etomidate

Overview

Etomidate is a carboxylated imidazole derivative
Etomidate consists of two isomers, with the (+) isomer having CNS effects
In the United States it is formulated as a 2 mg/mL propylene glycol (35% by volume) solution with a pH of 6.9
Etomidate is very water insoluble
It is characterized by hemodynamic stability, minimal respiratory depression, cerebral protection, and rapid recovery after either a single bolus or continuous infusion
Clearance for Etomidate is rapid ® 5X faster than thiopental, which accounts for its short elimination half-time
Etomidate is used for
o Induction of anesthesia in patients with cardiovascular disease, reactive airway disease, and intracranial hypertension
o Maintenance of anesthesia
o Sedation
Major Side Effects
o temporary inhibition of steroid synthesis even after a single dose
o pain on injection
o superficial thrombophlebitis
o myoclonus
o PONV

Pharmacokinetics

The pharmacokinetic profile of Etomidate is best described using an open three-compartment model
Important Pharmacokinetic Variables
o Vd_ss = 2.5-4.5 L/kg
o Clearance = 18-25 mL/kg/min
o Alpha Elimination Half-life = 2-4 min
o Beta Elimination Half-life = 3-5 hours
o 75% protein bound
Etomidate is water insoluble, and highly lipid soluble
o In contrast to sodium thiopental, etomidate does not precipitate when mixed with other commonly used anesthetics
Metabolism
o Metabolized by the liver ® ester hydrolysis or N-dealkylation
o Main metabolite is inactive
o 2% of the drug is excreted unchanged, 85% is excreted by the kidneys as metabolites, and 13% is excreted in the bile as metabolites
Effect of an induction dose (bolus) is terminated mainly by redistribution
Etomidate is 75% protein bound ® conditions altering serum proteins (i.e. hepatic or renal disease) can vary the amount of free drug and may cause etomidate to have an exaggerated effect
o -In patients with cirrhosis, the V_d is doubled, but the clearance remains unchanged, resulting in a doubling of the elimination half-life

Pharmacodynamics

CNS
o Primary effect of etomidate on the CNS is hypnosis
§ mechanism of action seems to be similar to propofol, as etomidate modulates GABA_A-receptor transmission
o Etomidate has NO analgesic activity, so it needs to be combined with an analgesic drug
o Etomidate decreases cerebral blood flow by 34% and decreases CMRO₂ by 45%. CPP is maintained or increased, and there is an increase in the cerebral oxygen supply-to-demand ratio
o ICP decreases by 50% in patients with increased ICP (returns to normal values)
o Cerebrovascular reactivity to CO₂is maintained with Etomidate, so hyperventilation may decrease ICP even more
o Etomidate has been associated with grand-mal seizures, and there is a frequent incidence of myoclonic movement during induction (although the two are unrelated)
Respiratory System
o Etomidate is a mild respiratory depressant
o Ventilatory response to CO₂ is depressed with etomidate, but it is still greater than that seen with methohexital
o Induction produces a brief period of hyperventilation, but is followed by a brief period of apnea, which results in an approximately 15% increase in PaCO₂, but no change in PaO₂
Cardiovascular system
o Induction dose results in a minimal change of cardiovascular function
o Myocardial oxygen supply-to-demand ratio is well maintained (both coronary blood flow and myocardial oxygen consumption decrease by similar amounts)

Uses

Induction of anesthesia
o Induction dose ® 0.2-0.6 mg/kg IV
§ Reduced by premedication with an opiate, BDZ, or barbiturate
o Onset of anesthesia is rapid ® equivalent to thiopental or methohexital (15-30 sec)
o Duration of anesthesia related to the dose given - each 0.1 mg/kg given results in 100 sec of LOC
o Recovery after multiple doses or an infusion is still rapid (short context sensitive halftime over a wide range of infusion times)
Maintenace of anesthesia
o Maintenance dose ® 10µg/kg/min IV with N₂O and an opiate
o During an infusion, hemodynamic status is stable, and adequate spontaneous ventilation is present

Side Effects/Contraindications

Endocrine Side Effects ® main reason why etomidate has largely been replaced by propofol
o Long-term infusion results in adrenocortical suppression
§ Dose-dependent reversible inhibition of 11b-hydroxylase (converts 11-deoxycortisol to cortisol) and to a lesser extent 17a-hydroxylase® results in a build-up of cortisol precursors and an increase in ACTH
o Minor adrenocortical suppressive effects seen after single induction dose with etomidate, but no adverse outcomes have been associated with the short-term adrenocortical suppression
o CONTRAINDICATED for prolonged sedation of ICU patients due to adrenocortical suppression and resultant inhibition of mineralcorticoid and corticosteroid production ® subsequent increase in morbidity
Other Side Effects
o When used for induction etomidate may cause
§ nausea/vomiting (30-40% incidence)
§ pain on injection (eliminated by lidocaine prior to injection)
§ myoclonic movement ® incidence is reduced by premedication with an opiate or midazolam given 90 sec before etomidate
§ hiccups
o Superficial thrombophlebitis may occur 48-72 hours after injection (20% incidence when etomidate is given alone through a small needle)

Mild respiratory depression

PO Box 800710

Charlottesville, VA 22908

434-924-2283

Last modified on March 30, 2010