Can a single dose of etomidate (amidate) cause adrenal insufficiency?

Adrenal Suppression with Single-Dose Etomidate

Yes, a single dose of etomidate causes adrenal suppression lasting 6-8 hours in most patients, with biochemical evidence of 11β-hydroxylase blockade persisting up to 48 hours in critically ill patients, though the clinical significance of this suppression in hemodynamically stable patients undergoing brief procedures remains uncertain. 1, 2

Mechanism and Duration of Adrenal Suppression

The FDA label explicitly states that reduced plasma cortisol and aldosterone levels occur following induction doses of 0.3 mg/kg etomidate, persisting for approximately 6-8 hours and appearing unresponsive to ACTH stimulation due to blockage of 11β-hydroxylase within the adrenal cortex. 1

More detailed investigation reveals the suppression is more prolonged than initially recognized:

• In critically ill patients, 80% (32/40) demonstrated etomidate-related adrenal insufficiency at 12 hours post-administration, defined by inadequate cortisol response to ACTH stimulation (<250 nmol/L rise) combined with excessive 11β-deoxycortisol accumulation. 2
• This incidence decreased significantly to 9% at 48 hours and 7% at 72 hours, indicating reversibility by 48 hours in most patients. 2
• The cortisol to 11β-deoxycortisol ratio improved significantly over time, reflecting recovery of 11β-hydroxylase enzyme function. 2

Clinical Significance by Patient Population

Hemodynamically Stable Patients (Procedural Sedation)

In pediatric and adult patients undergoing brief ED procedures, no clinically important adrenal suppression requiring corticosteroid replacement was documented despite biochemical changes. 3

• A retrospective study of 100 pediatric patients found zero cases requiring corticosteroids for suspected adrenal suppression during hospitalization, though inpatient records were available on 99 patients. 3
• Another pediatric study of 105 patients reported no episodes of adrenal suppression determined either clinically or with laboratory testing. 3
• A prospective randomized trial found that although etomidate decreased normal adrenal response at 4 hours, all measured cortisol levels remained within normal laboratory ranges throughout 24 hours, and levels were no longer affected by 12 hours. 3

Critical caveat: These studies evaluated clinical manifestations, not biochemical suppression, and may have missed subclinical adrenal dysfunction in patients not requiring prolonged hospitalization.

Critically Ill and Septic Patients

The evidence strongly argues against etomidate use in septic patients due to mortality impact:

• A systematic review and meta-analysis of 3,715 septic patients demonstrated a relative risk of death with etomidate of 1.22 (95% CI 1.11-1.35), representing a statistically significant and clinically relevant 22% increase in mortality. 4
• The Society of Critical Care Medicine acknowledges etomidate's effect on adrenal function, though guidelines note most studies show no significant mortality difference between etomidate and other induction agents in general critically ill populations. 5

For septic shock specifically, etomidate should be avoided entirely. 4

Trauma Patients

Small randomized controlled trials in trauma patients showed etomidate was associated with:

• Increased pneumonia incidence (56.7% vs 25.9% in controls) 4
• Prolonged ICU stay (6.3 vs 1.5 days) 4
• Prolonged hospital stay (11.6 vs 6.4 days) 4

Etomidate should be avoided in unstable trauma patients. 4

Risk Stratification and Prophylactic Management

The American Society of Anesthesiologists recommends administering hydrocortisone 100 mg IV bolus immediately before etomidate administration in high-risk patients. 5

High-risk populations requiring prophylactic steroids include:

• Patients with known Addison's disease or chronic steroid use 5
• Patients on long-term steroids for asthma, autoimmune diseases, or post-transplant 5
• Patients who have undergone recent pituitary or adrenal surgery 5
• Patients with unexplained hypotension not responding to fluids or vasopressors 5
• Patients with septic shock not improving despite adequate resuscitation 5

Clinical signs suggesting adrenal crisis:

• Persistent hypotension despite fluids/pressors 5
• Severe weakness, fatigue, collapse, altered mental status 5
• Nausea, vomiting, abdominal pain 5
• Laboratory findings: hyponatremia, hyperkalemia, hypoglycemia, low bicarbonate/mild metabolic acidosis 5

Alternative Induction Agents

Midazolam and ketamine are valid alternatives providing similar intubation and hemodynamic conditions as etomidate but without adrenal suppression effects. 4

Practical Recommendations

For hemodynamically stable patients undergoing brief procedures: Single-dose etomidate can be used with standard monitoring, as clinically significant adrenal insufficiency appears rare despite biochemical suppression. 3

For critically ill patients without sepsis: Consider empirical steroid supplementation (hydrocortisone 100 mg IV) for 48 hours following single-dose etomidate, as 80% demonstrate biochemical adrenal insufficiency at 12 hours. 2, 5

For septic or unstable trauma patients: Avoid etomidate entirely and use alternative agents (midazolam, ketamine) due to demonstrated mortality and morbidity increases. 4

Case reports document acute adrenal crisis: At least one case report describes acute adrenocortical insufficiency and crisis after standard induction dose of etomidate in an ICU patient presenting with hypotension refractory to standard vasopressor administration. 6