1. 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 1

2. Outline Epidemiology Anesthetic Drugs Clinical Features Causal Agents
Diagnostic Testing 2

3. Incidence of Perioperative
Epidemiology
Country
Incidence of Perioperative
Anaphylaxis
France
1 in 4600
Australia
1 in ,000
Thailand
1 in 5000
New Zealand
1 in
England
1 in 3500
Mertes PM et al. Immunol Allergy Clin N Am 2009;29: 3

4. 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

5. Anesthetic Drugs Perioperative Medications Used Period
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 5
Thong BYH et al. Ann Allergy Asthma Immunol 2004;92:619–28.

6. fentanyl, sufentanil, morphine pancuronium, rocuronium, vecuronium
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

7. Causal Agents of Perioperative Reactions in France
Substances Responsible for IgE-Mediated Hypersensitivity Reactions in France: Results from Seven Consecutive Surveys
Substance
(n=821)
(%)
(n=813)
(n=1030)
(n=734)
(n=486)
(n=518)
(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
4.6
5.0
3.1
4.0
2.8
Antibiotics
2.0
2.6
8.3
15.1
14.7
Other
2.2
2.9
Total
100
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51. 7

8. 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

9. 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

10. 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

11. 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

12. Perioperative Anaphylaxis: IgE vs. non-IgE
Clinical Signs Observed in IgE-Mediated Reactions Compared with Non–IgE-Mediated Reactions
Clinical Signs
IgE-Mediated Reactions
(%)
Non–IgE-Mediated Reactions
Cutaneous symptoms
326 (66.4)
206 (93.6)
Erythema
209
151
Urticaria
101
177
Edema 50 60
Cardiovascular symptoms
386 (78.6)
70 (31.7)
Hypotension
127
Cardiovascular collapse
249 12
Cardiac arrest 29 ––
Bronchospasm
129 (39.9)
43 (19.5)
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51. 12

13. 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

14. 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
Recommendations from a panel of experts from the European Network
for Drug Allergy (ENDA) and the European Academy of
Allergy and Clinical Immunology (EAACI) interest group on
drug allergy
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6): 14

15. 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): 15

16. 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): 16

17. Causal Agents of Perioperative Anaphylaxis17

18. 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

19. 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 19
Didier A et al. J Allergy Clin Immunol 1987;79:

20. 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

21. 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

22. Pholcodine Consumption Correlated with Sensitization to Suxamethonium
Regression
Coefficient
R 2
PHO
MOR
SUX
PAPPC
0.037
0.035
0.015
–0.001
0.767
0.843
0.633
0.004
Johansson SGO et al. Allergy 2010;65:498–502. 22

23. 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
0.5
0.9
Denmark
Copenhagen
179
0.6
1.1
USA
Lenexa
200
2.0
2.5
5.0
Germany
Freiburg
211
2.4
The Netherlands
Rotterdam
184
4.9
6.0
1.6
Finland
Helsinki
209
1.0
1.4
Norway
Bergen
199
7.0
5.5 UK
Manchester
France
Nancy
214
6.5
3.7
7.5
1.9
The results also indicate that other, yet
unknown, substances may lead to IgE-sensitization towards NMBAs. 23
Johansson SGO et al. Allergy 2010;65:498–502.

24. 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

25. 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 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: 25

26. 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-IgE-mediated reactions which may manifest with urticaria and even hypotension 26

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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 egg-allergic 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

33. 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

34. 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

35. 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
Gelatins
Dextrans
Albumin
Starches
Frequency of anaphylactic reactions
0.35%
0.27%
0.10%
0.06%
Laxenaire MC et al. Ann Fr Anesth Reanim 1994;13: 35

36. 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 36
Gedin H et al. Int Arch Allergy Appl Immunol 1976;52(1-4):

37. 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 and dextran use with dextran 1 between
Reduced severe reactions from 22/100,000 to 1.2/100,000 units
Reduced fatal reactions from 23 to 1 37
Ljungstrom KG et al. Anaesthesia 1988;43:

38. 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 38
Scherer K et al. Ann Allergy Asthma Immunol 2006;96:

39. 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: 39

40. 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 40
Mertes PM et al. J Allergy Clin Immunol 2008;122(2):

41. Blue Urticaria 41
Parvaiz MA et al. Anaesthesia 2012;67:1275–89.

42. Vital Blue Dyes
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 cross-reactivity
Keller B et al. Am J Surgery 2007;193:122-4. 42

43. Protamine Agent used to reverse heparin anticoagulation
Rare cause of anaphylaxis
Incidence %
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:
Koster A et al. Ann Thorac Surg 2010;90:276-7. 43

44. 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

45. 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: 45

46. 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: 46

47. Povidone- Iodine
Multiple case reports of anaphylaxis to topical povidone-iodine including during surgery
Positive skin tests have been reported
Betadine
Chong YY et al. Singapore Med J 2008;49(6):483-7. 47

48. 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

49. Diagnostic Approach to Perioperative Anaphylaxis49

50. Decisional Algorithm for a Patient Reporting a Hypersensitivity Reaction During Previous Anesthesia and Who Has Not Undergone an Allergy Workup 50
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):

51. 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

52. Laboratory Confirmation of Anaphylaxis
Plasma histamine
Peak observed within minutes of reaction
Elimination t ½ ~ minutes
False positives
Spontaneous lysis
Pregnancy > 6 months
Placental synthesis of diamine oxidase
Heparin
Increased diamine oxidase 52

53. 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): 53

54. 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: 54

55. Histamine and Tryptase in Perioperative Reactions
French survey of 1253 patients with perioperative allergic reactions
Histamine and tryptase measured in 599 cases
Histamine
(% elevated)
Tryptase
IgE-mediated
78.2%
60.5%
Non-IgE-mediated
42.0%
10.6%
Dong SW et al. Minerva Anestesiol 2012;78: 55

56. 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

57. 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

58. Skin Testing in Perioperative Anaphylaxis
Skin testing in association with history remains mainstay for diagnosis of IgE-mediated 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

59. 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

60. 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

61. NMBA Skin Tests in Healthy Controls
Forearm
ppd
10-7
10-6
10-5
10-4
10-2
250
200
150
Percent Change Forearm
100 50
120 healthy volunteers underwent skin tests with varying concentrations of all commercially available NMBAs; 100% change would be considered positive
–50
Rocuronium
Atracurium
Rapacuronium
Vecuronium
Mivacurium
Pancuronium
Cis-atracurium
Succinylcholine
Mertes PM et al. Anesthesiology 2007;107:245–52. 61

62. Concentrations of Anesthetic Agents Normally Nonreactive
in Practice of Skin Tests 62
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51.

63. Positive Rocuronium Skin Test63

64. 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
Chlorhexidine
Undiluted
0.5
1 / 100 5
Povidone iodine
100
1 / 10
10000
Patent blue 25
2500
Methylene blue 10
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6): 64

65. Positive Isosulfan Blue Skin Test
Negative Control
Patient 65

66. 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

67. Basophil Activation Tests
Few studies with NMBAs and beta-lactams
Not recommended as a routine diagnostic tests even in Europe
Commercially available tests in U.S, have not been studied 67

68. Challenge Tests Limited to few agents
Local anesthetics
b-lactams
Latex
Should only be considered if other diagnostic tests negative 68

69. 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 69
Moscicki RA et al. K Allergy Clin Immunol 1990;86:

70. 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 70
Soetens FM et al. Acta Anesthesiol Belg 2003;54:59-63.

71. 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 71
Fisher MM, Doig GS. Drug Safety 2004;26:

72. 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 72

73. 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

74. 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 74