What are the considerations for using etomidate (amidate) for induction of general anesthesia or sedation in patients with a history of adrenal insufficiency or at risk for it?

Etomidate Use in Patients with Adrenal Insufficiency Risk

Avoid etomidate in patients with known adrenal insufficiency or at high risk for adrenal crisis; if etomidate must be used in high-risk patients, administer hydrocortisone 100 mg IV bolus immediately before induction. 1

High-Risk Populations Requiring Prophylactic Steroids

Absolute contraindications or mandatory steroid coverage:

• Patients with known Addison's disease require hydrocortisone 100 mg IV before etomidate administration 1, 2
• Chronic steroid users (for asthma, autoimmune diseases, or post-transplant) need prophylactic steroid supplementation 1
• Recent pituitary or adrenal surgery patients should receive prophylactic steroids 1
• Patients with unexplained hypotension not responding to fluids or vasopressors warrant caution and steroid consideration 1
• Septic shock patients not improving despite adequate resuscitation should receive steroids or avoid etomidate entirely 1

Mortality Risk Stratification

The mortality risk from etomidate correlates directly with illness severity:

• In septic patients, etomidate increases relative mortality risk by 22% (RR 1.22,95% CI: 1.11-1.35), with a number needed to harm of 12.5 patients 2, 3
• Patients with predicted mortality >44% based on APACHE/SAPS scores show significantly increased mortality (RR 1.20, CI: 1.12-1.29) 3
• Patients with predicted mortality <44% show no increase in mortality risk 3
• Overall critically ill patients receiving etomidate have 19% increased mortality risk (RR 1.19,95% CI: 1.10-1.30) 4

Adrenal Suppression Evidence

Etomidate causes biochemical adrenal suppression in nearly all patients:

• Adrenal insufficiency occurs 64% more frequently with etomidate versus other agents (RR 1.64, range 1.52-1.77) 4
• In sepsis specifically, adrenal insufficiency risk increases 33% (RR 1.33,95% CI: 1.22-1.46) 5
• Single-dose etomidate suppresses cortisol synthesis for up to 24 hours via 11β-hydroxylase inhibition 6, 4

Clinical Decision Algorithm

For hemodynamically unstable patients requiring rapid sequence intubation:

1. Assess adrenal insufficiency risk factors:

   • Check for chronic steroid use, Addison's disease, recent adrenal/pituitary surgery 1
   • Evaluate for persistent hypotension despite resuscitation, severe weakness, altered mental status 1
   • Review labs for hyponatremia, hyperkalemia, hypoglycemia 1

2. If high-risk features present:

   • Administer hydrocortisone 100 mg IV bolus immediately before etomidate 1, 2
   • Alternative: dexamethasone 4-8 mg IV if diagnosis uncertain 1
   • Consider alternative induction agents (midazolam, ketamine) 2

3. If septic shock with predicted mortality >44%:

   • Strongly consider avoiding etomidate entirely and use midazolam or ketamine instead 2, 3
   • If etomidate used, mandatory hydrocortisone 100 mg IV 1

4. For low-risk, hemodynamically stable patients undergoing brief procedures:

   • Single-dose etomidate acceptable with standard monitoring 7
   • Despite biochemical suppression, clinically significant adrenal insufficiency appears rare in this population 7
   • Cortisol levels remain within normal laboratory ranges despite decreased adrenal response 8, 7

Critical Pitfalls to Avoid

Do not rely on ACTH stimulation testing:

• The Surviving Sepsis Campaign recommends against using ACTH stimulation tests to identify which septic shock patients need hydrocortisone (grade 2B) 2
• Testing does not distinguish responders from non-responders effectively 2

Monitor for delayed adrenal crisis:

• Suspect adrenal insufficiency in ICU patients with refractory hypotension after etomidate induction, even with standard vasopressor doses 9
• Adrenal suppression persists beyond the immediate post-induction period 6, 4

Special populations requiring dose adjustments:

• Elderly patients may require lower etomidate doses and are at higher risk for cardiac depression, particularly with hypertension 6
• Obese patients or those on CYP3A4 inducers may need higher hydrocortisone doses due to altered pharmacokinetics 1

Alternative Agents

When etomidate is contraindicated:

• Midazolam and ketamine provide similar intubation conditions and hemodynamic stability without adrenal suppression 2
• These alternatives are particularly appropriate in septic patients with high predicted mortality 2, 3