Presenter: Pawan Kumar Ray
Flow of content
Ideal anesthetic agents
Classification of anesthetic agents.
Stages of anesthesia.
Individual drugs and properties.`
During the Middle Ages, attempts were made to use
alcohol fumes as an analgesic during surgery.
Another inhaled technique, the soporific sponge, is
mentioned in numerous manuscripts written in the Middle
The first public demonstration of inhalation
anaesthetic was nitrous oxide used by Professor
Gardner Q. Colton and dentist Horace Wells on 11
On Oct 16th 1846 William Morton successfully
demonstrated Ether anaesthesia at Massachusetts
Ideal inhalational anaesthetic
(1) Stable over a range of temperatures
(2) Not be degraded by light
(3) Does not require the presence of a preservative
(4) Non-explosive and does not support combustion
(5) Odourless or has a pleasant smell
(6) Environmentally safe
(7) Does not react with other compounds (e.g. Soda
lime, plastic and metals etc.)
(8) Has a boiling point well above room temperature
(1) Predictable dose-related CNS depression
(2) Analgesic, anti-emetic and muscle relaxation properties
(3) Minimal respiratory depression, does not cause
coughing or bronchospasm
(4) Minimal cardiovascular effects.
(5) No increase in cerebral blood flow (and therefore
(6) Not epileptogenic
(7) Does not impair renal or hepatic function
(8) No effect on uterine smooth muscle
(9) Does not trigger of malignant hyperthermia
(1) Low blood: gas solubility co-efficient
(2) Low oil: gas solubility co-efficient
(3) Not metabolised or no active metabolites
(4) Is excreted completely by the respiratory system
In administering an anesthesia
Guides in determination of depth of anesthesia
Guedel describe depth of anaesthesia by dividing it
into stages and planes.
Stages of Anesthesia
Guedel’s criteria based on :
Presence or absence of various reflexes
Gillespie added other criteria
Secretion of tears
Response to skin incision
Evaluation of pharyngeal &
Stages were first described for ether anesthesia
Can be used with modification for all agents
Can be recognized during both induction & recovery
Starts from beginning of anaesthetic inhalation and
lasts up to the loss of consciousness.
Pain is progressively abolished.
Patient remains conscious, can hear and see, and feels
a dream like state
Stage I- Stage of Analgesia
Reflexes and respiration remain normal.
Some minor operations can be carried out during this
But it is difficult to maintain
Therefore use is limited to short procedures
Stage starts from loss of consciousness upto gain of
Respiration – Irregular and large in volume
Heart rate and BP raises
Pupils – Large and divergent
Muscle tone increased – jaw may be tight
Patient may shout or struggle
Involuntary micturation , or defecation
Stage II – Stage of Excitement
Extends from onset of regular respiration to cessation of
This has been divided into 4 planes:
o Plane 1- Roving eyeballs.
o This plane ends when eyes become fixed.
o Plane 2- Loss of corneal and laryngeal reflexes.
o Plane 3- Pupil starts dilating and light reflex is lost.
o Plane 4- Intercostal paralysis
Shallow abdominal respiration
Stage III- Surgical Anaesthesia
As anaesthesia passes to deeper planes
Progressively-muscle tone decreases
Heart Rate increases with weak pulse
Respiration decreases in depth and later in frequency
There is cessation of breathing leading to failure of
circulation and death.
Pupil is widely dilated
Muscles are totally flabby
Pulse is thready or imperceptible
BP is very low.
Stage IV- Stage of Medullary
,B:G partition coefficient 12
Guedel’s 4 stages of anaesthesia based on ether
Good Muscle Relaxant
Inflammable and explosive
Slow Induction and Recovery
High incidence of Nausea and Vomitting
High CVS stability ; no myocardial depression.
sympathetic stimulation and preservation of
No respiratory depression and no blunting of Hypoxic
Bronchodilatation and Preserves cilliary activity
• Not flammable but support combustion.
• Prepared by heating NH4NO3 at 245-270°C
NH4NO3 --> N2O + 2H2O
Small amounts of NH3 and HNO3 produced recombine to
NH4NO3 on cooling.
Small amounts of NO and NO2 are also produced-
- Can cause methaemoglobinaemia, pulmonary edema
- N2O must be purified to remove these contaminants
Colour of cylinder = blue.
MAC - 104%
Blood gas partition coefficient -0.46.
Pin index - 3;5
Unlike the potent volatile agents, nitrous oxide is a gas at
room temperature and ambient pressure.
It can be kept as a liquid under pressure because its critical
temperature lies above room temperature
With a MAC value of 104%, nitrous oxide, by itself is not
suitable as a sole anaesthetic agent.
Nitrous oxide is an effective analgesic but poor muscle relaxant
It undergoes minimal metabolism.
The circulatory effects of nitrous oxide are explained
by its tendency to stimulate the sympathetic nervous
Even though nitrous oxide directly depresses
myocardial contractility in vitro, arterial blood
pressure, cardiac output, and heart rate are essentially
unchanged or slightly elevated in vivo because of its
stimulation of catecholamine
By increasing CBF and cerebral blood volume, nitrous
oxide produces a mild elevation of intracranial
Nitrous oxide also increases cerebral oxygen
The second gas effect
The 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 anaesthetic
•At the end of anesthesia after discontinuation of N2O,
N2O diffuses from blood into the alveoli much faster
than N2 diffuses from alveoli into the blood.
• Total volume of gas in the alveolus → fractional
concentration of gases in the alveoli is diluted by N2O
→ ↓ PaO2 & PaCO2 → hypoxia.
•This occurs in the first 5-10 mins of recovery. Therefore
it is advised to use 100% O2 after discontinuation of
Toxicities – Nitrous Oxide
N2O antagonizes B12 metabolism
inhibition of methionine-synthetase
Decreased DNA production
RBC production depressed (megaloblastic anaemia)
Long term exposure to N2O is hypothesized to result in
neurologic disease similar to B12 deficiency
35 times more soluble in blood than nitrogen, N2 so fills and expands
any air-containing cavities:
intraocular air bubbles
may exacerbate pulmonary hypertension
50% N2O + 50% O2
Colour coding = blue body with blue &white quarters.
Pin index = 7
Poyinting effect: normally N2O is liquid at 2400 psig.
But If N2O is mixed with O2 it remains in gaseous
state called poyinting efect.
Use: 1)labour analgesia.
Volatile- kept in sealed bottles
Pleasant odor-suitable in pediatrics for inhalation
induction (although sevoflurane is now the agent
of choice )
Corrosive-Interaction – rubber and plastic tubing
20% metabolized in liver by oxidative pathways.
Major metabolites : bromin, chlorine, Trifloroacetic
acid, Trifloroacetylethanl amide
Systemic effects of Halothane
Generalized CNS depression
cerebrovascular dilation causes increased ICP
Autoregulation is blunted
• A dose-dependent reduction of arterial blood pressure is due to direct
• blunts baroreceptor reflex
•Although halothane is a coronary artery vasodilator,
coronary blood flow decreases, due to the drop in systemic
• Adequate myocardial perfusion is usually maintained, as
oxygen demand also drops- maybe advantages In pts with
•Halothane sensitizes the heart to the arrhythmogenic
effects of catecholamine
◦To minimize effects :
Avoid hypoxemia and hypercapnia
Avoid conc. Of adrenaline higher than 1 in 10000
best bronchodilator among the currently available volatile
attenuates airway reflexes and relaxes bronchial smooth muscle
by inhibiting intracellular calcium mobilization.
depresses clearance of mucus from the respiratory tract
(mucociliary function), promoting postoperative hypoxia and
-Both GFR and renal blood flow is decreased-because of
decrease cardiac output.
- associated with reversible reduction in GFR.
Gastro intestinal tract:-
Inhibition of gastrointestinal motility.
Cause sever post. Operative nausea & vomiting.
Halothane relaxes uterine muscle, may cause postpartum
Concentration of less than 0.5 % associated with increase
blood loss during therapeutic abortion.
Its cause skeletal muscle relaxation .
Postoperatively, shivering is common , this increase
oxygen requirement>>> which cause hypoxemia.
Post operative shivering (halothane shakes) and
hypothermia is maximum with halothane among
Halothane - Hepatic Toxicity
All inhaled AA can cause hepatic injury in animal
All inhaled AA have immunohistochemical
evidence of binding to hepatocytes
Thought that Trifluoroacetic acid metabolites are
Another theory is due to Hypoxia as halothane causes
Hepatic arterial constriction
The incidence of fulminant hepatic necrosis terminating
in death associated with halothane was found to be 1 per
Demographic factors ; It’s a idiosyncratic reaction,
susceptible population include Mexican Americans,Obese
women, , Age >50 yrs, , Familial predisposition, Severe
hepatic dysfunction while Children are resistant.
Prior exposure to halothane is a important risk factor &
multiple exposure increases the chance of hepatitis.
Mechanism of Toxicity
There are various proposed mechanisms:
• Metabolite-mediated direct toxicity
• Immunologically-mediated damage to liver cells
a proportion is biotransformed by hepatic microsomal enzyme CYP 2E1
to a trifluoroacetic acid which can be detected in the urine, but which
also can trifluoroacetylate hepatic proteins, some of which may be
immunogenic and induce cytotoxic reactions.
• Hypoxia alone
Two type of dysfunction:
1- Type I hepatotoxicity:-mild, associated with
derangement in liver function test , this result from
metabolic of Halothane in liver. results from reductive
(anaerobic) biotransformation of halothane rather than the
normal oxidative pathway.
2- Type II hepatotoxicity: fulminate (uncommon); sever
jaundice ,fever, progressing to fulminating hepatic
Its increased by repeated exposure of the drugs.
high mortality 30-70%
1- A careful anesthetic history .
2- repeated exposure of halothane within 3 months should be
3- History of unexplained jaundice or pyrexia after previous
exposure of halothane.
Recommendation for Halothane anesthesia:
1. Beta blockers and calcium channel blockers can
produce severe depression of cardiac function with
2. Aminophylline can produce serious ventricular
arrhythmias with halothane.
3 .Halothane sensitizes the heart to the
arrhythmogenic effects of epinephrine, so that doses
of epinephrine above 1.5 g/kg should be avoided.
susceptibility unexplained liver dysfunction after
previous halothane exposure
intracranial mass lesion
with aminophylline has been associated with severe
2-chloro 1-trifluro methyl-
MAC is 1.17 % B:G p co-ef is 1.17.
Isoflurane is characterized by extreme physical
stability, undergoing no detectable deterioration during 5 years of
storage or on exposure to carbondioxide absorbents or sunlight.
The stability of isoflurane obviates the need to add preservatives such
as thymol to the commercial preparation.
Initially, until deeper levels of anesthesia are reached,
isoflurane stimulates airway reflexes with:
increases in secretions
low concentration Vs High concentration.
Low : no change on the flow.
High : increase blood flow by vasodilatation of the cerebral
Generalized CNS depression; Rapid emergence
Increased ICP reversed by Hyperventilation
Agent of choice for neuro-anaesthesia.
myocardial depression, decreased vascular assistance &
Preserves baroreceptor reflex . So that reflex tachycardia
occurs in response to decrease B.P maintaining cardiac
Agent of choice for cardiac anaesthesia.
Coronary steal phenomenon
Isoflurane induced coronary artery vasodilatation can lead to
redistribution of coronary blood flow away from diseased areas
where arterioles are maximally dilated to areas with normal
responsive coronary arteries. This phenomenon is called
the coronary steal syndrome
Florinated Methyl –
Low blood:gas partition coefficient -0.69 (Rapid induction and
Compared with isoflurane, recovery from sevoflurane anesthesia
is 3 to 4 minutes faster and the difference is magnified in longer
duration surgical procedures (>3 hours)
Pleasant smell , non irritant,bronchodilatation and least airway irritation
among current volatile agents makes it acceptable for inhalation induction
• agent of choice for paediatric anesthesia.
• 2nd agent of choice for
• Neuro anesthesia.
• Cardiac anesthesia .
Does not sensitize the myocardium to catecholamines as much as
Does not result in carbon monoxide production with dry soda lime.
Sevoflurane may be 100-fold more vulnerable to metabolism
than desflurane -estimated 3% to 5% of the dose undergoing
metabolites - inorganic fluoride
cannot undergo metabolism to an acyl halide.
does not result in the formation of trifluoroacetylated liver
Therefore cannot stimulate the formation of
antitrifluoroacetylated protein antibodies.
So devoid of the potential to produce hepatotoxicity as well
as cross-sensitivity between drugs.
Sevoflurane and Compound A
Sevoflurane forms a degradation product, compound
ether] on contact with the soda lime in a rebreathing
Compound A is a dose-dependent nephrotoxin in rats.
A proposed mechanism for nephrotoxicity is the metabolism of
compound A to a reactive thiol via the β-lyase pathway.
Because humans have less than one-tenth of the enzymatic
activity for this pathway compared to rats, it is possible that
humans should be less vulnerable to injury by this mechanism.
Sevoflurane can also be degraded into hydrogen fluoride by
metal and environmental impurities present in manufacturing
equipment, glass bottle packaging, and anesthesia equipment.
Hydrogen fluoride can produce an acid burn on contact with
The risk of patient injury has been substantially reduced by
inhibition of the degradation process by adding water to
sevoflurane during the manufacturing process and packaging it
in a special plastic container.
Postoperative agitation may be more common in children then
seen with halothane.
2-fluro,1-trifluro methyl ethyl ether.
MAC =6.6 %
differs from isoflurane only by substitution of a fluorine atom for
the chlorine atom found on the alpha-ethyl component of
Fluorination rather than chlorination increases vapor pressure
(decreases intermolecular attraction), enhances
molecular stability, and decreases potency.
desflurane would boil at normal operating room temperatures
A new vaporizer technology addressed this property, producing
a regulated concentration by converting desflurane to a gas
(heated and pressurized vaporizer that requires electrical
power),which is then blended with diluent fresh gas flow
Solubility characteristics (blood:gas partition coefficient 0.45)
and potency (MAC 6.6%) permit rapid achievement of an
alveolar partial pressure necessary for anesthesia followed by
prompt awakening when desflurane is discontinued.
Pungent odor --desflurane less likely to be used for
inhalation induction compared to halothane or
Airway irritation, breath-holding, coughing,
laryngospasm,significant salivation, when >6%
desflurane administered to an awake patient.
Produces the highest carbon monoxide
concentrations, followed by enflurane and isoflurane
Dual-circuit gas–vapour blender
It was created specifically for the agent desflurane.
Desflurane boils at 23.5 ºC, which is very close to room
This means that at normal operating temperatures, the saturated
vapour pressure of desflurane changes greatly with only small
fluctuations in temperature.
A desflurane vaporiser (e.g. the TEC 6 produced by Datex-
Ohmeda) is heated to 39C and pressurised to 200kPa
Agent of choice for day care (fastest induction)
Agent of choice for geriatric (old) patients.
Agent of choice for hepatic failure
Agent of choice for renal failure
Anesthetic B:G PC MAC Features Notes
Halothane 2.3 0.74% PLEASANT Arrhythmia
Enflurane 1.9 1.69% PUNGENT Seizures
Isoflurane 1.4 1.17% PUNGENT Widely used
Sevoflurane 0.62 1.92% PLEASANT Ideal
Desflurane 0.42 6.1% IRRITANT Cough
Nitrous 0.47 104% PLEASANT Anemia
Most ideal inhalational agent.
Blood gas partition co-efficient is 0.14. least of all .least
soluble. so fastest induction and fastest recovery.
MAC is 70% so can be given with 30%O2.
No metabolism in body –least side effects non terratogenic.
Non inflamble,does not deplete ozone layer.
Disadvantages = costly, needs special equipment for
Acts on NMDA receptor
• increased ICP secondary to increased cerebral blood flow (CBF)
• produce fast frequency and high voltage on the EEG.
• Decrease the threshold for seizure-Epileptogenic inhalational
• It is primarily used for procedure in which a low threshold for
seizure generation is required like ECT.
• myocardial depressant
• decreased vascular resistance; decreased mean arterial pressure
Most potent analgesic agent - trielene
Reaction with sodalime :-
dichloroacetylene – neurotoxic- V, VII.
phosgene - pulmonary toxicity(ARDS)
1st agent used for labour analgesia.
Cardiotoxic- death due to ventricular fibrillation.
Most potent inhalational agent (mac-0.16%).
Slowest induction and recovery(b:g – 15).
Most nephro-toxic agent –high output renal failure
Reacts with rubber tubing of closed circuit
Most inflamable & explosive agent
Liquid gas-Orange cylinder.
Increases sympathetic tone and B.P.
Agent Of Choice in Shock