The Sibling Effect: Can Etomidate’s Analogues Offer Better Anaesthetic Induction for Cardiac Surgery?

Authors: Bugo S et al.

Journal of Cardiothoracic and Vascular Anesthesia, February 12, 2026 (Editorial)

Summary

This editorial reviews etomidate and its emerging analogues as potential induction agents for cardiac surgery, where preserving hemodynamic stability is paramount.

Cardiac surgical patients are especially vulnerable during induction due to limited cardiovascular reserve. Induction must balance hypnosis, analgesia, amnesia, and muscle relaxation while maintaining myocardial function and end-organ perfusion.

Current induction landscape in cardiac anesthesia:

• Propofol: Most commonly used; rapid and effective but frequently causes hypotension and myocardial depression.

• Ciprofol: Propofol analogue with less injection pain but similar hemodynamic depression.

• Benzodiazepines/Remimazolam: Hemodynamically modest; remimazolam shows lower hypotension rates versus propofol in some cardiac settings.

• Ketamine: Sympathomimetic but may worsen ventricular function and myocardial oxygen demand; potentially dangerous in catecholamine-depleted states.

• Volatiles: Myocardial-protective properties suggested, but limited role for adult IV induction and increasing environmental scrutiny.

Etomidate: Strengths and Liabilities

Etomidate remains uniquely attractive for cardiac induction:

• Rapid onset (3–5 minutes duration at 0.2–0.3 mg/kg).

• Preserves sympathetic tone and baroreflexes.

• Minimal respiratory depression.

• Lower rates of hypotension compared with propofol.

However, its inhibition of 11β-hydroxylase leads to transient adrenal suppression:

• 6–8 hours after single bolus.

• Up to 48 hours after infusion.

Observational data in sepsis have linked etomidate to increased mortality, prompting caution in critical care guidelines. However, in cardiac surgery cohorts:

• Meta-analyses show improved hemodynamic stability.

• No consistent increase in mortality.

• Reduced vasopressor needs versus other agents.

The problem arises primarily with prolonged infusion—not single bolus induction.

Next-Generation Etomidate Analogues

To preserve hemodynamic benefits while minimizing adrenal suppression, several derivatives have been developed:

MOC-etomidate

• Ultra–short acting via rapid ester hydrolysis.

• Short half-life (~4 min).

• Less prolonged adrenal suppression in preclinical models.

• Concern: metabolite (MOC-ECA) accumulation and delayed recovery with infusion.

Carboetomidate

• Structural modification reduces binding to 11β-hydroxylase.

• Less adrenal suppression in animal models.

• Slower onset than etomidate.

• Preserved hemodynamic stability.

• Possible antiemetic effects (5-HT3 interaction).

MOC-carboetomidate

• Combines rapid metabolism with reduced adrenal inhibition.

• Faster recovery than carboetomidate.

• Improved corticosterone levels vs etomidate in animal studies.

CPMM (ABP-700)

• Rapid esterase metabolism.

• Phase I human studies: rapid onset (~30 sec), minimal respiratory depression.

• Adrenal axis comparable to placebo.

• Mild HR/BP increases at higher doses.

• Most promising candidate to date.

ET-26

• Phase I human studies completed.

• Well tolerated up to 2.8 mg/kg.

• Bradycardia without hypotension.

• Transient cortisol suppression (3–4 hours) with recovery.

Takeaway

Etomidate remains unmatched for induction hemodynamic stability in cardiac surgery. Its Achilles’ heel is adrenal suppression. The next generation of analogues—especially CPMM and ET-26—aim to uncouple cardiovascular stability from endocrine suppression.

If phase II and III trials confirm preserved hemodynamics without clinically meaningful adrenal inhibition, these “siblings” may redefine induction strategies in cardiac anesthesia.

What You Should Know

1. Hemodynamics still dominate induction decision-making in cardiac surgery.

2. Single-dose etomidate does not consistently worsen cardiac surgical outcomes.

3. Prolonged infusions remain harmful.

4. CPMM (ABP-700) and ET-26 are the most clinically advanced analogues.

5. The future of cardiac induction may shift toward engineered ultra-short, hemodynamically neutral hypnotics.

Key Points

• Etomidate offers exceptional hemodynamic stability but suppresses adrenal steroidogenesis.

• Cardiac surgery data do not show clear mortality harm with single-dose use.

• Novel derivatives aim to preserve stability while minimizing endocrine risk.

• CPMM and ET-26 have progressed to early human trials.

• Ongoing phase II/III studies will determine whether these agents reshape cardiac induction practice.

Thank you to the Journal of Cardiothoracic and Vascular Anesthesia for allowing us to summarize and share this timely editorial on the evolving science of cardiac anesthesia induction.