L7- General Anesthesia

Dr Mohammed Alsbou
Professor of Clinical Pharmacology
College of Medicine, Ajman University

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 Objectives
Describe the mechanism of action, pharmacokinetics,
pharmacodynamics, classifications and adverse
reactions to common drugs used in general anesthesia

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 General anesthesia (GA) is essential to surgical
practice, because it renders patients analgesic,
amnesic, unconscious and provides muscle
relaxation and suppression of undesirable reflexes.
No single drug is capable of achieving these effects
both rapidly and safely.
Rather, several different categories of drugs are
utilized to produce optimal anesthesia

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 General anesthetics are classified into two groups
according to their route of administration:
o Inhaled anesthetics
o Intravenous anesthetics

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PATIENT FACTORS IN SELECTION OF
ANESTHESIA
Liver and kidney: they influence the distribution &
clearance of anesthetic agents and can also be target
organs for toxic effects
Respiratory system: The condition of the respiratory
system must be considered if inhalation anesthetics are
indicated. All inhaled anesthetics depress
respiratory system.

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 Preanesthetic medications
Preanesthetic medication serves to calm the patient,
relieve pain and protect against undesirable effects of
the subsequently administered anesthetic or the surgical
procedure

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 o Antiemetics
o Antihistamines
o Benzodiazepines
o Muscle relaxants
o Opioids

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 Preanesthetic medications
These agents facilitate smooth induction of anesthesia,
they lower dose of anesthetic required to maintain stage
III of anesthesia (surgical anesthesia)
Benzodiazepines, such as midazolam or diazepam, to
relief anxiety & facilitate amnesia
Antihistamines, such as diphenhydramine, for
prevention of allergic reactions

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  Ranitidine, to reduce gastric acidity
Opioids, such as fentanyl, for analgesia
Skeletal muscle relaxants, facilitate intubation and
suppress muscle tone to the degree required for
surgery

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 Stages of Anesthesia
Anesthesia can be divided into three stages: induction,
maintenance & recovery
 Induction is defined as the period of time from onset of
administration of anesthetic to development of effective
surgical anesthesia in the patient.
 Maintenance provides a sustained surgical anesthesia
Recovery is the time from discontinuation of
administration of the anesthesia until consciousness and
protective physiologic reflexes are regained.

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 Induction of anesthesia depends on how fast effective
concentrations of the anesthetic drug reach the brain;
Recovery is the reverse of induction and depends on
how fast the anesthetic drug diffuses from the brain

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 Induction
GA is normally induced with an intravenous
anesthetic like thiopental or propofol;, which
produce unconsciousness within 25 seconds after
injection
At that time, additional inhalation or intravenous
drugs may be given to produce surgical (Stage III)
anesthesia
This often includes coadministration of intravenous
skeletal muscle relaxant to facilitate intubation &
relaxation (pancuronium, atracurium and
succinylcholine)
 For children, without intravenous access, such as
halothane or sevoflurane, are used to induce general
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 Maintenance of anesthesia
Maintenance is the period during which patient is
surgically anesthetized
Anesthesiologist monitors vital signs & response to
various stimuli to carefully balance amount of drug
inhaled and/or infused with depth of anesthesia
Anesthesia is usually maintained by administration
of volatile anesthetics, because these agents offer
good minute-to-minute control over depth of
anesthesia
 Opioids, such as fentanyl, are often used for pain
along with inhalation agents
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 Recovery
Postoperatively, the anesthesiologist withdraws
anesthetic mixture and monitors return of patient to
consciousness
Anesthesiologist continues to monitor patient to be sure
that he or she is fully recovered with normal
physiologic functions (for example, is able to breathe
on his/her own)

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 Depth of anesthesia
The depth of anesthesia has been divided into four
stages
 Each stage is characterized by increased CNS
depression, which is caused by accumulation of
anesthetic drug in brain

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 Stage I—Analgesia: Loss of pain sensation results
from interference with sensory transmission in
spinothalamic tract. The patient is conscious &
conversational
Stage II—Excitement: The patient experiences
delirium and possibly violent & irregularity in blood
pressure. To avoid this stage of anesthesia,
propofol or a short-acting barbiturate, such as
thiopental, is given IV before inhalation anesthesia is
administered

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 Stage III—Surgical anesthesia: Regular respiration
and relaxation of skeletal muscles occur in this stage.
Surgery may proceed during this stage
Stage IV—Medullary paralysis: Severe depression
of the respiratory and vasomotor centers occur during
this stage

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 INHALATION ANESTHETICS
Inhaled gases are the mainstay of anesthesia and are
used primarily for the maintenance of anesthesia
after administration of an intravenous agent
Inhalation anesthetics have a benefit that is not
available with intravenous agents:
o because depth of anesthesia can be rapidly altered by
changing concentration of drug
o Inhalation anesthetics are also reversible, because most
are rapidly eliminated by exhalation

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 Mechanism of action
The focus is on interactions of inhaled anesthetics with
proteins comprising ion channels
The general anesthetics increase the sensitivity of the
γ-aminobutyric acid (GABA) receptors to
neurotransmitter, GABA
This causes a prolongation of inhibitory chloride ion
current, reduce neuronal excitability

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 Inhaled anesthetics
o Halothane
o Desflurane
o Enflurane
o Isoflurane
o Nitrous oxide
o Sevoflurane

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 Halothane
This agent is the prototype to which newer inhalation
anesthetics have been compared.
When halothane was introduced, its ability to induce
anesthetic state rapidly and to allow quick recovery
made it an anesthetic of choice.
 However, with the recognition of adverse effects &
availability of other anesthetics that cause fewer
complications, halothane is being replaced in
developed countries

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 Therapeutic uses
Whereas halothane is a potent anesthetic, it is a
relatively weak analgesic.
Thus, halothane is usually coadministered with nitrous
oxide, opioids
Halothane is not hepatotoxic in pediatric patients
(unlike its potential effect on adults), and combined
with its pleasant odor, this makes it suitable in
children for inhalation induction.
Halothane is metabolized in body to tissue-toxic
hydrocarbons (fever, anorexia, nausea & vomiting),
and patients may exhibit signs of hepatitis.
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 Adverse effects
Cardiac effects: vagomimetic (bradycardia), cardiac
arrhythmias, hypotension. Should it become necessary
to counter excessive hypotension during halothane
anesthesia, it is recommended that vasoconstrictor,
such as phenylephrine, be given
Malignant hyperthermia: In a very small percentage
of patients, may induce malignant hyperthermia (due
increase myoplasmaic calcium concentration)
Should a patient exhibit symptoms of malignant
hyperthermia, dantrolene is given
Therefore, halothane has been replaced by new agents
as sevoflurane & isoflurane
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 Isoflurane
It is widely used; is not tissue toxic.
Unlike the other halogenated anesthetic gases, isoflurane
does not induce cardiac arrhythmias and does not
sensitize heart to the action of catecholamines.
it produces hypotension due to peripheral vasodilation.
It also dilates the coronary arteries, increasing coronary
blood flow. This property may make it benefecial in
patients with ischemic heart disease.

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 Sevoflurane
Rapid onset & recovery
Not irritating to the airway
 Suitable for induction in children

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 Nitrous oxide
Nitrous oxide (“laughing gas”) is a potent analgesic but
a weak anesthetic.
It is not used alone in general anesthesia
It is therefore frequently combined with other, more
potent agents to attain pain-free anesthesia.
It has no effect on cardiovascular system, and it is the
least hepatotoxic of the inhalation anesthetics

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 INTRAVENOUS ANESTHETICS
Intravenous anesthetics are often used for the rapid
induction of anesthesia, which is then maintained with
an appropriate inhalation agent.
They rapidly induce anesthesia and must therefore be
injected slowly

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 INTRAVENOUS ANESTHETICS
o Barbiturates
o Benzodiazepines
o Etomidate
o Ketamine
o Opioids
o Propofol

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 Barbiturates
Thiopental is a potent anesthetic but a weak
analgesic
When thiopental is administered intravenously, it
quickly enters CNS & depress function, often in
less than 1 minute
All barbiturates can cause apnea, coughing,
laryngospasm, and bronchospasm

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 Benzodiazepines
The benzodiazepines are used in conjunction with
anesthetics to sedate the patient
The most commonly employed is midazolam, which
is available in many formulations, including oral.
Diazepam and lorazepam are alternatives.
All three facilitate amnesia while causing sedation

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 Opioids
 Because of their analgesic property, opioids are
frequently used together with anesthetics
 The most frequently employed opioid is fentanyl
 They are administered either intravenously, epidurally, or
intrathecally.
 Opioids can cause hypotension, respiratory depression,
and postanesthetic N & V
 Opioid effects can be antagonized by naloxone

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 Ketamine
 A short-acting, induces a dissociated state in which patient
is unconscious but appears to be awake and does not feel
pain
 This dissociative anesthesia provides sedation, amnesia &
immobility
 Ketamine interacts with N-methyl-D-aspartate (NMDA)
receptor
 It also stimulates central sympathetic outflow, which in
turn, causes stimulation of heart & increased blood pressure
& cardiac output. This property is especially beneficial in
patients with either hypovolemic or cardiogenic shock

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 However, it is not widely used, because it induces
postoperative hallucinations “nightmares”
particularly in adults

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 Propofol (Diprivan)
Is an intravenous sedative/hypnotic used in
induction or maintenance of anesthesia
It is widely used due to its rapid onset of action &
rapid recovery (40 seconds of administration).
 Supplementation with narcotics for analgesia is
required
 Propofol is widely used and has replaced thiopental
as first choice for anesthesia induction and sedation,
because it produces a euphoric feeling in patient &
does not cause postanesthetic N & V

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