Etomidate
Etomidate Prescribing Information
Etomidate Injection USP is indicated by intravenous injection for the induction of general anesthesia. When considering use of etomidate, the usefulness of its hemodynamic properties (see
Intravenous etomidate is also indicated for the supplementation of subpotent anesthetic agents, such as nitrous oxide in oxygen, during maintenance of anesthesia for short operative procedures such as dilation and curettage or cervical conization.
Do not administer unless solution is clear and container is undamaged. Discard unused portion (see
Etomidate Injection, USP is intended for administration only by the intravenous route (see
Smaller increments of intravenous etomidate may be administered to adult patients during short operative procedures to supplement subpotent anesthetic agents, such as nitrous oxide. The dosage employed under these circumstances, although usually smaller than the original induction dose, must be individualized. There are insufficient data to support this use of etomidate for longer adult procedures or for any procedures in pediatric patients; therefore, such use is not recommended. The use of intravenous fentanyl and other neuroactive drugs employed during the conduct of anesthesia may alter the etomidate dosage requirements. Consult the prescribing information for all other such drugs before using.
Etomidate anesthesia does not significantly alter the usual dosage requirements of neuromuscular blocking agents employed for endotracheal intubation or other purposes shortly after induction of anesthesia.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken by hand.
Etomidate is contraindicated in patients who have shown hypersensitivity to it.
The most frequent adverse reactions associated with use of intravenous etomidate are transient venous pain on injection and transient skeletal muscle movements, including myoclonus:
1. Transient venous pain was observed immediately following intravenous injection of etomidate in about 20% of the patients, with considerable difference in the reported incidence (1.2% to 42%). This pain is usually described as mild to moderate in severity but it is occasionally judged disturbing. The observation of venous pain is not associated with a more than usual incidence of thrombosis or thrombophlebitis at the injection site. Pain also appears to be less frequently noted when larger, more proximal arm veins are employed and it appears to be more frequently noted when smaller, more distal, hand or wrist veins are employed.
2. Transient skeletal muscle movements were noted following use of intravenous etomidate in about 32% of the patients, with considerable difference in the reported incidence (22.7% to 63%). Most of these observations were judged mild to moderate in severity but some were judged disturbing. The incidence of disturbing movements was less when 0.1 mg of fentanyl was given immediately before induction. These movements have been classified as myoclonic in the majority of cases (74%), but averting movements (7%), tonic movements (10%), and eye movements (9%) have also been reported. No exact classification is available, but these movements may also be placed into three groups by location:
a. Most movements are bilateral. The arms, legs, shoulders, neck, chest wall, trunk and all four extremities have been described in some cases, with one or more of these muscle groups predominating in each individual case. Results of electroencephalographic studies suggest that these muscle movements are a manifestation of disinhibition of cortical activity; cortical electroencephalograms, taken during periods when these muscle movements were observed, have failed to reveal seizure activity.
b. Other movements are described as either unilateral or having a predominance of activity of one side over the other. These movements sometimes resemble a localized response to some stimuli, such as venous pain on injection, in the lightly anesthetized patient (averting movements). Any muscle group or groups may be involved, but a predominance of movement of the arm in which the intravenous infusion is started is frequently noted.
c. Still other movements probably represent a mixture of the first two types.
Skeletal muscle movements appear to be more frequent in patients who also manifest venous pain on injection.
Etomidate Injection, USP is a sterile, nonpyrogenic solution. Each milliliter contains etomidate USP, 2 mg, propylene glycol USP, 35% v/v. The pH is 6.0 (4.0 to 7.0).
It is intended for the induction of general anesthesia by intravenous injection.
The drug etomidate is chemically identified as (R)-(+)-ethyl-1-(1-phenylethyl)-1H-imidazole-5-carboxylate and has the following structural formula:
Etomidate is a general anesthetic without analgesic activity. Intravenous injection of etomidate produces anesthesia characterized by a rapid onset of action, usually within one minute. Duration of anesthesia is dose dependent but relatively brief, usually three to five minutes when an average dose of 0.3 mg/kg is employed. Immediate recovery from anesthesia (as assessed by awakening time, time needed to follow simple commands and time to perform simple tests after anesthesia as well as they were performed before anesthesia), based upon data derived from short operative procedures where intravenous etomidate was used for both induction and maintenance of anesthesia, is about as rapid as, or slightly faster than, immediate recovery after similar use of thiopental. These same data revealed that the immediate recovery period will usually be shortened in adult patients by the intravenous administration of approximately 0.1 mg of intravenous fentanyl, one or two minutes before induction of anesthesia, probably because less etomidate is generally required under these circumstances (consult the package insert for fentanyl before using).
The most characteristic effect of intravenous etomidate on the respiratory system is a slight elevation in arterial carbon dioxide tension (PaCO2) (see
Reduced cortisol plasma levels have been reported with induction doses of 0.3 mg/kg etomidate. These persist for approximately 6 to 8 hours and appear to be unresponsive to ACTH administration.
The intravenous administration of up to 0.6 mg/kg of etomidate to patients with severe cardiovascular disease has little or no effect on myocardial metabolism, cardiac output, peripheral circulation or pulmonary circulation. The hemodynamic effects of etomidate have in most cases been qualitatively similar to those of thiopental sodium, except that the heart rate tended to increase by a moderate amount following administration of thiopental under conditions where there was little or no change in heart rate following administration of etomidate. However, clinical data indicates that etomidate administration in geriatric patients, particularly those with hypertension, may result in decreases in heart rate, cardiac index, and mean arterial blood pressure. There are insufficient data concerning use of etomidate in patients with recent severe trauma or hypovolemia to predict cardiovascular response under such circumstances.
Clinical experience and special studies to date suggest that standard doses of intravenous etomidate ordinarily neither elevate plasma histamine nor cause signs of histamine release.
Limited clinical experience, as well as animal studies, suggests that inadvertent intra-arterial injection of etomidate, unlike thiobarbiturates, will not usually be followed by necrosis of tissue distal to the injection site. Intra-arterial injection of etomidate is, however, not recommended.
Etomidate induction is associated with a transient 20% to 30% decrease in cerebral blood flow. This reduction in blood flow appears to be uniform in the absence of intracranial space occupying lesions. As with other intravenous induction agents, reduction in cerebral oxygen utilization is roughly proportional to the reduction in cerebral blood flow. In patients with and without intracranial space occupying lesions, etomidate induction is usually followed by a moderate lowering of intracranial pressure, lasting several minutes. All of these studies provided for avoidance of hypercapnia. Information concerning regional cerebral perfusion in patients with intracranial space occupying lesions is too limited to permit definitive conclusions.
Preliminary data suggests that etomidate will usually lower intraocular pressure moderately.
Etomidate is rapidly metabolized in the liver. Minimal anesthetic plasma levels of unchanged drug are equal to or higher than 0.23 mcg/mL; they decrease rapidly up to 30 minutes following injection and thereafter more slowly with a half-life value of about 75 minutes. Approximately 75% of the administered dose is excreted in the urine during the first day after injection. The chief metabolite is R-(+)-1-(1phenylethyl)-1H-imidazole-5-carboxylic acid, resulting from hydrolysis of etomidate, and accounts for about 80% of the urinary excretion. Limited pharmacokinetic data in patients with cirrhosis and esophageal varices suggest that the volume of distribution and elimination half-life of etomidate are approximately double that seen in healthy subjects.
In clinical studies, elderly patients demonstrated decreased initial distribution volumes and total clearance of etomidate. Protein binding of etomidate to serum albumin was also significantly decreased in these individuals.
Reduced plasma cortisol and aldosterone levels have been reported following induction doses of etomidate. These results persist for approximately 6-8 hours and appear to be unresponsive to ACTH stimulation. This probably represents blockage of 11 beta-hydroxylation within the adrenal cortex.