A critically ill patient needs intubation.

The blood pressure is 82/48 mmHg. The patient is tachycardic, exhausted, and barely maintaining oxygenation. Vasopressors are being prepared. Someone asks:

“Ketamine or etomidate?”

It sounds like a medication question.

In reality, it is a physiology question.

Etomidate remains one of the most useful induction agents in emergency and critical care because it can produce rapid unconsciousness with relatively little cardiovascular disturbance. But that does not mean the patient is protected from peri-intubation collapse.

Understanding that difference changes how we prepare, intubate, and manage the first few minutes afterward.

What does etomidate actually do?

Etomidate is a hypnotic anesthetic that primarily enhances activity at the GABA-A receptor.

In simple terms:

Etomidate → increased GABA-mediated chloride influx → neuronal hyperpolarization → reduced neuronal activity → rapid unconsciousness

It acts quickly because it reaches the brain rapidly, and its hypnotic effect is brief largely because of redistribution away from the central nervous system.

A standard induction dose produces only a few minutes of hypnosis.

That short duration is useful during induction.

But it also creates one of the easiest mistakes to make after RSI.

Etomidate puts the patient to sleep. It does not treat pain.

Etomidate has no meaningful analgesic effect.

Once a neuromuscular blocking agent has been given, the patient cannot move or communicate. Paralysis should never be mistaken for sedation.

If etomidate wears off while paralysis persists, an inadequately sedated patient may be awake but unable to move.

For the entire airway team, this means the intubation is not finished when the tube is secured.

Post-intubation analgesia and sedation should already be planned before RSI begins.

For nurses in particular, this is an important safety checkpoint: tube confirmation, ventilator connection, blood-pressure reassessment, and adequate analgosedation should happen as part of the same sequence—not as an afterthought.

Why does etomidate usually preserve blood pressure better?

This is where the drug becomes especially attractive in emergency medicine and critical care.

Many induction agents can remove the physiological mechanisms that are keeping a critically ill patient alive.

Propofol, for example, can produce vasodilation, reduce sympathetic tone, and depress myocardial function.

In a healthy patient, that may be well tolerated.

In a patient whose circulation is already dependent on endogenous catecholamines, it may not be.

Etomidate generally causes considerably less cardiovascular depression. At induction doses it has relatively little effect on cardiac output and the peripheral circulation, which explains its longstanding role in patients with limited hemodynamic reserve.

A useful mental model is:

Etomidate removes consciousness while interfering relatively little with the compensatory circulation.

But there is an important word in that sentence:

Relatively.

Etomidate is not cardiovascularly invisible.

Elderly patients, severely hypovolemic patients, and critically ill patients can still become hypotensive. The drug does not correct the shock state that existed before it was given.

And more importantly, the medication is only one part of intubation physiology.

The dangerous misconception: “I used etomidate, so the blood pressure should be fine.”

A patient can receive the most hemodynamically favorable induction agent available and still arrest after intubation.

Why?

Because intubation itself changes physiology.

Consider a patient in severe shock who is breathing spontaneously.

Before intubation, negative intrathoracic pressure during inspiration helps draw venous blood back toward the right heart.

Then we induce anesthesia, paralyze the patient, and apply positive-pressure ventilation.

Suddenly:

Intrathoracic pressure rises
→ venous return and RV preload may decrease
→ cardiac output and blood pressure may fall. This is a risk pathway, not an inevitable response; the hemodynamic response varies with ventricular function and loading conditions.

Now add:

• pre-existing hypovolemia,
• vasodilation from sepsis,
• severe RV dysfunction,
• high pulmonary vascular resistance,
• auto-PEEP,
• profound metabolic acidosis,
• or catecholamine-dependent circulation.

The patient may collapse despite receiving etomidate.

This is why the better question before RSI is not simply:

“Which induction agent should I use?”

It is:

“What is keeping this patient’s circulation alive right now, and what will induction and positive-pressure ventilation do to it?”

That question should influence fluid strategy, vasopressor preparation, ventilator settings, preoxygenation, positioning, and even whether the physiology can be partially optimized before attempting intubation.

What about adrenal suppression?

This is the main controversy surrounding etomidate.

Etomidate inhibits 11β-hydroxylase in the adrenal cortex.

This interferes with synthesis of cortisol and aldosterone.

So:

Etomidate → 11β-hydroxylase inhibition → decreased cortisol production

The effect is real.

Current prescribing information reports reduced cortisol and aldosterone after a typical 0.3 mg/kg induction dose, with the effect persisting for approximately 6–8 hours in the cited studies. This is not a firm recovery limit: studies in critically ill patients have documented adrenal suppression beyond this period, so adrenal function should not be assumed to have recovered by 8 hours.

This understandably raised concern in septic shock.

A patient with severe infection is already mounting a major stress response. Cortisol helps maintain vascular responsiveness to catecholamines and contributes to the physiological response to shock.

Suppressing cortisol therefore sounds dangerous.

Physiologically, the concern is reasonable.

But there is an important principle in critical care:

A plausible mechanism does not automatically mean a clinically important outcome.

We need outcome data.

Ketamine versus etomidate: newer evidence matters

For years, clinicians debated whether ketamine should replace etomidate in critically ill patients, particularly those with sepsis.

A large randomized trial published online in December 2025 and in the New England Journal of Medicine in 2026 provides important new evidence.

The analysis included 2,365 critically ill adults undergoing emergency tracheal intubation across 14 emergency departments and ICUs, randomized to ketamine or etomidate.

In-hospital death by day 28 occurred in:

• 28.1% with ketamine
• 29.1% with etomidate

The trial did not demonstrate a mortality benefit with ketamine and did not establish equivalence. The site-adjusted absolute risk difference was −0.8 percentage points (95% CI −4.5 to 2.9).

In this trial, cardiovascular collapse was the prespecified secondary composite: systolic blood pressure below 65 mmHg, new or increased vasopressors, or cardiac arrest, measured from induction through 2 minutes after intubation. These percentages describe the composite, not cardiac arrest alone.

Cardiovascular collapse during intubation occurred in:

• 22.1% with ketamine
• 17.0% with etomidate

The composite occurred more often with ketamine. Interpretation needs caution: clinicians knew the assigned drug, vasopressor treatment contributed to the endpoint, and secondary-outcome confidence intervals were not adjusted for multiple comparisons. The result does not establish universal superiority of etomidate.

This does not mean:

“Etomidate is always better than ketamine.”

Ketamine remains an extremely useful induction agent. It provides analgesia, has bronchodilatory properties, and may be particularly useful in specific clinical situations.

The lesson is different:

Do not automatically assume ketamine is hemodynamically safer simply because the patient is in shock.

Drug choice should follow the patient’s physiology.

The 2023 SCCM RSI guideline predates this trial. Its earlier assessment found no clear difference between etomidate and other induction agents for mortality or peri-intubation hemodynamic outcomes; interpret it alongside the newer trial. Separately, it suggests against corticosteroids solely to counter etomidate-induced adrenal suppression. This does not exclude corticosteroids for another established indication.

What should the bedside team expect after etomidate?

There are several predictable effects worth recognizing.

1. Myoclonus

Transient myoclonic movements are common after etomidate.

They can look dramatic.

But myoclonus after etomidate should not automatically be interpreted as a seizure. The prescribing information identifies myoclonus as a common neurological adverse effect.

The clinical context still matters, particularly in patients being intubated for status epilepticus or neurological emergencies.

2. Apnea and hypoventilation

Etomidate is often called “hemodynamically stable,” but this should never be confused with “respiratorily benign.”

Hypoventilation and apnea can occur.

Once induction begins, the airway team must already be prepared to manage oxygenation and ventilation.

3. Injection pain

Pain on injection and local venous irritation are recognized adverse effects.

This matters less during a life-saving RSI but is worth recognizing during procedural sedation or elective induction.

4. Rapid awakening

The hypnotic effect is brief. DailyMed describes a typical duration of approximately 3–5 minutes after a 0.3 mg/kg dose.

This is clinically important.

If rocuronium has been used, neuromuscular paralysis may persist far longer than the hypnotic effect of etomidate.

That mismatch is exactly why post-intubation sedation cannot wait.

A practical RSI approach

For adult induction, the usual labeled dose is 0.3 mg/kg IV, individualized to the patient and local protocol. Older patients may need a lower dose. This is not a pediatric dosing guide.

But during emergency airway management, the drug dose is only one part of the procedure.

Think of RSI as three physiological phases.

Before induction

Ask:

• Is the patient already hypotensive?
• Is circulation preload-dependent?
• Is there severe RV failure?
• Is the patient profoundly acidotic?
• Are vasopressors already required?
• Can oxygenation be improved before apnea?
• What will positive-pressure ventilation do to venous return?

Correct what can reasonably be corrected before the drugs are pushed.

During intubation

Everyone should know the plan.

The physician managing the airway, bedside nurse, medication nurse, respiratory therapist, and additional physician should anticipate:

• hypotension,
• desaturation,
• difficult laryngoscopy,
• need for vasopressor escalation,
• failed first attempt,
• and peri-intubation cardiac arrest.

A good RSI is a team procedure, not simply a laryngoscopy.

Immediately afterward

Do not mentally finish the procedure after seeing the capnography waveform.

Reassess:

Tube → oxygenation → ventilation → blood pressure → sedation → underlying physiology.

Look at the blood pressure again.

Look at the ventilator.

Look at the patient.

Ask whether positive-pressure ventilation has changed the circulation.

Start or continue appropriate analgesia and sedation promptly, alongside these checks, with doses suited to the circulation. Do not wait for movement in a paralyzed patient.

When is etomidate particularly attractive?

There is no induction agent that is ideal for every critically ill patient.

Etomidate becomes especially attractive when cardiovascular reserve is limited and avoiding additional myocardial depression or vasodilation is important.

This may include patients with severe shock, significant cardiovascular disease, or other conditions in which even a modest reduction in cardiac output or vascular tone may be poorly tolerated.

Ketamine may be a reasonable induction choice when analgesia or bronchodilation is useful. Its bronchodilator properties do not establish better outcomes in severe bronchospasm.

Propofol may be appropriate in patients who can tolerate its hemodynamic effects and when its pharmacological characteristics are desirable.

The decision should not begin with loyalty to a particular drug.

It should begin with the patient.

One more important point: do not use etomidate as a prolonged infusion

A single induction dose and prolonged exposure are very different clinical situations.

Because of ongoing inhibition of adrenal steroid synthesis, prolonged etomidate infusion is not recommended for routine sedation. Current prescribing information specifically warns against prolonged infusion because of sustained suppression of endogenous cortisol and aldosterone production.

Etomidate’s strength is as an induction agent, not as ongoing ICU sedation.

What should we remember during the next RSI?

Etomidate’s greatest advantage is not that it “raises the blood pressure.”

It is not a vasopressor.

Its advantage is that it usually disturbs cardiovascular physiology less than many alternative hypnotic agents.

That distinction matters.

A patient in shock may still deteriorate: induction can reduce sympathetic compensation, apnea stops spontaneous ventilation, and positive-pressure ventilation can reduce venous return.

So when the next unstable patient needs an airway, do not stop the discussion at:

“Etomidate or ketamine?”

Look one level deeper.

Ask:

What physiology is keeping this patient alive right now?

Then choose the induction drug, vasopressor strategy, oxygenation plan, ventilator approach, and post-intubation sedation accordingly.

Because in a critically ill patient, the safest airway is rarely determined by the induction drug alone.

It is determined by how well the entire team anticipates the physiology.

References and further reading

• Casey JD, et al. Ketamine or Etomidate for Tracheal Intubation of Critically Ill Adults. New England Journal of Medicine. DOI: 10.1056/NEJMoa2511420.
• Society of Critical Care Medicine. Guidelines for Rapid Sequence Intubation in the Critically Ill Adult Patient. 2023.
• National Library of Medicine. Etomidate injection prescribing information. DailyMed.
• Vinclair M, et al. Duration of adrenal inhibition following a single dose of etomidate in critically ill patients. Intensive Care Medicine. 2008;34:714–719. DOI: 10.1007/s00134-007-0970-y.