Etomidate

Question 1

What is the trade name for Etomidate?

Answer 1

Amidate

Question 2

What is the formal drug classification for Etomidate?

Answer 2

• IV general anesthetic
• ultra short acting non-barbiturate hypnotic
• The structure of Etomidate is a carboxylated imidazole

Question 3

What are the clinical uses for Etomidate? (5)

Answer 3

• used for induction and maintenance of anesthesia
• useful in hemodynamically unstable patients and those with poor CV function (pts with baseline low EF or pts with severe hypovolemia)
• may be preferable to Thiopental (and propofol) in patients at risk of circulatory failure
• NO analgesic properties
• may be used in hemodynamically unstable pts with intracranial pathology as it decreases CBF, Cerebral metabolism and ICP with minimal impact on CPP compared to other IV anesthetics

Question 4

What is the MOA of Etomidate?

Answer 4

• Augments the inhibitory tone of GABA in the CNS by binding to the GABAa receptor and increasing the affinity of GABA for the receptor; this subsequently increases chloride conductance and hyperpolarizes the POST-synaptic cell membrane producing hypnosis
• produces rapid induction of anesthesia with minimal CV effects

Question 5

Does Etomidate produce analgesia?

Answer 5

NO

Question 6

What receptor does Etomidate act on?

Answer 6

GABAa

Question 7

How is Etomidate metabolized?

Answer 7

• Clearance is by the liver 18 - 25 ml/kg/min, with hepatic extraction ratio of -.5 +/- 0.9
• Ethyl ester side chain is rapidly metabolized by hydrolysis via hepatic microsomal emzymes and plasma esterases to its carboxylic acid ester, which results in a water soluble, pharmacologically inactive compound
• Liver, ester hydrolysis or N-dealkylation to caroxylic acid
• Biotransformation 5x faster than TPL

Question 8

What are the CardioPulmonary Bypass considerations of Etomidate?

Answer 8

Hypothermic bypass causes an initial decrease of ~34% of plasma etomidate concentration that will return to ~11% of the pre-bypass value, which is then followed by increased metabolism on rewarming
-hepatic blood flow decreases during bypass may be important due to the high liver extraction of etomidate

Question 9

How is Etomidate redistributed?

Answer 9

• Effects of a bolus dose are terminated by redistribution

- Penetrates brain within 1 minute of IV administration

Question 10

What is the elimination route of Etomidate?

Answer 10

Clearance 10 -20 mL/kg/min; 85% renal, 13% Biliary excretion; 2% unchanged

Question 11

What is the volume of distribution of Etomidate?

Answer 11

Distribution 1/2 life - 2.7 min; Redisribution 1/2 life 29 min

Question 12

What is the E 1/2 life of Etomidate?

Answer 12

2.9 - 5.3 hours (3 - 5 hours)

Question 13

How is Vd of Etomidate changed in patients with cirrhosis?

Answer 13

Vd and E 1/2 life is doubled, clearance is normal

Question 14

What does a large Vd suggest of Etomidate?

Answer 14

considerable tissue uptake

Question 15

Is Etomidate protein bound?

Answer 15

75% protein bound

Question 16

What are the side effects of Etomidate? (6)

Answer 16

• Myoclonus due to subcortical disinhibition
• Adrenal Suppression
• N/V
• Venous irritation and superficial thrombophlebitis
• Hiccups
• Unwanted excitatory effects during induction and recovery

Question 17

Explain the side effect of Etomidate causing Adrenal Suppression.

Answer 17

• A single dose suppresses adrenal steroid synthesis for up to 24 hours!!
• Etomidate inhibits 11-B-Hydroxylase, an enzyme important in adrenal steroid production; also inhibits 17-alpha-hydroxylase
• prevents conversion from cholesterol to cortisol
• this has been associated with increased mortality in severly ill patients, therefore should not be used in patients with adrenal insufficiency

Question 18

What are the CV side effects of Etomidate?

Answer 18

-Minimal CV change due to lack of effect on SNS and baroreceptors; no change in BP to decreased, no change in HR

Question 19

What are the respiratory side effects of Etomidate?

Answer 19

Dose dependent, decreased resp rate and tidal volume, transient apnea may occur

• Ventilatory response to CO2 depressed minimally
• hiccups or coughing

Question 20

What pregnancy category is Etomidate?

Answer 20

C

Question 21

What are contraindications to administration of Etomidate?

Answer 21

• Hypersensitivity to Etomidate or any component of the formulation
• Pediatric use not recommended
• Small doses of Etomidate may elicit seizure activity in patients with an underlying seizure disorder

Question 22

What are the drug interactions with Etomidate?

Answer 22

No known drug interactions

Question 23

What is the induction of GA dose for Etomidate?

Answer 23

0.2 - 0.6 mg/kg IV (**0.3mg/kg) over 20-60 seconds **because of this drugs side effects profile, rarely would give it over this dose therefore learn 0.2 - 0.3 mg/kg as induction dose

Question 24

What is the maintenance dose for Etomidate?

Answer 24

5 - 20 mcg/kg/min IV; 10 mcg/kg/min with N2O and an opiate

Question 25

When does Etomidate lose CV protective effects?

Answer 25

when the induction dosing is increased over 0.2 - 0.3 mg/kg!! because of this drugs side effects profile, rarely would give it over this dose therefore learn 0.2 - 0.3 mg/kg as induction dose

Question 26

What should you consider with Etomidate administration in patients undergoing severe stress?

Answer 26

Corticosteroid replacement

Question 27

What is Etomidate a derivative of ?

Answer 27

Carboxylated Imidazole derivative

Question 28

How is Etomidate prepared?

Answer 28

- Propylene glycol solvent - pH 6.9 so it is water soluble in soln? - At physiologic pH, becomes HIGHLY lipid soluble

Question 29

What is important to consider regarding Hepatic clearance of Etomidate?

Answer 29

-High hepatic extraction ratio and clearance: changes in liver blood flow or function will prolong effects

Question 30

What are the CNS pharmacologic effects of Etomidate?

Answer 30

- Rapid loss of consciousness after single dose - NO ANALGESIA - interaction with GABAa receptor - Direct Cerebrovasoconstriction results in decreased CBF, ICP, and CMRO2, and IOP - Increases EEG activity in epileptogenic foci, has rare association with Grand mal seizure and produces myoclonic movement

Question 31

What is the sedative dose of Etomidate?

Answer 31

5-8 mcg/kg/min for short procedure

Question 32

Does Etomidate have any effects on NDMR?

Answer 32

enhances NDMR activity

Question 33

What is a potent side effect of Etomidate?

Answer 33

HIGH incidence of N/V

Question 34

What can administration of Etomidate cause in the IV?

Answer 34

pain on injection and/or thrombophlebitis