Can etomidate (amidate) cause hypoglycemia?

Etomidate Does Not Cause Hypoglycemia

Etomidate does not cause hypoglycemia—its primary metabolic concern is adrenal suppression through inhibition of cortisol synthesis, not glucose dysregulation. The drug's mechanism of action involves blocking steroidogenic enzymes (specifically 11β-hydroxylase and cholesterol side-chain cleavage enzyme), which suppresses cortisol production but does not directly affect glucose homeostasis 1.

Mechanism of Metabolic Effects

The key metabolic concern with etomidate is adrenal insufficiency, not hypoglycemia:

• Etomidate produces concentration-dependent blockade of mitochondrial cytochrome P-450-dependent enzymes in the adrenal steroidogenic pathway, specifically inhibiting cortisol and aldosterone synthesis 1
• This adrenal suppression occurs even after a single induction dose and can persist for hours to days after administration 2, 1
• The resulting adrenal insufficiency manifests as hemodynamic instability, hypotension refractory to vasopressors, and cardiovascular collapse—not hypoglycemia 2

Clinical Implications of Adrenal Suppression

The adrenal suppression caused by etomidate has significant mortality implications in critically ill patients:

• In patients with severe critical illness (predicted mortality >44%), etomidate increases relative mortality rate (RR = 1.20,95% CI: 1.12-1.29) with a number needed to harm of 12.5 3
• The Surviving Sepsis Campaign guidelines note that etomidate use before steroid therapy was associated with increased 28-day mortality in septic shock patients 4
• Acute adrenocortical crisis after etomidate presents with hypotension and cardiovascular instability, not glucose abnormalities 2

Why Hypoglycemia Is Not a Concern

Etomidate's metabolic effects are confined to the adrenal axis and do not involve glucose regulation:

• The drug specifically inhibits steroidogenic enzymes without affecting insulin secretion, glucose production, or glucose utilization 1
• None of the guideline documents addressing etomidate safety mention hypoglycemia as an adverse effect 4
• The documented adverse effects include myoclonus, pain on injection, nausea, vomiting, and adrenal suppression—but not hypoglycemia 4

Critical Pitfalls to Avoid

When using etomidate, clinicians should focus on adrenal complications, not glucose management:

• Avoid etomidate in patients with septic shock or severe critical illness without planning for corticosteroid supplementation 5, 3
• Pediatric critical care guidelines explicitly recommend against etomidate use in critically ill children, particularly those with septic shock, due to adrenal suppression 5
• Consider glucocorticoid supplementation in patients with severe critical illness who receive etomidate, as the drug effectively induces "pharmacological adrenalectomy" 3, 6
• Monitor for hypotension refractory to standard vasopressors as a sign of etomidate-induced adrenal insufficiency, not for hypoglycemia 2

Alternative Agents When Adrenal Function Is Critical

In critically ill patients where adrenal suppression poses significant risk, ketamine is preferred over etomidate:

• Ketamine maintains hemodynamic stability through sympathomimetic properties while preserving adrenal function 5
• The American College of Critical Care Medicine recommends ketamine over etomidate in pediatric septic shock specifically to avoid adrenal suppression 5