Which IV induction agent causes the MOST significant adrenocortical suppression and is therefore contraindicated in septic shock?

Explanation

## Adrenocortical Suppression and IV Induction Agents **Key Point:** Etomidate causes dose-dependent inhibition of 11β-hydroxylase, the enzyme responsible for cortisol synthesis, leading to acute adrenocortical suppression even after a single induction dose. ### Mechanism of Etomidate-Induced Adrenal Suppression Etomidate inhibits cytochrome P450 enzyme 11β-hydroxylase in the adrenal cortex, blocking the final step of cortisol synthesis. This occurs: - After a single induction dose (0.2–0.3 mg/kg IV) - Within minutes of administration - Lasting 4–8 hours post-dose - Causing a 50–80% reduction in plasma cortisol ### Comparative Adrenocortical Effects | Agent | Cortisol Suppression | Duration | Clinical Significance | | --- | --- | --- | --- | | **Etomidate** | Marked (50–80%) | 4–8 hours | **Contraindicated in sepsis/shock** | | **Propofol** | Mild (10–20%) | Brief | Minimal clinical impact | | **Ketamine** | None | — | No adrenal effect | | **Thiopentone** | None | — | No adrenal effect | **High-Yield:** Etomidate is absolutely contraindicated as an induction agent in septic shock, cardiogenic shock, or any critically ill patient requiring sustained cortisol response. A single dose can precipitate cardiovascular collapse in these settings. **Clinical Pearl:** In hemodynamically unstable patients, if etomidate is unavoidably used, concurrent hydrocortisone (50 mg IV every 6 hours) or dexamethasone must be given to prevent adrenal crisis. **Mnemonic:** **ETOMIDATE = ADRENAL THREAT** — Remember: Etomidate Threatens Adrenal function. **Warning:** Do NOT use etomidate for induction in septic or cardiogenic shock, even though it causes minimal direct myocardial depression. The adrenocortical suppression is the limiting factor.