Volatile Anesthetics Flashcards
What are the blood:gas coefficients for:
- Desflurane
- N2O
- Sevoflurane
- Isoflurane
- Halothane
- 0.42 (1ml of gas holds more than 1ml of blood)
- 0.47
- 0.65
- 1.4
- 2.4
1ml of blood holds 1.4x as much isoflurane as does 1ml of alveolar gas = “relatively soluble in blood”
What is a solubility or partition coefficient?
different physiologic mediums (mainly gas, blood, and tissue) have different capacities for carrying an anesthetic gas
difference b/w capacities of any two given mediums expressed as a ratio
How does anesthetic solubility effect agent equilibration b/w blood and alveolar gas?
a less soluble agent equalizes blood & gas partial pressures faster than a more soluble agent
What coefficient determines speed of induction and what is the relationship b/w anesthetic solubility and induction speed?
Blood:Gas
less soluble = faster maximum is dissolved = faster CNS effect/induction
What 3 factors affect time needed for given type of tissue to reach anesthetic equilibrium
solubility
mass of tissue
perfusion rate
What partition coefficient has greatest effect on anesthetic emergence?
Fat:Blood > muscle:blood
Fat = large relative mass, low perfusion, anesthetics very soluble
Is there more or less volatile anesthetic in vapor form if the vapor pressure is high?
More?
What will happen when you fill a SEVO vaporizer (157mmHg) with ISO (238mmHg)
Higher % of ISO will be delivered
Lower vapor pressure –> lower amount of gas in vapor form –> more fresh gas flow needed
What is the second gas effect?
A large volume of alveolar gas absorption –> inc rate of uptake of companion gas
- the impact that a high concentration of N2O has on the uptake of a volatile anesthetic
- wash-in of a large volume of N2O across the alveolar membrane will reduce alveolar volume. Since the volume of the second gas has not changed, its concentration is increased. Subsequently fresh inspired gas will flow in to replace the lost volume. The net result is a higher alveolar fraction [FA] of the second gas.
What is the likely mechanism of N2O?
Antagonism of excitatory NMDA receptors
What is the effect of volatile anesthetics on CMRO2 and CBF, ICP?
dec CMRO2
(SEVO-ISO > DES»_space;> HAL)
INC CBF, ICP
(HAL»_space; DES > ISO > SEVO) from vasodilation
Mismatch = “luxury perfusion”
What are some byproducts of volatile gases when CO2 absorbent is desiccated?
CO - Desflurane
Heat - Sevoflurane
Why should total gas flow of Sevo be >2 l/min if given for prolonged periods?
Production of Compound A is increased
How can halothane, isoflurane and desflurane cause immune-mediated hepatic injury?
Trifluouroacetic acid byproducts - bind liver proteins –> haptens
ISO & DES very low hepatic metabolism = very rare
What are the effects of volatile anesthetics on:
- Hepatic blood flow
- Renal blood flow
- Bronchi
- Dec hepatic BF (HAL - most)
- Dec RBF and GFR
- Potent bronchodilators except DES = irritant
Describe the effects of N2O on:
- Cardiovascular system
- Pulmonary vascular resistance
- CMRO2
- CBF
- Muscle
- Renal BF
- Mildly depresses + stim SNS –> little if slight inc HR, BP, CO, SVR
- PVR INC
- CMRO2 INC
- CBF INC (no uncoupling)
- No muscle relaxation
- RBF dec
Who may be at risk for neurologic injury with N2O use?
B12 deficiency, homocystinuria, folic acid metabolism
- oxidizes cobalt –> inactivates B12 functions (myelination)
What are the effects of N2O on a pneumothorax, tympanoplasty graft, intravitreal gas, ETT cuff?
- double size of ptx
- displace graft
- blindness w/ intravitreal gas
- inc pressure in ETT cuff
How does altitude affect DES delivery?
Its vaporizer delivers a constant % of gas
At high altitudes, the ambient pressure is lower = partial pressure of delivered DES will also be lower
What variables augment the elimination of anesthetic gas?
high fresh gas flows low circuit volumes decreased anesthetic solubility high cerebral blood flow increased ventilation
What variables affect the rate of rise of FI of inhaled anesthetics?
fresh gas flow rate
volume of breathing circuit
gas absorption by machine/circuit
What variables affect the rate of rise of FA of inhaled anesthetics?
blood:gas partition coefficient (solubility)
alveolar blood flow (cardiac output)
anesthetic partial pressure gradient between alveoli andvenous blood
Define MAC
[alveolar] of an anesthetic at atmospheric pressure that prevents gross, purposeful movement in 50% of patients in response to surgical stimuli
End-tidal partial pressures ~= [alveolar]
What do MAC and 1.3 MAC represent on a dose-response curve?
MAC = ED50
1.3 MAC = ED95
What is MAC-awake?
0.3-0.4 MAC
What is MAC intubation?
[alveolar] that would inhibit movement & coughing during intubation
> 1MAC b/w ED95 and MAC-BAR
What is MAC-BAR?
[alveolar] prevents adrenergic response to skin incision
1.7-2.0x MAC
What things increase MAC?
- Hyperthermia
- Hyperthyroidism (severe)
- Alcoholism (chronic)***
- Cocaine (acute intoxication)
- Ephedrine (Based on studies in dogs with ephedrine infusions)
- Younger age (i.e., children)***
What decreases MAC?
- Hypothermia***
* Severe hypotension (MAP
What factors have no effect on MAC?
- Duration of anesthesia
- Gender
- Metabolic acid-base status
- Hypercapnia and hypocapnia
- Isovolemic anemia
- Hypertension
- Hypothyroidism
What is the MAC of Sevo?
2.0
What is the MAC of Halothane?
0.75
What is the MAC of Isoflurane?
1.2
What is the MAC of Nitrous Oxide?
104
What is the MAC of Desflurane?
6.0
How do volatile anesthetics affect SSEPs, VEPs and MEPs?
INC cortical latency
dec cortical amplitude in dose dependent manner
Isoflurane»_space; desflurane and sevoflurane
Under what circumstances is a volatile agent most damaging to EP monitoring?
High (>1 MAC) and changing anesthetic levels
[High] can eliminate EPs all together
50% dec in amplitude +10% inc latency is significant
How does N2O affect SSEPs and VEPs?
Profoundly depresses
What EPs are most –> least sensitive to anesthetic effects?
Most = Motor EPs Middle = cortical EPs Least = brainstem auditory EPs
What are thought to be the receptors at which volatile anesthetics produce amnesia, sedation, immobility?
GABA - excitatory
Lesser and significantly variable at NMDA receptors
What is the primary difference between N2O and volatile gases in terms of receptor effects?
N2O = primarily NMDA
Activity assoc w/ learning, memory, pain (esp chronic)
Describe the effects of isoflurane, sevoflurane and desflurane on MAP, SVR, HR and CO.
Dec MAP, SVR
Inc HR slightly (preserved baroreceptor reflex)
Preserved CO
May dec CO if LV function compromised
What happens to HR and MAP with rapid rises in isoflurane and desflurance concentration?
HTN
Tachycardia
Induces sympathetic stimulation
How do volatile anesthetics affect heart ionotropy?
Negative ionotropes
Dec LV contractility offset by dec after load from dec SVR
How do volatile anesthetics affect cardiac electrophysiology (SA node, arrhythmias etc)?
Depress SA node activity
Prolong His-Purkinje conduction
Red VF
Prolong QTc (no reports of death however)
How does N2O affect hemodynamics?
Sympathomimetic –> maintains CO with slight inc in HR, MAP
Inc pulmonary vascular resistance
Does not dec myocardial injury like other gases
What effect do volatile anesthetics have on tidal volume and respiratory rate?
Dose-dependent decrease in tidal volume
INC in respiratory rate
Overall dec minute ventilation
Pulmonary stretch receptor sensitization
Inc CO2 tension enflurane >des = iso >sevo=halothane >Nitrous
How do inhaled anesthetics affect the response to hypoxia and hypercarbia?
Dose-dependent depression (brainstem & carotid bodies)
What concentration of volatile agent may attenuate hypercapnia-induced increases in ventilator drive?
Where is the major site where volatile anesthetics attenuate the ventilator response to hypoxia?
Peripheral chemoreceptors
Halothane > enflurane> isoflurane >sevoflurane > desflurane
Which inhaled anesthetic does not provide muscle relaxation?
N2O does NOT provide an muscle relaxation
Which inhaled anestheics potentiate neuromuscular blockade and how do they do this?
ALL
Shift AChR from normal to desensitized –> weakens transmission
Spinal cord mediated - NMDA and glycine receptors
What are the effects of volatile anesthetics on RBF, GFR and UOP?
Decrease
What organ metabolizes methoxyflurane to an inorganic compound that causes renal failure?
Kidneys –> inorganic fluoride –> polyuric renal insufficiency
Propofol actually causes most cases of renal injury and failure (infusion syndrome)
What catalyzes the breakdown of sevoflurane to compound A?
Base-catalyzed reaction w/ CO2 absorbents
How does halothane cause auto-immune hepatits?
Dose-dependent
Metabolized –> trifluoroacylated molecules –> bind host proteins –> immunogenic complexes
Peds = 1:10,000 Adults = 1:200,000
Describe how N2O –> reduction in DNA synthesis and megaloblastic anemia?
inactivation of methionine synthetase –> decreases methyltetrahydrofolate and homocysteine –> tetrahydrofolate and methionine
This –> a reduction in thymidine synthesis – a key component in DNA synthesis.
What two clinical syndromes are characteristic of prolonged N2O exposure?
- Megaoblastic anemia (12-24hrs of 50%)
2. Subacute combined degeneration of the spinal cord (chronic daily use)
What volatile anesthetics release inorganic fluoride when metabolized?
Methoxyflurane, enflurane and sevoflurane
What factors increase production of Compound A nephrotoxicity?
- low fresh gas flows
- [higher] sevo
- higher absorbent temp
- absorbent dessication
What clinically is seen in fluoride nephrotoxicity?
Polyuric renal insufficiency
Normal BUN
Normal Cr
What 4 volatile anesthetic are likely to cause liver toxicity from most to least likely?
Halothane > enflurane > isoflurane > desflurane
Define the concentration effect.
greater [inspired] of inhaled anesthetic –> more rapid equilibration between the concentrations of the inspired and alveolar gases
–> upward shift of the uptake curve (alveolar fraction [FA] / inspired fraction [Fi] over time).
What are the two components of the concentration effect?
The concentrating effect - effect of lung volume on alveolar gas concentrations
- Diffusion of anesthetic from the alveoli to the blood reduces the alveolar volume –> remaining anesthetic more concentrated
- alveolar gas has a high fraction of anesthetic = more volume change, and a greater effect on overall gas concentrations.
Augmented tracheal inflow - gas absorbed from alveolar space is replaced by fresh gas that flows in from the proximal lung regions
- actual inspired volume of gas»_space;> if there is a [high] of anesthetic agent present due to this replacement
- since the new gas will contain anesthetic agent at the inspired concentration [Fi], alveolar gas will have a higher [FA] than would be predicted by simply removing the absorbed gas from the alveolar gas.
What is the clinical significance of the concentration effect?
only clinically significant when nitrous oxide is being administered in very high concentrations - it affects its own uptake
The concentrations of other modern volatile agents are not high enough for the concentration effect to play an important role in their uptake. This difference is why the increase in [FA]/[Fi] is more rapid for nitrous oxide than desflurane, even though they have similar solubility in blood.
Name five properties that make nitrous oxide uniquely different to other inhaled anesthetics.
- not a halogenated hydrocarbon
- gas at ambient temperature
- MAC >100 = much less potent, NOT used as the sole anesthetic
- Much less soluble than all other inhaled anesthetics, except desflurane.
- only inhaled agent that provides analgesia
- only inhaled agent that does not cause significant uterine relaxation
- inactivates methionine synthase, which regulates vitamin B12 and folate metabolism and converts homocysteine to methionine –> worsen a pre-existing B12 deficiency
- may inc risk of PONV
Name three phenomena that occur with the onset or discontinuation of nitrous oxide.
- rate of rise of inc in the [alveolar] of inhaled anesthetic relative to the inspired concentration (PA/Pi) plotted against time is steep during first few minutes
- A concentration effect with high inspired concentrations of N2O (e.g. 70%) - Initial uptake of N2O is so rapid –> concentrate the gases that remain in the alveoli = shrink the total lung volume = second gas effect when used with another gas (sevo)
- outpouring of large volumes of N2O –> diffusion hypoxia by directly oxygen in the alveoli. First 5-10 minutes after nitrous oxide is discontinued.
Name 6 situations in which nitrous oxide is contraindicated
- venous air embolism and pneumothorax
- intracranial air (pneumocephalus following dural closure)
- pulmonary air cysts
- intraocular air or injected gas bubbles (i.e., SF6)
- tympanic membrane grafting
- obstructed bowel with air-fluid levels
- air embolism risk (e.g. posterior fossa craniotomy, laparoscopic surgery).
How does a liquid differ from a gas in regards to compressibility?
liquid is not very compressible
How is a gas different from a vapor?
A vapor may go from liquid to gas and can exist alongside its corresponding liquid
A vapor is a gas, but a gas is not necessarily a vapor
- some gases cannot be liquefied at room temperature; (nitrogen and oxygen)
A vapor is a gas below its critical temperature
How does temperature affect equilibrium vapor pressure of a liquid?
Vapor pressure is directly proportional to temperature
If the number of gas molecules and temperature are held constant, and the volume increases, what happens to the pressure?
PV = nRT
If the number of gas molecules and the temperature are held constant, and the pressure increased, then the volume must decrease by an inverse proportion
Why does an E cylinder of N2O contain liquid and gas, whereas an E cylinder of oxygen contains only gas?
The critical temperature O2 = -116°C = gas at room temperature.
N2O critical temperature = 36.5°C
N2O may be liquefied if temperature is kept below 36.5°C = E-cylinder contains both liquid and gas forms
What is a vapor’s critical temperature?
temperature above which further increasing the pressure is not effective in turning the vapor back into a liquid
What does the vapor pressure associated with a liquid volatile agent depend on?
the agent itself and temperature
Why does desflurane require its own special vaporizer?
its boiling point, which is near room temperature, is much lower than the other agents.
How does barometric pressure affect boiling point of a liquid?
A decrease in barometric pressure will cause the liquid to boil at a lower temperature.
This is why liquids boil at lower temperatures at high altitudes, creating more vapor
What is Volume %?
Vol % = (partial pressure due to vapor/ total ambient pressure) x 100 %
represents a relative ratio of gas molecules in a mixture, whereas partial pressure represents an absolute value measured in mmHg
Clinically, anesthetic potency and uptake are directly related to partial pressure, but only indirectly related to Vol %
What is the definition of latent heat of vaporization?
energy required to transform a liquid –> vapor phase
Why do vaporizers use materials of high thermal capacity?
allow for heat transfer to the liquid in order to compensate for the heat loss that occurs with vaporization (keep the liquid from cooling)
What 2 basic types of vaporizers are there?
variable bypass and measured flow
What is the splitting ratio in a variable bypass vaporizer?
The ratio of flow diverted into vaporizing chamber to become saturated with agent to the flow bypassing the chamber to dilute the saturated flow
controlled by adjusting the setting of the vaporizer’s concentration control dial to regulate the relative flow rates through the bypass and vaporizing chambers
How do vaporizers automatically compensate for changes in ambient temperature?
increasing the amount of bypass flow (increasing the splitting ratio) as temperature increases
- gas-filled bellows that expands with rising temperatures
- temperature-sensitive bypass valves
- bimetallic strips made from 2 metals with different coefficients of expansion that bend according to temperature and regulate flow
How can the hourly consumption of liquid volatile agent be approximated?
Liquid consumption in mL = 3 x Vaporizer setting in Vol % x FGF in L/min
Does the output of a vaporizer, when expressed in terms of the partial pressure of inhaled anesthetics, change with changes in atmospheric pressure?
No
saturated vapor pressure (SVP) and fraction of gas diverted to vaporization chamber are NOT affected by the ambient pressure
output Vol % of a conventional variable-bypass vaporizer calibrated at sea level will INCREASE at high altitudes and the [anesthetic agent] will exceed the [dialed-in]
How does adding air or N2O to O2 in the carrier gas affect vaporizer output in a vaporizer calibrated using 100% O2? Why?
Vaporizers calibrated using 100% O2 decrease their output slightly at low flow rates when air or N2O is added
Oxygen has a greater viscosity than air and N2O
How does the vapor pressure of desflurane compare to sevoflurane or isoflurane?
DES = high vapor pressure (681 mmHg) and is virtually boiling at room temperature
SEVO and ISO are much lower at room temperature (160 and 240 mmHg respectively) resulting in much less agent in the vapor form
What parameters are controlled in the Tec 6 vaporizer to compensate for desflurane’s unique properties?
electrically heated, pressurized device specifically designed to deliver desflurane over a wide range of environmental conditions
How does the Tec 6 vaporizer adjust for changes in fresh gas flow rates?
increases its internal working pressure in proportion to an increased fresh gas flow while keeping a constant 39°C temperature
Does fresh gas flow pass through the desflurane reservoir in a Tec 6 Vaporizer?
NO
A valve to the reservoir opens and allows pressurized vapor to leave
Using pressure as a surrogate measure of fresh gas flow rates, an electronic feedback system gathers pressure information from both limbs of this system in order to inject the proper concentration of DES into the fresh gas flow
Can the Tec 6 vaporizer be used during its warm-up period?
NO
internal shutoff valve remains closed to prevent use of the vaporizer
Why is the risk of anesthetic overdose decreased in the Tec 6 vaporizer when vaporizer is tilted?
An output valve prevents emptying of gas when powered off.
If the Tec 6 vaporizer is tilted for 10 seconds while the dial is ON and it is in operational mode, vapor delivery will be stopped, as indicated by the flashing NO OUTPUT light and auditory alarm.
Does the difference in viscosity between O2 and N2O significantly affect the delivery of desflurane delivered by the Tec 6?
low viscosity of N2O, the desflurane output DECREASES when N2O is added to oxygen (O2), but remains within 20% of the dial setting. Therefore, the differences are not significant and should have little effect in clinical practice.
What effect does high altitude have on the Tec 6 output of desflurane?
DES vaporizer dialed to 6% @ sea level and @ 10,000 feet (500 torr), the partial pressure of desflurane delivered to the patient is:
- 06 x 760 mm Hg = 45.6 mmHg DES @ sea level
- 06 x 500 mm Hg = 30 mmHg DES @ 10000 feet
Compensation is required: (Dial setting at sea level) x (760/ambient pressure torr) = the required dial setting at 10000 feet
At 10,000 feet the ambient pressure is 500 torr. 6% x (760/500) = 9% required on the dial to achieve the desired partial pressure
Setting a DES dial that has been calibrated at sea level to 6% –> lighter anesthesia at high altitude than it does at sea level
