inhalational agents: effects on neuro, hepatic, renal, and metabolism Flashcards
(59 cards)
1
Q
what are the effects of volatile agents on skeletal muscle?
A
- dose-dependent relaxation of skeletal muscle (not N2O)
- higher the MAC multiple, the greater the fad on tetanus
- can be used instead of NMB or to enhance the effect of NMB
2
Q
what is the effect of N2O on skeletal muscle?
A
muscle rigidity
3
Q
what MOA causes inhalation agents to enhance NMB?
A
may be from pre- or post-junctional effects
-pre: decreased release of ACh
-post: decreased sensitivity to ACh
or may be a direct effect on spinal motor neurons
4
Q
what are the benefits of inhalational skeletal muscle relaxation
A
- may decrease dose of nondepolarizing NMB
- decrease frequency of re-dosing (or may not need to)
- can avoid NMB all together (myasthenia gravis)
- pts. w/ hepatic or renal impairment
- also may reduce dose of neostigmine required to reverse NMB, leading to less PONV
5
Q
describe the duration of rocuronium when combined w/ different volatile agents
A
- longer duration depending on agent
- desflurane most effect: 90 min
- sevoflurane: 59 min
- isoflurane: 35 min
- propofol only prolongs to 35 min
6
Q
if recovery is prolonged from NMB and volatile concentration is still maintained, what should be done?
A
- blow off volatile to help get twitches back
- to maximize recovery from NMB at the end of a case, be sure volatile is off
- increased age is a factor prolonging recovery from NMB w/ volatile
- always check w/ peripheral nerve stimulator to maintain 1 twitch on TOF
7
Q
does volatile agents enhance effect of neostigmine on reversing NMB?
A
NO
- once volatile concentration is down, no longer provides enhanced skeletal muscle relaxation
- no lower doses are required to reverse
8
Q
which agent prolonged blocks w/ cisatracurium and rocuronium?
A
sevoflurane
9
Q
with vecuronium, which agents prolonged block?
A
- sevoflurane
- isoflurane
10
Q
what are the effects of isoflurane and nitrous oxide on succinylcholine?
A
- potentiates SCh
- isoflurane causes more rapid shift from phase I to phase II block w/ SCh infusion
11
Q
what does the amount of enhancement on NMB by volatiles depend on?
A
- time dependent
- sevo for 30 min. delayed recovery from vecuronium 89%
- sevo for 60 min. delayed recovery 100%
12
Q
since volatiles enhance skeletal muscle relaxation, what are the effects on reversal of nondepolarizing NMB?
A
- can impair reversal (not b/c it effects Neostigmine, just causes more relaxation)
- *carefully administer NMB, using twitch monitor and consider using relaxant effect of volatile instead of NMB if possible
- *check twitches, not time, d/t pt. variability
13
Q
what are the effects of volatile agents on uterine smooth muscle?
A
- dose-dependent relaxation of the uterine smooth muscle
- 0.5 MAC modest relaxation
- greater than 1 MAC, significant relaxation
14
Q
what are advantages and disadvantages of uterine smooth muscle relaxation by volatiles?
A
- positive: desirable relaxation for removal of retained placenta
- negative: contribute to increased blood loss w/ uterine atony
- may prefer to have uterine contractions after C-section or d&c to minimize blood loss
- reason C section high risk for awareness, don’t want much volatile on board; just explain up front
15
Q
what are the effects of volatiles on malignant hyperthermia?
A
- all agents can trigger (even w/o SCh)
- Halothane most potent trigger
- N2O much weaker trigger
16
Q
describe pathophysiology of malignant hyperthermia
A
- exposure to triggering agents cause the ryanodine receptor to release calcium from the sarcoplasmic reticulum to enter the muscle cell
- muscle contraction occurs d/t interaction of actin and myosin
- both aerobic and anaerobic muscle metabolism increase producing massive amounts of heat, carbon dioxide, and lactate (hypermetabolic state)
- muscle membrane permeability allows leakage
17
Q
what are early signs of malignant hyperthermia?
A
- a rapid increase in ETCO2, unable to correct w/ increased ventilation
- increase in HR
- *increase in temp is a late sign
- stop triggering factor and treat quickly w/ Dantrolene
18
Q
describe times to onset of MH w/ various sole volatile agent triggers
A
- desflurane: 260 min
- isoflurane: 140 min
- halothane: 35 min
- *times much faster if combined w/ SCh
19
Q
what are the effects of volatile agents on cerebral metabolic oxygen requirements (CMRO2)?
A
- all but N2O cause dose-dependent decrease in CMRO2 starting at approx. 0.4 MAC, as the pt. moves toward unconsciousness
- once an isoelectric EEG is produced, further increases in agent concentration does not further decreased in CMRO2
20
Q
what are the effects of N2O on CMRO2 and cerebral blood flow (CBF)?
A
- increases both CMRO2 and CBF
* but still uncoupling d/t a greater increase in CMRO2 than CBF
21
Q
describe effects of volatiles on CMRO2 compared to effects on CBF
A
- CMRO2 decreases
- CBF may increase, remain unchanged, or decrease
- if vascular resistance decreases: increased CBF, CBV, CSFP, ICP
- uncoupling: paradoxical decrease in CMRO2 at same time of increase in CBF
- no uncoupling (imbalance of supply and demand) if less than 1 MAC of halothane or isoflurane
22
Q
what factors affect the changes in CBF?
A
- dose of volatile
- other drugs administered (propofol, N2O)
- rate of change of concentration of volatile
- animal used in study
- w/ pentothal, cerebral vasoconstriction offset volatile dilation
- N2O decreases cerebral vascular resistance significantly
23
Q
describe effects of CBF in a normocarbic pt. w/ volatile greater than 0.6 MAC
A
- dose dependent increase in CBF
- cerebral vasodilation
- decreased cerebral vascular resistance
- increased CBF (potential increased ICP)
- but still decreased CMRO2
24
Q
in what order do agents increase cerebral vasodilation from greatest to least?
A
isoflurane and desflurane greater than sevoflurane
*clinically wont see much difference
25
how rapid does increased CBF occur?
within minutes of administration of inhaled agent
- independent of MAP
- sustained for as long as 4 hours during anesthetic
26
how do agents affect cerebral vascular reactivity to carbon dioxide?
- desflurane, sevoflurane, and isoflurane maintain reactivity to CO2 at less than 1 MAC
* can still hyperventilate to decrease CBF
27
describe agents affects on autoregulation of CBF
- isoflurane, desflurane, and sevoflurane at 1 MAC preserve autoregulation of CBF
* can hyperventilate to vasoconstrict after giving agent
* at 1.5 MAC, sevo preserves better than iso
- halothane eliminates autoregulation
* must hyperventilate PRIOR to giving agent to help keep down CBF
28
describe cerebral protectant effects of volatile agents
- CBF is maintained, CMRO2 is decreased (iso greater than halothane)
- once EEG is isoelectric, increasing agent concentration will not decrease CMRO2 any more
* *isoflurane may blunt necrotic processes resulting from cerebral ischemia d/t transient regional ischemia during carotid endarterectomy (protection does not apply to global ischemia like w/ cardiac arrest)
29
describe effects of agents on ICP
- cerebral vasodilation and increased CBF raise risks of increased ICP
- hyperventilation to decrease PaCO2 to 30 mmHg counters the increased ICP
* isoflurane, sevoflurane, and desflurane- start hyperventilation w/ start of agent
* halothane- start hyperventilation before agent is started
* *pt. w/ VP shunts
30
describe correlations of PaCO2 and CBF
- linear
- PaCO2 increased, increases CBF
- hyperventilate to decrease CBF
* lowest PaCO2 that will decrease CBF is 25 mmHg, no changes in CBF once under PaCO2 of 25
* *for every 1 mmHg drop in PaCO2, you decrease CBF 1-2
31
describe normal cerebral vascular response to CO2
- hypocarbia: vasoconstrict
* goal PaCO2 30-35 mmHg; effective 4-6 hrs.
- hypercarbia: vasodilate, increased CBF
* resp. depression and volatiles inhibit reaction to increased CO2 (used mech. ventilation)
* response altered in HTN and diabetic pts.
32
describe EEG changes seen w/ volatiles
- dose-dependent changes
- at 0.4 MAC, increased frequency and voltage, but activity shifts to anterior portions of the brain
- 1 MAC, increased voltage and decreased frequency (bigger, slower waves)
- 1.5 MAC, burst suppression (less than 1.5 MAC iso)
- 2.0 MAC, flat EEG (isoflurane)
* *halothane does not produce burst suppression at clinical levels
* *N2O has little effect on EEG at 1 atm., substitution for portion of MAC of volatile decreases EEG suppression
33
what are the effects of volatiles on seizure activity?
- des, iso, sevo suppress seizure activity r/t drugs like lidocaine (LA toxicity induced seizures)
* sevo has been associated w/ seizure activity (unknown MOA)
34
what increases the risk of seizure activity with sevoflurane?
- higher concentrations
- hypocarbia (doubles)
- repeated auditory stimulation
- pre existing seizure disorder
* *also an increased incidence of emergence delirium (possible link w/ seizure tendency)
* *cautious w/ kids
35
describe somatosensory evoked potentials and use of monitoring
- monitoring the transmission of the impulse from the periphery to/through the cord
- typically utilized w/ spinal fusions for scoliosis-monitoring to protect the spinal cord
36
how do volatiles effect somatosensory evoked potentials(SSEP)?
- dose dependent reduction in evoked potentials
- visual EP is most sensitive; brainstem EP is most resistant
- increase in latency and decrease in amplitude can be caused by ischemia or volatiles
37
what concentrations of volatiles are best to use when SSEP monitoring is occurring?
- sevoflurane and desflurane can use 1.3 MAC
- isoflurane 0.5-1 MAC
- halothane 0.5-0.7 MAC
- N2O may decrease amplitude of EP so AVOID
38
describe volatile effects on awareness and amnesia
- do not cause retrograde amnesia
- agents are not equal in effectiveness of preventing awareness
* 0.4 MAC isoflurane prevents awareness
* greater than 0.5 MAC N2O required (approx. .68 MAC)
- learning may be altered at low concentration (up to 0.2 MAC)
* surgical stimulation may increase the concentration required to prevent awareness (GO WELL ABOVE MACE AWAKE)
39
how do volatiles effect cerebral regulation of temperature control?
- impair regulation
- expands the vasoconstriction-to-shivering range of temperatures
* alters set point where vasoconstriction occurs and also the ability to vasoconstrict d/t vasodilation
* N2O affects less, so substitution impairs less
40
how do volatiles reset threshold for temperature regulation?
- reset threshold for regulation of temperature control to a lower level
- causes center for temp regulation to permit a broader range of temperatures to exist before cutaneous vasosconstriction occurs (at lower temps)
- permits a lower temperature before the body attempts to regulate heat loss and heat production
* *dose related
* *elderly have greater inhibition of temp regulation
* *must actively warm pts.
41
along w/ decreased temp. regulation, what also leads to heat loss?
- vasodilation
* heat transferred from core to periphery
* causes a decrease in core temperature of 0.5-1 degree C in the first half hour of anesthesia
42
how do volatiles affect cerebrospinal fluid production?
- isoflurane (des, sevo) does not change production of CSF, and decreases resistance to reabsorption
* results in minimal increases in ICP (but still will see ICP effects d/t CBF)
43
how much of halothane is metabolized?
15-40% (greatest metabolism)
44
how much of sevoflurane metabolized?
5-8%
45
how much of isoflurane metabolized?
0.2%
46
how much of desflurane metabolized?
0.02%
47
how much of nitrous oxide is metabolized, and where?
0.004% undergoes reductive metabolism to nitrogen in the GI tract
48
what is the concern of inhaled agent metabolism?
fluoride metabolites
- trifluroacetic acid
- inorganic fluoride
49
what is the metabolic pathway for des, iso, and sevo?
-oxidative (aerobic)
50
what is the harm of metabolism of halothane?
- principally oxidative by C-P450 enzymes when O2 is present*
* reductive metabolism when hepatocyte PO2 decreases
- trifluoroacetic acid: hepatotoxicity (halothane hepatitis)
51
describe halothane hepatitis
- d/t trifluoroacetic acid produced in liver w/ reductive metabolism of halothane (can see with others but metabolism % so low much less likely)
- immune mediated w/ an antigen-antibody reaction
* halothane hepatitis seen often w/ pts. re exposed to halothane within 20-30 days
52
describe trifluoroacetic acid
- produced also by biodegradation of halothane, iso and des
| * significant difference in percentage metabolized of des and iso vs. halothane
53
describe inorganic fluoride
- produced by biodegradation of sevo in the liver* (minimal in kidney, so little negative effect on kidneys)
- same level of inorganic fluoride produced w/ methoxyflurane (50mcgmol/L) which causes renal failure BUT no evidence of renal injury w/ sevo (even in pts. w/ existing renal damage)
* infrarenal production of inorganic fluoride seen w/ methoxyflurane is a bigger problem for nephrotoxicity than inorganic fluoride produced from hepatic metabolism w/ sevo
54
what levels of inorganic fluoride are considered toxic?
- no renal effects w/ peak plasma fluoride concentration less than 40 mcgmol/L
- subclinical toxicity when 50-80 mcm/L
- clinical toxicity when greater than 80 mcm/L
* level of 50 is used to indicate that renal damage may occur, but no renal damage even w/ levels exceeding 50
55
do inhalation agents cause renal impairment?
- no renal impairment after sevo
- cases of transient impairment of renal concentrating ability and increased excretion of NAG in pt. exposed to sevo and w/ peak plasma inorganic fluoride levels greater than 50 (theoretical, but don't risk w/ transplant)
* NAG considered an indicator of acute proximal renal tubular injury
* no elevation of BUN or creatinine
- no increased risk for damage w/ preexisting renal disease
56
what are renal effects of inhalation agents?
- renal blood flow reduced d/t decreased CO; may effect UOP intra-op
- decreased GFR
- decreased UOP
* pre-op hydration attenuates renal effects
* surgical stress (not inhaled agents which decrease) cause release of ADH; fluid status may also cause release to further add to decreased UOP
* still shoot for UOP 0.5 ml/kg/hr
57
describe effects of compound A
nephrotoxic
- may cause inability to concentrate urine, causing high output and decreased response to vasopressin
- no renal necrosis
- proteinuria, glucosuria, and enzymuria have been seen
58
how is compound A formed?
-w/ sevo degradation, a fluoride is lost from the chemical structure resulting in a double carbon bond (compound A)
59
how should you decrease the risk of compound A?
- minimum flows of 2 l/m if case longer than 2 hrs
- lower concentrations of sevo
- avoid KOH and NaOH in CO2 absorbent
- avoid increased temperature in CO2 absorbent (don't want dry absorbent)
* *increased flows reduces the rebreathing of compound A by washing it out and reduces the temperature of absorbent
