What is the recommended procedure for evaluating a suspected propofol allergy, including history, skin testing, and graded intravenous challenge?

Propofol Allergy Testing

Suspected propofol allergy should be evaluated through specialist referral for skin testing (prick and intradermal) performed 4-6 weeks after the reaction, as skin testing is technique-dependent and requires specialized training for proper interpretation. 1

When to Refer for Testing

Refer patients for propofol allergy evaluation only after a documented clinical event, not for routine screening. Specific indications include: 1

• Unexplained cardiovascular collapse (hypotension requiring active treatment) within minutes of propofol administration 1
• Unexplained bronchospasm with significant oxygen desaturation 1
• Widespread urticaria, angioedema, or anaphylaxis occurring shortly after propofol exposure 1

Pre-operative screening in patients without prior reactions has no value, as the sensitivity and specificity of tests are too low when pretest probability is minimal—neither positive nor negative results are predictive. 1

Timing and Preparation

Optimal Testing Window

• Perform skin testing 4-6 weeks after the suspected reaction to allow for full clinical recovery and restoration of mast cell mediators 2
• Testing too early may yield false-negative results 2

Medication Washout Requirements

Antihistamines must be discontinued before skin testing: 3

• Desloratadine: Stop ≥6 days before testing (elimination half-life ~27 hours) 3
• Second-generation antihistamines (cetirizine, fexofenadine, loratadine, levocetirizine): Stop 3-5 days before 3
• First-generation antihistamines (hydroxyzine, chlorphenamine): Stop 3-5 days before despite shorter half-lives due to potent suppression 3
• Tricyclic antidepressants also suppress skin reactivity and should be documented 3

Oral and inhaled corticosteroids do NOT need to be stopped. 1, 3

Testing Protocol

Skin Testing Components

The evaluation includes three complementary approaches: 2

1. Prick tests with propofol and Intralipid (the solvent)
2. Intradermal tests with propofol and Intralipid separately
3. Leukocyte histamine release test
4. IgE radioimmunoassay (RIA) against propofol

Testing must include both propofol AND Intralipid separately, as some patients react to propofol itself while others may react to the lipid vehicle. 2 In one study, 4 patients had positive tests to propofol but negative tests to Intralipid, confirming propofol-specific allergy. 2

Interpretation Standards

• Positive controls (histamine solution) and negative controls (physiological saline) must be used to validate results 4
• Measure wheal and erythema at 15-20 minutes after placement 4
• A wheal ≥3 mm indicates sensitization but requires clinical correlation to confirm true allergy 4
• Multiple positive tests strengthen the diagnosis: In a study of 14 patients with life-threatening propofol reactions, 13 had at least one positive test (2 had three positive tests, 4 had two positive tests, 7 had one positive test) 2

Alternative Testing When Skin Testing Is Not Feasible

If antihistamines cannot be safely discontinued or if the patient has contraindications to skin testing, use serum-specific IgE blood testing instead. 3

Blood-based IgE testing advantages: 3

• Unaffected by antihistamine use
• Sensitivity 58-90%, specificity 56-65% for allergen detection
• Particularly useful in patients with extensive eczema, dermatographism, or chronic urticaria where skin testing is impractical

Graded Intravenous Challenge

Graded IV challenge is NOT routinely recommended for propofol allergy evaluation. The evidence focuses on skin testing as the primary diagnostic modality. 1, 2

If challenge testing is considered after negative skin tests in a patient with high clinical suspicion, it must only be performed in specialist centers with full resuscitation equipment available, as systemic reactions including anaphylaxis are possible. 1, 4

Critical Clinical Context

Risk Factors to Document

Nine of 14 patients (64%) with confirmed propofol anaphylaxis had pre-existing allergic histories, including: 2

• Atopy
• Antibiotic allergies
• Muscle relaxant allergies
• Lidocaine allergy
• Colloid allergies

Notably, none had received propofol or Intralipid before their reaction, suggesting cross-reactivity with other substances containing phenyl nucleus or isopropyl groups. 2

Egg and Soy Allergy Controversy

There is no published evidence indicating propofol should be avoided in patients with egg or soy allergy, as the manufacturing process likely removes or denatures the allergenic proteins. However, a cautious approach is appropriate given propofol contains purified egg phosphatide and soybean oil. 1 One case report documented anaphylaxis with positive skin tests to both propofol and soybean, suggesting soy allergy as the mechanism. 5

Common Pitfalls

• Never perform skin testing without specialist training—results are highly technique-dependent and interpretation requires expertise 1
• Never give "test doses" in the operating room—predictive testing would require serial challenges with increasing doses over 30+ minutes, which is impractical and unsafe 1
• Do not test patients on antihistamines—this leads to false-negative results and missed diagnoses 3
• Do not confuse non-specific histamine release with true allergy—propofol can cause direct mast cell activation without IgE involvement 1