Assesment of general anesthesia

1. GENERAL
ANESTHESIA
BY: DR AMBIKA BHANDARI
MDS 2ND YEAR

2. PART 1
PHARMACOLOGICAL
ASPECT

3. CONTENTS
• Introduction
• History
• General considerations
• Drugs
• Inhalational anesthetics
• Intravenous anesthetics
• Pre anesthetic medications
• Other medications

4. INTRODUCTION
• Anesthesia – is a reversible condition of comfort,
quiescence and physiological stability in a
patient before, during and after performance of
a procedure.
• General anesthesia – for surgical procedure to
render the patient unaware / unresponsive to
the painful stimuli.

5. HISTORY
• Primitive man employed digital
compression of the carotid arteries
to produce anesthesia.
• The literal translation of the Greek
and Russian terms for the carotid
itself is “The Artery of Sleep.”
• About 3400 BC, Opium poppy
(Papaver somniferum) was
cultivated in lower
Mesopotamia by the
Sumerians
• The Hindus inhaled the fumes
of burning hemp (plant) in the
year 977 as an anesthetic. The
Chinese physician, Hoa -Tho,
called it "Ma-yo“
• In 1020s Inhaled anesthesia
described using a "soporific
sponge" soaked in hashish,
opium & other herbal
aromatics and placed under
the nose of the patient,
Avicenna - he died from an
accidental overdose of opium
later.

6. Dr William Thomas
Greene Morton
Sir James Simpson
Dr Horace Wells
The world is indebted to these great
men for their contribution….

7. • In 1772 nitrous oxide was first
prepared by Mr. Joseph B
Priestley, an English chemist &
clergyman.
• In 1799 it was suggested for
pain relief and called
"laughing gas" by Sir
Humphry Davy , a British
chemist & inventor.
• In 1844 N20 was used to
extract tooth from Dr Horace
Wells (a dentist) and
Extraction was done by Dr
John Riggs (dentist)
• In 1847 Chloroform was
first used clinically to
relieve labor pains by Sir
James Young Simpson in
Edinburgh (gynecologist)
- after experimenting on
himself & some friends at
the dinner table.
• In 1853 Chloroform was
used on Queen Victoria
for birth of 8th child -
Prince Leopold
administered by Dr John
Snow.
In 1846 William
T.G.Mortan participa
ted in a public
demonstration of
ether anesthesia on
October 16, at
the Ether
Dome in Boston.

8. GENERAL CONSIDERATIONS
• The physiologic state of general anesthesia
typically includes
 analgesia,
 amnesia,
 loss of consciousness,
 inhibition of sensory and autonomic
reflexes,
 skeletal muscle relaxation

9. WHAT IS SURGICAL STRESS……
• Evokes Hypothalamus pituitary axis and sympathetic
system.
• Tissue damage during
surgery induces
coagulation factors and
activates platelets leading
to hyper coagulability of
blood.
• The natural response to
injury includes:
■ Immobility/rest
■ Anorexia
■ Catabolism
• Anesthesia decreases the
components of surgical
stress response.

10. PHYSIOLOGICAL RESPONSE TO SURGICAL
INJURY ( Sir David Cuthbertson in 1930)
EBB
PHASE
INJURY
HOURS DAYS WEEKS
FLOW
PHASE RECOVERY
SHOCK CATABOLISM ANABOLISM

11. DRUGS
• General Anesthesia usually involves the
administration of 4 different types of drugs for:
 Premedication
 Induction of anesthesia
 Maintenance of anesthesia
 Recovery from anesthesia.
Molecular mechanism of the GA :
• GABA –A : Potentiation by Halothane,
Propofol, Etomidate; amino acids within the alfa
subunit of GABAa receptors may contribute to an
anaesthetic binding pocket for volatile anaesthetic
agents.
• NMDA receptors : inhibited by Ketamine

13. CLASSIFICATION
DRUGS
INHALATIONAL
GASES
NITROUS
OXIDE
LIQUIDS
HALOTHANE
ENFLURANE
DESFLURANE
SEVOFLURANE
ETC.
INTRAVENOUS
BARBITURATES
BENZODIAZEPENES
OPIOIDS
PROPOFOL
KETAMINE
MISCLENEOUS

14. INHALATIONAL ANESTHESIA
• Gas (non halogenated)
 Nitrous oxide,
• Liquids (halogenated hydrocarbons)
 Halothane,
 Enflurane,
 Isoflurane,
 Desflurane,
 Sevoflurane,
 Methoxyflurane

15. • These anesthetics are directly absorbed into the
bloodstream through the lungs then from alveoli
to brain.
• They remain unchanged in the body.
• Their action depends on various factors.

16. FACTORS ON WHICH ACTION DEPENDS
• Firstly the concentration of the anesthetic
depends upon its vapor pressure, boiling point
of the gas and the system being used.
• Secondly the transfer of anesthetic from alveoli
to blood stream this further depends on
▫ Solubility in the blood (blood : gas partition co-
efficient)
▫ Solubility in the fat (oil : gas partition co-efficient)

17. BLOOD: GAS PARTITION COEFFICIENT
• The blood : gas partition coefficient is the ratio of the
concentrations of anesthetic gas in the blood and gas phases at
equilibrium.
• Lower solubility in blood results in the blood becoming
saturated with the drug just after fewer gas molecules have
been transferred from the lungs.
• Once the "blood" compartment is saturated other anesthetic
molecules are readily transferred to rest of the compartments,
the most important, brain.

18. • Isoflurane for example has a blood/gas partition coefficient of
1.4, means that if the gas is in equilibrium the concentration in
blood will be 1.4 times higher than the concentration in the
alveoli.
• Lower the blood : gas co-efficient – faster the induction and
recovery – Nitrous oxide.
• Higher the blood : gas co-efficient – slower induction and
recovery – Halothane.

19. OIL : GAS PARTITION COEFFICIENT
• 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
• Another measure for potency is MAC minimum alveolar
concentration. 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 value of an anesthetic is that which prevents
movement in response to tracheal intubation in 50% of
subjects .
• The lower the MAC the more potent the anesthetic i.e. a
lower concentration is required to maintain a similar
anesthetic depth

20. ADVANTAGES (over intravenous agents)
• Easier to control and change
depth
• Excreted mainly by
respiration
• Recovery is rapid and there is
little metabolism
• Requires administration of
oxygen to the patient
• Endotracheal tube is present
so patent airway is available
• Minimal respiratory and
cardiovascular depression
• Provides some analgesia and
muscle relaxation
• Less accumulation

21. HALOTHANE
• Physical Properties:
▫ It is colorless liquid, volatile anesthetic.
▫ Pleasant to smell so excellent for induction in
children.
▫ Stored in amber colored bottles and contains
thymol 0.01% as preservative (to prevent
decomposition by light).
▫ Non inflammable, non explosive.
▫ Nonirritant, so induction is very smooth. Boiling
point of Halothane is 50°C.
▫ Halothane has highest fat/blood coefficient
(51) can get deposited in adipose tissue after
prolonged exposure.
• Anesthetic Properties :
▫ It is potent anesthetic (MAC = 0.74).
▫ Blood gas coefficient of 2.4 makes it agent with
moderate induction and recovery time.
▫ Not a good analgesic.
▫ Muscle relaxation is moderate.
▫ Contraindications for its use:
▫ History of previous halothane hepatitis.
▫ Patients with intracranial lesions and head
injury.
▫ Severe cardiac disease like aortic stenosis (as it
causes decrease in cardiac output).
▫ Pheochromocytoma (as it sensitizes
myocardium to adrenaline).
▫ Drug Interactions
▫ 1. Beta blockers and calcium channel blockers
can produce severe depression of cardiac
function withhalothane.
▫ 2. Aminophylline can produce serious
ventricular arrhythmias with halothane.
▫ 3. All cytochrome P450 enzyme inducers
enhance its metabolism.
▫ 4. Action of nondepolarizing muscle relaxants is
potentiated.

22. SYSTEMIC EFFECTS OF HALOTHANE :
Cardiovascular system:
▫ Decrease in cardiac output which is
because of direct depression of
myocardium and bradycardia .
▫ Blood pressure is decreased by direct
action on smooth muscle of blood vessels
as well as decreased central sympathetic
tone.
▫ It sensitizes the heart to adrenaline
producing severe ventricular arrhythmias.
So maximum permissible dose of
adrenaline with halothane for local
ischemia is 1.5 p.g/kg or not more than 30
mI/hr of 1 in 1,00,000 solution.
▫ Blunts the baroreceptor reflex.
Respiratory system:
▫ Both hypercarbic and hypoxic reflexes are
blunted.
▫ Laryngeal and pharyngeal reflexes are
depressed.
▫ It is a very potent bronchodilator and this
bronchodilatation is because of inhibition
of reflex pathways of bronchoconstriction.
That is why halothane is inhalational
agent of choice for asthmatics.
Central nervous system:
▫ There is marked increase in intracranial
tension with halothane.
Renal:
▫ Both GFR and urinary flow is decreased
which is because of decrease in cardiac
output.
Neuromuscular system:
▫ Halothane produces moderate muscle
relaxation (decreases the dose of muscle
relaxants by 20 to 30%).
Thermoregulation:
▫ Post operative shivering (halothane
shakes) and hypothermia is maximum
with halothane among inhalational
agents.

23. INTRAVENOUS ANESTHESIA
• Intravenous anesthetics may be used alone or in
combination with other drugs to achieve anesthesia
• These drugs include the following:
(1) barbiturates(thiopental, methohexital);
(2) benzodiazepines (midazolam, diazepam);
(3) opioid analgesics(morphine, fentanyl, sufentanil,
alfentanil, remifentanil);
(4) propofol;
(5) ketamine; and
(6)miscellaneous drugs (droperidol, etomidate,
dexmedetomidine)

24. PHARMACOKINETICS
• Depth of anesthesia is dependent upon the
concentration of anesthetic in the central
nervous system.
• The rate at which an effective brain
concentration is reached (the rate of induction of
anesthesia) depends on multiple
pharmacokinetic factors that influence the
uptake and distribution of the anesthetic.

25. • Intravenous drugs such as thiopental, etomidate,
ketamine, and propofol have an onset of
anesthetic action faster than the fastest of the
inhaled gaseous agents such as desflurane and
sevoflurane.

27. It is the use of drugs prior to anesthesia to make it
more safe and pleasant. eg.
• To relieve anxiety – benzodiazepines.
• To prevent allergic reactions – antihistaminics.
• To prevent nausea and vomiting – antiemetics.
• To provide analgesia – opioids.
• To prevent bradycardia and secretion –
anticholinergics.
PREANESTHETIC MEDICATION:

28. PRE-ANESTHETIC MEDICATION
• Advantages
▫ Advantages will differ
with different drugs but
may include
 Reduced stress to the animal
 Smoother induction and
recovery
 Decreased amount of
induction and, possibly,
maintenance agent required
 Analgesia intraoperatively
and post operatively
 Reduced secretions
 Reduced autonomic
responses
 Handler safety
• Disadvantages
▫ Are minimal
 Cost is a common concern
 Time factor
 Premedication given
subcutaneously usually takes 20
minutes to reach peak effect but
can last up to two hours
 If time is an issue, most
premedication can be given
intramuscularly (IM) or even
intravenously (IV) (with caution)
 Some (e.g. xylazine,
acepromazine, opioids and
diazepam) have been associated
with temporary behavior and
personality changes

29. Anticholinergics (Parasympatholytics)
atropine, glycopyrrolate
To reduce salivary and tear secretions
Blocks the stimulation of the vagus nerve
preventing bradycardia and reduced
cardiac output, Dilate pupils (mydriatic)
Reduces gastrointestinal activity by
inhibiting peristalsis
Phenothiazines
(Tranquilizers)
Chlorpromazine
Anti-emetic
Opioids
Morphine, Oxymorphone,
Butorphanol,
Hydromorphone,
Meperidine, Fentanyl
produces Analgesia,
Sedation, Dysphoria,
Euphoria excitement
Phencyclidines
Ketamine, Tiletamine
Produces cardiovascular
stimulation
Increases muscular rigidity
Causes salivation
Alfa 2 agonists
Xylazine, Romifidine, Detomidine
Medetomidine
Stimulates the α2-adrenoreceptors
causing a decrease in norepinephrine
Benzodiazepines
Diazepam, Midazolam,
Lorazepam
Convulsing/epileptic
patients
Ideal for older, depressed or
anxious patients
Neuroleptanalgesics
Any combination of
an analgesic and a
tranquilizer (i.e.
oxymorphone and
acepromazine)
PRE ANESTHETIC
MEDICATION
-TYPES,
EFFECTS

30. Anticholinergics
• Tachycardiac patients
• Possibly with geriatrics or with other
conditions such as congestive heart failure
that could not handle a potential tachycardia
• Conditions such as constipation and ileus
Phenothiazines
•Convulsing/epileptic patients, seizure history
or head trauma
•Shock (hypovolemia) and hypothermia because
of peripheral vasodilation that can lead to
hypotension
•Depressed patients
•Caution with geriatrics and pediatrics; use a
lower dose or consider alternative agents such
as benzodiazepines
•Liver or kidney disease
α2-Agonists
bradycardia, profound hypotension,
decreased contractility and stroke volume
and second degree heart block
respiratory function, hepatic and renal
functionReduces pancreatic secretions
causing transient hyperglycemia
(exacerbates dehydration)
Opioids will exacerbate these side effects
Opioids
•Bradycardia, Possible hypotension with
release of histamine.
•Morphine and meperidine increase
muscle contraction, Respiratory
depression is dose dependent
•Gastrointestinal effects depend on the
agent, may initially include diarrhea,
vomiting and flatulence. Constipation
may occur as a result of prolonged GI
stasis
•Addiction, increased responsiveness to
noise, Cough suppression, Excessive
salivation, Sweating
Phencyclidines
•Increases cranial pressure
•Increases ocular pressure
•Prolonged unreliable
recoveries
Neuroleptanalges
ics
Patient may
defecate or vomit
May hyperventilate,
May cause
bradycardia
SIDE EFFECTS AND
CONTRAINDICATIONS

31. Pre-anesthetic Medication
• Opioids
▫ Fentanyl patches
 Takes 8 to 12 hours to reach effectiveness but will
last for several days
 Very few cardiovascular side effects
 Does not significantly contribute to vasodilation or
hypotension
 Heating pads can increase transdermal uptake

32. Anesthesiology
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.

33. • In modern anesthesia practice, the distinctive
signs of each of the four stages described above
are usually obscured. Reasons for this include
the relatively rapid onset of action of many
intravenous and inhaled anesthetics compared
with ether and the fact that respiratory activity is
often controlled mechanically with muscle
relaxants.

34. • Atropine and glycopyrrolate are used to decrease
secretions; however, they also dilate the pupils.
Drugs such as tubocurarine and succinylcholine
affect muscle tone, and the opioid analgesics exert
depressant effects on respiration. The most reliable
indication that stage III (surgical anesthesia) has
been achieved is loss of the eyelash reflex and
establishment of a regular respiratory pattern. The
adequacy of depth of anesthesia for the specific
surgical requirements is assessed by changes in
respiratory and cardiovascular responses with
surgical stimulation

35. • While vital sign monitoring remains a common method of assessing
depth of anesthesia during
• surgery, newer techniques involving computer-assisted monitoring
of cerebral function appear to
• offer some advantages. Automated techniques available include
those based on the bispectral index
• (BIS), the physical state index (PSI) and the middle-latency auditory
evoked potential (MLAEP), all
• of which are processed variables derived from established effects of
anesthetics on the
• electroencephalogram. The application of such real-time cerebral
monitoring techniques has been
• shown to reduce the volatile anesthetic requirement, contributing to
a more rapid recovery from
• general anesthesia.

36. • The neuropharmacologic basis for the effects that characterize the stages of
anesthesia appears to be differential sensitivity of specific neurons or neuronal
pathways to the anesthetic drugs. Neurons in the substantia gelatinosa of the dorsal
horn of the spinal cord are very sensitive to relatively low anesthetic concentrations.
Interaction with neurons in this region interrupts sensory transmission in the
spinothalamic tract, including transmission of nociceptive (pain) stimuli. These
effects contribute to stage I analgesia and conscious sedation. The disinhibitory
effects of general anesthetics (stage II), which occur at higher brain concentrations,
result from complex neuronal actions including blockade of many small inhibitory
neurons such as Golgi type II cells, together with a paradoxical facilitation of
excitatory neurotransmitters. A progressive depression of ascending pathways in the
reticular activating system occurs during stage III of anesthesia, together with
suppression of spinal reflex activity, which contributes to muscle relaxation. Neurons
in the respiratory and vasomotor centers of the medulla are relatively insensitive to
the effects of the general anesthetics, but at high concentrations their activity is
depressed, leading to cardiorespiratory collapse (stage IV).

37. TECHNIQUES FOR ANESTHESIA
• Inhalational anesthesia
• Balanced anesthesia (inhalational anesthesia
and intravenous agents as adjuncts)
• Total intravenous anesthesia (TIVA)