Etomidate

Etomidate is a prescription medication used as anesthesia during surgery.  Etomidate belongs to a group of drugs called general anesthetics.  These work to put you to sleep during surgery.

This medication is available in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects of etomidate include injection site pain, muscle movements, and changes in breathing.

Sedative and hypnotic agent.1 2

• It is used to put you to sleep for surgery.
• It may be given to you for other reasons. Talk with the doctor.

• Tell all of your health care providers that you take etomidate. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until the effects of this medicine wear off and you feel fully awake.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• If you are 65 or older, use etomidate with care. You could have more side effects.
• Studies in young animals and children have shown that frequent or long-term use of anesthesia drugs or drugs used for sleep in children younger than 3 years of age may lead to long-term brain problems. This may also happen in unborn babies if the mother uses this medicine during the third trimester of pregnancy. Talk with the doctor.
• Use with care in children. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using etomidate while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

• If you need to store etomidate at home, talk with your doctor, nurse, or pharmacist about how to store it.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Etomidate have not been completed.

Studies to evaluate the mutagenic potential of Etomidate have not been completed.

In a fertility and early embryonic development study in which male and female rats were treated intravenously with 0.31, 1.25, and 5 mg/kg/day Etomidate (0.17, 0.68, and 2.7 times the human induction dose of 0.3 mg/kg based on body surface area) prior to mating, no adverse effects on fertility were noted.

Pregnancy

There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, fetal deaths and reduced pup survival were noted after intravenous administration of Etomidate to pregnant rats at doses 0.17 times the human induction dose of 0.3 mg/kg. Reduced pup survival was noted after intravenous administration of Etomidate to pregnant rabbits at 1.6 times the human induction dose. Published studies in pregnant primates demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity during the period of peak brain development increases neuronal apoptosis in the developing brain of the offspring when used for longer than 3 hours. There are no data on pregnancy exposures in primates corresponding to periods prior to the third trimester in humans [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Animal Data

No malformations or adverse fetal effects were noted in a study in which pregnant rats were intravenously administered 0.31, 1.25, or 5 mg/kg/day Etomidate (0.17, 0.68, or 2.7 times the human induction dose of 0.3 mg/kg based on body surface area) during organogenesis (Gestation Days 6 to 15).

Reduced pup survival was noted in all doses tested in a study in which pregnant rabbits were intravenously administered 1.5 or 4.5 mg/kg/day Etomidate (1.6 or 4.9 times the human induction dose of 0.3 mg/kg based on body surface area) during organogenesis (Gestation Day 6 to 18). These doses also produced maternal toxicity (increased mortality).

Increased still born fetuses and decreased pup survival was noted at all doses tested in a study where pregnant rats were intravenously administered 0.31, 1.25, or 5 mg/kg/day Etomidate (0.17, 0.68, or 2.7 times the human induction dose of 0.3 mg/kg based on body surface area) during gestation and throughout lactation (Gestation Day 16 through Lactation Day 21). These doses also produced maternal toxicity (decreased food consumption and increased mortality). In this study, offspring were not evaluated for sexual maturation, neurobehavioral function including learning and memory, or reproductive function.

In a published study in primates, administration of an anesthetic dose of ketamine for 24 hours on Gestation Day 122 increased neuronal apoptosis in the developing brain of the fetus. In other published studies, administration of either isoflurane or propofol for 5 hours on Gestation Day 120 resulted in increased neuronal and oligodendrocyte apoptosis in the developing brain of the offspring. With respect to brain development, this time period corresponds to the third trimester of gestation in the human. The clinical significance of these findings is not clear; however, studies in juvenile animals suggest neuroapoptosis correlates with long-term cognitive deficits (see WARNINGS, Pediatric Neurotoxicity, PRECAUTIONS, Pregnancy, and ANIMAL TOXICOLOGY AND/OR PHARMACOLOGY).

Labor and Delivery

There are insufficient data to support use of intravenous Etomidate in obstetrics, including Caesarean section deliveries. Therefore, such use is not recommended.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Etomidate is administered to a nursing mother.

Pediatric Use

There are inadequate data for Etomidate to make dosage recommendations for induction of anesthesia in patients below the age of ten (10) years; therefore, such use is not recommended (see also DOSAGE AND ADMINISTRATION).

Published juvenile animal studies demonstrate that the administration of anesthetic and sedation drugs, such as Etomidate, that either block NMDA receptors or potentiate the activity of GABA during the period of rapid brain growth or synaptogenesis, results in widespread neuronal and oligodendrocyte cell loss in the developing brain and alterations in synaptic morphology and neurogenesis. Based on comparisons across species, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately 3 years of age in humans.

In primates, exposure to 3 hours of ketamine that produced a light surgical plane of anesthesia did not increase neuronal cell loss, however, treatment regimens of 5 hours or longer of isoflurane increased neuronal cell loss. Data from isoflurane-treated rodents and ketamine-treated primates suggest that the neuronal and oligodendrocyte cell losses are associated with prolonged cognitive deficits in learning and memory. The clinical significance of these nonclinical findings is not known, and healthcare providers should balance the benefits of appropriate anesthesia in pregnant women, neonates, and young children who require procedures with the potential risks suggested by the nonclinical data (see WARNINGS, Pediatric Neurotoxicity, PRECAUTIONS, Pregnancy, and ANIMAL TOXICOLOGY AND/OR PHARMACOLOGY).

Geriatric Use

Clinical data indicates that Etomidate may induce cardiac depression in elderly patients, particularly those with hypertension (see CLINICAL PHARMACOLOGY and Other Adverse Observations, Circulatory System).

Elderly patients may require lower doses of Etomidate than younger patients. Age-related differences in pharmacokinetic parameters have been observed in clinical studies (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function.

Plasma Cortisol Levels

Induction doses of Etomidate have been associated with reduction in plasma cortisol and aldosterone concentrations (see CLINICAL PHARMACOLOGY). These have not been associated with changes in vital signs or evidence of increased mortality; however, where concern exists for patients undergoing severe stress, exogenous replacement should be considered.

Information for Patients

Studies conducted in young animals and children suggest repeated or prolonged use of general anesthetic or sedation drugs in children younger than 3 years may have negative effects on their developing brains. Discuss with parents and caregivers the benefits, risks, and timing and duration of surgery or procedures requiring anesthetic and sedation drugs (see WARNINGS, Pediatric Neurotoxicity).

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:
   1. 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.
   2. 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.
   3. 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.

Overdosage may occur from too rapid or repeated injections. Too rapid injection may be followed by a fall in blood pressure. No adverse cardiovascular or respiratory effects attributable to Etomidate overdose have been reported.

In the event of suspected or apparent overdosage, the drug should be discontinued, a patent airway established (intubate, if necessary) or maintained and oxygen administered with assisted ventilation, if necessary.

Vd, total clearance, and plasma protein binding are decreased in elderly patients.

Administer IV push over 30 to 60 seconds. Solution is highly irritating; avoid administration into small vessels; in some cases, preadministration of lidocaine may be considered.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience fatigue, nausea, vomiting, or twitching. Have patient report immediately to prescriber severe dizziness, passing out, vision changes, difficulty breathing, slow breathing, shallow breathing, tachycardia, bradycardia, abnormal heartbeat, involuntary eye movements, muscle rigidity, abnormal movements, severe headache, or injection site irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.