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Anaphylaxis in General
AnesthesiaFredric M. Hustey, MD
Associate Professor
Cleveland Clinic Lerner College of MedicineCase Western Reserve University
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Objectives
Discuss challenges in the diagnosis ofallergic reactions/anaphylaxis during general
anesthesiaList common precipitants of allergic and
anaphylactic reactions in the OR
Discuss management strategies for patientswith anesthesia induced anaphylaxis
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Not Uncommon
1/13,000 to as much as 1/3,180
mortality ranges between 3 and 9%
Moneret-Vaultrin et al. Anaphylaxis to General Anesthetics. ChemImmunology and Allergy 2010; 95:180-189.
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Mechanisms
IgE (cross-linked by allergen/drug)
Cardiovascular collapse and bronchospasmmore frequent in IgE-dependent rx
Complement activation via IgG or IgMbinding to antigen/drug
Direct complement activation via alternate
pathwayDirect activation of mast cells or basophils
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Leading Causes
Neuromuscular blocking agents (50-70% ofcases) IgE-dependent reactions predominant
Cross-reactions not uncommon
Second: latex allergy
Third: antibiotics (beta-lactams in general)
Anaphylaxis to intravenous hypnotics,plasma substitutes, aprotinin, protamineand other drugs can occur
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Diagnosis
90% of reactions appear at induction
Within seconds or minutes after IVadministration
Reactions appearing later (duringanesthesia maintenance
Latex
Volume expanders
Dyes
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Challenges in Diagnosis
Patient under general anesthesia cannotcomplain
Miss early warning signs Pruritis
Malaise
Dyspnea
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Challenges in Diagnosis
Draping
Difficult to appreciate skin manifestations suchas uriticaria
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Challenges in Diagnosis
Tachycardia, increased airway resistance,hypotension
Dose related side effects of drugs Inadequate depth of anesthesia
Surgical complications
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Challenges in Diagnosis
Clinical features can vary widely b/wpatients
May also occur in isolation Bronchospasm, hypotension with tachycardia
Mild cases (single symptom) may resolvedspontaneously without specific tx
Not recognized as allergic
Fatal re-exposure
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Most Commonly Reported Initial
FeaturesDifficulty ventilating
Desaturation
Pulselessness
Whittington et al. Anaphylactic and anaphylactoid reactions. ClinAnaesthesiol B Clin Anaesthesiol 1998; 12:301-323
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Management: Three Principles
Interrupt contact with offending agent
Modulate effect of released mediators
Inhibit further mediator production andrelease
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Primary Treatment
Cease all drugs/surgery when possible
Often difficult to identify precipitant
Multiple exposures in short timeframe
Fluids
Epinephrine
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Ring and Messmer Severity Scale
Grade I: cutaneous with or w/o angioedema
Grade II: moderate multi-organ involvement
Hypotension, tachycardia
Difficulty ventilating, bronchial hyper-reactivity
Grade III: Severe life threatening MOSinvolvement
Grade IV: Cardiac and/or respiratory arrest
Brown, SGA. Clinical features and severity grading of anaphylaxis. J AllergyClin Immunol 2004;114(2):371-376
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Epinephrine
Initial adult dosing depends on severity Grade I generally not necessary
Grade II 10-20 ug IV boluses
Grade III 100-200 ug IV boluses
Grade IV: ACLS (1mg IV bolus)
Titrate according to severity and responseRepeat q1-2 minutes as necessary
IV qtt
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Resistant to Epinephrine?
Norepinephrine qtt
Consider glucagon for patients on B-
blockers Initial dose of 3-5mg IV
*Vasopressin (2-10 unit increments IV)
*Methylene blue (inhibits NO mediation ofvascular smooth muscle relaxation)
*some data exists on these therapies but value is not
completely clear
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Secondary Treatment
Antihistamines
H1 and H2 blockers
CorticosteroidsB2 agonists for persistent bronchospasm
Observation
*Relapse can occur up to 24 hours later
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Neuromuscular Blocking Agents
Higher risk
*Succinylcholine 33.4%
*Rocuronium 29.3% *Atracurium 19.3%
*Vecuronium 10.2%
Lower risk
Pancuronium
Cisatracurium
*Mertes PM et al. Anaphylaxis during anesthesia in France: an 8 year nationalsurvey. J Allergy Clin Immunol 2011;128(2):366-373
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Neuromuscular Blocking Agents
Can occur during first administration fromcross sensitization via similar quaternaryammonium ions
Cosmetics
Toothpastes, soaps, shampoos
Foods
Drugs (cough suppressants)
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Neuromuscular Blocking Agents
Cross sensitization b/w NMBs is common
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Latex
Second most common cause of anaphylaxis
Risk increases with increased exposure
Health care workers Multiple surgeries
Primary cause of anaphylaxis in children subjected tomultiple surgeries (especially spina bifida)
Cross sensitization from food allergensAvocado, banana, kiwi, chestnut
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Antibiotics
Third most common etiology
Penicillins and cephalosporins account for
up to 70%Quinolones also common
Vancomycin allergy rare
Rxs related to basophil degranulation associatedwith rapid administration (red-man syndrome)
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Hypnotics
Less common
Propofol in patients with egg/soy allergy
Insufficient evidenceMidazolam, etomidate, ketamine
Rare
Isoflurane, desflurane, sevoflurane Exceedingly rare
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Colloids
All can precipitate but low incidence (.03-.2%)
Gelatins and dextrans > Albumin orhetastarch
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Post Anaphylaxis Analysis
Challenges
Was this a true allergic response?
What was the precipitating agent?
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Was This a True Allergic Response?
Analyze the clinical data (hx, timing, sxs,response to tx)
Serum markers of mast cell activation canbe sent intraoperatively
Triptase levels within 30-120 minutes ofsymptom onset
Serum histamine degraded quickly and may notbe reliable
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What was the Precipitating Agent?
Immunological assessment of suspectedallergen should be based on more than onetest
Avoid single test - no test is perfect
False positives exclude otherwise useful agent
False negatives can result in potential fatal re-
exposure
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What was the Precipitating Agent?
Referral for Allergy/Immunology testing
Quantification of specific IgE (best during thefirst 6 months after the event)
Skin testing (best within the first year after theevent)
Other biologic assays
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What was the Precipitating Agent?
AVOID RE-EXPOSURE
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Conclusion
Anaphylaxis in general anesthesia is rarebut life threatening
Diagnosis can be challenging in the ORenvironment
Early recognition and management is criticalto prevent morbidity and mortality
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Questions?