilation, and conc and second gas effects
what determines Fa
Why do we use PA as a measure of depth?
bc Pbr = Pa = FA
Why is solubility important?
The more poorly blood soluble agent has a faster speed of induction
What is a time constant and what are the %?
Capacity / flow
1 = 63%
2 = 86%
3 = 95%
There is circuit, lungs, and brain
BGSC x Content (A-V) x Q (CO)
The higher the uptake....
the slower the induction
High FA/FI ratio =
less difference btw inhaled and exhaled VA
The VRG is how much % of body wt and how much % of CO?
10 % body wt and 75% CO
What organs are in the VRG?
Brain, heart, liver, kidneys
The greater the VAlv / FRC ratio...
the faster induction
5:1 in neonates as compared to 1.5/1 in adults
What cases would it be wise to avoid N2O?
abdominal, bowel, craniotomies, sitting positions, anytime the wound is higher than the heart