Description*

1. General anesthetics
• Introduction & History
• Principles of General anesthesia
• General anesthetics
1. Inhalational anesthetics
2. Intravenous anesthetics

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

3. Anesthesiology
Original in the Royal College of Surgeons of England, London.

4. Ether
Massachusetts General Hospital,
16th October, 1846.

6. Anesthesiology
• Surgical stress evokes HPA axis and sympathetic
system.
• Tissue damage during surgery induces coagulation
factors and activates platelets leading to
hypercoagulability of blood.
• Most anesthetics are associated with
• decrease in systemic blood pressure – myocardial
depression and direct vasodilatation.
• reduce ventilatory drive and eliminate reflexes that
maintain airway patency.

7. General anesthesia - principles
• Goals of Balanced Anesthesia
• Amnesia
• Analgesia
• Attenuation of autonomic reflexes
• Immobility
• Unconsciousness

8. General anesthesia - principles
• Preanesthetic medications: It is the
use of drugs prior to anesthesia to make it
more safe and pleasant.
• To relieve anxiety – benzodiazepines.
• To prevent vomiting – antiemetics.
• To supplement analgesia – opioids.
• To prevent vagal stimulation and secretion –
atropine.

9. General anesthesia - principles
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.

10. General anesthetics - mechanism
Molecular mechanism of the GA :
• GABA –A : Potentiation by Halothane,
Propofol, Etomidate
• NMDA receptors : inhibited by
Ketamine

11. General anesthetics
There are two types of anesthetics :
• Inhalational --- for maintenance
• Intravenous --- for induction and short
procedures
• Inhalation anesthetics:
• Advantage of controlling the depth of
anesthesia.
• Metabolism is very minimal.
• Excreted by exhalation.

12. General anesthetics
Inhalational anesthetics :
• Nitrous oxide
• Halothane
• Enflurane – rarely used
• Isoflurane – most commonly used
• Desflurane
• Sevoflurane
• Methoxyflurane – not available in US
because of concerns of nephrotoxicity.

13. General anesthetics

14. General anesthetics
• The important characteristics of
Inhalational anesthetics which
govern the anesthesia are :
• Solubility in the blood
(blood : gas partition co-efficient)
• Solubility in the fat
(oil : gas partition co-efficient)

15. Inhalational anesthetics
Blood : gas partition co-efficient:
• It is a measure of solubility in the blood.
• It determines the rate of induction and
recovery of Inhalational anesthetics.
• Lower the blood : gas co-efficient – faster the
induction and recovery – Nitrous oxide.
• Higher the blood : gas co-efficient – slower
induction and recovery – Halothane.

17. BLOOD GAS PARTITION COEFFICIENT
Agents with low solubility in blood
quickly saturate the blood. The
additional anesthetic molecules are
then readily transferred to the brain

18. Inhalational anesthetics
Blood gas partition co-efficient affecting rate of induction and recovery

19. Inhalational anesthetics
Oil: gas partition co-efficient:
• 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

20. Inhalational anesthetics
• MAC value is a measure of inhalational
anesthetic potency.
• 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 values are additive and lower in the
presence of opioids.

21. OIL GAS PARTITION CO-EFFICIENT
Higher the Oil: Gas
Partition Co-efficient
lower the MAC .
E.g., Halothane
1.4 220
0.8

22. Inhalation
Anesthetic
MAC value % Oil: Gas partition
Nitrous oxide >100 1.4
Desflurane 7.2 23
Sevoflurane 2.5 53
Isoflurane 1.3 91
Halothane 0.8 220

23. Clinical case
• KJ is a 7-year-old, 20-kg boy who has been
undergoing multidrug chemotherapy for
aggressive osteosarcoma of his right femur. The
time has now come for a surgical resection.
• 8:00 PM (night before the operation): Dr. S, the
anesthesiologist, provides reassurance and revisits
the importance of fasting after midnight to prevent
aspiration of gastric contents while under general
anesthesia.
• 6:30 AM: KJ clings to his mother and appears
anxious, cachectic, and in some pain. His vital signs
are stable with an elevated pulse of 120 and a
blood pressure of 110/75.

24. Clinical case
• An oral dose of midazolam is given to relieve
anxiety and to allow KJ to separate from his
parents.
• 7:00 AM: Dr. S injects a small amount of
lidocaine subcutaneously before inserting
an intravenous catheter (which he carefully
conceals from KJ until the last possible
moment). Through the catheter, Dr. S
delivers an infusion of morphine sulfate for
analgesia.

25. Clinical case
• 7:30 AM: Dr. S rapidly induces anesthesia with an
intravenous bolus of 60 mg (3 mg/kg) of thiopental (a
barbiturate; Within 45 seconds, KJ is in a deep anesthetic
state. The doctor adds a dose of intravenous succinylcholine
(a depolarizing muscle relaxant) to facilitate endotracheal
intubation, and KJ is placed on artificial respiration.
• 7:32 AM: A mixture of inhaled general anesthetics consisting
of 2% isoflurane, 50% nitrous oxide, and 48% oxygen is
provided through the ventilator to maintain the anesthetic
state.
• 7:50 AM: KJ shows no response, either through movement or
increased sympathetic tone (e.g., increased heart rate,
increased blood pressure), to the first surgical incision.

26. Clinical case
• 12:35 PM: After a long surgery, Dr. S stops
the isoflurane and nitrous oxide and turns
on pure oxygen for a few minutes.
• 12:45 PM: In less than 10 minutes, KJ is
breathing spontaneously and is able to
respond to questions, although he is still
somewhat groggy. KJ's parents are relieved
to find him awake and alert after more than
5 hours of anesthesia.

27. Questions
1. What determines the rate of induction and
recovery from anesthesia?
2. What are the advantages of using a mixture
of two anesthetics (in this example, nitrous
oxide and isoflurane) instead of just one or
the other?
3. Why did Dr. S give pure oxygen for a few
minutes following the cessation of
anesthetic administration?

28. Inhalational anesthetics
Nitrous oxide:
• Safest inhalational anesthetic.
• Very weak anesthetic but a good analgesic.
• No toxic effect on the heart, liver and
kidney.
• Administered with more potent
anesthetics to hasten the uptake of the
other agent(s)

29. Inhalational anesthetics
Nitrous oxide
• Commonly used for dental procedures
• Quick induction and recovery.
• Caution about diffusional hypoxia
megaloblastic anemia.

30. Inhalational anesthetics
Halothane:
• It is a potent and pleasant anesthetic.
• It sensitizes the heart to catecholamines.
• It dilates bronchus – last resort in status
asthmaticus.
• It inhibits uterine contractions which can lead
to severe bleeding – not used in labor.
• Halothane hepatitis and malignant
hyperthermia can occur.

31. Inhalational anesthesia
Malignant Hyperthermia
• Side effect of halogenated anesthetics
• Fever of 110°F or more
• Life threatening
• Treatment: dantrolene (Dantrium)
• Dantrolene is a muscle relaxant that acts by
abolishing excitation-contraction coupling in
muscle cells, probably by action on the
ryanodine receptor.

32. Inhalational anesthetics
Isoflurane:
• It is commonly used with oxygen or
nitrous oxide.
• Its pungency can irritate the respiratory
system.
• No reports of hepatotoxicity.

33. Inhalational anesthetics
Desflurane:
• It is delivered through special vaporizer.
• It is a popular anesthetic for day care
surgery.
• Induction can be troublesome and it can
irritates the air passages producing cough
and laryngospasm.
• Recovery is fast as cognitive and motor
impairment are short lived.

34. Inhalational anesthetics
Sevoflurane:
• Induction and recovery is fast.
• It is an effective bronchodilator due to lack
of pungency.
• It is a good anesthetic in patients with
myocardial ischemia.
• Some concerns about nephrotoxicity.

35. Anesthetic B:G PC O:G PC Features Notes
Halothane 2.3 220 PLEASANT
Arrhythmia
Hepatitis
Hyperthermia
Enflurane 1.9 98 PUNGENT
Seizures
Hyperthermia
Isoflurane 1.4 91 PUNGENT Widely used
Sevoflurane 0.62 53 PLEASANT Ideal
Desflurane 0.42 23 IRRITANT Cough
Nitrous 0.47 1.4 PLEASANT Anemia

36. Respiratory effects of
inhalational anesthetics.
Spontaneous ventilation with all
of the halogenated inhalational
anesthetics reduces minute
volume of ventilation in a dose-
dependent manner (lower
panel).
This results in an increased
arterial carbon dioxide tension
(top panel).
Differences among agents are
modest.

37. General anesthetics
Parenteral anesthetics (IV):
• These are used for induction of anesthesia.
• Rapid onset of action.
• Also reduce the amount of inhalation
anesthetic for maintenance.
• E.g., Thiopental, Midazolam Propofol,
Etomidate, Ketamine.

38. Intravenous anesthetics
Thiopental (Pentothal):
• It is an ultra short acting barbiturates.
• A typical induction dose produces
duration of anesthesia of 5-8 minutes.
• The principal mechanism limiting
anesthetic duration after single dose is
redistribution from brain to other tissues
like skeletal muscle.
• A single dose can produce psychomotor
impairment for about 8 hrs.

39. Inhalational anesthetics
Thiopental
• It can be used for rapid control of seizures.
• Thiopental (barbiturates) can induce fatal
attacks of porphyria in patients with acute
intermittent or variegate porphyria
• Methohexital is another barbiturate which is
preferred anesthetic in patients undergoing
ECT because of its short duration of action.

40. Intravenous anesthetics
Propofol (Diprivan):
• Most commonly used IV anesthetic for
both induction and maintenance.
• Recovery is rapid and clearer than
thiopenthal makes it best for day care
surgery - residual impairment is less
marked.
• Anti-emetic in action.

41. Intravenous anesthetics
Propofol
• One of the most frequent side effects is
pain on injection.
• Rare and potentially fatal complication,
propofol infusion syndrome (PRIS),
after prolonged and high dose, which is
characterized by acidosis and
rhabdomyolosis.

42. Intravenous anesthetics
Etomidate:
• It is primarily used for anesthetic induction of
patients at risk of hypotension.
• It suppress the production of steroids from
the adrenal gland and not for long term
infusions.
• It can cause seizures and nausea/vomiting.
• CVS stability is the main advantage over
anesthetics.

43. Intravenous anesthetics
Ketamine : Dissociative anesthesia
• Produce - profound analgesia, involuntary
movements, amnesia and breathe
spontaneously.
• Acts by blocking NMDA receptors
• Heart rate and BP are elevated due to
sympathetic stimulation.
• Best suited for children and in patients with
asthma as respiration is not depressed.

44. Intravenous anesthetics
Ketamine:
• Emergence delirium, hallucinations and
vivid dreams occurs in 50% cases during
recovery.
• It is useful for burn dressing and trauma
surgery.
• Dangerous for hypertensive and myocardial
ischemia patients.

45. Intravenous anesthetics
Analgesics: Opioids
• Opioids are the primarily used analgesics during
perioperative period.
• The order of potency relative to morphine is:
• Sufentanil (1000 X )
• Remifentanil (300 X)
• Fentanyl (100 X), Meperidine ( 0.1 X)
• Respiratory depression is a major adverse effect.
• Antagonist naloxone (Narcan) reverse opioids
overdose and actions.

46. Benzodiazepines
• Used for short procedures and useful
in controlling seizures.
• Midazolam (Versed)
• Fast action, potent and short half
lifes are its salient features.
• Flumazenil (Romazicon) can reverse
overdose / actions of benzodiazepines.

47. Newer anesthetics i.v
α-2 adrenergic agonists:
Dexmedetomidine
• It is FDA approved for short term sedation in
non-intubated patients.
• Activation of α-2 receptors produces
sedation and analgesia.
• It is a sedative-hypnotic that produce
analgesia with little respiratory depression
and mild drop in blood pressure.

48. Anesthetic
I.V
Duration
mins
Analgesia
Muscle
relaxation
Others
Thiopental 5 - 10 --- ---
Respiratory
depression
Propofol 5-10 --- ---
Respiratory
depression
Ketamine 5-10 +++ --- Hallucinations
Midazolam 5-20 --- +++ Amnesia
Fentanyl 5-10 +++ ---
Respiratory
depression