Diagnostic Evaluation of
Perioperative Anaphylaxis
David A. Khan, MD
Professor of Medicine and Pediatrics
Southwestern Medical Center
Allergy & Immunology Program Director
Division of Allergy & Immunology
1
Outline
•
•
•
•
•
Epidemiology
Anesthetic Drugs
Clinical Features
Causal Agents
Diagnostic Testing
2
Epidemiology
Country
Incidence of Perioperative
Anaphylaxis
France
1 in 4600
Australia
1 in 5000-13,000
Thailand
1 in 5000
New Zealand
1 in 1250-5000
England
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429-51.
1 in 3500
3
Epidemiology
• Incidence remains poorly defined
– Few prospective studies
– Uncertainty in accuracy and completeness of
reports
• Immune-mediated reactions account for
> 60% reactions
• Mortality
– ~3-9%
4
Anesthetic Drugs
Perioperative
Period
Medications Used
Preoperative
Antibiotics, opioids, latex, chlorhexidine,
blood/colloids, benzodiazepines
Intraoperative
Neuromuscular blocking agents (NMBA),
hypnotics, opioids, neuroleptics,
benzodiazepines, local anesthetics,
dyes, contrast, latex, aprotinin,
chlorhexidine, blood/colloid
Postoperative
Opioids, NSAIDs, neostigmine,
atropine/glycopyrrolate
Thong BYH et al. Ann Allergy Asthma Immunol 2004;92:619–28.
5
Class of Drug
Name
Intravenous
anesthetic
Induction agents: thiopental, etomidate, propofol, ketamine
Inhalational
anesthetic
Volatile liquid anesthetics: halothane, enflurane, isoflurane,
desflurane, sevoflurane
Antimuscarinic
Atropine, hyoscine, glycopyrronnium
Sedative and
analgesics
Class
Example(s)
Benzodiazepine
midazolam
NSAIDs
ketorolac
Opioids
fentanyl, sufentanil, morphine
NMBA nondepolarizing
(aminosteroid)
pancuronium, rocuronium,
vecuronium
NMBA nondepolarizing
(benzylisoquinolinium)
atracurium, mivacurium
NMBA depolarizing)
succinylcholine
Opioid antagonist
naloxone
Benzodiazepine
antagonist
fluamzenil
6
Causal Agents of Perioperative
Reactions in France
Substances Responsible for IgE-Mediated Hypersensitivity Reactions in France:
Results from Seven Consecutive Surveys
1984-1989
(n=821)
(%)
1990-1991
(n=813)
(%)
1992-1994
(n=1030)
(%)
1994-1996
(n=734)
(%)
1997-1998
(n=486)
(%)
1999-2000
(n=518)
(%)
2001-2002
(n=502)
(%)
NMBAs
81.0
70.2
59.2
61.6
69.2
58.2
54.0
Latex
0.5
12.5
19.0
16.6
12.1
16.7
22.3
Hypnotics
11.0
5.6
8.0
5.1
3.7
3.4
0.8
Opioids
3.0
1.7
3.5
2.7
1.4
1.3
2.4
Colloids
0.5
4.6
5.0
3.1
2.7
4.0
2.8
Antibiotics
2.0
2.6
3.1
8.3
8.0
15.1
14.7
Other
2.0
2.8
2.2
2.6
2.9
1.3
3.0
Total
100
100
100
100
100
100
100
Substance
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51.
7
Perioperative Anaphylaxis:
Mayo Clinic Experience
• From 1992 to 2010, identified 38 patients with
perioperative anaphylaxis
• 18 patients had likely IgE-mediated reactions
– Antibiotics most common identified agent (50%)
• 7/9 cases due to cefazolin
– Induction agents (16.7%)
– Latex (16.7%)
– NMBA (11%)
– Others
• Chlorhexidine, isosulfan blue, protamine, flumazenil
Gurrieri C et al. Anesth Analg 2011;113:1202–12.
8
Clinical Features
• Clinical presentation of anaphylaxis differs
somewhat in anesthetized patients vs.
conscious patients
• Perioperative anaphylaxis
– No early warning subjective symptoms
• Pruritus, dizziness, dyspnea, and malaise absent
– Cutaneous findings not easily recognized
• No pruritus
• Patient is draped
9
Clinical Features of
Perioperative Anaphylaxis
• Changes in vitals signs or airway
resistance may be attributed to affects
from anesthesia medications
• Due to all of these features, anaphylaxis
may not be recognized early in the
anesthetized patient
10
Clinical Features of
Perioperative Anaphylaxis
• Cannot differentiate IgE vs. Non-IgE
mediated reactions on clinical features
alone
• Timing of anaphylaxis may suggest etiology
– 90% reactions within minutes of induction
• NMBA, antibiotic, induction agent
– Maintenance of anesthesia
• Latex, volume expanders, dyes, contrast
11
Perioperative Anaphylaxis: IgE vs. non-IgE
Clinical Signs Observed in IgE-Mediated Reactions Compared with
Non–IgE-Mediated Reactions
IgE-Mediated Reactions
(%)
Non–IgE-Mediated Reactions
(%)
326 (66.4)
206 (93.6)
Erythema
209
151
Urticaria
101
177
Edema
50
60
386 (78.6)
70 (31.7)
Hypotension
127
50
Cardiovascular collapse
249
12
Cardiac arrest
29
––
129 (39.9)
43 (19.5)
Clinical Signs
Cutaneous symptoms
Cardiovascular symptoms
Bronchospasm
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51.
12
Differential Diagnosis of
Perioperative Anaphylaxis
• Cardiovascular
– Arrhythmia, myocardial infarction, pericardial
tamponade
– Pulmonary edema, pulmonary embolism
– Overdose of vasoreactive drug
• Pulmonary
– Asthma, tension pneumothorax
• Sepsis
• Allergy and immunology
– HAE, mastocytosis, cold urticaria
13
High Risk Patients
• History of perioperative drug allergy
– Patients allergic to drugs or agents
likely to be used during anesthesia
– Patients with prior allergic reactions
during anesthesia
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):442-53.
14
High Risk Patients
• Latex allergy
– Patients with clinical signs of latex allergy
– Children who have undergone several
surgical interventions (e.g., spina bifida,
myelomeningocoele)
– Patients with food allergy to avocado, kiwi,
banana, chestnut, and buckwheat
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):442-53.
15
Severity Grading of Perioperative
Allergic Reactions
Grade of Severity for Quantification of Immediate
Hypersensitivity Reactions
Grade
Symptoms
I
Cutaneous signs: generalized erythema,
urticaria, angioedema
II
Measurable but not life-threatening symptoms
Cutaneous signs, hypotension, tachycardia
Respiratory disturbances: cough, difficulty inflating
III
Life-threatening symptoms: collapse, tachycardia
or bradycardia, arrhythmias, bronchospasm
IV
Cardiac and/or respiratory arrest
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):442-53.
16
Causal Agents
of Perioperative
Anaphylaxis
17
Neuromuscular Blocking Agents
(NMBA)
• Most common causal agent worldwide
– May not be as common in US
• Most reactions are IgE-mediated
• Quaternary and tertiary ammonium ions main
component of allergic epitopes
• Cross-sensitization is frequent amongst
NMBAs ~60-70%
– Higher with amino-steroid NMBAs
– Sensitization to all NMBAs rare
– Monosensitization frequent with succinylcholine
18
Divalency and Flexibility
of NMBAs
• NMBAs have 2 substituted ammonium ions per
molecule (divalent)
• Divalency allows bridging of IgE molecules by a
single NMBA molecule
• Suxamethonium (succinylcholine) is the NMBA
associated wit highest frequency of anaphylaxis
when adjusted for use
• Longer molecules and more flexible backbones
enhance mediator release
– characteristic of suxamethonium
Didier A et al. J Allergy Clin Immunol 1987;79:578-84.
19
Neuromuscular Blocking
Agents (NMBA)
• 15-50% cases NMBA anaphylaxis occurs
with first contact with an NMBA
• Theories on cross-reactive antibodies
– Exposure to substituted ammonium groups in
foods, cosmetics, disinfectants, industrial
material
– Pholcodine hypothesis
20
Pholcodine Hypothesis
• Pholcodine is a cough suppressant
containing quaternary ammonium ion
epitopes and is available in certain
countries
• International study compared pholcodine
consumption and IgE to suxamethonium
Johansson SGO et al. Allergy 2010;65:498–502.
21
Pholcodine Consumption Correlated with
Sensitization to Suxamethonium
Regression
Coefficient R 2
Johansson SGO et al. Allergy 2010;65:498–502.
PHO
0.037
0.767
MOR
0.035
0.843
SUX
0.015
0.633
PAPPC –0.001
0.004
22
IgE Sensitization to Suxamethonium High
in US Despite Lack of Pholcodine
Number of Sera Collected from the Participating Countries and the
Respective Percentages of Sera with IgE Antibody Levels of 3.5 kUA/I or
Higher to PHO, MOR, SUX and PAPPC
Country
City
Number of
Sera
PHO
%
SUX
%
MOR
%
PAPPC
%
Sweden
Stockholm
213
0
0
0.5
0.9
Denmark
Copenhagen
179
0.6
0
1.1
0.6
USA
Lenexa
200
2.0
2.5
5.0
2.0
Germany
Freiburg
211
0
0.5
0.9
2.4
The
Netherlands
Rotterdam
184
4.9
0
6.0
1.6
Finland
Helsinki
209
1.0
0
1.0
1.4
Norway
Bergen
199
7.0
1.0
5.5
0.5
UK
Manchester
209
2.4
0
2.4
0
France
Nancy
214
6.5
3.7
7.5
1.9
Johansson SGO et al. Allergy 2010;65:498–502.
23
NMBAs and Non-IgE Mediated
Reactions
• Non-IgE mediated reactions to NMBA occur
with similar frequency as IgE mediated
• Presumed to be due to direct nonspecific
mast cell/basophil activation
– Generally less severe
• NMBAs associated with greatest histamine
release
– D-tubocurarine, atracurium, mivacurium
– Rapacuronium (withdrawn from US)
24
Latex
• Often cited as the second most common
cause in large surveys but less common in
U.S. and other countries
• Study from Norway of anesthetic anaphylaxis
from 1996-2001 found only 3% cases due to
latex
– Noted systematic reduction of latex use in Norway
• Latex is the primary cause of anaphylaxis in
children with spina bifida who have frequent
surgeries
Harboe T et al. Anesthesiology 2005;102:897-903.
25
Antibiotics
• May be highest causative agent in the U.S.
with cefazolin being most common
• Beta-lactams most common overall
• Vancomycin a frequent cause of non-IgEmediated reactions which may manifest with
urticaria and even hypotension
26
Bacitracin
• Bacitracin anaphylaxis has been reported
with topical antibiotics
• Most reports of intraoperative anaphylaxis
from bacitracin are with irrigation during
surgery
• Skin testing may be positive with local
application only (without puncture)
• Bacitracin specific IgE has been detected in
some cases
Sharif S et al. Ann Allergy Asthma Immunol 2007;98:563–6.
27
Hypnotics
• Commonly used hypnotics include:
– Propofol, midazolam, thiopental, etomidate,
ketamine, and inhalational agents
• Allergic reactions to hypnotics are
relatively rare
• No immune-mediated reactions to
inhalational agents has been reported
28
Thiopental
• Most common barbiturate implicated in
perioperative anaphylaxis
• Women more likely than men to react
• Reactions thought to be IgE-mediated
• Skin testing has been shown to be helpful
in diagnosis
29
Propofol and Egg Allergy
• Propofol preparations are lipid suspensions
containing egg lecithin/phosphatide and soy oil
• Egg lecithin contains residual egg yolk but no
egg white proteins
– Estimated to be 5 mg
• Few case reports of suspected allergic
reactions to propofol in egg-allergic patients
• Warning labels for propofol vary by country
despite same manufacturer
30
Propofol and Egg Allergy
• Retrospective study of 32 egg-allergic
patients who received propofol at a
Children’s Hospital in Sydney
– IgE egg sensitization determined by
• Egg SPT ≥ 7 mm or egg spIgE > 7kUA/L without a
clinical history of egg allergy
• Egg SPT ≥ 3 mm or egg spIgE > 0.35kUA/L with a
clinical history of egg allergy
– N=19, 2 with anaphylaxis
Murphy A et al. Anesth Analg 2011;113:140-4.
31
Propofol and Egg Allergy
• Only 1 child had a reaction to propofol
(erythema and urticaria 15 minutes after 2nd
dose)
– History of egg anaphylaxis after sucking on
candy with egg albumin
• Propofol likely to be safe in majority of eggallergic children without egg anaphylaxis
• Authors recommend avoidance of propofol in
those with histories of egg anaphylaxis
Murphy A et al. Anesth Analg 2011;113:140-4.
32
Opioids
• Allergic reactions to opiates uncommon
with anesthesia
• Morphine, fentanyl, sufentanil most
commonly used
– Morphine more likely to cause non-IgE
mediated (pseudoallergic) reactions
• Rare reports of IgE-mediated reactions to
opiates
33
Local Anesthetics
• Extremely rare cause of perioperative
anaphylaxis
• Most adverse reactions related to
inadvertent intravascular injection with
resultant systemic effects from
– Local anesthetic (e.g. arrhythmias)
– epinephrine
34
Colloids
• All synthetic colloids used for volume
replacement have been reported to cause
anaphylaxis
• Dextrans and gelatins more common
causes than albumin or hetastarch
Colloid Volume
Expander
Frequency of
anaphylactic reactions
Gelatins
Dextrans
Albumin
Starches
0.35%
0.27%
0.10%
0.06%
Laxenaire MC et al. Ann Fr Anesth Reanim 1994;13:301-10.
35
Dextran
• Most common hypothesis for severe
anaphylactoid reactions to dextran is
related to dextran reactive antibodies
• High titer dextran reactive antibodies have
been correlated with severe reactions
– Immune complexes generate anaphylatoxins
stimulating mast cell/basophil activation
Gedin H et al. Int Arch Allergy Appl Immunol 1976;52(1-4):145-59.
36
Hapten inhibition Reduces
Dextran Anaphylaxis
• Very low molecular weight dextran (dextran 1)
has been infused prior to clinical dextran
injections to prevent anaphylactoid reactions
• Study from Sweden compared dextran use
between 1975-1979 and dextran use with
dextran 1 between 1983-1985
– Reduced severe reactions from 22/100,000 to
1.2/100,000 units
– Reduced fatal reactions from 23 to 1
Ljungstrom KG et al. Anaesthesia 1988;43:729-32.
37
Vital Blue Dyes
• Vital dyes have been used for many years in a variety
of settings
• Use for lymphatic mapping in the context of sentinel
lymph node biopsy in cancer surgery has increased
along with increasing reports of anaphylactic
reactions
• Montgomery et al (2002) performed a meta-analysis
of 2,392 patients, and calculated the incidence of
allergic reactions to vital blue dyes:
– Patent blue: 1.8%
– Isosulfan blue (lymphazurin): 1.4%
– Most reactions were mild
Scherer K et al. Ann Allergy Asthma Immunol 2006;96:497-500.
38
Vital Blue Dyes
• Most anaphylactic reactions occur with first
exposure to the dye
• An unproven hypothesis states sensitization
against vital dyes is facilitated by the
common use of patent blue and other
structurally closely related triarylmethane
dyes in everyday life
– color textiles, cosmetics, detergents, paints, inks,
antifreeze, cold remedies, laxatives, and
suppositories
Scherer K et al. Ann Allergy Asthma Immunol 2006;96:497-500.
39
Clinical Features of Dye Anaphylaxis
• Review of 14 cases of perioperative
anaphylaxis to patent blue V dye use in
lymphatic mapping
• Reactions characteristics
– Relatively severe 6/14 grade 3 reactions
– Average of 30 minutes to onset of symptoms
– 65% cases reactions prolonged requiring
continuous epinephrine infusion
– Skin tests were positive in all cases
• 8 on prick testing alone
Mertes PM et al. J Allergy Clin Immunol 2008;122(2):348-52.
40
Blue Urticaria
Parvaiz MA et al. Anaesthesia 2012;67:1275–89.
41
Vital Blue Dyes
Keller B et al. Am J Surgery 2007;193:122-4.
• Isosulfan blue and
patent blue V are
structurally similar
and have highest
rates of reaction
• Methylene blue
rare cause of
anaphylaxis
• Some patients
exhibit positive
skin tests to patent
blue and
methylene blue
suggesting
potential for crossreactivity
42
Protamine
• Agent used to reverse heparin anticoagulation
• Rare cause of anaphylaxis
– Incidence 0.19-0.69%
• Mechanisms unclear
– IgE, IgG, complement
• Multiple proposed risk factors
– Diabetics on NPH insulin
– Fish allergy, vasectomized men, other drug allergy
• Bivalirudin is an alternative for protamine
allergic patients
Park KW. Int Anesth Clin 2004;42:135-45.
Koster A et al. Ann Thorac Surg 2010;90:276-7.
43
Protamine and Fish Allergy
• Protamine prepared from sperm of salmon or
related species
• Case reports of fish allergic patients and
protamine anaphylaxis
• In vitro studies by Greenberger found no
evidence for cross-reactivity between IgE to
salmon and protamine
• Prospective evaluation of 6 fish allergic patients
found none had adverse reaction to protamine
Greenberger PA et al. Am J Med Sci 1989;298(2):104-8.
Levy JH et al. J Thorac Cardiovasc Surg 1989;98(2):200-4.
44
Antiseptics
• Chlorhexidine digluconate is a common
disinfectant
– Home uses: mouthwash toothpaste,
ointments, suppositories
– Medical uses: swabs for disinfection prior to
epidural/spinal anesthesia, surgical incisions,
urinary catheterization
• Chlorhexidine is becoming more recognized
as a cause of perioperative anaphylaxis
Garvey LH et al. J Allergy Clin Immunol 2007;120:409-15.
45
Chlorhexidine
• Retrospective study of 22 Danish patients
with history of chlorhexidine allergy
• 12/22 positive skin tests
• 11/22 positive chlorhexidine sp IgE
• Clinical characteristics
– Most patients males
– Most had previous mild reactions on prior
exposure
– Hypotension common
– Urologic procedures common precipitant
Garvey LH et al. J Allergy Clin Immunol 2007;120:409-15.
46
Povidone-Iodine
• Multiple case reports of anaphylaxis to
topical povidone-iodine including during
surgery
• Positive skin tests have been reported
Chong YY et al. Singapore Med J 2008;49(6):483-7.
47
Miscellaneous Causes of
Perioperative Anaphylaxis
• Numerous other agents have been reported
to cause perioperative anaphylaxis
–
–
–
–
–
Hydroxyzine
Oxytocin
Aprotinin
Pantoprazole
Hydrocortisone
–
–
–
–
–
NSAIDs
Neostigmine
Radiocontrast media
Blood products
Hydatid cyst rupture
48
Diagnostic Approach
to Perioperative
Anaphylaxis
49
Decisional Algorithm for a Patient Reporting a Hypersensitivity Reaction During
Previous Anesthesia and Who Has Not Undergone an Allergy Workup
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):442-53.
50
Practical Steps to Consider
• Patient history focused on prior known
drug allergies or other unexplained
reactions
• Comorbid factors
• Prior anesthetic history
• If recent reaction, serum tryptase from
stored sera may be helpful to confirm
anaphylaxis
51
Laboratory Confirmation of
Anaphylaxis
• Plasma histamine
– Peak observed within minutes of reaction
– Elimination t ½ ~ 15-30 minutes
– False positives
• Spontaneous lysis
• Pregnancy > 6 months
– Placental synthesis of diamine oxidase
• Heparin
– Increased diamine oxidase
52
Laboratory Confirmation of
Anaphylaxis
• Serum tryptase
– Optimal sampling time varies by severity
• 15-60 minutes for Grade 1 and 2
• 30 minutes to 2 hours for Grade 3 and 4
• May remain positive > 6 hrs in severe cases
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):442-53.
53
Assessing Tryptase in
Anaphylaxis
• Commercial labs measure total tryptase
• One can have anaphylaxis with a normal
total tryptase (< 11.4 ng/mL)
• Best to compare baseline to acute tryptase
(with anaphylaxis)
– an increase of >135% of baseline indicates mast
cell activation
• Example: baseline 5 ng/mL; with anaphylaxis 7 ng/mL
Borer-Reinhold M et al. Clin Exp Allergy 2011;41:1777-83.
54
Histamine and Tryptase in
Perioperative Reactions
• French survey 2005-2007 of 1253 patients
with perioperative allergic reactions
• Histamine and tryptase measured in 599
cases
Histamine
(% elevated)
Tryptase
(% elevated)
IgE-mediated
78.2%
60.5%
Non-IgE-mediated
42.0%
10.6%
Dong SW et al. Minerva Anestesiol 2012;78:868-78.
55
Practical Steps to Consider
• Obtain anesthesia and surgery record
including pre-op medications
– May need to contact anesthesiologist to
interpret
• Identify any suspect medications
– Don’t forget about antiseptics
• Consider lab work
– Baseline tryptase, latex-specific IgE
56
Practical Steps to Consider
• Obtain medications needed for testing
– If a neuromuscular blocking agent is
suspected, obtain other NMBAs to test
• Skin testing typically done after 4-6 weeks
to avoid “refractory” period of false
negatives
– No data exist on this for perioperative
anaphylaxis
• Inform patient of expectations for testing
– Prolonged, multiple skin tests
57
Skin Testing in Perioperative
Anaphylaxis
• Skin testing in association with history
remains mainstay for diagnosis of IgEmediated reactions
• Prick testing followed by intradermal testing
recommended
– Positive prick if ≥ 3mm than negative control
– Positive intradermal definition varies
• ≥ twice initial wheal
• We recommend initial 5 mm wheal and look for
increase of ≥ 3mm
58
Accuracy of Skin Testing
• True negative predictive value unknown
– Many drugs cannot be challenged with
safety in an office setting (e.g. NMBAs)
• Sensitivity for NMBAs estimated to be
94-97%
• b-lactam sensitivity also good
• Other agents vary
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51.
59
Concentrations for Testing
• Some controversy as to what is optimal
concentration for testing as well as site
– forearm vs. back
• Certain agents such as NMBAs will cause
positive reactions at higher concentrations
• Largest data from French Society of
Allergology (Societe Francaise
d’Allergologie et d’Immunologie Clinique)
60
NMBA Skin Tests in Healthy Controls
Forearm
ppd
250
200
10-6
10-5
150
10-4
10-2
100
50
Mertes PM et al. Anesthesiology 2007;107:245–52.
Succinylcholine
Mivacurium
Cis-atracurium
Atracurium
Pancuronium
Vecuronium
–50
Rapacuronium
0
Rocuronium
Percent Change Forearm
10-7
61
Concentrations of Anesthetic Agents Normally Nonreactive
in Practice of Skin Tests
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51.
62
Positive Rocuronium Skin Test
63
Concentrations for Dyes
and Antiseptics
Concentrations of Antiseptic and Dyes that Are Normally
Nonreactive in Skin Tests
Available
Agents
Skin Prick Tests
Intradermal Tests
Dilution
mg/mL
Dilution
mg/mL
Chlorhexidine
Undiluted
0.5
1 / 100
5
Povidone iodine
Undiluted
100
1 / 10
10000
Patent blue
Undiluted
25
1 / 10
2500
Methylene blue
Undiluted
10
1 / 100
100
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):442-53.
64
Positive Isosulfan Blue
Skin Test
Negative Control
Patient
65
In Vitro Specific IgE Tests
• Several studies with specific assays for IgE to
various anesthetic agents have been published
• Best results with NMBAs, latex, and thiopental
• Important to realize that performance
characteristics of these published assays likely
differ from commercially available assays in the
U.S.
• Sensitivity of latex CAP assay may be as low as
35%*
*Accetta Pedersen DJ et al. Ann Allergy Asthma Immunol 2012;108:94–7.
66
Basophil Activation Tests
• Few studies with NMBAs and betalactams
• Not recommended as a routine
diagnostic tests even in Europe
• Commercially available tests in U.S,
have not been studied
67
Challenge Tests
• Limited to few agents
– Local anesthetics
– b-lactams
– Latex
• Should only be considered if other
diagnostic tests negative
68
Subsequent Anesthesia after
Perioperative Anaphylaxis
• 11 patients from Boston evaluated for
perioperative anaphylaxis had subsequent
surgeries
– 7/11 had positive skin tests and agent avoided
– All premedicated using typical radiocontrast
media protocol
• No anaphylaxis
– 1 patient had urticaria and angioedema after
procedure
Moscicki RA et al. K Allergy Clin Immunol 1990;86:325-32.
69
Subsequent Anesthesia after
Perioperative Anaphylaxis
• 19 patients from Belgium with NMBA
anaphylaxis and positive skin tests
• Underwent 26 surgeries with skin test
negative NMBAs
• No reactions occurred
Soetens FM et al. Acta Anesthesiol Belg 2003;54:59-63.
70
Subsequent Anesthesia after
Perioperative Anaphylaxis
• Data from Sydney reported largest experience of
follow up of perioperative anaphylaxis patients
– 52 patients with negative skin and in vitro tests
• 1/52 had a reaction likely due to latex which was
not tested at the time
– 301 patients with positive skin tests
• 295 had no reaction
• 6/301 (2%) had 2nd anaphylactic reaction
– 2 NMBA not tested
– 4 NMBA with false-negative reaction
Fisher MM, Doig GS. Drug Safety 2004;26:393-410.
71
Diagnostic Testing Conclusions
• Skin testing and history is most useful tool
to identify causal agent
• 2/3 cases a causal agent can be identified
by skin testing
• 1/3 cases the causal agent is unclear
– Referred to as non-IgE-mediated reactions in
literature
• After diagnostic evaluation, majority of
patients undergo anesthesia safely
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Preventive Strategies
• Latex safe environments for latex allergy
• Premedication
– Antihistamine +/- corticosteroids will not reliably
prevent IgE-mediated anaphylaxis
– May be considered in cases where causal agent
cannot be found
• Choice of NMBA
– Cisatracurium appears to have lowest risk of
anaphylaxis of NMBAs
– Avoidance of NMBAs if possible
73
Conclusions
• Perioperative anaphylaxis remains
underestimated due to underreporting
• Antibiotics, NMBAs, latex remain common
causes but numerous causes exist
• Chlorhexidine reactions often unrecognized
• Systematic evaluation with comprehensive
skin testing can identify causal agents in 2/3
cases
• After diagnostic evaluation, majority of
patients can undergo anesthesia safely
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