Key Facts

Perioperative anaphylaxis is one of the most feared anaesthetic emergencies. Multiple drugs and substances are administered simultaneously during anaesthesia, making identification of the causative agent challenging. Immediate adrenaline administration is life-saving.

Epidemiology

NAP6 (2018) found the incidence of perioperative anaphylaxis to be approximately 1 in 10,000 anaesthetics. Mortality was approximately 3.8% (1 in 260,000 anaesthetics). Female patients are more commonly affected (2:1 ratio). NMBAs cause the majority of reactions.

Aetiology

Common triggers (NAP6 data):

• NMBAs: 56% (rocuronium and suxamethonium most common)
• Antibiotics: 22% (teicoplanin, co-amoxiclav most common)
• Chlorhexidine: 9%
• Patent blue dye: Used in sentinel lymph node biopsy
• Latex: Declining due to latex-free environments
• Colloids: Gelatins (Gelofusine) more than starches
• Other: Opioids, propofol (egg/soy allergy — rare), bone cement

Pathophysiology

Anaphylaxis is a type I (IgE-mediated) hypersensitivity reaction. Prior sensitisation produces specific IgE antibodies bound to mast cells and basophils. Re-exposure causes cross-linking of IgE, massive mast cell degranulation, and release of histamine, tryptase, prostaglandins, and leukotrienes → vasodilation, increased vascular permeability, bronchospasm, and myocardial depression → cardiovascular collapse.

Clinical Features (may present with any combination)

• Cardiovascular: Hypotension (most common feature under GA), tachycardia, cardiovascular collapse, cardiac arrest
• Respiratory: Bronchospasm (wheeze, increased airway pressures), laryngeal oedema, desaturation
• Cutaneous: Urticaria, erythema, angioedema — may be absent or late under drapes
• Gastrointestinal: Abdominal cramps, vomiting (if awake)

Grading (Ring and Messmer)

• Grade 1: Cutaneous signs only (urticaria, erythema)
• Grade 2: Moderate multisystem (hypotension, bronchospasm, cutaneous)
• Grade 3: Severe life-threatening (severe hypotension, severe bronchospasm, arrhythmia)
• Grade 4: Cardiac and/or respiratory arrest

Red Flags

• Sudden unexplained cardiovascular collapse at induction — anaphylaxis until proven otherwise
• Severe bronchospasm unresponsive to bronchodilators — consider anaphylaxis
• Hypotension refractory to fluids — adrenaline required
• Any reaction to chlorhexidine or latex exposure — remove all sources immediately

Bedside

• AAGBI standard monitoring: Continuous during event — note timing of drug administration relative to reaction onset
• Document: All drugs given with times, exact nature and timing of clinical features

Bloods

• Serum tryptase: Sample 1 — as soon as possible after initial treatment; Sample 2 — at 1-2 hours; Sample 3 — at >24 hours (baseline). Elevated tryptase confirms mast cell degranulation.
• ABG: Assess oxygenation, ventilation, lactate

Imaging

• CXR: If bronchospasm or laryngeal oedema — exclude pneumothorax

Special Tests

• Allergy testing at 6 weeks: Skin prick testing and intradermal testing for all potential triggers — performed at specialist allergy centres
• Specific IgE: For NMBAs, latex, chlorhexidine, antibiotics
• Component testing: Morphine quaternary ammonium IgE as surrogate for NMBA allergy
• Drug provocation test: In selected cases where skin tests are equivocal

Non-pharmacological

• Stop suspected trigger: Discontinue most recently administered drug
• Call for help: Declare anaphylaxis, assign roles
• Remove latex: If latex suspected, change gloves and equipment
• Position: Supine with legs raised (improves venous return)

Pharmacological

• Adrenaline (FIRST-LINE): 50mcg IV boluses (0.5mL of 1:10,000); titrate to response; up to 100-300mcg for severe reactions; infusion 0.05-1mcg/kg/min if refractory
• IV fluids: Aggressive crystalloid resuscitation — 20mL/kg bolus, repeat as needed (massive capillary leak may require >4L)
• Chlorphenamine: 10mg IV (antihistamine — second-line)
• Hydrocortisone: 200mg IV (prevents late-phase reaction — given after adrenaline)
• Bronchospasm: Salbutamol 250mcg IV or nebulised 5mg; aminophylline 5mg/kg IV over 20 min if refractory
• If cardiac arrest: ALS algorithm with adrenaline 1mg IV every 3-5 min; prolonged CPR may be needed

Surgical/Interventional

• Abandon or abbreviate surgery if possible during active anaphylaxis
• ICU transfer for observation (biphasic reaction may occur in 5-20% at 4-12 hours)

Referral Criteria

• ALL suspected perioperative anaphylaxis — refer to specialist allergy clinic at 6 weeks
• Complete AAGBI anaphylaxis reaction form
• Report to MHRA (Yellow Card Scheme)
• Issue patient with interim letter documenting suspected triggers and advising future avoidance

• Mortality: ~3.8% overall (NAP6); higher in grade 4-5 reactions
• Early adrenaline: Key determinant of survival — delayed adrenaline is the most common factor in fatal anaphylaxis
• Biphasic reaction: Occurs in 5-20% at 4-12 hours — observe in ICU/HDU for minimum 12-24 hours
• Future anaesthesia: Safe with avoidance of identified triggers — specialist allergy testing provides a 'safe drug list'
• Recurrence: Avoidable with appropriate investigation and planning

Perioperative Anaphylaxis Management Algorithm

NAP6 — Causes of Perioperative Anaphylaxis