Teaching Points::: ANAPHYLAXIS/EPI

[Ace844]

Hi Everyone,

After having read the wide variety of responses and posts to the Epi-Pens: BLS Usage? thread that perhaps I could make a teaching post on the subject of ANAPHYLAXIS and the reasons we administer Epi to our patients.... This first post will cover the physiology and the follow up will cover Epi, etc.... So if this helps or you like it, SOUND OFF!!! :!: :study: :computer: :idea:

Hope this helps,

Ace844

ANAPHYLAXIS

INTRODUCTION:

Anaphylaxis in its broadest sense represents a spectrum of clinical events from sneezing to shock depending on end organ sensitivity. Anaphylaxis is characterized as an explosive event resulting from release of histamine and preformed mediators causing profound end organ dysfunction (cardiac, respiratory, GI, dermatologic, neurologic).

Immediate hypersensitivity reactions to foreign proteins were first appreciated 4000 years ago, in descriptions of insect sting fatalities. Reactions to stinging insects still claim 50 lives annually. Subsequently, the use of horse serums, (tetanus, diphtheria) and penicillin focused attention on the overwhelming effect antigens in the right host could quickly elicit. These effects are varied and encompass clinical manifestations such as hypotension, cardiac arrhythmias, asthma, urticaria, angioedema, profuse diarrhea, nausea, vomiting and rhinitis. In l966 Drs. K. and T. Ishizaka identified the immunoglobulin in humans primarily responsible for these reactions, IgE. In the last 22 years, fascinating insights into the mechanism of this immunologic reaction, both in its "normal gate-keeper" function and its role in disease have been described.

DEFINITIONS:

IMMEDIATE HYPERSENSITIVITY: The result of re-exposure to an antigen capable of eliciting an IgE response in a susceptible individual producing a clinical reaction (flushing, urticaria, etc.), within seconds to minutes as a result of degranulation of mast cells/basophils. Non-immunologic stimuli can also provoke basophil/mast cell degranulation without prior exposure (radiocontrast media, morphine) producing a reaction mimicking an IgE immediate hypersensitivity response.

ATOPY: Describes the genetic predisposition to produce increased amounts of IgE antibody against common environmental antigens. This tendency is manifest by 20% of the population and is apparent clinically as anaphylaxis, asthma, eczema, hayfever, urticaria and angioedema dependent upon end organ susceptibility.

ALLERGY: The term allergy was originally coined in 1906 by von Pirquet meaning "changed reactivity of the host when meeting an agent on a second or subsequent occasion". Allergy has become synonymous with the type I hypersensitivity.

LATE PHASE RESPONSE: Reoccurrence of clinical symptoms four to twelve hours after antigen exposure mediated by the basophil, histamine releasing factors (HRF), the eosinophil and platelet activating factor.

I. MAJOR COMPONENTS OF TYPE I REACTIONS

A. IgE

1. Is glycoprotein MW 190,000 which is heat labile.

2. Has a serum half life of 2-3 days. Regulated by T cell factors (IgE binding factors) GEF, GIF.

3. Binds to basophils and mast cell through a high affinity Fc receptor.

4. Basal level is controlled by host factors: sex, age, race, skin and mucosal permeability.

5. Is 95% bound to cells for 3-4 weeks. Low IgE level is transmitted as an autosomal dominant.

6. Alternate pathway activation of complement is triggered by IgE-immune complexes. Is found in greater amounts in allergic individuals, and is a heterogeneous population (IgE+) (IgE-). IgE+ represents the response to histamine releasing factors. The greater the number of IgE+ an individual has the greater chance for disease through late phase response.

7. Normal increase in IgE with parasitic infections where IgE dependent binding of macrophages and eosinophils to parasites has been documented to cause cytotoxic reactions.

8. Low affinity Fc receptors for IgE are found on T-cells, B-cells, monocytes, macrophages, eosinophils and platelets indicating a regulatory function.

B. Mast cell

1. Has high affinity receptors for IgE (105 /mast cell).

2. Composed of two distinct populations:

a. Connective tissue mast cell: Predominantly found in skin w/stains intensely with metachromatic dyes. Forms prostaglandin D2 as metabolite

b. Mucosal mast cell: Found in lung and lamina propria of

the gut. Leukotriene C4 is major metabolite.

3. Has rounded nucleus with metachromatic staining granules, up to 1,000.

4. Has heterogeneous granules related to age, and polyanion of granule, i.e., Heparin sulfate or Chondroitin sulfate.

5. Originates in bone marrow.

6. Increases host response to parasitic infections.

C. Basophil

1. Is a polymorphonuclear leukocyte generated in the bone marrow.

2. Comprises 0.2% to 1% of nucleated cells in bone marrow and

peripheral blood.

3. Has lobulated nucleus with large metachromatic granules.

4. Has high affinity receptors for IgE.

5. Generates leukotriene C4.

6. Promotes late phase response i.e., asthma, contact dermatitis through IgE+ and histamine releasing factors.

7. Produce from precursors in the blood and bone marrow under the influence of IL-3.

D. Eosinophil

1. Plays a major role in allergic inflammation and disease.

2. Composes less than 3% of circulating population of peripheral leukocytes.

3. Has bilobed nucleus with refractile cytoplasmic granules staining bright red with login.

4. Originates in bone marrow under influence of granulocyte - macrophage colony stimulating factors and by T-lymphocyte factors, IL 3 and 5.

5. Responds to chemoattractant properties of C5a, PAF, LTB4.

6. Contains major basic protein (MBP), cationic protein and neurotoxin contribute to sloughing of airway epithelium and killing of parasites.

7. Is a major component of the late phase response.

E. Histamine Releasing Factors (HRF)

1. Produced by platelets, macrophages, lymphocytes.

2. Have a MW 15-30K, shared by a "family" of molecules.

3. Causes mediator release in the late phase as the result of HRF-

basophil interaction in individuals with increased IgE+.

4. Selectively causes release in atopics (IgE+).

5. May discriminate between "extrinsic" and "intrinsic" asthma and anaphylaxis.

II. MECHANISM OF IMMEDIATE HYPERSENSITIVITY

A. Antigen interacts with antigen specific cell-surface bound IgE. (dimer) on mast cells.

B. Generates a signal through the cross-linking of Fce IgE receptors.

C. Membrane lipid and adenine metabolism is initiated.

D. Granule solubilization and release of preformed amines, proteins, peptides and proteoglycans from granules occurs.

III. MEDIATORS OF IMMEDIATE HYPERSENSITIVITY

A. Preformed Mediators

1. Histamine is primary preformed vasoactive mediator in basophils and mast cells.

a. Acts on H1 to contact smooth muscles, increase vascular permeability, and generate prostaglandins.

b. Acts on H2 to increase vascular permeability, gastric acid secretion, stimulate suppressor lymphocytes, decrease PMN enzyme release, chemotaxis mast cell and basophil histamine release.

c. Acts on H3 receptors to inhibit neurotransmitter and histamine release.

2. ECF-A (mast cell) preformed attracts and deactivates eosinophils and increases eosinophils' complement receptors.

3. HMW-NCF (mast cell) attracts and deactivates neutrophils.

4. Tryptase in the mucosal mast cell is a preformed enzyme which cleaves C3.

5. Kallikrein similar to plasma kallikrein cleaves bradykinin from HMW Kininogenase and activated Hageman factor.

B. Newly Formed Mediators

1. PAF is generated by mast cells, macrophages, neutrophils and

eosinophils.

a. Aggregates platelets.

b. Releases platelet amines.

c. Generates platelet thromboxane.

d. Attracts eos, neutrophils.

2. Arachidonic acid metabolites, leukotrienes (C,D,E) are generated

by mast cells and basophils.

a. Constrict smooth muscle.

b. Increase vascular permeability.

c. Synergistic with histamine.

d. Cause cardiac depression.

e. Inhibit lymphocyte response to mitogen.

3. Leukotriene B4 (LTB4) is most potent chemotactic factor for neutrophils and eosinophils.

4. Prostaglandin D2 (mast cell) causes constriction on bronchial smooth muscle.

5. Adenosine inhibits platelet aggregation, is potent bronchoconstrictor and enhances mast cell release.

C. Granule - Associated Mediators

1. Heparin sulfate is the major preformed proteoglycan which binds histamine, inhibits complement activation, acts as a anticoagulant, binds platelet factor 4 and tryptase.

2. Chondroitin 4 an 6 sulfate is preformed in the basophil to bind histamine

IV. REGULATION OF MAST CELL DEGRANULATION

A. Intracellular cyclic nucleotides modulate mediator release.

1. Increased cAMP depresses mediator release.

2. Increased cGMP enhances mediator release.

3. Ca2 ion stores, intra and extracellular, modify Ag mediated histamine release.

B. Basophils and mast cells have additional surface receptors.

1. Beta receptors are present on mast cells and basophils which when stimulated increase cAMP.

2. Beta receptors may be abnormal or decreased in atopic disease.

3. Beta agonists (isoproterenol, epinephrine) increase cAMP.

4. Alpha adrenergic receptors present on smooth muscle cause vasoconstriction.

5. Cholinergic stimulation increases mucus secretion and smooth muscle constriction.

6. Alpha, beta and cholinergic receptor abnormalities predispose atopic individuals to end organ sensitivity.

7. Mast cells and basophils have for C3a, c5a anaphylatoxin generated by complement activation.

C. Eosinophils and neutrophils modulate responses provoked by mast cells and basophils in the late phase response.

V. CLINICAL MANIFESTATIONS OF ANAPHYLAXIS

A. Reactions are due to release of preformed mediators (histamine) and generation of leukotrienes, PAF. Severe reactions are marked by massive swelling of respiratory tract, constriction of bronchial smooth muscle and massive vasodilatation through mediator effect on capillary permeability.

1. Fatalities result in 3% of cases.

2.Significant upper and lower respiratory obstruction represent cause of death 70% of cases.

3. Cardiac arrhythmias and dysfunctions represent 24% of fatal cases.

4. Risk factors for fatalities include:

a. protracted course

b. Beta blockers

c. adrenal insufficiency

B. Host factors relevant to development of anaphylaxis include:

1. Antigen dose and mode of administration

2. Genetic predisposition

3. Stress/Chronic disease

4. Nutritional Status

C. Anaphylaxis may be uniphasic, biphasic or protracted.

1. Laryngeal edema occurs more frequently in protracted (57%) or biphasic (40%) cases.

2. With oral agents biphasic or prolonged reactions are more common than perceived previously.

3. Glucocorticoids do not reproducibly prevent biphasic or protracted anaphylaxis.

4. Patients with reactions need to be observed for greater than 12 hours especially if upper airway obstruction is involved.

D. Mechanisms involve IgE (atopy), IgE (non atopic) and non IgE.

1. Drugs IgE (non atopic).

a. Antibiotics - prototype is penicillin. Reactions rates are 0.7% to 8% (4-15 cases/10,000 courses of PCN) 20% of the population claim a history of PCN allergy. There is a 10% reaction rate with a negative history. Forty percent reaction rate with positive history. Skin testing is performed with the major determinant pencilloyl-poly-L-lysine (PrePen) and minor determinant (benzyl penicillin). Positive minor determinant skin test is associated with anaphylaxis. If skin tests are negative less than 3% chance of anaphylaxis. Desensitization is possible in a controlled environment. (cephalosporins, tetracyclines, nitrofurantoin, streptomycin, chloramphenicol, bacitracin, neomycin, amphotericin .

Non IgE - vancomycin, polymyxins.

2. Foreign Proteins IgE (non atopic).

a. Insulin

b. PTH

c. ACTH

d. Asparaginase

e. Chymopapain

f. Penicillinase

g. Seminal Plasma

h. Antilymphocyte globulin

i. Hymenoptera venom

j. Fire ant venom

Insect Stings cause 50 fatalities annually. Patients with systemic reactions can receive venom specific therapy (bee, wasp, yellow jacket, hornet and fire ant). Immunotherapy is maintained at 100 micrograms per antigen for 60 months. Specific IgE and IgG titers can then help predict continued need for therapy.

3. Therapeutic agents (IgE).

a. allergic extracts

b. muscle relaxants

c. estradiol

d. hydrocortisone

e. methylprednisolone

f. protamine

g. ethylene oxide

h. thiopental

i. local anesthetics

i. Reactions are usually secondary to bisulfites or epinephrine. To document safety of a particular agent provocative skin testing can be performed.

ii. Chemically there are two groups Group I (benzoic acid ester) or Group II (amide). There is cross reactivity in Group I not in Group II. If a reaction with a Group I agent occurs (Novocaine) a Group II agent (carbocaine) can be selected.

j. vaccines

k. streptokinase

4. Foods (IgE atopic).

Fatalities usually occur in victims with prior knowledge i.e., past anaphylaxis. Usually it is a meal away from home, with alcohol, denial, reliance on p.o. antihistamines and no Epi-Pen.

a. milk

b. egg white

c. nuts

d. citrus

e. wheat

f. soybean/legumes/peanuts

g. seeds (sunflower, pumpkin)

h. grains

i. cottonseed

j. fish

k. shellfish

l. bananas

m. beets

n. corn

o. safflower

p. chamomile tea

5. Therapeutic agents (Non IgE) Reactions are secondary to anaphylatoxin production.

a. Radiocontrast media reactions occur in 20% of all procedures. Patients with prior reactions have a 17-35% change of subsequent reaction. Pretreatment with antihistamines 50mg IM l hr. before the procedure and Prednisone 50mg 13, 7 and 1 hr. before the procedure has provided effective protection in 93% of patients with prior reactions (Greenberger et.al.). Reaction is not related to iodine. Atopics allergic to shellfish have a slightly increased risk. Low osmolality contrast media has decreased reactions with increased patient comfort.

b. Transfusion reaction

c. Gamma globulin infusion

6. Modulators of Arachidonic acid metabolism. Reactions are secondary to increases in by products of lipooxygenase pathway.

a. ASA

b. Nonsteroidal anti-inflammatory agents

c. Azo dyes

d. Yellow dye #5

e. Benzoates

7. Bisulfites which are used as sanitizing agents for food containers and fermentations equipment. FDA allows in non-thiamine containing foods. Sprayed on fresh vegetables, shellfish, beer, and wine. Ingest 20-100 mg per restaurant meal. Also found in medications. Mechanism of action thought to be secondary to stimulation of afferent cholinergic reflex arc by sulfur dioxide causing massive cholinergic discharge.

8. Exercise-induced anaphylaxis characterized by cutaneous warmth, pruritus, urticaria and vascular collapse. More common in atopics. may be related to specific food ingestion prior to exercise.

9. Idiopathic anaphylaxis (73 pts. reported by Boxer et.al.) no clear reproducible triggers.

a. Usually more common in atopic females (59%)

b. Reactions are infrequent 1-6 x a year (mild) (52%)

c. Reactions are frequent 48% requiring maintenance antihistamines (H1) and prednisone. Remission has required an average of 1 yr. of prednisone therapy.

10. Progesterone allergy females who are frequently atopic demonstrate sensitivity to medroxyprogesterone documented by skin testing. Treatment involves use of androgens or oophorectomy/hysterectomy.

E. Treatment

1. Epinephrine 0.3 - 0.ml (1:1000) S.C.

2. If profound hypotension, use IV Epinephrine 2-3 ml (1:10,000), although increase incidence of arrhythmias. Repeat dose every 15-20 min. as necessary.

3. Supportive therapy with fluids, vasopressors as necessary.

4. Addition of H1 blockers, H2 blockers

5. Corticosteroids (2-4 mg/kg q 4-6 hrs.) are helpful in preventing the late phase response.

6. Glucagon 1mg bolus in patients on Beta blockers.

F. Prevention of anaphylaxis and anaphylactic death

1. Thorough drug allergy history

2. Give drug orally rather than parenterally when possible

3. Patients to wait in office 30 minutes after drug administration

4. Check all drugs for proper labelling

5. Predisposed patients to carry warning identification

6. Predisposed patients taught self-injection of epinephrine

7. When antiserum essential, use human

8. Skin test and desensitize when appropriate

Background: Anaphylaxis refers to a severe allergic reaction in which prominent dermal and systemic signs and symptoms manifest. The full-blown syndrome includes urticaria (hives) and/or angioedema with hypotension and bronchospasm. The classic form, described in 1902, involves prior sensitization to an allergen with later re-exposure, producing symptoms via an immunologic mechanism. An anaphylactoid reaction produces a very similar clinical syndrome but is not immune-mediated. Treatment for both conditions is similar, and this article uses the term anaphylaxis to refer to both conditions unless otherwise specified.

Pathophysiology: Rapid onset of increased secretion from mucous membranes, increased bronchial smooth muscle tone, decreased vascular smooth muscle tone, and increased capillary permeability occur after exposure to an inciting substance. These effects are produced by the release of mediators, which include histamine, leukotriene C4, prostaglandin D2, and tryptase.

In the classic form, mediator release occurs when the antigen (allergen) binds to antigen-specific immunoglobulin E (IgE) attached to previously sensitized basophils and mast cells. The mediators are released almost immediately when the antigen binds. In an anaphylactoid reaction, exposure to an inciting substance causes direct release of mediators, a process that is not mediated by IgE. Increased mucous secretion and increased bronchial smooth muscle tone, as well as airway edema, contribute to the respiratory symptoms observed in anaphylaxis. Cardiovascular effects result from decreased vascular tone and capillary leakage. Histamine release in skin causes urticarial skin lesions.

The most common inciting agents in anaphylaxis are parenteral antibiotics (especially penicillins), IV contrast materials, Hymenoptera stings, and certain foods (most notably, peanuts). Oral medications and many other types of exposures also have been implicated. Anaphylaxis also may be idiopathic.

Frequency:

In the US: The true incidence of anaphylaxis is unknown, partly because of the lack of a precise definition of the syndrome. Some clinicians reserve the term for the full-blown syndrome, while others use it to describe milder cases. Fatal anaphylaxis is relatively rare; milder forms occur much more frequently. Some authors consider up to 15% of the US population "at risk" for anaphylaxis. The frequency of anaphylaxis is increasing and this has been attributed to the increased number of potential allergens to which people are exposed. Up to 500-1,000 fatal cases of anaphylaxis per year are estimated to occur in the US.

Internationally: Reactions to insects and other venomous plants and animals are more prevalent in tropical areas because of the greater biodiversity in these areas.

Mortality/Morbidity: Approximately 1 in 5000 exposures to a parenteral dose of a penicillin or cephalosporin antibiotic causes anaphylaxis. More than 100 deaths per year are reported in the United States. Fewer than 100 fatal reactions to Hymenoptera stings are reported each year in the United States but this is considered to be an underestimate. One to 2% of people receiving IV radiocontrast experience some sort of reaction. The majority of these reactions are minor, and fatalities are rare. Low molecular weight contrast causes fewer and less severe reactions.

Race: Well-described racial differences in the incidence or severity of anaphylaxis do not exist. Cultural and socioeconomic differences may influence exposure rates.

Sex: No major differences have been reported in the incidence and prevalence of anaphylactic reactions between men and women.

Age: Anaphylaxis occurs in all age groups. While prior exposure is essential for the development of true anaphylaxis, reactions occur even when no documented prior exposure exists. Thus, patients may react to a first exposure to an antibiotic or insect sting. Adults are exposed to more potential allergens than are pediatric patients. The elderly have the greatest risk of mortality from anaphylaxis due to the presence of preexisting disease.

History:

Anaphylactic reactions almost always involve the skin or mucous membranes. More than 90% of patients have some combination of urticaria, erythema, pruritus, or angioedema. The upper respiratory tract commonly is involved, with complaints of nasal congestion, sneezing, or coryza. Cough, hoarseness, or a sensation of tightness in the throat may presage significant airway obstruction.Eyes may itch and tearing may be noted. Conjunctival injection may occur.

Dyspnea is present when patients have bronchospasm or upper airway edema. Hypoxia and hypotension may cause weakness, dizziness, or syncope. Chest pain may occur due to bronchospasm or myocardial ischemia (secondary to hypotension and hypoxia).GI symptoms of cramplike abdominal pain with nausea, vomiting, or diarrhea also occur but are less common, except in the case of food allergy.In a classic case of anaphylaxis, the patient or a bystander provides a history of possible exposures that may have caused the rapid onset of skin and other manifestations. This history often is partial; exposure may not be recalled, or it may not be considered significant by the patient or physician. For example, when queried about medications, a patient may not mention over-the-counter (OTC) products. The clinician may not realize that, while reactions are usually rapid in onset, they also may be delayed.

Physical:

General

Physical examination of patients with anaphylaxis depends on affected organ systems and severity of attack. Vital signs may be normal or significantly disordered with tachypnea, tachycardia, and/or hypotension.

Place emphasis on determining the patient's respiratory and cardiovascular status.

Frank cardiovascular collapse or respiratory arrest may occur in severe cases. Anxiety is common unless hypotension or hypoxia causes obtundation. Shock may occur without prominent skin manifestations or history of exposure; therefore, anaphylaxis is part of the differential diagnosis for patients who present with shock and no obvious cause.

General appearance and vital signs vary according to severity of attack and affected organ system(s). Patients commonly are restless due to severe pruritus from urticaria. Anxiety, tremor, and a sensation of cold may result from compensatory endogenous catecholamine release. Severe air hunger may occur when the respiratory tract is involved. If hypoperfusion or hypoxia occurs, the patient may exhibit a depressed level of consciousness or may be agitated and/or combative. Tachycardia usually is present, but bradycardia may occur in very severe reactions.

Skin

The classic skin manifestation is urticaria (ie, hives). Lesions are red and raised, and they sometimes have central blanching. Intense pruritus occurs with the lesions. Lesion borders usually are irregular and sizes vary markedly. Only a few small or large lesions may become confluent, forming giant urticaria. At times, the entire dermis is involved with diffuse erythema and edema. Hives can occur anywhere on the skin.

In a local reaction, lesions occur near the site of a cutaneous exposure (eg, insect bite). The involved area is erythematous, edematous, and pruritic. If only local skin reaction (as opposed to generalized urticaria) is present, systemic manifestations (eg, respiratory distress) are less likely. Local reactions, even if severe, are not predictive of systemic anaphylaxis on re-exposure.Lesions typical of angioedema also may manifest in anaphylaxis. The lesions involve mucosal surfaces and deeper skin layers. Angioedema usually is nonpruritic and associated lesions are nonpitting. Lesions most often appear on the lips, palms, soles, and genitalia.

Pulmonary

Upper airway compromise may occur when the tongue or oropharynx is involved. When the upper airway is involved, stridor may be noted. The patient may have a hoarse or quiet voice and may lose speaking ability as the edema progresses. Complete airway obstruction is the most common cause of death in anaphylaxis.

Wheezing is common when patients have lower airway compromise due to bronchospasm or mucosal edema.

In angioedema, due to ACE inhibitors, marked edema of the tongue and lips may obstruct the airway.

Cardiovascular

Cardiovascular examination is normal in mild cases. In more severe cases, compensatory tachycardia occurs due to loss of vascular tone.

Intravascular volume depletion may take place as a consequence of capillary leakage. These mechanisms also lead to development of hypotension.

Relative bradycardia has been reported.

Causes:

A wide variety of substances can cause anaphylaxis. Anaphylaxis also may be idiopathic.

In the classic form of anaphylaxis, a foreign protein is the inciting agent (eg, antigen). On initial exposure, the antigen elicits generation of an IgE antibody. The antibody residue binds to mast cells and basophils. On re-exposure, the antigen binds to the antibody, and the receptors are activated. Clinical manifestations result from release of immune response mediators such as histamine, leukotrienes, tryptase, and prostaglandins. The same mechanism occurs when a nonimmunogenic foreign substance binds as a so-called hapten to a native carrier protein, creating an immunogenic molecule. Factors influencing severity of a reaction include degree of host sensitivity and dose, route, and rate of administration of the offending agent.

Parenteral exposures tend to result in faster and more severe reactions. Most severe reactions occur soon after exposure. The faster a reaction develops, the more severe it is likely to be. While most reactions occur within hours, symptoms may not occur for as long as 3-4 days after exposure.

Drugs

Penicillin and cephalosporin antibiotics are the most commonly reported medical agents in anaphylaxis. This prevalence is a function of the immunogenicity and overuse of these agents. Because of their molecular and immunologic similarity, cross-sensitivity may exist. Reports often assert that 10% of patients allergic to a penicillin antibiotic are allergic to cephalosporins. A recent report suggests that actual incidence of cross-reactivity is lower (perhaps 1%), with most reactions considered mild. A more recent review indicated that patients with a history of allergy to penicillin seem to have a higher risk (by a factor of about 3) of subsequent reaction to any drug and that the risk of an allergic reaction to cephalosporins in patients with a history of penicillin allergy may be up to 8 times as high as the risk in those with no history of penicillin allergy (ie, at least part of the observed cross reactivity may represent a general state of immune hyperresponsiveness, which represents true

cross-reactivity).

Reactions tend to be more severe and rapid in onset when the antibiotic is administered parenterally.

Anaphylaxis may occur in a patient with no prior history of drug exposure.

History of penicillin or cephalosporin allergy often is unreliable and is not predictive of future reactions. Up to 85% of patients reporting an allergic reaction to penicillin do not react on subsequent exposure. When a drug in either class is the drug of choice for a patient with a life-threatening emergency, a number of options exist. When the history is indefinite, the drug may be administered under close observation; however, when possible, obtain the patient's informed consent. Immediate alternate treatment measures should be available. Alternatively, when the history is more convincing, a desensitization or prophylactic pretreatment protocol may be instituted.

Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) commonly are implicated in allergic reactions and anaphylaxis. Bronchospasm is common in patients with reactive airway disease and nasal polyps. Cross-reactivity may occur between the various NSAIDs.

Intravenous radiocontrast media

IV administered by radiocontrast media causes an anaphylactoid reaction that is clinically identical to true anaphylaxis and is treated in the same way. The reaction is not related to prior exposure. Shellfish or "iodine allergy" is not a contraindication to use of IV contrast and does not mandate a pretreatment regimen. As with any "allergic" patient, give consideration to use of low molecular weight (LMW) contrast.

The term iodine allergy is a misnomer. Iodine is an essential trace element present throughout the body. No one is allergic to iodine. Patients who report iodine allergy usually have had either a prior contrast reaction or a shellfish allergy. Manage these patients as indicated earlier.Approximately 1-3% of patients who receive hyperosmolar IV contrast experience a reaction. Use of LMW contrast decreases incidence of reactions to approximately 0.5%. Personnel, medications, and equipment needed for treatment of allergic reactions always should be available when these agents are administered. Obtain consent before administration.Reactions to radiocontrast usually are mild (most commonly urticarial), with only rare fatalities reported. Risk of a fatal reaction has been estimated at 0.9 cases per 100,000 exposures.

Mucosal exposure (eg, GI, genitourinary [GU]) to radiocontrast agents has not been reported to cause anaphylaxis; therefore, a history of prior reaction is not a contraindication to GI or GU use of these agents.

Pretreatment with antihistamines or corticosteroids and use of LMW agents lead to lower rates of anaphylactoid reactions to IV contrast. Consider these measures for patients who have prior history of reaction, since rate of recurrence is estimated at 17-60%. Patients who are atopic and/or asthmatic also are at increased risk of reaction. In addition, allergic reaction is more difficult to treat in those taking beta-blockers.

Hymenoptera stings

Hymenoptera stings are a common cause of allergic reaction and anaphylaxis. An uncertain but enormous number of exposures occur; accurate reaction rates are difficult to estimate. In the United States, Hymenoptera envenomations result in fewer than 100 deaths per year.

Local reaction and urticaria without other manifestations of anaphylaxis are much more common than full-blown anaphylaxis. Generalized urticaria is a risk factor for subsequent anaphylaxis; but a local reaction, even if severe, is not a risk factor for anaphylaxis.

Caution patients treated and released from the ED after an episode of anaphylaxis or generalized urticaria from Hymenoptera envenomation to avoid future exposure when possible. Consider referral to an allergist for desensitization, particularly when further exposure is likely. Additionally, consider prescribing a treatment kit with an epinephrine auto-injector and oral antihistamine. Both are effective measures in preventing or ameliorating future reactions.

Allergies

Food allergy is common. Symptoms usually are mild and limited to the GI tract, but full-blown anaphylaxis can occur. Fatalities are rare compared to number of exposures; however, the number of exposures is so high that foods may be the commonest cause of anaphylaxis. Anaphylaxis due to foods may be an underrecognized cause of sudden death and an unappreciated cause of diagnosed anaphylaxis. Commonly implicated foods include nuts (especially peanuts), legumes, fish and shellfish, milk, and eggs.

Latex allergy is an increasingly recognized problem in medical settings, where use of gloves and other latex products is ubiquitous. Most reactions are cutaneous or involve the mucous membranes. Anaphylactic reactions occur and have been reported with seemingly benign procedures (eg, Foley catheter insertion, intraperitoneal exposure to gloves during surgery).

DIFFERENTIALS ::

Angioedema

Anxiety

Asthma

Conversion Disorder

Epiglottitis, Adult

Foreign Bodies, Trachea

Myocardial Infarction

Pulmonary Embolism

Toxicity, Scombroid

Urticaria

Other Problems to be Considered:

Globus hystericus

Hereditary angioedema

Monosodium glutamate poisoning (ie, Chinese restaurant syndrome)

WORKUP

Lab Studies:

The diagnosis of anaphylaxis is clinical and does not rely on laboratory testing. When typical symptoms are noted in association with a likely exposure, diagnosis is virtually certain. Ancillary testing may help assess severity of reaction, although this is primarily a clinical judgment. When unclear, ancillary testing may help establish the diagnosis.

The only potentially useful test at the time of reaction is measurement of serum mast cell tryptase. Tryptase is released from mast cells in both anaphylactic and anaphylactoid reactions. Levels are usually raised in severe reactions. Mast cell tryptase is raised transiently with blood levels reaching a peak approximately an hour after reaction onset.

Tryptase levels may aid in later diagnosis and treatment.

Consider the test in cases for which diagnosis of anaphylaxis is uncertain.

The utility of this test awaits full evaluation.

Cardiac monitoring in patients with severe reactions and in those with underlying cardiovascular disease is important, particularly when adrenergic agonists are used in treatment. Pulse oximetry also is useful.

Imaging Studies:

Imaging studies are not generally useful in the diagnosis and management of anaphylaxis, although they may be used as diagnostic aids when diagnosis is unclear.

Other Tests:

Sensitivity testing

Testing for sensitivity to penicillin antibiotics may be useful when a penicillin or cephalosporin antibiotic is the drug of choice for a serious infection in a patient who has a history of severe allergic reaction. Obtain informed consent, and ensure that resuscitative equipment is immediately available. Protocols for acute testing for allergy to penicillin or cephalosporin antibiotics involve administration of increasing IV doses of the chosen antibiotic, while observing the patient for pruritus, flushing, urticaria, dyspnea, hypotension, or other manifestations of anaphylaxis. If no manifestations are observed, a full dose of the antibiotic may be administered safely.

A suggested protocol for IV testing begins with 0.001 mg of the chosen drug. At 10-min intervals, incrementally increase the dose (eg, 0.001 mg, 0.005 mg, 0.01 mg, 0.05 mg, 0.1 g, 0.5 mg, 1 mg, 10 mg, 50 mg, 100 mg, full dose), while observing the patient. Many other protocols exist. In most circumstances, perform desensitization on an inpatient basis. If the necessary resources are available, desensitization may be performed in the ED.

Procedures:

Intravenous contrast reaction prevention

Patients with a history of severe reactions to IV contrast material may require use of contrast in an urgent or emergency situation. Alternatives (eg, spiral CT scan for ureteral stone, Doppler ultrasound for deep venous thrombosis [DVT]) should be considered but are not always feasible. In these circumstances, a prophylactic regimen of corticosteroids and antihistamines may be used. The precise efficacy of these regimens is difficult to evaluate, but they generally are considered effective. One author states that the recurrence rate for patients with a previous reaction was reduced from 17-60% to 9% when conventional contrast material was used; the rate was reduced to less than 1% when low osmolality material was employed after a pretreatment regimen.

The use of H2 blockers has not been shown to decrease the risk of reaction to IV contrast. One study suggests H2 blockers actually appear to increase the risk.

A widely quoted protocol for prevention of reactions to IV contrast suggests the following:

Use low osmolality contrast.

Administer hydrocortisone (200 mg IV); wait 2 hours if clinically appropriate.

Administer diphenhydramine (50 mg IM) immediately before the procedure.

Desensitization regimens

Desensitization regimens for penicillin and cephalosporin antibiotic allergy have been shown effective. Because these regimens are lengthy (approximately 6 h), they have limited applicability to the ED. When patients wait for long periods in the ED or in an observation unit, consider desensitization regimens.

A typical desensitization regimen involves administering the antibiotic of choice in an initial dose of 0.01 mg. While observing the patient, double the dose every 10-15 minutes until a full dose has been administered.

Desensitization regimens do not protect against non–IgE-mediated reactions that may be severe or even life threatening (eg, Stevens-Johnson syndrome).

While theoretically attractive, premedication regimens have not been clinically shown to decrease incidence or severity of IgE-mediated allergic reactions to antibiotics.

TREATMENT::

Prehospital Care:

Prehospital patients with symptoms of severe anaphylaxis should first receive standard interventions. Interventions include high-flow oxygen, cardiac monitoring, and IV access. These measures are appropriate for an asymptomatic patient who has a history of serious reaction and has been re-exposed to the inciting agent. Additional treatment depends upon the condition of the patient and the severity of the reaction. Measures beyond basic life support (BLS) are not necessary for patients with purely local reactions.

Immediately assess airway patency due to the potential for compromise secondary to edema or bronchospasm. Active airway intervention may be difficult due to laryngeal or oropharyngeal edema. In this circumstance, it may be preferable to defer intubation attempts, and instead ventilate with a bag/valve/mask apparatus while awaiting medications to take effect. In extreme circumstances, cricothyrotomy or catheter jet ventilation may be lifesaving. Inhaled beta-agonists are used to counteract bronchospasm and should be administered to patients who are wheezing.

The IV line should be of large caliber due to the potential requirement for large-volume IV fluid resuscitation. Isotonic crystalloid solutions (ie, normal saline, Ringer lactate) are preferred. A keep vein open (KVO) rate is appropriate for patients with stable vital signs and only cutaneous manifestations. If hypotension or tachycardia is present, administer a fluid bolus of 20 mg/kg for children and 1 L for adults. Further fluid therapy depends on patient response. Large volumes may be required in the profoundly hypotensive patient.

Administer epinephrine to patients with systemic manifestations of anaphylaxis. With mild cutaneous reactions, an antihistamine alone may be sufficient, thus the potential adverse effects of epinephrine can be avoided. Patients on beta-blocker medications may not respond to epinephrine. In these cases, glucagon may be useful. The Medication section describes dosage, routes of administration, and contraindications for medications discussed in this section. Antihistamines (eg, H1 blockers), such as diphenhydramine (Benadryl) are important and should be administered for all patients with anaphylaxis or generalized urticaria.

Corticosteroids are used in anaphylaxis primarily to decrease the incidence and severity of delayed or biphasic reactions. Corticosteroids may not influence the acute course of the disease; therefore, they have a lower priority than epinephrine and antihistamines.

Emergency Department Care:

ED care begins with standard monitoring and treatment, including oxygen, cardiac monitoring, and a large-bore IV with isotonic crystalloid solution. Further intervention depends on severity of reaction and affected organ system(s).

Rapidly assess airway patency in patients with systemic signs or symptoms. If required, intubation may be difficult to achieve because of upper airway or facial edema. Standard rapid sequence induction (RSI) techniques can be used but may cause loss of the airway in a patient whose airway anatomy is altered by edema. Epinephrine may rapidly reverse airway compromise, and bag/valve/mask ventilation may be effective in the interim when intubation is not possible. Surgical airway intervention using standard cricothyrotomy is an option when orotracheal intubation or bag/valve/mask ventilation is not effective.

Wheezing or stridor indicates bronchospasm or mucosal edema. Treatment with epinephrine and inhaled beta-agonists is effective for these indications.

Recommendations to treat refractory bronchospasm with corticosteroids have been made because of their effectiveness in reactive airway disease. As in asthma therapy, onset of action is delayed for several hours. Aminophylline also has been recommended for bronchospasm in anaphylaxis and may be more rapidly effective than corticosteroids.

Hypotension in anaphylaxis usually is due to vasodilatation and capillary fluid leakage. Epinephrine is the primary pharmacologic treatment for these findings. H1-blocking antihistamines also may have a role in reversing hypotension. Some authors also recommend H2-blocking agents. Large volume fluid resuscitation with isotonic crystalloid often is needed to support the circulation in patients with cardiovascular manifestations of anaphylaxis.

Refractory hypotension first should be treated with large volumes of crystalloid and repeated doses of epinephrine or a continuous epinephrine infusion. If this is not effective, other pressors with alpha-adrenergic activity, such as levarterenol (Levophed) or dopamine, may be considered. Cases of effective use of military antishock trousers (MAST) for refractory hypotension have been reported.

Mediators of anaphylaxis are not considered to have direct myocardial toxicity. In patients with preexisting heart disease, ischemic myocardial dysfunction may occur due to hypotension and hypoxia. Epinephrine still may be necessary in patients with severe anaphylaxis, but remember the potential for exacerbating ischemia. If pulmonary congestion or evidence of cardiac ischemia is present, fluid resuscitation should be approached more cautiously.

Patients taking beta-blockers may be resistant to the effects of epinephrine. Larger than usual doses may be needed. Glucagon may be effective in this circumstance, because it increases intracellular cyclic adenosine monophosphate (cAMP) levels by a mechanism that does not depend upon beta-receptors.

Cutaneous effects of anaphylaxis are uncomfortable but not life threatening. Patients often respond promptly to epinephrine and H1 antihistamines. Some authors state that corticosteroids help prevent recurrence of symptoms (both cutaneous and systemic) that may occur 6-8 hours after successful treatment (so-called biphasic reaction). H2 blockers may have an added effect.

GI symptoms in anaphylaxis respond to H1 antihistamines and epinephrine.

Consultations:

Acute manifestations of anaphylaxis usually respond to ED treatment. In refractory cases, consult with an allergist, cardiologist, pulmonologist, or other intensivist.

Consultation with an allergist (when available) is appropriate when desensitization to an antibiotic is contemplated.

When a patient at high risk for contrast reaction is under consideration for a contrast study, consultation with the radiologist regarding pretreatment and choice of contrast agent is appropriate.

Refer patients who are treated and released from the ED after an episode of anaphylaxis or generalized urticaria to their primary care physician or to an allergist for follow-up. At that time, consideration can be given to skin testing and possible desensitization.

MEDICATION

Primary drug treatments for acute anaphylactic reactions are epinephrine and H1 antihistamines. These agents clearly are effective; do not delay or defer their use in favor of other treatments. Inhaled beta-agonists lack some of the adverse effects of epinephrine. Inhaled beta-agonists are useful for cases of bronchospasm, but they may not have additional effects when optimal doses of parenteral epinephrine are used. Corticosteroids mainly are effective in preventing biphasic (ie, delayed) reactions. Due to this delayed effect, corticosteroids are not first-line treatments. H2-blocking antihistamines theoretically are attractive agents, but evidence supporting their clinical effectiveness is less than for H1-blocking agents. Glucagon may be useful in treating refractory cardiovascular effects in patients taking beta-blockers.

Drug Category: Parenteral adrenergic agents -- Reverse cardiovascular, cutaneous, GI, and pulmonary manifestations of anaphylaxis.

Drug Name Epinephrine (EpiPen, Adrenalin) -- DOC for shock, angioedema, airway obstruction, bronchospasm, and urticaria in severe anaphylactic reactions. Administered SC or IM, except for patients in extremis for whom it is administered IV. May be administered SL or via ET when no IV access available. Continuous infusion may be administered in cases of refractory shock.

Adult Dose 0.3-0.5 mL 1:1000 soln SC or IM q15min

1 mL 1:10,000 soln (diluted in 10cc NS) IV; slow administration; repeat prn

0.3-0.5 mL 1:1000 soln SL q15min

1.0 mL 1:1000 soln ET in approximately 10 cc NS

IV infusion: 0.1-1 mcg/kg/min

Pediatric Dose 0.01 mL/kg (minimum 0.1 mL) 1:1000 soln SC or IM q15min

0.01 mL/kg (minimum 0.1 mL) 1:10,000 soln IV prn

0.01 mL/kg (minimum 0.1 mL) 1:1000 soln SL q15min

0.01 mL/kg (minimum 0.1 mL) 1:1000 soln ET in approximately 1-3 cc NS

IV infusion: 0.1-1.0 mcg/kg/min

Contraindications May be administered in life-threatening anaphylactic reactions, even when the following relative contraindications are present: (1) coronary artery disease, (2) uncontrolled hypertension, (3) serious ventricular arrhythmias, and (4) second stage of labor

Interactions Sympathomimetics cause additive effects; beta-blockers antagonize therapeutic effects of epinephrine; digitalis potentiates proarrhythmic effect of epinephrine; TCAs and MAOIs potentiate cardiovascular effects of epinephrine; phenothiazine causes a paradoxical decrease in BP

Pregnancy B - Usually safe but benefits must outweigh the risks.

Precautions Adverse effects include cardiac ischemia or arrhythmias, fear, anxiety, tremor, and hypertension with subarachnoid hemorrhage; use with caution in elderly and in patients that have diabetes mellitus, hyperthyroidism, prostatic hypertrophy, hypertension, cardiovascular disease, and cerebrovascular insufficiency; rapid IV infusions also may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Drug Category: Inhaled beta-agonists -- Used to treat bronchospasm. Doses are identical to those used in the treatment of asthma.

Drug Name Albuterol (Proventil, Ventolin) -- Numerous inhaled beta-agonists are used for treatment of bronchospasm; albuterol is the most commonly used preparation.

Adult Dose 0.5 mL 0.5% soln in 2.5 cc NS nebulized q15min

Pediatric Dose 0.03-0.05 mL/kg 0.5% soln in 2.5 cc of NS via nebulizer q15min

Contraindications In a life-threatening anaphylactic reaction, albuterol may be administered even in the presence of (1) severe coronary insufficiency or (2) uncontrolled, severe hypertension

Significant effects are much less likely than with parenteral sympathomimetics

Interactions Sympathomimetics cause additive effects; beta-blockers antagonize therapeutic effects; digitalis potentiates proarrhythmic effects; TCAs and MAOIs potentiate cardiovascular effects; phenothiazine causes a paradoxical decrease in BP

Pregnancy B - Usually safe but benefits must outweigh the risks.

Precautions Inhaled beta-agonists are relatively well-tolerated; beta 2-agonists, such as albuterol, have relatively few cardiovascular adverse effects when compared with agents that also have beta 1-agonist activity or with parenteral sympathomimetics

Drug Category: H1-receptor blockers (Antihistamines) -- Primarily effective against cutaneous effects of anaphylaxis. Also may help antagonize cardiac and respiratory effects; should be used routinely in most cases of anaphylaxis. IV administration is preferable when a rapid effect is desired. IM dosing also is effective but has a slower onset than IV and may cause local tissue irritation. PO doses must be larger than parenteral doses because of 50% first-pass metabolism in the liver. Most recommendations for use of antihistamines state that they should be continued for 2-3 days after treatment of the acute anaphylactic event.

Drug Name Diphenhydramine (Benadryl) -- Many effective H1 blockers exist; diphenhydramine is effective and widely available.

Adult Dose 25-50 mg IV/IM q4-6h

50 mg PO q4-6h

Pediatric Dose 1-2 mg/kg IV/IM q4-6h

2 mg/kg PO q4-6h

Contraindications Documented hypersensitivity, MAOIs

Interactions Potentiates effect of CNS depressants; due to alcohol content, do not give syrup dosage form to patient taking medications that can cause disulfiramlike reactions

Pregnancy C - Safety for use during pregnancy has not been established.

Precautions May exacerbate angle closure glaucoma, hyperthyroidism, peptic ulcer, and urinary tract obstruction

Drug Category: H2-receptor blockers (Antihistamines) -- H2 blockers are used commonly by clinicians in treatment of allergic reactions and urticaria. Evidence of additive effect with H1-blocker anaphylaxis exists, but they should not be considered first-line therapy.Drug Name

Cimetidine (Tagamet) -- Many H2 blockers are available. Cimetidine is the prototype drug; other agents have much less evidence of effectiveness in anaphylaxis.

Adult Dose 300 mg PO/IV/IM q6h

Pediatric Dose 5-10 mg/kg PO/IV/IM q6h

Contraindications Documented hypersensitivity

Interactions Multiple drug interactions are related to inhibition of hepatic microsomal enzymes; cimetidine is known to increase blood concentration of (1) warfarin, (2) benzodiazepines, (3) lidocaine, (4) TCAs, (5) terfenadine, (6) phenytoin, and (7) theophylline

Pregnancy C - Safety for use during pregnancy has not been established.

Precautions Cimetidine carries relatively few serious adverse effects, particularly when only short-term acute use is considered; in the acute setting consider important adverse effects to include (1) headache and confusion and (2) cardiac arrhythmias and hypotension from rapid IV administration

Drug Category: Corticosteroids -- These agents have a role in reversing bronchospasm and cutaneous effects of anaphylaxis. Corticosteroids have a delayed onset of action and do not reverse the cardiovascular effects of anaphylaxis. These agents should be used in severe reactions, but the use of epinephrine and H1 antihistamines has a higher priority. Some authors state that corticosteroids help prevent or ameliorate recurrent (biphasic) anaphylaxis, but the true incidence of this condition has not been determined, and recurrences are usually less severe than the initial attack.

While corticosteroids usually are administered IV in patients with anaphylaxis for presumed rapidity of effect, PO and IV corticosteroids are equally efficacious in asthma therapy. When administered acutely, corticosteroids commonly are continued for 2-3 days. In asthma treatment, large parenteral doses customarily are administered acutely, followed by lower PO dosing for varying periods. Long-acting parenteral preparations may be administered as an alternative and have been shown effective in asthma therapy. Optimal dosage range for corticosteroids has not been established; thus, a range of dosages is provided based on published recommendations.Drug Name

Methylprednisolone (Solu-Medrol, Adlone, Medrol, Depo-Medrol) -- A multitude of corticosteroid preparations are available. Methylprednisolone is widely available in the ED because of other uses (ie, acute asthma, spinal cord injury). Supplied in both parenteral and oral formulations. Discussed here as typical drug of this class.

Adult Dose 40-250 mg IV/IM q6h

2-60 mg PO qd

Pediatric Dose 1-2 mg/kg IV/IM q6h

1 mg/kg PO qd

Contraindications Other than a previous severe reaction to the drug, there are no absolute contraindications to the use of corticosteroids for treatment of severe anaphylaxis

Interactions The most important interactions in the acute setting are (1) ulcerogenesis with NSAIDs, (2) increased weakness in patients who have MyG with anticholinesterases, and (3) possible viral dissemination with live virus vaccines

Pregnancy C - Safety for use during pregnancy has not been established.

Precautions Short-term use of corticosteroids, even in large doses, has minimal harmful effects; multiple adverse effects from chronic usage; benefits and risks should be considered in pregnant females; patients who are immunosuppressed and are receiving corticosteroids are at risk for dissemination or activation of certain infections

Drug Category: Antidote, Hypoglycemia -- Glucagon appears to benefit by stimulating the release of endogenous catecholamines.Drug Name

Glucagon -- Has inotropic, chronotropic, and vasoactive effects that are independent of beta-receptors. Glucagon also causes endogenous catecholamine release. Patients taking beta-blocking agents may be resistant to effects of epinephrine or other adrenergic agents used to treat the cardiovascular effects of anaphylaxis. Glucagon may be effective in these patients. Should be used in addition to epinephrine, not as a substitute. Reports of effectiveness of glucagon in anaphylaxis are anecdotal; therefore, it is difficult to specify a dose. Smaller doses are effective in elevating blood sugar in patients with hypoglycemia, but larger doses have been recommended in beta-blocker overdose.

Given parenterally. IV route is preferable, if available.

Adult Dose 1-10 mg IV/IM/SC; typically 1-2 mg q5min to effect

Pediatric Dose Not established; adult dose is approximately equivalent to 0.02 mg/kg

Contraindications Documented hypersensitivity

Interactions Effects of anticoagulants may be enhanced by glucagon (although onset may be delayed); monitor PT activity and for signs of bleeding in patients receiving anticoagulants; adjust dose accordingly

Pregnancy C - Safety for use during pregnancy has not been established.

Precautions Monitor blood glucose levels in hypoglycemic patients until they are asymptomatic; glucagon is effective in treating hypoglycemia only if sufficient liver glycogen is present; since liver glycogen availability is necessary to treat hypoglycemic patients, glucagon has virtually no effects on patients in states of starvation, adrenal insufficiency, or chronic hypoglycemia

Further Inpatient Care:

Most patients with anaphylaxis may be treated successfully in the ED and then discharged. Treatment success operationally may be defined as complete resolution of symptoms followed by a short period of observation. The purpose of observation is to monitor for recurrence of symptoms (ie, biphasic anaphylaxis).

Hospital admission is required for patients who (1) fail to respond fully, (2) have a recurrent reaction or a secondary complication (eg, myocardial ischemia), (3) experience a significant injury from syncope, or (4) need intubation. As with many other conditions, consider a lower admission threshold when patients are at age extremes or when they have significant comorbid illness.

The presenting manifestation(s) of anaphylaxis dictate inpatient care. Essentially, this care consists of continuing the care initiated in the ED.

Consider ICU admission for patients with persistent hypotension. The primary means of support are adrenergic agents (eg, epinephrine, dopamine) and fluid resuscitation. Persistent hypotension in the face of pressors and fluid resuscitation is an indication for invasive hemodynamic monitoring with evaluation of cardiac function and peripheral vascular resistance. Use of these parameters provides the basis for objective decisions regarding the use of fluids and pressors.

Inpatient management of airway compromise consists of continuation of parenteral and inhaled adrenergic agents and corticosteroids that were initiated in the ED.

Cutaneous manifestations of anaphylaxis are treated with repeated doses of antihistamines.

Further Outpatient Care:

Discharged patients who have been successfully treated for anaphylaxis usually should continue antihistamines for 2-5 days to prevent recurrence. When corticosteroids have been used as part of the initial treatment, common practice continues that treatment for a short period.

In/Out Patient Meds:

Inpatient medications are identical to those listed for ED care (see Medication).

Outpatient medications

Outpatient medications primarily consist of oral forms of the medications used in ED treatment. Adrenergic medications are not listed in this chapter, as it is assumed that patients who require these on an on-going basis will be admitted.

Consider patients who experience severe reactions to bites, stings, food, or other possibly unavoidable causes, as candidates for an epinephrine auto-injector prescription. These injectors may be packaged as kits that also contain an oral antihistamine.

The following regimens are used commonly by clinicians, though very little hard data concerning the natural history of anaphylaxis treated in the ED exists. In light of this, do not construe the following as an unqualified recommendation or as a standard of care. Evidence for efficacy of H2-blocker antihistamines is particularly sparse. The newer nonsedating antihistamines have not been studied in the context of treatment for anaphylaxis.

H1-blocker antihistamines

Diphenhydramine (Benadryl) - Adults: 25mg PO q6h for 2-5d; Children: 1mg/kg PO q6h for 2-5d

Hydroxyzine (Atarax) - Adults: 25mg PO q8h for 2-5d; Children: 1mg/kg PO q8h for 2-5d

Corticosteroids

Prednisone - Adults: 20-80 mg PO qd for 2-5d; Children: 1-2 mg/kg PO qd for 2-5d

Many other glucocorticoid preparations may be used.

H2-blocker antihistamines

Cimetidine - 300 mg PO qid for 2-5d; Children: Not recommended

Epinephrine auto-injectors prefilled syringes: A number of forms are available. Instructions for self-administration are included.

Ana-Kit (Bayer): This product is a syringe with 0.3 cc 1:1000 epinephrine solution packaged with four 2-mg chewable chlorpheniramine tablets. The syringe has 0.1 cc gradations, allowing the injection of smaller doses for pediatric patients.

EpiPen and EpiPen Jr. Auto-Injector (Center): This product is an auto-injecting syringe containing 0.3 cc 1:1000 epinephrine solution (EpiPen) or 0.3 cc 1:2000 solution (EpiPen Jr).

Transfer:

Requirements for treating a patient with anaphylaxis are likely to exist in most hospitals within the United States and Canada; therefore, transfer of patients with anaphylaxis would be a very unusual occurrence in these locations.

Deterrence/Prevention:

Preventive therapy for anaphylaxis depends on identification of the inciting agent. When the agent has been identified, the key to prevention is avoidance. Certain prophylactic or preventative therapies may be employed when re-exposure cannot be avoided. When the inciting agent is not obviously known from the history, allergy testing may help identify it. When the allergen is a therapeutic agent for which subsequent usage is medically necessary, desensitization or pretreatment protocols may be employed.

Desensitization therapy for reactions to Hymenoptera venom is partially effective in preventing or ameliorating subsequent severe reactions.

At minimum, patients discharged from the ED after a severe reaction to Hymenoptera venom should be informed of the availability of this treatment. Referral to the patient's primary care source or directly to an allergist also may be appropriate.

Complications:

Complications from anaphylaxis are rare, and most patients completely recover.

[JakeEMTP]

Good Job Ace!

As I am starting medic school in January, I find this most informative and a great read.

Keep up the good work, I will need all the help I can get!

[ptemt]

ACE,

That was quite the read! Certainly more in depth than Brady's 10 th edition. It would be nice to have it distilled down to a more basic level along side of the full presentation to help us basics better understand it.

Thanks!

[Ace844]

ACE,

That was quite the read! Certainly more in depth than Brady's 10 th edition. It would be nice to have it distilled down to a more basic level along side of the full presentation to help us basics better understand it.

Thanks!

This was meant to be a "something for everyone" post and suit all levels. It is watered down "alittle". If there are things in there that you want to see more of... or learn about feel free to speak up...

out here,

Ace844

[morris1]

Hello Every one well this post is really need to appreciates .Some problem happens due to the lungs like problem in taking breath .Chronic lung diseases makes the things tough in breathing .What's the solutions for this problem .Well you know there are lots of medication available for this purpose but which one will be best is the matter .I heard that Ipra medication are doing very well in this situation well i think this must be discussed.

Please go through the link for more...

http://www.drugdelivery.ca/s3576-s-Ipra.aspx

[Ace844]

Hello Every one well this post is really need to appreciates .Some problem happens due to the lungs like problem in taking breath .Chronic lung diseases makes the things tough in breathing .What's the solutions for this problem .Well you know there are lots of medication available for this purpose but which one will be best is the matter .I heard that Ipra medication are doing very well in this situation well i think this must be discussed.

Please go through the link for more...

http://www.drugdelivery.ca/s3576-s-Ipra.aspx

What???????......Ipratropium Bromide is related to this thread how again...? Please explain and clarify your post...

out here,

Ace844

[EmtJim]

ACE,

Excellent - need more posts like yours.

[Ace844]

Thank you..

[Ace844]

Here's a link to the NAEMSP Position paper on 'SUB-Q EPI ADMIN IN ANAPHYLAXSIS'::

http://72.14.209.104/search?q=cache:Q7zmA0...=clnk&cd=17

http://www.emtcity.com/phpBB2/viewtopic.php?t=1050

http://www.emtcity.com/phpBB2/viewtopic.php?p=68703

Hope this Helps,

ACE844