Allergy to Neuromuscular Blocking Agents and Pholcodine Exposure

Study Overview
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Brief Summary
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The main objective of this study is to compare pholcodine exposure in patients having presented with a perianaesthetic anaphylactic reaction to a NMBA (cases) to pholcodine exposure in matched anaesthetised patients with injection of NMBA, who did not present with an anaphylactic reaction (controls). The secondary objectives of the study are: To compare anti-pholcodine IgE, anti-ammonium IV IgE and total IgE levels between the case and control groups. To study the concordance between exposure to pholcodine in cases and controls, by means of a patient self-questionnaire on the one hand and, on the other hand, by a computerized drug history, supplemented where relevant by the drug master file. To study the impact of taking 1, 2 or 3 sources in account for pholcodine exposition. To study the association between exposure to pholcodine and the presence/levels of pholcodine-specific IgE, reflecting sensitisation to pholcodine. To study NMBA and pholcodine cross-sensitisation by testing skin reactions to pholcodine in case patients allergic to (at least) one NMBA.

Official Title
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Anaphylaxis to Neuromuscular Blocking Agents and Pholcodine Exposure. Case-control Study

Conditions
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Neuromuscular Blocking Agents Anaphylaxis

Intervention / Treatment
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* Other: intradermal pholcodine allergy test in cases
* Other: Blood sampling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age ≥ 2 years old. Referred to anaesthesia-allergy consultation within (approximately) 6 to 12 weeks of occurrence of peranaesthetic anaphylactic reaction during anaesthesia with administration of NMBAs (only for case patient). Having given his/her consent (or the 2 parents consent for minors). Affiliated with a social security scheme or dependent. Able to answer a medicinal product intake questionnaire In a clinical condition compatible with skin tests (no skin disease or psychiatric illness, etc.) (only for case patient) Having stopped any anti-histamine treatment at least 8 days previously (only for case patient). With positive skin test for the suspected NMBA (ony for case patient). Patient anaesthetised in a control recruitment centre (only for control patients) Having undergone anaesthesia with NMBA injection, without onset of peranaesthetic anaphylactic reaction whatever his medical history (only for control patients) Exclusion Criteria: Patients who have refused, or are unable to give their consent Patients who have had negative control skin tests Anaphylaxis suspected to be related to other drugs given on induction of anaesthesia, eg. antibiotics Having presented with anaphylactic reaction during a previous anaesthesia without NMBA injection Pregnant females at inclusion or during 12 months before anaesthesia

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cases with NMBA anaphylaxis<br>Patients who experienced NMBA anaphylaxis during anesthesia | Other: intradermal pholcodine allergy test in cases<br> <br> Other: Blood sampling<br> <br> |
| Other: controls<br>Patients who underwent anesthesia with NMBA injection but did not experience anaphylaxis | Other: Blood sampling<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exposure to pholcodine | Exposure is measured by autoquestionnaire, patient's pharmaceutical file and drug history by the pharmacist's | within the 12 months before the anesthetic procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-pholcodine IgE, anti-ammonium IV IgE and total IgE levels between the case and control groups. | Cases: 6 to 12 weeks after the general anesthetic procedure (corresponding to the day of inclusion) Controls: during their hospitalisation after the general anesthetic procedure (Maximum 90 days after the general anesthetic procedure, corresponding to the day of inclusion) | Between 1 day to 12 weeks after the general anesthetic procedure | 
| Concordance between exposure to pholcodine in cases and controls, by means of a patient self-questionnaire on the one hand and, on the other hand, by a computerized drug history, supplemented where relevant by the drug master file. |  | within the 12 months preceeding the general anesthesia | 
| Impact of non subjective sources in pholcodine exposure assessment | We will study if pholcodine exposure criteria measured by autoquestionnaire is modified by taking into account non subjectives sources which are the patient's pharmaceutical file and his drug history by his pharmacist's | within the 12 months preceeding general anesthetic procedure | 
| Association between exposure to pholcodine and the presence/levels of pholcodine-specific IgE, reflecting sensitisation to pholcodine. | IgE measurements: total IgE, IgE specific for pholcodine, quaternary ammoniums (KU/L) | within the 12 months preceding the general anesthetic procedure | 
| NMBA and pholcodine cross-sensitisation by testing skin reactions to pholcodine in case patients allergic to one NMBA. | Only for Cases : Intradermal tests with diluted pholcodine. Intradermal tests with diluted NMBAs (as usual) | 6 to 12 weeks after the general anesthetic procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anaphylaxis, pholcodine, neuromuscular blocking agents