Investigation of a Suspected Anaphylactic
or Anaesthetic Drug Allergy Reaction

Malcolm Fisher
revised 01/10/02


1.  Suspicion
2.  Investigations
   A.  Mast Cell Tryptase
   B.  Skin Tests
      a)  Anaesthetic drugs
      b)  Local Anaesthetic drugs
   C.  RAST tests
3.  Advice To Patients


  • Unexplained hypotension
  • Bronchospasm
  • Angioedema

Likelihood of anaphylaxis increased if:

  • More than one feature present
  • Associated erythema, rash or urticaria
  • Particularly severe reaction

Bronchospasm occurs in all asthmatics who get anaphylaxis and occurs as a sole manifestation of anaphylaxis in about 10% of patients. Some drugs esp propofol,vecuronium,atracurium can release large quantities of histamine directly from lung mast cells and produce asthma but this is probably less common than anaphylaxis. Other histamine releasers like morphine rarely if ever produce bronchospasm. Indeed histamine infusion in asthmatics does not produce bronchospasm unless they are beta blocked.

Asthma due to intubation seems to me to get better fairly quickly and "horrendous bronchospasm" should be investigated. Difficulty in inflating the lungs prior to intubation is one of the commonest early signs of anaesthetic anaphylaxis. A Mast Cell tryptase would help if there is any serum around from 1-6 hours after the incident as it does not become elevated in asthma due to local histamine release or intubation induced asthma.

Local anaesthetic allergy is very rare. We have seen only two reactions to local and two to additives, while over the same period we have seen 500 reactions to drugs used during general anaesthesia (where the estimated incidence in Australia is one in 20,000 cases). The consequences of a spurious history of local allergy are, however, painful!



Serum (clotted sample, eg crossmatch tube) needs to be taken 1-4 hours after onset of reaction. Separate the serum from cells if possible. Transport frozen if this can be arranged.

If the patient ultimately died, but lived for one hour or more, take blood for serum. The sample can be taken up to 3 days after death. Try and also get some serum that was taken before the reaction (ie, from your lab or at your treatment place). This may be important for you medico-legally.

Mast Cell Tryptase assays are no longer performed at RNSH by Brian Baldo (due in part to funding difficulties). Don't send blood to RNS or to Malcolm Fisher anymore as it WILL NOT be tested by them and the sample will be wasted. First try your own pathology service. If they can't, Royal Prince Alfred or Royal Newcastle might - phone first to check that someone is available to do it!

Results and Interpretation:

If tryptase is positive, the patient needs skin testing to identify the agent responsible. Do this 4-6 weeks after the reaction. We will look at blood for antibodies but this is less reliable under most circumstances. Often positive in the dead ones. Result of tryptase may not be available before skin testing is necessary.

Positive mast cell tryptase = lgE mediated reaction (ie, anaphylaxis).

Negative mast cell tryptase tests are only rarely associated with positive skin tests and antibody tests. While, if taken at the correct time, they usually mean anaphylaxis has not occurred, a small number of patients who are probably having reactions related to basophils rather than mast cells, will have MCT levels that are not elevated in association with anaphylaxis. The three we have documented all had a convincing clinical history. Unfortunately these few patients mean that MCT levels cannot be used to show that skin testing is unnecessary.


a) Anaesthetic drugs

Test all available relaxants if one was used. Asthmatic patients should be skin tested at one month off anti asthma medications if possible. For practical advice see:

Fisher MM. Intradermal testing after anaphylactoid reactions to anaesthetic drugs: Practical aspects of performance and interpretation. Anaesth Intens Care. 1984:l2; 115-120.

Additional dilutions:

  • Propofol 1:100
  • Fentanyl 1:100
  • Vecuronium 1:1000
  • Atracurium 1:10.000

To really understand what tests mean and their limitations see:

Fisher MM and Baldo BA. Anaphylaxis during anaesthesia: Current aspects of diagnosis and prevention. European J Anaesthesiology 1994; 11:263-284.

b) Local Anaesthetic Drugs

1. Immediate Reactions

For percutaneous testing, solutions of a 1:100 dilution of additive free 1% local anaesthetic (0.5% for bupivacaine) are first injected intradermally to raise a 1mm bleb. If this is uneventful a 1mm bleb of undiluted local is used 10 minutes later. If this is uneventful 2ccs of the local anaesthetic are used.

If vasovagal reactions are suspected, it may be helpful to give 2ccs of normal saline rapidly subcutaneously prior to testing the drugs involved. If a vasovagal reaction occurs it facilitates convincing the patient of the aetiology. CAUTION: some patients react very negatively to being informed of the psychological basis to their reaction!

A positive test is a wheal of greater than 0.8cms. If significant flares occur to a specific drug we recommend alternative drugs be used. This testing does not exclude allergy to additives. I don't know how to test for this. We suggest that additive free local (dental vials) except for prilocaine/syntocinon and multi dose bottles are used in future.

The testing differs from the methods described by others in omitting the initial prick testing. Prick testing is generally used prior to intradermal testing for perceived safety reasons, but does not produce results that correlate with allergy

2. Delayed reactions

If reactions are delayed for up to four hours the patients are kept under observation. Testing for severe delayed systemic reactions and reactions such as Stevens Johnson Syndrome should be performed in hospital.

It may be preferable to test with an alternate local to the one implicated.

For swelling reactions the undiluted local injections are widely separated and clearly labelled and the patient asked to return if swelling occurs within 48 hours.

For delayed cutaneous reactions we soak the gauze portion of a square Elastoplast dressing with local anaesthetic, saline control, and a dry patch and label them and attach them to the skin for 48 hours or until symptoms occur.


If tryptase is positive, and skin tests are negative, the RAST may determine the agent responsible in 3%, or add valuable cross sensitivity information. Only we do them (to anaesthetic drugs) in Australia - send serum to BA Baldo, Kolling Institute, Royal North Shore Hospital, with a letter indicating which drugs were given, what happened to the patient, and what your skin test results were. No history or skin test results = no test.


Give patient a detailed letter so the next anaesthetist can see exactly what happened, what was given, and the basis for your conclusions. If patient is to wear a bracelet or medallion, instruct them to write "see letter" on it and always carry the letter. Details of subsequent anaesthetics are also valuable. Encourage the patient to ask the next anaesthetist to record the drugs he/she gave (preferably on the letter). This is particularly important if the anaesthetic was uneventful.

If you want Malcolm Fisher at RNS to see the patient, send him a formal referral letter regarding the patient. This must include a detailed anaesthetic history, a list of all drugs given, the time of onset, severity and clinical course of the reaction, MCT sample collection times and finally the actual results of the MCT assay and who did it (a photocopy of the actual result is best). It is your responsibility to put all this together and get it to Malcolm - medicolegally it's also your responsibility to check the patient actually was seen by him!

If you have a problem, feel free to contact me:

Malcolm Fisher
Head, Intensive Therapy Unit
Royal North Shore Hospital
St Leonards, NSW 2065
Phone (02) 9926 8656 - (international +61 2 9926 8656)
Fax (02) 9439 8418 - (international +61 2 9439 8418)

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