Upload
lillian-bailey
View
222
Download
1
Tags:
Embed Size (px)
Citation preview
Diagnostic Evaluation of Diagnostic Evaluation of Perioperative AnaphylaxisPerioperative Anaphylaxis
David A. Khan, MDProfessor of Medicine and Pediatrics
Southwestern Medical CenterAllergy & Immunology Program Director
Division of Allergy & Immunology
1
OutlineOutline
• Epidemiology
• Anesthetic Drugs
• Clinical Features
• Causal Agents
• Diagnostic Testing
2
EpidemiologyEpidemiology
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429-51.
CountryIncidence of Perioperative
Anaphylaxis
France 1 in 4600
Australia 1 in 5000-13,000
Thailand 1 in 5000
New Zealand 1 in 1250-5000
England 1 in 3500
3
EpidemiologyEpidemiology
• 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 DrugsAnesthetic Drugs
Thong BYH et al. Ann Allergy Asthma Immunol 2004;92:619–28.
Perioperative Period
Medications Used
PreoperativeAntibiotics, opioids, latex, chlorhexidine, blood/colloids, benzodiazepines
Intraoperative
Neuromuscular blocking agents (NMBA), hypnotics, opioids, neuroleptics, benzodiazepines, local anesthetics, dyes, contrast, latex, aprotinin, chlorhexidine, blood/colloid
PostoperativeOpioids, NSAIDs, neostigmine, atropine/glycopyrrolate
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
fluamzenil6
Causal Agents of Perioperative Causal Agents of Perioperative Reactions in FranceReactions in France
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51.
Substances Responsible for IgE-Mediated Hypersensitivity Reactions in France:Results from Seven Consecutive Surveys
Substance
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
7
Perioperative Anaphylaxis:Perioperative Anaphylaxis:Mayo Clinic ExperienceMayo 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 FeaturesClinical 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 Clinical Features of Perioperative AnaphylaxisPerioperative 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
• 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
Clinical Features of Clinical Features of Perioperative AnaphylaxisPerioperative Anaphylaxis
11
Perioperative Anaphylaxis: IgE vs. non-IgEPerioperative Anaphylaxis: IgE vs. non-IgE
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51.
Clinical Signs Observed in IgE-Mediated Reactions Compared withNon–IgE-Mediated Reactions
Clinical SignsIgE-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 50
Cardiovascular collapse 249 12
Cardiac arrest 29 ––
Bronchospasm 129 (39.9) 43 (19.5)
12
Differential Diagnosis of Differential Diagnosis of Perioperative AnaphylaxisPerioperative 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 urticaria13
High Risk PatientsHigh 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 PatientsHigh 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 PerioperativeSeverity Grading of PerioperativeAllergic ReactionsAllergic Reactions
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):442-53.
Grade of Severity for Quantification of ImmediateHypersensitivity Reactions
Grade Symptoms
ICutaneous signs: generalized erythema,urticaria, angioedema
IIMeasurable but not life-threatening symptomsCutaneous signs, hypotension, tachycardiaRespiratory disturbances: cough, difficulty inflating
IIILife-threatening symptoms: collapse, tachycardiaor bradycardia, arrhythmias, bronchospasm
IV Cardiac and/or respiratory arrest
16
Causal AgentsCausal Agentsof Perioperative of Perioperative
AnaphylaxisAnaphylaxis
17
Neuromuscular Blocking Agents Neuromuscular Blocking Agents (NMBA)(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 FlexibilityDivalency and Flexibilityof NMBAsof 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 BlockingNeuromuscular BlockingAgents (NMBA)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 HypothesisPholcodine 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 Pholcodine Consumption Correlated with Sensitization to SuxamethoniumSensitization to Suxamethonium
Johansson SGO et al. Allergy 2010;65:498–502.
PHO
MOR
SUX
PAPPC
0.037
0.035
0.015
–0.001
RegressionCoefficient R 2
0.767
0.843
0.633
0.004
22
IgE Sensitization to Suxamethonium HighIgE Sensitization to Suxamethonium Highin US Despite Lack of Pholcodinein US Despite Lack of Pholcodine
Johansson SGO et al. Allergy 2010;65:498–502.
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 CityNumber of
SeraPHO
%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
23
NMBAs and Non-IgE Mediated NMBAs and Non-IgE Mediated ReactionsReactions
• 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
LatexLatex• 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
AntibioticsAntibiotics
• 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
BacitracinBacitracin• 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
HypnoticsHypnotics
• 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
ThiopentalThiopental
• 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 AllergyPropofol 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 g
• 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 AllergyPropofol 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 AllergyPropofol 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
OpioidsOpioids
• 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 AnestheticsLocal 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
ColloidsColloids
• All synthetic colloids used for volume replacement have been reported to cause anaphylaxis
• Dextrans and gelatins more common causes than albumin or hetastarch
Laxenaire MC et al. Ann Fr Anesth Reanim 1994;13:301-10.
Colloid Volume Expander
Gelatins Dextrans Albumin Starches
Frequency of anaphylactic reactions
0.35% 0.27% 0.10% 0.06%
35
DextranDextran• 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 Hapten inhibition Reduces Dextran AnaphylaxisDextran 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 DyesVital 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 DyesVital 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 AnaphylaxisClinical 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 requiringcontinuous 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 UrticariaBlue Urticaria
Parvaiz MA et al. Anaesthesia 2012;67:1275–89.41
Vital Blue DyesVital 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
ProtamineProtamine• 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 AllergyProtamine 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
AntisepticsAntiseptics
• 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
ChlorhexidineChlorhexidine• 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-Povidone- IodineIodine
• 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 Miscellaneous Causes of Perioperative AnaphylaxisPerioperative 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 Diagnostic Approach to Perioperative to Perioperative
AnaphylaxisAnaphylaxis
49
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):442-53.
Decisional Algorithm for a Patient Reporting a Hypersensitivity Reaction During Decisional Algorithm for a Patient Reporting a Hypersensitivity Reaction During Previous Anesthesia and Who Has Not Undergone an Allergy WorkupPrevious Anesthesia and Who Has Not Undergone an Allergy Workup
50
Practical Steps to ConsiderPractical 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 Laboratory Confirmation of AnaphylaxisAnaphylaxis
• 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 Laboratory Confirmation of AnaphylaxisAnaphylaxis
• 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 Assessing Tryptase in AnaphylaxisAnaphylaxis
• 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 Histamine and Tryptase in Perioperative ReactionsPerioperative Reactions
• French survey 2005-2007 of 1253 patients with perioperative allergic reactions
• Histamine and tryptase measured in 599 cases
Dong SW et al. Minerva Anestesiol 2012;78:868-78.
Histamine(% elevated)
Tryptase(% elevated)
IgE-mediated 78.2% 60.5%
Non-IgE-mediated 42.0% 10.6%
55
Practical Steps to ConsiderPractical 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 ConsiderPractical 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 Skin Testing in Perioperative AnaphylaxisAnaphylaxis
• 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
Accuracy of Skin TestingAccuracy 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%
• -lactam sensitivity also good
• Other agents vary
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51. 59
Concentrations for TestingConcentrations 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 ControlsNMBA Skin Tests in Healthy Controls
Mertes PM et al. Anesthesiology 2007;107:245–52.
Ro
curo
niu
m
Ra
pa
curo
niu
m
Ve
curo
niu
m
Pa
ncu
ron
ium
Atr
acu
riu
m
Cis
-atr
acu
riu
m
Miv
acu
riu
m
250
Pe
rce
nt
Ch
an
ge
Fo
rea
rm
ppd
10-7
10-6
10-5
10-4
10-2
200
150
100
50
0
–50
Forearm
Su
ccin
ylch
olin
e
61
Mertes PM et al. Immunol Allergy Clin N Am 2009;29:429–51.
Concentrations of Anesthetic Agents Normally NonreactiveConcentrations of Anesthetic Agents Normally Nonreactivein Practice of Skin Tests in Practice of Skin Tests
62
Positive Rocuronium Skin TestPositive Rocuronium Skin Test
63
Concentrations for DyesConcentrations for Dyesand Antisepticsand Antiseptics
Mertes PM et al. J Investig Allergol Clin Immunol 2011;21(6):442-53.
Concentrations of Antiseptic and Dyes that Are Normally Nonreactive in Skin Tests
AvailableAgents
Skin Prick Tests Intradermal Tests
Dilution mg/mL Dilution g/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
64
Positive Isosulfan BluePositive Isosulfan BlueSkin TestSkin Test
Negative Control Patient
65
In Vitro In Vitro Specific IgE TestsSpecific 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 TestsBasophil 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
Challenge TestsChallenge Tests
• Limited to few agents– Local anesthetics
– -lactams
– Latex
• Should only be considered if other diagnostic tests negative
68
Subsequent Anesthesia afterSubsequent Anesthesia after Perioperative Anaphylaxis 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
procedureMoscicki RA et al. K Allergy Clin Immunol 1990;86:325-32. 69
Subsequent Anesthesia afterSubsequent Anesthesia after Perioperative Anaphylaxis 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 afterSubsequent Anesthesia after Perioperative Anaphylaxis 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 ConclusionsDiagnostic 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
Preventive StrategiesPreventive 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 possible73
ConclusionsConclusions• 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