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Anaphylaxis in General Anesthesia

Fredric M. Hustey, MD Associate Professor Cleveland Clinic Lerner College of Medicine Case Western Reserve University

Objectives
► Discuss

challenges in the diagnosis of allergic reactions/anaphylaxis during general anesthesia ► List common precipitants of allergic and anaphylactic reactions in the OR ► Discuss management strategies for patients with anesthesia induced anaphylaxis

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. Chem Immunology and Allergy 2010; 95:180-189.

Mechanisms ► IgE (cross-linked by allergen/drug)  Cardiovascular collapse and bronchospasm more frequent in IgE-dependent rx ► Complement activation via IgG or IgM binding to antigen/drug ► Direct complement activation via alternate pathway ► Direct activation of mast cells or basophils .

aprotinin.Leading Causes ► Neuromuscular cases) blocking agents (50-70% of  IgE-dependent reactions predominant  Cross-reactions not uncommon ► Second: latex allergy ► Third: antibiotics (beta-lactams in general) ► Anaphylaxis to intravenous hypnotics. protamine and other drugs can occur . plasma substitutes.

Diagnosis ► 90% of reactions appear at induction  Within seconds or minutes after IV administration ► Reactions appearing later (during anesthesia maintenance  Latex  Volume expanders  Dyes .

Challenges in Diagnosis ► Patient under general anesthesia cannot complain     Miss early warning signs Pruritis Malaise Dyspnea .

Challenges in Diagnosis ► Draping  Difficult to appreciate skin manifestations such as uriticaria .

 Dose related side effects of drugs  Inadequate depth of anesthesia  Surgical complications .Challenges in Diagnosis ► Tachycardia. hypotension increased airway resistance.

hypotension with tachycardia  Mild cases (single symptom) may resolved spontaneously without specific tx ►Not recognized as allergic ►Fatal re-exposure .Challenges in Diagnosis ► Clinical features can vary widely b/w patients ► May also occur in isolation  Bronchospasm.

12:301-323 .Most Commonly Reported Initial Features ► Difficulty ventilating ► Desaturation ► Pulselessness Whittington et al. Clin Anaesthesiol B Clin Anaesthesiol 1998. Anaphylactic and anaphylactoid reactions.

Management: Three Principles ► Interrupt contact with offending agent ► Modulate effect of released mediators ► Inhibit further mediator production and release .

Primary Treatment ► Cease all drugs/surgery when possible  Often difficult to identify precipitant  Multiple exposures in short timeframe ► Fluids ► Epinephrine .

9NS boluses ► When volume exceeds 30cc/kg switch to colloids  Initial dose 10cc/kg .Fluids ► IV .

J Allergy Clin Immunol 2004. tachycardia  Difficulty ventilating.114(2):371-376 . Clinical features and severity grading of anaphylaxis. bronchial hyper-reactivity ► Grade III: Severe life threatening MOS involvement ► Grade IV: Cardiac and/or respiratory arrest Brown. SGA.Ring and Messmer Severity Scale ► Grade I: cutaneous with or w/o angioedema ► Grade II: moderate multi-organ involvement  Hypotension.

Epinephrine ► Initial adult dosing depends on severity I generally not necessary II 10-20 ug IV boluses III 100-200 ug IV boluses IV: ACLS (1mg IV bolus)     Grade Grade Grade Grade ► Titrate according to severity and response ► Repeat q1-2 minutes as necessary ► IV qtt .

Resistant to Epinephrine? ► Norepinephrine qtt ► Consider glucagon for patients on Bblockers  Initial dose of 3-5mg IV ► *Vasopressin (2-10 unit increments IV) ► *Methylene blue (inhibits NO mediation of vascular smooth muscle relaxation) *some data exists on these therapies but value is not completely clear .

Secondary Treatment ► Antihistamines  H1 and H2 blockers ► Corticosteroids ► B2 agonists for persistent bronchospasm ► Observation *Relapse can occur up to 24 hours later .

128(2):366-373 .4% *Rocuronium 29.3% *Atracurium 19.Neuromuscular Blocking Agents ► Higher risk     *Succinylcholine 33. J Allergy Clin Immunol 2011.3% *Vecuronium 10. Anaphylaxis during anesthesia in France: an 8 year national survey.2% ► Lower risk  Pancuronium  Cisatracurium *Mertes PM et al.

Neuromuscular Blocking Agents ► Can occur during first administration from cross sensitization via similar quaternary ammonium ions     Cosmetics Toothpastes. shampoos Foods Drugs (cough suppressants) . soaps.

Neuromuscular Blocking Agents ► Cross sensitization b/w NMBs is common .

Latex ► Second most common cause of anaphylaxis ► Risk increases with increased exposure  Health care workers  Multiple surgeries ►Primary cause of anaphylaxis in children subjected to multiple surgeries (especially spina bifida) ► Cross sensitization from food allergens  Avocado. chestnut . kiwi. banana.

Antibiotics Third most common etiology ► Penicillins and cephalosporins account for up to 70% ► Quinolones also common ► Vancomycin allergy rare  Rxs related to basophil degranulation associated with rapid administration (red-man syndrome) .

Hypnotics Less common ► Propofol in patients with egg/soy allergy  Insufficient evidence ► Midazolam. sevoflurane  Rare ► Isoflurane.  Exceedingly rare . ketamine desflurane. etomidate.

Colloids ► All can precipitate but low incidence (.03.2%) ► Gelatins and dextrans > Albumin or hetastarch .

Post Anaphylaxis Analysis Challenges ► Was this a true allergic response? ► What was the precipitating agent? .

sxs. response to tx) ► Serum markers of mast cell activation can be sent intraoperatively  Triptase levels within 30-120 minutes of symptom onset  Serum histamine degraded quickly and may not be reliable . timing.Was This a True Allergic Response? ► Analyze the clinical data (hx.

What was the Precipitating Agent? ► Immunological assessment of suspected allergen should be based on more than one test  Avoid single test .no test is perfect  False positives exclude otherwise useful agent  False negatives can result in potential fatal reexposure .

What was the Precipitating Agent? ► Referral for Allergy/Immunology testing  Quantification of specific IgE (best during the first 6 months after the event)  Skin testing (best within the first year after the event)  Other biologic assays .

What was the Precipitating Agent? ► AVOID RE-EXPOSURE .

Conclusion ► Anaphylaxis in general anesthesia is rare but life threatening ► Diagnosis can be challenging in the OR environment ► Early recognition and management is critical to prevent morbidity and mortality .

Questions? .