intravenous anesthetic agents Flashcards
what are primary uses of IV anesthetic agents?
- IV induction that allows for rapid recovery
- used for sedative/hypnotic allowing for a deeper sleep but not unconsciousness
ex: during a breast biopsy, used for injection of local anesthetic which is painful - TIVA
what is the MOA of IV anesthetics?
changes the level of consciousness by depressing the reticular activating system either by:
- enhancing the inhibition properties of GABA
- or inhibiting the NMDA excitatory synapses
what are the different IV anesthetic agents?
- propofol
- ketamine
- thiopental
- methohexital
- etomidate
- benzodiazepines
what is the primary mechanism of terminating the central effect of IV anesthetic agents?
redistribution from the central, highly perfused compartment (blood, brain) to the larger and less-well perfused “peripheral” compartments (skeletal muscles)
*with drugs like pentothal, may still be in the body, but not at effect site
what are characteristics of the IDEAL IV anesthetic?
- water soluble with chemical stability and IV fluid compatible
- rapid onset w/o unwanted movement or unpredictable CV or CNS side effects
- rapid (lipid soluble) and predictable recovery
- anticonvulsant, antiemetic, analgesic (ketamine), amnesic
- no renal/liver impairment, steroid synthesis (etomidate), teratogenicity
- no pain on injection (propofol hurts)
- low histamine release (pentothal causes histamine release)
- rapidly metabolized to inactive substances with minimal accumulation
- “dialable” or rapidly responsive to titration (propofol)
- decreases cerebral metabolism proportional to CBF and no increase in ICP (pentothal)
- no hangover or headache (pentothal causes “hangover”)
Describe thiopental (Pentothal)
- barbiturate (thiobarbiturate)
- 2.5% sodium salt preparation is water soluble (25 mg/cc)
- highly alkaline (10.5 pH) making bacteriostatic
- unstable once reconstituted (last 6 days at rm temp, 2 weeks in refrig)
- no pain on injection
- precipitate if mixed with opioids, catecholamines, NMB, and other acidic fluids (LR) so flush well after!
what is the mechanism of action for thiopental?
- increases duration of GABA activating its receptor causing the chloride ion channels to remain open longer, allowing more influx and hyperpolarization and inhibition of the cell
- mimics GABA at its receptor to directly cause Cl- channels to open
- also activates other receptors (glutamine, adenosine, nACh) to depress SNS ganglia transmission causing hemodynamic effects and desensitize nACh receptors to ACh with large doses
what are CV effects of thiopental?
- minimal BP decrease
- increase in HR unless on beta blockers or hypovolemic and have greater drop in BP
- peripheral vasodilation: venous pooling, decreased venous return (possible decreased CO) BUT offset by normal sympathetic activation
- possible histamine (greater drop in BP d/t arterial and venous dilation)
- effects prominent in hypovolemia
- myocardial depression less than volatile agents
- CV effects considered MINIMAL
what are respiratory effects of thiopental?
- decrease sensitivity of medullary ventilator center to stimulation of CO2
- respirations return as small TV and slow RR (drop in MV)
- reflexes remain intact with apnea, allowing possibility of laryngospasm (not good with LMA or intubation w/o NMB)
- apnea more likely when other depressant drugs, opioids, and benzos are also used (so not good with sedation cases)
what are CNS effects of thiopental?
- decreases ICP by decreasing cerebral blood volume d/t cerebral vasoconstriction
- decreases cerebral metabolic oxygen requirements by 55% (decreases demand more than decrease supply)
- careful of hypotension with large doses which would decrease CPP (MAP-ICP) below adequate pressure
- tolerance and physical dependence may occur
what are renal and liver effects of thiopental?
no damage
what is the effect of thiopental on heme?
increases the production of heme, which may exacerbate acute intermittent porphyria
**do not give to porphyria patients
what dose of thiopental is safe for the fetus?
up to 4 mg/kg maternal dose
what may occur with thiopental d/t histamine release?
anaphylactoid and anaphylaxis reactions
what happens to thiopental at physiological pH?
becomes highly lipid soluble
how much of thiopental is protein bound?
85%
*decrease dose with elderly who have decreased albumin
what is the distribution 1/2 life and elimination 1/2 life of thiopental?
- distribution 1/2 life: 2-4 min
- elimination 1/2 life: 10-12 hrs (reason have hangover effects even though desired effects last only minutes)
what is the dose of thiopental?
3-5 mg/kg
*decrease with elderly or if using benzos or other depressant drugs
what is the onset and duration of thiopental?
onset: 30 sec
duration: 5-10 min
what are the basic characteristics of thiopental?
- “gold standard”
- minimal CV effects
- good cerebral protection
- minimal pain on injection
- hangover
- moderate emetic (makes nauseated)
- precipitation
- don’t give with porphyria patients
describe methohexital (Brevital)
- barbiturate (oxybarbiturate)
- less lipid soluble than thiopental
- 1% solution (10 mg/cc; more potent d/t higher % nonionized at blood pH 7.4)
- stable when reconstituted (refrigerate up to 6 weeks)
- MOA like thiopental and distribution limits central effects like thiopental
describe metabolism of methohexital compared to thiopental?
- 3-4x faster d/t decreased lipid solubility
- smaller VOD allows more to stay in plasma and go past liver more allowing quicker elimination
- more rapid awakening with no hangover effects or groggy, but not a startling wake up like with propofol
what is the elimination 1/2 time of methohexital?
3.9 hours (10-12 with thiopental)
what is the advantage of methohexital?
a more rapid recovery
- good with cataract procedures; allows for retrobulbar block needle insertion
- good with elderly when don’t want benzo or opioids
what are the disadvantages of methohexital?
- more excitatory activity: myoclonus, hiccups
- dose dependent
- decreased by keeping dose between 1.0-1.5 mg/kg and including opioids preop
- infusion associated with postop seizures
what are CV effects of methohexital?
- similar to thiopental with equivalent doses
- less hypotension d/t increase in HR better preserved
- no histamine release
what are CNS effects of methohexital?
similar to thiopental EXCEPT for excitatory activity
what is the effect of methohexital on heme?
can cause an exacerbation of porphyria like thiopental
what are the dosages of methohexital?
induction: 1-2 mg/kg
sedation: 0.2-0.4 mg/kg (local/retrobulbar block; 1.5-3cc)
rectal: 25 mg/kg
what are the onset and duration of methohexital?
onset: 30 sec (rectal < 5 min)
duration: 5-10 min (rectal 30-90 min)
what is the distribution 1/2 time of methohexital? how fast is it eliminated?
- distribution 1/2 time: 5.6 min
- elimination time: 2-5 hrs
what are basic characteristics of methohexital?
- more rapid recovery
- excitatory activity (hiccups, myoclonus)
- moderate emetic
- don’t give with porphyria
describe etomidate
- chemically unrelated to any other IV anesthetic
- carboxylated imidazole-containing compound
- water-soluble at an acidic pH and lipid soluble at physiologic pH (like versed) but still uses carrying agent
- pain on injection
- 0.2% (2mg/cc)
what is the MOA of etomidate?
-mimics the inhibitory effects of GABA by increasing the receptors affinity to GABA thus depressing reticular activating system
what are CV effects of etomidate?
- great hemodynamic profile
- mean arterial BP decrease slightly (15%)
- minimal changes in HR, SV, CO
- decrease in SVR
- depresses myocardium less than thiopental
- no decrease in renal blood flow
- no histamine release
what are respiratory effects of etomidate?
- less effect on respiration than barbiturates
- decreased TV, but increased RR
- good when spontaneous ventilation desired
- greater risk for apnea if rapid injection or combined with volatile agents or opioids
- not great if want a decrease in resp. reflexes
what are CNS effects of etomidate?
- decrease in CMRO2 35-45%
- CPP well maintained d/t good CV profile
- excitatory activity causing myoclonus in 30-60% of pts.
- avoid using with seizure disorder pts.
- myoclonic activity can be minimized with preop opioids
what effect does etomidate have on adrenocortical?
adrenocortical suppression
- inhibition of the conversion of cholesterol to cortisol
- decreased cortisol and aldosterone levels approx. 30 min after a single dose
- last 4-8 hrs. after dose; may last up to 48 hrs.
- *septic and bleeding patients need to have an appropriate stress response
- steroid doses DONT help
- although good for heart problems, think of long term effects if pt. really sick
describe etomidate onset and metabolism compared to thiopental
- highly lipid soluble, large % nonionized produces rapid onset
- action limited by redistribution like thiopental
- metabolism by hepatic microsomal enzymes and plasma esterases
- clearance 5x faster than thiopental
what is the dose of etomidate?
0.3 mg/kg
what are the onset and duration of etomidate?
onset: 14-45 sec
duration: 3-12 min
what are the distribution and elimination times of etomidate?
- distribution 1/2 time: 2-4 min
- elimination: 2-5 hrs
what are basic characteristics of etomidate?
- pain on injection
- commonly emetic (will throw up!)
- adrenocortical suppression
- GOOD CV
- excitatory activity (myoclonus, seizures)
describe dexmedetomidine (Precedex)
- alpha2 adrenergic agonist (brain/sedation; heart/brady; vessels/constrict and dilate with decreased NE; renal; temp)
- 8x more selective for alpha2 receptors than clonidine (sister drug)
- used more as an adjunct
- may be used as an infusion outside of OR
what is the MOA of dexmedetomidine?
- in spinal cord and locus coeruleus
- hyperpolarization with efflux of K+ (causes sedation)
- reduced NE release d/t presynaptic receptors (cause of side effects)
- decrease cAMP concentration by inhibiting adenylyl cyclase
what are CV effects of dexmedetomidine?
- HTN r/t loading dose (don’t bolus)
- may cause decreased HR and BP (be careful with heart blocks)
- *increased risk hypotension with high sympathetic tone (vasoconstriction d/t trauma), diabetic, elderly, hypovolemia
what are CNS effects of dexmedetomidine?
- sedation and analgesia with little depression of ventilation
- less delirium than benzos
- sedation similar to physiologic sleep
- easily arousable
- good for awake craniotomy
- weaning of vent without titration
how does dexmedetomidine affect MAC?
decreases > 90%
what is dexmedetomidine approved for?
- NOT approved for general anesthesia
- approved for infusions of 24 hrs. and sedation cases
- alternative to propofol (more likely to become apneic and change in hemodynamics )for sedation in MRI
- require increased infusion 2mcg/kg/hr and longer recovery
- alternative to ketamine (hallucinations and increased secretions and ICP) for awake fiberoptic intubations
- antisialagogue effect is beneficial
what is the distribution 1/2 life of dexmedetomidine?
6-8 min
what is the context sensitive 1/2 time for dexmedetomidine?
- after 1 hr.: 25-120 min
- after > 6 hrs.: 87-250 min
what is the loading dose and infusion rate of dexmedetomidine?
loading dose: 0.5-1 mcg/kg over 10 min
infusion rate: 0.2-1.4 mcg/kg/hr
what are basic characteristics of dexmedetomidine?
- some analgesic effect (not same as ketamine)
- augments opioid effects by spinal and supraspinal mechanisms (can be added to neuraxial)
- only limited amnesia
- reduces shivering making more susceptible to hypothermia (provide heat replacement)
which IV anesthetic is an antiemetic?
propofol
how do IV anesthetics compare in terms of recovery?
- thiopental has longer lasting “hangover” effects
- propofol has no hangover, but quick startling arousal
- ketamine produces hallucinations
which IV anesthetic is the worst offender for an emetic effect?
etomidate
how do IV anesthetics compare with respiratory effects?
- ketamine: encourages respirations; can offset depression of propofol; can cause slight depression with opioid use
- etomidate: least resp depressin; may have apnea with pre treatment opioids
- thiopental: apnea
- propofol: apnea and loss of reflexes
- *worse with pts. with pulmonary pathologies like COPD
which drugs must be avoided with porphyria?
thiopental, methohexital, and etomidate
*ketamine okay to use
how much are IV anesthetics protein bound?
- all except ketamine are 75% and >
- ketamine 12%
which IV anesthetic affects adrenalcortical?
etomidate
which IV anesthetics cause an excitatory CNS effect?
methohexital and etomidate
when should dosages be decreased?
- use of opioids
- use of benzos
- elderly (start with smaller doses to see how they respond; can always give more)
