General anesthetics(GA)

What is GA?
 Depress CNS to the extent that permit performance of
surgery & other noxious/unpleasant procedures
 Physiologic state induced by GA
 analgesia
 amnesia
 loss of consciousness
 inhibition of sensory & autonomic reflexes
 skeletal muscle relaxation
 The first general anesthetic, ether, was introduced by
Dr. William T. Morton in 1846.
 Prior to this, surgery was a brutal and exquisitely painful
ordeal, undertaken only in the most desperate
circumstances
18th Century Surgery
STAGES AND DEPTH OF ANESTHESIA

 Three stages
 Induction

 Maintenance

 recovery

 Induction is defined as the period of time from the onset of

administration of the potent anesthetic to the development of
effective surgical anesthesia in the patient.
 Maintenance provides a sustained surgical anesthesia
 Recovery is the time from discontinuation of administration of
anesthesia until consciousness and protective physiologic reflexes
are regained
 Depth of anesthesia is the degree to which the CNS is
depressed
 Stage I: Analgesia
 Stage II: Excitement
 Stage III: Surgical anesthesia
 Stage IV: Medullary paralysis
Property of an Ideal anesthetic
1. For patient
•Pleasant, non-irritant, not cause nausea, vomiting &
with wide margin of safety
•Fast induction & recovery without after effect
2. For the surgeon
•Adequate analgesia, immobility and muscle relaxation

3. For the anesthetist

•Easy administration, controllable
 No single anesthetic has all of these qualities
 Balanced anesthesia,
 Short-acting barbiturates (for induction of anesthesia),
 neuromuscular blocking agents (for muscle relaxation), and
 opioids and nitrous oxide (for analgesia).
 pre and post operative medications are required
Mechanism of action
 Not precisely known
 lipid theory : potency correlated with lipid solubility
 anesthetics dissolve into neuronal membranes, disrupt

their structure, and thereby suppress axonal

conduction and possibly synaptic transmission
 Effect on ion channels: recent theory
 anesthetics work by enhancing transmission at inhibitory
synapses and by depressing transmission at excitatory synapses
 Most anaesthetics enhance activity of inhibitory GABAA receptors, and
inhibit activation of excitatory receptors such as glutamate and nAch
receptors
 However individual anaesthetics differ in their actions and affect cellular
function in several different ways
 Halogenated hydrocarbons
 Activation of K+channel
 Enhance GABA effect
 Nitrous oxide and Ketamine
• Don’t affect GABA or glycine gated Cl - channel
• Selectively inhibit excitatory NMDA type of glutamate receptor

Classification

 General anesthetics are divided into two groups on the

basis of their route of administration
 inhalation anesthetics

 Intravenous anesthetics
1. Inhaled anesthetics (gases or volatile
liquids)
 Halothane
 Desflurane
 Sevoflurane
 Isoflurane
 Enflurane
 Ethoxyflurane
 Nitrous oxide
 Diethyl ether
The minimum alveolar concentration

 Is an index of inhalation anesthetic potency

 The MAC is defined as the minimum concentration of
drug in the alveolar air that will produce immobility in
50% of patients exposed to a painful stimulus
 A low MAC indicates high anesthetic potency
General actions of inhaled anesthetics
 Depress respiration
 Depression of renal blood flow and urine output
 High concentrations will relax skeletal muscle
 Generalized reduction in arterial pressure and
peripheral vascular resistance
 Conc-dependent decrease in hepatic blood flow
Adverse effects
 Respiratory and Cardiac Depression
 Malignant hyperthermia
 characterized by muscle rigidity and a profound

elevation of temperature
 greatest when an inhalation anesthetic is combined

with succinylcholine
 Hepatotoxicity
Halothane
 is the prototype of the volatile inhalation anesthetics
 Is the most widely used agent, highly lipid soluble
 Has a high-potency anesthetic: MAC (0.75%)
 Induction of anesthesia is smooth and relatively rapid
 induction is usually produced with thiopental, a rapid-acting
barbiturate
 Halothane is a weak analgesic
 Morphine and nitrous oxide are used
 Although halothane has muscle relaxant actions, the
degree of relaxation is generally inadequate for surgery
 neuromuscular blocking agent (eg, pancuronium) is usually required
Halothane contd...
 Halothane is oxidatively metabolized in the body to tissue-toxic
hydrocarbons (for example, trifluoroethanol) and bromide ion
 Hepatic necrosis

 has occurred in adults only

 halothane anesthesia shouldn’t not repeated at intervals of less

than 2 to 3 weeks.
 Halothane causes a dose-dependent reduction in blood pressure

 Malignant hyperthermia-a rare life-threatening condition.

 high when combined with succinylcholine

 Dantrolene is used for treatment

Enflurane
 Has pharmacologic properties very similar to those of halothane
 The MAC of enflurane is 1.68%, compared with 0.75% for halothane
 Poorly metabolized in the liver, thus less toxic than halothane
 Faster induction and recovery than halothane (less accumulation
in fat)
 High doses of enflurane can induce seizures, a response not seen
with halothane
Isoflurane
 Is potent (MAC =1.15%)
 It is a very stable molecule that undergoes little
metabolism and is not, therefore, toxic to the liver or
kidney
 may precipitate myocardial ischemia in patients with
coronary disease
 It has a pungent odor and stimulates respiratory reflexes
(salivation, coughing, and laryngospasm) and is,
therefore, not used for inhalation induction
 Desflurane
 similar to isoflurane but with faster onset and recovery
 respiratory irritant, so liable to cause coughing and laryngospasm
 which are caused by the drug's pungency
 Sevoflurane
 similar to desflurane with lack of respiratory irritation
 In contrast to desflurane, sevoflurane has a pleasant odor and is
not a respiratory irritant
 suitable for inhalation induction in pediatric patients
 as an effective labor analgesic
Nitrous oxide(aka “laughing gas”)
 Odorless and colourless gas
 It has very low anesthetic potency
 The MAC of nitrous oxide is very high: greater than 100%

 It has very high analgesic potency

 nitrous oxide is frequently combined with other inhalation agents

to enhance analgesia
 low potency, therefore must be combined with other agents

 Nitrous oxide alone is used for analgesia in dentistry and during

delivery
 It is a relatively free of serious unwanted effects
 Maternal drowsiness in 0 –24% of laboring women
Ether
 obsolete except where modern facilities are not
available
 easy to administer and control
 slow onset and recovery, with postoperative
nausea and vomiting
 analgesic and muscle relaxant properties
 irritant to respiratory tract
2.Intravenous anesthetics
 Barbiturates (eg, thiopental, methohexital)
 Benzodiazepines (midazolam, diazepam,
lorazepam)
 Opioids (fentanyl)
 Propofol
 Ketamine
 Etomidate
 I.V. anaesthetics have faster onset of action than the
most rapid inhaled agents (eg. desflurane and
sevoflurane)
 Used for induction of general anesthesia
 Also used for short ambulatory (outpatient) surgical
procedures
Thiopental
 It is an ultrashort-acting barbiturate with high lipid solubility
 Rapid action (onset<20min) due to rapid transfer across
BBB
 Short duration due to redistribution
 Single dose produces only a brief period of
unconsciousness (rapid removal from brain)
 No analgesic effect
 narrow margin between anesthetic dose and dose
causing cardiovascular depression
Benzodiazepines
 are used in conjunction with anesthetics to sedate the
patient
 The most commonly used is midazolam
 Diazepam and lorazepam are alternatives.
 All three facilitate amnesia while causing sedation
 Side Effects
 Fluctuations in vital signs, including decreased respiratory rate,
apnea, variations in blood pressure & pulse rate are common
 Midazolam should not be administered by rapid injection
in the neonatal population
 Severe hypotension and seizures
Opioids
 are most commonly used in cardiovascular surgery and
other types of high-risk surgery
 mechanical respiratory assistance must be provided
because of respiratory depression caused by these agents
 The most commonly used opioids is fentanyl
 induces analgesia more rapidly than morphine does

 Opioids are not good amnesics, and they can all cause
hypotension, respiratory depression, and muscle
rigidity as well as postanesthetic nausea and vomiting
 CI-pregnancy (the fetus may become physically
dependent in utero)
 Opioid effects can be antagonized by naloxone
Etomidate
 A hypnotic with no analgesic activity
 Similar to thiopental but more quickly metabolized (onset
of action: 1 min, duration: 3-5 min)
 Causes minimal cardiovascular and respiratory
depression (compared to other i.v. anesthetics)
 Used for induction of anesthesia in patients with limited
cardiovascular reserve
 Minimal hypotension even in elderly patients with poor
cardiovascular reserve
Etomidate....
Adverse effects
Pain on injection
Postoperative nausea and vomiting
Prolonged use may cause suppresses of adrenal
steroids(cortisol and aldosterone) production
Prolonged infusion to critically ill patients may
result in
 hypotension and electrolyte imbalance
 oliguria
Propofol
 has a rapid onset and short duration of action
 Unconsciousness develops within 60 seconds and

lasts for 3 to 5 minutes following a single injection

 For induction and maintenance of anesthesia as part of
total intravenous or balanced anesthesia
 Propofol 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 postanesthetic nausea and

vomiting
 SEs- apnea, decreased cardiac output,

hypotension
Ketamine
 produces a state known as dissociative anesthesia
 the patient is unconscious (but may appear to be awake; their

eyes may open & their limbs may move involuntarily ) and does
not feel pain.
 causes sedation, immobility, analgesia, and amnesia
 Ketamine interacts with the N-methyl-D-aspartate receptor
 It also stimulates the central sympathetic outflow, which, in turn,
causes stimulation of the heart with increased blood pressure and
CO.
 it is not widely used, because it increases cerebral blood flow and
induces postoperative hallucinations (“nightmares”), particularly in
adults.
Anesthetic during pregnancy
 Risks
 teratogenic effects of anesthetics

 Derangement of fetal homeostasis

 Recommendations
 Elective surgery should be postponed until after

delivery.
 In semielective cases, it is best if surgery can be

postponed until after the first trimester

 If possible, regional anesthesia, e.g., spinal, epidural,

or nerve block, is advisable.

 However, general anesthesia can be administered if

necessary
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