This page shows what was measured, who it was measured in, and what that does not settle.
What Etomidate does in the body
Etomidate holds open the brain's main inhibitory gate, the same one propofol uses, and consciousness stops within a minute.
What makes it different is what it does not do: it barely touches the nerves and receptors that set blood pressure, so a patient who is already shocked does not get worse at the moment of induction. The problem is a coincidence of chemistry. The ring that makes the molecule work also fits the active site of an enzyme in the adrenal gland that makes cortisol, and after a single dose that enzyme stays blocked for six to eight hours.
Why people take it. Putting a person to sleep for surgery when their blood pressure will not tolerate the usual drug
What happened in people
Labelled incidence of transient skeletal muscle movements about 32% and venous pain about 20%
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
That a single induction dose causes clinically important harm — the randomised trial's primary endpoint came back at P=0.056 and the mortality signal comes from a non-randomised exposure
Where it acts
Chloride channel of the type A GABA receptor throughout the brain, and — unintentionally — the mitochondria of adrenal cortical cells
Kind of result
Symptoms and quality of life
Supervision
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · Z22628B598 · read 2026-08-29
Where each sentence above came from
A person wrote this explanation into the record, with the studies named in the path below.
The recorded use, written for a reader without medical training. Not signed off.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 130 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Absolute difference
An absolute difference is how many more people in a hundred were affected.
A picture of it, and where the picture fails
It is like counting heads in two rooms of a hundred.
Where that stops being true. Heads are easy to count. Study results carry a margin of error too.
What people get wrong. It is confused with a percentage change, which can look far larger.
The arithmetic difference in event rates between arms.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Maximum sequential organ failure assessment score during the first three days in the intensive care unit
✗ The study did not show it
Who was studied
KETASED — etomidate versus ketamine for rapid sequence intubation in acutely ill patients (NCT00440102)
Mean maximum SOFA 10.3 (SD 3.7) with etomidate versus 9.6 (SD 3.9) with ketamine; mean difference 0.7, 95% CI 0.0 to 1.4, P=0.056. Adrenal insufficiency odds ratio 6.7 (95% CI 3.5 to 12.7)
Repeated elsewhere
Partially Replicated
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. Analysed as modified intention-to-treat in 469 of 655 enrolled, excluding those who died before hospital arrival or left intensive care within three days — an exclusion rule that removes the sickest and the least sick from a severity-scored endpoint. Intubation conditions were identical, median difficulty score 1 in both groups.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Sterile non-pyrogenic solution of 2 mg/mL etomidate in 35% v/v propylene glycol at pH 6, for intravenous injection only; single-dose vials and prefilled syringes
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
NCT00440102 — KETASED, etomidate versus ketamine for rapid sequence intubation (NCT00440102) · a recorded source, not a stored snapshot
Corticotropin response and all-cause 28-day mortality in patients receiving etomidate
✓ The study showed what it set out to show
Who was studied
CORTICUS a-priori sub-study of etomidate exposure in septic shock
How many people
499
Study design
Prospective a-priori sub-study within a randomised double-blind placebo-controlled trial
Compared against
A dummy treatment
Kind of result
Living longer, or avoiding a major event
What was found
Non-responders to corticotropin 61.0% versus 44.6%, P=0.004. 28-day mortality 42.7% versus 30.5%; P=0.02 univariate, P=0.06 and P=0.03 in two multivariate models correcting for severity of illness
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Hydrocortisone did not change mortality among those who had received etomidate, 45% versus 40% — a finding that undercuts the steroid-deficiency mechanism the mortality signal is usually attributed to. Etomidate exposure was not randomised, so confounding by indication cannot be excluded.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Sterile non-pyrogenic solution of 2 mg/mL etomidate in 35% v/v propylene glycol at pH 6, for intravenous injection only; single-dose vials and prefilled syringes
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
NCT00440102 — KETASED, etomidate versus ketamine for rapid sequence intubation (NCT00440102) · a recorded source, not a stored snapshot
Mortality in critically ill multiple trauma patients sedated by etomidate infusion
✓ The study showed what it set out to show
Who was studied
Ledingham and Watt observation of etomidate infusion sedation in multiple trauma
How many people
0
Study design
Observational report
Compared against
Not recorded for this study
Kind of result
Living longer, or avoiding a major event
What was found
A one-page correspondence rather than a controlled comparison. No effect estimate is quoted here because the report is not a trial and this page does not manufacture one.
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. The strength of the response — worldwide abandonment of infusion use and a capitalised label warning — is out of proportion to the strength of the study design, which is itself worth recording in an audit.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Sterile non-pyrogenic solution of 2 mg/mL etomidate in 35% v/v propylene glycol at pH 6, for intravenous injection only; single-dose vials and prefilled syringes
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
NCT00440102 — KETASED, etomidate versus ketamine for rapid sequence intubation (NCT00440102) · a recorded source, not a stored snapshot
What we know
RNAWiki holds 3 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Etomidate
What a person takes: Sterile non-pyrogenic solution of 2 mg/mL etomidate in 35% v/v propylene glycol at pH 6, for intravenous injection only; single-dose vials and prefilled syringes.
The measurement behind this step
The vehicle is part of the drug's clinical profile rather than an inert detail. Etomidate is poorly water-soluble and the marketed formulation dissolves it in 35% propylene glycol, which accounts for much of the venous pain reported in about a fifth of patients and adds a solvent burden that would compound over any prolonged administration. Lipid emulsion formulations exist in some markets specifically to reduce injection pain. The label restricts the drug to intravenous injection for induction and for supplementing subpotent agents in short procedures, and states in capitals that it is not intended for administration by prolonged infusion.
Getting in
Injected in a solvent, not in water
The molecule does not dissolve well in water, so it is supplied dissolved in a syrupy alcohol. That solvent is a large part of why the injection stings.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The injection is 2 mg/mL in 35% v/v propylene glycol at pH 6. Transient venous pain occurs in about 20% of patients, more often in small distal veins than in larger proximal ones, and the label notes it is not associated with an increased incidence of thrombophlebitis. The co-solvent load is also part of why prolonged infusion was never a benign proposition independent of the adrenal problem.
Onset is within roughly one circulation of the blood, and the effect of a single dose is over in three to five minutes as the drug redistributes out of the brain.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The label describes rapid onset usually within one minute and a dose-dependent but brief duration. Plasma concentrations fall rapidly for the first 30 minutes and then more slowly, with a half-life around 75 minutes; offset of a single dose is redistribution rather than elimination. Volume of distribution and half-life are roughly doubled in cirrhosis, and initial distribution volume, clearance and albumin binding are all reduced in older patients.
It binds the brain's main inhibitory receptor at the same spot propofol uses, on a different part of the protein from where benzodiazepines act.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
The site involves asparagine 265 in transmembrane domain 2 of the beta subunit. Beta3(N265M) knock-in mice lose etomidate's immobilising action entirely and most of its hypnotic action, while volatile anaesthetics still work in the same animals — a positive and a negative control in one experiment.
Blood pressure barely moves, which is the entire point
Unlike almost every other induction agent, this one does not open up the blood vessels or weaken the heart. In a patient who is already shocked, that is the difference that matters.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The label reports that intravenous administration of up to 0.6 mg/kg to patients with severe cardiovascular disease has little or no effect on myocardial metabolism, cardiac output, peripheral circulation or pulmonary circulation, with haemodynamic effects mostly similar to thiopental except for the heart rate response. It also notes that in older patients, particularly those with hypertension, decreases in heart rate, cardiac index and mean arterial pressure can occur — so the stability is a strong tendency rather than a guarantee.
The imidazole ring that makes the drug work also fits the iron atom at the heart of the enzyme that makes cortisol. That enzyme stays blocked for six to eight hours after a single dose.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
The free imidazole nitrogen coordinates the haem iron of steroid 11-beta-hydroxylase, the same mechanism by which imidazole antifungals inhibit their cytochrome P450 targets. The label attributes reduced plasma cortisol and aldosterone after induction doses to this blockade, persisting six to eight hours and unresponsive to ACTH. The defect is in stimulated output rather than in a resting level, which is why a single cortisol measurement can be misleading.
An enzyme snips the ester off the molecule, leaving an inactive acid that the kidneys remove. About three quarters of the dose is out within a day.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The chief metabolite is R-(+)-1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid, formed by ester hydrolysis and accounting for about 80% of urinary excretion; approximately 75% of the administered dose appears in the urine on the first day. Notably, recovery of consciousness runs well ahead of recovery of adrenal function: the anaesthetic is gone in minutes and the enzyme block persists for hours, which is the pharmacokinetic root of the entire controversy.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 6 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Patients being intubated in an emergency department, in shock, or with severe cardiac disease; and patients having electroconvulsive therapy, where its seizure characteristics are useful.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Where the result stopped carrying
Prolonged infusion sedation was abandoned worldwide after a one-page 1983 report, and the label now forbids it in capital letters
KETASED failed to show organ-failure equivalence cleanly, landing at P=0.056 with a confidence interval touching zero, and its authors recommended ketamine in sepsis
The steroid-deficiency explanation for the mortality signal failed its own test: hydrocortisone did not rescue etomidate-exposed patients in CORTICUS
The original development programme failed to assay adrenal steroidogenesis at all, despite the molecule being an imidazole — the same chemistry used deliberately to inhibit P450 enzymes in antifungals
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
The product may not be what it says
Contents of a sold product are not always what the label states.
On this record: This is sold as a supplement, so no agency checked what is in a given tub before it was sold.
Other reasons RNAWiki checked and found nothing for (10)
It was studied for a different goal
The studies measured something else entirely. Nothing in this record points to this reason.
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Given by a clinician
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Sterile non-pyrogenic solution of 2 mg/mL etomidate in 35% v/v propylene glycol at pH 6, for intravenous injection only; single-dose vials and prefilled syringes
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. A regulator classifies this substance in a way that restricts how it is supplied.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Suppression classes recorded: S1.
No source is stored against this line.
What is in the pack
The vehicle is part of the drug's clinical profile rather than an inert detail.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: Etomidate is poorly water-soluble and the marketed formulation dissolves it in 35% propylene glycol, which accounts for much of the venous pain reported in about a fifth of patients and adds a solvent burden that would compound over any prolonged administration. Lipid emulsion formulations exist in some markets specifically to reduce injection pain. The label restricts the drug to intravenous injection for induction and for supplementing subpotent agents in short procedures, and states in capitals that it is not intended for administration by prolonged infusion.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
The label's central warning, in capitals, is that because of the hazards of prolonged suppression of endogenous cortisol and aldosterone production, the formulation is not intended for prolonged infusion. A single induction dose reduces cortisol and aldosterone for six to eight hours and leaves the adrenal unresponsive to ACTH. Transient skeletal muscle movements including myoclonus occur in about 32% of patients and venous pain in about 20%. The drug has no analgesic activity whatsoever. It carries the class Pediatric Neurotoxicity warning describing animal evidence of neuronal apoptosis with exposures over three hours in the developing brain, with clinical significance stated as unclear. Distribution volume and half-life roughly double in cirrhosis, and clearance falls in older patients. No dosing guidance appears on this page.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Sterile non-pyrogenic solution of 2 mg/mL etomidate in 35% v/v propylene glycol at pH 6, for intravenous injection only; single-dose vials and prefilled syringes
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
A recorded note compares this form with the others that are sold. It is kept below, word for word.
§ A fixed RNAWiki sentence
Where this came from
Wording RNAWiki always uses, not a finding about this substance.
The recorded note, unchanged: Etomidate is poorly water-soluble and the marketed formulation dissolves it in 35% propylene glycol, which accounts for much of the venous pain reported in about a fifth of patients and adds a solvent burden that would compound over any prolonged administration. Lipid emulsion formulations exist in some markets specifically to reduce injection pain. The label restricts the drug to intravenous injection for induction and for supplementing subpotent agents in short procedures, and states in capitals that it is not intended for administration by prolonged infusion.
No source is stored against this line.
What is recorded as being sold
30 products list this as an active ingredient in the United States drug directory. 30 of them contain it and nothing else.
FDA National Drug Code directory · 72485-509 · read 2026-08-29
They are sold as injection, injection, solution, powder and solution, taken intravenous.
FDA National Drug Code directory · 72485-509 · read 2026-08-29
The regulator's established pharmacologic class for it is general anesthesia [pe] and general anesthetic [epc].
FDA National Drug Code directory · 72485-509 · read 2026-08-29
17 published labels name it as an active ingredient. 17 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 0635683b-880a-0cd4-e063-6394a90ab73e · read 2026-08-29
Those labels are classed as human prescription drug.
US prescribing information · 0635683b-880a-0cd4-e063-6394a90ab73e · read 2026-08-29
ETOMIDATE injection, solution is intravenous at HOW SUPPLIED Etomidate Injection, USP is a sterile, non-pyrogenic, clear, colorless solution, free from visible particles and is supplied as follows: 20 mg per 10 mL (2 mg / mL) 10 mL Single-Dose Vials in a Carton of 10…, recorded as fda label in effect 2023-09-25 in the United States.
US prescribing information · 0635683b-880a-0cd4-e063-6394a90ab73e · read 2026-08-30
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of Etomidate studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That a single induction dose causes clinically important harm — the randomised trial's primary endpoint came back at P=0.056 and the mortality signal comes from a non-randomised exposure
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the transience of the biochemical effect makes a single dose safe — no adequately powered randomised mortality trial exists in the population where it matters
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the mortality association is explained by steroid deficiency, when giving hydrocortisone to the exposed patients did not change their mortality
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That haemodynamic stability at induction translates into any downstream benefit; nothing measured here shows that it does
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Etomidate are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
The same single residue that carries propofol carries etomidate
In plain words
Mice with one amino acid changed in the GABA receptor stopped responding to etomidate entirely, while gas anaesthetics still worked on them. It is the same mutation that abolishes propofol anaesthesia.
What was measured
Suppression of noxious-evoked movement and loss of righting reflex in beta3(N265M) knock-in mice versus wild type, with volatile anaesthetic controls
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Jurd and colleagues generated mice carrying an N265M point mutation in the second transmembrane region of the GABA-A receptor beta3 subunit. In those animals, suppression of noxious-evoked movement by intravenous etomidate and propofol was completely abolished, while it was only slightly decreased for enflurane and halothane. The mutants also showed a profound reduction in loss of righting reflex duration in response to intravenous but not volatile anaesthetics, and cortical slice recordings showed the anaesthetics were significantly less effective at enhancing GABA-A currents and at reducing spontaneous action potential firing. The result establishes that a single residue in the beta3 subunit is a major determinant of the behavioural response to both intravenous agents, and that the volatiles act through a broader spectrum of targets. For etomidate specifically it also frames the drug's central problem: the anaesthetic action is precisely localised and well understood, and the action that has generated forty years of argument happens somewhere else entirely.
Written into the record, not signed off as a reviewed claim
1983: a one-page Lancet letter ended the drug's use as an infusion
In plain words
An intensive care unit noticed that badly injured patients sedated with an etomidate infusion were dying more often than expected. The finding was published in a single page in the Lancet, and infusion use of the drug stopped worldwide.
What was measured
That a drug's haemodynamic stability makes it suitable for prolonged sedation — an inference that ignored an off-target enzyme inhibition nobody had assayed for
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Ledingham and Watt reported an association between etomidate infusion sedation and increased mortality in critically ill multiple trauma patients in a one-page Lancet correspondence in 1983. The mechanism was identified shortly afterwards as inhibition of adrenal steroidogenesis, and the approved United States label now carries it in capitals in its warnings: because of the hazards of prolonged suppression of endogenous cortisol and aldosterone production, this formulation is not intended for administration by prolonged infusion. This is a genuine reversal and an unusually consequential one. Etomidate had been introduced as a sedative infusion for intensive care precisely because of its cardiovascular stability, that use was abandoned within about a year of a short observational report, and the abandonment has never been seriously challenged. It also set up the argument that has followed ever since: if hours of infusion are lethal, what does a single induction dose do?
Written into the record, not signed off as a reviewed claim
One induction dose blocks cortisol synthesis for six to eight hours
In plain words
The label states it plainly: after a single dose used to induce anaesthesia, cortisol and aldosterone fall, stay down for six to eight hours, and do not respond to the hormone that normally tells the adrenal gland to make more.
What was measured
Duration of reduced plasma cortisol and aldosterone after an induction dose, and unresponsiveness to ACTH stimulation
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The approved label reports that reduced plasma cortisol and aldosterone levels have been reported following induction doses of etomidate, that these persist for approximately six to eight hours, and that they appear to be unresponsive to adrenocorticotropic hormone administration — which it attributes to blockade of 11-beta-hydroxylation within the adrenal cortex. The chemistry is straightforward and was foreseeable: the free nitrogen of the imidazole ring coordinates the haem iron of the cytochrome P450 enzyme steroid 11-beta-hydroxylase, the same way the imidazole antifungals inhibit their P450 targets. The important detail is not that cortisol is low but that the gland cannot be stimulated. A single blood cortisol drawn after etomidate can look adequate; the defect is in the response to stress, which is exactly the reserve a critically ill patient is drawing on.
Source
FDA-approved US prescribing information for AMIDATE (etomidate) injection, CLINICAL PHARMACOLOGY (DailyMed SPL b7ed5bf8-ba75-44dc-8f81-96b4ad5766be)
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
KETASED: sixfold more adrenal insufficiency, and organ failure that just missed
In plain words
Six hundred and fifty-five critically ill patients were randomised to etomidate or ketamine for emergency intubation. Adrenal insufficiency was six to seven times more common with etomidate. Organ failure over the next three days was slightly worse and just missed statistical significance.
What was measured
Maximum sequential organ failure assessment score over the first three intensive care days, and incidence of adrenal insufficiency
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Jabre and colleagues ran a randomised, single-blind, controlled trial at 12 emergency medical services or emergency departments and 65 intensive care units in France, enrolling 655 patients needing sedation for emergency intubation and assigning them to etomidate (n=328) or ketamine (n=327). In the modified intention-to-treat analysis of 469 patients — 234 etomidate, 235 ketamine — the primary endpoint, mean maximum sequential organ failure assessment score during the first three intensive care days, was 10.3 (SD 3.7) against 9.6 (SD 3.9): mean difference 0.7, 95% CI 0.0 to 1.4, P=0.056. Intubation conditions did not differ, with a median intubation difficulty score of 1 in both groups (P=0.70). Adrenal insufficiency was significantly more common with etomidate, odds ratio 6.7 (95% CI 3.5 to 12.7). No serious adverse events were recorded with either drug. The authors concluded that ketamine is a safe and valuable alternative and should be considered in patients with sepsis. A confidence interval running from exactly 0.0 to 1.4 with P=0.056 is a result that cannot be read as reassurance in either direction, and this page does not read it as one.
Written into the record, not signed off as a reviewed claim
CORTICUS sub-study: higher 28-day mortality, and steroids did not fix it
In plain words
Among 499 patients with septic shock, the 96 who had received etomidate before enrolment were much more likely to fail an adrenal stimulation test and more likely to be dead at 28 days. Giving them hydrocortisone did not change that.
What was measured
Proportion of non-responders to corticotropin and all-cause 28-day mortality in patients given etomidate within 72 hours before inclusion
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
Cuthbertson and colleagues ran an a-priori sub-study of CORTICUS, a multicentre randomised double-blind placebo-controlled trial of hydrocortisone in septic shock, collecting use and timing of etomidate administration. Of 500 patients recruited, 499 were analysable, and 96 (19.2%) had received etomidate within the 72 hours before inclusion. Non-response to corticotropin was significantly more frequent in those patients: 61.0% against 44.6%, P=0.004. Etomidate was associated with higher 28-day mortality in univariate analysis (P=0.02) and, after correction for severity of illness, 42.7% against 30.5% with P=0.06 in one multivariate model and P=0.03 in the other. Crucially for the mechanism, hydrocortisone administration did not change mortality among those who had received etomidate — 45% against 40% — which is difficult to reconcile with a purely steroid-deficiency explanation and is exactly the kind of result that keeps an argument alive. The authors recommended extreme caution. This remains a post-hoc analysis of a non-randomised exposure within a randomised trial, and confounding by indication is unavoidable: the sickest patients are the ones an anaesthetist chooses etomidate for.
Written into the record, not signed off as a reviewed claim
Forty years on, the induction-dose question is still not settled either way
In plain words
Everyone agrees a single dose suppresses the adrenal gland for several hours. Whether that harms the patient has been argued since 1983 without a trial large enough to answer it, and the drug is still used because nothing else does its job as well.
What was measured
Both directions are inferred here: that a single induction dose meaningfully increases mortality, and that it is safe because the biochemical effect is transient. Neither has been established by an adequately powered randomised trial.
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The evidence has a consistent shape and an unresolved conclusion. The biochemical effect is certain and labelled: cortisol and aldosterone fall for six to eight hours and do not respond to ACTH. The infusion harm is accepted, on the strength of a 1983 observational report and a label warning written in capitals. The single-dose harm is where it stops. KETASED randomised the question and its primary endpoint came back at P=0.056 with a confidence interval touching zero. The CORTICUS sub-study found more deaths but is a non-randomised exposure analysed within a randomised trial, and found that hydrocortisone did not rescue those patients, which weakens the very mechanism it appears to support. What no one has produced is a randomised trial powered for mortality in the population where it matters. This page files the induction-dose harm as an open inference rather than as an established harm or an established non-harm, and notes that a drug this useful in shock has an unusually strong incentive structure working against that trial ever being run.
Source
Jabre P et al. Lancet 2009;374:293-300; Cuthbertson BH et al. Intensive Care Med 2009;35:1868-1876; FDA-approved US prescribing information for AMIDATE, WARNINGS and CLINICAL PHARMACOLOGY
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
contested
Review state
Written into the record, not signed off as a reviewed claim
A third of patients twitch and a fifth report a burning arm
In plain words
The label puts numbers on the two commonest problems: involuntary muscle movements in about a third of patients and pain on injection in about a fifth, and the indication section says these should be weighed against the drug's advantages.
What was measured
Labelled incidence of transient venous pain (about 20%) and transient skeletal muscle movements including myoclonus (about 32%)
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The label records transient venous pain immediately after intravenous injection in about 20% of patients, with reported incidences from 1.2% to 42%, usually mild to moderate and occasionally judged disturbing, less frequent in larger proximal arm veins and more frequent in small distal hand or wrist veins; it notes the pain is not associated with more than the usual incidence of thrombosis or thrombophlebitis. Transient skeletal muscle movements including myoclonus were noted in about 32% of patients, with reported incidences from 22.7% to 63%, mostly mild to moderate and some judged disturbing. The indications section is unusually candid in telling the prescriber to weigh the usefulness of the drug's haemodynamic properties against the high frequency of transient skeletal muscle movements. The venous pain is at least partly the vehicle rather than the drug: the injection is 35% v/v propylene glycol, not an aqueous solution.
Source
FDA-approved US prescribing information for AMIDATE (etomidate) injection, INDICATIONS AND USAGE, ADVERSE REACTIONS and DESCRIPTION
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
Where else this substance is registered
FDA substance identifier (UNII)
Z22628B598
RxNorm concept
1654006
Checks this page had to pass
✓ Passed
Identity resolved
no open identity hold
✓ Passed
No unresolved merge across substance families
no quarantine open
✓ Passed
Every public sentence names a source
The opening statement carries the origin: Written into the record, not signed off.
✗ Not passed
Trial roles classified for highlighted evidence
No registered study is classified as testing this substance.
✓ Passed
No internal keys in reader text
enforced by the copy-contract test over the rendered page
✓ Passed
Safety mode resolved
Suppression classes recorded: S1.
✓ Passed
Canonical metadata present
slug and display name present
What is missing or unclear◇Read from sources, not yet reviewed
How this medicine reached us
Kept near the foot of the page. A historical event moves up only when it changes something about this substance today.
What the approval register records
12 approved applications cover products containing this substance. The earliest was NDA018227, approved 19820907 to HOSPIRA.
This order is fixed in code and does not count clicks or time on the page.
What is not here
7 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
How close this is to real life — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
The induction agent that abolishes consciousness without dropping blood pressure — proved to act at the GABA-A beta3 subunit by the same single-residue knock-in that abolishes propofol anaesthesia — and which, in the trial that compared it with ketamine for emergency intubation of 469 critically ill patients, produced no significant difference in organ failure (maximum SOFA 10.3 against 9.6, P=0.056) alongside a sixfold higher odds of adrenal insufficiency (odds ratio 6.7, 95% CI 3.5 to 12.7).
Recorded evidence blocks (9)
Q2
On the Etomidate label: indicated for what?
"AMIDATE is indicated by intravenous injection for the induction of general anesthesia. When considering use of AMIDATE, the usefulness of its hemodynamic properties (see CLINICAL PHARMACOLOGY ) should be weighed against the high frequency of transient skeletal muscle movements (see ADVERSE REACTIONS ).": indications and usage on Etomidate's label. DailyMed label · b7ed5bf8-ba75-44dc-8f81-96b4ad5766be · 2026-05-20
Q3
50 registered trials of Etomidate — at which phases?
Registered studies posting no result
42 of 50
50 registered studies of Etomidate: 26 phase4, 15 na, 4 na or unstated, 4 phase3, 1 early phase1, 1 phase2. CLINICALTRIALS_SNAPSHOT · 2026-09-01
terminated; "The study has achieved its objectives of showing feasibility, safety, and trend for improved mRS. FDA and LRS agreed that this study should be terminated, and that a new, PIVOTAL trial should be started."
NCT04120870
terminated; "Due to difficulties in obtaining consent because of emergency situation"
NCT04291521
withdrawn; "PI left institution."
recorded 2026-09-01 · last checked 2026-09-04
Q5
Human studies of Etomidate used Etomidate 0.3 mg/kg — over how long?
studies of Etomidate used the recorded amount. ClinicalTrials.gov · 2026-09-01
7 recorded entries; human; also "Etomidate 0.3 mg/kg", "Etomidate 0.15 mg/kg", "Etomidate Injection 0.2 mg/kg"
Show the evidence
human
NCT03820388
Etomidate 0.3 mg/kg
NCT03820388
Etomidate 0.15 mg/kg
NCT04120870
Etomidate Injection 0.2 mg/kg
NCT05358535
Admixture of propofol and etomidate at a ratio by volume of 75%/25% (P7E2)
NCT05358535
etomidate 25% by volume
NCT05358535
Admixture of propofol and etomidate at a ratio by volume of 25%/75% (P2E7)
1 more recorded row
humanNCT05358535
etomidate 75% by volume
recorded 2026-09-01 · last checked 2026-09-04
Q6
Etomidate's half-life is 30 minutes — which schedules were studied?
30 minutes, the half-life Etomidate's label states: "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." DailyMed label · b7ed5bf8-ba75-44dc-8f81-96b4ad5766be · 2026-05-20
Show the evidence
half lifeclinical_pharmacology
30 minutes; 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.
metabolismclinical_pharmacology
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.
recorded 2026-05-20 · last checked 2026-09-04
Q7
Which 19 trials of Etomidate posted no result?
Posted no result
19 of 19 completed trials
Registrations
NCT00440102, NCT00451776, NCT00415701, NCT01729897, NCT01792037 and NCT01495949, and 13 more
Completion dates
oldest 2008-03; newest 2024-01-31
Show the evidence
Trial
NCT00440102
2008-03
NCT00451776
2008-10
NCT00415701
2009-12
NCT01729897
2012-10
NCT01792037
2013-03
NCT01495949
2013-12
13 further recorded trials
NCT02667353
2015-12
NCT02711917
2016-01
NCT02500225
2017-02
NCT03240055
2017-07-15
NCT02066077
2017-12-31
NCT02822144
2020-08
NCT02910206
2020-11-20
NCT04865614
2020-12-01
NCT03852797
2022-01-19
NCT05407870
2022-11-24
NCT05223907
2022-12-31
NCT05748665
2024-01-26
NCT06664138
2024-01-31
Q8
At the median, Etomidate's trials enrolled 119 people — anything larger?
Median enrolment
119
Largest enrolment
2367
Registered trials counted
50
Q9
What do 247 spontaneous reports say about Etomidate — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Etomidate appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 247 reaction mentions were counted: bradycardia 44; cardiac arrest 34; hypotension 32; anaphylactic shock 30. FAERS via Open Targets · CHEMBL681 · 2026-06-24
Show the evidence
bradycardia
44
cardiac arrest
34
hypotension
32
anaphylactic shock
30
coma
26
drug interaction
22
4 more recorded rows
myoclonus
19
tachycardia
15
respiratory depression
13
ejection fraction decreased
12
recorded 2026-06-24 · last checked 2026-09-04
Q10
Which 10 reactions does Etomidate's label not list?
ChEMBL 37 — CC BY-SA 3.0 Unported · ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Open Targets 26.06 — CC0 · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 6 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.