INHALATION ANESTHETICS

ANDY OMEGA
Outline

 History
 Mechanism of Action
 Physical properties
 Pharmacokinetics
 Pharmacodynamics
 Effects on organ system
 Toxicity
 History

Figure 1. The history of anesthesia

Mckay Eshima R. Inhaled Anesthesia. In: Miller DR, Pardo MC, editors. Basic of anesthesia. Seventh ed. Philadelphia: Elsevier; 2018. p. 83–102.
 Physical properties

Figure 3. Molecular structures of nitrous

Figure 2. Molecular structures of potent volatile anesthetics oxide
Mckay Eshima R. Inhaled Anesthesia. In: Miller DR, Pardo MC, editors. Basic of anesthesia. Seventh ed. Philadelphia: Elsevier; 2018. p. 83–102.
Mechanism of Action

Central Nervous System

Enhancing the function

Central nervous of inhibitory ion
depression and ion channels →
channels hyperpolarization of the
neuron
 Measurable Immobility and
characteristics amnestic effects

• Their actions on the spinal cord →

Immobility inhibit nociceptive input in the
dorsal horn of the spinal cord

Amnestic • Target : amygdala, hippocampus,

effect and cortex
 Pharmacokinetics

 Figure 4. Inhalation
anesthetic from the
anesthesia machine
to the brain.

Butterworth JF, Mackey DC, Wasnick JD. Inhalation anesthetics. In: Clinical anesthesiology. 6th ed. Mc-Graw Hill; 2018.
 Factors affecting Factors affecting Factors affecting
Factors affecting
inspiratory alveolar arterial concentration
elimination
concentration (FI) concentration (FA) (Fa)
• Fresh gas flow rate • Uptake • Ventilation / • Elimination of
• The volume of • Ventilation perfusion mismatch rebreathing
breathing system • Concentration • High fresh gas flows
• Any absorption by • Low anesthetic-
the machine or circuit volume
breathing circuit • Low absorption by
the anesthetic
circuit
• Decresed solubility
• High cerebral blood
flow
• Increased
ventilation
I. Factors affecting inspiratory concentration (Fi)

 The actual composition of the inspired gas mixture depends mainly

on the fresh gas flow rate, the volume of the breathing system,
and any absorption by the machine or breathing circuit
 The higher the fresh gas flow rate, the smaller the breathing
system volume, and the lower the circuit absorption, the closer the
inspired gas concentration will be to the fresh gas concentration
 Clinically, these attributes translate into faster induction and
recovery times.
II. Factors affecting alveolar concentration (FA)

A. Uptake
• The concentration of a gas is proportional to its partial pressure → Henry law
• The alveolar partial pressure determines the partial pressure of anaesthetic in the
blood and the brain.
• The partial pressure of the anaesthetic in the brain is proportional to its brain tissue
concentration → clinical effect

The greater the

difference
The greater the between The slower rate
uptake inspired and of induction
alveolar
concentration
 The three factors affecting uptake

1. Solubility in blood

The higher The greater The greater its Alveolar partial

the the uptake by the pressure rises to
blood/gas anesthetic’s pulmonary a steady state
coefficient solubility circulation more slowly
Table 1. Partition coefficient of volatile anesthetics at 37˚C
2. Alveolar blood flow

The rise in
Cardiac Anesthetic alveolar
The induction
output uptake partial
is delayed
increases increases pressure
slows

The rate of rise in alveolar
Low-output states
concentrations increased
Predispose patients to
overdosage with soluble
agents
3. The partial pressure difference between alveolar gas and
venous blood
The gradient depends on tissue uptake

The transfer of anesthetic from blood to tissues is determined by three factors :

Tissue/blood partition coefficient

Tissue blood flow

The difference in partial pressure between arterial blood and the

tissue
 Table 3. Tissue groups based on perfusion and
solubilities

Figure 5. The uptakes of individual tissue groups

Butterworth JF, Mackey DC, Wasnick JD. Inhalation anesthetics. In: Clinical anesthesiology. 6th ed. Mc-Graw Hill; 2018.
B. Ventilation

 The lowering of alveolar partial pressure by uptake can be countered by

increasing alveolar ventilation.

C. Concentration
• The slowing of induction due to uptake from alveolar gas can be reduced by
increasing the inspired concentration.
• Two phenomena increase the alveolar concentration and its rate of rise
• Concentrating effect → more significant with nitrous oxide than with the
volatile anaesthetics.
• Augmented inflow effect
  Second-gas effect: a high concentration of nitrous oxide will augment (by the
same mechanism) not only its own uptake, but theoretically that of a
concurrently administered volatile anesthetic.

Figure 6. Second Gas Effect N20

Hannallah M. Concentration and gas effect. In: Freeman BS, Berger JS, editors. Anesthesiology core review Part one: basic exam. Mc Graw Hill; 2014. p. 29–30.
III. Factors affecting arterial concentration (Fa)

An increase in the alveolar partial

Ventilation/Perfusion mismatch pressure for highly soluble agents
V/Q Mismatch acts as a
restriction to flow
A decrease in the arterial partial
pressure (more pronounced in poorly
soluble agents)

Greatest effect of shunting is found with less soluble agent (Sevo, Des)
 IV. Factors affecting elimination

 Recovery from anesthesia depends on lowering the concentration of anesthetic in

brain tissue.
 Anesthetic can be eliminated by:
 Biotransformation → the elimination of soluble anesthetics that undergo extensive
metabolism
 Transcutaneous loss → insignificant

 Exhalation → the most important route for elimination is the alveolus.

 Pharmacodynamics

• Unconsciousness and amnesia are mediated by cortical anesthetic action.

Macroscopic
• The suppression of purposeful withdrawal from pain relates to subcortical structure
site of action (spinal cord or brainstem).

• All inhalation agents share a common mechanism of action at the molecular level
• Meyer-Overtone rule : the anesthetic potency of inhalation agents correlates directly
with their lipid solubility.
The molecular • General anesthetic action could be due to alteration in any of several cellular systems,
level including voltage-gated ion channels, ligand-gated ion channels, second messenger
functions, or neurotransmitter receptors.
• Anesthetic agent enhance GABA inhibition of the CNS.
• Modulation on nicotinic acetylcholine receptors and NMDA receptors
Anesthetic Neurotoxicity

One large study Sun and colleagues reported that

demonstrated children among healthy children with a single
receiving anesthetics may anesthesia exposure before 36
be more likely to be months of age, when compared with
diagnosed with learning healthy siblings with no anesthesia
difficulties. exposure, there were no significant
differences in IQ scores later in
childhood.
Anesthetic Cardiac Preconditioning

 In the heart :
 Actions at adenosine triphosphate (ATP)-sensitive
potassium (KATP) channels → less mitochondrial
calcium ion concentration and reduction of reactive
oxygen species (ROS) production.
Minimum Alveolar Concentration
1 MAC = The alveolar concentration that prevents
movement in 50% of patients in response to a
standardized stimulus (surgical incision).

1.2 - 1.3 MAC of any of the volatile anesthetics (example:

halothane: 1.3 x 0.75% = 0.97%) has been found to
prevent movement in about 95% of patients.

1.5 MAC = MAC BAR → blunt adrenergic response

0.3 – 0.4 MAC is associated with awakening from

anesthesia (MAC awake)

Butterworth JF, Mackey DC, Wasnick JD. Inhalation anesthetics. In: Clinical anesthesiology. 6th ed. Mc-Graw Hill;
2018.
Physical and chemical properties of inhaled anesthetics
 Minimum Alveolar
Concentration

The MAC values for different

anesthetics are roughly additive.
 Example :
 0.5 MAC of nitrous oxide
(53%) + 0.5 MAC of halothane
(0.37%) produces the same
likelihood that movement in
response to surgical incision
will be suppressed as 1.0 MAC
of isoflurane (1.2%) or 1.0
MAC of any other single
agent.

Butterworth JF, Mackey DC, Wasnick JD. Inhalation anesthetics. In: Clinical anesthesiology. 6th ed. Mc-Graw Hill; 2018.
Table 5. Factors
affecting MAC
 Effects on
Organ Systems

Table 6. Clinical
pharmacology of inhalational
anesthetics

Butterworth JF, Mackey DC, Wasnick JD. Inhalation anesthetics. In: Clinical anesthesiology. 6th ed. Mc-Graw Hill; 2018.
 Table 7. Properties of
Volatile Anesthetics

Wu J. Inhalation agents. In: Atchabahian A, Gupta R, editors. The Anesthesia Guide. Mc Graw Hill; 2013. p. 255–7.
 Toxicity

Desflurane Sevoflurane Isoflurane Nitrous oxide

Liver Metabolized to Rarely causes hepatitis
inorganic fluoride
Renal Nephrotoxicity in
animals
Soda lime CO production Compound A
interaction associated with dry produced when flows
soda lime are low for prolonged
time
Malignant May trigger May trigger May trigger Safe to use in MH-
hyperthermia susceptible patient
References

 Mckay Eshima R. Inhaled anesthesia. In: Miller DR, Pardo MC, editors.
Basic of anesthesia. Seventh ed. Philadelphia: Elsevier; 2018. p. 83–102.
 Butterworth JF, Mackey DC, Wasnick JD. Inhalation anesthetics. In:
Clinical anesthesiology. 6th ed. Mc-Graw Hill; 2018.
 Hannallah M. Concentration and gas effect. In: Freeman BS, Berger JS,
editors. Anesthesiology core review Part one: basic exam. Mc Graw Hill;
2014. p. 29–30.
 Wu J. Inhalation agents. In: Atchabahian A, Gupta R, editors. The
Anesthesia Guide. Mc Graw Hill; 2013. p. 255–7.
Thank You