General inhalational and intravenous anesthesia

1
General (inhalational and intravenous) anesthesia

• Béla Fülesdi

2
Phases of anesthesia

• Premedication
• Anesthesia induction
• Anesthesia maintainance
• Recovery phase
• Postoperative observation

3
Goals of premedication

• Decreasing preoperative anxiety
• Decreasing secretion
• Potentiating of the hypnotic effect of narcotics
  and analgetics
• Decreasing PONV
• Amnesia
• Minimizing gastric content
• and increasing its pH
• Decreasing vagal reflexes
• Decreasing sympatho-adrenal reflexes

4
The most important components of general
anesthesiaanalgesiahypnosisamnesiaanxiolysis
vegetative stability(muscle relaxation)
5
Thus, the main groups of drugs used in anesthesia
are

• Sedato-hypnotics
• Inhalational, intravenous or both
• Goals
• Decreasing anxiety
• Providing sedation
• Amnesia
• Opioid analgetics pain killing
• Muscle relaxants, if necessary

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Classification

• Inhalational
• Total intravenous
• Combined
• Intravenous induction
• Inhalational maintainance

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Inhalation anesthesia
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Physical properties

• Gas at room temperature nitrogen oxidul, xenon
• Fluid at room temperature aether, halothan,
  enflurane, isoflurane, methoxyflurane,
  sevoflurane, desflurane vaporizer is needed

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Vaporizers
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Site of action

• GABA-associated chloride channel stimulation
• Voltage-dependent Ca-channels (T, L and N type)
  isoflurane
• NMDA receptor nitrogen oxidul, xenon
• Muskarinic effect inCNS (memory and
  consciousness) desflurane (M1), isoflurane (M1
  and M3),sevoflurane (M1), halothane (M1 and M3)
• Nicotinergic all
• Voltage-dependent Na-channel inhibition
  halothane, enflurane, isoflurane, desflurane,
  sevoflurane

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Inhalation anesthesia
Inhaled gas mixture
Alveolo-capillary diffusion
Blood solubility circulation minute volume
Tissues
12
Distribution of inhalational anesthetics
Inspiratory concentration
Alveolar concentration
Vessel rich group (heart, brain)
Muscle
Fat
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Determinants of inhalation anesthesia

• Partial pressure of the inhaled anesthetics
  within the alveoli
• Alveolo-capillary gradient (Oswald-ratio).
• Blood solubility
• Tissue perfusion.

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Minimal alveolar concentration (MAC)

• Reflects how strong the inhalational agent is
• MAC the alveolar concentration on which surgical
  incision can be performed in 50of the patients.
• Modified MACs
• MAC EI50 MACEI95 in 50, or 95 of the patients
  laryngoscopy and intubation possible
• MAC BAR50 and MAC BAR95 adrenergic reactions to
  incision are blocked in 50, or 95 of the
  patients

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Factors infleuncing MAC

• Decreases combination with oher inhalationals,
  hypothermia, hypothyreosis, gravidity, hypoxia,
  hypotonia, anemia, sedatohypnotics,
  tranquillants, neuroleptics, opioids
  antihistamins, antihypertensives
• Increases age (children), hyperthermia,
  hyperthyreosis, sympathomimetics

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Oswald-ratio

• Reflects blood/alveolar gas distribution ratio of
  the anesthetics.
• Below 1 wrong blood solubility
• Greater amount is necessary from the lung to
  reach the needed concentration
• But if it is in the blood soluble form, the
  diffusion to the tissues is easier
• Above 1 better solubility in blood

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Oswald-ratio and MAC of some inhalational agents
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Blood solubility

• Henry-low the amount of anesthetic in solube
  form is proportional to its partial pressure in
  the blood.
• Thus solubility can be increased by incresing
  partial pressure.
• The speed of narcotic effect is dependent on
  blood solubility
• Low solubility fast
• High solubility slow

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Distribution of the circulation minute volume

• 75 vessel rich group (brain and heart)
• 8-10 fat
• 15 muscle group
• rest vessel poor group
• Blood-tissue coefficient is different in the
  groups.
• Fat takes relative large amount of anesthetics ?
  will be important in the recovery period.

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Uptake of inhaled anesthetics within the
different compartments

Vessel rich group
Muscle
Fat
Vessel poor group
time
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Thus, what are our possibilities for influencing
inhalation anesthesia?

• Alveolar concentration
• Ventilation
• Circulation minute volume
• Duration of anesthesia

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Effect on alveolar concentration on anesthetic
depth

• Alveolar concentration is proportional to partial
  pressure of the gas within the brain
• Low blood soluble anesthetics anesthesia ma not
  be make deeper by increasing alveolar
  concentration.
• High blood soluble anesthetics narcotic depth
  may be increased by increasing alveolar
  concentration.

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Effect of ventilation an anesthetic depth

• Low blood solubility altering ventilation has no
  effect
• High blood solubility Anesthetic depth may be
  increased by increasing ventilation.

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Altering circulation minute volume

• Low blood solubility altering CMV does not
  change depth of anesthesia.
• High blood solubility depth of anesthesia may
  be increased by increasing CMV

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Effect of anesthesia duration on recovery time

• Low blood solubility no effect
• Glood blood solubility recovery time increases
  along with szer esetén az anesztézia hosszával
  arányosan az ébredési fázis megnyúlik.

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Practical conduct of inhalation anesthesia

• Fast intravenous induction (barbiturate, BDZ,
  propofol)
• Muscle relaxation.
• Inhalational agent for maintainance.
• For analgsia nitrogen oxidul and/or opioid.
• Usually not used for inhalational induction
  (except for Sevorane in child anesthesia)

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Anesthesia systems

• Open
• Semi-open
• Semi-closed
• Closed systems

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Open system

• Inhalational anesthetics enters the patient as a
  transported gas by the room air
• There is a continouos connection between patients
  airway system and room air
• Exhalation occurs into room air
• Balloon is not necessary
• For instance Schimmelbusch masc

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Semi-open system

• Narcotics is carried to the patient by fresh gas.
• Fresh gas and expired gas are divided , no
  rebreathing is possible
• Needs a valve to make rebreathing impossible

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Semi-closed systems

• A certain amount of exhaled gases will be
  rebreathed, another amount will be removed
• Advantage
• Less heat and humidity leaves the system
• Less fresh gas is necessary

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Closed system

• Exhaled gas mixture is given back in its total
  amount to the system, after CO2-absorption.
• Needed fresh gas flow only for the patients
  metabolism O2 (4 ml/tskg).

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Intravenous anesthetic agents
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Classification of intravenous anesthetics

• Rapidly acting (primarly induction) agents
• Barbiturates methohexital and thiobarbiturates
• Imidazol compounds ethomidate
• Sterically hindered alkyl phenols propofol
• Slower acting (basal narcotic) agents
• Ketamine
• Benzodiazepines diazepam, flunitrazepam,
  midazolam
• Large-dose opioids fentanyl, alfentanil
  sufentanil, remifentanil
• Neurolept combination opioid neuroleptic

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Advantages for intravenous maintainance of
anesthesia (IVA)

• Minimal cardiovascular depression
• Rapid recovery profile (with propofol only)
• High oxigen concentration in some circumstances,
  such as
• One-lung anesthesia
• Severe trauma
• Some procedures (laryngoscopy, bronchoscopy,
  electroshock)
• Situations where avoidance of N2O is necessary

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Techniques of administration

• Intermittent injection large dose fluctuations
• Manual infusion techniques
• Target-controlled infusion techniques (TCI)
  computer-based system.
• Prevoius programming of the computer by
  appropriate pharmacokinetic data
• Closed-loop system TCI measurement of depth of
  anesthesia

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Muscle relaxants
37
Motor nerve membrane
Inhibited by Central muscle relxants Local
anesthetics
Voltage-sensitive Ca-channel opens
Ca-influx
Ca-calmodulin complex
Cholinestherase metabolizes
Ach release
Negative feedback on production
Postsynaptic Ach receptor on ion channel
(2alpha, beta, gamma and delta subunits) (fetalis
and denervated different)
Depolarizing effect (agonistic)
Ach binding site on alpha subunit (Na- and Ca-
in, K- outflow)
Ach binding only to one alpha-subunit Non-depolar
izing agent
Ach binding to both alpha subunits
ENDPLATE-DEPOLARISATION
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ENDPLATE DEPOLARISATION
Forwarded action potential
Ca-outflow from horisontal tubuli of sarcolemma
Dantrolene blocks
Coffein, malignant hyperpyrexia stimulates
Ca-outflow from longitudinal tubuli
CONTRACTION
Action potential finishes
Anti-cholinestherase blocks
Ach release from binding site, cholinestherase
metabolizes
Depolarizing relaxant
Endplate-repolarisation (Na/K pump balance)
Ca gets back to longitudinal tubuli
Decrease in Ca-concentration CONTRACTION
DISAPPEARS
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Depolarizing block (phase- 1 block)

• Agonistic effect on Ach receptors depolarisation
  occurs
• Double-phase effect
• depolarisation fasciculations (cranio-caudal)
• Relaxants remains at the site, therefore no
  secondary stimulation is possible phase of
  relaxation

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Non-depolarizing block

• Competitive antagonistic effect against Ach at
  the postsynaptic nicotinergic receptors, by
  blocking one of the alpha-subunits

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Dual block

• If a depolarizing agent is given second times or
  through infusion pump.
• No depolarizing effect (fasciculation),
  continouos relaxation

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Duration of action

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Depolarizing relaxants

• Succinyl choline
• Decamethonium

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Non depolarizing relaxants

• Bikvaterner benzil izokinolons
• Atracurium (Tracrium)
• Cisatracurium (Nimbex)
• Mivacurium (Mivacron)
• Rocuronium (Esmeron)
• Aminosteroids
• Pancuronium (Pavulon)
• Vecuronium (Norcuron)
• Pipecuronium (Arduan)

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Classification according to duration of action

• Ultrashort succinyl choline
• Short Mivacurium
• Medium Atracurium, Vecuronium, Rocuronium
• Long D-tubocurarin, Pancuronium, Metocurin,
  Pipecuronium, Doxacurium

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Indications

• Endotracheal intubation succinyl choline or
  rapacuronium
• Surgical relaxation
• Mivacurium shorter than 15 min.
• Vecuronium, atracurium, Rocuronium lt30 min.
• Pancuronium, Doxacurium, Pipecurium gt 90 min.
• ICU use
• Mechanical ventilation
• Decreasing shivering
• Epileptic status

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Opioids
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Classification

• Natural opioids
• Morphin
• Codein
• Papaverine
• Tebain
• Semisynthetic
• Heroin
• Dihydromorphon/morphinon
• Thebain derivates (etorphin, buprenorphin)
• Synthetic
• Morphinan group levorphanol, butorphanol
• Diphenylpropilamin group methadon
• Benzomorphan group pl. pentazocin
• Phenylpiperidine group meperidin, sufentanyl,
  fentanyl, alfentanyl, remifentanyl

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Classification according to effect

• Agonist able to produce all the characteristic
  effects on a given concentration
• Partial agonist does not cover the whole
  characteristic spectrum
• Mixed agonist-antagonist agonist on one
  receptor, antagonist on the other
• Antagonist no agonist effect

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Opiate receptors

• µmorphin
• ? deferens (vas deferens)
• ? ketociklazocin

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Effects of opioid receptor activation
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Depth of anesthesia
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The most important compnenents of general
anesthesiaanalgesiahypnosisamnesiaanxiolysis
vegetative stability
54
Is it important to monitor depth of anesthesia?

• Intraoperative awarness, with recall 0,2-3
• In high risk patients 40
• Increased risk
• Polytrauma
• Cesarean section
• Cardiac surgery
• Hemodynamic unstability
• Consequences
• Anxiety, panic disorder,
• sleeping disturbance
• Vegetative distrubances,
• Hypertension

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How to monitor depth of anesthesia?

• Traditional (subjective) based on clinical signs
• Breathing
• Pulse rate and blood pressure
• Vegetative signs
• Reflexes (ciliary reflex)
• Level of consciousness
• Instrumental (objective)
• Superficial EMG
• Heartrate-variability
• EEG and derived indices (BIS, entropy)
• Evoked potentials AEP, VEP, SEP, AEI

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Correlation between electrical activity and brain
metabolism
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Stimlus (click)
Brainstem
Early cortical
Late cortical
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AAI and depth of anesthesia
100
Conscious
80
60
50
Superficial anesthesia
30
20
Surgical anesthesia
15
Deep hypnosis
0
100 burst supression