Download Lecture notes of International Edcation General anaesthetics

Lecture notes of International Edcation
General anaesthetics
1. Definition
General anaesthetics (GAs) are drugs which producereversible
loss
of
all
sensations and consciousness. General anaesthetics (GAs) are
drugs used to
depress the CNS to a sufficient degree to permit the performance of surgery
and other noxious or unpleasant procedures.
Triad of General Anesthesia:
–need for unconsciousness
–need for analgesia
–need for muscle relaxation
2.
history
Joseph Priestly – discovers N 2 O in 1773
Crawford W. Long – 1842. Country Dr. in Georgia first used ether for neck
surgery. Did not publicize, in part because of concerns about negative fallout
from “frolics”.
Tried to claim credit after Morton’s demonstration
but…Important lesson learned – if you don’t publish it, it didn’t happen.
Sir Humphrey Davy – experimented with N 2 O, reported loss of pain, euphoria
Traveling shows with N 2 O (1830’s – 1840’s)
Horace Wells 1844. Demonstrated N 2 O for tooth extraction – deemed a failure
because patient “reacted”.
William Morton, dentist – first demonstration of successful surgical anesthesia
with ether 1846
John C. Warren, surgeon at MGH says “Gentlemen, this is no humbug!” – birth
of modern anesthesia
Dr. John Snow administers chloroform to Queen Victoria (1853) – popularizes
anesthesia for childbirth in UK
He becomes the first anesthesia specialist.
Note that ether became anesthesia of choice in US, chloroform in UK
3.
Phases of General Anesthesia
(1)Induction- initial entry to surgical anesthesia
(2)Maintenance- continuous monitoring and medication. Maintain depth of
anesthesia, ventilation, fluid balance, hemodynamic control, hoemostasis
(3)Emergence- resumption of normal CNS function
Stage I: Analgesia─Starts from beginning of anaesthetic inhalation and lasts
upto the loss of consciousness.Patient remains conscious and feels a dream like
state. Reflexes and respiration remain normal. Use is limited to short
procedures.
Stage II: Delirium (Excitement) ─From loss of consciousness to beginning of
regular respiration. Apparent excitement is seen. Heart rate and BP may rise ,
and pupils dilate. No stimulus should be applied or operative procedure carried
out during this stage.
Stage III: Surgical (continued) ─Extends from onset of regular respiration to
cessation of spontaneous breathing. This has been divided into 4 planes:
Plane 1 : 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.
Plane4:Intercostal paralysis shallow abdominal, respiration, dilated pupils.
Stage IV: Medullary Depression ─ Cardio-respiratory collapse due to
depression of respiratory and vasomotor centers of medulla.
Fortunately,
neurons are relatively insensitive to depressant effects of GA.Observed only at
toxic doses. Fixed, dilated pupils = signs of pending coma or death
4.Mechanism of action
In summary , general anaesthetics inhibit excitatory channels (especially
glutamate receptors) and facilitate inhibitory channels (particularly GABAA
but also glycine and certain potassium channels), and these interactions are
targeted at specific hydrophobic domains of channel proteins.
Individual anaesthetics differ in their actions and affect cellular function in
several different ways.
5.
Pharmacokinetics of inhaled GAs
Factors that influence the uptake and distribution of GAs :
 Solubility
Blood/Gas Partition coefficient
Oil/Gas partition coefficient

GA
Concentration
in
the
inspired
air:
inspired
anaesthetic
concentration increase the rate of induction by increasing the rate of
transfer into the blood.

Pulmonary ventilation: hyperventilation increases the speed of
induction of anesthesia with inhaled anesthetics that would normally
have a slow onset

Pulmonary blood flow: an increase in pulmonary BF slows the rate of
rise in arterial tension particularly for those inhaled GAs with moderate
to high blood solubility – speed of onset of anesthesia is reduced.

Arteriovenous concentration gradient
The important characteristics of Inhalational anesthetics which govern the
anesthesia are :
 Solubility in the blood
(blood/gas partition coefficient)─It is a measure
of solubility in the blood.It determines the rate of induction and recovery of
Inhalational anesthetics. Lower the blood/gas coefficient is faster the induction
and recovery such as Nitrous oxide. Higher the blood/gas coefficient is
slower induction and recovery such as Halothane.
 Solubility in the fat
(oil/gas partition coefficient) ─It is a measure of
lipid solubility. Lipid solubility - correlates strongly with the potency of the
anesthetic.
Minimum alveolar Concentration (MAC) ─ 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.Values of MAC are additive:
6.commonly used GAs
(1) Ether
 First anesthetic (1842)
 Liquid at room temp, readily vaporizes & easy to administer
 Inflammable, explosive & irritating
(2)Chloroform
 Next anesthetic that received wide use (1847)
 Have a pleasant odor, nonflammable
 Is hepatotoxic & severe CV depressant
(3)Cyclopropane
 Accidentally discovered -1929
 Flammable & explosive
(4)HALOTHANE (Fluothane)
 Very widely used in children.
Not so in adults due to fear of hepato-toxicity
 CVS ─ Decreases mean arterial pressure, decreases Cardiac output
and myocardial depressant effects.
 Respiration system ─ Decreases TV, minute volume, mucociliary
function. Increases RR.
 Brain ─ Increases cerebral BF, decreases cerebral vascular resistance
with decreased metabolic rate of brain.
 Renal ─ Decreases GFR, RPF. Increases FF,RENAL vascular
resistance.
 Liver ─ Decreases hepatic BF and is hepatotoxic
 Advantages
─ Good
Physical
properties
(pleasant
odor,
non-explosive);Potent Anaesthetic (MAC 0.75%); Potent Inhibitor of
Laryngeal and Pharyngeal Reflexes; Potent Relaxant of Masseter
Muscles – easy intubation; Does not cause Laryngospasm, Bronchospasm and
Coughing ; Produces Bronchodilatation (useful in asthmatic patients) ;
Used to produce Controlled Hypotension è Bloodless field during
plastic/vascular surgery
 Disadvantages ─
Poor muscle relaxant ; Respiration depressant ;
Profound hypotension if given in more than 2% concentration ;
Increases Parasympathetic tone cause Bradycardia; Sensitizes the
ventricular muscle & conduction tissue to Adrenaline cause
Arrhythmias
(5) ISOFLURANE
Most widely used volatile anesthetic. It is similar to Enflurane in many
aspects.Resemble Halothane Except:
 Less incidence of hypotension
 Less sensitization of heart to Catecholamines
 Less toxic
 Powerful Coronary vasodilator
 No pro-convulsive properties
 Not cost effective
(6) NITROUS OXIDE (N2O)
 Rapid onset & offset
 Good analgesic
 Entonox (50% oxygen & nitrous oxide) for labor pain
 Low potency (MAC >100)
 Used mostly as an adjuvant
 Second gas effect
 DIffusion hypoxia
 Toxicity
 Inhibits methionine synthetase
 Leucopenia & megaloblastic anemia
 Expands gas spaces in the body
Advantages ─
 Non-inflammable
 Non-irritating
 Very Potent Analgesic:

30 – 40 % Analgesia

65 – 70 % Loss of consciousness

80 % plane one of Surgical Anaesthesia

80 % will produce hypoxia
 Non-explosive, however supports combustion
 Rapid induction and recovery.
 Use in procedures of short durations (tooth extraction, obstetrical
analgesia, cleaning and debridement of wounds and cauterization).
 First Stage of Parturition.
Disadvantages ─
 Not a potent anesthetic & muscle relaxant
 Violent excitement (laughing gas)
 Carbon dioxide accumulation and hypoxia
 Specialized apparatus to control its administration
 Expansion of pocket of trapped air( pneumothorax, intestinal loop, renal
cyst, hepatic, pneumothorax encephalogram because Blood: Gas
Partition Coefficient is 34 times higher than that of Nitrogen and a lot of
it is available for exchange with Nitrogen. 80 times expansion takes
place in the pockets).
 Increase the frequency of abortion & fetal abnormalities
7. Intravenous Induction Agents
Commonly used IV induction agents include Prpofol, Sodium Thiopental and
Ketamine. They modulate GABA ergic neuronal transmission. (GABA is the
most common inhibitory neurotransmitter in humans). The duration of action
of IV induction agents is generally 5 to 10 minutes, after which time
spontaneous recovery of consciousness will occur.
(1) Thiopentone sodium (Pentothal)
 Very high lipid solubility
 Rapid action because of rapid transfer across blood – brain barrier; short
duration (about 5 minutes) because of redistribution, mainly to muscle
and fat. Slowly metabolised and liable to accumulate in body fat;
therefore, may cause prolonged effect if given repeatedly.
 Ease of Administration
 Non-explosive
 Induction is rapid & pleasant
 No irritation of mucous membranes
 Less incidence of vomiting & excitement
 No sensitization of myocardium to Adrenaline
 No incidence of post operative vomiting
 Quick recovery
 Low incidence of post-anaesthetic complications Stages of anaesthesia
cannot be recognized
 Pupils remain normal or constricted
 During induction unpleasant and fatal reactions like Apnea, Coughing,
Hiccough, Laryngospasm & Bronchospasm may develop.
 Depression of Respiration centre
 Depression of Vasomotor centre & Myocardium
 Rapid injection may cause Hypotension & Cardiac Arrhythmias
 Inadequate Muscular Relaxation
(2) Propofol
 Most popular IV anaesthetic
 Rapid OOA like barbiturates
 Rapid recovery
 Reduction in postop N & V and a sense of well being Used for both
induction & maintenance
MOA:Facilitate GABA mediated inhibition at GABAA receptor site.
GABAA receptor chloride channel is a major mediator of inhibiting Synaptic
transmission.
 Rapid Induction
 Very rapid recovery as Compared to Thiopental, without any hangover
effect
 Patient feels better in immediate post operative period – No hangover,
no N & V, euphoric effect.
 Post operative nausea and vomiting is uncommon as has antiemetic
actions. No cumulative effect
But it is Very expensive; Apnoea can occur ; CVS depression ; Pain at site
of injection ; Clinical infections
(3) Ketamine
 Ketamine is a general dissociative anaesthetic.
 Ketamine is classified as an NMDA Receptor Antagonist.
 The effect of Ketamine on the respiratory and circulatory syst ems is
different . When used at anaesthetic doses, it will usually stimulate
rather than depress the circulatory system.
MOA: Involve the blockade of the membrane effects of the excitatory NT
glutamic acid at the NMDA (N – methyl – D - aspartate) receptor sub type.The
drug exerts its effect by entering and blocking the open channels
(4) Benzodiazepines ─Diazepam, Lorazepam & Midazolam
Not normally used as GA
 Produce a slower onset of CNS depression-not adequate for surgical
anesthesia stage
 Using larger doses to achieve deep sedation prolongs the postanesthetic
recovery period, also can produce high incidence of anterograde
amnesia
 Depress respiration
(5) Opiod analgesics
 Used for pre-anaesthetic medication
 Used for induction of anaesthesia
 Used for Neurolept analgesia & Neurolept anaesthesia
 GAs in high doses in combination with large doses of BDZs --- in
cardiac/major surgery in pts having Low circulatory reserves . For
conscious sedation with BDZ.
(6) Neuroleptanesthesia
 It is a method of IV anaesthesia which combines the use of a neuroleptic
drug with a narcotic analgesic drug.
 A dministration of such a combination produces a state which differs
from the classical general anaesthesia in that the subject is conscious
and is able to cooperate during the operative procedure .
 The most common combination is that of Droperidol (neuroleptic) and
Fentanyl (opioid analgesic)
(7) Neuromuscular-blocking drugs
 Block neuromuscular transmission at the neuromuscular junction.
 Used as an adjunct to anesthesia to induce paralysis.
 Mechanical ventilation should be available to maintain adequate
respiration.