muscles when exposed to triggering agent
#4.INHALATIONAL ANESTHESIA
Sherwin F. Revibes, M.D.
Otherwise known as Volatile Anesthetics/ Gas Anesthetics
Stages of General Anesthesia
Defined by Guedel after careful observation of patient
responses during induction of diethyl ether. Induction with
modern anesthetic agents is sufficiently rapid that these
descriptions of individual stages are often not applicable or
appreciated. Mydriasis-dilation adrenergic
Stage 1 (Amnesia) – begins with induction of anesthesia and
ends with the loss of consciousness(loss of eyelid reflex). Pain
perception threshold is not lowered.
Stage 2 (Delirium/Excitement) – uninhibited excitement,
agitation ,delirium, irregular respiration and breath holding.
Pupils are dilated and gaze may be divergent. Responses to
noxious stimuli can occur during this stage( vomiting,
laryngospasm, hypertension, tachycardia and uncontrolled
movement). Desirable induction drugs accelerate transition
through this stage.
Stages of General Anesthesia
Stage 3(Surgical Anesthesia) – characterized by central gaze,
constricted pupils and regular respiration. Target depth of
anesthesia is suffficient when painful stimulation does not
elicit somatic reflexes or deleterious autonomic responses
(hypertension and tachycardia)
Stage 4 (Impending Death/ Overdose) – characterized by
onset of apnea, dilated and nonreactive pupils and
hypotension to complete failure of the circulation.
- Anesthesia should be lightened immediately. Use of
reversal agents.
Inhalational Anesthesia
Most common drugs used for the provision of general
anesthesia resulting in a state of unconsciousness and
amnesia.
There is no one perfect anesthestic agent. Inhalation agents
come closest to providing the component of a complete
anesthetic (i.e., analgesia, amnesia, hypnosis and muscle
relaxation) as a single agent.
When combined to intravenous adjuvants such as opioid,
benzodiazepines and muscle relaxants, a balanced technique is
achieved that results in further sedation/hypnosis and
analgesia.
Properties of an Ideal Anesthetic Gas
1. Have a predictable action and rapid onset of induction
and emergence.
1. 2.Provide muscle relaxation, cardiostability and
brochodilation.
2. Not trigger malignant hyperthermia or other significant
side effects.
*Malignant hyperthermia-hereditary defect of the
calcium-release channels of the SR of skeletal muscles.
This defect causes sustained contraction of skeletal
(succinylcholine and all volatile anesthetic agents)
3. Be inflammable.
4. Undergo no transformation within the body.
5. Allow easy estimation of concentration at the site of
action.
History
Nitrous oxide -1844
Ether – 1846
Chloroform – 1846-1847
Halothane-1956
Methoxyflurane- 1960
Enflurane- 1972
Isoflurane- 1980
Desflurane- 1993
Sevoflurane 1995
Horace Wells use nitrous oxide in his painless dentistry
practice then came William Morton also a Boston dentist
applied ether in his dental practice and demonstrate at Mass
Gen Hosp on “ether day” October 16, 1846. Although
Crawford Long administered diethyl ether four years ago
before demonstration of ether into public but failed to
publicize. James Simpson an obstetrician from Scotland for
relief of pain during labor and delivery.
Old Inhalational Anesthetics
No longer used due to unfortunate properties and side effects
1. Cyclopropane and Diethyl ether- flammable gases
2. Chloroform and Trichloroethylene- non flammable but
associated with hepatic toxicity and neurotoxicity
3. Halothane- fulminant hepatic necrosis
4. Methoxyflurane- slow induction and dose-related
nephrotoxicity
5. Enflurane- seizure activity on the electroencephalogram
Advances in fluorine chemistry in the 1940’s allowed safe
incorporation of fluorine into molecules.
Fluorine substitution for other halogens on the ether molecule
lowered the boiling point, increased stability and generally
decreased toxicity.
Theories on How Inhalational Anesthetic Works
Questions occur about where in the nervous system
inhaled anesthetics act, what molecules they interact with to
produce their effect, and the nature of the biologic interaction
between anesthetic and substrate that requires an ability to
measure anesthetic effects.Although inhaled anesthetics have
been used to provide surgical anesthesia for more than 160
years, there is no accepted fact on its MOA.
1. Agent-specific theory: Each agent works on different
receptors and mechanism.
2.Unitary hypothesis: All inhalational anesthetics share a
common mechanism:
A. Meyer Overton rule: Anesthesia results from agents
dissolving at specific sites.
B. Critical Volume Hypotheis: Anesthesia results from 5. Elimination:
expanding lipid bilayer. - Most of the inhaled agents are exhaled unchanged
by the lungs.
Unique Features of Inhaled Anesthetics - Hyperventilation, a small FRC (Functional Residual
1. Speed of action Capacity), a low solubility ,a low cardiac output or a
2. Gas state large mixed venous – alveolar tension gradient
3. Lung route of administration increases the rate of decay.

Physical Characteristics of Inhaled Anesthetics 6. Diffusion Hypoxia

- results from dilution of alveolar oxygen
concentration by the large amount of N2O leaving
GOAL
the pulmonary capillary blood at the conclusion of
- Produce the anesthetic state by establishing a specific
N2O administration. This can be prevented by filling
concentration of anesthetic molecules (partial pressure)
the patient's lungs with oxygen at the conclusion of
in the central nervous system.
N2O administration
- This is achieved by establishing the specific partial
- the highly perfused vessel-rich group (brain, heart,
pressure of the agent in the lungs which ultimately
liver, kidney, and endocrine organs) is the first to
equilibrates with the brain and spinal cord.
take up appreciable amounts of anesthetic
- At equilibrium, CNS partial pressure equals blood partial
pressure which equals alveolar partial pressure
6.Diffusion Hypoxia
P CNS= P Blood= P alveoli
- Moderate solubility and small volume limit the
capacity of this group, so it is also the first to fill (ie.,
Factors Affecting Anesthetic Gas Uptake
arterial and tissue partial pressures are equal).
- The muscle group (skin and muscle) is not as well
1. Partition Coefficient- describes the distribution of a given
perfused, so uptake is slower.
agent at equilibrium between 2 substances at the same
- Perfusion of the fat group nearly equals that of the
temperature, pressure and volume.
muscle group, but the tremendous solubility of
A. Blood:Gas Partition Coefficient
anesthetic in fat leads to a total capacity
- “Blood solubility” of an anesthetic
(tissue/blood solubility x tissue volume) that would
- describes the relative affinity of an anesthetic for the
take days to fill. The minimal perfusion of the vessel-
gas and for the blood
poor group (bones, ligaments, teeth, hair, and
B. Brain:Bood
cartilage) results in insignificant uptake.
C. Fat: Blood
D. Muscle: Blood
E. Oil: Gas Minimum Alveolar Concentration (MAC)

NOTE: The higher the solubility, the more delayed the onset of The alveolar concentration of volatile anesthetic in volume
anesthetic effect in the brain. percent necessary to prevent purposeful movement in 50% of
patients during skin incision.
2. Overpressurization and Concentration Effect
- Analogous to IV bolus Provides a measure of partial pressure of drug necessary to
- Administration of a higher partial pressure of produce anesthesia.
anesthetic than alveolar concentration (FA) actually
desired for the patient 1. MAC Awake- MAC of a given volatile anesthetic at which a
patient will open his or her eyes on command.
3. Second Gas Effect 2. MAC Intubation- inhibit movement and coughing during
- Uptake of large volume of a first or a primary gas endotracheal intubation.
(usually N2O) from alveoli increases the rate of 3. MAC BAR (Block adrenergic response) MAC necessary to
increase in alveoli concentration of a second gas blunt the sympathetic response to noxious stimuli
(volatile anesthesia)
MAC Values for Commonly Used Inhalational Agents (%)
4. Perfusion Effect Halothane -0.75
Enflurane -1.63
Increased Cardiac Output Isoflurane -1.15
- More blood travels through the lungs thereby Desflurane -6.06
removing more anesthetic from the gas phase and Sevoflurane -1.85
resulting in a lower alveolar concentration Nitrous Oxide -104

Decreased Cardiac Output Factors Increasing MAC

- With decreasing blood flow through the lungs less Drugs
anesthetic is taken up by blood and alveolar - Amphetamine (acute use), Cocaine
concentration increases more rapidly - Ephedrine, Ethanol (chronic use)
Age chlorine atom resulting in a lower blood:gas
- Highest at age 6 months solubility and less of potency
Electrolytes - Desflurane lowest blood:gas solubility of the potent
- Hypernatremia inhaled anesthetics 0.42.. Meaning least soluble
- Hyperthermia making it the characteristic of rapid induction and
Red hair fast emergence of the patient which is ideal for
ambulatory surgery
Factors Decreasing MAC
Drugs 4. Desflurane
- Propofol - -has near absent metabolism to serum
- Etomidate trifluoroacetate making hepatotoxicity extremely
- Barbiturates unlikely
- Benzodiazepines - -most pungent of the volatile anesthetics
- Ketamine - -has the lowest blood:gas solubility of the potent
- a2-Agonists (clonidine, dexmedetomidine) volatile anesthetics
- Ethanol (acute use)
- Local anesthetics 5. Sevoflurane
- Opiods - -sweet smelling, completely fluorinated methyl
- Amphetamines (chonic use) isopropyl ether
- Lithium - half as potent as isoflurane
- Verapamil - has minimal odor, no pungency and is potent
brochodilator making it excellent for administration
Age via facemask induction of anesthesia in both children
- Elderly patients and adults
Electrolyte Disturbance - The induction agent of choice in pediatric patients.
- Hyponatremia - it is not metabolized to trifluoroacetate
Other factors - breaks down to form compund A
- Anemia (hemoglobin <5 g/dL)
- Hypercarbia 6. Nitrous Oxide
- Hypothermia - -sweet smelling, non flammable gas of low potency
- Hypoxia - -relatively insoluble in blood
- Pregnancy - -does not produce significant muscle relaxation but
have analgesic effect
Factors that Do Not Affect MAC - -has adverse effect related to absorption and
Gender expansion into air-filled structure and bubbles
Thyroid function - -has effect on embryonic development
PaCO2 between 15 and 95 mmHg - The blood-gas partition coefficient of nitrous oxide is
34x greater than nitrogen meaning that it can leave
Clinical Overview of Current Inhaled Anesthetics the blood to enter an air-filled cavity 34 times more
rapidly than nitrogen can leave the cavity to enter
1. Halothane the blood. As a result, the volume or pressure of the
- Alkane air filled cavity increases. That’s why N2O is
- most potent of currently used volatile anesthetic contraindicated in bowel surgery, pneumothorax,
- relatively non pungent hence can be inhaled via patients with pulmonary blebs, px prone for air
facemask embolism, middle ear surgery, neurosurgery most
- associated with immune mediated hepatitis especially involving the cerebral ventricles and
2. Enflurane supratentorial subdural space
- halogenated methyl ethyl ether is an isomer of
isoflurane Effects of the Inhalational Agents on Organ
- pungent System
- its use in high concentration has been associated
with seizure-like activity on EEG I.Cardiovascular Effect
3. Isoflurane Agents Contractility PVR SBP
- halogenated methyl ethyl ether Halothane  -- 
- has high degree of pungency Enflurane   
- second most potent volatile anesthetic in clinical use Isoflurane,
- associated with rare occurrence for coronary ‘steal” Desflurane, --  
- ”gold standard” anesthetic since its introduction Sevoflurane
4. Desflurane
- fluorinated methyl ethyl ether that differs from
isoflurane by substitution of fluorine atom for a
II. Central Nervous System Effects
- inhalational anesthetics produce dose related
reversible depression and/or excitation of brain
function resulting in unconsciousness and analgesia

A. Halothane- most potent cerebral vasodilator

B. Enflurane- can produce seizure at high concentration
C. Isoflurane- least potent cerebral vasodilator

III. Renal Effects

- All volatile anesthetics cause decreased renal
function that can be alternated or abolished by pre
operative hydration.
- Fluoride induced nephrotoxicity, a problem with
methoxyflurane is rare at usual anesthetic
concentration and duration of usage.
- After isoflurane and desflurane administration,
fluoride release does not affect the kidneys.

Clinical Pharmacology of Inhalational Anesthetics

Halothane does not cause tachycardia because it inhibits the

baroreceptor reflexes