Exam 2- Induction Agents Flashcards
Low dose IV anesthetics produce __________ and high doses produce __________________
sedation; unconsciousness
T/F: All IV anesthetics are sedative-hypnotics and produce dose-dependent CNS depression
true
what modeling map does propofol follow?
three-compartment model
half-life
the time it takes for the plasma concentration of a drug to decrease to 50% of its original concentration
what is the best example of a drug with context-sensitive half-time?
remifentanil
which drug is an ultrashort opioid agonist?
remifentanil
which drug has an ester component structure and is eliminated rapidly due to metabolism by plasma esterased?
remifentanil
The context-sensitive half-life is independent of
the infusion duration
propofol primary mechanism of action
GABA-A receptor agonist (enhancement of GABA inhibition)
propofol CNS effects
CNS depressant, neuroprotective, anticonvulsant, decreases CMRO2, CBF, and ICP
propofol CV effects
significant decrease in SVR, stroke volume and cardiac output
drop in systolic and diastolic without increasing HR
propofol pulmonary effects
respiratory depressant in higher doses and potent bronchodilator (due to direct effect on intracellular calcium)
propofol misc. effects
Major side-effects: pain with injection and propofol infusion syndrome
which agent treats and prevents PONV?
propofol
is propofol safe for use in patients with MH?
yes
key clinical use of propofol
General anesthesia induction and maintenance
Good for TIVA
where is propofol primarily metabolized?
by the liver
inactive and water-soluble metabolites are excreted by the kidneys
how does propofol produce an unconscious state?
by enhancement of GABA inhibitory pathways and perhaps central cholinergic transmission, NMDA or alpha-adrenergic sites
what does a low dose of propofol produce
sedation and possible paradoxical excitation
higher doses of propofol produce
loss of consciousness and apnea, relaxation of muscles, need for airway support
propofol neuroprotective effects
lowers cerebral metabolic oxygen consumption (CMRO2), decreased ICP by lowering CBF
propofol and cerebral perfusion
cerebral perfusion pressure lowered
what does propofol do in patients with seizures?
treat status epilepticus, shorten seizure duration
propofol vascular effects
vasodilation and venodilation
is apnea present w propofol?
yes in higher doses
maintenance doses of propofol causes what respiratory effects?
diminished TV and increased RR
how can PONV be treated?
propofol 10-15 mg IV
or infusion 10 ug/kg/min
propofol pruritus effects
can treat opioid-induced pruritus in a dosage of 10 mg IV
propofol IV induction dose
1-2.5 mg/kg (2mg/kg) produces unconsciousness in 30s.
propofol IV continuous infusion
25-75 mcg/kg/min
propofol anesthesia maintenance
100-200 mcg/kg/min
what is propofol usualy concentration
10mg/mL
propofol issues
Allergic potential related to its phenyl nucleus and di-isopropyl side chain
Anaphylaxis has been reported
Egg lecithin (fatty part of yolk), proteins from eggs cause allergy
Generic propofol contains sodium metabisulfite, which is contraindicated in patients with sulfite sensitivity
pain on injection in 60-70% of population
propofol doses in children
Children have larger volumes of distribution and faster clearance so may need more
which population requires larger dose requirements?
chronic alcoholics
which population has prolonged effects from propofol?
Elderly have prolonged effects and increased sensitivity due to decreased cardiac output and clearance
which populations should propofol not be used in?
CV disease, trauma, hypotension, bleeding
how long is propofol good in an opened vial
up to 12 hours
how long is propofol good for after being drawn into a syringe
6 hours
propofol infusion syndrome (PRIS) symptoms
acute refractory bradycardia potentially leading to asystole
unexplained conditions: metabolic acidosis, hyperkalemia, rhabdomyolysis, hyperlipidemia, and/or enlarged liver, renal failure, EKG changes, arrhythmias
can also be seen in cardiomyopathies, skeletal myopathy, or hyperkalemia
when is PRIS usually seen
in critically ill adults
PRIS hepatic effects
Can cause green urine. Increased extrahepatic metabolism of propofol and excretion of these metabolites in urine, also with longer infusions urine may become milky colored
etomidate site of action
GABA-A receptor agonist
which induction agent is hemodynamically stable?
etomidate
which induction agent can cause adrenocortical suppression in critically ill patients
etomidate
which induction agent can cause PONV
etomidate
which population is etomidate good for?
cardiac, trauma, elderly
which induction agent is a carboxylated imidazole derivative
etomidate
will etomidate result in vaso-irritation?
yes from solvents in the propylene glycol formation
can etomidate be given via continuous infusion
not really; limited due to possible adrenal suppression
where is etomidate metabolized?
by the liver and plasma esterases
where is etomidate excreted?
80% by kidneys; 20% by the bile
what % of etomidate is protein bound?
75%, highly protein bound
what is etomidate elimination half life
3-6 hours
what is etomidate initial distribution half-life
2.7 minutes
what is etomidate redistribution of half life
29 min
what is etomidate volume of distribution
2.5-4.5 L/kg
what is etomidate induction dose
0.2-0.3 mg/kg
what is etomidate usual concentration
2 mg/cc
etomidate mechanism
binds as an agonist to the GABA-A
etomidate CNS effects
vasoconstrictor that reduces CBF, ICP, and CMRO2
what can etomidate cause on induction
seizure-like myoclonic movements; treat with versed/opioid
which induction agent is hemodynamically stable on induction
etomidate
etomidate cardiovascular effects
minimal to no effect on MAP, PA pressure, PCWP, CVP, SV, CI, SVR and PVR
etomidate risks
adrenocortical suppression
Inhibits the activity of 11 β-hydroxylase and prevents conversion of cholesterol to cortisol
which induction agent is a PCP derivative
ketamine
what kind of CNS effects does ketamine have
analgesia and anesthetic, dissociation, emergence delirium & hallucinations
which induction agent is a racemic mixture?
ketamine
which induction agent has high lipid solubility and low protein binding
ketamine
ketamine bioavailability
IM, transnasal, rectal, and oral
ketamine lipid solubility
high lipid solubility and low protein binding
which induction agent has rapid redistribution
ketamine
what is ketamine mostly metabolized by
the liver CYP450 enzymes
how does the liver metabolize ketamine
demethylation to norketamine
ketamine onset of IV
30-60 seconds
ketamine duration
10-20 min
ketamine induction dose IV and IM
0.5-2 mg/kg IV
4-5 mg/kg IM
ketamine usual concentration
10 mg/cc
ketamine produces functional dissociation between
thalamocortical and limbic systems
ketamine CNS effects are primarily related to its
antagonistic activity at the N-methyl-D-aspartate (NMDA) receptor
what other receptors does ketamine bind to
Non-NMDA glutamate receptors
Nicotinic receptors
Cholinergic receptors
Monoaminergic receptors
Mu, delta and kappa-opioid receptors
It also inhibits neuronal Na+ channels (Local anesthetic action) and Ca+ channels (Cerebral vasodilation)
ketamine clinical state
dissociative
unconscious with eyes open (nystagmus)
maintain spontaneous respiration
no reaction to painful stimuli
ketamine induction dose side effects
associated with increased hr and bp
what drug is a good choice for hemodynamically unstable
ketamine
what is a good drug choice for OB
ketamine
when should ketamine be used with caution
cardiac patients with sever right heard dysfunction because it increases PVR
ketamine can also be used for
management of acute pain and depression
which induction agent can be used in opioid abuse patients
ketamine
ketamine CNS effects
potent cerebral vasodilator
increase in CBF of 60-80% during normocapnia that can be attenuated with hyperventilation
when is ketamine contraindicated
patients with elevated ICP
ketamine airway effects
does not produce significant depression of ventilation
maintains airway reflexes
can increase secretions d/t its effect on muscarinic receptors
does ketamine bronchodilate?
yes
ketamine cardiovascular effects
SNS stimulation
everything goes up (MAP, CO, myocardial oxygen requirements, SVR)
what is the ideal induction agent for a patient with hypovolemia
ketamine
however, in a shock patient →
profound hypotension
emergence delirium
A phenomenon associated during the postoperative period in patients who have received ketamine anesthesia
Visual, auditory illusions
Confusion
Delirium
incidence of emergence delirium
5-30%
how to prevent emergence delirium
preop midazolam
recover patient in calm and quiet environment
how does dexmedetomidine work
It is a highly selective, specific, and potent α-2 adrenergic agonist
what does dexmedetomidine inhibit
norepi release in locus coeruleus
which induction agent mimics natural sleep like state
dexmedetomidine
what does dexmedetomidine produce
dose-dependent sedation and analgesia with mild respiratory depression
dexmedetomidine protein binding
highly protein bound, 94%
dexmedetomidine metabolism
rapid hepatic metabolism involving conjugation, N-methylation, and hydroxylation
how is dexmedetomidine excreted
urine and feces
dexmedetomidine relation to CYP enzymes
weak inhibitory effects that could cause increased plasma concentrations of opioids
dexmedetomidine CNS effects
It has sedative, anxiolytic, and analgesic effects (spinal cord and brain)
Patients are sedated but easily arousable, and able to follow commands
The analgesic effects reduce postsurgical opioid requirements
dexmedetomidine ventilatory depression?
yes, less than other sedative-hypnotic and opioid anesthetics
what kind of dexmedetomidine administration reduces minute ventilation
bolus administration
dexmedetomidine cardiovascular effects
increased potential for hypotension and bradycardia because of high α- 2- adrenoreceptor activity
what induction agent blunts hemodynamic effects of direct laryngoscopy and improves hemodynamic stability when given as an adjuvant
dexmedetomidine
in which population may dexmedetomidine cause severe bradycardia
children –> best to titrate
When is dexmedetomidine used
critical care environment when controlled ventilation is required
after extubation
adjuvant during induction or maintenance
blunts SNS response to laryngoscopy
which induction agent is good for procedural sedation
dexmedetomidine
dexmedetomidine sedation dose
0.5-1 mcg/kg over 10 min
followed by infusion of 0.2-0.7 mcg/kg/hr
dexmedetomidine usual syringe concentration
4 mcg/mL
dexmedetomidine side effects
hypotension
bradycardia (40%)
dry mouth and nausea
hypertension
how can dexmedetomidine bradycardia be treated
Can be treated with atropine, ephedrine or volume
Omitting the loading dose can decrease incidence of bradycardia
which induction agent has anticonvulsant properties
benzodiazepines
benzodiazepines effects
amnesia
minimal cardiovascular or resp depression
central skeletal muscle relaxant
anxiolysis and sedation
benzodiazepines mechanism of action
GABA-A
what do benzodiazepines increase
chloride conductance causing hyperpolarization of the membrane increasing nerve resistance to stimulation
do benzodiazepines burn on injection
usually not because they are more water soluble (versed)
how can benzodiazepines be administered
PO, IV, IM, rectally, intranasally, infusion
benzodiazepine absorption
rapid absorption from the gut >50% undergo first pass hepatic excretion
benzodiazepine protein binding
highly protein bound, high lipid solubility
benzodiazepine ICP effect
can decrease CMRO2 and CBF with little effect on ICP
what do benzodiazepines do to upper airway reflexes
may be decreased as well as central respiratory drive
what do benzodiazepines do cardiovascularly
can decrease SVR and BP
which drug class produces anterograde amnesia
benzodiazepines
how to reverse benzodiazepine administration?
flumazenil
flumazenil dose
0.15 mg IV over 15 seconds
if after 45 seconds no response give 0.2 mg
repeat at 1 min intervals (do not exceed 4 doses)
children common midazolam dose before OR
0.5 mg/kg 30 min prior to OR
adult midazolam dose
1-2 mg in preop
which benzodiazepine is water soluble
midazolam
undergoes conformational change in the bloodstream before becoming more lipophilic
which benzodiazepines are not water soluble
lorazepam and diazepam (often cause vein irritation)
what kind of barbiturate is methohexital
oxybarbiturate
barbiturate metabolizm
primarily hepatic
inactive metabolites are excreted in urine and bile
barbiturate mechanism of action
cortical and brainstem GABA inhibitory pathways
barbiturate effects
loss of consciousness, respiratory and cardiovascular depression
hypnotic effects from inhibition of central excitatory pathways
thiopental elimination half-life
12 hours
anticonvulsant to treat status epilepticus
thiopental
which induction agent may be used for induction of anesthesia in patients with ↑ ICP, as well as the treatment of ↑ ICP that is resistant to hyperventilation alone
thiopental
how does thiopental protect the brain
Cerebrovascular vasoconstriction
This leads to ↓ cerebral blood flow
Subsequent ↓ in intracranial pressure
Decreased cerebral metabolic O2 consumption
what does thiopental stimulate
release of histamine from mast cells
what precipitates with thiopental
succinylcholine, rocuronium, and lidocaine
acute intermittent porphyria
disorder of porphyrin enzyme metabolism, either in the liver or the bone marrow.
all barbiturates can precipitate an attack and must be avoided in patients with a hx of this disorder
5 P’s of AIP
pain in abdomen
polyneuropathy
psychological abnormalities
pink urine
precipitated by medicines (sulfur containing drugs)
methohexital elimination half life
4 hours
which agent can cause proconvulsant activity
methohexital
which is the agent of choice in electroconvulsive therapy
methohexital
methohexital pain on injection?
yes.
methohexital induction dose
1-2 mg/kg IV
20-30 mg/kg rectally
thiopental induction dose
2.5-5 mg/kg IV
reduce dose by 30-35% in elderly
