Download Effects of inhaled anesthetics

Inhaled anesthetics
Inhaled anesthetics
• The agents currently used in clinical practice are:
– Nitrous oxide
– Easily vaporized liquid halogenated hydrocarbons,
including:
• Halothane
• Desflurane
• Enflurane
• Isoflurane
• Methoxyflurane
Pharmacokinetics
• Because the standard pressure of total inhaled
mixture is atmospheric pressure (760 mm Hg at
sea level), the partial pressure may also expressed
in percentage.
• Thus 50% nitrous oxide in the inhaled air would
have 380 mm Hg.
• They administered as gases; their partial pressure
in the inhaled air or in blood or in tissue is the
measure of their concentration.
Theories for Mechanism of Action
1. Theory #1
– Gas movement into lipid membrane disrupting ion
channels and action potential propagation
2. Theory #2
– Binding theory = anesthetics bind to hydrophobic
portion of the ion channel
3. Theory #3
– Neuromodulator theory = anesthetics bind to cellsurface receptors.
– Increased Cl- flux (possible GABA mediation)
Factors affect the speed of induction
of inhaled anesthetics
1. Solubility:
– The more the drug equilibrates with the blood,
the more quickly the drug passes in to the brain
to produce effect.
– This means the induction will be slower with
more lipid soluble gases and faster with less
soluble ones.
Factors affect the speed of induction
of inhaled anesthetics
• For a given concentration of 2 gases in inspired
air, it will take much longer time with halothane
than nitrous oxide for the blood partial pressure
to rise to the same partial pressure as in the
alveoli.
• Because the concentration in the brain can rise
no faster than the blood, the onset will be
slower with halothane than with nitrous oxide.
Factors affect the speed of induction
of inhaled anesthetics
2. Inspired gas partial pressure:
– A high partial pressure of the gas in the lungs
results in more rapid achievement of
anesthetic levels in the blood.
3. Ventilation rate:
– The greater the ventilation, the more rapid is
the rise in the alveolar and blood partial
pressure of the agent and the onset of
anesthesia
Factors affect the speed of induction
of inhaled anesthetics
4. Pulmonary blood flow:
– At high pulmonary blood flows, the gas partial
pressure rises at slower rate; thus, the speed
of onset of anesthesia is reduced. At low flow
rates, onset is faster.
– In case of circulatory shock
Elimination
• Anesthesia is terminated by redistribution of the
drug from the brain to the blood and elimination of
the drug through the lung.
• The rate of recovery from anesthesia using agent
with low blood:gas partition coefficients is faster
than that with high blood solubility
Elimination
• Desflurane and sevoflurane are characterized by
recovery times that are considerably shorter than
older agent.
• Halothane and Methoxyflurane are metabolized
by liver to significant extent
• This could play a role in potential toxicity of these
anesthetics in case of liver disease
Minimum Alveolar Concentration
(MAC)
• Defined as the concentration of anesthetic that
prevents movement induced by a painful stimulus
in 50 % of subjects.
• MAC of anesthetic measures potency of anesthetic
vapour. High MAC means low potency
• Each agent has a defined MAC but this value may
vary among patients depending on age,
cardiovascular status, and use of adjuvant drugs
Minimum Alveolar Concentration
• Estimation of MAC value suggest a relatively
“steep” dose-response relationship for inhaled
anesthetics
• MAC for infant and elderly are lower than that
for young adults
• When
several
anesthetics
are
used
simultaneously, their MAC values are additive
Effects of inhaled anesthetics
1. CNS effects:
– Reduction of metabolic rate in the brain
– Increase cerebral blood flow
– Increase in ICP (intracranial pressure)
– High concentration of Enflurane may cause
changes on EEG and muscle twitching, but
this effect is unique to this drug.
– Although nitrous oxide has low anesthetic
potency (high MAC), it exerts marked
analgesic and amnesic effect
Effects of inhaled anesthetics
2. Cardiovascular effects:
– Most of inhaled agents decrease arterial
blood pressure moderately.
– Enflurane and halothane are myocardial
depressant that decrease cardiac out put
– Isoflurane, Desflurane and sevoflurane cause
peripheral vasodilatation
– Nitrous oxide is less likely to lower blood
pressure than are other inhaled anesthetics
Effects of inhaled anesthetics
• Blood flow to the liver and kidney is decreased by
most inhaled agents.
• Inhaled anesthetics depress myocardial function –
nitrous oxide least
• Halothane and to lesser extent Isoflurane, may
sensitize the myocardium to the arrhythmogenic
effects of catecholeamines.
Effects of inhaled anesthetics
3. Respiratory effects:
– Increase the rate of respiration associated with a
decrease in tidal volume.
– The net effect results in a decrease of minute
ventilation and therefore in increase of PaCO2.
– Central response to higher CO2 levels is decreased
due to a direct depressant effect of these drugs on
the medullary ventilatory center.
•
•
•
In addition, all inhaled anesthetics depress the
ventilatory response to arterial hypoxemia.
Nitrous oxide has the smallest effect on respiration
Most of inhaled anesthetics are bronchodilators,
but Desflurane is a pulmonary irritant and may
cause bronchospasm.
Toxicity of inhaled anesthetics
• Post-operative hepatitis may occur rarely after
halothane anesthesia in patients experiencing
hypovolemic shock or other severe stress (may be
immune mediated or due to formation of reactive
metabolite).
• Fluoride released by metabolism of Methoxyflurane
(and possibly Enflurane and sevoflurane) may cause
renal insufficiency after prolong anesthesia
Toxicity of inhaled anesthetics
• Prolonged exposure to nitrous oxide decreases
methionine synthase activity and lead to
megaloblastic anemia
• Susceptible patient may develop malignant
hyperthermia when anesthetics are used
together with neuromuscular blockers (especially
succinylcholine).
Focus Points
• Induction of anesthesia is through use of any
of the IV agents (Barbiturates: Thiopental,
Opiate: Fentanyl, Benzodiazepines: Midazolam,
Dissociative: Ketamine, Others: Propofol,
Etomidate and Droperidol)
• Maintenance of anesthesia is through use of
any of the inhalation agents
– N2O (70% in oxygen) is not suitable alone
– N2O is usually combined with another
inhalation agent or with opioids e.g. fentanyl
Good luck