October 16th, 1846:

First public demonstration of the use of ether in anesthesia at

Massachusetts Gen Hosp. with Dr. J.C. Warren in attendance

The First General Anesthetic

Chloroform

(toxic)
Ether (flammable)
Methoxyflurane (nephrotoxic)
Nitrous oxide (useful up to now)
Halothane (dysrhythmia, hepatotoxic)
Enflurane
Isoflurane
Desflurane
Sevoflurane (nephrotoxic?)

Advantages of Inhalational Anesthesia

Provide

completely painless induction of anesthesia.

No intravenous access needed.
Most rapid appearance of drug in arterial blood (agent
goes direct from lungs to left heart and aorta,
bypassing venous system and right heart).
Easily and safely administered by modern anesthesia
machine.

Pharmacokinetics
The

depth of anesthesia depends on the partial

pressure or gas fraction exerted by the inhalational
agent in the patients brain (b).
Brain partial pressure depends on arterial (a) partial
pressure which depends on alveolar partial pressure
(A) which depends on partial pressure in the inspired
gas (I).
PIPA Pa Pb or FI FA Fa Fb.
partial pressure of component gas : fraction of total
gas x total pressure (Pc : Fc x P)
To change Fb in patients brain, we monitor and
control FI and indirectly FA and Fa

Factors Affecting Inspiratory

Concentration (FI)
Actual composition of the inspired gas mixture depends
on:
Fresh gas flow rate
Volume of the breathing system
Absorption by the machine
Fresh gas flow rate >>
Breathing system volume <<
Circuit absorption <<

Inspired gas
concentration ~ Fresh
gas concentration

Faster induction and

recovery times

Factors Affecting Alveolar Concentration

(FA)

Uptake of agents >>

Rate of rise of FA <<

FA/FI Ratio <<

Factors Affecting Alveolar Concentration

(FA)
The

concentration of a gas is directly proportional to

its partial pressure.
Alveolar partial pressure determines the partial
pressure of anesthetic in blood and brain.
The greater the uptake, the greater the difference
between inspired and alveolar concentration, the
slower rate of induction.
Three factors affect anesthetic uptake:
Solubility in the blood.
Alveolar blood flow
Difference in partial pressure between alveolar gas and venous
blood

Factors Affecting Alveolar Concentration

(FA)
Solubility

in the blood

Anesthetic solubility >>

Uptake by the pulmonary

circulation >>

Rise in alveolar partial

pressure <<

Rate of induction <<

Factors Affecting Alveolar Concentration

(FA)
Alveolar

blood flow

It is essentially equal to cardiac output.

CO >>

Anesthetic
uptake >>

Rise in alveolar partial

pressure <<
Rate of induction <<

Difference

in partial pressure between alveolar gas and

venous blood.
This gradient depends on tissue uptake, that determined by:
Tissue solubility of the agent (tissue/blood partition coefficient),
Tissue blood flow,
Blood/tissue partial pressure difference.

Factors Affecting Alveolar Concentration

(FA)
Tissue Groups Based on Perfusion and Solubilities
Characteristic

Vessel
Rich

Muscle

Fat

Vessel
Poor

Percentage of body
weight

10

50

20

20

Percentage of
cardiac output

75

19

Perfusion
(mL/min/100 g)

75

20

Relative solubility

Factors Affecting Alveolar Concentration

(FA)

The rise and fall in alveolar partial pressure precedes that of other tissues.

Factors Affecting Alveolar Concentration

(FA)

Factors Affecting Alveolar Concentration

(FA)

Factors Affecting Arterial Concentration

(Fa)

Factors Affecting Elimination

Recovery

from anesthesia depends on lowering the

concentration of anesthetic in brain tissue.
Elimination through:
Biotransformation: minimal, usually for soluble
anesthetic agents that undergo metabolism.
Trancutaneous loss: insignificant.
Exhalation: most important route. Affected by:

Extent of rebreathing
Fresh gas flow
Volume of breathing system
Absorption by breathing system components
Solubility of agent
Cerebral Blood Flow
Ventilation

Factors Affecting Elimination

Factors Affecting Elimination

Diffusion hypoxia:
During recovery from anesthesia, wash out of
high concentration of N2O results in lowering
alveolar concentration of O2 and CO2 (outpouring
of N2O from the blood into the alveoli when
inhalation of this gas is discontinued can dilute
the PAO2).
Recovery from anesthesia also depends on
length of time anesthetic administration.

Pharmacodynamics
Minimum Alveolar Concentration (MAC)
MAC

is the alveolar concentration that prevents

movement in 50% of patients in response to a
standardized stimulus (eg, surgical incision).
Describes
the brain partial pressure, allows
comparisons of potency between agents, provides
standard evaluations.
MAC can be altered by several physiological and
pharmacological variables, eg temperatture, age,
blood pressure, etc.

Properties of Inhalational Anesthetics

Factors Affecting MAC

Variable

Effect on MAC

Temperature
Hypothermia
Hyperthermia

Age
Neonates
Infants
Young
Elderly

Gender

Duration of anesthesia

Anesthetic metabolism

Alcohol
Acute intoxication
Chronic abuse

Anemia (Ht < 10%)

Factors Affecting MAC

Variable

Effect on MAC

PaO2
< 40 mmHg
> 40 mmHg

PaCO2
15-95 mmHg
> 95 mmHg

Thyroid
Hyperthyroid
Hypothyroid

Blood pressure
MAP < 40 mmHg
MAP > 40 mmHg

Electrolytes
Hypercalcemia
Hypernatriemia
Hyponatriemia
Pregnancy

Factors Affecting MAC

Variable
Drugs
Local anesthtics
Opioids
Ketamine
Barbiturates
Benzodiazepines
Verapamil
Lithium
Sympatholytics
Methyldopa
Clonidine
Dexmedetomidine
Sympathomimetics
Amphetamine
Chronic
Acute
Cocaine
Ephedrine
Monoamine oxidase inhibitors
Cardiopulmonary bypass

Effect on MAC

Equipments for Inhalational Anesthesia

Anesthesia machine

12

1.
2.
3.
4.

7
8
10
11

Corrugated tube
Infusion pump
Reservoir bag
Patients medical
record
5. Vital Sign Monitor
6. Vaporizer
7. ?
8. Flow meter
9. ?
10.Ventilator
11.CO2 Absorbance
12.Gas line

Physical Properties
Nitrous oxides = laughing gas inorganic anesthetic gas.
Colorless, odorless
Nonexplosive and nonflammable, but support combustion.
As a gas in room temperature and ambient pressure.
As a liquid in under pressure.

Effects on Organ Systems

Effects on Organ Systems

Result of central venous stimulation and

activation of pulmonary stretch receptor.
Minimal change in minute ventilation and
resting CO2 levels.

Effects on Organ Systems

Biotransformation & Toxicity

Almost all eliminated by exhalation.
N2O inhibits enzymes that vitamin B12 dependent, by
irreversibly oxidizing the Co atom in vitamin B12.
methionine synthetase: myelin formation
thymidylate synthetase: DNA synthesis
Prolonged exposure bore marrow depression
(megaloblastic anemia) and neurological deficiencies
(peripheral neuropathies and pernicious anemia).
Teratogenic effects.
Affect chemotaxis and motility of PMN leukocytes.

Contraindications
Although N2O is less soluble than other agent, but N2O is
35 times more soluble than nitrogen in blood diffuse into
air-containing cavities more rapidly than nitrogen in the
bloodstream.
Contraindicated in:
Air embolism
Pneumothorax
Related with air Acute intestinal obstruction
containing
Intracranial air
cavities
Pulmonary air cysts
conditions
Intraocular air bubbles
Tympanic membrane grafting
Pulmonary hypertension

Physical Properties
Halogenated

alkane
Nonflammable & nonexplosive
Odorless
Thymol preservative and ambercolored bottles retard spontaneous
oxidative decomposition.

Effects on Organ Systems

Effects on Organ Systems

Effects on Organ Systems

Malignant Hyperthermia

Effects on Organ Systems

Biotransformation & Toxicity

Contraindications
Malignant hyperthermia susceptibility
Unexplained liver dysfunction
Intracranial mass lesions
Hypovolemic patients
Severe cardiac disease (aortic stenosis)
Pheochromocytoma
Severe
ventricular
dysrhythmias
(associated
aminophylline).

with

Physical Properties
Nonflammable
Pungent

ethereal odor
Chemical isomer of enflurane

Effects on Organ Systems

Effects on Organ Systems

Effects on Organ Systems

Biotransformation & Toxicity

Contraindication

Physical Properties
The structure is almost similar to isoflurane, except for the
fluorine atom Halogenated fluorine.
High vapor pressure
Low boiling point
Needs special vaporizer
Low solubility
ultrashort duration of action
Rapid wake up time
Pungent

Effects on Organ Systems

Effects on Organ Systems

Biotransformation & Toxicity

Minimal metabolism.
Fluoride fluid levels unchanged.
Carbon monoxide toxicity (due to desflurane is degraded by
CO2 absorbent into potentially clinically significant levels of
carbon monoxide, that is difficult to diagnose).

Contraindication
Suspected malignant hyperthermia
Severe hypovolemia
Intracranial hypertension

Physical Properties
Halogenated fluorine
Odorless
Rapid in alveolar concentration
Relative low solubility

Smooth and rapid

inhalation induction

Effects on Organ Systems

Effects on Organ Systems

Effects on Organ Systems

Biotransformation & Toxicity

Metabolized by liver microsomal enzyme P-450.
No association between renal dysfunction and fluoride fluid
levels.
Alkali
can degrade sevoflurane to compound A
(nephrotoxic end products)
Slightly RBF
Impaired renal tubule function.

Contraindication
Malignant hyperthermia susceptibility.
Severe hypovolemia.
Intracranial hypertension.
Preexisting renal dysfunction.