Anaphylaxis

Description

An acute, life-threatening reaction with an onset of minutes to hours. It is usually, but not always, the result of an immunologic mechanism that involves IgE-mast cell or basophil mediator release; such mediators can include histamine, leukotrienes, and prostaglandins.
The newest definition of anaphylaxis encompasses 1 of 3 scenarios:
- Acute onset (minutes to hours) of skin and mucosal manifestations, as well as respiratory compromise, hypotension, or shock
- Signs as above, after exposure to a likely antigen, in addition to GI symptoms
- Hypotension after exposure to a known antigen

Epidemiology

Incidence

During anesthesia: Ranges from 1:4,000 to 1:25,000 anesthetics
Hospital inpatients in the US: 1:3,000; in Europe, the incidence is reported to be much lower.
In the US, it is estimated that between 1.25% and 16% of the general population is at risk for possibly experiencing an episode of anaphylaxis.

Prevalence

Lifetime prevalence from all triggers: 0.05–2%
Food triggers: 90% of anaphylaxis cases are caused by milk, soy, eggs, wheat, peanuts, tree nuts, fish, and shellfish.

Morbidity

Food allergies account for 30,000 ER visits a year; it is more common among children than adults.
Latex anaphylaxis is responsible for >200 cases/year.

Mortality

In the US: ~2 in 100,000 anaphylaxis cases
In the UK: 0.65–2% of anaphylaxis cases
Risk factors age 10–35 years old: Active asthma, peanut allergy, and delayed administration of epinephrine
Risk factors age 55–85 years old: Cardiovascular or respiratory illness, use of antibiotics or anesthetic agents.

Etiology/Risk Factors

History of a prior anaphylactic episode remains the most important factor in establishing cause and risk factors.
Outpatient setting:
- Drug-induced: Penicillin and other antibiotics, aspirin, and NSAIDs
- IV contrast dye
- Food: Peanuts, tree nuts, fish, shellfish, soy, egg, cow's milk
- Other: Exercise-induced, idiopathic, insect stings, seminal fluid
Perioperative setting:
- Neuromuscular blockers (most common)
- Natural rubber latex
- Antibiotics
- Hypnotics (propofol, thiopental)
- Aprotinin
- Bupivacaine
- Radiographic contrast material
- Opioids
- Protamine
- Blood transfusions
- Methylmethacrylate (bone cement; associated with hypotension but no IgE mechanism has been found)
- Rare causes include etomidate, ketamine, midazolam, and amide local anesthetics.

Physiology/Pathophysiology

Anaphylactic and anaphylactoid reactions stem from the systemic release of mediators from mast cells and basophils. The pathogenesis of anaphylactic reactions involves an immunologic mechanism in which IgE is created in response to allergen exposure. Receptors on the surface of mast cells and basophils bind with IgE.
Re-exposure of the allergen results in activation of IgE-bound mast cells and basophils with the resultant release of pre-formed mediators that are stored in cellular granules (histamine, tryptase, heparin, chymase, cytokines). In addition, arachidonic acid is metabolized to prostaglandins and leukotrienes and also released.
Anaphylaxis often produces signs and symptoms within minutes of exposure but there are also biphasic reactions that can occur 1–72 hours after the initial attack.
Increased vascular permeability is a hallmark of anaphylaxis that allows the transfer of large amounts of intravascular fluid into the extravascular space within 10 minutes. As a result, cardiovascular collapse may be the first sign of anaphylaxis with little or no cutaneous or respiratory signs.

Prevantative Measures

Primary prevention is based on allergen desensitization through immunotherapy.
Venom immunotherapy is highly successful in preventing anaphylaxis.
Pharmacologic prophylaxis (steroids, antihistamines) can be used to help prevent occurrences to radiographic contrast material, fluorescein, and other dyes.
for idiopathic anaphylaxis, prophylaxis with daily oral prednisone, combined with H1 antagonists, has resulted in decreased incidence.
Most importantly, patient education and avoidance of known triggering substances is key in prevention.
A "TIME OUT" should be performed prior to any procedure and identify the presence of any known drug allergies.

Diagnosis ⬆ ⬇

Acute onset of reaction (minutes to hours)
Cutaneous: Skin, mucosa, or both can present with hives, urticaria, angioedema, pruritus, flushing, swollen lips and tongue.
Respiratory: Bronchospasm, wheezing, dyspnea, stridor, reduced peak expiratory flow, hypoxemia, respiratory arrest
Cardiovascular: Hypotension or symptoms of end-organ dysfunction (cardiovascular collapse), tachycardia
Gastrointestinal: Persistent vomiting, diarrhea
RAST testing (radioallergosorbent test) detects specific IgE antibodies to suspected or known allergens. The suspected antigen is bound to an insoluble material and the patient's serum is added. If the serum contains antibodies to the allergen, those antibodies bind to the allergen. Radiolabeled anti-human IgE antibody is added where it binds to those IgE antibodies already bound to the insoluble material.
Skin manifestations may be masked by surgical drapes and are not as common in the setting of general anesthesia as in other settings.
Bradycardia is, surprisingly, more common with anaphylaxis in the setting of general anesthesia (not tachycardia).
Cardiovascular collapse may be the only sign of anaphylaxis.

Differential Diagnosis

Acute asthma exacerbation
Syncope
Panic attack/anxiety disorders
Acute generalized hives
Vocal cord/paradoxical vocal cord dysfunction
Vasovagal reactions
Nonimmunologic reactions that involve mechanisms outside of IgE mediation (transfusion reactions, IgG or IgM antibody-mediated, antigen–antibody complexes and complement)
Anaphylactoid reactions: The World Allergy Organization has suggested that the term be eliminated in favor of calling all similar reactions "anaphylaxis." Generally, the term is used to describe non-IgE-mediated reactions; the initial treatment is the same, regardless of the mechanism.
Cardiovascular disorders: Pulmonary embolism, cardiogenic shock, etc.
Flushing disorders: Carcinoid, "red-man" syndrome from vancomycin, medullary carcinoma of the thyroid
Other: Mastocytosis (systemic mast cell disease [SCMD]) is a clonal disorder characterized by overproduction of mast cells in different tissues.
Postprandial syndromes
Diagnostic tests and interpretation:
- Serum tryptase peaks 60–90 minutes after the onset of anaphylaxis and persists for 6 hours; obtain between 1 and 2 hours after the first symptoms appear.
- Plasma histamine levels begin to rise within 5–10 minutes and remain elevated for 30–60 minutes.
- 24-hour urinary histamine metabolite
- Urinary vanillylmandelic acid to rule out pheochromocytoma and carcinoid syndrome
- Skin tests (or in vitro tests) determine the presence of specific IgE antibodies to foods, medications (e.g., penicillin).

Treatment ⬆ ⬇

Discontinuation of the inciting factor (e.g., anesthetic agent or drug)
Place the patient in the recumbent position (pertinent if antibiotics or medication is being given on the floor or preoperative holding area)
ABC’s: Manage airway, delivery 100% oxygen, and intubate (if appropriate)
Rapid IV fluid replacement
Epinephrine is the most important aspect of treatment for anaphylaxis and should be administered immediately:
- IV: 5–10 mcg boluses
- IV drip: 1 mcg/min
- SQ: 200–500 mcg q5 minutes (aqueous 1:1,000 dilution which is equivalent to 1 mg/mL or 0.2–0.5 mL)
- IM: 200–500 mcg into the vastus lateralis, or lateral aspect of the thigh (aqueous 1:1,000 dilution which is equivalent to 1 mg/mL or 0.2–0.5 mL)
- Cardiopulmonary arrest during anaphylaxis: 1–3 mg IV over 3 minutes, followed by 4–10 mcg/min infusion
- Severe or refractory anaphylaxis that is unresponsive to epinephrine has been reported with patients on beta-blockers; it has been characterized by bradycardia, profound hypotension, and severe bronchospasm; consider treating with glucagon 1–5 mg IV over 4 minutes, followed by an infusion of 5–15 mcg/min.
Histamine 1 blocker. Diphenhydramine 1–2 mg/kg or 25–50 mg IV dose.
Histamine 2 blockers. Ranitidine 50 mg IV diluted in 5% dextrose (total volume of 20 mL) can be administered over 5 minutes. Alternatively, cimetidine 4 mg/kg IV may be given.
Inhaled beta-2 agonists if bronchospasm is present
Glucocorticoids are not helpful acutely but potentially can help prevent recurrences and shorten the duration of attack.
Monitors: Large-bore IV access, if not already in place, should be placed. Arterial line placement can aid with monitoring blood pressure (particularly if chest compressions); however, it should not interfere with immediate resuscitation with IV fluids and epinephrine.

Follow-Up ⬆ ⬇

Biphasic anaphylaxis can occur in up to one-fourth of episodes, and symptoms may recur within hours after apparent resolution of initial presentation.
Following resolution of the initial episode, patients should be provided with an epinephrine pen and instructions for administration as well as instructions to go to the nearest emergency room at the first hint of recurrence of symptoms.
Patients should also be referred to an allergist/immunologist for further workup, possibly including skin testing and desensitization, if appropriate.

References ⬆ ⬇

Lieberman P , Nicklas R , Oppenheimer J , et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol. 2010;126:477–480.
Hepner D , Castells M. Anaphylaxis during the perioperative period. Anesth Analg. 2003;97:1381–1395.
Estelle F , Simons R. Anaphylaxis. J Clin Immunol. 2010;S161–S180.
Kemp S , Lockey R. Anaphylaxis: A review of causes and mechanisms. J Allergy Clin Immunol. 2002;110(3):341–348.
Leiberman P. Anaphylactic reactions during surgical and medical procedures. J Allergy Clin Immunol. 2002;110(2):s64–s69.
Matasar M , Neugut A. Epidemiology of anaphylaxis in the United States. Curr Allergy Asthma Rep. 2003;3:30–35.

Additional Reading ⬆ ⬇

See Also (Topic, Algorithm, Electronic Media Element)

Latex Allergy

Codes ⬆ ⬇

ICD9

995.0 Other anaphylactic reaction
995.60 Anaphylactic reaction due to unspecified food

ICD10

T78.00XA Anaphylactic reaction due to unspecified food, init encntr
T78.2XXA Anaphylactic shock, unspecified, initial encounter
T78.2XXD Anaphylactic shock, unspecified, subsequent encounter
T78.2XXS Anaphylactic shock, unspecified, sequela
T78.00XD Anaphylactic reaction due to unspecified food, subs encntr
T78.00XS Anaphylactic reaction due to unspecified food, sequela

Clinical Pearls ⬆ ⬇

Epinephrine, patient position, and oxygen are the most important therapeutic modalities in treating anaphylaxis. Treatment (in order of importance) includes:
- Epinephrine
- Patient position (recumbent)
- Oxygen
- IV fluids
- Nebulized beta-2 agonists
- Vasopressors
- Antihistamines
- Corticosteroids
Propofol and egg allergy: This topic has been a source of some controversy among anesthesia providers. Propofol is formulated in a lipid emulsion containing soybean oil, glycerol, egg lecithin, and disodium edetate with sodium hydroxide to adjust for pH.
- The egg lecithin component is a highly purified egg yolk component. The principal protein of eggs is ovalbumin which is present in the egg white. Most egg allergies are related to the egg white (albumin) and not the egg yolk (lecithin).
- Most allergic-type reactions to propofol are nonimmunologic because propofol can cause direct stimulation of histamine release.
- Skin testing of egg-allergic patients is not consistent with allergies to propofol.
- However, there are case reports in the literature of anaphylaxis associated with propofol in egg-allergic individuals.
- Furthermore, the propofol package insert monograph clearly states under contraindications: "Propofol Injectable Emulsion is contraindicated in patients with allergies to eggs, egg products, soybeans or soy products."
It is the author's opinion that if propofol can be avoided in egg-allergic individuals, then an appropriate substitute should be used. If propofol cannot be avoided, epinephrine, large-bore IV access, and resuscitation equipment should be readily available.

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Basics ⬇