Lab Update 63 – Perioperative Hypersensitivity Reactions
Authors: Dr Sylvia van den Berg, Dr Carla van Heerden, Dr Louise Murray
Published: May 2025
Overview
Immediate perioperative hypersensitivity reactions (POH) present significant diagnostic challenges due to the simultaneous exposure to multiple substances and the complexity of differential diagnoses in surgical settings. Incidence estimates range from 1 in 353 to 1 in 18,600 procedures.
Common triggers include:
- Neuromuscular blocking agents (NMBAs)
- Antibiotics (especially β-lactams)
- Chlorhexidine
- Latex
Mechanisms of POH include:
- IgE-mediated type 1 hypersensitivity
- Non-allergic reactions (e.g., MRGPRX2 receptor activation)
Accurate diagnosis requires distinguishing between these mechanisms and identifying the specific trigger among multiple exposures.
What’s New: Chlorhexidine IgE and CAST Testing
Chlorhexidine accounts for 9–10% of allergic reactions in some countries. Though rare, its use is increasing, raising the risk of hypersensitivity.
Chlorhexidine IgE and CAST tests are now available to detect:
- IgE-mediated sensitisation
- Basophil-mediated reactions
These tests are crucial for diagnosing severe allergic responses (including anaphylaxis) during surgery, catheterisation, or consumer use of chlorhexidine-containing products. They help guide the use of alternative antiseptics for sensitised individuals.
Investigative Approach
A systematic approach is recommended to identify the cause of POH:
- Detailed Clinical History
Document all substances the patient was exposed to during the perioperative period. - Skin Testing
Conduct skin prick and intradermal tests with suspected agents (e.g., antibiotics) in a specialist clinic with resuscitation facilities. - Blood Tests
- Serum Tryptase: Collect within 1 hour of the reaction and again after 24 hours. Elevated baseline levels may indicate mast cell disorders.
- Specific IgE: Test for allergens like penicillin.
- CAST/BAT: Useful for all drugs, adjuvants, and additives. Perform 4–6 weeks post-reaction. If no commercial allergen is available, submit the drug in pill or ampoule form for modified CAST testing.
- Drug Provocation Tests (DPT)
Conducted under medical supervision in specialised centres if other tests are inconclusive.
Diagnostic Considerations
- Collaborate closely with the anaesthetist during the acute phase for sample collection.
- Compare acute and post-24h tryptase levels to confirm type 1 hypersensitivity.
- Investigate elevated baseline tryptase for conditions like hereditary alpha-tryptasaemia or systemic mastocytosis.
Common Triggers of POH
- NMBAs: Suxamethonium, rocuronium, vecuronium, atracurium, cisatracurium
- Antibiotics: Penicillin, cephalosporins, vancomycin, quinolones
- Opioids: Morphine, fentanyl, codeine (often non-IgE mediated)
- Hypnotics: Propofol (especially in egg/soy allergy), thiopental, etomidate
- Other Drugs: Local anaesthetics, NSAIDs, heparin, protamine, blood products
- Colloids: Gelatin-based solutions, dextran, hydroxyethyl starch
- Chlorhexidine: Antiseptic in surgical prep and catheter coatings
- Latex: Gloves, catheters, medical devices
- Dyes: Methylene blue, patent blue, indocyanine green
- Non-specific Triggers: Iodinated contrast media, iodine antiseptics, bone cement