|
|
Pharmacology: Inhalation Anesthetics
|
|
This is an edited and abridged version of:
Pharmacology: Inhalation Anesthetics by Jch Ko, DVM, MS,
DACVA
Oklahoma State University -
Veterinary Medicine, February 8, 2002
© 1996-2002, Oklahoma State University College of Veterinary
Medicine, all rights reserved
Overview
Commonly Used Inhalation Anesthetics
- Isoflurane
- Sevoflurane
Less Commonly Used Inhalation Anesthetics
- Methoxyflurane
- Halothane
- Desflurane
- Nitrous oxide
Clinical
Considerations of Selecting an Inhalation Agent
Metabolism
|
Percentage
of Anesthetic Recovered as Metabolites |
|
|
Methoxyflurane |
Up to 50% is metabolized by the liver and kidneys |
|
Halothane |
Up to 20-25% is metabolized by the liver and kidneys |
|
Sevoflurane |
3.0 % is metabolized by the liver and the kidneys |
|
Isoflurane |
0.17% is metabolized by the liver and the kidneys |
|
Desflurane |
No documented metabolism |
|
Nitrous Oxide |
No documented metabolism |
|
·
Major elimination route of inhalation anesthetics
is via respiration. ·
For a patient with hepatic dysfunction, the choice
of inhalation anesthetic is isoflurane, sevoflurane or desflurane - less
liver metabolism. ·
Although nitrous oxide has almost no liver
metabolism, it is not commonly used in veterinary anesthesia, see below for
details |
|
Anesthetic
Potency
- What
is MAC?
Ø
MAC is the minimal alveolar concentration of an
anesthetic (in volume %) at which 50% of the patients will not respond to
painful stimuli (e.g., surgery-skin incision, tail clamp).
Ø
MAC is used to compare inhalation anesthetic potency.
(Similar to mg/kg for injectable anesthetics).
Ø
Clinically, achieving a surgical plane of anesthesia usually
requires 1.2 to 1.5 times MAC to ensure 99.9% of the patients will not respond
to the surgical stimulation.
- The lower the MAC value, the more
potent the anesthetic agent.
Ø
MAC values from the table below demonstrate that
methoxyflurane is the most potent and nitrous oxide is the least potent
inhalant anesthetics. Halothane, isoflurane and sevoflurane are somewhere
in between. Sevoflurane is less potent than halothane and isoflurane.
Ø
The clinical implication of anesthetic potency is mainly
related to the cost of the inhalant. The less potent the inhalant
anesthetic, the higher the percentage of the inhalant anesthetic agent that
will have to be used for anesthesia maintenance, and therefore the higher cost.
|
Comparison
of anesthetic potency of inhalant anesthetics using MAC (volume %). |
||||
|
|
Mouse |
Rat |
Dog |
Human |
|
Methoxyflurane |
--- |
--- |
0.23 % |
0.16 % |
|
Halothane |
--- |
--- |
0.87 % |
0.74 % |
|
Isoflurane |
--- |
--- |
1.28 % |
1.15 % |
|
Sevoflurane |
--- |
--- |
2.1-2.36% |
1.7% |
|
Desflurane |
--- |
--- |
7.2% |
|
|
Nitrous
oxide |
--- |
--- |
188 % |
105 % |
|
|
||||
- Nitrous
oxide is not commonly used in veterinary anesthesia for the following
reasons:
Ø
Weak analgesic property when used alone in domestic animal
species (MAC is roughly 200% - it is twice as potent in humans).
Ø
Its use together with a primary inhalation anesthetic (such
as halothane, isoflurane) only reduces the amount of primary inhalation
anesthetic by 25% to 30% of the control value (using halothane or isoflurane
alone) at the most. This may not significantly reduce the amount of the primary
anesthetic.
Ø
Because nitrous oxide is a weak analgesic agent and must be
used in high concentrations, the inspired oxygen concentration is
proportionally reduced. This is not suitable for patients with pulmonary
diseases that may require as much as 100% inspired oxygen to maintain
acceptable blood oxygenation.
Ø
The use of nitrous oxide requires a higher fresh gas flow
rate than would be used with oxygen alone. Accordingly the total amount
of the primary anesthetic that is vaporized is increased - more anesthetic is
wasted, and therefore cost is increased.
Ø
Nitrous oxide diffuse rapidly into closed gas cavities
within body, at a faster rate than nitrogen diffuses out of the cavity,
resulting in either an increase in volume or pressure. Patients with
gastric or intestinal distension or pneumothorax will suffer further.
Ø
Risk of diffusion (dilutional) hypoxia. This occurs at the
time when the nitrous oxide is turned off and the patient is disconnected from
the breathing circuit and starts to breathe room air (21% oxygen). Nitrous
oxide is usually used in large volumes during anesthesia (> 50%), and when it
is turned off its uptake is reversed and it moves from the blood to the
alveoli. Thus, during the first 5 to 10 minutes after discontinuing the nitrous
oxide, the volume moving into the lung is large and dilutes the oxygen in the
alveoli. If breathing room air, this may result in hypoxia. To avoid dilutional
hypoxia, the animal should breathe 100% oxygen for the first 5-10 minutes after
discontinuing nitrous oxide.
Rate of
Induction, Rate of Change in Anesthetic Depth, and Rate of Recovery
- Rate
of induction, change in anesthetic depth, and rate of recovery are related
to the blood/gas solubility of each inhalation anesthetic.
- The
higher the blood/gas solubility, the slower the induction and recovery
rates.
- The
higher the blood/gas solubility, the slower rate of change in depth of
anesthesia.
|
|
|||
|
Comparison
of solubility, vapor pressure, and use of preservatives |
|||
|
Anesthetic Agent |
Blood/gas |
Vapor |
Preservatives |
|
Methoxyflurane |
12 |
23 |
Required |
|
Halothane |
2.4 |
243 |
Required |
|
Isoflurane |
1.4 |
240 |
None |
|
Sevoflurane |
0.69 |
160 |
None |
|
Desflurane |
0.42 |
664 |
None |
|
Nitrous
oxide |
0.47 |
--- |
None |
|
|
|||
- Based on the table
above, induction, recovery and changes in anesthetic depth are slowest with
methoxyflurane and fastest with nitrous oxide and desflurane.
- Mask induction is
impractical using methoxyflurane because of its high solubility and
therefore very slow speed of induction. In addition, attempts to speed
induction with high anesthetic concentration is limited by the maximum
concentration achievable with methoxyflurane (approximately 3% - due to
its low vapor pressure). Clinically we often use isoflurane for mask
induction. With sevoflurane’s lower blood/gas solubility, it may
provide an advantage for mask induction.
- Because of its low
solubility, nitrous oxide is used to facilitate the induction and rate of
change in anesthetic depth when used together with one of the primary
anesthetics such as halothane or isoflurane (this is called the 2nd gas
effect).
- Because of its low
blood/gas solubility, isoflurane is used extensively in avian anesthesia
for rapid induction and recovery. Sevoflurane may be even better for
avian species once it becomes more commonly used.
Cardiopulmonary
Aspects
Overall, all inhalant anesthetics depress cardiopulmonary
function in a dose-dependent manner as shown by the decreases cardiac output,
blood pressure, respiratory rate and increase in partial pressure in CO2
concentrations.
- Myocardial depression:
Halothane > or = methoxyflurane > isoflurane =
sevoflurane = desflurane > N2O
- Reduction
in cardiac output:
Halothane > or = methoxyflurane > isoflurane =
sevoflurane = desflurane > N2O
- Reduction
in systemic vascular resistance:
Isoflurane = sevoflurane = desflurane >
methoxyflurane > or = halothane > N2O
- Respiratory
depression:
Isoflurane = sevoflurane = desflurane >
methoxyflurane > halothane > N2O
Cost
- Desflurane > sevoflurane > isoflurane >
halothane
- Methoxyflurane is relatively
expensive due to lack of production (it is no longer being produced by the
company that produced it for many years; another smaller company may have
picked up production, but availability is questionable).
- Isoflurane has lost its
patent and the cost has decreased significantly in the last few years.
- Sevoflurane is a new agent
and costs about four times more than isoflurane when compared on an ml/ml
basis.
- Desflurane requires a special
vaporizer (due to its high vapor pressure) that is only compatible with
the newest human anesthetic machines - both the vaporizer and the
anesthetic machines are very expensive. Desflurane itself costs about the
same as sevoflurane. Because of the equipment considerations, only
sevoflurane is currently making inroads into the veterinary market.
Clinical Use
of Inhalant Anesthetics
Inhalant anesthetics are used for
induction and maintenance of general anesthesia.
- Induction Advantages:
Ø
It offers the advantage of accurately controlling anesthetic
depth during induction with the safety of being able to discontinue the
administration of the inhalant anesthetic immediately if problems arise.
Ø
Furthermore, should problems arise, the inhalant anesthetic
(sevoflurane, isoflurane or halothane) can be eliminated quickly through ventilation.
Ø
High-inspired oxygen is usually provided with inhalant
anesthetic during induction.
- Induction Disadvantages:
Ø
The pungent smell of the isoflurane or halothane may prompt
the animal to hold their breath during induction and therefore prevents the
uptake of the inhalant anesthetic and slows the speed of induction. (This can be remedied through use of an
induction chamber.)
Ø
Sevoflurane is supposed to be the best for inhalant anesthetic
induction…less irritation to the airway and faster speed of induction. It
has been the main inhalant anesthetic for using in human infants and children
for mask induction.
Ø
Pollution of the work environment during induction. Waste
inhalant anesthetic gas may cause headaches and other health problems. (This can be controlled by using a properly
functioning waste gas evacuation system.
Many choices are available.)
Ø
It is not suitable for healthy, unpremedicated dogs because
of the relatively slow speed of induction via inhalant anesthetic. The
induction is also frequently accompanied with vocalization, excitement,
defecation, urination, and vigorous struggling (if you are strong enough to
hold the struggling dog and willing to clean up the mess after the induction,
you may consider this induction method as suitable for your clinic).
- Maintenance Advantages:
Ø
Protection of the airway - since almost all patients
anesthetized with inhalation anesthetic are intubated.
Ø
The depth of anesthesia during maintenance is easily
controlled by adjusting the vaporizer output, ventilation pattern and the total
flow rate.
Ø
High-inspired oxygen is usually provided with inhalant
anesthetic during the maintenance. This will augment the oxygen content
of the blood. It is especially helpful to the patient with low oxygen-carrying
capacity (patients with anemia or respiratory dysfunction).
Ø
Rapid recovery when compared to most of the injectable
combinations. (Inhalant anesthetics are mostly eliminated through ventilation,
whereas injectable anesthetics rely on the liver and kidney for
metabolism/elimination).
Chamber
Induction:
- Suitable in small intractable animals.
- Provides a "hands
free" induction with minimal physical restraint to the patients. Safe
to the patient as well as personnel.
- 5% isoflurane or 8%
sevoflurane with high flow rates of oxygen (5+ lpm) is used until the
animal losses its righting reflex. The animal is then taken out of
the chamber, placed on a facemask, and anesthetic administration is
continued until the patient is unconscious and ready for endotracheal
intubation.
Facemask /
Nosecone Induction:
- Select a tight-fitting facemask and place it on
the face of the animal. Use the smallest mask possible to minimize dead
space ventilation. (Nosecones work
best for rodents.)
- Suitable in birds, neonate
ruminants or foals, debilitated dogs or cats, or in healthy dogs or cats
following profound premedication (acepromazine,
opioids, or alpha-2 agents).
- Facemask induction is not
practical in adult large animals (equine, bovine, porcine).
- Facemask induction usually
begins with 4-5% of halothane, isoflurane, or 5-8% sevoflurane and
continues until the animal is unconscious and able to be intubated.
- Using facemask induction in
healthy animals with isoflurane without profound premedication usually
results in excitement.
- Sevoflurane is markedly
better for mask inductions than isoflurane
- Debilitated
patients (diseased dogs, cats, birds, other small ruminants or foals).
Ø
Mask induction usually begins with 2-3% of halothane,
isoflurane, or sevoflurane and continues until the patient is unconscious and
ready for intubation
Ø
Debilitated patients are already depressed by the disease and
they are more sensitive to the inhalation anesthetics, therefore reducing the
inhalant anesthetic % is usually a good idea.
Ø
Debilitated animals are less likely to become excited or
struggle during induction.
Maintenance
of General Anesthesia
- All major inhalant anesthetics (methoxyflurane,
halothane, isoflurane and sevoflurane) are maintained with 1.2 to 1.5
times MAC for general anesthesia.
- Premedication with a
tranquilizer or an opioid will reduce the maintenance concentration of
inhalation anesthetics.
- In
general, inhalation anesthetics are maintained with following
concentrations:
Ø
Methoxyflurane: 0.5 - 1.5%
Ø
Halothane: 0.75 - 2.0%
Ø
Isoflurane: 1 - 2.5 %
Ø
Sevoflurane: 2.5 - 4.0%
Factors
Affecting MAC
Although
all inhalant anesthetics are maintained with 1.2 to 1.5 times MAC for
general anesthesia, factors that affect MAC have to be considered during the
maintenance of general anesthesia.
- Factors that decrease MAC:
Ø
Hypotension
Ø
Anemia ( PCV < 13%).
Ø
Hypothermia
Ø
Metabolic acidosis
Ø
Extreme hypoxia (PaO2 < 38 mmHg)
Ø
Age: older animal require less anesthetic
Ø
Premedication (opioids, sedatives, tranquilizers)
Ø
Local anesthetics
Ø
Pregnancy
Ø
Hypothyroidism
- Factors that increase MAC:
Ø
Increasing body temperature – increases cerebral metabolic
rate of brain
Ø
Hyperthyroidism
Ø
Hypernatrimia
- Factors NOT affecting MAC:
Ø
Type of stimulation
Ø
Duration of anesthesia
Ø
Species - MAC varies by only 10-20% from species to species
Ø
Sex
Ø
PaCO2 between range of 14-95 mmHg
Ø
Metabolic alkalosis
Ø
PaO2 between range of 38-500 mmHg
Ø
Hypertension
Ø
Potassium – no effect