Week 5 Inhalation Anesthetics Flashcards
A single specific anesthetic receptor has yet to be found
True or false
True
_______ sites of action and proteins targets probably exist
Multiple
We do know that once a ________ _______ of a drug enters the brain and spinal cord, loss of consciousness ensues
Critical concentration
Level of anesthesia is related to ______ concentration
Alveolar
(Measured through end tidal)
Partial pressure of anesthetic in ______ is assumed to be the same as in the ______
This is why the dose of an individual drug is expressed in terms of ______ ______ ______ (_____)
Lungs, brain
(ex: end tidal sevo 1.8, assume its 1.8 in the brain)
Minimum alveolar concentration (MAC)
MAC is the minimum alveolar concentration required to produce anesthesia in ____ % of the population upon surgical stimulation
Gauged by _________
50%
Lack of movement
We start with a drug supplied as a ______, vaporizing it in an anesthesia machine, and delivering it to the patient’s _______ and other tissues via the ______
Liquid
Brain
Lungs
Main factors influencing ability to anesthetize patients are (5)
Technical or machine specific
Drug related
Respiratory
Circulatory
Tissue related
Primary factors that influence ABSORPTION of inhalation anesthetics (5)
SOLUBILITY of the anesthetic drug
in the blood
Uptake into the blood
Alveolar-to-venous blood partial-
pressure difference
Ventilation
Cardiac output
Factors that may affect UPTAKE early in anesthetic administration (2)
-Drug solubility in the rubber and
plastic machine parts (minimal)
-Total machine liter FGF of gases
chosen
How do FGFs affect uptake early in anesthetic administration?
-Low flows = slows delivery of anesthetic gases
-High flows = speeds process up
What is FGF of 1L O2, 1L air?
2L FGF
Carrier gases (O2, air, N2O that flow through vaporizers to pickup and carry volatile anesthetics into patient)
Blood/Gas solubility
An indicator of the _______ of uptake and elimination
Speed
Blood/Gas solubility
Reflects proportion of anesthetic that will be ______ in the blood, and not readily enter the ________
Soluble, tissues
Blood/Gas solubility
Increased solubility means anesthesia will be achieved________ (faster/slower)
Slower
Blood/Gas solubility
The ______ soluble the drug, the slower the brain and spinal cord uptake drug, anesthesia is achieved slower
more
Sevoflurane MAC
2
Isoflurane MAC
1.15
Nitrous oxide MAC
105
Desflurane MAC
5.8
Sevoflurane Blood/Gas Coefficient
0.6
Isoflurane Blood/Gas Coefficient
1.4
Nitrous oxide Blood/Gas Coefficient
0.47
Desflurane Blood/Gas Coefficient
0.42
Blood/Gas Solubility
Agents with ____ solubility ( ____ blood/gas coefficient) leave the blood quickly and enter the tissues, producing a rapid anesthetic state
low, low
ex: Desflurane (0.42- lower solubility) faster than Isoflurane (1.4- higher solubility)
The ventilation effect:
The ______ and more _______ a patient breathes or is ventilated, the _______ the patient loses consciousness at the start of anesthesia and emerges at the end
faster, deep, faster
(can get more volatile agent into and out of patient faster)
The ventilation effect
__________ in pediatrics results in faster loss of consciousness
Crying
_______ -_______ deficits or poor lung function hinder inhalation drug administration
Ventilation-perfusion
During first minutes of gas administration, a higher concentration of drug, or loading dose, is delivered to speed initial uptake
Commonly referred to as what?
Overpressuring or the concentration effect
__________ can speed the effect of slow agents (i.e. Isoflurane)
Overpressuring
In overpressuring, after the first few minutes the dose is ________ to the normal maintenance level
decreased
__________ administration of a relatively slow agent with a faster drug in high concentrations can speed the onset of the slower agent
Referred to as what?
Simultaneous
Second Gas Effect
Example of the Second Gas Effect
Isoflurane with nitrous oxide
Sevoflurane with nitrous oxide
(pedi induction)
Second Gas Effect
Mechanism of second-gas effect not clearly definitive but traditionally explained as the _______ volume uptake of nitrous oxide concentrating the other alveolar gases
large
The second gas effect occurs during ____________ as well
emergence
(if want to get agent off faster, can use second gas effect)
Oil/Gas Solubility Coefficient is an indicator of _________
potency
Oil/Gas Solubility Coefficient
Higher the __________ the more potent the drug
solubility
Oil/Gas Solubility Coefficient
High solubility reflects high _____ solubility
lipid
Oil/Gas Solubility Coefficient
Highly ______ -soluble drugs tend to be the most potent
lipid
Oil/Gas Solubility Coefficient
__________ (99) is the most potent, _________ (1.4) is the least
Isoflurane, nitrous oxide
Oil/Gas Solubility Coefficient
Sevoflurane
50
Oil/Gas Solubility Coefficient
Isoflurane
99
Oil/Gas Solubility Coefficient
Nitrous Oxide
1.4
Oil/Gas Solubility Coefficient
Desflurane
18.7
Two major influences on anesthetic uptake and distribution:
- Blood leaving the lungs deliver anesthetic to _______ compartment first vs _______ compartment
The _______ the administration the greater the saturation in all compartments
- During induction, ________ in cardiac output slow onset
_______ cardiac output removes more anesthetic from the lungs, which slows the rise in lung and brain concentrations
- central, peripheral
Longer,
(the longer infused, closer to equilibrium in the central and peripheral compartments)
- Increases
Increased
(removing volatile anesthetic from lungs will slow the rise in lung concentration, and ultimately brain concentration)
__________ metabolized
Minimally
Possible toxic _________ formation is not currently a clinical issue
metabolite
_______ was known to be hepatotoxic
Halothane
(repeated exposure = higher risk for hepatitis)
Although sevoflurane is metabolized ___ - ___ % releasing free _____ ions, no related clinically significant toxicity has been noted
5-8%
flouride
Anesthetic metabolism
Sevoflurane: __ - __ metabolized
Nitrous oxide: < __ % metabolized
Isoflurane: < __ % metabolized
Desflurane: < __ % metabolized
5-8%
< 1%
< 1%
< 0.1%
Temperature
_________ results in slow induction, with slower emergence due to increased tissue capacity and slower perfusion
Hypothermia
Temperature
Hyperthermia ________ anesthetic requirements and cardiac output, leads to _______ induction
Increases, slower
Emergence
In general the ______ an anesthetic is administered, the slower the patient emerges
longer
Emergence
Greatest (slowest) with the _____ soluble agent, ________, and less with _______ and ________
most, isoflurane
sevoflurane, desflurane
Emergence
Residual anesthetic has been shown to remain in the body for ________ following a routine anesthetic
several days
Diffusion Hypoxia
During emergence, when _____ concentrations of a rapid insoluble anesthetic (________) have been given and then stopped, the drug exits the body quickly through the _____ and is replaced by _____ soluble nitrogen in the air
This results in a transient _______ of normal respiratory gases
Administration of _____ % oxygen will prevent this potential problem
high
Nitrous oxide
lungs
less
(N20 leaves, nitrogen replaces it)
dilution
(brief hypoxic episodes)
100%
ex: running 50% N20, turn off N2O, turn on 100% O2 = wont see diffusion hypoxia
________ diffuses into air-containing cavities in the body
Nitrous oxide
Examples of Nitrous oxide diffusing into air-containing cavities of in the body (7)
air embolism
pneumothorax
acute intestinal obstruction
intraocular air bubbles
pneumoperitoneum
ENDOTRACHEAL TUBE
LMA
*If running N2O for prolonged time, check cuff pressures; can trend upward over course of case
uptake ________ in children than in adults
faster
child’s ______ alveolar ventilation per weight accounts for faster uptake
higher
infants and children have higher cardiac outputs per weight than adults
This would normally slow onset
Cardiac output is distributed to __________ group in children, as well as ______ muscle mass, means more agent delivered to vital organs
Vessel-rich
lower
Risk factors for emergence agitation (4)
Difficult parental separation
behavior
Anxiety
Age 2-5
Postop pain
Drugs that reduce incidence of emergence agitation (4)
Fentanyl
DEXMEDETOMIDINE (gold standard)
Propofol
Ketamine
Do midazolam, serotonin antagonists, or parental presence upon emergence have an effect on emergence agitation?
No
Obesity
Some clinicians prefer __________ because of its low solubility and lipophilicity
This appears to promote a slightly _______ recovery
desflurane
faster
Obesity
Long procedures and morbid obesity allow for an ______ in deposition of anesthetics into fat
This may ________ recovery
increase
prolong
Pregnant women have a ______ (higher/lower) minute ventilation
higher
Pregnant women have a ______ (higher/lower) cardiac output
higher
In pregnant women, uptake of anesthetics is ___________ to nonpregnant women
similar
(Because higher minute ventilation [speeds up onset] and higher cardiac output [slows onset] cancel eachother out)
Right-to-left shunt
______ (speeds/slows) induction of anesthesia
Slows
b/c shunted blood mixes with and dilutes blood coming from ventilated alveoli, resulting in reduction of alveolar partial pressure of anesthetic
takes longer to build up concentration
Right-to-left shunt
_______ or part of anesthetic ( ____ lung ventilation)
Pathologic (one )
Right-to-left shunt
Shunted blood mixes with and ________ blood coming from ventilated alveoli resulting in ________ of alveolar partial pressure of the anesthetic
dilutes, reduction
= slows induction of anesthesia (takes longer to build up concentration)
Left-to-Right shunt
Causes anesthetic partial pressure in mixed venous blood to _______ (increase/decrease) more rapidly than it would in absence of shunt
increase
Left-to-Right shunt
Slightly _________ rate of anesthetic delivery or uptake into the brain, muscle, and other tissue is a result
increased
Cardiopulmonary bypass
________ characteristics of modern membrane oxygenators are more limited than lungs
transfer
Cardiopulmonary bypass
During bypass _______ concentrations of volatile anesthetic agent are given compared to that which is required when administered by normal lung inhalation
higher
Ether was made in ______
Sevoflurane was made in ______
1842
1995
All commonly used inhalation agents are ______ or _______ ________ with no more than 4 carbon atoms
ethers (R-O-R)
aliphatic hydrocarbons
Halogenation of hydrocarbons and ethers influences: (4)
Anesthetic potency
Arrhythmogenic properties
Flammability
Chemical stability
Halogenation entails the addition of: (4)
Fluorine
Chlorine
Bromide
Iodine
Volatile anesthetics interact with main repolarizing cardiac ________ channels, as well as with _____ and _____ channels at slightly higher concentrations
potassium
calcium
sodium
(cardiac depressants)
Inhibition of the ion channels by volatile anesthetics alters both ______ ______ shape (triangulation), and _______ _______ conduction
This may facilitate arrhythmogenesis by volatile anesthetics per se, and is potentiated by _____________
action potential
electrical impulse
catecholamines
Flammability is reduced and chemical stability enhanced by substituting _____ atoms with ______
hydrogen, halogens
Desflurane contains _____ as its only halogen
This results in a molecule that strongly resists _________
fluorine
biodegradation (stable molecule)
Do we know the exact mechanism of action of inhalation anesthetics?
No, exact mechanisms remain elusive
A popular hypothesis of MOA proposes that general anesthesia results from direct multisite interactions with multiple and diverse _____ _______ in the brain
ion channels
MAC is useful to compare the _______ of inhalation agents
potencies
MAC is where ____ % of subjects will not respond to a painful stimulus
A response is defined as _____, ______ movement of the head or extremities
50%
gross, purposeful
The MAC represents the _____ dose of the anesthetic
required
MAC requirements is ____ dependent
Peaks at ___ months of age, and gradually ______ with age
age
6 months, decreases
(6 month old = highest MAC requirement)
The MAC at which 50% of subjects will respond to command “open your eyes”
MAC-awake
(about 1/3 of MAC)
MAC necessary to block adrenergic response to skin incision
MAC-BAR (block adrenergic response)
(About 1.6 times higher than MAC)
From a clinical standpoint patients usually require anesthetic concentrations that exceed the MAC by ___ - ____ % (____ - ____times MAC)
20-30%
1.2-1.3
(If running primarily on volatiles)
Increased age
Reduces MAC
Hypothermia
Reduces MAC
Administration of sedative hyptonics
Reduces MAC
Coadministration of other anesthetics
Reduces MAC
Alpha-agonists
Reduces MAC
Opioids
Reduces MAC
Acute ethanol consumption
Reduces MAC
Hypoxemia
Reduces MAC
Hyponatremia
Reduces MAC
Anemia (less than 4.3 mL O2/dL blood
Reduces MAC
Hypotension (MAP < 50 mmHg)
Reduces MAC
Pregnancy
Reduces MAC
Lithium
Reduces MAC
Young age
Increases MAC
Hyperthermia
Increases MAC
Hyperthyroidism
Increases MAC
Hypernatremia
Increases MAC
Acute administration of CNS stimulant drugs
Increases MAC
Red hair in females
Increases MAC
Chronic alcohol abuse
Increases MAC
Duration of anesthesia
No effect on MAC
Gender
No effect on MAC
Hypocapnia or hypercapnia
No effect on MAC
Metabolic alkalosis
No effect on MAC
Hypertension
No effect on MAC
Hyperkalemia or hypokalemia
No effect on MAC
Hypermagnesemia
Reduce MAC
MAC is expressed as a ___ of ___ atmosphere
% of 1 atmosphere
When combined with 60-70% N20, MAC ______
decreases
______ is the primary site of action of volatile anesthetics, which exhibit ____ -_______ effects with significant clinical considerations
CNS
dose-dependent
Inhalation anesthetic (iso, sevo, des) effect on
Cerebral metabolic rate of O2 (CMRO2) and cerebral blood flow (CBF)
Decrease CMRO2
Increase in CBF (dose-dependent)
N20 effect on
Cerebral metabolic rate of O2 (CMRO2) and cerebral blood flow (CBF)
Increases CMRO2
Increases CBF
Volatile anesthetics produce dose dependent _____ in CBF
This effect depends on the balance between vasoconstrictive properties, due to ____ -________ coupling, and the direct cerebral ________ action of the anesthetics
increase
flow-metabolism
vasodilatory
(decreases in CMRO2 and increases in CBF = uncoupling occurs)
When vascular resistance is decreased, CBF, cerebral blood volume, and CSF pressure _______
increase
(need to be aware of these changes in high risk patients)
Uncoupling of cerebral blood flow (CBF) and metabolism
When ______ in CMRO2 are accompanied by _______ in CBF, uncoupling is said to occur
decreases, increases
Uncoupling of cerebral blood flow (CBF) and metabolism
This response does not seem to occur with ___ MAC or less of ______ or _________
1.0
desflurane, isoflurane
(if keep volatiles < 1 MAC can keep this phenomenon from occurring; use a “balanced technique” to prevent uncoupling, ex: volatile anesthetic with remifentanil or a different opioid of choice)
Cerebral vascular responsiveness to CO2
Normal physiologic response of the cerebral vasculature to CO2 is to _____ in the presence of hypocapnia and ___________ with hypercarbia
vasoconstrict
vasodilate
Cerebral vascular responsiveness to CO2
In patients in which a reduction in intracranial volume is desired (ex: increased ICP) partial pressure of arterial carbon dioxide should be maintained around ____ to _____ mmHg
Effective for approximately ____ -____ hours
30-35 mmHg
4-6 hours
(decrease CO2 with hyperventilation = vasoconstriction)
Done in neurosurgical patient population
Electroencephalogram (EEG)
Volatile agents produce dose-dependent _______ of EEG activity
suppression
Electroencephalogram (EEG)
Burst suppression can be achieved at ____ - _____ MAC with desflurane, and ____ MAC with isoflurane or sevoflurane
(Burst suppression = EEG temporarily stops recording)
1.5-2
2
Evoked Potentials
Volatile agents and N2O produce a dose-dependent _________ in evoked potentials
___________ evoked potentials most sensitive
___________evoked potentials most resistant
reduction
Visual-evoked potentials
Brainstem-evoked potentials
Evoked potentials
An increase in latency or decrease in amplitude of evoked potentials can reflect _____, or may be secondary to the __________
ischemia
volatile agent
(issue b/c monitoring these as part of maintaining safety of patient during procedure = may actually reflect ischemia OR be result of volatiles anesthetic)
Work to provide anesthetic that will allow for optimal monitoring without dampening signals more than necessary (balanced technique, TIVA)
Emergence and neurologic assessment in adults
_______ emergence in neurosurgical patients can have devastating consequences
Makes ___________ assessment difficult
Delayed
Neurologic
(ex: want to do a neuro assessment after wake-up from carotid endartectomy, craniotomy)
Emergence and neurologic assessment in adults
Conflicting data on superiority of _____ vs _______ anesthetics
TIVA vs inhalation
Emergence and neurologic assessment in adults
Are inhalation agents still widely used in most neurosurgical procedures?
Yes
(want a technique that allows for prompt wakeup with minimal long term complicating effects of neuro assessment; ex: avoid benzos so not lingering around)
Developmental neurotoxicity
FDA advised that repeated or lengthy use of general anesthetics and sedative drugs in children younger than _____ or in pregnant women during the ________ trimester may affect the development of the child’s brain
3
third
Developmental Neurotoxicity
Recommended to keep anesthesia and surgery as _____ as possible and to use _____-acting drugs and/or a combination of general anesthesia and multimodal anesthesia including systemic analgesics and local or regional anesthesia to ______ overall drug dosages
short, short
reduce
Emergence phenomenon in children
Occurs after ______ and ______ in preschool-aged children
sevoflurane, desflurane
Emergence phenomenon in children
Usually lasts about ___ minutes and will ______ _______ once the child eliminates more of the anesthetic
15
resolve spontaneously
Treatment for Emergence phenomenon in children
Dexmedetomidine
Cardiovasular system
All capable of altering _______ (dose-dependent)
Hemodynamics
Cardiovascular system
Extent volatiles alter hemodynamics related to preoperative and intraoperative factors:
- _______ status classification
-Co-administration of: (4)
Physical status classification
Co-administration of:
vasoactive drugs
opioids
benzodiazepines
propofol
Cardiovascular system
Isoflurane, desflurane, sevoflurane all _______ CO and CI in a dose dependent fasion
reduce
Cardiovascular system
Isoflurane, desflurane, and sevoflurane all _____ MAP via _____ in SVR
N2O activates the ________ and increases _______
reduce, reduction
symapthetic nervous system
SVR
(can have more stable hemodynamic pattern in certain patients if decrease volatile agent and use N20 as strategy to achieve full MAC of anesthesia for patient)
Cardiovascular system
Dose dependent changes in heart rate noted
Rapid increases in inhaled concentrations of _______, and especially _______ can lead to increase in HR and BP
_______ activation due to an irritant effect
isoflurane
desflurane
symapthetic
Cardiovascular system
Sevoflurane has _________ HR effects
Minimal
Cardiovascular system
As MAC hours of anesthesia increase, CI and HR _____ slightly
increase
(for long procedures, increase over time)
Cardiovascular system
____________ is a reduction in the perfusion of ischemic myocardium with simultaneous improvement of blood flow to ________ tissue
Coronary steal
nonischemic
Cardiovascular system
Coronary steal:
Blood is taken from the “_____” and given to the “______”
Poor, rich
Cardiovascular system
Coronary steal
When _______ is maintained, a steal phenomenon is ablated
Maintain within ___ % of baseline to avoid coronary steal
normotension
20%
(coronary steal is not an ideal situation because want ischemic area to receive blood flow)
Cardiovascular system
Arrhythmias
Have both _________ and _________ actions
proarrhythmic and antiarrhythmic
Cardiovascular system
Arrhythmias
All ______ QT interval
prolong
Cardiovascular
Arrhythmias
All agents with the exception of _______ and probably ________ are conducive to the development of ________ and disturbances in ____ nodal conduction
isoflurane, desflurane
bradycardia
AV
Cardiovascular
Arrhythmias
When fibers become ischemic or injured, volatile agents are prone to producing ________ excitation
reentrant
Cardiovascular
Arrhythmias
Ability of volatile agents to reduce the quantity of catecholamines necessary to evoke arrhythmias is commonly, but inaccurately, called _______
More accurate to describe as an __________
Keep epinephrine dose less than _____ mcg/kg
sensitization
adverse drug reaction
10
In normal adults, PVR has a small _____ with N2O
May become clinically significant with preexisting ____________ which results in larger increases in PVR
Increase
Pulmonary hypertension
Volatile agents ________ pulmonary artery pressure
decrease
Responsiveness to CO2 is _______
depressed
Tidal volume _______ as concentration of agent increases
reduces
Compensatory increases in RR as a response to decreased TV is not sufficient to prevent elevations in ______
CO2
___________ helps to overcome respitatory-depressant effects of volatile agents
Surgical stimulation
________ of renal circulation generally remains intact
Autoregulation
Reductions in SBP are accompanied by compensatory _______ in renal vascular resistance
Can still result in ________ in GFR
This may contribute to the commonly seen intraoperative _____ in urinary output
decreases
decline
reduction
FDA guidelines recommend caution with use of ___________ in renal insufficient patients
Past concern with ___________’s degradation within anesthesia circuits by older CO2 absorbents
This resulted in the production of potential toxin referred to as ________, and dictated fresh gas flow rates
sevoflurane
sevoflurane’s
Compound A
millions of sevoflurane anesthetics have failed to demonstrate any significant untoward renal outcomes
Volatile anesthetics have the potential to impair liver function
________ in particular is associated with significant risk of postoperative liver failure = __________
Halothane, halothane hepatitis (especially with repeat exposure)
Extremely rare for _______, _______, and ________ to produce clinically significant liver damage
isoflurane, sevoflurane, desflurane
All volatile agents produce dose-dependent ________ of skeletal muscle, as well as additive effect with ________ and _________ muscle relaxants
relaxation
depolarizing and nondepolarizing
Neuromuscular sytems
Multifactorial mechanism:
_______ neural activity in the CNS
________and _________ effect at NMJ
Reduced
Presynaptic and postsynaptic
Malignant hyperthermia
Which volatile agents are capable of triggering?
All volatile agents except N2O
Medications used to treat malignant hyperthermia in adults and children
Raynodex and dantrolene
Pregnant patients have a ____ to ____ % chance of developing a medical condition that requires a general surgical intervention during pregnancy
0.2% to 0.75%
Elective surgery should be _______ until after delivery in pregnant women, and nonurgent surgery should be performed in the _____ trimester
delayed
second
_____ exposure has been linked to both spontaneous abortion and _____ fertility in workers
N2O, reduced
