Airway 8: Anaphylaxis Portal
Overview and Orientation
Allergic(and allergic-like) reactions manifest in a wide spectrum of clinical
presentations. The body responds to what it perceives as foreign
substances and/or stimuli in a number of complex ways. The most common
presentation in emergency settings is when the body’s mast and basophil
cells are stimulated to release sufficient amounts of chemical
mediators of inflammation into the plasma, with subsequent deleterious
effects on target tissues. This response is often referred to as a
hypersensitivity response.
Numerous disorders can mimic these reactions.1
Stimulation of mast and basophil cells to release their mediators
occurs by one of two mechanisms:
- The classical IgE-mediated allergic mechanism (also called immediate
hypersensitivity). At some prior point in time, the body’s immune
system identifies allergens (proteins, called antigens, or incomplete
antigens, called haptens) as foreign to itself. Allergens enter the
body in various forms and routes:
- foods (peanuts, shellfish, eggs, fruits, others)
- drugs (antibiotics, vaccines, allergy shots, others)
- environmental (inhaled proteins such as pollens, molds, mites)
- skin products (lotions, latex products, others)
- envenomations (bee stings, snake bites)
- semen
- others
Once the immune system has identified these foreign substances, it then produces IgE antibodies to these allergens. Once manufactured, the IgE subsequently is bound to the surface membranes of the body’s mast and basophil cells, where they lie in wait for the allergen(s) to reappear. When the allergens do reappear in the now-sensitized individual, they come into contact with the IgE that is bound to these cells. This interaction then stimulates the mast and basophil cells to release a variety of chemical mediators into the plasma.
- The non-IgE mediated mechanism (which does not involve immunologic factors
like IgE antibodies). In these situations, the mast/basophil cells are
somehow directly stimulated. (Technically, these stimuli are not
referred to as allergens.) Reactions that are thought to work by this
mechanism include:
- drugs (opiates, salicylates, radio-contrast agents)
- anxiety, stress
- temperature, pressure, exercise
- combinations of the above
Some agents/stimuli cause a hypersensitivity reaction by either the immunologic or the direct mechanism. Non-steroidal anti-inflammatory drugs (NSAIDs) may be dual acting.
Given these mechanisms, anyone can become sensitized to almost anything, at any time, including agents a person has had no reaction to previously. Therefore, don’t discount any history, and refer patients with severe reactions to appropriate specialists for follow-up care.
The release of the chemical mediators from the cells has two stages:
- The immediate release of stored mediators (histamine, kallikreins, and others). The sooner the reaction occurs from a known agent, the greater the probability the reaction will be severe.
- A stimulus to produce and release freshly synthesized chemical mediators (prostaglandins, lipoxygenase products, leukotrienes, platelet-activating factor, and others). These chemical mediators cause reactions that vary widely in severity, depending on many factors and their interactions, such as the rate/route/quantity of foreign substance, the amount of IgE present, the responsiveness/sensitivity of the target organ(s), and so on. Severe reactions can occur in a delayed manner, remote in time from the introduction of the offending agent, further complicating the diagnosis.
The effects of these chemical mediators are seen clinically in several phases:
- Within minutes the preformed mediators cause vascular dilatation (with
leakage) and smooth muscle contraction. Various possible combinations
of signs and symptoms can arise from the organ systems that are
affected:
- Skin: flushing, pruritis, urticaria, angioedema (localized edema in the deeper layers)
- Cardiovascular: hypotension, dizziness, syncope, chest discomfort
- Respiratory: airway edema, wheezing, dyspnea,
- GI: nausea, esophageal discomfort (presents as chest pain), vomiting, abdominal cramps, diarrhea,
- Others (less commonly occurring)
- Late phase reaction includes infiltration of tissues with eosinophils, neutrophils, mononuclear cells, and fibrin, leading to subsequent cellular/tissue destruction.
For terminology purposes, definitions for a severe multi-organ reaction follow:
- anaphylaxis (literally meaning “without protection”) is the classic allergic reaction involving IgE, and
- anaphylactoid reaction is direct stimulation not involving IgE.
By either mechanism, the result is the release of the same chemicals from the same cells; therefore, treat both the same.
Conditions that may mimic severe allergic reactions but involve other mechanisms and therefore require different emergency treatment include:
- Hereditary angioedema (HAE) is an inherited deficiency of C1 esterase inhibitor. This angioedema commonly involves the face, mouth, upper airway, and esophagus, and is not responsive to standard anaphylaxis treatment. HAE swelling usually resolves spontaneously in 2 to 4 days; however, treat severe cases with aggressive airway management (if the upper airway is involved). Treat with intravenous C1 esterase inhibitor concentrate (C1NHRP) 500 to 1000 U IV (or fresh frozen plasma [FFP] 2 U IV if C1INHRP is not available). a
- Acquired angioedema (AAE), a C1 esterase inhibitor deficiency that may be related to lymphoproliferative disorders and/or autoimmune disorders. This angioedema also commonly involves the face, mouth, upper airway, and esophagus, and is not responsive to standard anaphylaxis treatment. Severe cases are treated with aggressive airway management (if the upper airway is involved) and C1 esterase inhibitor concentrate (or fresh frozen plasma if C1INH is not available).
- ACE (angiotensin converting enzyme) inhibitor angioedema, which commonly involves the upper airway. These medications are commonly used to treat hypertension. This disorder is thought to involve the metabolism of kinins, and is poorly responsive to standard anaphylaxis treatment. Aggressive airway evaluation and management is indicated. RSI may be contraindicated in difficult cases.
Remember, just as all that wheezes is not asthma, all that swells is not allergic. Careful history taking and a high index of suspicion are needed to identify and successfully treat these conditions.
Treatment of Anaphylaxis/Anaphylactoid Reactions
These conditions cause death from airway obstruction/respiratory failure and circulatory collapse. While the ABCs of resuscitation help to organize thinking about the management of these reactions, in real time, these actions often take place simultaneously.
Secure and maintain an adequate airway.
Airway obstruction is due to edematous tissue, and airway edema poses some of
the most difficult airway management conditions imaginable. In this
dynamic situation, a patient’s condition can deteriorate rapidly.
Anticipate the difficulty of securing the patient’s airway and think
ahead of all airway options.
If possible, allow patients to sit upright in order to use their natural protective mechanisms during the initial evaluation of the airway.
- If the airway is edematous and/or has upper airway signs and
symptoms—voice change, hoarseness, stridor, dyspnea—associated with
this reaction:
- Administer epinephrine immediately. Route of administration (IM, SQ, or IV) depends on the severity. (See Drugs and adjunctive treatment at the end of this portal.)
- 100% O2 if dyspneic
- Heliox may prove helpful while preparing for intubation. (Vol II—AIR3 Heliox Treatment)
- Intubate as necessary after rapid but thorough upper airway
evaluation. If time permits, strongly consider early intubation. RSI
may prove problematic with profound airway edema. If a paralyzed
patient is unable to be intubated, the distorted, edematous anatomy may
render BVM ventilation useless. Consider awake intubation with or
without fiberoptic guidance.
- If feasible, orotracheally intubate the patient. (Vol III—AIR1 Rapid Sequence Intubation 9; Vol II—Air Skills 3 Orotracheal Intubation)
- If you are unable to intubate the patient, consider performing transtracheal needle ventilation (Vol II—Air Skills 16 Transtracheal Needle Ventilation) and re-attempting orotracheal intubation.
- If you are unable to intubate the patient, (PEDS) perform a tracheostomy in children < 8 years old or a cricothyrotomy (Vol II—Air Skills 14 Tracheotomy) in children > 8 years old and in adults.
Breathing
- Use oxygen generously.
- Treat bronchospasm (lower airway obstruction) with inhaled albuterol, 2.5 mg in 2.5 cc NS.
- Ipratropium bromide 0.5 mg in 2.5 cc NS is useful for bronchospastic patients on beta blockers.
- Epinephrine (by any route) is effective in treating allergic bronchospasm.
Circulation
Be aware that anaphylaxis can present with pure circulatory
signs and symptoms (such as tachycardia, chest discomfort, and hypotension)
without itching or wheals. Fluids and epinephrine are the treatment
mainstays of circulatory collapse.
Fluids: If the patient is hypotensive, use large bore IVs and aggressively use NS IV or lactated Ringer’s fluids. (Patients may third space up to 40% of their vascular volume. After fluid loading, patients may appear edematous or to be in acute pulmonary edema with frothy sputum. This edema is due to capillary leakage rather than pulmonary vascular overload; this leakage counter-intuitively seems to respond favorably to volume loading. More invasive monitoring may be needed in such cases.)
- PEDS: In children, administer a 20 mL/kg saline bolus IV and continue volume loading until achieving a CVP (Vol II—Circ Skills 3 Central Venous Pressure Measurement) of about 15 cm H2O (as estimated from neck vein filling). If this physical finding is not reliable, central venous access (Vol II—Circ Skills 2 Central Venous Access) is needed to measure CVP in order to guide fluid resuscitation.
- In adults, administer a 1 L NS or lactated Ringer’s IV. Continue volume loading until achieving a CVP of about 15 cm H2O. If the neck veins are not clearly seen, establish central venous access in order to monitor filling pressures via CVP.
- Monitor urinary output.
Drugs and adjunctive treatment
- Epinephrine is the preferred drug for initial treatment of the systemic
reactions of anaphylaxis. Epinephrine counteracts the vasodilatation,
bronchoconstriction, and other adverse effects of anaphylactic
mediators on the target tissues as well as inhibits the further release
of mediators from mast cells and basophils. A potent drug with a
significant complication profile, epinephrine may be used safely, even
for geriatric patients.2
- Administer epinephrine immediately. Route of administration depends on the severity of the anaphylactic reaction.
- As an initial dose, consider giving epinephrine IM/SQ: 0.01 mL/kg (up to 0.3 mL) of 1:1000 solution; repeat every 5 minutes as needed.
- For severe anaphylaxis, epinephrine IM may result in higher, more rapid, and more predictable peak plasma epinephrine concentrations than the SQ route.3,4 In these cases, use epinephrine IM 0.3 to 0.5 mg (0.3 to 0.5 mL/kg of the 1:1000 dilution) into the anterior of the lateral thigh. Repeat every 5 to 15 minutes, with intervals shortened to 3 to 5 minutes if needed. PEDS: In children, use epinephrine IM 0.01 mL/kg of the 1:1000 dilution (max 0.5 mL), preferably in the anterior or lateral thigh.
- In more extreme cases (life-threatening circumstances, severe/persistent hypotension despite fluids and initial IM or SQ epinephrine, unresponsive patients), use an IV drip. Give 1 mg in 500 mL NS (2 µg/mL) IV drip at rate determined by the seriousness of the situation and patient’s response. Usual doses are from 2 to 10 µg/minute IV (or 1 to 5 mL/minute of the solution of 1 mg of epinephrine/500 mL of NS). Higher doses may be needed if the patient is clinically unresponsive to lower doses but the dose must be carefully titrated under direct supervision while monitoring BP and cardiac rhythm. If continuous infusion is necessary, switch to a pump-controlled regimen when feasible/available. Cardiac monitoring is indicated if giving epinephrine intravenously. PEDS: In younger children, start the epinephrine drip at 0.1 µg /kg/min (0.05 mL/kg/min) and titrate up to 1 µg /kg/min (0.5 mL/kg/min) with the dose not to exceed the adult dose of 10 µg /min (5 mL/min).
- Nebulized drugs: Administer nebulized albuterol, 2.5 mg in 2.5 cc NS, and/or ipratropium bromide, 0.5 mg in 2.5 cc NS, if bronchospasm is a major component of this reaction. Consider using these nebulized medications together if needed. For continuous administration of nebulized drugs, see Vol III—AIR7 Status Asthmaticus.
- Antihistamines: H1
receptor antagonists like diphenhydramine (Benadryl) and H2 receptor
antagonists like cimetidine (Tagamet) are not initial drugs for
treatment of anaphylaxis but are standard therapy after the initial
treatments have been instituted. The antihistamines help to reduce the
histamine-induced cardiac arrhythmias and vasodilation and provide more
sustained effects than epinephrine. In more serious cases, administer
intravenously. H1 and H2 antagonists may be more effective if both are
given.5
- PEDS: diphenhydramine (Benadryl) dosage is 1 mg/kg IV or PO in children
- Adults: diphenhydramine (Benadryl) dosage is 50 to 100 mg IM or PO or IV.
- Adults: cimetidine (Tagamet) dosage is 300 mg IV or PO every 6 hours.
- Corticosteroids are useful in most allergic reactions that present in
an emergency setting, and work by a number of mechanisms. In severe
reactions give IV:
- PEDS: Methylprednisolone, 1 to 2 mg/kg IV
- Adults: Methylprednisolone, 125 mg IV
- Glucagon. This short-acting drug may work in those patients on beta
blockers who respond poorly to epinephrine, as glucagon bypasses those
blocked receptors.6 Consider its use in these patients and others who
are not responding to the above therapy.
- Dose: 1 to 2 mg IV every 5 minutes titrated to effect; may need a drip at 1 to 5 mg/h.
- Activated charcoal helps to absorb orally ingested antigens and thereby reduce the severity and length of the allergic process. Administer 1 g/kg PO or NG tube.
- Stinger removal: If the anaphylactic reaction is the result of a bee sting, inspect the site to see if the stinger is still there: lift the stinger out of the skin with a blade to avoid injecting more venom. Inject 1/2 of the first dose of epinephrine injection near the site of the sting. If possible, apply a venous tourniquet proximal to the sting until hypotension has been relieved. Cold packs may decrease absorption.
- Monitor the patient appropriately: cardiac, O2 sats, BP, urinary output, CVP if necessary. Use judgment in ordering lab tests; most add little to initial evaluation and treatment.
- Disposition. All
patients with significant anaphylactic reactions and/or high risk need
to be hospitalized with the appropriate care for their needs. Symptoms
can reoccur or present as a late phase reaction. It would be prudent to
observe all others for at least 4 to 6 hours. Prescribe discharge
medications with the thought of blunting late allergic
responses/relapses:
- antihistamines, short course non-tapering corticosteroids, Ana-Kit/Epi-Pen
- Education and Referral. Educate about antigen avoidance (if known) and medication usage. If the antigen is unknown, an allergy work-up by a specialist is needed. Immunotherapy has been proven to be effective in reducing the risk of repeat anaphylaxis from stinging insect exposures.7
References
- Middleton E Jr., et al. Allergy principles and practice. St Louis: Mosby; 1998.
- Cydulka R, Davison R, Gramer L, et al. The use of epinephrine in the treatment of older adult asthmatics. Ann Emer Med. 1988;17:322-326.
- Hughes G, Fitzharris P. Managing acute anaphylaxis: New guidelines emphasize importance of intramuscular adrenaline. BMJ. 1999;319:1-2.
- Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 2001;108:871-873.
- Runge JW, Martinez JC, Caravati EM, et al. Histamine antagonists in the treatment of acute allergic reactions. Ann Emer Med. 1992;21:237-242.
- Pollack CV. Utility of glucagon in the emergency department. J Emerg Med. 1993;11:195.
- Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allerg Clin Immunol. 2001;108:871-873.