A 42-year-old woman with a history of adrenal insufficiency (on replacement hydrocortisone) presents for emergency appendicectomy. She is hemodynamically stable (BP 118/76 mmHg, HR 82 bpm). Induction is planned. Which IV induction agent should be avoided in this patient and why?

Explanation

## Etomidate and Adrenal Suppression: A Critical Drug–Disease Interaction ### The Problem: Etomidate's Mechanism of Adrenal Toxicity **Key Point:** Etomidate inhibits the enzyme **11β-hydroxylase** (cytochrome P450 11B1), which catalyzes the final step of cortisol synthesis in the adrenal cortex. Even a single induction dose causes transient but significant suppression of plasma cortisol for 4–8 hours post-administration. ### Cortisol Synthesis Pathway and Etomidate's Site of Action ```mermaid flowchart TD A[Cholesterol] -->|P450scc| B[Pregnenolone] B -->|17α-hydroxylase| C[17-OH Pregnenolone] C -->|17,20-lyase| D[DHEA] D -->|17β-HSD| E[Androstenediol] E -->|3β-HSD| F[Testosterone] B -->|3β-HSD| G[Progesterone] G -->|17α-hydroxylase| H[17-OH Progesterone] H -->|17,20-lyase| I[Androstenedione] I -->|17β-HSD| F G -->|21-hydroxylase| J[11-Deoxycorticosterone] J -->|11β-hydroxylase| K[Corticosterone] H -->|21-hydroxylase| L[11-Deoxycortisol] L -->|11β-hydroxylase:::urgent| M[Cortisol] style M fill:#ff6b6b classDef urgent fill:#ff6b6b,stroke:#c92a2a,color:#fff ``` **High-Yield:** Etomidate blocks the **final, rate-limiting step** of cortisol synthesis. In a patient with pre-existing adrenal insufficiency (already cortisol-deficient), even transient suppression can precipitate acute adrenal crisis with refractory hypotension, hyponatremia, and cardiovascular collapse. ### Clinical Consequence in This Patient This 42-year-old is on hydrocortisone replacement for adrenal insufficiency. Her baseline cortisol production is already zero or near-zero. If etomidate is used: 1. **Immediate effect:** Blocks residual/replacement cortisol production 2. **Timeline:** Suppression lasts 4–8 hours post-induction 3. **Risk:** Acute adrenal crisis intraoperatively or in immediate post-operative period 4. **Presentation:** Refractory hypotension, bradycardia, hyponatremia, altered mental status ### Why Other Agents Are Safer | Agent | Adrenal Effect | Safety in Adrenal Insufficiency | Recommendation | |-------|----------------|--------------------------------|----------------| | **Propofol** | No direct adrenal suppression | Safe; monitor BP due to vasodilation | ✓ Acceptable | | **Etomidate** | **11β-hydroxylase inhibition** | **CONTRAINDICATED** | ✗ Avoid | | **Ketamine** | No adrenal suppression; sympathomimetic | Safe; maintains BP | ✓ Preferred | | **Thiopentone** | No adrenal suppression | Safe but less commonly used | ✓ Acceptable | ### Clinical Pearl **Warning:** Even in patients WITHOUT baseline adrenal insufficiency, a single induction dose of etomidate causes measurable cortisol suppression. In critically ill patients (sepsis, trauma, ICU admission), this transient suppression may increase mortality. Etomidate is now often avoided for induction in ICU settings for this reason. ### Perioperative Management for This Patient 1. **Induction:** Use **ketamine** (preferred) or propofol (with fluid support) 2. **Stress-dose steroids:** Administer IV hydrocortisone 50–100 mg at induction, then 25–50 mg every 6–8 hours intraoperatively and for 24–48 hours post-operatively 3. **Avoid:** Etomidate absolutely 4. **Monitoring:** Watch for intraoperative hypotension; have vasopressors ready ### Mnemonic **ETOMIDATE = Endocrine Toxicity — Omit In adrenal Deficiency**