General anesthesia: a reversible state of central nervous
system depression resulting in loss of response to and
perception of external stimuli
For patients undergoing surgical and other medical
procedures anesthesia provides these benefits:
⮚ Sedation and reduction of anxiety
⮚ Lack of awareness and amnesia
⮚ Skeletal muscle relaxation
⮚ Suppression of undesirable reflexes
⮚ Analgesia
Because no single agent can provide all thosebenefits,
several drugs are used in combination to produce optimal
anesthesia.
• Serve to calm the patient, relieve the pain and protect against
undesirable effects of anesthetics or the surgical procedure
▫ Antacids (neutralize stomach acidity)
▫ H2 blockers like famotidine (Reduce gastric acidity)
▫ Anticholinergics like glycopyrrolate (Prevent bradycardia and
secretion of fluids)
▫ Antiemetics like ondansetron (Prevent aspiration of stomach
contents and postsurgical nausea and vomiting and)
▫ Antihistamine like diphenhydramine (Prevent allergic reactions)
▫ Benzodiazepines like diazepam (Relieve anxiety)
▫ Opioids like fentanyl (Provide analgesia)
▫ Neuromuscular blockers (Facilitate intubation and relaxation)
◦ Neuromuscular blockers
⮚ Pancuronium
⮚ Succinylcholine
❑ Induction: the period of time from the onset of
administration of the potent anesthetic to the
development of effective surgical anesthesia in the
patient.
▫ Depends on how fast effective concentration of the drug
reaches the brain
Maintenance of anesthesia: providing a sustained
surgical anesthesia
Recovery: the time from discontinuation of administration
of anesthesia until consciousness and protective
physiologic reflexes are regained
❑ Depends on how fast the drug leaves the brain
General anesthesia in adults is normally induced with an
IV anesthetic like propofol
At that time, additional inhalation and/or IV anesthetic
drugs may be given to produce the desired depth of
surgical anesthesia
Often includes coadministration of an IV skeletal muscle
relaxant such as rocuronium, vecuronium, or
succinylcholine to facilitate intubation and muscle
relaxation
For children without IV access, inhalation induction is
used such as halothane or sevoflurane, to induce general
anesthesia
Maintenance is the period during which the
patient is surgically anesthetized.
Patient’s vital signs and response to various stimuli
are monitored continuously throughout the surgical
procedure Opioids such as fentanyl are often used
for pain relief.
IV infusions of various drugs may also be used.
❑ Postoperatively, the anesthetic admixture is
withdrawn, and the patient is monitored for
the return of consciousness
❑ If skeletal muscle relaxants have not been fully
metabolized, reversal agents may be used.
❑ The anesthesiologist continues to monitor the
patient for full recovery, with normal physiologic
functions.
• Depth of anesthesia is the
degree to which the CNS is
depressed.
• Useful parameter for
individualizing anesthesia.
▫ Stage I Analgesia
▫ Stage II Excitement
▫ Stage III Surgical anesthesia
▫ Stage IV Medullary paralysis
▫ Stage I
Analgesia
❑ Loss of pain sensation
❑ Drowsiness
❑ Amnesia and reduced awareness of pain
▫ Stage II Excitement
❑ Delirium
❑ Rise and irregularity in blood pressure and respiration
❑ Risk of laryngospasm
❑ To shorten this period a rapid acting anesthetic like
propofol is administered IV before inhaled anesthetic
▫ Stage III Surgical
anesthesia
❑ Loss of muscle tone and reflexes
❑ Ideal stage for surgery
Requires careful monitoring
▫ Stage IV Medullary paralysis
❑ Severe depression of the respiratory and vasomotor
centers
❑ Death can occur unless respiration and circulation are
maintained
Potent general anesthetics are delivered
via inhalation or IV injection
◦ Inhaled general anesthetics
◦ Intravenous general anesthetics
Used for maintenance of anesthesia after
administration of an IV agent
The depth of anesthesia can be altered rapidly by
changing inhaled concentration of the drug
Narrow therapeutic index (from 2 -4)
No antagonists exist
Mechanism of
action
◦ No specific receptor has been identified as the locus of
general anesthetic action
◦ Anesthetics increase the sensitivity of GABA receptors to the
neurotransmitter GABA prolonging the inhibitory chloride ion
current after GABA release, reducing the postsynaptic
neurons excitability
◦ Anesthetics increase the activity of the inhibitory glycine
receptors in the spinal motor neuron
◦ Anesthetics block excitatory postsynaptic nicotinic
currents
◦ The mechanism by which the anesthetics perform these
modulatory roles is not understood
❑ Potent anesthetic, weak analgesic.
❑ Administered with nitrous oxide, opioids or local
anesthetics
❑ Being replaced by other agents due to its adverse
effects
Adverse
effects
◦ Cardiac effects: Vagomimetic effects, bradycardia, can
cause cardiac arrhythmias
◦ Malignant hyperthermia:
Rare and life threatening condition
Uncontrolled increase in skeletal muscle oxidative
metabolism, which overwhelms the body’s capacity to
supply oxygen, remove carbon dioxide, and regulate body
temperature
If untreated would cause circulatory collapse and
death
Treatment: Dantrolene administration
❑ Undergoes little metabolism, not toxic to the liver or
kidney
❑ Does not induce cardiac arrhythmias
❑ Produces dose-dependent hypotension due to
peripheral vasodilation
Provides very rapid onset and recovery due to its
low blood solubility, the lowest of all the volatile
anesthetics
Popular anesthetic for outpatient surgery
Irritating to the airway and can cause
laryngospasm, coughing, and excessive
secretions,
Degradation is minimal, tissue toxicity is rare
❑ Low pungency, allowing rapid induction without
irritating the airway, making it suitable for
inhalation induction in pediatric patients
❑ Replacing halothane for this purpose
❑ Metabolized by the liver, and compounds formed in
the anesthesia circuit may be nephrotoxic
Non-irritating and a potent analgesic but a weak general anesthetic
Nitrous oxide is frequently employed at concentrations of 30–50% in
combination with oxygen for analgesia, particularly in dental surgery.
Nitrous oxide at 80 percent (without adjunct agents) cannot produce
surgical anesthesia
Combined with other, more potent agents to attain pain-free anesthesia
Mechanism of action is unresolved, might involve activity on GABA A and
NMDA receptors
Least hepatotoxic of all inhaled anesthetics
❑ Used in situations that require short duration
anesthesia (outpatient surgery)
❑ Primarily used as adjuncts to inhalationals
❑ Rapidly induce unconsciousness
❑ In lower doses, they may be used to provide
sedation
Induction
After entering the blood stream, a percentage of the drug
binds to the
plasma proteins, and the rest remains unbound (free)
The drug is carried by venous blood to the heart
The majority of the CO (70%) flows to the brain, liver, and
kidney
Once the drug has penetrated the CNS tissue, it exerts its
effects
The exact mechanism of action of IV anesthetics is unknown
Recovery
Recovery from IV anesthetics is due to redistribution from
sites in the CNS
Propofol
Fospropofol
Barbiturates
Benzodiazepines
Opioids
Ketamine
IV sedative/hypnotic used in the induction or
maintenance of anesthesia
Widely used and has replaced thiopental as first choice for
anesthesia induction and sedation, because it does not
cause postanesthetic nausea and vomiting
The induction of anesthesia occurs within 30–40
seconds of administration
Supplementation with narcotics for analgesia is
required
Propofol decreases blood pressure without depressing the
myocardium
It also reduces intracranial pressure due to systemic
vasodilation
Approved only for sedation
Prodrug of propofol
o The barbiturates are not significantly analgesic, require some
type of supplementary analgesic administration during
anesthesia to avoid objectionable changes in blood pressure and
autonomic function. Can cause apnea, coughing, chest wall
spasm, laryngospasm, and bronchospasm.
Thiopental
◦ Potent anesthetic but a weak analgesic
◦ Ultrashort-acting barbiturate
◦ Has minor effects on the cardiovascular system, but it may
contribute to severe hypotension in patients with hypovolemia or
shock.
Used in conjunction with anesthetics to sedate the
patient
Facilitate amnesia while causing sedation
Enhance the inhibitory effects of various
neurotransmitters, particularly GABA
Minimal cardiovascular depressant effect
Potential respiratory depressants
Commonly used with anesthetics due to their analgesic property
The choice of opioid used perioperatively is based
primarily on the duration of action needed
Fentanyl, remifentanil
◦ Induce analgesia more rapidly than morphine
◦ Administered intravenously, epidurally, intrathecally
A short-acting nonbarbiturate anesthetic
Used for short procedures
Induces a dissociated state in which the patient is
unconscious and does not feel pain`
This dissociative anesthesia provides sedation,
amnesia, and immobility
Interacts with the N-methyl-D-aspartate receptor
Stimulates the central sympathetic outflow, which, in turn,
causes stimulation of the heart with increased blood
pressure and CO
◦ Beneficial in patients with hypovolemic or cardiogenic shock
and in patients with asthma)
◦ Not used in hypertensive or stroke patients
Causes post-operative hallucinations
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