General anesthesia involves administering medications to induce a state of unconsciousness and loss of pain sensation. It uses intravenous and inhaled agents to allow surgery while maintaining vital organ function. The choice of anesthetic depends on factors like the procedure, patient characteristics, and organ function. Common inhaled agents include nitrous oxide, desflurane, sevoflurane, and isoflurane. Intravenous options include propofol, etomidate, ketamine, and opioids. All work primarily by enhancing the action of the inhibitory neurotransmitter GABA or by blocking NMDA receptors.

1. General
Anesthetics

2. 2

3. General Anesthesia 3
General anesthesia (GA) is the state produced
when a patient receives medications for
analgesia, muscle relaxation, and sedation. An
anesthetized patient can be thought of as being
in a controlled, reversible state of
unconsciousness.
General anesthetics depress the central nervous
system to a sufficient degree to permit the
performance of surgery and other noxious or
unpleasant procedures.

4. General anesthesia uses intravenous
and inhaled agents to allow adequate
surgical access to the operative site.
A point worth noting is that general
anesthesia may not always be the best
choice; depending on a patient’s
clinical presentation, local or regional
anesthesia may be more appropriate.
4

5. CLASSIFICATION
5
General
anesthetics
Inhalational
Gas
Nitrous oxide
Volatile
liquids
halothane
enflurane
isoflurane
desflurane
Sevoflurane
methoxyflurane
Intravenous
Slower acting
Dissociative
anesthesia
ketamine
opioid
fentanyl
Benzodiazepines
diazepam
lorazepam
midazolam
Inducing agents
Thiopentone
methohexitone
propofol
Etomidate
Dexmedetomidin
e

6. General Anesthesia 6
General anesthesia is a reversible state of CNS depression, causing
loss of response to and perception of stimuli.
medical procedures,
For patients undergoing surgical or
anesthesia provides five important benefits:
Sedation and reduced anxiety
Lack of awareness and amnesia
Skeletal muscle relaxation
Suppression of undesirable reflexes
Analgesia

7. Because no single agent provides all
desirable properties both rapidly and
safely, several categories of drugs are
combined (I.V and inhaled
anesthesia and preanesthetic
medications) to produce optimal
anesthesia known as a Balanced
anesthesia.

8. Stages and depth of anesthesia
8
General anesthesia has three stages: induction, maintenance, and recovery.
Use preanesthetic medication
↓
Induce by I.V thiopental or suitable alternative
↓
Use muscle relaxant → Intubate
↓
Use, usually a mixture of N2O and a halogenated hydrocarbon→
maintain and monitor.
↓
Withdraw the drugs → recover

9. Patient factors in selection of
anesthesia
9
Drugs are chosen to provide safe and efficient
anesthesia based
on:
1. The type of the surgical or diagnostic procedure
2. Patient characteristics such as organ function,
medical conditions, and concurrent
medications. e.g., HTN, bronchial asthma.

10. Status of organ systems 10
Respiratory system:
All inhaled anesthetics depress the respiratory system. They are
bronchodilators.
Liver and kidney:
The release of fluoride, bromide, and other metabolic products of the
halogenated hydrocarbons can affect these organs, especially with
repeated anesthetic administration over a short period of time.

11. 1.Nitrous oxide can cause aplastic anemia in the
unborn child. Oral clefts have occurred in the
fetuses of women who have received
benzodiazepines.
2.Diazepam should not be used routinely during
labor, because it results in temporary hypotonia
and altered thermoregulation in the newborn.
Pregnancy:
Effects on fetal organogenesis are a major
concern in early pregnancy.

12. Preanesthetic Medications
12
Preanesthetic medications serve to
 calm the patient, relieve pain,
 Protect against undesirable effects of the
subsequently administered anesthetics or the
surgical procedure.
 facilitate smooth induction of anesthesia,
 lowered the required dose of anesthetic

13. Preanesthetic Medicine:
Benzodiazepines; midazolam or diazepam:
Anxiolysis &
amnesia.
Diphenhydramine: Prevention of allergic
reactions: antihistamines
H2 receptor blocker- famotidine, ranitidine:
Reduce gastric
acidity.

14. Preanesthetic medications:
14
Antiemetics- ondansetron:
Prevents aspiration of stomach
contents and post surgical vomiting:
Acetaminophen or opioids (fentanyl) for
analgesia
Anticholinergics: (glycopyrolate, scopolamine):
 Reduce bronchial and salivary secretion:
irritant inhaled anesthetic cause excessive
salivation and secretion.

15. Stages and depth of anesthesia/
Induction 15
Induction: The period of time from the onset of administration of
the anesthetic to the development of effective surgical anesthesia
in the patient. It depends on how fast effective concentrations of
the anesthetic drug reach the brain.
Thus GA is normally induced with an I.V thiopental, which
produces unconsciousness within 25 seconds or propofol
producing unconsciousness in 30 to 40 seconds after injection.
At that time, additional inhalation or IV drugs may be given to
produce the desired depth of surgical stage III anesthesia. This
often includes an IV neuromuscular blocker such as rocuronium,
vecuronium, or succinylcholine to facilitate tracheal intubation
and muscle relaxation.
Inhalation induction: For children without IV access, non pungent
agents, such as halothane or sevoflurane, are used to induce GA.

16. Stages and depth of anesthesia/
Maintenance 16
Maintenance: After administering the anesthetic, vital signs and
response to stimuli are monitored continuously to balance the
amount of drug inhaled and/or infused with the depth of
anesthesia.
Maintenance is commonly provided with volatile anesthetics,
which offer good control over the depth of anesthesia.
Opioids such as fentanyl are used for analgesia along with
inhalation agents, because the latter are not good analgesics.

17. Stages and depth of anesthesia/
Recovery
17
Recovery: The time from discontinuation of administration of
the anesthesia until consciousness and protective physiologic
reflexes are regained. It depends on how fast the anesthetic
drug diffuses from the brain.
For most anesthetic agents, recovery is the reverse of
induction. Redistribution from the site of action (rather
than metabolism of the drug) underlies recovery.
The patient is monitored to assure full recovery, with
normal physiologic functions (spontaneous respiration,
acceptable blood pressure and heart rate, intact reflexes,
and no delayed reactions such as respiratory depression).

18. Depth of Anesthesia (GUEDEL’S
Signs) 18
Guedel (1920) described four sequential stages with anaesthesia, dividing the
stage into 4 planes.
Stage of
Analgesia
• analgesia and amnesia, the patient is conscious and
conversational. Starts from beginning of anaesthetic inhalation
and lasts upto the loss of consciousness
• Pain is progressively abolished
• Reflexes and respiration remain normal
• Use is limited to short procedures
Stage of
Delirium
• From loss of consciousness to beginning of regular respiration
• Patient may shout, struggle and hold his breath; muscle tone
increases, jaws are tightly closed, breathing is jerky; vomiting,
involuntary micturition or defecation may occur
• Heart rate and BP may rise and pupils dilate due to
sympathetic stimulation
• No operative procedure carried out
• Can be cut short by rapid induction, premedication

19. Depth of Anesthesia (GUEDEL’S
Signs) 19
Surgical
anaesthesia
• Extends from onset of regular respiration to cessation of
spontaneous breathing. This has been divided into 4 planes
which may be distinguished as:
• Plane 1 moving eye balls. This plane ends when eyes become
fixed.
• Plane 2 loss of corneal and laryngeal reflexes.
• Plane 3 pupil starts dilating and light reflex is lost.
• Plane 4 Intercostal paralysis, shallow abdominal respiration,
dilated pupil.
Medullary
paralysis • Cessation of breathing to failure of circulation and death.

20. Inhalation
anesthetics
Inhaled gases are used primarily for maintenance of anesthesia.
Depth of anesthesia can be rapidly altered by changing the
inhaled concentration.
Common features of inhaled anesthetics
Modern inhalation anesthetics are nonflammable, nonexplosive
agents.
Decrease cerebrovascular resistance, resulting in increased
perfusion of the brain
Cause bronchodilation, and decrease both spontaneous ventilation
and hypoxic pulmonary vasoconstriction (increased pulmonary
vascular resistance in poorly aerated regions of the lungs,
redirecting blood flow to more oxygenated regions).
Movement of these agents from the lungs to various body
compartments depends upon their solubility in blood and tissues,
as well as on blood flow. These factors play a role in induction and
recovery.
18

21. MAC
(potency)
MAC (potency): the minimum alveolar concentration, the end-
tidal concentration of inhaled anesthetic needed to eliminate
movement in 50% of patients stimulated by a standardized
incision.
MAC is the ED50 of the anesthetic.
the inverse of MAC is an index of potency of the anesthetic.
MAC expressed as the percentage of
gas in a mixture required to achieve
the effect.
Numerically, MAC is small for potent
anesthetics such as sevoflurane and
large for less potent agents such as
nitrous oxide.
19

22. Uptake and distribution of inhalation
anesthetics
22
The principal objective of inhalation anesthesia is a constant and
optimal brain partial pressure (Pbr) of inhaled anesthetic (partial
pressure equilibrium between alveoli [Palv] and brain [Pbr]).
Thus, the alveoli are the “windows to the brain” for inhaled
anesthetics.
The partial pressure of an anesthetic gas at the origin of the
respiratory pathway is the driving force moving the anesthetic
into the alveolar space and, thence, into the blood (Pa), which
delivers the drug to the brain and other body compartments.
Because gases move from one compartment to another within
the body according to partial pressure gradients, a steady state
(SS) is achieved when the partial pressure in each of these
compartments is equivalent to that in the inspired mixture.
Palv = Pa = Pb

23. Factors Determine the time course for attaining Steady State:
Solubility in the blood: called the blood/gas partition
coefficient.
The solubility in blood is ranked in the following order:
halothane>enflurane>isoflurane>sevoflurane>desflurane>N
2O.
An inhalational anesthetic agent with low solubility in blood
shows fast induction and also recovery time (e.g., N2O), and
an agent with relatively high solubility in blood shows slower
induction and recovery time (e.g., halothane).
23

24. Factors Determine the time course for attaining Steady
State:
24
Effect of different tissue types on anesthetic uptake:
It is also directly proportional to the capacity of that tissue to
store anesthetic (a larger capacity results in a longer time
required to achieve steady state).
Capacity, in turn, is directly proportional to the tissue’s volume
and the tissue/ blood solubility coefficient of the anesthetic.

25. Factors Determine the time course for attaining Steady State:
Four major tissue compartments determine the time
course of anesthetic uptake:
a. Brain, heart, liver, kidney, and endocrine glands: these
highly perfused tissues rapidly attain a steady-state with
the PP of anesthetic in the blood.
b. Skeletal muscles: poorly perfused, and have a large
volume, prolong the time required to achieve steady-state.
c. Fat: poorly perfused. However, potent GA are very lipid
soluble. Therefore, fat has a large capacity to store
anesthetic. This combination of slow delivery to a high
capacity compartment prolongs the time required to
achieve steady-state.
d. Bone, ligaments, and cartilage: these are poorly perfused
and have a relatively low capacity to store anesthetic.
25

26. Wash out: when the administration of anesthetics
discontinued, the body now becomes the “source”
that derives the anesthetic into the alveolar space.
The same factors that influence attainment of
steady-state with an inspired anesthetic determine
the time course of clearance of the drug from the
body. Thus N2O exits the body faster than
halothane.
26

27. MECHANISM OF ACTION OF
ANAESTHESIA 27
No specific receptor has been identified. The fact that
chemically unrelated compounds produce anesthesia argues
against the existence of a single receptor.
The focus is NOW on proteins comprising ion channels:
GABAA receptors, Glycine receptors,
NMDA glutamate receptors (nitrous oxide and ketamine ):
Nicotinic receptors: Blocks the excitatory postsynaptic current
of the nicotinic receptors.

28. Currently, there are 5 inhalational and 5
intravenous anesthetics used to induce or maintain
general anesthesia: Inhalational:
Nitrous Oxide, Isoflurane, Sevoflurane, Desflurane
and Xenon. Intravenous: Propofol, Etomidate,
Ketamine, Methohexital and Thiopental. These 10
general anesthetic drugs are often accompanied by
sedative benzodiazepines: midazolam, diazepam
and lorazepam.
28

29. Of these 10 general anesthetics:
ketamine, nitrous oxide and xenon inhibit
ionotropic glutamate receptors, with the strongest
effects being seen on the NMDA receptor subtype.
These anesthetics also have modest effects on
many other receptors, including GABAARs, but their
primary action is the blockade of NMDA receptors.
29

30. The other 7 general anesthetics and 3 sedatives
share a common target and mechanism of action,
they all enhance the function of GABAARs, the most
abundant fast inhibitory neurotransmitter receptor
in the CNS. These 7 general anesthetics also have a
spectrum of modest to strong effects on other ion
30
glycine receptors,
channels,
nicotinic
receptors
including
receptors,
and
5-HT3
the
receptors,
potassium
neuronal
glutamate
channels.
Mechanisms underlying the anesthetic effect are
not properly known yet.

31. Halothane
(Prototype)
31
Advantages:
Potent anesthetic, rapid induction & recovery
Neither flammable nor explosive, sweet smell, non irritant
Does not augment bronchial and salivary secretions.
Low incidence of post operative nausea and vomiting.
Relaxes both skeletal and uterine muscle, and can be used in
obstetrics when uterine relaxation is indicated.
Combined with its pleasant odor, this makes it suitable in
children for inhalation induction.

32. Halothane :
32
Disadvantages:
Weak analgesic (thus is usually coadministerd with N2O,
opioids)
Is a strong respiratory depressant
Is a strong cardiovascular depressant; halothane is
vagomimetic and cause atropine-sensitive bradycardia.
Hepatotoxic: is oxidatively metabolized in the liver to tissue-
toxic hydrocarbons (e.g., trifluroethanol and bromide ion).
Malignant hyperthermia

33. Enflurane 33
Advantages:
Less potent than halothane, but produces rapid induction and
recovery
~ 2% metabolized to fluoride ion, which is excreted by the
kidney
Has some analgesic activity
Disadvantages: CNS excitation at twice the MAC, Can induce
seizure

34. Desflurane
: 34
Rapidity of induction and recovery: outpatient surgery
Less volatility (must be delivered using a special vaporizer)
It decreases vascular resistance and perfuse all major tissues very well.
Irritating cause apnea, laryngospasm, coughing, and excessive
secretions
Sevoflurane:
Has low pungency, not irritating the airway during induction; making
it suitable for induction in children
Rapid onset and recovery:
Metabolized by liver, releasing fluoride ions; thus, like enflurane, it
may prove to be nephrotoxic.
Methoxyflurane
The most potent and the best analgesic anesthetic available for clinical
use. Nephrotoxic and thus seldom used.

35. Nitrous oxide
(N2O)
35
It is a potent analgesic but a weak general anesthetic.
Rapid onset and recovery:
Does not depress respiration, and no muscle relaxation.
Clinical use: dental surgery, obstetrics, postoperative
physiotherapy, refractory pain in terminal illness, and
maintenance of anesthesia.
The least hepatotoxic, Teratogenic, bone marrow
depression.

36. Intravenous anesthetics 36
Barbiturates (thiopental, methohexital)
Potent anesthetic but a weak analgesic
High lipid solubility; quickly enter the CNS and depress
function, often in less than one minute, and redistribution
occur very rapidly as well to other body tissues, including
skeletal muscle and ultimately adipose tissue (serve as a
reservoir).
All barbiturates can cause apnea, coughing, chest wall spasm,
laryngospasm, and bronchospasm

37. Intravenous anesthetics/
Propofol
37
Propofol, Phenol derivative, It is an IV sedative-hypnotic
used in the induction and or maintenance of anesthesia.
Onset is smooth and rapid (40 seconds)
Decrease BP without depressing the myocardium, it also
reduce intracranial pressure.
It is widely used and has replaced thiopental as the first
choice for anesthesia induction and sedation, because it
produces a euphoric feeling in the patient and does not
cause post anesthetic nausea and vomiting.
Poor analgesia.

38. Intravenous anesthetics/
ketamine
38
Ketamine (phencyclidine derivative) a short-acting, anesthetic,
induces a dissociated state in which the patient is unconscious
(but may appear to be awake) and does not feel pain.
This dissociative anesthesia provides sedation, amnesia, and
immobility.
Ketamine is also a potent bronchodilator.
Therefore, it is beneficial in patients in asthmatics. Conversely,
it is contraindicated in hypertensive or stroke patients.
Ketamine is used mainly in children and elderly adults for
short procedures.
It is not widely used, because it increases cerebral blood flow
and may induce hallucinations, particularly in young adults.

39. Dexmedetomidine
is a sedative used in intensive care settings and surgery. It is
relatively unique in its ability to provide sedation without
respiratory depression.
Like clonidine, it is an α2 receptor agonist in certain parts of
requirements without causing significant respiratory
depression.
37

40. Adjuvants/BDZs & Opioids (fentanyl,
sufentanil)
Benzodiazepine (midazolam, lorazepam and diazepam) Are used
in conjunction with anesthetics to sedate the patient.
Opioids:
Analgesic, not good amnesic, used together with anesthetics.
They are administered either I.V, epidurally, or intrathecally
38

41. Anesthetic Toxicity 41
The conventional view of general anesthesia is that
anesthetics produce a reversible loss of consciousness and
that CNS function returns to basal levels upon termination
of anesthesia and recovery of consciousness. Recent data,
however, have cast doubt upon this notion. Exposure of
rodents to anesthetic agents during the period of birth
results in widespread neurodegeneration in the developing
brain. This neuronal injury, which is apoptotic in nature,
results in disturbed electrophysiologic function and
cognitive dysfunction in adolescent and adult rodents that
were exposed to anesthetics during the neonatal period. A
variety of agents, including isoflurane, propofol,
midazolam, nitrous oxide, and thiopental, manifest this
toxicity.

42. Thank you
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