Induction Drugs (Etomidate & Ketamine) (Exam II) Flashcards
In general, thiobarbiturates are much more _____ soluble and have a greater _______ than oxybarbiturates.
What atom do thiobarbiturates have in lieu of an oxygen in the second position (like oxybarbiturates)?
- Lipid; potency
- Sulfur
What is unique about Etomidate’s organic chemical structure?
It is the only carboxylated imidazole containing compound.
When is etomidate water-soluble vs lipid-soluble?
- H₂O-soluble at acidic pH.
- Lipid-soluble at physiologic pH.
Compared to propofol, how much analgesia does etomidate produce?
Always a trick question, etomidate has NO pain modulation
* You will need multimodal anesthesia (need opioid use with laryngoscopy/ traceal intubation)
What percentage of etomidate is propylene glycol? What is the result of this?
- 35% propylene glycol resulting in pain on injection.
Which induction agent can be given without an IV? How is this?
Etomidate - can be given sub-lingual.
Etomidate is the only induction drug discussed with direct systemic absorption in oral mucosa that bypasses hepatic metabolism
Why does etomidate have a low incidence of myoclonus?
- Trick Question. Etomidate has a high incidence of myoclonus and actually the highest rate of myoclonus among induction drugs discussed.
- 50% to 80% Etomidate > 17% Thiopental > 13% Methohexital > 6% after propofol
What is the onset of etomidate?
How much of it is protein bound?
What protein does it bind to?
- Onset: 1 minute
- 76% albumin bound
Acidic drugs primarily bind to albumin, while basic drugs primarily bind to alpha-1 acid glycoprotein (AAG) in the bloodstream.
What is etomidate’s Vd?
How does clearance compare to thiopental?
What is the result of this clearance?
- Large Vd
- 5x faster clearance than thiopental resulting in a prompt awakening.
What metabolizes etomidate?
What is the elimination profile?
- CYP450’s AND plasma esterases
- Elimination ½ time = 2-5 hours with 85% via urine and 10 - 13% via bile.
What is the induction dosage range for etomidate?
- 0.2 - 0.4 mg/kg
Our class standard dose will be 0.3mg/kg
What is the best use for etomidate?
- Induction for unstable cardiac patients (Especially with little or no cardiac reserve).
CARDIOPROTECTIVE AGENT
‣ Good for patients with low EF
‣Minimal changes in HR, SV, CO, Contractility
‣ “Caution” SUDDEN HYPOTENSION w/ HYPOVOLEMIA and high 0.45 mg/kg IV induction dose
‣ ❌ histamine or intra-arterial damage
What needs to be used concurrently with etomidate when performing a laryngoscopy? Why?
- Opioids, etomidate has no analgesic effects.
What is Etomidate’s most common side effect?
How often does this occur?
- Involuntary Myoclonic Movements ( 50 - 80 %) of administrations.
Caution: patients with history of seziure activity!
What should be administered with (prior to) etomidate to prevent involuntary myoclonic movements?
Fentanyl 1-2 μg/kg IV or a benzodiazepine
Etomidate causes an alteration in balance of inhibitory and excitatory influences on the thalamocortical tract→myooclonic movements
Etomidate has a dose dependent inhibition of the conversion of cholesterol to _________.
What does this mean clinically?
- Cortisol
- Etomidate decreases SNS capability to respond to stress (longer vent times, hypotension, etc.)
How long does adrenocortical suppression with etomidate last?
What two pathologies would cause you to hesitate before giving etomidate?
- 4-8 hours.
- Sepsis & hemorrhage (anything where you need an intact cortisol response).
Compared to thiopental, etomidate will lower plasma concentrations of what substance?
Cortisol
What are etomidate’s effects on CBF & CMRO₂ ?
Why is this and what does it do?
- Etomidate = ↓CBF & ↓CMRO₂ (coupled response) due to being a direct cerebral vasoconstrictor.
- Will also ↓ICP.
CMRO₂ is couple with both CBF and _______.
CMRG (cerebral metabolic requirement of glucose)
What is the EEG profile of etomidate?
- More excitatory than thiopental
- May activate seizure foci
- Augments SSEP amplitude.
Though etomidate is great for cardiac patients, what condition can result in significant hypotension if not treated prior to induction?
- Hypovolemia
Histamine release via etomidate is mediated through what?
- Trick question. Etomidate does not release histamine.
What is the pulmonary profile of etomidate?
- No change in minute ventilation.
- Less respiratory depression than barbiturates
- Rapid IV produces apnea
- Stimulates CO₂ medullary centers
What type of drug is ketamine?
What type of anesthesia does it produce?
What two properties does it possess?
- Phenycyclidine derivative; NMDA receptor antagonist (PCP; “angel dust”)
- Dissociative anesthesia
- Amnestic & intense analgesia
What signs and symptoms does dissociative anesthesia (ketamine) produce?
“Zonked” state
- Non-communicative but awake
- Hyptonus & purposeful movements
- Eyes open but “no one’s home”.
What are ketamine’s two greatest advantages over propofol or etomidate?
- No pain at injection (no propylene glycol)
- Profound analgesia at sub-anesthetic doses.
What are the two greatest disadvantages of ketamine?
- Emergence delirium
- Abuse potential
AKA Psychedelic Effects in 5% to 30% of patients
- Can be prevented by giving benzo 5 min prior or when giving precedex/clonidine concurrently
What is Benzethonium Chloride? What is it’s relevance?
- Ketamine preservative that inhibits ACh receptors
Differentiate S(+)Ketamine vs R(-)Ketamine.
S-Ketamine (left-handed isomer) essentially better version of R-Ketamine
- More intense analgesia
- ↑metabolism & recovery
- Less salivation
- Lower emergence delirium
What benefits does a racemic ketamine mixture offer?
- Less fatigue & cognitive impairment
- Inhibits catecholamine reuptake at nerve endings (like cocaine).
What is Ketamine’s main mechanism of action?
- Non-competitive inhibition of NMDA (N-methyl-D-aspartate) receptors by inhibiting pre-synaptic release of glutamate.
- Glutamate (most abundant excitatory neurotransmitter in CNS)
- Glycine is an obligatory co-agonist.
What are Ketamine’s secondary receptor sites?
- Weak GABAA effects.
- Opioid (μ, δ, and κ)
What is Ketamine’s time of onset? (IV & IM)
When would this drug be utilized IM?
- IV: 1 min
- IM: 5 min (mostly for pediatric patients)
What is Ketamine’s duration of action?
What about its lipid solubility?
What is the result of this?
- 10-20 min
- Highly lipid soluble (5-10x greater than thiopental).
- Results: Brain → non plasma bound → peripheral tissue.
What is the Vd and E½ time of ketamine?
- Vd = 3L/kg
- E ½ = 2-3 hours
Name the pharmacokinetic profile of ketamine:
- Clearance:
- Metabolism:
- Excretion:
- Clearance: high hepatic clearance (1L/min)
- Metabolism: CYP450’s.
- Excretion: kidneys
What is the primary metabolite of ketamine and what its its significance?
Norketamine is metabolite (⅓ potency and prolongs analgesia).
In what patient population is ketamine tolerance most often seen?
Burn patients
What is the induction dose of ketamine IV?
What if it is given intramuscularly?
- 0.5 - 1.5 mg/kg IV
- 4 - 8 mg/kg IM
What is the maintenance dosing of ketamine?
- 0.2 - 0.5 mg/kg IV
- 4 - 8 mg/kg IM
What is the subanesthetic/analgesic dose of ketamine?
- 0.2 - 0.5 mg/kg IV
What is the post-operative sedation and analgesia dosing for ketamine in pediatric cardiac surgery cases?
1-2 mg/kg/hour
What is the neuraxial epidural analgesia dosing of ketamine?
What about intrathecal route?
- 30mg epidural
- 5 - 50 mg via intrathecal/spinal/subarachnoid
Neuraxial anesthesia involves the administration of medications directly into or around the spinal cord to produce anesthesia or analgesia.
* Neuraxial refers to the CNS overall, while intrathecal refers to a specific space within the CNS.
Ketamine is a potent sialagogue. What does this mean for your clinical practice?
- Manage excessive secretions during intubation & watch for coughing/laryngospasm.
What drug and dosing of said drug should be used to treat excessive salivary secretions from ketamine administration?
Glycopyrrolate: 0.2mg
Glyco>atropine or scopalamine b/c no sedation
You gave ketamine and the patient fell asleep within 30 seconds. If you gave no more doses when would you expect the patient to:
- Wake up?
- Be fully conscious?
- Start remembering things?
- Wake up in 10-20 minutes
- Full consciousness in 60 - 90 min
- Amnestic effects should also wear off in 60 - 90 min.
What patient populations is ketamine best used for?
- Acutely hypovolemic patients
- Asthmatics
- Mental health patients
Ketamine produces an SNS-like response which is usually great in trauma (especially compared to potential hypotension with propofol/etomidate). Also, asthmatics like having a patent airway so there is that.
When would you do an IM induction of a patient?
- Uncooperative and difficult-to-manage mentally challenged patients.
Though ketamine has many indications, when should it be avoided?
- Patients with pulmonary HTN and ↑ICP.
B/C of the SNS-like response, ketamine will increase CBF substantially (up to 60%) and cause and increase in ICP. Caution in PulmHTN as well due to increaing pressures.
What are Ketamine’s effects on ICP? Why?
- ↑ICP via ↑CBF by 60% (uncoupled)
- Potent cerebral vasodilator.
At what dosing will the ICP increasing effects of ketamine plateau?
- 0.5-2mg/kg IV
Ketamine has a ceiling effect on ICP
Due to ketamine’s increased excitatory EEG activity, how much does seizure potential increase with administration?
Trick question. No increase in seizure potential with ketamine.
Increased amplitude with SSEP —> reduced by N20
What does the cardiovascular profile of ketamine look like?
How can this side effect profile be blunted?
- SNS stimulation ( ↑ in sBP, PAP, HR, CO, etc.)
- Blunted via pre-med with benzo’s, volatiles, or nitrous.
Say you just gave ketamine and you have an unexpected drop in systolic BP and CO. What happened? How do you treat it?
- Depleted catecholamine stores
- Treat with direct-acting SNS agents (ex. phenylephrine) vs indirect (ex. ephedrine).
If the patient has exhausted their own catecholamines, giving an indirect agonist (ephedrine) won’t matter. You can’t tell the body to give you something that isn’t there right?
What is the Pulmonary profile of ketamine?
- No depression of ventilation with CO₂ response maintained.
- ↑ salivary excretion
- Intact upper airway tone & reflexes.
- Bronchodilator with no histamine release.
Be sure to manage the salivation with an antisialagogue (glyco) as needed.
What does emergence delirium present like with ketamine?
- Visual, auditory, proprioceptive illusions. Morbid & vivid dreams up to 24 hours.
What is the proposed physiologic mechanism of action for emergence delirium occurrence with ketamine?
Depression of inferior colliculus & medial geniculate nucleus.
What percentage of patients will develop ketamine induced emergence delirium?
How can it be prevented?
- Psychedelic effects in 5 - 30% of patients.
- Pre-med with midazolam & glycopyrrolate.
What “other systems” effects does ketamine have?
- Non-depolarizing NMBs enhancement.
- Succinylcholine prolongation via plasma cholinesterase inhibition.
- PLT aggregation inhibition
What are ketamine’s most common drug interactions?
- Volatiles → hypotension
- Non-depolarizing NMBs → enhancement
- Succinylcholine → prolongation
Why does ketamine prolong succinylcholine’s effects?
Ketamine is a plasma cholinesterase inhibitor.
Which induction agent has the highest analgesic properties?
- Ketamine
Why would ketamine be a decent induction drug for an OSA patient? Why not?
- Preservation of upper airway reflexes & ventilatory function.
- Sialagogue.
Good luck intubating a 20”+ neck, 400lb patient with extra saliva in the way.
