general anesthesia. 2010
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General Anesthesia
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Definition:
A reversible state of analgesia, amnesia, loss of consciousness, inhibitionof sensory and autonomic reflexes and variable degrees of skeletal
muscle relaxation.
Mechanism of action
the general anesthetics increase the sensitivity of the (GABAA) receptorsto the neurotransmitter, GABA.
Binding of GABA causes the chloride Ion channel to open, leading to
hyperpolarization of the cell.
Postsynaptic neuronal excitability is thus diminished.
the activity of the inhibitory glycine receptors in the spinal motor neurons
is increased.
block excitatory postsynaptic current of the nicotinic receptors.
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INDUCTION, MAINTENANCE, AND RECOVERY FROM ANESTHESIA
InductionAim: During induction, it is essential to avoid the dangerous excitatory phase
(Stage II delirium).
Induction occurs with an intravenous anesthetic like thiopental, which
produces unconsciousness within 25 seconds after injection.
Maintenance of anesthesiaDef. Maintenance is the period during which the patient is surgically
anesthetized.
Anesthesia is usually maintained by the administration of volatile
anesthetics, because these agents offer good minute-tominute control over
the depth of anesthesia.
Recovery Posoperatively, the anesthesiologist withdraws the anesthetic mixture and
monitors the return of the patient to consciousness.
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INHALATION ANESTHETICS
Inhaled gases are used primarily for the maintenance of anesthesia
after administration of an intravenous agent.
A. Common features of inhaled anesthestics
Inhalation anesthetics are nonflammable, nonexplosive agents.
These agents decrease cerebrovascular resistance, resulting in
increased perfusion of the brain.
They also cause bronchodilation.
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Potency
MAC is the concentration of anesthetic gas needed to eliminate
movement among 50% percent of patients exposed to a noxious
stimulus.
MAC is small for potent anesthetics, such as halothane, and large for
less potent agents, as nitrous oxide.
Therefore, the inverse of MAC is an index of potency of the
anesthetic.
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a. Solubility in the blood: (blood/gas partition coefficient).
An anesthetic gas with low blood solubility (nitrous oxide), diffuses
from the alveoli into the circulation, little of the anesthetic dissolvesin theblood. Therefore, the equilibrium between the inhaled
anesthetic and arterial blood occurs rapidly.
An anesthetic gas with high blood solubility (halothane), dissolves
more completely in the blood and greater amounts of the anesthetic
and longer periods time are required to raise arterial partial
pressure. This results in increased times of induction as well as
recovery.
The solubility blood is ranked in the following order: halothane >
enflurane> isoflurane > sevoflurane > desflurane > nitrous oxide.
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3. Effect of different tissue types on anesthetic uptake:
The time required to achieve a steady-state is inversely
proportional to the blood flow to that tissue; e.g. faster flow results
in a more rapidly achieved steady-state.
The time required to achieve a steady-state is directly proportional
to the capacity of that tissue, a larger capacity results in a longer
time required to achieve steady-state.A- Brain, heart, liver, kidney, and endocrine glands:highly
perfused tissues rapidly attain a steady-state with the partial
pressure of anesthetic in the blood.
B- Skeletal muscles:poorly perfused tissuesprolong the timerequired to achieve steady-state.
C- Fat:poorly perfused tissues and has a large capacity so prolong
time to achieve steady state.
d-Bone, ligaments, and cartilage:These are poorly perfused and
have a relatively low capacity to store anesthetic.
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Halothane
Therapeutic uses:
halothane is a potent anesthetic, it is a relatively weak analgesic.
Halothane relaxes both skeletal and uterine muscle.
Halothane is not hepatotoxic in pediatric patients, and, combinedwith its pleasant odor, this makes it suitable in children for inhalation
induction.
Safe for asthmatics
Pharmacokinetics:
Halothaneis metabolized to tissue-toxic hydrocarbons (for example,
trifluroethanol and bromide ion.
50% of patients will die of hepatic necrosis. not repeated at intervals less
than two to three weeks.
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Adverse effects:1. Hepatitis
2. Cardiac effects:
halothaneis vagomimetic and causes bradycardia.
halothanecauses cardiac arrhythmias due to increase in the plasma
concentration of catecholamines.
Halothane, produces concentration-dependent hypotension.
3. Malignant hyperthermia:
all of the halogenated hydrocarbon anesthetics as well as the
muscle relaxant succinylcholine
have the potential to inducemalignant hyperthermia. (Genetic defect in muscle calcium)
a dramatic increase in the myoplasmic calcium concentration.
Treated by dantrolene.
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F. Enflurane less potent than halothane, but produces rapid induction and
recovery.
About 2% of the anesthetic is metabolized to fluoride ion,
which is excreted by the kidney. Therefore, enfluraneis
contraindicated in patients with kidney failure.
Advantages:
Enfluraneanesthesia exhibits the following differences fromhalothane:
fewer arrhythmias.
less sensitization of the heart to catecholamines.
greater potentiation of muscle relaxants due more potent
"curare-like" effect.
disadvantage:
Nephrotoxic (fluoride ion). central nervous system (CNS) excitation at twice the MAC For
this reason, it is not used in patients with seizure disorders.
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Isofurane It is very stable molecule that undergoes little metabolism; as a result,
little fluoride is produced.
Advantages:1. isofluraneis not tissue toxic.
2. isoflurane does not induce cardiac arrhythmias and does not sensitize
the heart the action of catecholamines.
3. Adequate muscle relaxation.
Disadvantages:1. It produces concentrationdependent hypotension due to peripheral
vasodilation.
2. All halogenated inhalation anesthetics have been reported to cause
hepatitis, but at a much lower incidence than with halothane.3. Irritant on bronchi
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Sevoflurane
Advantages:
Sevoflurane has low pungency, allowing rapid uptakewithout irritating the airway during induction, thus making it
able for induction in children.
The drug has low solubility in blood, and is rapidly takenand excreted.
Recovery is faster than with other anesthetics.
Disadvantages:
It is metabolized by the liver, releasing fluoride ions; thus,
like enflurane, may prove to be nephrotoxic.
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Nitrous oxide
Nitrous oxideis a potent analgesic but a weak general anesthetic.
Nitrous oxide is poorly soluble in blood and other tissues, allowing
it move very rapidly in and out of the body.
nitrous oxide isused at concentrations of 30% in combination with oxygen
for analgesia, particularly in dental surgery.
nitrous oxide at 80% (without adjunct agents) cannot produce
surgical anesthesia. It is combined with other, more potent agents to attain pain-free
anesthesia.
Advantages:
it has moderate to no effect on the cardiovascular systemDisadvantages:
diffusion hypoxia.
This anesthetic doesnot produce muscle relaxation
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V. INTRAVENOUS ANESTHETICS
Barbiturates
Thiopental: is a potent but a weak analgesic. It is an ultra-short acting barbiturate and has a high lipid solubility.
1. Rapid and pleasant induction, Rapid recovery.
Benzodiazepines (Medazolam)
Opioids:
the combination ofmorphine and nitrous oxide provides good anesthesia for
cardiac surgery.
The most frequently employed opioids arefentanyl and, sufentanil,because
they induce analgesia more rapidly than does morphine.
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Etomidate:
Advantages: little to no effect on the heart and circulation.
It is only used for coronary artery disease or cardiovascularDisadvantages:
a decrease in plasma cortisol and aldosterone levels.
produce more involuntary movements during induction.
to cause postoperative nausea and vomiting
Ketamine: (Dissociative anesthesia)
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Ketamine: (Dissociative anesthesia)
a short-acting, nonbarbiturate anesthetic.
Dissociated state in which the patient is unconscious but appears to be
awake and does not feel pain.
The drug is lipophilic and enters the brain very quickly, itredistributes to other organs and tissues.
It is metabolized in the liver, but small excreted unchanged.
Mechanism of action:interact with -N-methyl-D-aspartate receptor
Advantages:
1. provides sedation, amnesia, and immobility.
2. Profound analgesia
3. Cardiovascular stimulation through central sympathetic stimulation(increase blood pressure, heart rate and cardiac output).
4. No respiratory depression.
5. No laryngospasm.
Contraindicated in hypertensive or stroke patients.
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Disadvantages:
1. it increases cerebral blood flow2. induces postoperative hallucinations ("nightmares"),
particularly in adult
3. Unpleasant dreams.
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Propofol
Propofol is an intravenous sedative/hypnotic used in the induction or
maintenance of anesthesia.
Onset is smooth, occurs within about 40 seconds of administration.
Supplementation with narcotics for analgesia is required.
Disadvantages:
1. propofolfaclitates depression in the CNS, it is occasionally accompaniedby excitatory phenomena, such as muscle twitching, spontaneous
movement, or hiccups.
2. Propofoldecreases blood pressure without depressing the myocardium.
Advantages:
1. It is the first choice for anesthesia induction and sedation.
2. it produces euphoric feeling in the patient
3. does not cause postanesthetic nausea and vomiting.
4. It reduces intracranial pressure.5. T his makes propofolvery useful for such surgeries as resection of
spinal tumors.
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Neuroleptanesthesia: (Inovar)
It is a state of sedation, reduced motor activity, analgesia and
amnesia but without loss of consciousness.
the combined use of neuroleptic droperidol with a powerful
opioid fentanyl and nitrous oxide with oxygen.
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