Q:

7/12/2014
I need to skin test a patient to Propofol. It comes in a 10mg/ml concentration as an emulsion. Is there a protocol for skin testing to this agent, and is it permissible to perform an intradermal skin test with an emulsion? I also need to test this patient to Fentanyl but I read it is preferred not to skin test with this agent and instead perform a drug challenge. Would you use the patch or nasal spray to perform the challenge?

A:

Thank you for your inquiry.

There are numerous sources by which you can find appropriate skin test concentrations to use for testing to both propofol and fentanyl. I have copied several of these sources for you below. Probably the easiest one for you to access is the Brockow, et al. Position Paper entitled "Skin test concentrations for systemically administered drugs" which appeared in Allergy in 2013. Some of the information used to establish these skin test concentrations appearing in that paper were obtained from the other sources copied below.

In addition, we have dealt with a similar question on our Academy "Ask the Expert" website, and I have copied that question and answer for you below as well.

In review of these references, several concentrations have been used. For your convenience, in the Brockow article mentioned above, for fentanyl, a skin prick test was performed using an undiluted preparation containing 0.05 mg/ml, and an intradermal test was performed with a 1:10 dilution which contained 0.005 mg/ml. For propofol, the skin prick test was performed with an undiluted concentration of 10 mg/ml; and an intradermal test was performed using a 1:10 dilution containing 1 mg/ml.

Again, this article can be obtained free of charge online if you wish more details regarding this issue. And there are suggested skin test concentrations for a number of other drugs in this reference.

In regards to your final question, I have no familiarity with patch or nasal spray testing to these drugs, and could not find any reference to this form of test in the literature.

Thank you again for your inquiry and we hope this response is helpful to you.

Allergy 2013; 68: 702–712.
POSITION PAPER
Skin test concentrations for systemically administered drugs – an ENDA/EAACI Drug Allergy Interest Group Position Paper
Brockow, et al:on behalf of the ENDA/EAACI Drug Allergy Interest Group

Previous entry on "Ask the Expert" website:
Evaluation for possible fentanyl allergy
Question:
Any recommendations for evaluation of possible Fentanyl allergy. I doubt IGE mechanism but patient interested in making sure however she is reluctant to have skin testing performed for fear of reaction. She had fentanyl after a surgical procedure few years back. Chest tight, not sure about hives, etc. Thanks.

Answer:
Unfortunately there is no available test for serum specific IgE to fentanyl of which I am aware. In addition, a literature search failed to turn up any lab offering this test. Therefore I am afraid the only testing procedure you can pursue is skin testing.

Fentanyl, as you know, has been reported to cause anaphylactic episodes, and skin tests have been used on several occasions to detect fentanyl allergy. Fentanyl, unlike other opiates, does not cause primary non-IgE-mediated release of histamine, and therefore skin testing to fentanyl is probably a valid way to detect IgE to this drug.

Several protocols have been used. I have copied below the most recent reference that I could find related to skin testing to fentanyl. If you do wish to proceed with skin tests, it would give you not only the concentration to use, but should refer you to a bibliography with other related studies using skin tests to identify IgE to fentanyl.

Thank you again for your inquiry and we hope this response is helpful to you.

Reference:
Milojevic I et al
Anaphylactic reaction during general anaesthesia associated with positive skin test to fentanyl.
Anaesth Intensive Care. 2009 May;37(3):502-3.

A Critical Incident Report: Propofolp Anaphylaxis

Anesthesiology. 1992 Aug;77(2):275-80.
Life-threatening anaphylactoid reactions to propofol (Diprivan)
Laxenaire MC1, Mata-Bermejo E, Moneret-Vautrin DA, Gueant JL.
Author information
1Department of Anesthesiology and Surgical Intensive Care Unit, CHU-Hôpital Central, Nancy, France.
Abstract
Fourteen patients who had had a life-threatening reaction within a few minutes after receiving propofol (Diprivan) were investigated for anaphylaxis 4-6 weeks after the incident. Three kinds of immunologic tests were carried out: skin tests (prick tests and intradermal tests with the drugs used and Intralipid, the solvent for propofol), a leukocyte histamine release test, and a radioimmunoassay (RIA) of immunoglobulin E (IgE) against propofol and muscle relaxants, when they had been given with propofol. It had been previously shown that these were always negative in patients anesthetized with propofol without any complications. Thirteen of the 14 patients had at least one positive test supporting hypersensitivity to propofol; 2 patients had three tests positive; 4 had two tests positive; and 7 had one test positive. The skin tests with Intralipid were negative in 4 patients whose tests with propofol were positive. Two patients who had been given muscle relaxants at the same time as the propofol had positive IgE-RIA to both drugs. In one patient, results of all the tests remained negative, and the mechanism involved in the reaction remained unidentified. It is note-worthy that 9 patients of 14 had allergic histories that were known before the anesthetic (atopy; allergy to antibiotics, muscle relaxants, lidocaine, colloids) and that none of the patients had ever received propofol or Intralipid before. It is possible that the IgE that linked abnormally with the propofol had specific binding sites for the phenyl nucleus and the isopropyl groups, which are present in propofol and many other drugs

Allergy Asthma Immunol Res. 2012 Jan;4(1):46-8. doi: 10.4168/aair.2012.4.1.46. Epub 2011 Nov 18.
A case of propofol-induced oropharyngeal angioedema and bronchospasm.
You BC1, Jang AS, Han JS, Cheon HW, Park JS, Lee JH, Park SW, Kim DJ, Park CS.
Author information
1Division of Allergy and Respiratory Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
Abstract
Propofol (2,6-diisopropylphenol) is an ultrashort-acting sedative agent with sedative and amnestic effects that is used not only for anesthesia but also for sedation during minor outpatient procedures and endoscopic examinations. Rare cases of anaphylaxis following propofol administration have been reported in the medical literature. Documentation of anaphylaxis is often lacking because the cause and effect relationship is often hard to prove. Only a minority of patients get referred for allergy testing to confirm the offending drug. Here we report a 74-year-old woman who had an anaphylactic reaction with severe oropharyngeal edema and bronchospasm for a few minutes after receiving propofol during endoscopic examination. An allergy skin test was positive for both propofol and soybean. Soybean in the intralipid is one component of propofol, and we concluded that this anaphylaxis was caused by soybean.

Sincerely,
Phil Lieberman, M.D.

AAAAI - American Academy of Allergy Asthma & Immunology