inhalational agents: MOA; effects on ventilation and circulation Flashcards
what defines anesthesia?
- muscle relaxation
- unconsciousness
- analgesia
- suppression of autonomic reflexes
according to Eger, what is absolutely essential for anesthesia?
- 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
what is the MOA for immobility caused by inhalation agents?
- site of action: spinal cord
- not sure exactly where in spinal cord
- one suggestion is the motor neuron
describe the theory of effect on receptors as MOA for immobility
- 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)
which receptors do not affect MAC
- GABA
- ACh
- 5-HT
describe the Meyer Overton hypothesis for immobility MOA of inhalation agents
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)
describe the membrane expansion theory of MOA for immobility r/t inhalation agents
- 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”
what were the facts contradicting Meyer Overton (M-O) theory?
- 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
what is the 3rd theory for MOA of inhalation agents to cause immobility?
- 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
describe the 5-angstrom theory of immobility from inhalation agents
- 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)
describe the MOA of inhalational agents to cause amnesia
- 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
what is the theory for the MOA causing narcosis?
- 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
describe Geudel’s Stage 1
- analgesia
- ends w/ loss of eyelash reflex and unconsciousness
describe Geudel’s Stage 2
- excitement
- irregular breathing, struggling
- dilated pupils
- susceptible to vomiting, coughing, laryngospasm
- ends w/ onset of automatic breathing and loss of eyelid reflex
describe Geudel’s Stage 3, plane I
- until eyes central w/ loss of conjunctival reflex
- pupils normal or small
- lacrimation increased (can tell if pt. getting light)
- pharyngeal reflex abolished
describe Geudel’s Stage 3, plane II
- 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
describe Geudel’s Stage 3, plane III
- until complete intercostal paralysis
- shallow breathing
- lacrimation depressed
describe Geudel’s Stage 3, plane IV
- until diaphragmatic paralysis
- carinal reflexes abolished
describe Geudel’s Stage 4
- overdose
- apnea
- dilated pupils
what are signs of light anesthesia?
- 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
what are the effects of inhalation agents on ventilation in regards to depression?
dose related respiratory depression
what are the effects of response to CO2 and O2?
- dose dependent depressed response to increase in CO2
- non dose dependent depressed response to decrease in O2 (oxyhemoglobin saturation)
describe breathing w/ light anesthesia compared to deeper planes
- 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)
how is ventilation affected by inhalation agents?
- 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)
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
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)
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
at what levels do desflurane and sevoflurane lead to apnea?
b/w 1.5 and 2 MAC
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
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
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
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
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
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
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
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
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
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
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
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
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)
what does decreased myocardial contractility result in?
dose-dependent reduction in O2 demand
- protectant
- however, excessive concentrations can cause CV collapse
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
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)
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
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
which agent has the better beta 2 agonist effect (vasodilation)?
isoflurane
what is N2O effect on SVR?
- does not decrease SVR
- may actually cause vasoconstriction of cutaneous vessels
- may offset drop in SVR
how do agents compare in order from greatest change to least change in SVR?
isoflurane-desflurane-sevoflurane
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
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
who are increases in HR more frequently seen w/?
- younger patients
- accentuated by vagolytic agents like atropine and pancuronium
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
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
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)
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.
define reperfusion injury
cellular injury caused by the reinstitution of the blood flow, not d/t the ischemia itself
what are signs of a reversible reperfusion injury?
- cardiac dysrhythmias
- contractile dysfunction
- microvascular injury
what may be the MOA of cardioprotectant?
-protection probably results from an action on ATP-dependent potassium channels
with 1-1.5 MAC in healthy individuals, in what order from greatest to least do agents decrease MAP?
halothane/isoflurane/desflurane-sevoflurane
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
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
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
with 1-1.5 MAC, which agent increases sensitivity to catecholamines?
halothane
