A 38-year-old woman with asthma and a history of anaphylaxis to penicillin is scheduled for emergency appendectomy. During rapid sequence intubation, she is induced with thiopental 5 mg/kg IV. Within 2 minutes of induction, she develops bronchospasm, hypotension (BP 78/45 mmHg), and a diffuse erythematous rash. Oxygen saturation drops to 88% on 100% O₂. Which of the following is the MOST likely mechanism underlying this adverse reaction?

Explanation

## Thiopental-Induced Histamine Release ### Mechanism of Adverse Reaction **Key Point:** Thiopental is a **direct mast cell degranulator** that triggers non-IgE-mediated histamine release. This is a dose-dependent pharmacological effect, NOT an allergic reaction, though the clinical presentation mimics anaphylaxis. ### Histamine-Mediated Effects in This Patient Histamine release from mast cells causes: 1. **Bronchospasm** — H₁ receptor activation on airway smooth muscle → bronchoconstriction 2. **Hypotension** — H₁ and H₂ receptor activation on vascular endothelium → vasodilation and increased vascular permeability 3. **Erythematous rash** — cutaneous vasodilation and increased capillary permeability 4. **Hypoxaemia** — secondary to severe bronchospasm despite 100% O₂ ### Why This Patient Is at Higher Risk **Clinical Pearl:** Patients with **pre-existing asthma and atopy** (history of anaphylaxis) have: - Increased mast cell burden in airways and skin - Enhanced mast cell degranulation sensitivity - Baseline airway hyperreactivity Thiopental's direct degranulation effect is therefore more pronounced and clinically significant in this population. ### Distinction: Pharmacological vs. Allergic | Feature | Thiopental Histamine Release | True IgE-Mediated Allergy | |---|---|---| | **Onset** | Rapid (seconds–minutes) | Rapid (seconds–minutes) | | **Dose-dependent** | Yes | No (all-or-nothing) | | **Prior exposure required** | No | Yes (sensitization) | | **Skin testing** | May show non-specific reactivity | Positive IgE-specific test | | **Rechallenges** | Reproducible with same dose | Unpredictable; may be severe | | **Mechanism** | Direct degranulation | IgE cross-linking | **High-Yield:** Thiopental is **contraindicated in asthmatic patients** because its direct mast cell degranulation effect is amplified by airway mast cell hyperreactivity. Propofol or etomidate are safer alternatives. ### Management of Acute Reaction ```mermaid flowchart TD A[Thiopental-induced histamine release]:::outcome --> B[Stop thiopental immediately]:::action B --> C[100% O₂ + manual ventilation]:::action C --> D[Adrenaline IM 0.3-0.5 mg]:::action D --> E{Bronchospasm controlled?}:::decision E -->|No| F[IV salbutamol or aminophylline]:::action E -->|Yes| G[IV H₁ blocker: chlorpheniramine 10 mg]:::action G --> H[IV H₂ blocker: ranitidine 50 mg]:::action H --> I[IV corticosteroid: hydrocortisone 100 mg]:::action I --> J[Fluid resuscitation for hypotension]:::action ``` **Mnemonic:** **AABC** for thiopental anaphylaxis management: - **A** — Adrenaline (IM 0.3–0.5 mg) - **A** — Airway (secure, consider cricothyrotomy if severe) - **B** — Bronchodilators (IV salbutamol, aminophylline) - **C** — Corticosteroids + antihistamines [cite:KD Tripathi 8e Ch 12]