A 42-year-old woman with a history of adrenal insufficiency (on replacement hydrocortisone) presents for emergency appendicectomy. She is hemodynamically stable: BP 130/82 mmHg, HR 92/min, RR 16/min. The anesthetist is deciding between propofol and etomidate for rapid sequence induction. Which agent should be **avoided** in this patient and why?

Explanation

## Clinical Context This patient has **known adrenal insufficiency** and is on hydrocortisone replacement. The question tests understanding of which induction agent causes **iatrogenic adrenocortical suppression** and why it is contraindicated in this setting. ## Etomidate and Adrenocortical Suppression **Key Point:** Etomidate inhibits **11β-hydroxylase** in the adrenal cortex, blocking the final step of cortisol synthesis. Even a **single induction dose** causes adrenocortical suppression lasting **24 hours or more**. ### Mechanism of Etomidate-Induced Adrenal Suppression 1. **Target**: 11β-hydroxylase (cytochrome P450 11B1), which catalyzes the conversion of 11-deoxycortisol → cortisol. 2. **Onset**: Suppression begins within minutes of IV administration. 3. **Duration**: Plasma cortisol remains suppressed for 24–48 hours even after a single induction dose. 4. **Clinical consequence**: In a patient with **pre-existing adrenal insufficiency**, etomidate-induced suppression on top of baseline deficiency can precipitate **acute adrenal crisis** (hypotension, hyponatremia, hyperkalemia, cardiovascular collapse). ## Why Hydrocortisone Replacement Does Not Prevent Etomidate-Induced Crisis **High-Yield:** The patient's baseline hydrocortisone replacement is calculated to cover **basal and minor stress needs**. Etomidate suppresses the **remaining endogenous cortisol production**, and the fixed replacement dose may be insufficient to cover the acute surgical stress + etomidate-induced suppression. **Clinical Pearl:** Patients with adrenal insufficiency undergoing surgery require: - **Perioperative steroid coverage**: 50–100 mg hydrocortisone IV at induction, then 25–50 mg every 6–8 hours intraoperatively and for 24–48 hours postoperatively. - **Avoidance of etomidate**: Even with steroid coverage, etomidate is contraindicated because it compounds the adrenal deficit. ## Comparison: Propofol vs. Etomidate in Adrenal Insufficiency | Agent | Adrenocortical Effect | Hemodynamic Effect | Use in Adrenal Insufficiency | |-------|----------------------|-------------------|------------------------------| | **Propofol** | No direct suppression | Vasodilation, ↓ BP | Acceptable with steroid coverage and careful dosing | | **Etomidate** | **Inhibits 11β-hydroxylase** | Minimal hemodynamic change | **Contraindicated** — suppresses endogenous cortisol | | **Ketamine** | No adrenocortical effect | Sympathomimetic, ↑ or ↔ BP | **Excellent choice** in adrenal insufficiency | | **Thiopentone** | No direct suppression | Severe ↓ BP | Poor choice due to hypotension | ## Why Not the Other Options? - **Option 0 (Propofol causes adrenocortical suppression)**: Propofol does **not** inhibit 11β-hydroxylase; it causes hypotension and myocardial depression but not adrenocortical suppression. With adequate steroid coverage and careful dosing, propofol is acceptable. - **Option 2 (Propofol causes severe hypotension in all adrenal-insufficient patients)**: While propofol does cause hypotension, this is a **hemodynamic** issue, not an adrenocortical one. The question specifically asks about adrenal crisis prevention. - **Option 3 (Etomidate causes apnea and airway obstruction)**: Etomidate does **not** cause prolonged apnea or airway obstruction; it maintains airway reflexes well. The problem is adrenocortical suppression, not respiratory depression. **Mnemonic:** **ETOMIDATE = Endocrine Threat (11β-hydroxylase Inhibition)**