inhalational agents: MOA; effects on ventilation and circulation Flashcards
(64 cards)
1
Q
what defines anesthesia?
A
- muscle relaxation
- unconsciousness
- analgesia
- suppression of autonomic reflexes
2
Q
according to Eger, what is absolutely essential for anesthesia?
A
- immobility (r/t spinal cord)
- amnesia (r/t higher CNS, brain)
- analgesia cant be assessed under anesthesia
- unconsciousness and muscle relaxation not important as long as pt. is still and has amnesia
3
Q
what is the MOA for immobility caused by inhalation agents?
A
- site of action: spinal cord
- not sure exactly where in spinal cord
- one suggestion is the motor neuron
4
Q
describe the theory of effect on receptors as MOA for immobility
A
- indirect effect
- depression of excitatory receptors N-methyl-D-asparate (NMDA) and AMPA; both mediate fast excitatory transmission at most synapses in the CNS
- responds to changes in extracellular ligands like glutamate, the main excitatory neurotransmitter CNS
- Na ion channels- hyperpolarized; inhibit presynaptic release of NTs, esp. glutamate (how lidocaine decreases MAC)
5
Q
which receptors do not affect MAC
A
- GABA
- ACh
- 5-HT
6
Q
describe the Meyer Overton hypothesis for immobility MOA of inhalation agents
A
states that there is a direct correlation b/w the anesthetic potency and the lipophilicity (oil:gas partition coefficient)
- suggests the site of action is likely lipid portion of the membrane, on the neuronal lipid bilayers
- and indirect relationship b/w MAC and oil:gas partition coefficient (greater the coefficient, more lipophilic and higher the potency or lower MAC)
7
Q
describe the membrane expansion theory of MOA for immobility r/t inhalation agents
A
- agent moves into the lipid portion of the lipid bilayer causing a disruption of synaptic transmission or receptor function
- 1950s study showed that anesthetized animals could be awakened by hyper pressurizing them to 100 atm. which “restored the cell membranes to the pre-anesthetic density”
8
Q
what were the facts contradicting Meyer Overton (M-O) theory?
A
- some transitional agents take much higher concentrations than M-O would suggest to cause immobility
- other non-immobilizers, never cause immobility although M-O would suggest that it could (lipophilic but don’t cause immobility)
- alcohols have a greater potency than M-O would suggest (hydrophilic but good immobilizers)
- all three of these have water solubility or hydrophilicity component
9
Q
what is the 3rd theory for MOA of inhalation agents to cause immobility?
A
- anesthetic agents must be lipophilic and hydrophilic to work on both lipid and water portion of the lipid bilayer membrane
- in doing so, agents change the amount or order of the motion of the lipid constituents; this changes the surface tension and the cellular and membrane function
10
Q
describe the 5-angstrom theory of immobility from inhalation agents
A
- site of action may actually be two sites of action (5 angstrom apart)
- maximum potency is achieved w/ a molecule of 5 carbons long w/ two active sites at each end (less than or over 5, not as potent)
11
Q
describe the MOA of inhalational agents to cause amnesia
A
- site not at the spinal cord
- possible site: reticular activating system- enhance inhibitory synaptic transmission, esp. involving GABA, the major inhibitory NT in the brain
- Glycine: inhibitory NT in the cord and brainstem, is enhanced
- other possible sites: hippocampus, amygdala, caudate putamen, parts of the cerebral cortex
- may be d/t inhibition of release of excitatory NTs: may be d/t action on presynaptic Na channels or calcium ion channels
- occurs at a site deeper than the membrane than site causing immobility
12
Q
what is the theory for the MOA causing narcosis?
A
- inhaled agents bind to specific sites on the membranes of proteins as opposed to disrupting lipid bilayers
- sites may be GABA-a and glycine receptors
13
Q
describe Geudel’s Stage 1
A
- analgesia
- ends w/ loss of eyelash reflex and unconsciousness
14
Q
describe Geudel’s Stage 2
A
- excitement
- irregular breathing, struggling
- dilated pupils
- susceptible to vomiting, coughing, laryngospasm
- ends w/ onset of automatic breathing and loss of eyelid reflex
15
Q
describe Geudel’s Stage 3, plane I
A
- until eyes central w/ loss of conjunctival reflex
- pupils normal or small
- lacrimation increased (can tell if pt. getting light)
- pharyngeal reflex abolished
16
Q
describe Geudel’s Stage 3, plane II
A
- until onset of intercostal paralysis
- deep regular breathing
- laryngeal reflexes abolished
- loss of corneal reflex
- pupils larger
- when diaphragm pulls down, may see chest sink in
17
Q
describe Geudel’s Stage 3, plane III
A
- until complete intercostal paralysis
- shallow breathing
- lacrimation depressed
18
Q
describe Geudel’s Stage 3, plane IV
A
- until diaphragmatic paralysis
- carinal reflexes abolished
19
Q
describe Geudel’s Stage 4
A
- overdose
- apnea
- dilated pupils
20
Q
what are signs of light anesthesia?
A
- lacrimation, tearing
- tachycardia
- HTN
- sweating
- reactive, dilated pupils (can be d/t anticholinergics, opioids, etc.)
- movement and laryngospasm (if no NMB utilized)
- SNS stimulation seen since MAC BAR much higher than MAC
21
Q
what are the effects of inhalation agents on ventilation in regards to depression?
A
dose related respiratory depression
22
Q
what are the effects of response to CO2 and O2?
A
- dose dependent depressed response to increase in CO2
- non dose dependent depressed response to decrease in O2 (oxyhemoglobin saturation)
23
Q
describe breathing w/ light anesthesia compared to deeper planes
A
- light: breath holding, irregular pattern of breathing; irregular depths of breaths
- as anesthesia deepens, breathing changes to regular, faster rate w/ smaller tidal volumes (Vm changes little, but alveolar ventilation decreases w/ smaller Vt causing more dead space ventilation)
- even deep plane, intercostal muscle function fails (may need help w/ positive pressure)
24
Q
how is ventilation affected by inhalation agents?
A
- minute ventilation may not change
- alveolar ventilation decreases w/ increased dead space ventilation
- resp. rate may be increased, tidal volume decreased
- PaCO2 increases during spontaneous ventilation in proportion w/ the increase in the concentration of inhaled agent (response curve shifts right)
25
how does nitrous oxide affect the respiratory depression caused by potent volatile agents?
- does not increase the CO2
- if used, and concentration of volatile agent is decreased, there is less ventilatory depression compared to equivalent MAC of volatile alone
26
how do volatile agents shift the CO2 response curve?
- response curve shifted right
* takes a higher CO2 to produce the increase in Vm
* opioids also shift curve right (additive effect), so don't give opioids on induction
- response improves overtime, but not to normal (5 hrs better than at 1 hr)
27
at 1 MAC of either halothane, isoflurane, or desflurane, how much CO2 is required to stimulate breathing?
- halothane: 42 mmHg CO2
- isoflurane: 45 mmHg CO2
- desflurane: 50 mmHg CO2
28
at what levels do desflurane and sevoflurane lead to apnea?
b/w 1.5 and 2 MAC
29
how can surgical stimulation affect CO2 response shift?
- stimulation of surgery increase Vm by 40% and can decrease PaCO2 by 10%
- increased production of CO2 offsets Vm
- so w/ LMA, if deep for incision, may get apneic, but will start to breathe again on incision d/t stimulation
30
what effect do inhalation agents have on hypoxic drive?
- depress the response to hypoxemia, when PaO2 falls below 55 torr
- response is blunted (50-70% depression) by as little as 0.1 MAC of halothane, isoflurane, and sevoflurane (not dose dependent)
- 0.1 MAC of desflurane decreased the response by 30% w/ hypercapnia (w/ normocarbia, des doesn't affect hypoxic drive much if at all)
* 1.1 MAC causes 100% depression of hypoxic response
31
what is doxepram good for?
- respiratory stimulation
- makes carotid bodies think PaO2 is as low as 38 mmHg
- good for COPD pts., esp. if need to put deep but still want to breathe
32
what are the effects of volatile agents on bronchi?
- all agents cause bronchodilation if constricted (good for asthmatics)
- greatest to least: sevoflurane-isoflurane-desflurane
* w/o preexisting bronchoconstriction, airway resistance is essentially unchanged (may see 5% increase in resistance d/t low bronchomotor tone)
* desflurane causes increased resistance in smokers
33
what blunts the irritability of airways caused by desflurane?
- prior administration of fentanyl 1 mcg/kg or morphine 0.1 mg/kg
- addition of nitrous also blunts irritability
* both desflurane and sevoflurane have been given to asthma pts. w/o causing vasoconstriction
34
how much desflurane is ok to use, not causing bronchoconstriction?
- up to 1 MAC, should be bronchodilation
- over 1 MAC causes bronchoconstriction
* can use desflurane w/ RAD, but if any slight signs of constriction (increases PiPs) just be safe and switch agents
35
why is airway diameter reduced w/ volatile agents?
- reduced lung volumes
- reduced elastic forces keeping small, non-cartilaginous airways open
* smaller airways (children) will see significant retractions so give positive pressure to help keep airways open
36
describe airway irritation caused by some agents
- pungent desflurane is an bronchial irritant above 6% (1 MAC), but does not cause irritation below 6%
- increases w/ concentrations greater than MAC of isoflurane also
- higher incidence in smokers
* increases in mucociliary activity may reflect the effect of the airway irritant (desflurane-isoflurane/halothane)
* only sevoflurane good for inhalation inductions
37
what are ways to minimize airway irritation?
- premedicate w/ an opioid (fentanyl 1.5 mcg/kg)
- slower increase in desflurane concentration
- induction w/ propofol (v. inhalation induction)
- humidification of inspired gases
38
what is the effect of inhalation agents on hypoxic pulmonary vasoconstriction (HPV)?
- all can alter HPV, but at clinical doses of inhaled anesthetics, do not prevent HPV
- typically causes vasodilation, but little effect on pulmonary vasculature
39
describe the effects of inhalation agents on mean arterial pressure
- dose-dependent decrease in MAP w/ all agents
- at 2 MAC, BP decreases by 50% w/o stimulation
* surgical stimulation minimizes decrease
* lower MAP d/t changes in cardiac output, venous capacitance, and SVR
* more drastic in elderly
- different agents alter BP by different mechanisms
* substituting a portion of the MAC w/ N2O decreases extent of drop on MAP
40
by what mechanism does each agent decrease MAP?
- halothane: decrease in inotropic effect (CO and SV)
- all others decrease by drop in SVR
* iso and des to a greater extent than sevo
41
how do inhalation agents affect cardiac output?
- all cause myocardial depression to some degree in a dose-dependent manner
- LV stroke volume decreased 15-30%
- decreased LV stroke volume may not translate into decreased CO d/t vasodilation and decreased SVR caused by des, iso, and sevo
* *halothane cause dose dependent decrease in CO in healthy volunteers (greatest effect of depression)
42
what does decreased myocardial contractility result in?
dose-dependent reduction in O2 demand
* protectant
* however, excessive concentrations can cause CV collapse
43
what is unique about N2O effect on CO?
- directly a myocardial depressant
| - d/t mild sympathomimetic effects w/ increased catecholamine, usu. see an increase in CO
44
describe inhalation agents effect on right atrial pressure
- all agents BUT SEVO cause increased RAP (decreased function of LV cause fluid back up)
- decreased forward pump causes higher pressure in the venous side or right atrium
* N2O increases RAP d/t increased pulmonary vascular resistance (PVR)(avoid w/ pulm. HTN, congenital hearts, r to l shunts)
45
describe inhalation agents effect on systemic vascular resistance
- inhaled agents decrease the resistance to the skin, muscle, and the brain; but increase resistance to the splanchnic system
- venodilators (decrease in venous return)
- attenuate vasoconstriction r/t sympathetic stimulation
* more exaggerated hypotension seen w/ HTN pts. when normotensive pt. (even if well controlled)
* *can use to your advantage to dilate peripheral veins for IV
46
w/ decreased SVR causing increase peripheral blood flow to skin, muscle, and brain, what are the results?
increased perfusion to these areas, resulting in :
- skin: temp decreases and heat loss; high risk for hypothermia and shivering
- muscle: delivery of NMB improved
- brain: increased CBF; increased ICP
- wasted perfusion compared to needs
47
which agent has the better beta 2 agonist effect (vasodilation)?
isoflurane
48
what is N2O effect on SVR?
- does not decrease SVR
- may actually cause vasoconstriction of cutaneous vessels
* may offset drop in SVR
49
how do agents compare in order from greatest change to least change in SVR?
isoflurane-desflurane-sevoflurane
50
how do agents affect pulmonary vascular resistance (PVR)?
- little effect of volatile agents on PVR
- N2O causes increased pulmonary vascular resistance
* neonates are vulnerable (closure not complete; increased PVR can open back up)
* congenital heart defects/ shunts may be increased
51
how do agents affect heart rate?
- agent specific effect and concentration specific effect
* sevo increases HR only at concentrations more than 1.5 MAC
* iso and des increased HR at lower concentration
* des worst offender (control by increasing slowly)
* halothane does not increase HR d/t conduction effects (bradycardia)
* response not impeded by meds (beta blockers)
- effects ANS activity, SA node firing, and myocardial conduction
52
who are increases in HR more frequently seen w/?
- younger patients
| - accentuated by vagolytic agents like atropine and pancuronium
53
how do agents affect the baroreceptor reflex response?
- dose dependent depression of the reflex responses
- some agents eliminate baroreceptor reflex at low concentration
- des attenuates response, but does not abolish
- iso abolishes at 1.25 MAC v. 1.5
- sevo, increasing to 4% (about 2 MAC) decreases response
54
what happens when the baroreceptor reflex is abolished?
- when BP decreases, there is no reflex response of an increase in HR
* impacts us clinically r/t volume loss or position changes during anesthesia
55
describe the volatile agents effect on coronary blood flow
- coronary vasodilators acting on SMALL coronary arteries, can cause shift of blood from ischemic areas to non ischemic areas
- coronary steal syndrome w/ iso (not clinically significant)
56
describe cardioprotectant effects of inhalation agents
- preconditioning
- brief exposure of myocardium to volatile agents before myocardial ischemia results in faster recovery after reperfusion of ischemic myocardium and reduction in infarct size
- similar effect on vascular endothelium may provide protection to other tissues also
- isoflurane as low as 0.25 MAC may be effective
- sevo has ben shown to be protective for CPB pts.
57
define reperfusion injury
cellular injury caused by the reinstitution of the blood flow, not d/t the ischemia itself
58
what are signs of a reversible reperfusion injury?
- cardiac dysrhythmias
- contractile dysfunction
- microvascular injury
59
what may be the MOA of cardioprotectant?
-protection probably results from an action on ATP-dependent potassium channels
60
with 1-1.5 MAC in healthy individuals, in what order from greatest to least do agents decrease MAP?
halothane/isoflurane/desflurane-sevoflurane
61
with 1-1.5 MAC in healthy individuals, in what order from greatest to least do agents decrease SVR?
isoflurane/desflurane-sevoflurane
* none w/ halothane
* w/ HTN, SVR effect is much more dramatic
62
with 1-1.5 MAC in healthy individuals, in what order from greatest to least do agents decrease CO?
halothane-sevoflurane-(maybe a little w/ desflurane)
| *none w/ isoflurane
63
with 1-1.5 MAC in healthy individuals, in what order from greatest to least do agents increase HR?
isoflurane-desflurane (unless concentration increased slow)
* none w/ sevoflurane
* decreased HR w/ halothane
64
with 1-1.5 MAC, which agent increases sensitivity to catecholamines?
halothane
