Induction Drugs (Etomidate/Ketamine) (2)

Question 1

What is the chemical structure of etomidate?

Answer 1

The only carboxylated imidazole containing compound

Question 2

What type of drug is etomidate (weak acid or weak base)? When is it water/lipid soluble?

Answer 2

Weak base
Water soluble at acidic pH
Lipid soluble at physiologic pH (basic)

Question 3

Etomidate is ___% propylene glycol

Answer 3

35: pain at injection and venous irritation

Prevent by giving lidocaine before

Question 4

Etomidate has a high incidence of ________.

Answer 4

myoclonus: involuntary movements

Question 5

Why is etomidate good for peds?

Answer 5

Only drug with direct systemic absorption in oral mucosa that bypasses hepatic metabolism

Question 6

What is the MOA of etomidate?

Answer 6

Indirectly/directly open Cl- channels of GABA(A) receptors

Cell hyper polarization

Question 7

What is the onset for etomidate?

Answer 7

1 minute after IV push

Question 8

Is etomidate protein bound? How does this effect its clearance?

Answer 8

76% albumin bound but clearance 5x faster than thiopental

Prompt awakening

Question 9

How is etomidate metabolized?

Answer 9

Hydrolysis (hepatic microsomal enzymes and plasma esterases)

Question 10

What effect does etomidate have on liver and renal patients?

Answer 10

Does not have negative effect since its not metabolized by CYP450

Question 11

How is etomidate eliminated?

Answer 11

85% urine
10-13% bile

Question 12

What is the half life of etomidate?

Answer 12

2-5 hours

Question 13

What is the time to peak drug effect for etomidate?

Answer 13

2 min

Question 14

What is etomidate dose?

Answer 14

0.3 mg/kg IV

Question 15

What patient group is etomidate best for?

Answer 15

Best with unstbale CV system; especially with little/no cardiac reserve

Question 16

What needs to be given with etomidate during induction?

Answer 16

No analgesic effects

Opioid during induction

Question 17

What causes myoclonic movement from etomidate? How can these movement be decreased?

Answer 17

An alteration in balance of inhibitory and excitatory influences on the thalamocortical tract.

Prior admin of opioids or benzos (fent1-2mcg/kg or versed)

Question 18

How do the induction meds rank from most likely to cause myoclonus to least?

Answer 18

Etomidate (50-80%)
Thiopental (17%)
Methohexital (13%)
Propofol (6%)

caution with seizure history

Question 19

Answer 19

1.5mL

Question 20

What are adverse side effects of etomidate?

Answer 20

Adrenocortical supression: dose dependent inhibition of conversion of cholesterol to cortisol
→causes severe hypotension, longer mechanical ventilation
→enzyme inhibition lasts 4-8 hours after initial dose
→caution with sepsis/hemorrhage (need intact cortisol)

without stress hormone there is no drive from adrenal medulla to produce catecholamines and not enough CO2 drive for patient to spontaneously breathe

Question 21

What is the time associated with decrease cortisol levels after etomidate is given? What need to be given?

Answer 21

0-4 hours

Need to supplement with steroids

Question 22

CNS side effects of Etomidate:

Answer 22

Decreased CBF/CMRO2 35-45%
potent direct cerebral vasoconstrictor (decreases ICP)
More frequent excitatory spikes on EEG
May increase amplitude of SSEP

Question 23

How does etomidate affect CV system?

Answer 23

Minimal changes to HR, SV, CO, contractility

decreases PAP

Mild decrease in MAP d/t decrease SVR

hypotension with hypovolemia (with high 0.45mg/kg induction dose)

Question 24

How does etomidate affect ventilation?

Answer 24

More vent depressant than barbs
Apnea with rapid IV injection
Stimulates CO2 medullary centers (start breathing on own sooner)
VT decreases but offset by increase in rate (only last 3-5 min)

Question 25

What is the main use for ketamine?

Answer 25

Analgesia→blocks and helps with pain

Question 26

What are some characteristics of ketamine?

Answer 26

Question 27

What is a concern with hypertonus from ketamine?

Answer 27

Potential for rhabdo

Question 28

What are some reasons why ketamine is better than etomidate or propofol?

Answer 28

No pain at injection site Profound analgesia at subanesthetic doses

Question 29

What are disadvantages of ketamine?

Answer 29

Emergence delirium Abuse

Question 30

What is the preservative in ketamine?

Answer 30

Benzethonium chloride

Question 31

What are properties of S ketamine?

Answer 31

Question 32

What are properties of R ketamine?

Answer 32

Question 33

Which isomer is the most commonly used version of ketamine?

Answer 33

Racemic mixture is most common

Question 34

What is the MOA of ketamine?

Answer 34

Binds non-competitively to N-methyl-D-aspartate (NMDA) receptors Inhibits NMDA receptor activation by glutamate and decreases presynaptic release of glutamate Glycine is co-agonist

Question 35

What is the most abundant excitatory neurotransmitter in the CNS?

Answer 35

Glutamate

Question 36

What are other receptor sites for ketamine?

Answer 36

opioid (µ, δ, and κ; weak σ), monoaminergic, muscarinic, and voltage-sensitive sodium and L-type calcium channels & neuronal nicotinic acetylcholine receptors →analgesic effects

Question 37

Ketamine has weak actions at ________ receptors.

Answer 37

GABA(A)

Question 38

What side effect of ketamine can be mitigated by giving antimuscarinic to minimize?

Answer 38

Salivation

Question 39

What is the onset and peak plasma concentrations of ketamine?

Answer 39

rapid onset (similar to thiopental) peak plasma conc at 1 min after IV, 5min IM

Question 40

What is ketamines duration of action?

Answer 40

10-20 min 60-90 min to return to full orientation

Question 41

Is ketamine plasma protein bound?

Answer 41

High lipid solubility (5-10x thiopental) and not protein bound→ distributes to tissues

Question 42

What is the Vd for ketamine? What is the elimination half time?

Answer 42

Large: 2.5-3.5 L/kg E1/2 time: 2-3 hours

Question 43

How is ketamine processed and cleared?

Answer 43

High hepatic clearance rate (1L/min) Metabolized by CYP450 Excreted by kidneys

Question 44

Does ketamine produce metabolites?

Answer 44

Yes, Norketamine: 1/3-1/5 potency→causes prolonged anesthesia

Question 45

When can tolerance develop with ketamine?

Answer 45

With burn patients

Question 46

What is the ketamine induction dose for IV, IM, and PO?

Answer 46

0.5-1.5 mg/kg IV 4-8 mg/kg IM 10 mg/kg PO

Question 47

What is maintenance doing for ketamine IV and IM?

Answer 47

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

Question 48

What is the subanesthetic (analgesic) dose for ketamine?

Answer 48

0.2-0.5 mg/kg IV

Question 49

What is the Post op sedation and analgesia dose for ketamine?

Answer 49

1-2 mg/kg/hr (pediatric cardiac surgery)

Question 50

What is the dose of ketamine for neuraxial analgesia?

Answer 50

30 mcg epidural 5-50 mg in 3 mL of saline intrathecal/spinal/subarachnoid

Question 51

What is the best med to use in conjunction with ketamine to reduce salivary secretions with induction?

Answer 51

Antisialagogue preop med Glycopyrrolate: better because doesnt cross BB so no emergence delirium can use atropine/scopolamine (emergence delirium)

Question 52

What are the loss of consciousness effects with ketamine induction for IV and IM?

Answer 52

IV: 30sec-1min IM: 2-5 min

Question 53

When does return of consciousness occur after ketamine induction?

Answer 53

10-20 min full consciousness 60-90 min

Question 54

How long does amnesia persist after return of consciousness post ketamine admin?

Answer 54

60-90min

Question 55

Answer 55

4mL

Question 56

Which anesthetics have a favorable influence on bronchomotor tone?

Answer 56

Question 57

What are the clinical uses for ketamine? What patient populations?

Answer 57

Acutely hypovolemic patients (stimulates SNS) Asthmatic and MH patients: bronchodilator

Question 58

What is the "coronary artery disease cocktail"?

Answer 58

Diazepam: 0.5mg/kg IV Ketamine: 0.5mg/kg IV Continuous ketamine infusion: 15-30mcg/kg/min

Question 59

How is ketamine given for pediatric induction?

Answer 59

Can be given IM

Question 60

When is ketamine clinically indicated?

Answer 60

Burn dressing changes, debridements, skin grafting procedures Reversal of opioid tolerance Improvement of psych disorders (depression, PTSD, OCD) Restless leg syndrome (PO dose)

Question 61

What patient population is ketamine avoided in or used with caution?

Answer 61

Pulmonary: systemic/pulm HTN Neuro: increased ICP (cerebral vasodilator)

Question 62

What are CNS side effects of ketamine?

Answer 62

Potent cerebral vasodilator (graph shows modest decrease in ICP--low dose better to prevent increase ICP) Increases CBF by 60%

Question 63

What ketamine dosage prevents further increases in ICP?

Answer 63

0.5-2mg/kg IV

Question 64

Ketamine can cause _________ amplitude with SSEP. This can be reduced by _______.

Answer 64

Increased, N2O

Question 65

What are CV side effects of ketamine?

Answer 65

Resembles SNS stimulation: increase SBP, PAP, HR, CO, MRO2 increases plasma epi and NE levels

Question 66

How are CV effects of ketamine blunted?

Answer 66

Pre-med with benzo or inhaled anesthetic and N2O

Question 67

What does it mean if a patient on ketamine has unexpected drop in SBP and CO?

Answer 67

Catecholamine stores are depleted→direct myocardial depressant

Question 68

What CV factors remain constant when using ketamine?

Answer 68

SV, SVR, LVEDP,

Question 69

What are respiratory side effects of ketamine?

Answer 69

No significant depression of ventilation Ventilatory response to C02 is maintained PaCO2 is unlikely to increase more than 3 mmHg. Upper airway skeletal muscle tone and reflexes maintained & intact ↑ salivary and tracheobronchial mucous gland secretions: give antimuscarinic ✅ ✅ ✅ Bronchodilator activity; no histamine release.

Question 70

What percent of patients are have emergence delirium (psychedelic effects) from ketamine? What are the S/S?

Answer 70

5-30% visual, auditory, proprioceptive, and confusional illusions morbid/vivd dreams in color and hallucinations up to 25hrs

Question 71

What is the MOA of ketamine causing emergence delirium?

Answer 71

Depression of the inferior colliculus and medial geniculate nucleus

Question 72

How can emergence delirium from ketamine be avoided?

Answer 72

Benzo IV 5 minutes prior OR clonidine and precedex (Alpa 2 agonists)

Question 73

What are other potential side effects of ketamine?

Answer 73

Inhibit platelet aggregation Inhibit cytosolic free CA++ conc. Prolongs apnea from Succinylcholine (inhibit plasma cholinesterases?)

Question 74

What drug interactions does ketamine have?

Answer 74

Volatile anesthetic (Iso/Sevo/Des) →hypotension Non-Depolarizing Neuro Muscular Blocker (NDNMB) drugs →enhanced Succinylcholine →prolonged

Question 75

What are the risks and benefits of ketamine use for OSA?

Answer 75

Risks: Psychiatric Effects, SNS activation, hypersalivation Benefits: Upper airway preservation and ventilatory function

Question 76

Answer 76

C) Ketamine

Question 77

The mixing of _______ with any other drug is not recommended

Answer 77

Propofol: its not chiral

Question 78

When you draw up drugs you must give them within ___ hours.

Answer 78

4