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.