Inhalational Agents: MoA, Effects on Ventilation and Circulation Flashcards
what defines anesthesia?
- muscle relaxation
- unconsciousness
- analgesia
- suppression of autonomic reflexes
what is absolutely essential according to Eger to define anesthesia?
- immobility
- amnesia
mechanism of action of immobility- site of action is
spinal cord (not sure exactly where in the cord); one suggestion is the motor neuron
theory of immobility
effect on receptors
1. depression of excitatory- NMDA, AMPA
2. enhancement of inhibitory- glycine receptors
3. Na ion channels- hyper polarization, inhibit release of glutamate
mechanism of action- immobility theory- the site is likely
lipid portion of the membrane
Meyer-Overton hypothesis states that
there is a direct correlation between the anesthetic potency and the lipophilicity (oil:gas partition coefficient)
Meyer-Overton states that there is an ___ relationship between MAC and oil:gas partition coefficient
indirect
the membrane expansion theory on the MoA of immobility
agent moves into the lipid portion of the lipid bilayer causing a disruption of synaptic transmission or receptor function
in the membrane expansion theory, studies shows that anesthetized animals could
be awakened by hyperpressurixing them to 100atm which “restored the cell membranes to the preanesthesia density”
the problem with the membrane expansion theory was that
some transitional agents take much higher concentration than M-O would suggest to cause immobility
with the membrane expansion theory, nonimmobliizers ____ although M-O would suggest otherwise
never cause immobility
__ have greater potency with the membrane expansion theory than M-O would suggest
alcohols
transitional agents, non immobilizers, and alcohols have a ___ or ___ component
water-soluble or hydrophilicity
the modified theory for mechanism of action of immobility
anesthetic agents must be lipophilic and hydrophilic to work on both lipid and water portion of the lipid bilayer membrane
per the modified theory, inhalation agents change the amount or order of ___ which changes ___
the motion of the lipid constituents
the surface tension and the cellular and membrane function
5-angstrom theory says the site of action may actually be
two sites of action at either end of the molecule
5-angstrom theory says maximum potency is achieved
with a molecule 5 carbons long with 2 active sites at each end
5-angstrom theory says that CF2 has
no anesthetic effect itself
5-angstrom theory says increased potency up to
5 carbons, then started decreasing
amnesia is not possible at
the spinal cord
possible site of amnesia MoA
reticular activating system
reticular activating system is a site of amnesia MoA because
enhance inhibitory synaptic transmission especially involving GABA, the major inhibitory NT in the brain
other possible sites for MoA of amnesia
hippocampus, amygdala, caudate putamen, and parts of the cerebral cortex
during amnesia, __ is enhanced
glycine the inhibitory NT in the cord and brainstem
amnesia may be due to
inhibition of release of excitatory NT, specifically glutamate; maybe be due to action on presynaptic Na channels or calcium ion channels
inhaled agents bind to
specific sites on the membrane of proteins as opposed to disrupting lipid bilayers
sites where inhaled agents bind may be
GABAa and glycine receptors
stage 1
analgesia
stage 1 ends with
loss of eyelash reflex and unconsciousness
stage 2
excitement
stage 2 signs
- irregular breathing
- struggling
- dilating pupils
in stage 2, patients are susceptible to
vomiting, coughing, laryngospasm
stage 2 ends with
onset of automatic breathing and the loss of eyelid reflex
stage 3
surgical anesthesia
stage 3 plane 1 is until
eyes central with loss of conjunctival reflex, pupils normal are small, lacrimation increased, pharyngeal reflex abolished
stage 3 plane 2 is until
onset of intercostal paralysis, deep regular breathing, laryngeal reflexes abolished, loss of corneal reflex, pupils larger
stage 3 plane 3 is until
complete intercostal paralysis, shallow breathing, lacrimation depressed
stage3 plane 4 is until
diaphragmatic paralysis, carinal reflexes abolished
stage 4
overdose
stage 4 signs
apnea and dilated pupils
signs of light anesthesia
- lacrimation, tearing
- tachycardia
- hypertension
- sweating
- reactive, dilated pupils
- movement and laryngospasm (no NMB utilized)
inhaled agents cause ___ respiratory depression
dose-related
inhaled agents depress the ventilatory response to an increase in
carbon dioxide, dose dependent
inhaled agents depress the ventilatory response to a decrease in
oxygenation (oxyhemoglobin saturation), not dose-dependent
ventilation in light anesthesia
breath holding and irregular pattern or breathing and irregular depths of breaths
as anesthesia deepens, breathing changes to
regular, faster rate, smaller tidal volumes
in an even deeper plane, _____ muscle function fails
intercostal
minute ventilation may not change but ___ decrease with increased ___
alveolar ventilation
dead space ventilation
respiratory rate may be increased and tidal volume decreased
___ increased during spontaneous ventilation in proportion with the increase in the concentration of inhaled agent
PaCO2
___ does not increase the CO2
nitrous oxide
in an unanesthetied patient, the increased PaCO2 would stimulate
increased minute ventilation
in patients under inhaled anesthesia, increase PaCO2 response is
decreased; shifted to the right- it takes a higher CO2 to produce the increase in MV
studies have shown that the stimulation of surgery increases ___ and decreases ___
minute ventilation by 40%
PaCO2 only by about 10%
increased production of CO2 offsets
increased MV
inhaled anesthetics cause depression of the response to
hypoxemia when PaO2 falls below 55 torr
the response to hypoxemia is blunted by
as little as 0.1 MAC of halothane, isoflurane, and sevoflurane (aka when they are waking up they won’t respond to hypoxemia)
___ MAC causes 100% depression of hypoxic response
1.1
all agents cause broncho___
dilation
bronchodilating effect in order from most to least
sevo > iso > des
without preexisting bronchoconstriction, airway resistance is
essentially unchanged
may see 5% increase in bronchial resistance due to
low bronchomotor tone normally
desflurane causes increased bronchial resistance in
smokers
irritability of airways with des is blunted by
prior admin of fentanyl 1 mcg/kg or morphine 0.1 mg/kg or addition of nitrous
des and servo have been given to patient with asthma without
causing bronchoconstriction
airway diameter is reduced due to
reduced lung volumes and reduced elastic forces keeping small non-cartilaginous airways open
pungent desflurane is a bronchial irritant above
6% but does not cause irritation below 6%
airway irritation increases with
concentrations greater than MAC of isoflurane
airway irritation has a higher incidence in
smokers
minimize airway irritation by
- premeditate with an opioid (fentanyl 1.5 mcg/kg)
- slower increase in desflurane concentration
- induction with propofol (v. inhalation induction)
- humidification of inspired gases (HME)
hypoxic pulmonary vasoconstriction (HPV) causes ___ but has little effect on ___
vasodilation typically
pulmonary vasculature
HPV is not prevented by
concentrations that are used clinically of inhaled anesthetics
___ decrease in MAP
dose-dependent
at 2 MAC the BP decreases by
50% without surgical stimulation
___ minimizes the decrease in MAP
surgical stimulation
lower MAP due to changes in
cardiac output, venous capacitance, and systemic vascular resistance
halothane decreases
myocardial contractility and cardiac output
isoflurane, desflurane, and sevoflurane decrease
SVR which causes decreases in BP
all agents cause myocardial depression to some degree in a ___ manner
dose-dependent
halothane causes dose-dependent decrease in
CO
decreased LV stroke volume may not translate into decreased CO due to
the vasodilation and decreased SVR caused by des, iso, sevo
the decreased myocardial contractility results in a dose-dependent reduction in
oxygen demand (agent variable)
excessive concentrations of agents can cause ___ collapse
cardiovascular
___ increased CO reflecting mild sympathomimetic effects
nitrous oxide
___ cause increased RAP
all agents but sevo
decreased forward pump causes
higher pressures in the venous side or right atrium
nitrous oxide increase RAP due to
increased pulmonary vascular resistance
inhaled agents decreased the vascular resistance to __, ___, ___
skin
muscle
brain
inhaled agents increase the vascular resistance to the
splanchnic system
inhaled agents are veno___
dilators
inhaled agents attenuate vasoconstriction related to ___ and is more exaggerated in ____
sympathetic stimulation
hypotension seen with hypertensive patients than normotensive patients
increased peripheral blood flow effects
- temperature decrease and heat loss due to vasodilation
- better delivery of NMB and NMJ
- wasted perfusion compared to needs
isoflurane has __ effect
beta agonist
nitrous oxide does not decrease __ and may actually cause ___
SVR
vasoconstriction of cutaneous vessels
pulmonary vascular resistance has little effect of volatile agents on
pulmonary vasculature
___ causes increased pulmonary vascular resistance
nitrous oxide
at risk populations for increased pulmonary vascular resistance from nitrous oxide
- neonates
- congenital heart defects/shunts
sevo increases HR only at concentrations
great than 1.5 MAC
iso and des increase HR at
lower concentration
halothane effect on heart rate
does not increase
increases in HR are more frequently seen with
younger patients
increased in HR are accentuated by
vagolytic agents like atropine and pancuronium
___ activity, ___ firing, ___ conduction are all affected by inhalation agents
ANS
SA node
myocardial
___ depression of the baroreceptor-reflex response
dose-dependent
__ attenuates baroreceptor-reflex response at low concentrations
des
___ abolishes baroreceptor-reflex response at 1.25 MAC versus some response at 1.5 MAC
iso
___ increasing to 4% decreases baroreceptor-reflex response
sevo
when BP decrease, there is no
baroreceptor-reflex response of an increase in HR which impacts us clinically related to volume loss or position changes during anesthesia
coronary vasodilators acting on small coronary arteries can cause
shift of blood from ischemic areas to non-ischemic areas; “Coronary Steal Syndrome”
Coronary Steel Syndrome is only going to happen if
MAP < 60
preconditioning for cardioprotection
brief exposure of the myocardium to volatile agents before myocardial ischemia
brief exposure of the myocardium to volatile agents before myocardial ischemia results in
faster recovery after reperfusion of ischemic myocardium and reduction in infarct size
____ as low as 0.25 MAC may be effective as cardioprotectant
isoflurane
__ have been shown to be protective in CPB patients
sevo
reperfusion injury
cellular injury caused by the reinstitution of the blood flow, not due to the ischemia itself
signs of reversible reperfusion injury
- cardiac dysrhythmias
- contractile dysfunction
- microvasucalr injury
the cardioprotection probably results from
an action on ATP-dependent potassium channels
if given during reperfusion, __ may slightly increase myocardial ATP
sevo
