GENERAL ANAESTHESIA

Dr Dewa Ayu Mas Shintya Dewi, SpAn

SMF Anastesi dan Intensive Care
FK UNUD/RSUP Sanglah
ANESTHESI

AN: without, ESTHETOS: perception

“Oliver Holmes” 1846

It is a reversable blocking of pain feeling in

whole body or in a part of it using
pharmacology or other methods
ANESTHESI DIVISION
Local- regional anesthesia, patient is
conscious or sedated
General- anesthesia interact with whole
body, function of central nervous system is
depressed:
– Intravenous
– Inhalation (volatile)
– Combined, balanced
TIVA

Total
Intra
Venous
Anaesthesia
VIMA

Volatile
Induction and
Maintain
Anaesthesia
PARTS OF GENERAL ANETHESI

• Hypnosis- pharmacological sleep,

reversible lack of consciousness
• Analgesia-pain management
• Areflexi-lack of reflexes
• Relaxation musculorum- muscle
relaxation,
Pharmacological reversible neuromuscular
blockade
Parts of general anesthesia must be in balance

HYPNOSIS ANALGESIA

RELAXATION
STAGE OF GENERAL ANESTHESIA

Stadium analgesia (analgesia and sedation stage)

Stadium excitations (excitation stage)

Stadium anesthesia (anesthesia for surgery)

Stadium paralysis (respiration intoxication, respiratory arrest)

I.Analgesia stage
• Pasient consciouss
• Spontaneus respiration
• Reflexes present
• Possible small surgery procedures
like dressing change in burn
II. Excitation stage
-Possible uncontrolled movements,
vomitings

-Increase in respiratory rate

III. Anesthesia for surgery
• It begins with lack of lid reflex
• 4 substages
• Airway opening necessary
• Possible surgery except for abdominal
opening if no relaxants are used
• Possible endotracheal intubation
IV. Paralysis
• Respiratory arrest
• If anaesthesia not discontinued possible
cardiac arrest
picture
Modern methode stages of anesthesia

-Clinical sign: blood pressure, heart rate,

movement, sweat, tears
Instrumental monitoring: skin
conductance, surface electromyogram,
heart rate variability

-Brain EEG monitors (Bispectral Index)

MOLECULAR MECANISM of anesthetic action

A. Meyer overthon theory

Corelation beween lipid solubility (oil: gas partition

coefficient) of inhaled anaesthesia and MAC,
suggested that anaesthesia occurs when
sufficient number of inhalation anaesthetic
The greater is the lipid
solubility of the compound
in the olive oil the greater is
it anaesthesic potency
B. Modern lipid hypothesis
1954…accumulation of anesthetic molecule
use distorsion and thickening sel neural
(lipid bilayer)volume displacement or
expansion membrane concept

Supported by pressure reversal theory

1990…lipid hypothesis
C.Objective to outdate lipid hypotheses

a. Sterioisomer of an anaesthetic drug

b. Immobility or nonimmobilizer
Sterioisomer
- Possibility of spesific protein receptor
interaction as the basis anesthesia

-Levoisomer being more poten than

dextroisomer in enhaching potassium
conductance in neuron

-Example: Dexmedetomidine
Immobility or non immobilizer
All general anaesthetic induce
immobilization (absence of movement in
respon to noksius stimuli throught
depression of spinal cord), amnestic action
exerd within the brain
• Althoght opioids and stimulation alpha 2
adrenergic receptor decrease MAC, it is
unlikely that immobility produce by inhaled
anesthetic
• GABA receptor:
– Ionotropic receptor (GABA A):ligant gate ion chanel
(GABA neurotransmiter bind directly to chanel
protein)
– Metabopronic receptor (GABA B): G-protein ion
receptor
• GABA receptor:
– Ionotropic receptor (GABA A):ligant gate ion
chanel (GABA neurotransmiter bind directly to
chanel protein)

– Metabopronic receptor: G protein coupled

receptor----second messenger activate
proteinkinase or calcium, potasium chanel
GABA A RECEPTOR

1.Potensial action
2.Influc calcium
3.Neurotransmiter GABA release---presinap cleft
4.Tight GABA to receptor
5.Influks chlorida to posinap--Inhibisi posinaptic
potensial---repolarisasi to hyperpolarisasi
6.Comunication intercel -
Glutamat receptor
D. Membran protein hypothesis
General anaesthesia medication do not all interact
with the same molecular target:

a.Voltage gate ion chanel

b.Ligant gate ion chanel (ionotropic recp)
GABA A receptor (prime anesthetic target,
chanel protein that are selective to chloride ion),
glycine, nAChR (nuromuscular block), 5-HT
receptor,NMDA recp (ketamine)
Sedative-Hypnotics Analgesic
Benzodiazepines, The Anesthetized Opioid
propofol, etomidate, Alpha 2 agonists
steroid anesthetics State

Inhibiition of ca and
Activation of GABA A Sedation, loss K channel
receptor Analgesia,
of memory, activation—
Cl chanel---neural loss of pain
consciousness preynaptic
inhibition inhibition

Unitary
Mechanism
Inhibition of Alteration in
glutamate receptors intracelular ca
regulation
Inhalational
Ketamine Anesthetics
FARMACODYNAMIC INTRAVENOUS DRUGS

1.Excitable transmembran protein reseptor

(voltage sensitive ion chanel, ligand-gate ion
chanel, transmembran receptor)

2.Concetration of receptor
receptor in lipid portion “dynamic”---down-
regulation, up-regulation

3.Caracteristics of drugs-receptor interaction

4.Receptor occupancy theory
5.State of receptor activation
6.Drug receptor bond

7.Plasma drug concentrations

8.Initial and maintenance dose
Plasma drugs concentrations
Free fractions Protein
drugs bounds drugs

Plasma drugs
Receptor
Pharmacologic concentrations
concentration
effect drugs

Dose drugs
administered,
intensity of drug
effect
NEUROFISIOLOGY
THANKS