Induction Drugs (Etomidate & Ketamine) (Exam II)

Question 1

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)?

Answer 1

• Lipid; potency
• Sulfur

Question 2

What is unique about Etomidate’s organic chemical structure?

Answer 2

It is the only carboxylated imidazole containing compound.

Question 3

When is etomidate water-soluble vs lipid-soluble?

Answer 3

Etomidate is a weak base
- H₂O-soluble at acidic pH.
- Lipid-soluble at physiologic pH.

Question 4

Compared to propofol, how much analgesia does etomidate produce?

Answer 4

Always a trick question, etomidate has NO pain modulation
* You will need multimodal anesthesia (need opioid use with laryngoscopy/ traceal intubation)

Question 5

What percentage of etomidate is propylene glycol? What is the result of this?

Answer 5

• 35% propylene glycol resulting in pain on injection.

Question 6

Which induction agent can be given without an IV? How is this?

Answer 6

Etomidate - can be given sub-lingual.

Etomidate is the only induction drug discussed with direct systemic absorption in oral mucosa that bypasses hepatic metabolism

Question 7

Why does etomidate have a low incidence of myoclonus?

Answer 7

• 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

Question 8

What is the onset of etomidate?
How much of it is protein bound?
What protein does it bind to?

Answer 8

• Onset: 1 minute
• 76% albumin bound

Genearally, acidic drugs primarily bind to albumin, while basic drugs primarily bind to alpha-1 acid glycoprotein (AAG) in the bloodstream.

Question 9

What is etomidate’s Vd?
How does clearance compare to thiopental?
What is the result of this clearance?

Answer 9

• Large Vd
• 5x faster clearance than thiopental resulting in a prompt awakening.

Question 10

What metabolizes etomidate?
What is the elimination profile?

Answer 10

• CYP450’s AND plasma esterases (pretty nice for liver patients?)
• Elimination ½ time = 2-5 hours with 85% via urine and 10 - 13% via bile.

Question 11

What is the induction dosage range for etomidate?

Answer 11

• 0.2 - 0.4 mg/kg

Our class standard dose will be 0.3mg/kg

Question 12

What is the best use for etomidate?

Answer 12

• 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

Question 13

What needs to be used concurrently with etomidate when performing a laryngoscopy? Why?

Answer 13

• Opioids, etomidate has no analgesic effects.

Question 14

What is Etomidate’s most common side effect?
How often does this occur?

Answer 14

• Involuntary Myoclonic Movements ( 50 - 80 %) of administrations.

Caution: patients with history of seziure activity!

Question 15

What should be administered with (prior to) etomidate to prevent involuntary myoclonic movements?

Answer 15

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

Question 16

Etomidate has a dose dependent inhibition of the conversion of cholesterol to _________.
What does this mean clinically?

Answer 16

• Cortisol
• Etomidate decreases SNS capability to respond to stress (longer vent times, hypotension, etc.)

Question 17

How long does adrenocortical suppression with etomidate last?
What two pathologies would cause you to hesitate before giving etomidate?

Answer 17

• 4-8 hours.
• Sepsis & hemorrhage (anything where you need an intact cortisol response).

Question 18

Compared to thiopental, etomidate will lower plasma concentrations of what substance?

Answer 18

Cortisol

Question 19

What are etomidate’s effects on CBF & CMRO₂ ?
Why is this and what does it do?

Answer 19

• Etomidate = ↓CBF & ↓CMRO₂ (coupled response) due to being a direct cerebral vasoconstrictor.
• Will also ↓ICP.

Question 20

CMRO₂ is couple with both CBF and _______.

Answer 20

CMRG (cerebral metabolic requirement of glucose)

Question 21

What is the EEG profile of etomidate?

Answer 21

• More excitatory than thiopental
• May activate seizure foci
• Augments SSEP amplitude.

Question 22

Though etomidate is great for cardiac patients, what condition can result in significant hypotension if not treated prior to induction?

Answer 22

• Hypovolemia

Question 23

Histamine release via etomidate is mediated through what?

Answer 23

• Trick question. Etomidate does not release histamine.

Question 24

What is the pulmonary profile of etomidate?

Answer 24

• No change in minute ventilation.
• Less respiratory depression than barbiturates
• Rapid IV produces apnea
• Stimulates CO₂ medullary centers

Question 25

What type of drug is ketamine? What type of anesthesia does it produce? What two properties does it possess?

Answer 25

- Phenycyclidine derivative; NMDA receptor antagonist (PCP; "angel dust") - Dissociative anesthesia - Amnestic & intense analgesia

Question 26

What signs and symptoms does dissociative anesthesia (ketamine) produce?

Answer 26

**"Zonked" state** - Non-communicative but awake - Hyptonus & purposeful movements - Eyes open but "no one's home".

Question 27

What are ketamine's two greatest advantages over propofol or etomidate?

Answer 27

- No pain at injection (no propylene glycol) - Profound analgesia at sub-anesthetic doses.

Question 28

What are the two greatest disadvantages of ketamine?

Answer 28

- Emergence delirium - Abuse potential ## Footnote AKA Psychedelic Effects in 5% to 30% of patients - Can be prevented by giving benzo 5 min prior or when giving precedex/clonidine concurrently

Question 29

What is Benzethonium Chloride? What is it's relevance?

Answer 29

- Ketamine preservative that inhibits ACh receptors

Question 30

Differentiate S(+)Ketamine vs R(-)Ketamine.

Answer 30

S-Ketamine (left-handed isomer) essentially better version of R-Ketamine - More intense analgesia - ↑metabolism & recovery - Less salivation - Lower emergence delirium

Question 31

What benefits does a racemic ketamine mixture offer?

Answer 31

- Less fatigue & cognitive impairment - Inhibits catecholamine reuptake at nerve endings (like cocaine).

Question 32

What is Ketamine's main mechanism of action?

Answer 32

- Non-competitive inhibition of NMDA (N-methyl-D-aspartate) receptors by inhibiting pre-synaptic release of **glutamate.** ## Footnote * Glutamate (most abundant excitatory neurotransmitter in CNS) * Glycine is an obligatory co-agonist.

Question 33

What are Ketamine's secondary receptor sites?

Answer 33

- Weak GABA_A effects. - Opioid (μ, δ, and κ)

Question 34

What is Ketamine's time of onset? (IV & IM) When would this drug be utilized IM?

Answer 34

- IV: 1 min - IM: 5 min (mostly for pediatric patients)

Question 35

What is Ketamine's duration of action? What about its lipid solubility? What is the result of this?

Answer 35

- 10-20 min - Highly lipid soluble (5-10x greater than thiopental). - Results: Brain → non plasma bound → peripheral tissue.

Question 36

What is the Vd and E½ time of ketamine?

Answer 36

- Vd = 3L/kg - E ½ = 2-3 hours

Question 37

Name the pharmacokinetic profile of ketamine: - Clearance: - Metabolism: - Excretion:

Answer 37

- Clearance: high hepatic clearance (1L/min) - Metabolism: CYP450's. - Excretion: kidneys

Question 38

What is the primary metabolite of ketamine and what its its significance?

Answer 38

Norketamine is metabolite (⅓ potency and prolongs analgesia).

Question 39

In what patient population is ketamine tolerance most often seen?

Answer 39

Burn patients

Question 40

What is the induction dose of ketamine IV? What if it is given intramuscularly?

Answer 40

- 0.5 - 1.5 mg/kg IV - 4 - 8 mg/kg IM

Question 41

What is the maintenance dosing of ketamine?

Answer 41

- 0.2 - 0.5 mg/kg IV - 4 - 8 mg/kg IM

Question 42

What is the subanesthetic/analgesic dose of ketamine?

Answer 42

- 0.2 - 0.5 mg/kg IV

Question 43

What is the post-operative sedation and analgesia dosing for ketamine in pediatric cardiac surgery cases?

Answer 43

1-2 mg/kg/**hour**

Question 44

What is the neuraxial epidural analgesia dosing of ketamine? What about intrathecal route?

Answer 44

- 30mg epidural - 5 - 50 mg via intrathecal/spinal/subarachnoid ## Footnote 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.

Question 45

Ketamine is a potent sialagogue. What does this mean for your clinical practice?

Answer 45

- Manage excessive secretions during intubation & watch for coughing/laryngospasm.

Question 46

What drug and dosing of said drug should be used to treat excessive salivary secretions from ketamine administration?

Answer 46

**Glycopyrrolate: 0.2mg** ## Footnote Glyco>atropine or scopalamine b/c no sedation

Question 47

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?

Answer 47

- Wake up in 10-20 minutes - Full consciousness in 60 - 90 min - Amnestic effects should also wear off in 60 - 90 min.

Question 48

What patient populations is ketamine best used for?

Answer 48

- Acutely hypovolemic patients - Asthmatics - Mental health patients ## Footnote 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.

Question 49

When would you do an IM induction of a patient?

Answer 49

- Uncooperative and difficult-to-manage mentally challenged patients.

Question 50

Though ketamine has many indications, when should it be avoided?

Answer 50

- Patients with **pulmonary HTN and ↑ICP**. ## Footnote 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.

Question 51

What are Ketamine's effects on ICP? Why?

Answer 51

- ↑ICP via ↑CBF by 60% (uncoupled) - **Potent cerebral vasodilator**.

Question 52

At what dosing will the ICP increasing effects of ketamine plateau?

Answer 52

- 0.5-2mg/kg IV ## Footnote Ketamine has a ceiling effect on ICP

Question 53

Due to ketamine's increased excitatory EEG activity, how much does seizure potential increase with administration?

Answer 53

Trick question. **No increase in seizure potential with ketamine**. ## Footnote Increased amplitude with SSEP ---> reduced by N20

Question 54

What does the cardiovascular profile of ketamine look like? How can this side effect profile be blunted?

Answer 54

- SNS stimulation ( ↑ in sBP, PAP, HR, CO, etc.) - Blunted via pre-med with benzo's, volatiles, or nitrous.

Question 55

Say you just gave ketamine and you have an unexpected drop in systolic BP and CO. What happened? How do you treat it?

Answer 55

- Depleted catecholamine stores - **Treat with direct-acting SNS agents (ex. phenylephrine)** vs indirect (ex. ephedrine). ## Footnote 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?

Question 56

What is the Pulmonary profile of ketamine?

Answer 56

- No depression of ventilation with CO₂ response maintained. - ↑ salivary excretion - **Intact upper airway tone & reflexes**. - **Bronchodilator with no histamine release**. ## Footnote Be sure to manage the salivation with an antisialagogue (glyco) as needed.

Question 57

What does emergence delirium present like with ketamine?

Answer 57

- Visual, auditory, proprioceptive illusions. Morbid & vivid dreams up to 24 hours.

Question 58

What is the proposed physiologic mechanism of action for emergence delirium occurrence with ketamine?

Answer 58

Depression of inferior colliculus & medial geniculate nucleus.

Question 59

What percentage of patients will develop ketamine induced emergence delirium? How can it be prevented?

Answer 59

- Psychedelic effects in **5 - 30%** of patients. - **Pre-med with midazolam & glycopyrrolate**.

Question 60

What "other systems" effects does ketamine have?

Answer 60

- **Non-depolarizing NMBs enhancement.** - **Succinylcholine prolongation via plasma cholinesterase inhibition.** - PLT aggregation inhibition

Question 61

What are ketamine's most common drug interactions?

Answer 61

- Volatiles → hypotension - Non-depolarizing NMBs → enhancement - Succinylcholine → prolongation

Question 62

Why does ketamine prolong succinylcholine's effects?

Answer 62

Ketamine is a plasma cholinesterase inhibitor.

Question 63

Which induction agent has the highest analgesic properties?

Answer 63

- Ketamine

Question 64

Why would ketamine be a decent induction drug for an OSA patient? Why not?

Answer 64

- Preservation of upper airway reflexes & ventilatory function. - Sialagogue. ## Footnote Good luck intubating a 20"+ neck, 400lb patient with extra saliva in the way.

Question 65

According to sterile compounding practices (referencing USP 797), how long do we have to administer a drug once we, the CRNA, hascompounded it?

Answer 65

4 hours - This is a recenct change as the previous gideline gave us only 1 hour. - Maintain antiseptic practices when compounding your drugs to keep your patient safe.