Which IV induction agent is contraindicated in patients with porphyria?

Explanation

## Porphyria and IV Induction Agents ### Thiopentone and Acute Porphyria **Key Point:** Thiopentone is an absolute contraindication in acute intermittent porphyria (AIP) and variegate porphyria because it induces hepatic δ-aminolevulinic acid synthase (ALAS), precipitating life-threatening porphyric crisis. ### Mechanism of Porphyria Precipitation 1. Thiopentone (and other barbiturates) induce hepatic cytochrome P450 enzymes 2. Increased P450 activity ↑ heme consumption 3. Compensatory ↑ in ALAS activity (rate-limiting enzyme of heme synthesis) 4. Accumulation of toxic porphyrin precursors (δ-ALA, porphobilinogen) 5. **Acute porphyric crisis:** severe abdominal pain, neuropsychiatric symptoms, autonomic instability, potentially fatal **High-Yield:** All **barbiturates** (thiopentone, pentobarbital) are contraindicated in porphyria. Non-barbiturate agents are safe. ### Safe Induction Agents in Porphyria | Agent | Safety in Porphyria | Mechanism | |-------|---------------------|----------| | **Ketamine** | ✓ Safe | Non-barbiturate; does not induce ALAS | | **Propofol** | ✓ Safe | Non-barbiturate; minimal enzyme induction | | **Etomidate** | ✓ Safe | Non-barbiturate; no porphyrinogenic effect | | **Thiopentone** | ✗ **CONTRAINDICATED** | Barbiturate; induces ALAS → porphyric crisis | **Clinical Pearl:** Patients with known or suspected porphyria require careful anesthetic planning: - Avoid all barbiturates - Preferred agents: ketamine, propofol, etomidate, volatile anesthetics (sevoflurane, isoflurane) - Avoid NSAIDs, sulfonamides, and other known porphyrinogenic drugs - Maintain normothermia and adequate hydration perioperatively **Mnemonic:** **SAFE agents in porphyria = Sevoflurane, Atropine, Fentanyl, Etomidate** (and propofol, ketamine) **Warning:** Thiopentone-induced porphyric crisis can present with severe autonomic instability (tachycardia, hypertension, arrhythmias), mimicking sepsis or anaphylaxis, leading to diagnostic delay. [cite:Gupta & Sharma Essentials of Anaesthesia Ch 8; Harrison 21e Ch 381]