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General anesthetics
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Patient factors in selection of
anesthesia:
Drugs are chosen to provide safe and efficient
anesthesia based on:
1. The type of the surgical or diagnostic procedure
2. Patient characteristics such as organ function,
medical conditions, and concurrent medications. e.g.,
IHD, HTN, hypovolemic shock, bronchial asthma.
Status of organ systems:
Cardiovascular system:
whereas the hypotensive effect of most anesthetics is
sometimes desirable, ischemic injury of tissues could
follow reduced perfusion pressure.
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Status of organ systems:
Respiratory system:
All inhaled anesthetics depress the respiratory system. Interestingly,
they are bronchodilators.
Liver and kidney:
The release of fluoride, bromide, and other metabolic products of the
halogenated hydrocarbons can affect these organs, especially with
repeated anesthetic administration over a short period of time.
Pregnancy:
Effects on fetal organogenesis are a major concern in early
pregnancy.
1.nitrous oxide can cause aplastic anemia in the unborn child. Oral
clefts have occurred in the fetuses of women who have received
benzodiazepines.
2.Diazepam should not be used routinely during labor, because it
results in temporary hypotonia and altered thermoregulation in the
newborn.
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Status of organ systems:
Nervous system:
the existence of neurologic disorders (e.g., epilepsy or
myasthenia gravis) influences the selection of anesthetic.
A patient history of a genetically determined sensitivity to
halogenated hydrocarbon-induced malignant
hyperthermia an autosomal dominant genetic disorder
of skeletal muscle that occurs in susceptible individuals
undergoing general anesthesia with volatile agents and
muscle relaxants (eg, succinylcholine).
The malignant hyperthermia syndrome consists of the
rapid onset of tachycardia and hypertension, severe
muscle rigidity, hyperthermia, hyperkalemia, and acid-base
imbalance.
Rx Dantroline
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Preanesthetic medications:
Preanesthetic medications serve to
calm the patient, relieve pain,
protect against undesirable effects of the subsequently
administered anesthetics or the surgical procedure.
facilitate smooth induction of anesthesia,
lowered the required dose of anesthetic
Preanesthetic Medicine:
Benzodiazepines; midazolam or diazepam: Anxiolysis &
amnesia.
barbiturates; pentobarbital: sedation
Diphenhydramine: Prevention of allergic reactions:
antihistamines
H2 receptor blocker- famotidine, ranitidine: Reduce gastric
acidity.
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Preanesthetic medications:
Antiemetics- ondansetron: Prevents aspiration of stomach
contents and post surgical vomiting:
acetaminophen, celecoxib or opioids (fentanyl) for analgesia
Anticholinergics: (glycopyrrolate, scopolamine):
Amnesia
Reduce bronchial and salivary secretion: irritant inhaled anesthetic
cause excessive salivation and secretion.
Reduce any tendency to bronchospasm
Prevent bradycardia and hypotension: manipulation of visceral
organs stimulates vagus leading to bradycardia.
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Stages and depth of anesthesia
General anesthesia has three stages: induction,
maintenance, and recovery.
Use preanesthetic medication
Induce by I.V thiopental or suitable alternative
Use muscle relaxant Intubate
Use, usually a mixture of N2O and a halogenated
hydrocarbon maintain and monitor.
Withdraw the drugs recover
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Stages and depth of anesthesia/
Induction
Induction: the period of time from the onset of administration
of the anesthetic to the development of effective surgical
anesthesia in the patient. It depends on how fast effective
concentrations of the anesthetic drug reach the brain.
Thus GA is normally induced with an I.V thiopental, which
produces unconsciousness within 25 seconds or propofol
producing unconsciousness in 30 to 40 seconds after injection.
At that time, additional inhalation or IV drugs may be given to
produce the desired depth of surgical stage III anesthesia. This
often includes an IV neuromuscular blocker such as rocuronium,
vecuronium, or succinylcholine to facilitate tracheal intubation
and muscle relaxation.
Inhalation induction: For children without IV access, non
pungent agents, such as halothane or sevoflurane, are used to
induce GA.
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Stages and depth of anesthesia/ Maintenance
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Stages and depth of anesthesia/ Recovery
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Depth of Anesthesia (GUEDELS Signs)
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Depth of Anesthesia (GUEDELS Signs)
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Inhalation anesthetics
Inhaled gases are used primarily for maintenance of anesthesia.
Depth of anesthesia can be rapidly altered by changing the inhaled
concentration, very narrow therapeutic index, No antagonists exist.
Common features of inhaled anesthetics
Modern inhalation anesthetics are nonflammable, nonexplosive
agents.
Decrease cerebrovascular resistance, resulting in increased
perfusion of the brain
Cause bronchodilation, and decrease both spontaneous ventilation
and hypoxic pulmonary vasoconstriction (increased pulmonary
vascular resistance in poorly aerated regions of the lungs,
redirecting blood flow to more oxygenated regions).
Movement of these agents from the lungs to various body
compartments depends upon their solubility in blood and
tissues, as well as on blood flow. These factors play a role in
induction and recovery.
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MAC (potency)
MAC (potency): the minimum alveolar
concentration, the end-tidal concentration of
inhaled anesthetic needed to eliminate movement
in 50% of patients stimulated by a standardized
incision.
MAC is the ED50 of the anesthetic.
the inverse of MAC is an index of potency of the
anesthetic.
MAC expressed as the
percentage of gas in a mixture
required to achieve that effect.
Numerically, MAC is small for
potent anesthetics such as
sevoflurane and large for less
potent agents such as nitrous
oxide.
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MAC (Potency)
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uptake and distribution of inhalation
anesthetics
The principal objective of inhalation anesthesia is a constant and
optimal brain partial pressure (Pbr) of inhaled anesthetic (partial
pressure equilibrium between alveoli [P alv] and brain [Pbr]).
Thus, the alveoli are the windows to the brain for inhaled
anesthetics.
The partial pressure of an anesthetic gas at the origin of the
respiratory pathway is the driving force moving the anesthetic
into the alveolar space and, thence, into the blood (P a), which
delivers the drug to the brain and other body compartments.
Because gases move from one compartment to another within
the body according to partial pressure gradients, a steady state
(SS) is achieved when the partial pressure in each of these
compartments is equivalent to that in the inspired mixture.
Palv = Pa = Pb
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Factors Determine the time course for attaining
Steady State:
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Factors Determine the time course for attaining Steady
State:
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Factors Determine the time course for attaining
Steady State:
b. Cardiac output: CO affects removal of
anesthetic to peripheral tissues, which are not
the site of action.
For inhaled anesthetics, higher CO removes
anesthetic from the alveoli faster and thus slows
the rate of rise in alveolar concentration of gas.
It therefore takes longer for the gas to reach
equilibrium between the alveoli and the site of
action in the brain. higher CO equals slower
induction. Low CO (shock) speeds the rate of rise
of the alveolar concentration of gas, since there
is less removal to peripheral tissues.
c. Alveolar to venous partial pressure
gradient of the anesthetic: this is driving
force of delivery. The greater the difference in
anesthetic concentration between alveolar 22
Factors Determine the time course for attaining
Steady State:
3. Effect of different tissue types on anesthetic
uptake:
It is also directly proportional to the capacity of that tissue
to store anesthetic (a larger capacity results in a longer
time required to achieve steady state).
Capacity, in turn, is directly proportional to the tissues
volume and the tissue/ blood solubility coefficient of the
anesthetic.
The time required for a particular tissue to achieve a
steady-state with PP of an anesthetic gas in the inspired
mixture is
inversely proportional to the blood flow to that tissue.
directly proportional to the tissues volume and the
tissue/blood solubility coefficient of the anesthetic
molecules (tissue capacity).
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Factors Determine the time course for attaining
Steady State:
Four major tissue compartments determine the time course of anesthetic
uptake:
a. Brain, heart, liver, kidney, and endocrine glands: these highly perfused
tissues rapidly attain a steady-state with the PP of anesthetic in the blood.
b. Skeletal muscles: poorly perfused, and have a large volume, prolong the
time required to achieve steady-state.
c. Fat: poorly perfused. However, potent GA are very lipid soluble. Therefore,
fat has a large capacity to store anesthetic. This combination of slow delivery
to a high capacity compartment prolongs the time required to achieve
steady-state.
d. Bone, ligaments, and cartilage: these are poorly perfused and have a
relatively low capacity to store anesthetic.
4. Wash out: when the administration of anesthetics discontinued, the
body now becomes the source that derives the anesthetic into the
alveolar space. The same factors that influence attainment of steady-
state with an inspired anesthetic determine the time course of clearance
of the drug from the body. Thus N2O exits the body faster than halothane.
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MECHANISM OF ACTION OF
ANAESTHESIA
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Halothane (Prototype)
Advantages:
Potent anesthetic, rapid induction & recovery
Neither flammable nor explosive, sweet smell,
non irritant
Does not augment bronchial and salivary
secretions.
Low incidence of post operative nausea and
vomiting.
Relaxes both skeletal and uterine muscle, and can
be used in obstetrics when uterine relaxation is
indicated.
Not hepatotoxic in pediatric patient, and
combined with its pleasant odor, this makes it
suitable in children for inhalation induction.
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Halothane :
Disadvantages:
Weak analgesic (thus is usually coadministerd with
N2O, opioids)
Is a strong respiratory depressant
Is a strong cardiovascular depressant; halothane is
vagomimetic and cause atropine-sensitive
bradycardia.
Cardiac arrhythmias: serious if hypercapnia
develops due to hypoventilation and an increase
in the plasma concentration of catecholamines)
Hypotensive effect (phenylephrine recommended)
Hepatotoxic: is oxidatively metabolized in the liver
to tissue-toxic hydrocarbons (e.g., trifluroethanol
and bromide ion).
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Malignant hyperthermia
Enflurane
Advantages:
Less potent than halothane, but produces rapid
induction and recovery
~2% metabolized to fluoride ion, which is excreted by
the kidney
Has some analgesic activity
Differences from halothane:
Fewer arrhythmias,
less sensitization of the heart to catecholamines,
and greater potentiation of muscle relaxant due to more
potent curare-like effect.
Disadvantages: CNS excitation at twice the MAC, Can
induce seizure
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Isoflurane:
Advantages:
A very stable molecule that undergoes little
metabolism
Not tissue toxic
Does not induce cardiac arrhythmias
Does not sensitize the heart to the action of
catecholamines
Produces concentration-dependent hypotension
due to peripheral vasodilation
It also dilates the coronary vasculature, increasing
coronary blood flow and oxygen consumption by
the myocardium, this property may make it
beneficial in patients with IHD. 29
Desflurane:
Rapidity of induction and recovery: outpatient surgery
Less volatility (must be delivered using a special vaporizer)
Like isoflurane, it decreases vascular resistance and perfuse all
major tissues very well.
Irritating cause apnea, laryngospasm, coughing, and excessive
secretions
Sevoflurane:
Has low pungency, not irritating the airway during induction;
making it suitable for induction in children
Rapid onset and recovery:
Metabolized by liver, releasing fluoride ions; thus, like
enflurane, it may prove to be nephrotoxic.
Methoxyflurane
The most potent and the best analgesic anesthetic available for
clinical use. Nephrotoxic and thus seldom used.
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Nitrous oxide (N2O) laughing
gas
It is a potent analgesic but a weak general anesthetic.
Rapid onset and recovery:
Does not depress respiration, and no muscle relaxation.
No effect on CVS or on increasing cerebral blood flow
Clinical use: dental surgery, obstetrics, postoperative
physiotherapy, refractory pain in terminal illness, and
maintenance of anesthesia.
The least hepatotoxic, Teratogenic, bone marrow
depression.
Second gas effect: N2O can concentrate the halogenated
anesthetics in the alveoli when they are concomitantly
administered because of its fast uptake from the alveolar
gas.
Diffusion hypoxia: speed of N2O movement allows it to
retard oxygen uptake during recovery.
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Intravenous anesthetics
Barbiturates (thiopental, methohexital)
Potent anesthetic but a weak analgesic
High lipid solubility; quickly enter the CNS and
depress function, often in less than one minute,
and redistribution occur very rapidly as well to
other body tissues, including skeletal muscle and
ultimately adipose tissue (serve as a reservoir).
Thiopental has minor effects on the CVS but it may
cause sever hypotension in hypovolemic or shock
patient
All barbiturates can cause apnea, coughing, chest
wall spasm, laryngospasm, and bronchospasm
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Intravenous anesthetics/ Propofol
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Intravenous anesthetics/ Etomidate
Is used to induce anesthesia, it is a hypnotic
agent but lacks analgesic activity.
Induction is rapid, short acting
It is only used for patients with coronary artery
disease or cardiovascular dysfunction,
No effect on heart and circulation
Adverse effects: a decrease in plasma cortisol and
aldosterone levels which can persist for up to
eight hours. This is due to inhibition of 11-B-
hydroxylase
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Intravenous anesthetics/ ketamine
Ketamine (phencyclidine derivative) a short-acting, anesthetic,
induces a dissociated state in which the patient is unconscious
(but may appear to be awake) and does not feel pain.
This dissociative anesthesia provides sedation, amnesia, and
immobility.
Ketamine stimulates central sympathetic outflow, causing
stimulation of the heart with increased blood pressure and CO.
It is also a potent bronchodilator.
Therefore, it is beneficial in patients with hypovolemic or
cardiogenic shock and in asthmatics. Conversely, it is
contraindicated in hypertensive or stroke patients.
Ketamine is used mainly in children and elderly adults for short
procedures.
It is not widely used, because it increases cerebral blood flow
and may induce hallucinations, particularly in young adults.
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Dexmedetomidine
is a sedative used in intensive care settings and
surgery. It is relatively unique in its ability to
provide sedation without respiratory depression.
Like clonidine, it is an 2 receptor agonist in certain
parts of the brain.
Dexmedetomidine has sedative, analgesic,
sympatholytic, and anxiolytic effects that blunt
many cardiovascular responses.
It reduces volatile anesthetic, sedative, and
analgesic requirements without causing significant
respiratory depression.
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Adjuvants/ BDZs & Opioids (fentanyl,
sufentanil)
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Properties of Intravenous Anesthetic
Agents
Drug Induction and Main Unwanted Notes
Recovery Effects
thiopental Fast onset Cardiovascular and Used as induction agent
(accumulation respiratory depression declining. CBF and O2
occurs, giving slow consumption
recovery) Hangover Injection pain
etomidate Fast onset, fairly fast Excitatory effects Less cvs and resp
recovery during induction depression than with
Adrenocortical thiopental, Injection site pain
suppression
propofol Fast onset, very fast cvs and resp Most common induction
recovery depression agent. Rapidly metabolized;
Pain at injection site. possible to use as
continuous infusion. Injection
pain. Antiemetic
ketamine Slow onset, after- Psychotomimetic Produces good analgesia
effects common effects following and amnesia. No injection
during recovery recovery, Postop site pain
nausea, vomiting
salivation
midazolam Slower onset than Minimal CV and resp Little resp or cvs depression.
other agents effects. No pain. Good amnesia. 38