03/02/2020

5:00-6:00 Inhalational Anesthetics

M Anesthesiology
LDT Maria Victoria Hofileña, M.D.

OUTLINE Classification of Inhalational Anesthetics

I. Introduction Outdated Gases Volatile Agents

II. Minimum Alveolar Concentration Ether Nitrous oxide Halothane
III. Pharmacokinetics Trilene Xenon Enflurane
IV. Effects on Organ Systems
Methoxyflurane Isoflurane
V. Recovery from Anesthesia
Cyclopropane Sevoflurane
VI. Inhaled Anesthetic Agents
VII. Toxicities Chloroforrm Desflurane
VIII. Sources
Uptake and Distribution of Anesthetics
INTRODUCTION

Inhalational Anesthesia refers to the delivery of gases into the

respiratory system to produce anesthesia
Before the use of IV medications, man has inhaled vapors or
volatile agents to mitigate pain.
The most commonly used anesthetics are halothane,
enfluranes, etc. (these are your volatile agents)

History of Anesthesia

 Nitrous oxide
First synthesized by Joseph Priestly in 1772.
It was widely used as a recreational drug until 27 years (1800s)
later that Davy observed it to produce anesthesia and analgesia
when he used on himself during an episode of toothache.
Horace Wells later demonstrated the hypnotic and analgesic
effects of volatile anesthetics in a painless dental surgery in
Massachuccets General Hospital. Anesthetics are delivered into the respiratory system and its
Even until now, even in the emergence of newer volatile agents, main target is the brain.
nitrous oxide still remains as a very useful inhalational anesthetic. Its action is extremely rapid because the lung is one organ that
receive 100% of your cardiac output.
From the outside, volatile agents are delivered in the alveoli,
diffused in the circulatory system, reach the brain and excreted
via the venous system and then exhaled out through the lungs.

Mechanism of Action

Inhalational anesthetics have been used to provide surgical

anesthesia for over 200 years but there is still no definition what
constitute your anesthetic state.
 Unknown
 No single, accepted definition of what constitutes the anesthetic
state
 Operational definition:
o Immobility in response to surgical stimulation
o Amnesia for intraoperative events

MINIMUM ALVEOLAR CONCENTRATION (MAC)

Immobility is measured by MAC

 MAC is a measure of anesthetic potency
 1 MAC means a Minimum Alveolar Concentration at which 50%
of humans have no response to surgical stimulus
During anesthesia and surgery the stimulus is usually the skin
incision and the response elicited is movement.

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 Going back to the operational definition, you measure your (PA) and therefore the alveolar partial pressure (Pa) mirrors that of
immobility through elicited response the brain partial pressure (Pbr) and also the index of the anesthetic
However, both amnesia and analgesia are difficult to measure. depth.
Only surrogate measure of pain is measured, like increase in
BP or increase in heart rate that suggest that inhaled anaesthe- Factors That Determine Alveolar Partial Pressure (PA)
tics don’t supress perception of pain stimuli.
 Pi
List of Mac of the Different Inhalational Anesthetics  Alveolar ventilation
 Anesthetic breathing system
Agent MAC Potency  Solubility
Methoxyflurane 0.16% Most potent  Cardiac Output
Halothane 0.74%  Alveolar to venous partial pressure difference
Isoflurane 1.17%
1. Inspired Anesthetic Partial Pressure
Enflurane 1.7%
 A high Pi is necessary during induction or initial administration
Sevoflurane 2.05%
of anesthetics
Desflurane 6.0%  Concentration Effect
Nitrous Oxide 10.4% Least potent o The higher the concentration of an inhaled anesthetic, the
faster the alveolar concentration approaches the inhaled
Nitrous Oxide: Least potent, Highest MAC concentration.
Methoxyflurane: Most potent, Lowest MAC

Factors That Influence MAC

Factor Increases MAC Decreases MAC

Age Max. inc. 6 months Dec. with age
0
Temperature Inc. up to 42 C Dec. with
temperature
O2 Hypoxia
CO2 Hypercarbia
Alcoholism Chronic Acute
Barometric Inc. pressure, inc.
pressure MAC Lungs has the capacity of 4L. When the patient inhales 2L of
Hemoglobin Anemia oxygen together with 2L of nitrous oxide, that’s 50%
IV agents Yes concentration.
Since, nitrous oxide diffuses very rapidly into your blood
Pregnancy Yes
compared to other gases. It leaves only 1L of nitrous oxide in
Local Cocaine Others decreases your alveoli, leaving only 3L of volume in your lungs. This
anesthetics new concentration of your nitrous oxide is 33%. As the
Sodium Hypernatremia Hyponatremia patient inhales 1L of your anesthetics, this increases the
Magnesium Hypomagnesenia Hypermagnesenia concentration to 37.5%. This is called your concentration
effect.
Calcium Hypocalcemia Hypercalcemia
Because after the uptake of nitrous oxide into your blood
there will be negative pressure that will absorb the remaining
 MAC is not affected by: 1L into your lungs giving additional concentration of your
o Sex (Male=Female) nitrous oxide. This is called the ventilating effect.
o Thyroid disease
 Second Gas Effect
PHARMACOKINETICS o The ability of the large volume uptake of one gas (First Gas) to
accelerate the rate of rise of the PA of a concurrently
 Describes the uptake of inhaled anesthetics from the alveoli, administered companion gas (Second Gas)
circulation, distribution, elimination and metabolism of inhaled o It is a consequence of the concentration effect
anesthetics Wherein the first gas such as nitrous oxide, as it moves
 Objective: achieve a constant and optimal brain partial pressure rapidly from the lungs to the plasma, this increases the alveolar
of anesthetic concentration therefore increases the rate of uptake of the
second gas

The brain and all other tissues will equilibrate with the partial
pressure of inhaled anesthetics delivered to them by arterial blood

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 The lower the OIL: Gas partition coefficient, the lesser
potency. So nitrogen, being the least potent and halothane
as the most potent.

nd
We will use the same illustration to explain the 2 gas effect by
adding Isoflurane. The mixture of 1% isoflurane of 4L of the
inhaled anesthetics, will have 50% uptake of the nitrous oxide.
Half of this nitrous oxide will diffuse quickly into the blood and
the alveolar volume will again be 3L, so the alveolar
concentration of isoflurane from 1% will increase to 1.3%
because of the 50% uptake of nitrous oxide. So as the patient
inhales another volume of gas mixture, it will add 0.3% to your
isoflurane. With the inhalation of 1L of mixture, isoflurane will
increase again by another percent because of your nitrous
oxide.

2. Alveolar Ventilation
 Increase alveolar ventilation promotes uptake of more inhaled Blood Gas Partition Coefficient: this is the principal
anesthetic into the blood. determinant of the rate at which the alveolar concentration
 The Higher VA (alveolar ventilation/breathing/respiratory rate), increases toward a constant inspired concentration. It
the more rapid rate of increase of PA (alveolar pressure) = correlates with the rate of induction. It is how fast the agent
faster induction can cause consciousness. Nitrous oxide has a faster rate of
induction compared to halothane.
3. Solubility
Solubility of the anesthetics in the blood and tissues is denoted
by partial pressure coefficient or distribution ratio of how the PARTITION CO-EFFICIENTS
inhaled agent distributes itself between two phases at
equilibrium.
 Partition Co-Efficients
 Example:
Oil: Gas Partition Co-Efficient
o Indicates the amount of gas that is soluble in oil phase
o Measure of lipid solubility of the anesthetic
o Indicates anesthetic potency
o Explained by Meyer-Overton Rule

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 Uterine smooth  Halogenated anesthetics are potent
Desflurane and Nitrous Oxide with the lower blood gas muscle relaxants
partition coefficient has a faster induction compared to  increase uterine bleeding
halothane and methoxyflurane.
RECOVERY FROM ANESTHESIA

A reverse of induction process

o Rate at which the PA decreases with time
o Elimination through lungs
As the alveolar partial pressure decreases (PA) the anesthetic is
subsqequently transferred from the tissue into the alveoli and is
expelled out
o Influenced by
Tissue concentration
Metabolism

For agents with low blood/gas partition coefficient, meaning

they are relatively insoluble and they will equilibrate rapidly
into the blood because it has very little uptake by other
tissues so the faster the FA reaches FI, the faster the rate of
induction. The higher the solubility the greater the uptake of
the alveolus and therefore there is a slower rise of your FA
to meet FI.

 FA/FI
o Ratio of alveolar agent to inhaled agent
o Higher the blood/gas partition coefficient (solubility) the greater
the uptake from the alveolus
o The slower the rise of FA to meet the FI
o Factors affecting: Minute ventilation, CO, FGF, IV agents
*FA: alveolar concentration
*FI: constant inspired concentration

All the factors mentioned are involved to achieve and

maintain constant optimal brain concentration. Once you
achieved this, surgery can begin and you have to maintain
the level of anaesthesia during the surgery.

EFFECTS INHALATION ANESTHETICS ON ORGAN SYSTEMS

Circulatory System  Decrease blood pressure Tissue Concentrations

 Some decrease cardiac output  Serve as a reservoir
Respiratory  Decrease tidal volume  Influenced by:
 Increase respiratory rate o Duration of anesthesia
 Depress mucociliary function= o Solubility
pooling of mucus and atelectasis
Brain  Decrease brain metabolic rate Example: recovery is prolonged in a more soluble
 Decrease cerebral vascular anesthetics like isoflurane compared to sevoflurane or
resistance thus increasing cerebral desflurane which are poorly soluble anesthetics.
blood flow
Kidney  Decrease GFR, decrease renal blood
flow
Liver  Decrease hepatic blood flow

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 INHALED ANESTHETIC AGENTS

 Nitrous Oxide (N2O)

 Halothane
 Enflurane
 Isoflurane
 Desflurane
 Sevoflurane
 Xenon
 Ether
 Tricholoroethylene
 Chloroform

Nitrous Oxide  History: used by John Culton during the

public demonstration of anesthesia
 Liquid gas, odorless and colorless
 Still used in practice today
 Used as Entonox
o 50% N2O + 50% O2
o Poyinting effect: where N2O is mixed
with O2 and it remains in gaseous state
o Use:
Labor analgesia
Field analgesia
 Contraindications of N2O
Metabolism o N2O is 35x more soluble in blood than
N2
 Important difference between induction and recovery o Fills and expands any air-containing
Compared to induction, metabolism has a potential impact to cavity
recovery especially in highly soluble anesthetic Air embolism
 Impact of metabolism on the rate of decrease PA Pneumothorax
 Highly lipid soluble agents (ex. methoxyflurane, halothane) Lungs cysts
 Principal determinant of rate of decreased PA is metabolism Tympanoplasty
During the recovery of anesthesia when Nitrous oxide is Intraoccular bubbled
discontinued, large amount of nitrous oxide diffuses back from o May exacerbate pulmonary
the blood into the alveoli (because of the low blood solubility of hypertension
nitrous oxide) will result to dilution hypoxia. Use cautiously in high risk patients
Dilution hypoxia: as the large volume of nitrous oxide diffuses
back into the alveoli it will dilute the oxygen concentration in the Halothane  Thymol presevative
alveoli.  Pleasant smell, non-irritant,
There’s also dilution of inspired carbon dioxide which bronchodilation
subsequently lead to a decrease in arterial carbon dioxide that  Potent = induce anesthesia in single puff
will lead to a decrease respiratory drive. for pedia
The risk of dilution hypoxia persists only to about 3-5 minutes  Ideal for asthmatics ( it causes
after the discontinuation of nitrous oxide, therefore what we do vasodilation)
is to initiate recovery with 100% oxygen inhalation  Toxicity
o Most arrhythmogenic: sensitizes the
heart to catecholamines
o Max decrease in BP, SVR, HR-
bradycardia
o Uterus: atony
o Post-op shivering
o Malignant hyperthermia
o Halothane hepatitis: caused by
metabolite Trifluoroacetic acid

Enflurane  Epileptogenic
 Contraindications:
o MH susceptibility
o Seizure disorder
o Preexisting kidney disorder, intracranial
hypertension

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 Isoflurane  Only agent that preserves baroreceptor TOXICITIES
reflex
 Causes coronary steal Carbon monoxide toxicity
 Has minimal increase in intracranial
pressure  Carbon monoxide is a by-product of all agents as it reacts with
 Agent of choice for cardiac and soda lime.
neuroanesthesia  Desflurane> Enflurane> Isoflurane> Sevoflurane >Halothane
More recent anesthetics used in (from more toxic, to least toxic)
practice.
Fluoride nephrotoxicity
Sevoflurane  More commonly used inhalation
anesthetic  Fluoride: a nephrotoxic by-product of metabolism in liver and
 Pleasant smell, non-irritant and kidney
bronchodilator o It opposes ADH leading to polyuria
 Choice for pediatric anesthesia  Methoxyflurane> Sevoflurane> Isoflurane> Desflurane
nd
 2 choice for: (from more nephrotoxic to least)
∘ Neuroanesthesia  Results in potentially permanent renal injury
∘ Cardiac anesthesia
∘ Asthmatics Malignant Hyperthermia

Xenon  Most ideal inhalational agent  Autosomal malignant genetic disorder of skeletal muscle
 Characteristics:  Mutation in Ryanodine receptor
o Least blood-gas partition coefficient  Exposure leads to continual release of calcium from
o least soluble, fastest induction sarcoplasmic reticulum
o fastest recovery  Characterized by sudden hyperthermia, tachycardia,
 Most cardiostable hypertension, muscle rigidity, hyperkalemia
 Not metabolized, non-flammable  Treatment: Dantrolene
 Disadvantages:
o very costly SOURCES
o needs special equipment for delivery
causes bronchospasm  Doc’s powerpoint
 Recordings
Ether  First used anesthetic agent in public
demonstration in 1886
 Most complete anesthetic agent
 Has maximum muscle relaxation
 Does not depress respiration
It preserves cilliary function
 Causes nausea and vomiting
It has the highest incidence of n/v

Methoxyflurane  Most potent, slowest induction and

recovery
 Most nephrotoxic

Cyclopropane  Most flammable and explosive

 Causes cyclopropane shock

Tricholoroethylene  Most potent analgesic agent

 Reacts with soda lime;
dichloroacetylene- neurotoxic phosgene-
pulmonary toxicity- ARDS

Choloroform  1 anaesthetic agent for labor analgesia

st

 Cardiotoxic: ventricular fibrillation

 Hepatotoxic, causes profound
hyperglycemia

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