1. General Anesthesia

2. General Anesthesia
 Definition:The word
anaesthesia is derived from
the Greek: meaning insensible
or without feeling
 Is the loss of response to &
perception of all external
stimuli.
 General anaesthetics are the
drugs which causes reversible
loss of all the sensations and
consciousness

6. Components of General
Anesthesia:
 1.Unconsciousness
 2. Analgesia
 3. Muscle relaxation

7. ROLE OF
ANAESTHESIOLOGIST
So we can summarize the role of anaesthesiologist in:
1. Knowing physiology of body well.
2. Knowing the pathology of patient disease and co-existing
disease
3. Study well the pharmacology of anaesthetic drugs and
other drugs which may be used intra-operatively.
4. Use anaesthetics in the way and doses which is adequate to
patient condition and not modified by patient pathology
with no drug toxicity.
5. Lastly but most importantly administrate drug to
manipulate major organ system, to maintain homeostasis
and protect patient from injury by surgeon or theatre
conditions.

8. APPROACH TO
ANAESTHESIA
The empirical approach to anaesthetic drug
administration consists of selecting an
initial anaesthetic dose {or drug} and then
titrating subsequent dose based on the
clinical responses of patients, without
reaching toxic doses.
The ability of anaesthesiologist to predict
clinical response and hence to select
optimal doses is the art of anaesthesia

9. TOOLS OF
ANAESTHESIA
Knowing physiology, pathology ,and
pharmacology is not enough to
communicate safe anesthesia
But there is need for two important tools:
1. Anaesthetic machine.
2. Monitoring system.

10. ANAESTHETIC MACHINE
1. Oxygen gas supply.
2. Nitrous oxide gas supply.
3. Flow meter
4. Vaporizer specific for every agent
5. Mechanical ventilator
6. Tubes for connection.

11. MONITORING
1. Pulse, ECG
2. Blood pressure
3. Oxygen saturation.
4. End tidal CO2
5. Temperature
6. Urine output, CVP, EEG, bispectral index,
muscle tone, ECHO, drug concentration.

12. Phases of Anesthesia
 Induction: keeping the patient to sleep
 Maintenance: keeping the patient
asleep
 Emergence: waking the patient up

13. STAGES OF GENERAL
ANESTHESIA
 STAGE 1 (Analgesia):
From induction of anesthesia to loss of conciousness (loss of
eyelid reflex). Pain is progressively abolished in this stage.
 STAGE 2 (Delirium/Excitement):
From loss of consiousness to beginning of regular respiration.
Characterized by uninhibited excitation. Pupils are dilated and
eyes divergent. Agitation, delirium, irregular respiration, and
breatholding are commonly seen. Potentially dangerous
responses can occur during this stage including vomiting,
laryngospasm, HTN, tachycardia, and uncontrolled movement.

14.  STAGE 3 (Surgical Anesthesia):
Regular respiration to caessation of spontaneous breathing
Central gaze, constricted pupils, and regular respirations.
Target depth of anesthesia is sufficient when painful
stimulation does not elicit somatic reflexes or deleterious
autonomic reflexes.

15. Plane 1 From the return of regular
respirations to the cessation of REM.
Plane 2 The Surgical Plane
From the cessation of REM to the onset of
paresis of the intercostal muscles.
Plane 3 From the onset to the complete
paralysis of the intercostal muscles.
Plane 4
From the paralysis of the intercostal of
this plane the patient will be apneic.

16.  STAGE 4 (Impending Death/Overdose):
Onset of apnea, dilated and nonreactive pupils, and
hypotension to complete circulatory failure.

17. Classic Stages of Anesthesia*
 Stage 1: Analgesia
– decreased awareness of pain, amnesia
 Stage 2: Disinhibition
– delirium & excitation, enhanced reflexes, retching,
incontinence, irregular respiration
 Stage 3: Surgical Anesthesia
– unconscious, no pain reflexes, regular respiration, BP is
maintained
 Stage 4: Medullary Depression
– respiratory & CV depression requiring ventilation &
pharmacologic support.
* Seen mainly with Ether. Not all stages are observed with modern GAs.

18. Mechanisms of Action
Enhanced GABA effect on GABAA Receptors
1.
–
–
–
- Etomidate
- Propofol
Block nicotinic receptor subtypes (analgesia)
1.
–
Moderate to high conc’s of inhaled anesthetics
Activate K channels (hyperpolarize )
1.
–
Nitrous oxide, ketamine, xenon
Inhibit NMDA (glutamate) receptors
1.
–
1.
Inhaled anesthetics
Barbiturates
Benzodiazepines
Nitrous oxide, ketamine, xenon, high dose barbiturates
Enhance glycine effect on glycine R’s (immobility)

19. Regional Effects
 Immobilization in response to surgical incision
(spinal cord)
 Sedation, loss of consciousness (↓thalamic firing)
 Amnesia (↓hippocampal neurotransmission)

20. CLASSIFICATION
 INTRAVENOUS
INDUCING AGENTS
Thiopentone sodium
Methohexital
Propofol
Etomidate
SLOWER ACTING
Diazepam
Lorazepam
Midazolam
DISSOCIATIVE ANAESTHESIA
Ketamine
OPIOID ANALGESIA
Fentanyl
 INHALATIONAL
GAS
Nitrous oxide
LIQUID
Ether
Halothane
Enflurane
Desflurane
Sevoflurane

21. Parenteral Anesthetics
(Intravenous)
 Most commonly used drugs to induce
anesthesia
–
–
–
–
–
Barbiturates (Thiopental* & Methohexital)
Benzodiazepines (Midazolam)
Opioids (Morphine & Fentanyl)
Propofol*
Etomidate
* Most commonly used for induction

22. Barbiturates & Benzodiazepines MOA:
GABA
Barbiturate
BZDS
1) Both bind to GABAA
receptors, at different sites
• Both cause increase Clinflux in presence of GABA
• BNZ binding can be
blocked by flumazenil.
2) Barbs at high doses - are
also GABA mimetic, block
Na channels
NMDA/glutamate R

23. Dose Response Relationships
Coma
Barbiturates
CNS Effects
Medullary depression
Benzodiazepines
Anesthesia
Hypnosis
Sedation, disinhibition,
anxiolysis
Increasing dose
Possible selective
anticonvulsant & musclerelaxing activity

24. Barbiturates
 Thiopental & methohexital are highly lipid soluble & can produce
unconsciousness & surgical anesthesia in <1 min.
 Rx: induction of anesthesia & short procedures
 Actions are terminated by redistribution
 With single bolus - emergence from GA occurs in ~ 10 mins
 Hepatic metabolism is required for elimination

26. Thiopental (3-5mg/kg)
 Barbs are respiratory & circulatory depressants
(Contraindicated: hypovolemia, cardiomyopathy, betablockade,etc.)
 Psychomotor impairment may last for days after use of a
single high dose
 Taste of garlic prior to anesthesia
 Potentially fatal attacks of porphyria in pts with a history of
acute or intermittent porphyria.
 Delay giving other drugs (e.g. NMJ blockers) until barb has
cleared the i.v. line to avoid precipitation.

27. Propofol
 Propofol is a diisopropylphenol intravenous
hypnotic agent that produces rapid
induction of anesthesia with minimal
excitatory activity
 It undergoes extensive distribution and
rapid elimination by the liver

28. Propofol
 Produces anesthesia as rapidly as i.v. barb’s & but
recovery is more rapid than barb’s.
 Recovery is not delayed after prolonged infusion (due
to more rapid clearance).**
 Patients are able to ambulate sooner & patients “feel
better” in the post-op period compared to other i.v.
anesthetics.
 Antiemetic effects (pts w/ ↑risk of nausea), marked
hypotension (>barbs)
 Commonly used as component of “balanced
anesthesia” for maintenance of anesthesia following
induction of anesthesia.
** More rapid discharge from the recovery room

29. INDICATIONS
 Conscious sedation
 Induction agent of anesthesia
 Maintenance of anesthesia
 Antiemetic

30. DOSE AND ROUTES
 Conscious sedation
25 - 50 mg IV, Titrate slowly to desired effect
(on set of slurred speech)
 Induction
2 - 2.5 mg/kg IV, given slowly over 30
seconds in 2 - 3 divided doses
 Maintenance
25 - 50 mg IV bolus
Infusion 100 - 200 mcg/kg/min
 Antiemetic
10mg IV

31. ADVERSE REACTIONS,
PRECAUTIONS, AND
INTERACTIONS
 Reduce doses in elderly, hypovolemic, high
risk surgical patients and with use of
narcotics and sedative hypnotics
 Minimize pain by injecting into a large vein
and/or mixing IV lidocaine (0.1 mg/kg)
with the induction dose of Propofol

32. ADVERSE REACTIONS,
PRECAUTIONS, AND
INTERACTIONS
 Not recommended for patient with
increased intracranial pressure
 Should be administered with caution to
patients with a history of epilepsy or
seizures disorder

33. Etomidate
 Rapid induction (~1 min), Short duration of action (3-5
mins)
 Used as a supplement with nitrous oxide for short surgical
procedures
 Hypnotic, but not analgesic
 Little effect on CV & Respiration
 Can cause post-op nausea & decrease cortisol production w/
long term infusion*.
 Primarily used in pts w/ limited cardiac or respiratory
reserve (safer than barbs or propofol in pts w/ coronary
artery dx., cardiomyopathy, etc.)

34. Benzodiazepines
 Midazolam (> Diazepam & Lorazepam)
– Used to produce anxiolysis, amnesia & sedation
prior to induction of GA w/ another agent.
– Sedative doses achieved w/in 2 min, w/ 30 min
duration of action (short duration).
– Effects are reversed with flumazenil.

35. INDICATIONS Midazolam
 pre-op sedative
 induction of anesthesia
 Conscious sedation
 commonly used for short diagnostic or
endoscopic procedures

36. DOSE AND ROUTES
Midazolam
 may be given IM, PO, or IV
 Pre-op sedation: 0.07-0.08 mg/kg IM 1 hr
prior
 Induction of anesthesia: 0.050 - 0.350
mg/kg IV
 Basal sedation: 0.035 mg/kg initially, then
titrated slowly to a total dose of 0.1 mg/kg

37. • Recovery half times from anesthesia can be
Recovery Half Time (mins)
“Context Sensitive”
150
Diazepam
100
Midazolam
50
0
Thiopental*
Propofol
Etomidate
0
2
4
6
8
Infusion Duration (hours)
*Unconsciousness can last for
days after prolonged administration
10

38. Opioids (Fentanyl & Remifentanil*)
 GAs do not produce effective analgesia (except for ketamine).
 Given before surgery to minimize hemodynamic changes
produced by painful stimuli. This reduces GA requirements.
 High doses can cause chest wall rigidity & post-op respiratory
depression
 Therapeutic doses will inhibit respiration (↑CO2)
 Used for post-op analgesia, supplement anesthetic in balanced
anesthesia.
 Remifentanil is an ester opioid metabolized by plasma
esterases. It is very potent but w/ a short t (3-10 mins).

39. Ketamine
 Nonbarbiturate, rapid acting general
anesthetic
 Dissociated from the environment,
immobile, and unresponsive to pain
 Profound analgesic

40. Ketamine
 Selectively blocks the associative pathways
producing sensory blockade
 Preserved pharyngeal-laryngeal reflexes
 Normal or slightly enhanced skeletal
muscle tone
 Cardiovascular and respiratory stimulation

41. INDICATIONS Ketamine
 Sole agent for procedures that do not
require skeletal muscle relaxation
 Induction of anesthesia prior to the
administration of other anesthetic agents
 Supplementation of low potency agents

42. DOSE AND ROUTES
Ketamine
 may be injected IM or IV
 Induction: 1-2 mg/kg Slow IV
 Maintenance: 30-90 mcg/kg/min IV drip
 Intramuscular: 6.5-13 mg/kg IM
 10 mg/kg IM will produce approximately
12-25 min of surgical plane.

43. ADVERSE REACTIONS,
PRECAUTIONS, AND
INTERACTIONS Ketamine
 contraindicated in pts. with known
hypersensitivity or can't tolerate a
significant increase in blood pressure
 IV dose should be administered over 60
seconds. Rapid administration may cause
respiratory depression or apnea

44. ADVERSE REACTIONS,
PRECAUTIONS, AND
INTERACTIONS Ketamine
 BP, pulse rate, and respiratory rate are often
stimulated
 Concomitant use of barbiturates or narcotics
prolong recovery time

45. Ketamine (1.5mg/kg)
 A “dissociative anesthetic” that produces a cataleptic state
that includes intense analgesia, amnesia, eyes open,
involuntary limb movement, unresponsive to commands or
pain.
 Increases heart rate & blood pressure (opposite of other
GAs)
 Can be used in shock states (hypotensive) or patients at
risk for bronchospasm.
 Used in children & young adults for short procedures
 Side Effects: nystagmus, pupillary dilation, salivation,
hallucinations & vivid dreams

46. Inhaled Anesthetics

47. Inhaled Anesthetics
 Easily vaporized liquid halogenated hydrocarbons
 Administered as gases
(gas)

48. Inhaled Anesthetics
 Partial pressure or “tension” in inspired air is a measure
of their concentration
 The speed of induction of anesthesia depends on:
– Inspired gas partial pressure (GA concentration)
– Ventilation rate
– GA solubility (less soluble GAs equilibrate more
quickly with blood & into tissues such as the brain)

49. Minimum Alveolar
Concentration
 The minimum alveolar anesthetic concentration
required to eliminate the response to a painful stimulus
in 50% of patients
 A measure of GA potency.
 It’s “a population average”.
 1.3 MAC - 100% will not respond to stimuli.
 When several GAs are mixed, their MAC values are
additive (e.g. nitrous oxide is commonly mixed w/
other anesthetics).

50. Elimination
 Anesthesia is most commonly terminated by redistribution
of drug from brain to the blood & out through the lungs.
 The rate of recovery from anesthesia for GAs with low
blood: gas PCs is faster than for highly soluble Gas.
 Time is $$ in the O.R. & recovery room
Blood: Gas P. Coeff
– Haltothane
– Desflurane
– Sevoflurane
2.30
0.42
0.69
 Halothane & methoxyflurane undergo hepatic metabolism
& can cause liver toxicity.

51. Properties of Inhaled anesthetics
Nitrous Oxide
– MAC > 100% : Incomplete anesthetic
– Good analgesia
– No metabolism
– Rapid onset & recovery
– Used along w/ other anesthetic; fast induction &
recovery
* fewer side effects also seen in children

52. Halothane
•The first halogenated inhalational anesthetic
•Not pungent (use for induction w/ children)*
•Medium rate of onset & recovery
•Although inexpensive, its use has declined
•Sensitizes the heart to epi-induced arrhythmias
•Rare halothane induced hepatitis

53. Desflurane
– Most rapid onset of action & recovery of
the halogenated GAs
– Widely used for outpatient surgery
– Irritating to the airway in awake patients & causes
coughing, salivation & bronchospasm (poor induction
agent)
– Used for maintenance of anesthesia
Sevoflurane
– Very low blood:gas partition coefficient w/ relatively
rapid onset of action & recovery *
– Widely used for outpatient surgery*
– Not irritating to the airway
– Useful induction agent, particularly in children
* Similar to Desflurane

54. Isoflurane
– Medium rate of onset & recovery
– Used for induction & maintenance of anesthesia
– Isoflurane “was” the most commonly used inhalational GA in
the US. Has been largely replaced by Desflurane
Methoxyflurane
– Now widely considered obsolete
– Slow onset & recovery
– Extensive hepatic/renal metabolism, w/ release of F- ion
causing renal dysfunction

55. Toxicity
 Malignant Hyperthermia
– Esp. when halogenated GA used with succinylcholine
– Rx: dantrolene (immediately)
 Halothane:
– Halothane undergoes >40% hepatic metabolism
– Rare cases of postoperative hepatitis occur
– Halothane can sensitize the heart to Epi (arrhythmias)
 Methoxyflurane
– F release during metabolism (>70%) may cause renal insufficiency
after prolonged exposure.
 Nitrous oxide
– Megaloblastic anemia may occur after prolonged exposure due to
decreases in methionine synthase activity(Vit B12 deficiency).

56. PREANAESTHETIC MEDICATION
 Opioids:
Morphine-10 mg
Pethidine 50-100mg i.m.
 Sedatve antianxiety :
Diazepam 5-10mg orally
Lorazepam 2mg i.m.
 Anticholinergics :
Atropine 0.6mg i.m./ i.v
Glycopyrolate 0.1-0.3mg i.m
 Neuroleptics:
Chlorpramazine 25mg
 H2 blockers :
Ranitidine 150mg
Famotidine 40mg
 Antiemetics :
Metoclopramide 10-20mg i.m

57. Airway
Alveoli
Blood
Blood:Gas PC
Brain
Nitrous
Oxide
Airway
Alveoli
Blood
0.47
Brain
Halothane
2.30
•
Why induction of anesthesia is slower with more soluble anesthetic gases. In this schematic
diagram, solubility in blood is represented by the relative size of the blood compartment (the
more soluble, the larger the compartment). Relative partial pressures of the agents in the
compartments are indicated by the degree of filling of each compartment. For a given
concentration or partial pressure of the two anesthetic gases in the inspired air, it will take
much longer for the blood partial pressure of the more soluble gas (halothane) to rise to the
same partial pressure as in the alveoli. Since the concentration of the anesthetic agent in the
brain can rise no faster than the concentration in the blood, the onset of anesthesia will be
slower with halothane than with nitrous oxide.

58. Solubility Effects Arterial Anesthetic Levels
Arterial anesthetic tension
(% of inspired tension)
Blood:Gas PC
Nitrous Oxide
0.47
Halothane
2.30
Equilibration with a soluble GA may take hours
to achieve. Time is $$ in the O.R.
Methoxyflurane
•
Time (min)
12
Tensions of three anesthetic gases in arterial blood as a function of time after beginning inhalation.
Nitrous oxide is relatively insoluble (blood:gas partition coefficient = 0.47); methoxyflurane is much
more soluble (coefficient = 12); and halothane is intermediate (2.3).

59. Ventilation Rate’s Effect on Arterial Anesthetic Tension
Arterial anesthetic tension
(% of inspired tension)
Ventilation (L/min)
Nitrous Oxide
Halothane
Hyperventilation increases the speed of
induction for Gas with normally slow onset
Time (min)
•
Ventilation rate and arterial anesthetic tensions. Increased ventilation (8 versus 2 L/min) has a much
greater effect on equilibration of halothane than nitrous oxide.

60. NMJ Blockers
 Succinylcholine, Pancuronium
 Used to:
– relax skeletal muscle
– facilitate intubation**
– insure immobility
 Reversed by neostigmine* &
glycopyrrolate* during post-op period
* quaternary drugs; * intubation is usually needed for
airway maintenance & to prevent aspiration.

61. Dantrolene
 Interfers with the release of calcium from the
sarcoplasmic reticulum through the SR calcium
channel complex.
 Used to prevent or reverse malignant hyperthermia
(which is otherwise fatal in ~50% of cases w/o
dantrolene).
 Given by i.v. push at the onset of symptoms (e.g. an
unexpected rise in CO2 levels)
 Supportive measures & 100% O2 are also used to treat
malignant hyperthermia

62. Nausea & Vomiting
 General anesthetics effect the chemoreceptor
trigger zone & brainstem vomiting center
(cause nausea & vomiting)
 Rx:
- Ondansetron (5-HT3 antagonist) to prevent
- Avoidance of N2O
- Propofol for induction
- Keterolac vs. opioid for analgesia
- Droperidol, metaclopromide & dexamethasone