Inhalational agents - effects on MSK, neuro, hepatic, renal, and metabolism Flashcards
inhaled volatile agents cause a dose dependent _______ ______ _______
relaxation of skeletal muscle
but ______ has no effect on skeletal muscle relaxation
N2O
the higher the MAC multiple, the greater the _____ ____ ______
fade on tetanus
inhaled anesthetics can be used instead of ________ or to enhance the effect of ______
NMB
NMB
this enhanced effect of NMB may be from _____ or _____-______ effects or from effects on the spinal ______ _____
pre or post-synaptic
motor neurons
agents inhibit ______ receptors incompletely at MAC
nicotinic
practical application of inhaled anesthetics (4)
- decreases doses of nondep NMB 25% (50%)
- decreases frequency of redosing
- myasthenia gravis patient - give NO NMB
- patient with hepatic or renal impairment
Roc has a ______ duration depending on the volatile agent interaction:
Des ___ mins
Sevo ___ mins
Iso ___ mins
Prop ___ mins
longer
Des 90 mins
Sevo 59 mins
Iso 35 mins
Prop 35 mins
Roc duration explains the prolonged ______ from ______ when volatile concentration is maintained
recovery from NMB
One study examined the effect of decreasing the concentration of volatile on the twitch height when a vecuronium infusion was maintained. As the % concentration decreased, the twitch height ______, although the vecuronium infusion was ________.
increased
unchanged
Eger demonstrated the “substitution” of ___ ________ for NMB with an abdominal surgery in which muscular relaxation was desired by the surgeon
9% Desflurane
Effects on neuromuscular system: _______ results with ______ agents
different
different
Effects on neuromuscular system: may be explained by ______ of _____
methodology of study
Effects on neuromuscular system: with cisat and roc, _______ caused a prolonged block, and ______ didn’t
sevo
iso
Effects on neuromuscular system: with vecuronium, _____ and _____ both prolonged block
sevo and iso
Effects on neuromuscular system: all volatile agents have an ______ effect with ______
additive effect with succinylcholine
Effects on neuromuscular system: iso causes more rapid shift from ______ to ________ block with succ infusion
phase 1 to phase 2
Effects on neuromuscular system: TIME-dependent enhancement of _________
non-depolarizing NMB (recovery of ToF 1 twitch)
Effects on neuromuscular system: sevo 30 mins delayed recovery from vec ____
89%
Effects on neuromuscular system: sevo 60 mins delayed recovery from vec _____
100%
Effects on neuromuscular system: volatile agents can cause impairment of ______ of ________ NMB
reversal
non-depolarizing
Effects on neuromuscular system: take home message
CAREFULLY administer NMB, use your twitch monitor, and consider using relaxant effect of volatile in lieu of NMB, if possible
Uterine smooth muscle: volatile anesthetics cause dose-dependent ________ of the uterine smooth muscle
relaxation
Uterine smooth muscle: ___ ____ - modest relaxation
0.5 MAC
Uterine smooth muscle: ____ ____ - significant relaxation
greater than 1 MAC
Uterine smooth muscle: positive implication - desirable relaxation for ______ of ______ ______
removal of retained placenta
Uterine smooth muscle: negative implication - contribute to increased _____ ______ with uterine ______
blood loss
uterine atony
Uterine smooth muscle: _____ does not alter uterine contractility in doses used to provide analgesia during vaginal delivery
N2O
Uterine smooth muscle: N2O can be useful to ______ volatile and ______ benzodiazepines/opioids
decrease
avoid
Effect on uterine blood flow: ______ in maternal blood flow
decreases
Effect on uterine blood flow: decreases in uterine blood flow
- maintain ____ _____
- evidence of _____ ______ not present
< 1.5 MAC
fetal distress
Effect on uterine blood flow: ______ with no neonatal distress
amnesia
Effect on uterine blood flow: amnesia with no neonatal distress
- ____ MAC with ____ ____
- consider avoiding _____ in fetal distress
- 0.5 MAC with 50% N2O (total equivalent of 1 MAC)
- consider avoiding N2O in fetal distress
Malignant Hyperthermia: ____ ____ agents can trigger MH (even without ______)
all volatile
succinylcholine
Malignant Hyperthermia: _______ is the most potent trigger
halothane
Malignant Hyperthermia: ______ is a much weaker trigger and is on the MHAUS safe list
N2O
Malignant Hyperthermia: is a pathologic change in _____, ________ state
muscle
hypermetabolic
Malignant Hyperthermia: exposure to triggering agents cause the ______ ______ to release calcium from the ______ _____ to enter the muscle cell
ryanodine receptor
sarcoplasmic reticulum
Malignant Hyperthermia: muscle contraction occurs due to interaction of _____ and _____
actin and myosin
Malignant Hyperthermia: both aerobic and anaerobic muscle metabolism increase producing massive amounts of _____, _____, and ______
heat, CO2, and lactate
Malignant Hyperthermia: muscle membrane permeability allows ______
leakage
Malignant Hyperthermia: time to onset with volatile agent trigger only
- Des ____ minutes
- Iso _____ minutes
- Halo ____ minutes
- Des 260 mins (pt could even be home at this time)
- Iso 140 mins
- Halothane 35 minutes
CNS: CMRO2 requirements decrease at approx. ______ as the patient moves towards unconsciousness
0.4 MAC
CNS: reduction in CMRO2 is _____ ______
dose dependent
CNS: once an ______ _____ is produced, further increases in the agent concentration do not further decrease CMRO2
isoelectric EEG
CNS:
- CMRO2 - ______ ______ 60% + _____ _____ 40%
electrical activity
cellular homeostasis
CNS:
CMRO2 decreases normal response with no volatile anesthesia: brain _____ (____) its blood flow with its ______ ______
matches (couples)
metabolic requirements
CNS:
CMRO2 decreases when ______ _____ decrease, blood vessels _______, and _____ decreases
metabolic demands
constrict (CVR increases)
CBF
CNS:
2 opposing factors with volatile anesthetics
- vasoconstriction from _______ of _____
- vasodilation from _______ _____ _____
- reduction of CMRO2
- anesthetic agent directly
CNS: no uncoupling if ______ of des or iso
less than or equal to 1 MAC
CNS: ________ can occur at higher doses
uncoupling
CNS: N2O causes increased ______ and _____.
CMRO2 and CBF
CNS: However, with N2O there is still _______ due to the greater increase in ______ than ______
uncoupling
CMRO2
CBF
CBF: may ______, remain _______, or _______ - different studies
increase
unchanged
decrease
What affects change in CBF? (5)
- dose of volatile
- other drugs administered (prop, opioids, barbiturates, nitrous)
- rate of change of concentration of volatile
- ventilation (hyper- )
- animal used in study
she alluded that this was a test question
CBF: volatiles cause dose-dependent ______ in CBF
increase
CBF: normocarbia, > 0.6 MAC causes (4 things)
- cerebral vasodilation
- decreased CVR
- increased CBF (potential increased ICP)
- OBTW: decreased CMRO2 (coupling should result in decreased CBF)
cerebral vasodilation: ____ = ____ > ____
iso = des > sevo
increase in CBF occurs _____ _____ of administration of inhaled agent
within minutes
increased CBF is independent of _____ and can be sustained for as long as ___ ____ during an anesthetic
MAP
4 hours
greater decrease in CMRO2 by ______ may explain why CBF is not significantly increased at ____ _____
isoflurane
< 1 MAC
lower metabolism = ____ _____ production, _____ ____dilation
less CO2
less vasodilation
CNS: ______, ______, & _______ maintain the cerebral vascular reactivity to CO2 at less than __ MAC
desflurane, sevoflurane, and isoflurane
< 1 MAC
CNS: Iso, Des, and Sevo at ___ ____ preserve autoregulation of _____
1 MAC
CBF
CNS: Halothane _____ ______
eliminates autoregulation
CNS: at 1.5 MAC _____ preserves autoregulation better than ____
sevo
iso
CNS: as dose increases above 1 MAC, _______ is affected (CBF is more dependent on _____)
autoregulation
MAP
CBF is maintained (unchanged or higher). CMRO2 is _____. (iso>halothane) = _______ at ______ doses
decreased
uncoupling at higher doses (> 1 MAC)
CNS: _____ may blunt necrotic processes resulting from ______ ischemia due to transient _____ ischemia during ______ ______
isoflurane
cerebral
regional
carotid endarterectomy
CNS: bc isoflurane may blunt necrotic processes, cerebral _____ _____-_____ ______ is improved
oxygen supply-demand balance
cerebral vasodilation and increased CBF raise risks of ______ _____
increased ICP
CNS: hyperventilation to decrease the _____ to ____ mmHg counters the increased ICP
PaCO2 to 30 mmHg
CNS: iso, sevo, des - start hyperventilation with _____ ___ _____
start of agent
CNS: halothane - start hyperventilation ______ _______ _____
before agent is started
CNS: iso does not change production of ____, but decreases resistance to ________
CSF
reabsorption (increases reabsorption)
CNS: the result of iso increasing CSF reabsorption is only _______ ______ in ______ (even if CBF increases)
minimal increases in ICP
CNS: des may _____ or not change CSF production
increase
CNS: sevo ______ CSF production
decreases
CNS: N2O ___ ____ in CSF production
no increase
CNS: normal response to hypocarbia and PaCO2 goal
vasoconstrict
goal is PaCO2 30-35 mmHg - effective 4-6 hrs
CNS: normal response to hypercarbia
vasodilate
CNS: differences in literature (3)
- type of surgical procedure
- pathophysiology
- coexisting diseases
EEG effects: less than 0.4 MAC, ______ _____ and _____
increased frequency and voltage
EEG effects: at 0.4 MAC, activity shifts to ______ portions of the brain, transition from ______ to _______
anterior
excitement to unconsciousness
EEG effects: typically, ______ voltage and ______ frequency at about 1 MAC
increased voltage
decreased frequency (bigger slower waves)
EEG effects: the deeper the level of anesthesia, _____ ______ occurs (1.5 MAC) and possibly _____ _____ (2 MAC)
burst suppression
flat EEG
EEG effects: exception - ________ does not produce burst suppression at clinical levels
halothane
EEG effects: des, iso, and sevo can suppress ______ activity related to drugs like ______
seizure
lidocaine
EEG effects: however, _______ has been associated with seizure activity but MOA is uncertain
sevoflurane
EEG effects: sevo associate with seizures - increased incidence with higher concentrations (__ ____), ____carbia, repeated auditory _____, and pre-existing _____ _____
2 MAC
hypocarbia
stimulation
seizure disorder
EEG effects: question regarding a possible link between this seizure tendency and increased risk of ______ on emergence with sevo
delirium
Evoked Potentials is monitoring the transmission of the impulse from the _______ to/through the _____
periphery
cord
Evoked Potentials are typically utilized with ____ _____ for _____
spinal fusions for scoliosis (monitoring to protect the spinal cord)
Evoked Potentials: ALL potent inhaled anesthetics depress ______
SSEP
Evoked Potentials: inhaled anesthetics have a dose-dependent ______ in evoked potentials with _____ _____ being the most sensitive and _______ _____ being the most resistant
reduction
visual EP
brainstem EP
Evoked Potentials: an increase in _______ or decrease in _______ are indications of ischemia OR can be related to the volatile agent
latency (time of stimulus in periphery and onset of EP recorded by scalp electrode)
amplitude
Evoked Potentials: clinically at ____ -____ MAC
0.5-0.7 MAC
Evoked Potentials: research shows sevo and des can be utilized at ____ ____
1.3 MAC
Evoked Potentials: research shows that isoflurane can be utilized at ____-____ ____
0.5-1 MAC
Evoked Potentials: research shows halothane can be utilized at ___-___ ____
0.5-0.7 MAC
Evoked Potentials: _____ may profoundly decrease amplitude of evoked potentials so AVOID
N2O
Awareness: volatile agents do not cause ____ _____
retrograde amnesia
Awareness: volatile anesthetics are ____ _____ in the effectiveness of preventing awareness
not equal
0.4 MAC iso prevents awareness whereas > 0.5 - 0.6 MAC N2O is required
Awareness: ______ may be altered at low concentrations (as low as _____)
learning
0.2 MAC
Awareness: surgical stimulation may increase the concentration required to _____ ______
prevent awareness
Temp Regulation: impairment of ______ ______ of temperature control
cerebral regulation
Temp Regulation: inhaled agents reset the ______ for regulation of temperature control to a _____ level
threshold
lower
Temp Regulation: _____ has less of an effect; substitution of ______ impairs the threshold less
N2O
N2O
Temp Regulation: inhaled agents cause center for temp regulation to permit a lower range of temperatures to exist before _______ _______ occurs
cutaneous vasoconstriction
Temp Regulation: inhaled agents permit a lower temp before the body attempts to regulate ____ ____ and ____ _____
heat loss and heat production
It is DOSE-RELATED
Temp Regulation: _______ can also lead to temp loss
vasodilation
Temp Regulation: vasodilation results in heat transferred from _____ to ______ and this causes a decrease in core temp of 0.5-1 degree celsius in the first ____ ____ of anesthesia
core
periphery
half hour
Temp Regulation: elderly have greater _____ of temp regulation than other
inhibition
Neuroapoptosis: neurotoxicity in _______
animals
Neuroapoptosis: no predominant mechanism - altered neurogenesis, _____ growth, and _____ formation contributing to remodeling of ____ _____ and _______ remodeling
neurite
synapse
neuronal circuitry
developmental
Neuroapoptosis: ______ deficits, delayed _____
cognitive
learning
Neuroapoptosis: impaired memory ______ and ______
formation and retention
Neuroapoptosis: altered _____ and _____ development
motor and behavioral development
Neuroapoptosis: FDA issued a safety announcement advising that repeated or lengthy exposures to anesthetic or sedative drugs prior to age _____ have the potential to harm children’s brains
3
Hepatic Blood Flow: Iso (___), Des, and Sevo _______ total hepatic blood and artery flow
1.5%
maintained
Hepatic Blood Flow: iso/des/sevo increased ____ _____ _____ _____
increased portal vein blood flow (hepatic vasodilator)
Hepatic Blood Flow: halothane is a hepatic ______ ______
artery vasoconstrictor
% of anesthetic biodegraded: desflurane
0-0.02%
% of anesthetic biodegraded: isoflurane
0-0.2%
% of anesthetic biodegraded: sevoflurane
5-8%
% of anesthetic biodegraded: halothane
15-40%
% of anesthetic biodegraded: N2O
trick question
N2O isnt metabolized in the liver but in the gut by normal flora (0.004%)
Determinants of metabolism: chemical structure (2)
chemical bond
carbon-halogen bond
Determinants of metabolism: hepatic enzyme activity (2)
cytochrome p-450 induced or depressed
obese - increased fluoride concentrations
Determinants of metabolism: blood concentration - < 0.1 MAC undergoes extensive metabolism in the _____ (less soluble - quicker out via _____)
liver
lungs
Determinants of metabolism: all inhaled anesthetics are metabolized, just to _____ _____
varying degrees
Determinants of metabolism: the concern is the ______
fluoride
Determinants of metabolism: the metabolites of concern are ________ _____ and ______ ______
trifluoroacetic acid (TFA)
inorganic fluoride
Determinants of metabolism: metabolic pathways are oxidative for ____, _____, _____
des, iso, sevo
Harmful metabolism: metabolism of halothane - principally ______ by cytochrome p-450 enzymes when ______ is present, but _______ metabolism when hepatocyte PO2 decreases
oxidation
oxygen
reductive
Harmful metabolism: TFA is produced by biodegradation of ____, ____, and _____. It causes acetylation of proteins on the surface of hepatocytes to form ______ to which ______ form
hal, iso, des
antigens
antibodies
Harmful metabolism: TFA - connection between its hepatic production and hepatotoxicity via an _____ _____
immune pathway
Harmful metabolism: TFA - significant difference in percentage of _____ & ____ metabolized vs ______
iso & des
halothane
Inorganic fluoride - nephrotoxicity: produced by the biodegradation of sevo in the _____ and only minimally in the _____. Thus, little effect on the ______.
liver
kidneys
kidneys
Inorganic fluoride - nephrotoxicity: same level of inorganic fluoride produced as with ________ which causes renal failure, but no evidence of renal injury, even in patients with existing renal damage
methoxyflyrane (50 mcgmol/L)
Inorganic fluoride - nephrotoxicity: _______ production of inorganic fluoride (methoxyflurane) is a bigger problem for nephrotoxicity than inorganic fluoride produced from _____ metabolism (sevo)
infrarenal
hepatic
Inorganic fluoride - nephrotoxicity: historically -
no renal effects @ ______
subclinical toxicity @ _____
clinical toxicity @ _______
no renal effects @ < 40 mcm/L
subclinical toxicity @ 50-80 mcm/L
clinical toxicity @ > 80 mcm/L
Inorganic fluoride - nephrotoxicity: level of _____ is the indicator that renal toxicity may occur - however, no _____ _____ even with levels exceeding this level.
50
renal damage
Inorganic fluoride - nephrotoxicity: ____ and _____ are less soluble and exhaled more and less metabolized
Enf and Sevo
Inorganic fluoride - nephrotoxicity: high out put renal failure is unresponsive to ______, and has an inability to _____ urine, _______, hyper______, hyper______, increased plasma _______
vasopressin
concentrate
polyuria
hypernatremia
hyperosmolarity
creatinine
Renal effects: studies show no renal _____ after ______
necrosis
sevo
Renal effects: have been cases of transient impairment of renal ______ ability and increased excretion of ____-____-_______ in patient exposed to sevo and with peak plasma inorganic fluoride levels > ______
concentrating ability
beta-N-acetylglucosaminidase (NAG)
50 mcm/L
Renal effects: NAG is an indicator of _____ ____ ____ ____ injury
acute proximal renal tubular injury
Renal effects: no elevation in ______ or _______
BUN or creatinine
(not super sensitive indicators)
Renal effects: patients with pre-existing renal disease
no increased risk for damage
Renal effects: renal blood flow is
reduced (may effect urine output intraoperatively)
Renal effects: decreased _____
GFR
Renal effects: decreased ____ ____
urine output
Renal effects: due more to the decrease in ____ and systemic _____. preop ______ attenuates renal effects
CO
BP
hydration
Renal effects: _____ ____, not inhaled anesthetics, cause release of ADH
surgical stress
Renal effects: fluid status changes might also cause _____ release to contribute to _____ urine output
ADH
decreased
Compound A: may cause inability to ____ ____ causing high _____ and decreased response to _____
concentrate urine
output
vasopressin
Compound A: no ____ ____ has been seen
renal necrosis
Compound A: however, have seen ______, ______, and _______
proteinuria, glucosuria, enzymuria
Compound A: to decrease risk, minimum flows of _____ if case longer than _____
2L/min
2 hours
Compound A: _____ if case is less than 2 hours
1L/min
Compound A: lower concentrations of ______
sevo
Compound A: avoid ____ and _____ in CO2 absorbent
KOH
NaOH
Compound A: avoid increased ______ in CO2 absorbant
temperature