Inhalant Anesthesia

Horatiu V. Vinerean DVM, DACLAM

Director, Laboratory Animal Research
Attending Veterinarian

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Inhalation Anesthesia - History

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 Inhalation Anesthesia
• This is the technique of administering anesthetic
agents to the animals via the lungs.
• This consists of a volatile agent being vaporized
by oxygen in a vaporizer and then being
administered to the patient through an
anesthetic breathing circuit.

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Vaporization of volatile anesthetics
• A vapor is a gas below its critical temperature. Both
liquid and gaseous phases exist simultaneously and in a
closed container a state of equilibrium is attained when
the number of molecules leaving the liquid phase
equals the number of molecules re-entering it.
• In this situation, the vapor is said to be saturated and
the partial pressure that the vapor exerts is the
saturated vapor pressure (s.v.p.) that depends only
upon the nature of the liquid and the temperature.

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 Anesthetic Uptake
• The depth of anesthesia is related to the partial
pressure of anesthetic agents in the brain. This is in turn
related to the partial pressure in the blood and this, in
turn, is related to the partial pressure of the agent in
the alveoli of the lungs.
• The mechanism for a gas to dissolve in the patients
blood and other tissues relies on pressure and pressure
gradients between the tissues or phases.
• For an anesthetic action to occur the anesthetic agent
must be capable of crossing the blood brain barrier to
the central nervous system (lipid soluble).
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Physics laws of anesthetic uptake
• Dalton's Law of Partial Pressure: The constituent gases
in gas mixtures act independently of each other and
exert the pressure that each would have exerted in
isolation in the given volume. Thus the pressure exerted
by a mixture of gases is the sum of the individual
pressures exerted by each gas. The component of total
pressure that each gas exerts is termed its partial
pressure.
• Graham's Law: The rate of diffusion of gases through
certain membranes is inversely proportional to the
square root of their molecular weight.
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Physics laws of anesthetic uptake
• Fick's Law of Diffusion: The rate of diffusion is
proportional to the concentration gradient.
• Partition Coefficient: The ratio of the amount of the
solute present in equal volumes of the two phases, at a
stated temperature and when the two phases are in
equilibrium. It is independent of pressure. This
partition, or distribution coefficient can be used to
describe the uptake and distribution of anesthetic
gases.

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Physics laws of anesthetic uptake
• The greater the pressure gradient between the alveoli and
the brain, the faster induction will occur. Since the blood
flow in the body tissues varies there is a certain order in
which the body tissues are saturated with anesthetic agent.
• During induction of anesthesia, the anesthetic agent
molecules will move along a pressure gradient as follows:
» Inspired Gas > Alveoli > Tissues with high blood flow and /
lipid (brain, heart, kidney, etc.) > Skeletal muscle > Fat
• The brain and other blood flow rich tissues will reach
equilibrium with the alveoli fairly quickly, while
equilibration in muscle and fat will take longer.
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Physics laws of anesthetic uptake
There are other factors which will influence the rate at which
the anesthetic partial pressure in the brain reaches the
pressure in the alveoli:
• Ventilation: As ventilation increases, the amount of gas
reaching the alveoli increases and therefore the amount of
gas taken up and carried up to the brain increases.
• Cardiac Output: the effect of cardiac output on anesthetic
uptake is perplexing. If there is more blood passing through
the lungs to pick up the anesthetic agent it would seem
logical to assume that a patient with a high cardiac output
would be induced quickly but this is not true.

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Physics laws of anesthetic uptake
• High cardiac output removes the anesthetic agent so
quickly from the alveoli that the partial pressure in the
alveoli does not have time to increase and neither does
that in the blood. This is one reason why it is difficult to
induce an excited patient with an inhalation agent (and
why premedication and/or intravenous induction agents
are used in healthy or excited patients). In ill or shocked
patients, anesthetic uptake is faster, because of the
reduced cardiac output in these patients. Induction of
anesthesia will be faster than expected and the patient
may `go too deep' sooner. (In sick patients the vaporizer
should not be turned too high).

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Physics laws of anesthetic uptake
• Solubility: If the anesthetic agent is highly fat soluble then the fat
in the body will take up much of the anesthetic agent and slow
down the rate of equilibration of the brain partial pressure with
that of the alveoli.
• This has the effect of slowing down the speed of induction
and is why it takes longer to induce a patient with ether
(highly fat soluble) compared to isoflurane (less fat
soluble).
• The fat solubility of the anesthetic agent also affects the
recovery rate. The adipose tissue can `hold‘ more of a
highly fat soluble agent and its longer, gradual release
from the tissues down a concentration gradient via blood
to the lungs can slow recovery
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Physics laws of anesthetic uptake
• Delivered Concentration: when inducing an animal with an
inhalation agent, the vaporizer is set at a level much higher
than that is required for maintenance. This helps to increase
the pressure gradient and the `driving force' and get a more
rapid uptake. Induction occurs more quickly.
• Recovery: the tension gradients are the reverse of those of
induction. Recovery cannot be accelerated because inspired
tensions cannot be decreased below zero.

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Physics laws of anesthetic uptake
• Second Gas Effect: this effect occurs when a relatively
insoluble gas is present in high concentrations with a gas of
greater solubility e.g. N2O and halothane in oxygen. The
relatively insoluble gas (because the partial pressure is
greater) crosses into the bloodstream quickly.

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 Inhalation Anesthetics
Ideal Characteristics of Inhalant Anesthetics
• Stable, nonflammable, non-explosive, high
potency, low solubility in blood, nonirritating, not
metabolized, cardiovascular and respiratory
systems unaffected, compatible with other drugs,
easily delivered and affordable.
Advantages of Inhalant Anesthetics
• Concentrations can be continuously measured
• Most potent: Methoxyflurane
• Least potent: Nitrous oxide
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 Inhalation Anesthetics
Minimum Alveolar Concentration (MAC)
• The MAC value is a measure of anesthetic potency and it
is inversely proportional to MAC value: an inhalant having
a low MAC value is more potent than an inhalant having a
high MAC value.
• The value given is the concentration of the inhalant
anesthetic that will prevent gross movement in response
to painful stimulus in 50% of patients (MAC50). To increase
this to 95%, just multiply the MAC by 1.5 (MAC95), this will
provide a surgical plane of anesthesia.
• MAC values do not take into consideration any pre-
medications that may have been given and they will lower
the MAC.
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 Inhalation Anesthetics

Minimum Alveolar Concentration (MAC) Values

Inhalant Anesthetic MAC

Halothane 0.8 – 0.9% both dogs and cats

Isoflurane 1.28% in dogs; 1.63% in cats

Sevoflurane 2.4% in dogs; 2.6% in cats

Desflurane 7.2% in dogs

Enflurane 2.1% in dogs

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 Inhalation Anesthetics
Factors that influence MAC
• Circadian rhythm in rats (high activity requires
higher MAC).
• Body temperature - decreased body temperature
leads to decreased anesthetic requirement.
• Age - old animals have lower MAC values versus
neonates that have the highest MAC requirements.
• Hypercarbia above 95 mmHg is depressant and
therefore will lower the MAC.

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Inhalation Anesthetics

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 Inhalation Anesthetics
• Nitrous Oxide (NO2)
• Ether
• Methoxyflurane
• Halothane
• Isoflurane
• Enflurane
• Sevoflurane
• Desflurane
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 Inhalation Anesthetics: Nitrous Oxide
• Weak anesthetic, mainly used in humans.
• Cardiovascular and respiratory depression is
minimal.
• Low blood/gas solubility- rapid uptake/elimination
• Use 2nd gas effect to increase uptake of other
inhalants (animals > 2kg)

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 Inhalation Anesthetics: Nitrous Oxide
• Supplied as a combination of liquid and gas in
cylinders the same size as used for oxygen (the
room temperature is below the critical temperature
for nitrous oxide). The pressure within nitrous oxide
cylinders is 750 psi (the saturated vapor pressure),
and the pressure gauge will indicate this pressure
while there is still liquid in the cylinder to vaporize.
Once the liquid has been used the pressure gauge
will indicate a falling pressure to `empty' over the
following 5-10 minutes depending on the flow.
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 Inhalation Anesthetics: Ether
• Explosive Not recommended because explosive at
concentrations used to produce anesthesia and
highly irritating to respiratory system

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 Inhalation Anesthetics - Methoxyflurane

• Low volatility, high blood solubility- safe for use in non-

precision systems, fruity smell.
• Very potent ED50 less than 0.25%
• Extensively metabolized
• Renal toxicity in people
• Causes nephrotoxicity in F344 rats and induces Diabetes
Insipidus (from fluoride ion-induced renal damage).
• Respiratory depression: significant
• Cardiovascular effects: mild (less myocardial sensitization
than halothane)
• Not available in the US.
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 Inhalation Anesthetics: Halothane

• Good potency, low blood/gas solubility high

volatility, produces anesthesia rapidly.
• Dose dependent respiratory depression.
• Myocardial muscle depression and relaxation of
vascular smooth muscle.
• Sensitizes heart to catecholamines.
• Malignant hyperthermia.

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 Inhalation Anesthetics: Isoflurane
• Isoflurane is a stable compound which does not break
down on contact with soda-lime or presence of light.
• Relatively insoluble leading to fast inductions and
recoveries. It is non-flammable and has a saturated vapor
pressure similar to halothane.
• It does have a fairly pungent odor and so should be
introduced to the patient slowly for a mask induction.
• Isoflurane is more of a respiratory depressant than
halothane, resulting in hypoventilation and hypercapnia.

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 Inhalation Anesthetics: Enflurane

• Discontinued in veterinary medicine due to

sevoflurane and desflurane.
• Chemical isomer of Methoxyflurane.
• Cardiovascular and respiratory depression similar to
Isoflurane.
• Seizure like muscle contractions with deep surgical
level.

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 Inhalation Anesthetics: Sevoflurane
• Low solubility in blood- rapid equilibration and
precise and rapid changes in depth.
• Very rapid induction and recovery and mild odor
are associated with less struggling during mask
induction.
• Cardiovascular and respiratory effects-similar to
Isoflurane, not significantly metabolized.
• Decomposes in soda lime producing a toxic
compound (olefin – compound A).
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 Inhalation Anesthetics: Desflurane

• High molecular stability, low toxicity

• Lowest blood/gas coefficient of all inhalant
anesthetics (0.42) - fastest induction onset.
• Low boiling temperature - requires a special heated
vaporizer.

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 Anesthetic Machines

• Can be divided into components:

• The high pressure system
» Oxygen source
» Pressure Gauges
» Pressure regulators
• The low pressure system
» Flowmeters
» Flush Valves
» Vaporizers
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 Anesthetic Machines – High Pressure
Oxygen source:
• Vital for the life of the patient and used to vaporize
the volatile anesthetic agent.
• Stored in cylinders (E size, 700 liters) on the
anesthetic machine itself or it can be delivered
through a pipeline system from a bank of larger
tanks (H size 7,000 liters).
• The pressure in oxygen cylinders is 2,200 psi. Since
the oxygen is a compressed gas when the cylinder is
half empty the pressure will read 1,100 psi 30
 Anesthetic Machines – High Pressure
Pressure Gauges:
• There is one gauge, which shows the cylinder
pressure, and a second gauge to show the line
pressure.
• A pressure gauge is often added to the breathing
circuit to show how much pressure is in the circuit,
and how much pressure is applied to the patient's
airway when positive pressure ventilation is
performed.
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 Anesthetic Machines – High Pressure
Pressure Regulators (Pressure Reducing Valves)
• Used to bring the line pressure to between 40 and
50 psi.
• The reducing valves also serve to keep the pressure
in the line constant since the pressure within a
cylinder of oxygen will vary depending on how full
the cylinder is.

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 Anesthetic Machines – Low Pressure
Flowmeters:
• Necessary to measure how much gas is being supplied to the
breathing circuit and to the patient. There are various designs of
flowmeters with different type of indicators to indicate the flow.
• Flowmeters with aluminum balls should be read from the middle of
the ball whereas bobbin type indicators should be read from the top
of the bobbin.
• Each flowmeter is calibrated for the particular gas it is to measure
because the flow and calibration depends on the viscosity and
density of the gas. Do not try to pass another gas through a flow
meter designed for different gas (O2 versus CO2).
• Flow is measured in liters/minute.
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 Anesthetic Machines – Low Pressure
Flush Valves
• Oxygen flush valve delivers oxygen from the
reducing valve to the breathing circuit without
going through the vaporizer.
• This allows the circuit to be flushed with 100% O2.
• An oxygen flush will deliver the gas to the patient's
airway at 40-50 psi with a flow of 30 L/min, and
could seriously damage the lungs.

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 Anesthetic Machines – Low Pressure
Vaporizers
• The fresh gas vaporizes the volatile agent used to
anesthetize the patient. Specially designed vaporizers fitted
to the anesthetic machine do this.
• There are two positions in which the vaporizer can be
placed: either vaporizer IN Circuit (VIC) or vaporizer OUT of
Circuit (VOC).
• Vaporizers are constructed of a highly conductive metal so
that heat from the surrounding is transferred to the
volatile agent in order to supply the latent heat of
vaporization.
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 Anesthetic Machines – Low Pressure
Vaporizers
• Once the gas enters the chamber, it usually flows over a
wick, which dips into the volatile agent, to enable the gas
to be fully saturated.
• A wick keeps the surface area of the volatile agent constant
and so it does not matter what level of volatile agent is
present in the chamber. So long as it is not empty or
overfull, the vaporizer will give the concentration indicated
on the dial.

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 Anesthetic Machines – Low Pressure
Vaporizers
• Care should be taken not to tip the anesthetic machine
over an angle of 45° or to shake it vigorously during
transport. Anesthetic liquid may enter the bypass channel
of variable bypass vaporizers, and potentially lethal
concentrations can be delivered to the next patient.
• If the anesthetic machine has been knocked over run
oxygen through the vaporizer with the control dial off for
about 15 minutes (outside!) to vaporize any agent in the
bypass. If the anesthetic machine is to be transported it is
best to empty the vaporizer completely.
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 Rodent Anesthesia

• Isoflurane is the method of choice for rodent anesthesia. It

is safe and very easy to use. Induction and awakening are
rapid. Gas waste must be scavenged properly.
• Anesthesia Induction:
• Place the animal in the induction chamber.
• Adjust the flowmeter to 0.8–1.5 L/min.
• Adjust the isoflurane vaporizer to 2%–3%.

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 Rodent Anesthesia
• Anesthesia maintenance:
• Use the nosecone connected to the non-rebreathing circuit
and adjust the flowmeter to 400–800 mL/min.
• Adjust the isoflurane vaporizer to ~ 1.8%.
• Prevent heat loss until the animal recovers.

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 Rodent Anesthesia - Non-rebreathing Circuit
• Fresh gases from the anesthetic machine pass into an
inspiratory tube and the patient breathes from that tube.
Exhaled gases pass into an expiratory tube.
• In this circuit, the pause the patient takes before inhalation
is the crucial moment. During this time the fresh gas
entering the circuit does not enter the patient, but enters
the expiratory limb and flushes the exhaled gases further
down this limb until they leave the system. When the
patient takes the next breath, fresh gas is inhaled directly
from the inspiratory limb and (now fresh gas in
composition) from the expiratory limb.
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 Rodent Anesthesia - Non-rebreathing Circuit
• Thus the important point is the Total Fresh Gas Flow to the
circuit from the anesthetic machine to drive the exhaled
gases down the expiratory limb and `away' from the
patient's next breath and also the active scavenging system
used to drive the flow
• The big disadvantage is the high fresh gas flow, which can
be expensive.

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 Rodent Anesthesia - Non-rebreathing Circuit
• The advantage is that they have little resistance and are
therefore better suited for small patients, which cannot
cope with high resistance circuits while under anesthesia.
They can also have very little mechanical (apparatus) dead-
space.
• Oxygen flush devices should not be used or barotraumas
will result.

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