Perioperative drug reactionsL23.3; L24.4; L25.1; L27.0; L27.1;

Hypersensitivity to drugs that were administered as a result of an operative measure in direct temporal connection to this - before, during or after the operative intervention.

Among the most common (about 60% of cases) triggers of POAR are muscle relaxants (atracurium, cis-atracurium, mivacurium, pancuronium, suxamethonium). They can be triggered both IgE-mediated and non-immunologically. Furthermore:

• Natural latex: 20% of cases
• Antibiotics: penicillins, cephalosporins about 15% of cases.
• Other (rather rare) triggers are chlorhexidine, NSAIDs (non-steroidal anti-inflammatory drugs), general anaesthetics (e.g. propofol, ketamine, thiopental, etomidate), opioids, heparins, benzodiazepines (midazolam), X-ray contrast media (iotrolane, iodixanol), (local anaesthetics (lidocaine).

1.10.000 (Pützner W et al. 2018)

As a rule, these are immediate reactions (occurrence < 1 hour after administration of the triggering drug). About 2/3 of the reactions are IgE-mediated, 1/3 are non-immunologically mediated. A few cases can be classified as late T-cellular reactions.

Most frequently, cutaneous, cardiovascular (hypotension, tachycardia, paradoxical bradycardia) and respiratory symptoms are detectable. On the skin, urticaria, flush are described.

Late reactions manifest as:

• heparin allergy (dermatitic reactions at the injection site)
• delayed urticaria/angioedema (e.g. NSAR hypersensitivity)
• as well as urticarial or maculo-papular exanthema after antibiotic applications.

If POAR is suspected, serum should be collected 1-2 hours after the first clinical symptoms to determine mast celltryptase. In 80% of cases of anaphylastic reaction forms, this shows an increase compared to the basal value. An increase of 2ng/ml is considered positive.

In vitro tests such as the lymphocyte transformation test, CAST or basophil activation test are critical in their sensitivity and specificity (Bonadonna P et al. (2015).

Skin tests (8 in the order: prick test, intradermal test if i.v. of AM is available) are particularly recommended for anaphylactic reactions.

Overview of maximum skin test concentrations of drugs in anaesthetic induction (var. according to Brockow K et al. 2013).

• Midazolam (5.0 mg/ml) - Prick test (5.0 mg/ml) - Intracutaneous test 0.5 mg/ml
• Propofol (10 mg/ml) - Prick test (10 mg/ml) - Intracutaneous test 1.0 mg/ml
• Ketamine (10 mg/ml) - Prick test (10 mg/ml) - Intracutaneous test 1.0 mg/ml
• Thiopental (25 mg/ml) - Prick test (25 mg/ml) - Intracutaneous test 2.5 mg/ml
• Etomidate (2.0 mg/ml) - Prick test (2.0 mg/ml) - Intracutaneous test 0.2 mg/ml
• Morphine (10.0 mg/ml) - Prick test (1.0 mg/ml) - Intracutaneous test 0.01 mg/ml
• Fentanyl (0.05 mg/ml) - Prick test (0.05 mg/ml) - Intracutaneous test 0.05 mg/ml
• Sufentanyl (0.05 mg/ml) - Prick test (0.05 mg/ml) - Intracutaneous test 0.005 mg/ml
• Alfentanyl (0.5 mg/ml) - Prick test (0.5 mg/ml) - Intracutaneous test 0.05 mg/ml
• Atracurium (10.0 mg/ml) - Prick test (1.0 mg/ml) - Intracutaneous test 0.01 mg/ml
• Cis-Atracurium (2.0 mg/ml) - Prick test (2.0 mg/ml) - Intracutaneous test 0.02 mg/ml
• Suxamethonium (50.0 mg/ml) - Prick test (10.0 mg/ml) - Intracutaneous test 0.1 mg/ml

In accordance with the recommendations for their administration to people allergic to X-ray contrast media, methylprednisolone 32mg p.o. can be administered 12 or 2 hours before elective procedures or 40mg i.v. 1-4 hours before emergency procedures. Additionally Dimetinden 4mg i.v. 30 min. before surgery.

1. Asserhøj LL et al (2016) No evidence for contraindications to the use of propofol in adults allergic to egg, soy or peanut†. Br J Anaesth 116:77-82.
2. Bonadonna P et al (2015) Drug hypersensitivity in clonal mast cell disorders: ENDA/EAACI position paper. Allergy 70:755-763.
3. Brockow K et al (2013) Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper. Allergy 68:702-712.
4. Pützer W et al (2018) Perioperative drug reactions - practical recommendations for allergy testing and patient management. Allergo J Int 27: 126-129