INHALATION ANESTHETICS
Prof. Ayman Hussein KahlaProf. of Anesthesia Technology
Public Health & Health Informatics FacultyUMM ALQURA UNIVERSITY
Anesthesia
A state of temporary & reversible loss of
awareness and reflex reactions induced
by drugs to render surgery painless,
possible & comfortable. General anesthesia for surgical
procedure to render the patient unaware /
unresponsive to the painful stimuli.
Receptor Theory of Anesthesia
GABA: major inhibitory neurotransmitter
(point of action of anesthetic drugs) Membrane structure and function: future of
the anesthesiology Glutamate: major excitatory neurotransmitter Endorphins: analgesia. Unitary hypothesis of the inhalation agents.
MECHANISM OF ACTION Act in different ways at the level of the central
nervous system. Disrupt normal synaptic transmission - interfering with release of neurotransmitters
from pre-synaptic nerve terminal (enhance or depress excitatory or inhibitory transmission).
- altering re-uptake of neurotransmitters, - Changing the binding of neurotransmitters to
the post-synaptic receptor sites or - Influencing the ionic conductance change that
follows activation of the post-synaptic receptor by neurotransmitters.
Meyer-Overton Theory postulates that it is the number of molecules dissolved in the lipid cell membrane.
Protein Receptor Hypothesis postulates that protein receptors in the central nervous system.
Activation of GABA receptors. may inhibit certain calcium channels and therefore
prevent the release of neurotransmitters and inhibit glutamate channels.
Inhalation Anesthetic Agents
Nitrous oxide Halothane (Fluothane) Methoxyflurane (Penthrane) Enflurane (Ethrane) Isoflurane (Forane) Desflurane (Suprane) Sevoflurane (Ultane)
STRUCTURE OF DIETHYL ETHER
N=N=O
Nitrous Oxide Halothane Enflurane
F HF – C – C* – Br F Cl
F F FCl – C* – C – O – C – H H F F
F H F
F– C – C* – O – C – H
F Cl F
Isoflurane
F F H H
CF C O C FF C H
F F
Sevoflurane
F H F
F – C – C* – O – C – H
F F F
Desflurane
Obsolete Volatile Anesthetics
- Aliflurane - Chloroform - Cyclopropane - Diethyl ether - Enflurane - Ethylene - Halothane - Methoxyflurane - Methoxypropane - Roflurane - Teflurane - Trichloroethylene - Vinyl ether
DEFINITION It is a chemical compound possessing
general anesthetic properties that can be delivered via inhalation.
They are administered by anesthetists (anesthesiologists, nurse anesthetists, and anesthesiologist assistants) through an anesthesia mask, LMA or ETT connected to some type of anesthetic vaporizer and an anesthetic delivery system.
Inhalational Anesthetic Agents
Inhalational anesthesia refers to the
delivery of gases or vapors from the
respiratory system to produce anesthesia
Pharmacokinetics-- uptake, distribution,
and elimination from the body.
Pharmacodyamics - MAC value.
Inhaled anesthetic agents remain popular for maintenance and induction of anesthesia.
Inhalation induction is the technique of choice for:
Predicted difficult airway. Difficult intravenous access. Needle phobia, including children.
History of Anesthesia
1845 - Horace Wells- N2O 1846 - William Morton- Ether 1847 - Simpson- Chloroform 1934 - Cyclopropane 1956 - Halothane
Pharmacokinetics and Pharmacodymanics
Pharmacokinetics: how the body affects the drug
Pharmacodymanics: how the drugs affects the body
Anesthetic Uptake Solubility in blood Alveolar blood flow Differences in partial pressure between
alveolar gas and venous blood Therefore: low output states predispose
patients to overdosage of the soluble agents
ELIMINATION
Biotransformation: cytochrome P- 450
(specifically CYP 2EI) Transcutaneous loss or exhalation Alveolus is the most important in
elimination of the inhalation agents Diffusion hypoxia” and the nitrous oxide
Elimination
Redistribution from brain to blood to air
Anesthetics that are relatively insoluble in blood and brain are eliminated faster
Pharmacokinetics
The concentration of a gas in a mixture of gases is proportional to the partial pressure.
Inverse relationship between blood : gas solubility and rate of induction.
Pharmacokinetics
Increase in inspired anesthetic concentration
will increase rate of induction Direct relationship between ventilation rate and
induction rate Inverse relationship between blood flow to
lungs and rate of onset MAC = minimum concentration in alveoli needed
to eliminate pain response in 50% of patients
Hallmark of Anesthesia
Amnesia / Unconsciousness Analgesia Muscle relaxation
Basic Principles of Anesthesia
Anesthesia defined as the abolition of sensation
Analgesia defined as the abolition of pain
“Triad of General Anesthesia” Need for Unconsciousness Need for Analgesia Need for Muscle relaxation
STAGES OF ANESTHESIA
Stage I : Analgesia Stage II : Excitement, combative behavior – dangerous state Stage III : Surgical anesthesia Stage IV : Medullary paralysis –
respiratory and vasomotor control ceases.
Anesthetics are associated with
- Decrease in systemic blood pressure –
myocardial depression and direct
vasodilatation.
- Blunting of baroreceptor control and
decreased central sympathetic tone.
Side Effects
Reduce metabolic rate of the brain Decrease cerebral vascular resistance
thus increasing cerebral blood flow = increase in intracranial pressure
The main target of inhalation anesthetics is the brain.
The important characteristics of Inhalational
anesthetics which govern the anesthesia are : Solubility in the blood
(blood : gas partition co-efficient) Solubility in the fat (oil : gas partition co-
efficient)
BLOOD GAS PARTITION COEFFICIENT
Agents with low solubility in blood quickly saturate the blood. The additional anesthetic molecules are then readily transferred to the brain.
Blood gas partition co-efficient affecting rate of induction and recovery
OIL GAS PARTITION CO-EFFICIENT Higher the Oil: Gas
Partition Co-efficient lower the MAC . E.g., Halothane
1.4 220
0.8
Oil: gas partition co-efficient: It is a measure of lipid solubility. Lipid solubility - correlates strongly with
the potency of the anesthetic. Higher the lipid solubility – potent
anesthetic. e.g., halothane
Ideal Inhaled Anesthetic Pleasant odor Non-irritant Low blood gas solubility. Chemically stable. Non inflammable. Potent. Inert. Not metabolized. Non-toxic. Analgesic. No Cardiovascular & respiratory depression.
Minimal Alveolar Concentration (MAC)
Concentration of inhaled anaesthetics in the
alveolar gas that prevents movements in 50% of
patients in response to a standardized stimulus (eg
surgical incision)
MAC is important to compare the potencies of
various inhalational anesthetic agents.
1.2-1.3 MAC prevent movement in 95% of patients.
MAC
MAC value is a measure of inhalational anesthetic potency.
It is defined as the minimum alveolar anesthetic concentration ( % of the inspired air) at which 50% of patients do not respond to a surgical stimulus.
MAC values are additive and lower in the presence of opioids.
MAC TYPES MAC awake: MAC allowing voluntary response to
command in 50% of patients
MAC 95%: MAC that prevents movement in 95 % of patients
MAC intubation: MAC that allows intubation without muscle relaxant, coughing or bucking in 50% of patients.
MAC-BAR (1.7-2.0 MAC), which is the concentration required to block autonomic reflexes to nociceptive stimuli.
Increase MAC
Hyperthermia. Chronic drug abuse (Ethanol). Acute use of amphetamines. Hyperthyroidism. Reducing age.
Decrease MAC Increasing Age. Hypothermia. Other anesthetic (Opioids). Acute drug intoxication (Ethanol). Pregnancy. Hypothyroidism. Other drugs ( Clonidine ,Reserpine).
No Effect on MAC
Gender Duration of anesthesia Carbon dioxide tension (21-95 mmHg) Metabolic Acid base status Hypertension Hyperkalemia
Inhalation Anesthetic
MAC value %
Oil: Gas partition
Nitrous oxide 104 1.4
Desflurane 7.3 23
Sevoflurane 2.05 53
Isoflurane 1.15 91
Halothane 0.77 220
MACN2O = 105%Halothane = 0.75%Isoflurane = 1.15%Euflurane = 1.68%Sevoflurane = 2%Deslurane = 6%
N2O alone is unable to produce adequate anesthesia ( require high conc. )
Inhalational Agent Reaches The Alveoli
1. Increasing the delivered concentrations of
anesthetic
2. The gas flow rate through the anesthetic
machine
3. Increasing minute ventilation MV = Respiratory Rate × Tidal volume
Inhalational Agent Reaches The Brain
1) The rate of blood flow to the brain
2) The solubility of the inhalational agent in
the brain
3) The difference in the arterial and venous
concentration of the inhalational agent
Inspiratory Concentration (Fi)
Increase FGF rate.
Decrease Breathing System Volume.
Decrease absorption of the breathing
system of the anesthetic machine.
All closer inspired gas
concentration to the fresh gas concentration.
Alveolar Concentration (FA)
The greater uptake of an anesthetic agent; the lower rate
of rise of FA The greater difference between Fi and Fa; the slower the
rate of induction The higher the blood gas solubility coefficient; the
greater the anesthetic solubility, and the slower the onset
of induction and recovery. Increased alveolar blood flow increases anesthetic
uptake.
Solubility in blood Alveolar blood flow Partial pressure difference
between alveolar gas & venous blood (PA- PV)
Arterial Concentration (Fa)
Mainly ventilation perfusion mismatching
Normally, alveolar and arterial anesthetic
pressures are assumed to be equal.
Presence of ventilation perfusion
mismatching increases alveolar arterial
differences
Anesthetic delivery to alveoli
Ventilation Concentration Apparatus Dead Space
Types of Tissues
CO% Relative Solubility
Vessel rich group:Brain, heart, liver, kidney, endocrine glands
75 1
Muscle group: Skin & Muscles
19 1
Fat group: 6 20Vessel poor group:Bone, ligaments, teeth, hair & cartilages
0 0
Nitrous oxide
Safest inhalational anesthetic.
Weak anesthetic but a good analgesic.
No toxic effect on the heart, liver and
kidney.
Caution about diffusional hypoxia.
Megaloblastic anemia.
Nitrous Oxide (N2O)
Physical Property:
laughing Not flammable Odorless Colorless Tasteless
NITROUS OXIDE
Prepared by Priestly in 1776 Anesthetic properties described by Davy in 1799 Characterized by inert nature with minimal
metabolism Colorless, odorless, tasteless, and does not
burn
NITROUS OXIDE
Simple linear compound Not metabolized Only anesthetic agent that is
inorganic
Nitrous Oxide Systemic Effects
Minimal effects on heart rate and blood pressure
May cause myocardial depression in sick patients
Little effect on respiration Safe, effective agent
Nitrous Oxide Side Effects
Manufacturing impurities toxic Hypoxic mixtures can be used Large volumes of gases can be
used Beginning of case: second gas
effect End of case: diffusion hypoxia
Nitrous Oxide Side Effects
Major difference is low potency MAC value is 105% Weak anesthetic, powerful analgesic Needs other agents for surgical
anesthesia Low blood solubility (quick recovery)
Nitrous Oxide Side Effects
Inhibits methionine synthetase (precursor to DNA synthesis)
Inhibits vitamin B-12 metabolism Dentists, OR personnel, abusers at
risk
N2O PHARMACOLOGY
Good Analgesic Weak anesthetic Excreted via lungs MAC = 105% Lower water solubility Not Metabolized in the body
N2O SIDE EFFECTS
Diffusion Hypoxia. Closed gas spaces (N2O can diffuse 20 times faster
into closed spaces than it can be removed, resulting in expansion of pneumothorax, bowel gas, or air embolism or in an increase in pressure within noncompliant cavities such as the cranium or middle ear.
CVS depression Toxicity Teratogenic
Diffusion Hypoxia A decrease in PO2 usually observed as the
patient is emerging from an inhalational anesthetic where N2O was a component.
The rapid outpouring of insoluble N2O can displace alveolar oxygen, resulting in hypoxia.
All patients should receive supplemental O2 at the end of an anesthetic and during the immediate recovery period.
Concentration Effect
Concentration effect states that with higher inspired concentrations of an anesthetic, the rate of rise in arterial tension is greater.
Second Gas Effect
The ability of the large volume uptake of one gas
(first gas) to accelerate the rate of rise of the
alveolar partial pressure of a concurrently
administered companion gas (second gas).
Second Gas Effect
Usually refers to nitrous oxide combined with an inhalational agent. Because nitrous oxide is not soluble in blood, its' rapid absorption from alveoli causes an abrupt rise in the alveolar concentration of the other inhalational anesthetic agent.
Halothane
It is a potent anesthetic. Induction is pleasant. It sensitizes the heart to catecholamines. It dilates bronchus – preferred in asthmatics. It inhibits uterine contractions. Halothane hepatitis and malignant
hyperthermia can occur.
Enflurane
Sweet and ethereal odor. Generally do not sensitizes the heart to
catecholamines. Seizures occurs at deeper levels –
contraindicated in epileptics. Caution in renal failure due to fluoride.