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

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, plasma substitutes, aprotinin, protamine and other drugs can occur

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

Challenges in Diagnosis
Tachycardia,

hypotension

increased airway resistance,

Dose related side effects of drugs Inadequate depth of anesthesia Surgical complications

Challenges in Diagnosis
Clinical

features can vary widely b/w patients May also occur in isolation
Bronchospasm, hypotension with tachycardia Mild cases (single symptom) may resolved spontaneously without specific tx
Not

recognized as allergic Fatal re-exposure

Most Commonly Reported Initial Features

Difficulty

ventilating Desaturation Pulselessness

Whittington et al. Anaphylactic and anaphylactoid reactions. Clin Anaesthesiol B Clin Anaesthesiol 1998; 12:301-323

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

Fluids
IV

.9NS boluses When volume exceeds 30cc/kg switch to colloids

Initial dose 10cc/kg

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 MOS involvement Grade IV: Cardiac and/or respiratory arrest
Brown, SGA. Clinical features and severity grading of anaphylaxis. J Allergy Clin Immunol 2004;114(2):371-376

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

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 national survey. J Allergy Clin Immunol 2011;128(2):366-373

Neuromuscular Blocking Agents

Can

occur during first administration from cross sensitization via similar quaternary ammonium ions
Cosmetics Toothpastes, soaps, shampoos Foods Drugs (cough suppressants)

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, banana, kiwi, chestnut

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,

etomidate, ketamine desflurane, sevoflurane

Rare
Isoflurane,

Exceedingly rare

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?

Was This a True Allergic Response?

Analyze

the clinical data (hx, timing, 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

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?