Dr.

Umer Sufyan M
 Anaesthesia is a reversible condition of comfort,
quiescence and physiological stability in a patient before,
during and after performance of a procedure.

General anaesthesia is for surgical procedure to render

the patient unaware / unresponsive to the painful
stimuli.
 Pre-1846 - the foundations of anaesthesia

1846 - 1900 - establishment of anaesthesia

20th Century - consolidation and growth

21st Century - the future

SOME STRANGE METHODS OF ANAESTHESIA

Strangulation Assyrians
Cerebral concussion
Applying intense cold or compression
 Status of surgery
Barber shop surgeons

Types of surgery
Amputations & dental
extractions
No antisepsis
Appalling mortality

Indications
Unbearable pain
Crippling deformity
Imminent death

Surgeons used to boast of speed of surgery

 Drug methods Non-drug methods
Cold
Alcohol
Concussion
Opium (poppy)
Carotid compression
Hyoscine (Mandrake) Nerve compression

Cannabis (Hemp) Hypnosis

Blood letting
Cocaine (New World)
 Middle Ages the anesthetic effects of cold water and ice were
recognized.
In 17th century, Marco Aurelio Severino described the
technique of refrigeration anesthesia in which snow was
placed in parallel lines across the incisional plane such that
the surgical site became insensate within minutes. The
technique never became widely used, likely because of the
challenge of maintaining stores of snow year-round.
 manipulation of the psyche to relieve surgical pain was
undertaken by French physicians Charles Dupotet and Jules
Cloquet in the late 1820s with hypnosis, then called
mesmerism.
Greek physician from the first century AD, commented on
the analgesia of mandragora, a drug prepared from the bark
and leaves of the mandrake plant. He observed that the plant
substance could be boiled in wine, strained, and used in the
case of persons about to be cut or cauterized, when they
wish to produce anesthesia.Mandragora was still being used
to benefit patients as late as the 17th century.
 Alcohol was another element of the pre-ether
armamentarium because it was thought to induce stupor and
blunt the impact of pain
Laudanum was an alcohol-based solution of opium first
compounded by Paracelsus in the 16th century. It was wildly
popular in the Victorian and Romantic periods, and
prescribed for a wide variety of ailments from the common
cold to tuberculosis. it was frequently misused and abused.
Laudanum was given by nursemaids to quiet wailing infants
and abused by many upper-class women, poets, and artists
who fell victim to its addictive potential.
 In 1773 Nitrous oxide was first prepared by Joseph Priestley.
In 1799 Davy commented that nitrous oxide transiently
relieved a severe headache, obliterated a minor headache,
and briefly quenched an aggravating toothache. quoted ; As
nitrous oxide in its extensive operation appears capable of
destroying physical pain, it may probably be used with
advantage during surgical operations in which no great
effusion of blood takes place.Davy's lasting nitrous oxide
legacy was coining the phrase laughing gas to describe its
unique property.
 Michael Faraday

1818: Michael Faraday (1791-1867) described narcotic effects

of ether
1821: Benjamin Brodie (1783-1862) demonstrated to Royal
College of Surgeons that ether inhalation could induce
insensibility in a guinea pig - .ether acted like a narcotic
poison
In 1831 David Waldie suggested
chloroform, which had first been prepared.

Benjamin Brodie
 Horace well

In Dec 10 1844 Horace Wells observed a lecture-exhibition

on nitrous oxide by an itinerant scientist, Gardner Quincy
Colton, who encouraged members of the audience to inhale a
sample of the gas. Wells observed a young man injure his leg
without pain while under the influence of nitrous oxide.
Sensing that it might provide pain relief during dental
procedures, Wells contacted Colton and boldly proposed
 Horace Wells, The next day Wells had a tooth extracted
while breathing nitrous oxide. An attempt in 1845 by Wells
to demonstrate his discovery at the Massachusetts General
Hospital in Boston ended in failure when the patient cried
out and nitrous oxide fell into disuse.
 In january 1842 William E. Clarke, a medical student from
Rochester, New York, given the first ether anesthetic.
Clarke entertained his companions with nitrous oxide and
ether. By these experiences, he administered ether, from a
towel, to a young woman named Hobbie. One of her teeth
was then extracted without pain by a dentist named Elijah
Pope but it was suggested that the woman's unconsciousness
was due to hysteria and Clarke was advised to conduct
no further anesthetic experiments.
 March 30, 1842, Crawford Williamson Long administered
ether with a towel for surgical anesthesia in Jefferson,
Georgia. His patient, James M. Venable, was a young man
who was already familiar with ether's exhilarating effects,
enable had two small tumors on his neck but refused to have
them excised because he feared the pain that accompanied
surgery.
Knowing that Venable was familiar with ether's action,
Dr. Long proposed that ether might alleviate pain and gained
his patient's consent to proceed. After inhaling ether from the
towel and having the procedure successfully completed,
Venable reported that he was unaware of the removal of the
tumors. In determining the first fee for anesthesia and
surgery, Long settled on a charge of $2.00.
 In 1846 William T.G. Morton, a Boston dentist and medical
student, performed the first public demonstration of general
anesthesia using diethyl ether.

William T G Morton
Inventor and Revealer of
Inhalational Anaesthesia:
Before Whom, in All Time,
Surgery was Agony;
By Whom, Pain in Surgery was
Averted and Annulled;
Since Whom, Science has
Control of Pain.
 Oct 16 1846 Gilbert Abbott underwent surgical excision of a
neck tumor at the Massachusetts General Hospital in the
operating room now known as "the ether dome." The era of
modern anesthesia and a revolution in the medical care of the
surgical patient had begun.
 Nov 4 1847 James young Simpson and his friends inhaled
chlorofom after dinner at a party in Simpson's home on the
evening and they promptly fell unconscious and, when they
awoke, were delighted with their success. Simpson quickly
set about encouraging the use of chloroform.
The relief of obstetric pain had significant social
ramifications and made anesthesia during childbirth a
controversial subject.
Simpson argued against the prevailing view, which held that
relieving labor pain opposed God's will. Simpson asserted
that labor pain was a result of scientific and anatomic causes,
and not the result of religious condemnation.
He did articulate many concepts that his contemporaries
were debating at the time.
 John Snow (1813-1858)

Chlorofom Popularised by James.Y.Simpson & practiced by

John Snow
John Snow used chlorofom to deliver the last two children of
Queen Victoria
Snow gave analgesic doses of chloroform on a folded
handkerchief. This technique was soon termed
chloroform la reine
Victoria abhorred the pain of childbirth and enjoyed
the relief that chloroform provided. She wrote in her
journal, Dr. Snow gave that blessed chloroform and
the effect was soothing, quieting, and delightful
beyond measure.
 In 1934 The anesthetic properties of cyclopropane were
discovered accidentally by Ralph Waters chemists
analyzing impurities in propylene.
In 1956 came the introduction of halothane by Charles
Suckling, a nonflammable volatile halogenated alkane that
quickly became the dominant anesthetic.
DEFINITION:
General anaesthetics are the drugs which produce reversible
loss of all sensations and consciousness.

FEATURES OF GENERAL ANAESTHETICS:

Loss of all sensations particularly, pain
Sleep and amnesia
Immobility and muscle relaxation
Abolition of reflexes

23
GENERAL LOCAL
ANAESTHETICS ANAESTHETICS

Act on CNS. Act on peripheral nerves.

Whole body is involved.
Consciousness is lost.
Care of vital functions is
essential.
Can be given in non-
cooperative pts.
Preferred in major
surgeries.
Restricted areas of body
involved.
Consciousness is
unaltered.
Care of vital functions
not essential.
Not possible in non-
cooperative pts.
Preferred in minor
surgeries.

24
STAGES OF ANAESTHESIA:
By GUEDEL in 1920 referring to the anaesthetic
Ether

Stage I. Stage of analgesia:

Starts from beginning of anaesthetic inhalation and lasts
upto the loss of consciousness.
No amnesia ,Conciousness and sense of touch present
Stage II. Stage of excitement and delirium:

Patient shows violent combative behaviour but definitely

amnesic
Irregular rise in BP &RR

25
Stage III. Surgical Anaesthesia:
Regular respiration and relaxation of skeletal muscle occurs
Plane 1 - Roving eyeballs, respiration and skeletal muscle
tone are normal.
Plane 2 - Loss of corneal & laryngeal reflexes, respiration is
slow but regular.
Plane 3 - Dilatation of pupil , loss of light, corneal and
laryngeal reflexes.
Plane 4 - Complete muscle relaxation, pupils dilated,
respiration is abdominal

26
Stage IV . Medullary paralysis:
Stage appears due to overdosing

Severe deppression of respiratory centre as well as

vasomotor center in medulla, this stage is fatal and death
ensue .

27
MECHANISM OF ACTION:
Ligand gated ion channels are the major targets
GABA A - R gated Cl- channel : inhalational
anaesthetics, barbiturates, BZD, propofol, potentiate the
action of inhibitory transmitter GABA to open Cl-
channel.
Glycine: in the spinal cord & medulla is augmented by
barbiturates , propofol & inhalational anaesthetics
Fluorinated anaesthetics & barbiturates: inhibit neuronal
cation channel gated by nicotinic cholinergic receptor
 N2O & ketamine inhibit the excitatory NMDA type of
glutamate receptor.
GA inhibit release of the presynaptic excitatory
neurotransmitters. Also alter the postsynaptic responsiveness to
the released neurotransmitter by increasing the activity of the
inhibitory ion channels in the post synaptic receptors and
enhance inhibitory neurotransmission within the CNS
Main site of causation of ;

Unconsciousness Thalamus or RAS

Amnesia Hippocampus
Immobility on surgical stimulation Spinal cord.

Important properties which determine the potency of

inhalational anaesthetics :-
MAC value
Blood-gas partition coefficient

31
 MAC(minimum alveolar conc.):
It is the conc. of anaesthetic required to prevent
movement in 50% of patients in response to a standard
surgical incision.
Smaller MAC value- more potent is the anaesthetic.
Anaesthetic with high lipid solubility has lower MAC
value
Methoxyflurane - most potent with least MAC value.
Nitrous oxide - least potent with highest MAC value.

32
BLOOD-GAS PARTITION COEFFICIENT:
Determined by solubility of an agent in the blood.
It determines the speed of onset & recovery of an
anaesthetic drug.
Greater the blood-gas partition effect, lesser is the speed
of onset & recovery.
Desflurane is the fastest acting drug as it has least BGP
coefficient.

33
 Breathing Circuits

Open system
Open is the old fashioned method of dropping
ether or chloroform over a gauze or lint. Later
modernised by the likes of the Schimmelbusch Schimmelbusch
mask. mask
 In the early 1950s, Prof. WW Mapleson from University of
Wales, Cardiff, classified the several breathing systems
around depending on what components they contained and
what position they took in the system.
It is known today as The Mapleson Alphabet
Partial rebreathing is allowed through a partially closed
valve.conditions are intermediate with moderate flow rates.
 Closed system

Closed systems use a CO2

absorbent so that the gases
are re-circulated, the
classification is defined by
the amount of fresh gas flow.

Sodalime are used to absorb

co2.Preferred in conditions
with high production of co2.
CLASSIFICATION:

General
anaesthetics

Inhalational Intravenous

37
Inhalational: Intravenous:
Gas: Nitrous Oxide Inducing agents:

Volatile liquids: Thiopentone,

Methohexitone sodium,
Ether
propofol and etomidate
Halothane Benzodiazepines (slower
Enflurane acting):
Isoflurane Diazepam, Lorazepam,
Desflurane Midazolam
Dissociative anaesthesia:
Sevoflurane
Ketamine
NITROUS OXIDE:
Colourless ,odourless non irritating and non-inflammable gas.

Good analgesic but weak anaesthetic agent due to high MAC.

Produces analgesia when inhaled in a conc. of 35- 40% with air.

ENTONOX - 50% Nitrous oxide + 50% Oxygen.

If administered along with air, produces a stage of excitement and

delirium and also produces amnesia. hence, it is known as
laughing gas.

Safest anaesthetic agent. Has no serious, deleterious effects on

circulation, respiration, liver and kidneys.

39
 SECOND GAS EFFECT Nitrous oxide is insoluble in
blood and thus rapid induction and rapid reuptake of
Nitrous oxide from alveolar gas leads to rapid rise in
concentration of coadministered halogenated anaesthetic
agent and it increases the speed of induction of these
volatile anaesthetic agents

When anaesthetic is discontinued ;the anaesthetic moves

from blood to alveoli.

40
In case of NO the amount may be about 10% of expired
volume and this may be sufficient to reduce the alveolar
partial pressure of oxygen causing transient mild Hypoxia
known as Second Effect & the hypoxia is called Diffussion
hypoxia.

This hypoxia can be prevented by administration of 100%

oxygen 5-10 min after discontinuing nitrous oxide
Therapeutic uses:
Tooth extraction.

Obstetric analgesia.

Painful procedures such as change of dress in burns pts,

cleaning and debridement of wounds and cauterisation

Used as a carrier gas for inhalational agents like

Halothane.

42
Advantages:
Non inflammable and non irritant.
Rapid induction and recovery due to low B/G Partition
coefficient.
Analgesic property
Nausea and vomiting are uncommon.

Disadvantages:
Not a potent anaesthetic.
Poor muscle relaxant.
Special apparatus is required.
Carbon dioxide accumulation & hypoxia on prolonged use

43
 Bone marrow depression and megaloblastic anaemia
seen on prolonged use.
ETHER:
Colourless volatile liquid with a pungent odour..
Ether when exposed to air, moisture or light form ether
peroxides or acetic aldehyde which are irritant.
To avoid this, ether is stored in sealed containers or
amber coloured bottles.
Potent anaesthetic .
Marked muscle relaxant action.

44
advantages:

Can be administered without complicated apparatus.

Can be used during an emergency without pre-

anaesthetic medication.

Can be used during delivery.

Good bronchodilator ,safe in asthmatics.

Causes satisfactory muscle relaxation.

45
Disadvantages:

Inflammable and explosive.

Induction and recovery are slow.

Irritant and may cause nausea and vomiting.

Increase in salivary and bronchial secretion may

cause cough or laryngeal spasm.

46
HALOTHANE:
Volatile liquid structurally similar to chloroform with a
characteristic sweetish & fruity odour.

Produces loss of consciousness in a conc. of 2 - 3% in

oxygen vapour.

P/K

60-80% of halothane is eliminated unchanged through

lungs in first 24 hrs. About 20% is retained in the body
and is metabolized.

47
Advantages:

Non-irritant and non inflammable.

Inhibit pharyngeal and laryngeal reflexes, making tracheal

intubation easy.

Potent anesthetic , speedy induction & recovery

Inhalational agent of choice in bronchial asthma.

Disadvantages:

Special apparatus is required.

Causes malignant hyperthermia in susceptible individuals.

Halothane induced hepatitis.

48
 Causes hypotension by direct depression of
myocardium .

Sensitizes heart to catecholamines causing cardiac

arrhythmias.

Can raise intracranial tension due to cerebral

vasodilatation.

49
MALIGNANT HYPERTHERMIA:
Autosomal dominant inheritance.

Features- rapid rise in body temp, muscle rigidity,

tachycardia, hyperkalemia, rhabdomyolysis, acidosis.

Physiology - caused by heat production in skeletal

muscle due to excessive release of calcium from
sarcoplasmic reticulum.

Associated with mutations in the gene encoding for

RYANODINE receptors which controls calcium release
from sarcoplasmic reticulum.

50
 Triggered by halogenated anaesthetics and neuromuscular
blocking drugs.

The most reliable test to establish genetic susceptibility is the

caffeine-halothane contracture test using skeletal muscle biopsy

tissue.

Diagnosis - increase co2, rise in creatine kinase levels,

myoglobinuria, muscle biopsy.

Treatment - early detection, hyperventilation, IV

Dantrolene(1mg/kg), ice packs/cooling blankets, lasix/
mannitol / fluids.

51
ENFLURANE:
Anaesthesia by enflurane resembles to anaesthesia by
halothane

Non irritant and non inflammable .

Like halothane it causes hypotension.

Causes bronchodilatation.

Cause uterine relaxation.

Sensitizes heart to the action of catecholamines

It is contra indicated in epileptic patients.

ISOFLURANE:
Advantage :
Rapid induction and recovery.
Stable and non inflammable.
Bronchodilator.
Good muscle relaxant.
Potent coronary vasodilator.
Does not sensitize myocardium to adrenaline.
Disadvantages:
Respiratory irritant
CORONARY STEAL PHENOMENON
DESFLURANE:
Properties are similar to those of isoflurane but with
faster onset and recovery.
Respiratory irritant, causes cough and laryngospasm.
Useful for daycare surgery.

SEVOFLURANE:
More potent than desflurane and does not cause
respiratory irritation.
Inhalational agent of choice in children
can produce a nephrotoxic metabolite
METHOXYFLURANE:
Most potent inhalational agent due to least MAC.

Slowest induction and recovery.

Nephrotoxic and hepatotoxic due to highest amount of

flouride.
 INTRAVENOUS ANAESTHETICS

THIOPENTONE SODIUM:
Ultra short acting barbiturate which induces anaesthesia
within a minute.

Crosses BBB rapidly following an I.V. bolus inj

Due to its high lipid solubility diffuses rapidly out of brain

and is redistributed to body fats, muscles and other tissues.

Induction dose is 3-5 mg/kg.

56
Therapeutic uses;

Induction of general anaesthesia.

As anaesthetic agent for operations of short duration like

fracture reduction, dilatation and curettage, laryngoscopy and
bronchoscopy.

In pts with H/O malignant hyperthermia.

As an anticonvulsant in emergency treatment of intractable

seizures.

57
Adverse effects:

Laryngospasm may occur when intubation is attempted

while anaesthesia is light.

No muscle relaxant activity.

No analgesic activity.

Bronchospasm hence contraindicated in asthmatics.

Can ppt fulminant attack in acute intermittent porphyria.

58
ETOMIDATE:
Similar to thiopental in all aspects but rapidly metabolised
than thiopental& causes less hangover.
Less cardiovascular & respiratory depression than thiopental.
Causes involuntary movements during induction, post
operative nausea and vomiting & pain at the injection site.
On prolonged use causes adrenocortical suppression. Hence
CI in adrenal insufficiency.

59
PROPOFOL

Di isopropyl alcohol

Available as 1% or 2% emulsion in soyabean oil

Induction of anaesthesia with 1.5- 2.5 mg/kg occurs within

30 sec and reversal is also rapid.

No nausea and vomiting.

60
Therapeutic uses:

Good agent for day care surgery.

Can be given in Porphyrias and also in Neurosurgeries.

Malignant hyperthermia.

Adverse effects:

Pain at the site of injection.

Apnoea.

Cv unstable - BP&HR due to PR.

Depresses respiratory centre.

KETAMINE:
It is related to phencyclidine.
Acts as an antagonist at NMDA receptors.
Potent bronchodilator.
It induces a state of DISSOCIATIVE ANAESTHESIA
characterised by complete analgesia combined with amnesia
and sedation without actual loss of consciousness. Patient
can open his eyes & can obey instructions.

62
 Anesthesia can be induced by both IM (5-10 mg/kg) and
IV(1-2 mg/kg) routes.

It increases BP, heart rate and CO by raising blood levels of

Nor adrenaline. Can be used in pts with shock.

It should be avoided in pts with ischaemic heart disease.

Therapeutic uses:

Used as an inducing agent & for maintenance of anesthesia

during diagnostic procedures like cardiac catheterisation and
bronchoscopy.

63
 Can be used in short procedures like dressing of burns,
forceps delivery, manual removal of placenta and dental
work.

Disadvantages:

May cause nystagmus, involuntary movements &

hypertonus.

Increases intraocular and intracranial pressures.

It is a drug of abuse.

May cause delirium, hallucinations.

64
Contraindications:

Pts suffering from HTN, cardiac decompensation or

cerebrovascular accident.

During operations of eye as it intraocular pressure.

Barbiturates & Diazepam are chemically incompatible with

ketamine.So, they should never be administered from same
syringe.

65
METHOHEXITONE:
3 times more potent than thiopentone.

Induces seizures, so it is an agent of choice for

electroconvulsive therapy.

MIDAZOLAM:
Short acting BZD .

Used in premedication as IM or for sedation as IV in

endoscopic procedures.
It is water soluble & less irritant to veins than Diazepam.

66
PREANAESTHETIC MEDICATION:
Drugs used prior to the administration of an anaesthetic
agent to make anaesthesia more safer & more agreeable to
the pt. It is given ;
For sedation to reduce anxiety & apprehension.
To obtain an additive or synergistic effect so that induction
is smooth & rapid.
To counteract some adverse effects of anaesthetic drugs
such as salivation, bradycardia & vomiting.
To relieve pre and post operative pain.
 to suppress respiratory secretions and to reduce reflex
excitability.
Usually, a combination of drugs are used. Most commonly used
drugs for preanaesthetic medication are:

OPIOID ANALGESICS - morphine(10-15mg IM), pethidine(50-

100 mg IM), buprenorphine(300 mcg IM).These drugs possess
very strong analgesic activity.

- may depress respiration & cause resp.arrest.

- may cause vasomotor depression.

- may induce vomiting & cause antidiuresis.

SEDATIVES - BZD are preferred because of their safety,
muscle relaxant property and less resp.depression.

ANTIMUSCARINIC DRUGS - Anticholinergic drugs (eg,

atropine and glycopyrrolate) may be used to decrease
oral and airway secretions and to treat bradycardia;

H2 BLOCKER/PROTON PUMP INHIBITOR

Ranitidine (150mg)/famotidine (20mg)/

omeprazole (20mg ) given night before and in the

morning reduces chance of regurgitation.

69
ANTIEMETICS Metoclopramide 10-20mg IM
preoperatively effective in reducing post operative vomiting

Domperidone is nearly as effective and doesn't produce

extrapyramidal side effects
NEUROLEPT ANALGESIA:
Neuroleptics- drugs which induce state of apathy and
mental detachment- pt is mildly sedated & uncaring about
his surroundings.

Neurolept analgesia combined use of neuroleptic drug

with an opioid analgesic.

Most commonly used combination is the neuroleptic

Droperidol 2.5 mg and opioid analgesic Fentanyl citrate
50 mcg.

71
 Neurolept analgesia can be converted to Neurolept-anaesthesia
by concurrent administration of 65% Nitrous oxide and 35 %
Oxygen

DRUG INTERACTIONS :

1. Patients on antihypertensives given general anaesthetics -

BP may fall markedly.

2. Narcoleptics, opioids, clonidine and monoamine oxidase

inhibitors potentiate anaesthetics.

3. Halothane sensitizes heart to Adrenaline.

4. If a patient on corticosteroids is to be anaesthetized,

100 mg of hydrocortisone is given intraoperatively

because anaesthesia is a stress can precipitate adrenal
insufficiency and cardiovascular collapse

5. Insulin need of a diabetic is increased during GA :

Switch over to plain insulin even if the patient is on oral

hypoglycaemics.

73
References:-
Rang & Dale - Pharmacology
sixthEdition
R.S.Satoskar - Pharmacology &
Therapeutics Twenty second Edition.
Goodman & Gilman's
The Pharmacological Basis Of -
Therapeutics - twelth Edition.
H.L Sharma & K.K Sharma The Principle
of Pharmacology second Edition.
K.D Tripathi - Essentials Of Medical
Pharmacology. Seventh Edition
Lippincotts - Illustrated Reviews
Pharmacology - Fourth Edition.
Barash clinical anaesthesia sixth Edition
Millers anaesthesia seventh edition
74