Anaphylactic & Anaphylactoid Reactions During Surgery - An Outline
Below is an outline from a talk given to the Department of
Anesthesia at UCSF. A case presentation was given on a patient
who had two life-threatening episodes of anaphylaxis after
opthalmologic surgery. The second episode might have been
prevented if the proper workup had been performed.
Although specific skin testing instructions are given below,
the following is not intended as a guide for diagnosing and
treating surgical anaphylaxis.
Implicated Substances In Perioperative Period
- latex - a true IgE-mediated allergy, it is becoming
recognized as a major health issue. A reasonably good RAST is
available for latex.
- thiopental (up to 50% in one study), IgE-mechanism
implicated, skin testing may be helpful.
- propofol, possible IgE mechanism, possible
cross-reactivity with muscle relaxants, ? whether reasonable to
skin test (only reported by one group).
- muscle relaxants (6/27 patients in one study)
esp. succinylcholine. IgE-mechanism implicated, and skin testing
may be helpful. There is cross-reactivity among drugs of the same
class, but reactions may occur less often with certain ones -
vecuronium, for example).
- Opioids (non-immunologic release of histamine from mast
cells) - difficult to interpret skin test.
- local anesthetics - if true allergy exists at all, it
is VERY rare.
- IV contrast - unclear mechanism, although not thought to
be IgE-mediated. There is a misconception: contrast allergy
has no relation to seafood allergy.
- antibiotics (esp. penicillin and other beta-lactam drugs).
- Protamine (esp. diabetics or vasectomized males).
- ethylene dioxide (sterilizing equipment).
- methylmethacrylate (bone cement) ? allergic mechanism.
- volume expanders: all can probably cause direct-histamine
release.
- dextran (even with prophylaxis with dextran-1) - no good skin
test since not IgE-mediated
- gelatins, not that uncommon
- albumin
- Hetastarch, reaction rate 0.0004 to 0.006 %. No
standardized skin test
High Risk Groups
- Females in regards to muscle relaxant allergy. There may
be sensitization to quaternary ammonium compounds common in
cosmetics.
- Atopic patients (?). There is a higher (in some studies)
incidence of atopics in reactors.
Skin Tests
As mentioned above, skin testing may be helpful in certain cases.
Immediate-type skin tests are the most rapid and reliable method for
demostrating the presense of IgE-antibody. They are best used to
evaluate allergy to drugs that are high-molecular weight proteins,
i.e., complete antigens (chymopapain, insulin, streptokinase,
heterologous serum). Skin testing for low-molecular weight
drugs, or incomplete antigens (sulfas, thiobarbiturates,
muscle relaxants) are less reliable because we don't know
the metabolites that end up forming the haptens. These
haptens are essential in promoting the immune response.
Exception: penicillin and related drugs, since the
metabolites are well characterized. So, skin testing can be very
informative.
Procedure:
- Patient must be off histamine-blocking agents.
- Positive(Histamine) and negative (saline) controls
must be used.
- Use standard dilutions, the highest dilutions that have
been shown to not cause irritant or non-specific reactions in
controls. If no standard known, you must use control volunteers
to determine a proper, non-irritating dilution.
- Do the skin testing approximately 2-4 weeks, and
less than 3 months, after the event. If too soon, there may be
may have depletion of mediators or IgE.
- Have resusitation equipment available, as there is a
theoretic risk of a severe reaction.
- Always do prick test first, usually at 1:10 or
undiluted. Put a drop of solution on forearm (or upper back) and
prick through with a sharp needle (27 gauge, e.g.). If
negative at 15-20 minutes, perform intradermal test.
- Intradermals: inject 0.02 ml of solution, just enough
to raise a small (2mm) bleb. Read results at 15-20 minutes.
- Positive test consists of a wheal of approximately 4mm
(or at least 50% of control) with erythema. N.B. what constitutes
a positive reaction is not at all standardized, it is different for
different authors.
- Results are uninterpretable if a wheal and flare is present
where the negative saline control was applied (i.e., dermatographism),
or if there is no reaction to histamine (pt. on antihistamines
or antidepressants).
Considerations when doing skin testing:
False positive:
- irritant reaction
- non-immunologic histamine release (opiates, muscle relaxants,
thiobarbituates, vancomycin, gelatin).
False negative:
- non-IgE mechanism of event
- mediator or IgE depletion (tested too soon after event)
- anti-histamine therapy
- testing material is not the relevant antigen
Sensitivity and Specificity of skin testing for most drugs is
not known because of lack of challenge data (mainly due to
ethical considerations - near deaths have resulted from challenges).
For penicillin and hymenoptera venom, rechallenge of skin test
positive patients results in 50% reaction rate. Reaction rate
for skin test negative patients is very low for PCN and
hymenoptera - but these antigens are well characterized.
Because of the paucity of studies on this subject, there is only
relatively reliable evidence of validity of testing to
thiopental, succinylcholine, and latex. These three have
had an IgE mechanism reasonably confirmed by RAST testing. However,
it is reasonable to test to other drugs.
Management:
- Skin test positive: A positive test is helpful, and may
represent true hypersensitivity. It can give you some good
information on what to avoid and on the risks to the patient.
Plan:
- avoid drug and cross-reactors
- premedicate with Prednisone (usually 40 to 60 mg in an adult)
at 13, 7, 1 hours and benadryl at one hour before the procedure.
- all drugs thought to cause direct histamine release
(opiates, for example) should be given SLOWLY, and at the lowest
possible dose.
- Skin test negative: Negative test not that helpful, may
be "missing the boat".
- premedicate regardless
- carefully give histamine releasers
PREMEDICATION IS NOT A SUBSTITUTE FOR AVOIDANCE - IT WILL NOT
RELIABLY PREVENT IgE-MEDIATED ANAPHYLAXIS
Lastly, it's important to note that you can you can confirm a
anaphylactic(-oid) reaction with serum tryptase within 4
hours of the event. Tryptase is a protease contained in mast cells,
and is a very good marker for mast cell activity. Histamine levels
may also be helpful, but it must be drawn immediately after the event
(histamine has a much shorter half-life than tryptase).
Neil Gershman, M.D.
May 13, 1994
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