inhalational agents: effects on neuro, hepatic, renal, and metabolism Flashcards
what are the effects of volatile agents on skeletal muscle?
- 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
what is the effect of N2O on skeletal muscle?
muscle rigidity
what MOA causes inhalation agents to enhance NMB?
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
what are the benefits of inhalational skeletal muscle relaxation
- 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
describe the duration of rocuronium when combined w/ different volatile agents
- longer duration depending on agent
- desflurane most effect: 90 min
- sevoflurane: 59 min
- isoflurane: 35 min
- propofol only prolongs to 35 min
if recovery is prolonged from NMB and volatile concentration is still maintained, what should be done?
- 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
does volatile agents enhance effect of neostigmine on reversing NMB?
NO
- once volatile concentration is down, no longer provides enhanced skeletal muscle relaxation
- no lower doses are required to reverse
which agent prolonged blocks w/ cisatracurium and rocuronium?
sevoflurane
with vecuronium, which agents prolonged block?
- sevoflurane
- isoflurane
what are the effects of isoflurane and nitrous oxide on succinylcholine?
- potentiates SCh
- isoflurane causes more rapid shift from phase I to phase II block w/ SCh infusion
what does the amount of enhancement on NMB by volatiles depend on?
- time dependent
- sevo for 30 min. delayed recovery from vecuronium 89%
- sevo for 60 min. delayed recovery 100%
since volatiles enhance skeletal muscle relaxation, what are the effects on reversal of nondepolarizing NMB?
- 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
what are the effects of volatile agents on uterine smooth muscle?
- dose-dependent relaxation of the uterine smooth muscle
- 0.5 MAC modest relaxation
- greater than 1 MAC, significant relaxation
what are advantages and disadvantages of uterine smooth muscle relaxation by volatiles?
- 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
what are the effects of volatiles on malignant hyperthermia?
- all agents can trigger (even w/o SCh)
- Halothane most potent trigger
- N2O much weaker trigger
describe pathophysiology of malignant hyperthermia
- 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
what are early signs of malignant hyperthermia?
- 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
describe times to onset of MH w/ various sole volatile agent triggers
- desflurane: 260 min
- isoflurane: 140 min
- halothane: 35 min
- *times much faster if combined w/ SCh
what are the effects of volatile agents on cerebral metabolic oxygen requirements (CMRO2)?
- 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
what are the effects of N2O on CMRO2 and cerebral blood flow (CBF)?
- increases both CMRO2 and CBF
* but still uncoupling d/t a greater increase in CMRO2 than CBF
describe effects of volatiles on CMRO2 compared to effects on CBF
- 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
what factors affect the changes in CBF?
- 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
describe effects of CBF in a normocarbic pt. w/ volatile greater than 0.6 MAC
- dose dependent increase in CBF
- cerebral vasodilation
- decreased cerebral vascular resistance
- increased CBF (potential increased ICP)
- but still decreased CMRO2
in what order do agents increase cerebral vasodilation from greatest to least?
isoflurane and desflurane greater than sevoflurane
*clinically wont see much difference
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
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
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
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)
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
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
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.
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
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)
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
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
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
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
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)
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
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.
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
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)
how much of halothane is metabolized?
15-40% (greatest metabolism)
how much of sevoflurane metabolized?
5-8%
how much of isoflurane metabolized?
0.2%
how much of desflurane metabolized?
0.02%
how much of nitrous oxide is metabolized, and where?
0.004% undergoes reductive metabolism to nitrogen in the GI tract
what is the concern of inhaled agent metabolism?
fluoride metabolites
- trifluroacetic acid
- inorganic fluoride
what is the metabolic pathway for des, iso, and sevo?
-oxidative (aerobic)
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)
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
describe trifluoroacetic acid
- produced also by biodegradation of halothane, iso and des
* significant difference in percentage metabolized of des and iso vs. halothane
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
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
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
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
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
how is compound A formed?
-w/ sevo degradation, a fluoride is lost from the chemical structure resulting in a double carbon bond (compound A)
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
