Drugs List

Therapeutic Indications

Uses

Induction of general anaesthesia.

Administration

Injection solution
For administration by slow intravenous injection (e.g. 10ml over 30-60 seconds).

The drug should be injected at a reduced rate (e.g. 10ml in 1min) in debilitated patients. See Additional Dosage section.

Injection emulsion
For administration by intravenous injection, usually over approximately 30 seconds.

Handling

Injection emulsion
Containers should be shaken before use. If two layers can be seen after shaking the product should not be used. Discard any unused product.

Etomidate injection emulsion contains no antimicrobial preservatives and supports growth of micro-organisms. Immediately after opening the ampoule, the emulsion should be drawn up into a syringe under aseptic conditions.

Compatibilities

Injection solution
Etomidate may be diluted with sodium chloride infusion 0.9% or glucose infusion.

Injection emulsion
Etomidate may be injected into the tubing of an infusion of isotonic sodium chloride having temporarily been stopped.

Incompatibilities

Etomidate is not compatible with compound sodium lactate infusion (Hartmann's solution) or combinations with pancuronium bromide.

Contraindications

Porphyria

Neonates

Precautions and Warnings

Etomidate must be administered by a doctor skilled in endotracheal intubation. Resuscitation equipment should be readily available in case of apnoea.

The injection should be administered slowly.

The manufacturer states that neonates and infants up to 6 months old should not receive etomidate injection emulsion unless imperative due to the indication.

Use with caution in:
Elderly - see Dosage: Elderly
Pregnancy - see Pregnancy section
Breastfeeding- see Lactation section
Hepatic cirrhosis - see Dosage: Hepatic impairment
Surgery of the mouth, pharynx, or larynx (extreme care required)
Hypovolaemia (reduce dose and/or rate of administration)
Acute circulatory failure (shock)
Cardiovascular disease (reduce dose and/or rate of administration)
Fixed cardiac output
Epilepsy

Patients with reduced adrenal cortical function (e.g. sepsis) should be treated with caution.

Induction doses of etomidate have been associated with a reduction in plasma cortisol and aldosterone concentrations. These have not been associated with changes in vital signs or evidence of increased mortality. However, supplementation with exogenous cortisol should be considered for patients undergoing severe stress if there is causes for concern.

Reduced serum cortisol levels, unresponsive to ACTH injections, have occurred in some patients during the induction of anaesthesia but are more likely to occur when etomidate is used for the maintenance of anaesthesia. For this reason, etomidate should not be used for maintenance of general anaesthesia. When etomidate is used for induction, the post-operative rise in serum cortisol is delayed for approximately 3 to 6 hours.

Special care should be taken in patients who may be vulnerable to the possible hypotensive effect caused by etomidate. Induction with etomidate may be accompanied by a slight and transient drop in blood pressure due to a reduction of peripheral vascular resistance.
Debilitated patients - (see Additional dosage) The occurrence of hypotension may be hazardous in these patients.

Use with caution in premedicated patients (reduced dose may be required).

Convulsions may occur in patients who did not receive premedication.

Etomidate has no analgesic effect, therefore appropriate analgesics should be administered.

Spontaneous muscle movement (ascribed to subcortical disinhibition) may occur when no premedication has been administrated. These can be prevented by the intravenous administration of small doses of fentanyl, with droperidol or diazepam 1-2 minutes before induction with etomidate.

Patients should be advised not to drive or operate machinery for at least 24 hours after administration of etomidate.

The dangers of taking alcohol should be emphasised.

Use in Porphyria

Contraindicated

Pregnancy and Lactation

Pregnancy

Use with caution. Etomidate may be administered during pregnancy only if the potential benefits outweigh the possible risks.

Safety in human pregnancy has not been established. Etomidate may cross the placenta during obstetric anaesthesia. Etomidate has no primary effect on fertility, and embryotoxic or teratogenic effects have not been observed. Etomidate is an inhibitor of steroid biosynthesis. One manufacturer states the extent and clinical effects of steroid synthesis inhibition in the infantile adrenal cortex are not known, therefore etomidate should be administrated to pregnant women only if there is not alternative. However, etomidate has been found to reduce serum cortisol concentrations in neonates following the use of etomidate during delivery without any long-term consequences. Etomidate may also reduce neonatal respiration if used during delivery. Schaefer recommends that etomidate may be used in pregnancy, but if it is used in labour then the baby should be observed for possible respiratory depressant effects.

Decreased survival was observed when maternally toxic doses were administered in animal studies (rats).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Recommended for use by manufacturer? - Use with caution. Neonates and infants up to 6 months old should not receive etomidate injection emulsion unless imperative due to the indication.

Effects on neonate - Reduced neonatal respiration and reduced serum cortisol concentrations.

Other information - Observe neonate for respiratory depressant effects.

Animal data - Decreased survival at maternally toxic doses.

Lactation

Use with caution.

Etomidate is excreted in human milk, however the amounts in milk are very small and decrease rapidly. Schaefer comments that no systematic studies on tolerance of etomidate during breastfeeding have been completed, however no noteworthy symptoms have been reported in the infant when the mother has breastfed.

Information published on LactMed indicates that no waiting period or discarding of milk is required before resuming breastfeeding after etomidate anaesthesia. Breastfeeding can be resumed as soon as the mother has sufficiently recovered. However, the manufacturer suggests if etomidate must be given during breastfeeding, nursing is to be interrupted and not resumed for 24 hours after administration. When a combination of anaesthetic agents is used for a procedure, follow the recommendations for the most problematic medication used during the procedure.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Yes, in small amounts.

Licensed in infants? - Yes, however neonates and infants up to 6 months old should not receive etomidate injection emulsion unless imperative due to the indication.

Side Effects

Local pain (injection site)
Thrombophlebitis
Nausea
Vomiting
Hypersensitivity reactions
Bronchospasm
Anaphylactoid reaction
Apnoea
Respiratory depression
Convulsions
Cough
Hiccough
Shivering
Laryngospasm
Involuntary muscle contractions
Cardiac arrhythmias
Dyskinesia
Anaphylactic shock
Adrenal cortex insufficiency
Hypertonia
Nystagmus
Bradycardia
Extrasystoles
Cardiac arrest
Complete AV block
Hypotension
Phlebitis
Hypertension
Shock
Hyperventilation
Stridor
Hypersalivation
Rash
Erythema
Stevens-Johnson syndrome
Urticaria
Trismus
Excitation
Hypoventilation
Muscle rigidity
Deep vein thrombosis (DVT)
Myoclonus

Presentation

Solution for injection containing 2mg etomidate per ml.

Emulsion for injection containing 2mg etomidate per ml.

Drugs List

Therapeutic Indications

Uses

Induction of general anaesthesia.

Dosage

The dosage should be adjusted according to the individual response and clinical effect.

Adults

Elderly

Children

Patients with Hepatic Impairment

Additional Dosage Information

Administration

Injection solution
For administration by slow intravenous injection (e.g. 10ml over 30-60 seconds).

The drug should be injected at a reduced rate (e.g. 10ml in 1min) in debilitated patients. See Additional Dosage section.

Injection emulsion
For administration by intravenous injection, usually over approximately 30 seconds.

Handling

Injection emulsion
Containers should be shaken before use. If two layers can be seen after shaking the product should not be used. Discard any unused product.

Etomidate injection emulsion contains no antimicrobial preservatives and supports growth of micro-organisms. Immediately after opening the ampoule, the emulsion should be drawn up into a syringe under aseptic conditions.

Compatibilities

Injection solution
Etomidate may be diluted with sodium chloride infusion 0.9% or glucose infusion.

Injection emulsion
Etomidate may be injected into the tubing of an infusion of isotonic sodium chloride having temporarily been stopped.

Incompatibilities

Etomidate is not compatible with compound sodium lactate infusion (Hartmann's solution) or combinations with pancuronium bromide.

Contraindications

Porphyria

Neonates

Precautions and Warnings

Etomidate must be administered by a doctor skilled in endotracheal intubation. Resuscitation equipment should be readily available in case of apnoea.

The injection should be administered slowly.

The manufacturer states that neonates and infants up to 6 months old should not receive etomidate injection emulsion unless imperative due to the indication.

Use with caution in:
Elderly - see Dosage: Elderly
Pregnancy - see Pregnancy section
Breastfeeding- see Lactation section
Hepatic cirrhosis - see Dosage: Hepatic impairment
Surgery of the mouth, pharynx, or larynx (extreme care required)
Hypovolaemia (reduce dose and/or rate of administration)
Acute circulatory failure (shock)
Cardiovascular disease (reduce dose and/or rate of administration)
Fixed cardiac output
Epilepsy

Patients with reduced adrenal cortical function (e.g. sepsis) should be treated with caution.

Induction doses of etomidate have been associated with a reduction in plasma cortisol and aldosterone concentrations. These have not been associated with changes in vital signs or evidence of increased mortality. However, supplementation with exogenous cortisol should be considered for patients undergoing severe stress if there is causes for concern.

Reduced serum cortisol levels, unresponsive to ACTH injections, have occurred in some patients during the induction of anaesthesia but are more likely to occur when etomidate is used for the maintenance of anaesthesia. For this reason, etomidate should not be used for maintenance of general anaesthesia. When etomidate is used for induction, the post-operative rise in serum cortisol is delayed for approximately 3 to 6 hours.

Special care should be taken in patients who may be vulnerable to the possible hypotensive effect caused by etomidate. Induction with etomidate may be accompanied by a slight and transient drop in blood pressure due to a reduction of peripheral vascular resistance.
Debilitated patients - (see Additional dosage) The occurrence of hypotension may be hazardous in these patients.

Use with caution in premedicated patients (reduced dose may be required).

Convulsions may occur in patients who did not receive premedication.

Etomidate has no analgesic effect, therefore appropriate analgesics should be administered.

Spontaneous muscle movement (ascribed to subcortical disinhibition) may occur when no premedication has been administrated. These can be prevented by the intravenous administration of small doses of fentanyl, with droperidol or diazepam 1-2 minutes before induction with etomidate.

Patients should be advised not to drive or operate machinery for at least 24 hours after administration of etomidate.

The dangers of taking alcohol should be emphasised.

Use in Porphyria

Contraindicated

Pregnancy and Lactation

Pregnancy

Use with caution. Etomidate may be administered during pregnancy only if the potential benefits outweigh the possible risks.

Safety in human pregnancy has not been established. Etomidate may cross the placenta during obstetric anaesthesia. Etomidate has no primary effect on fertility, and embryotoxic or teratogenic effects have not been observed. Etomidate is an inhibitor of steroid biosynthesis. One manufacturer states the extent and clinical effects of steroid synthesis inhibition in the infantile adrenal cortex are not known, therefore etomidate should be administrated to pregnant women only if there is not alternative. However, etomidate has been found to reduce serum cortisol concentrations in neonates following the use of etomidate during delivery without any long-term consequences. Etomidate may also reduce neonatal respiration if used during delivery. Schaefer recommends that etomidate may be used in pregnancy, but if it is used in labour then the baby should be observed for possible respiratory depressant effects.

Decreased survival was observed when maternally toxic doses were administered in animal studies (rats).

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Recommended for use by manufacturer? - Use with caution. Neonates and infants up to 6 months old should not receive etomidate injection emulsion unless imperative due to the indication.

Effects on neonate - Reduced neonatal respiration and reduced serum cortisol concentrations.

Other information - Observe neonate for respiratory depressant effects.

Animal data - Decreased survival at maternally toxic doses.

Lactation

Use with caution.

Etomidate is excreted in human milk, however the amounts in milk are very small and decrease rapidly. Schaefer comments that no systematic studies on tolerance of etomidate during breastfeeding have been completed, however no noteworthy symptoms have been reported in the infant when the mother has breastfed.

Information published on LactMed indicates that no waiting period or discarding of milk is required before resuming breastfeeding after etomidate anaesthesia. Breastfeeding can be resumed as soon as the mother has sufficiently recovered. However, the manufacturer suggests if etomidate must be given during breastfeeding, nursing is to be interrupted and not resumed for 24 hours after administration. When a combination of anaesthetic agents is used for a procedure, follow the recommendations for the most problematic medication used during the procedure.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - Yes, in small amounts.

Licensed in infants? - Yes, however neonates and infants up to 6 months old should not receive etomidate injection emulsion unless imperative due to the indication.

Effects on Ability to Drive and Operate Machinery

Patients should be advised not to drive or operate machinery for at least 24 hours after administration of etomidate.

Return to normal alertness may vary according to duration of operation, total dose of etomidate and concomitant medication used. Therefore the decision to allow driving must be a judgement made by the post-anaesthesiology team.

Counselling

Patients should be advised not to drive or operate machinery for at least 24 hours after administration of etomidate.

The dangers of taking alcohol should be emphasised.

Side Effects

Local pain (injection site)
Thrombophlebitis
Nausea
Vomiting
Hypersensitivity reactions
Bronchospasm
Anaphylactoid reaction
Apnoea
Respiratory depression
Convulsions
Cough
Hiccough
Shivering
Laryngospasm
Involuntary muscle contractions
Cardiac arrhythmias
Dyskinesia
Anaphylactic shock
Adrenal cortex insufficiency
Hypertonia
Nystagmus
Bradycardia
Extrasystoles
Cardiac arrest
Complete AV block
Hypotension
Phlebitis
Hypertension
Shock
Hyperventilation
Stridor
Hypersalivation
Rash
Erythema
Stevens-Johnson syndrome
Urticaria
Trismus
Excitation
Hypoventilation
Muscle rigidity
Deep vein thrombosis (DVT)
Myoclonus

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Storage instructions vary - consult individual product literature.

Further Information

Last Full Review Date: July 2012

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of Product Characteristics: Etomidate-Lipuro. B Braun. Revised August 2014.

Summary of Product Characteristics: Hypnomidate. Janssen-Cilag Ltd. Revised September 2015.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 31 August 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Etomidate. Last revised: 10 March 2015.
Last accessed: 13 November 2015.