Anaphylaxis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Key Recommendations

Anaphylaxis is a medical emergency that requires rapid identification and treatment.[53] In all patients the primary goal is cardiopulmonary support and reversal of the effects of anaphylaxis with epinephrine (adrenaline).[76]

Patients may present with symptoms that range in severity, but cardiac collapse and respiratory compromise cause the most urgent concern. Patients presenting with milder symptoms can rapidly deteriorate and should be closely monitored.[12]

Regardless of severity, all patients with a diagnosis of anaphylaxis should be kept under observation until signs and symptoms have fully resolved.[12]

Cardiopulmonary arrest

If patient is in cardiopulmonary arrest, cardiopulmonary resuscitation with intubation and ventilation, intravenous fluid replacement, and intravenous epinephrine are indicated.[76]

Tracheal intubation: animated demonstration

How to insert a tracheal tube in an adult using a laryngoscope.

Bag-valve-mask ventilation: animated demonstration

How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.

Airway management

As even minor airway compromise can quickly progress to complete airway occlusion, immediate airway assessment and support is critical. If possible, airway assessment and management should be performed by a skilled anesthesiologist or emergency physician.

Supplemental oxygen should be considered for all patients with anaphylaxis regardless of their respiratory status, and must be administered to any patient with respiratory or cardiovascular compromise and to those who do not respond to initial treatment with epinephrine.[53][80]

Early prophylactic intubation or even cricothyrotomy may be necessary, especially if there is inspiratory stridor or evidence of worsening oral swelling (e.g., tongue, lip, or uvular swelling).[76][80] Inadequate respiratory efforts may indicate the need for ventilatory support.

Cardiac support

Unless precluded by shortness of breath or vomiting, the patient should be placed in a supine position with legs elevated (shock or Trendelenburg position). This will augment venous return, and thereby increase preload and enhance cardiac output. Studies have shown that an upright position may contribute to a fatal outcome.[81] Intravenous access should be established; aggressive intravenous fluid replacement may be indicated for patients with ongoing cardiovascular instability after epinephrine due to the intravascular volume redistribution into venous capacitance vessels and the interstitial tissue.[53] The human vascular system consists of a high-pressure small-volume arterial system and a large low-pressure venous reservoir that expands in anaphylaxis, absorbing much of the circulating blood volume. To make up for this intravascular fluid loss, adults should be administered a 20 mL/kg bolus (approximately 1 L to 2 L) of crystalloid fluid (e.g., normal saline) intravenously.[53] Fluid overload is a potential complication in patients with renal failure or congestive heart failure. Children should also receive a fluid bolus; see Volume depletion in children.

Epinephrine (adrenaline)

Immediate administration of adequate doses of epinephrine will decrease patient mortality and morbidity.[12][76]

All patients with signs of a systemic reaction, especially hypotension, airway swelling, or difficulty breathing, should receive immediate intramuscular epinephrine in the anterolateral thigh.[76][82][83][84][85] This dose may be repeated every 5 to 15 minutes as needed.[6][12][76][86] The anterolateral thigh is superior over intramuscular administration in the deltoid or subcutaneous injection.[87][88]

The alpha-1, beta-1, and beta-2 agonist actions of epinephrine play a key role in reversing effects of anaphylaxis. Stimulation of the alpha-1 receptors leads to increased vascular tone and thus reversal of the effects of massive vasodilation triggered by immune mediators. Beta-2 receptor stimulation causes bronchodilation and impairs release of mediators from mast cells and basophils.[39][89]

Intravenous epinephrine is administered to patients in cardiopulmonary arrest, and to profoundly hypotensive patients who have not responded to intravenous fluids and several doses of intramuscular epinephrine.[12][74][76] Continuous infusion of epinephrine, titrated to effect, is reserved for experienced practitioners. No intravenous dose regimen is universally recognized.

It is usual practice to provide a prescription for two epinephrine auto-injectors after any episode of anaphylaxis due to the risk of severe anaphylaxis or a biphasic recurrence requiring multiple doses, although it may be reasonable to adopt a risk-stratified approach.[55][90] The patient or caregiver should carry both at all times and be familiar with their use.[83] For children at risk of anaphylaxis, the epinephrine auto-injectors should be prescribed in conjunction with a personalized written emergency plan.[83][91] American Academy of Pediatrics: allergy and anaphylaxis emergency plan Opens in new window

Patients with coronary artery disease

The alpha-1 agonist action of epinephrine can lead to severe hypertension, especially in those with poorly controlled hypertension. Beta-1 receptor stimulation has positive inotropic and chronotropic effects (i.e., the heart rate and contractility are increased), but an overshooting response can result in unwanted tachycardia, potentially harming a patient with coronary artery disease (CAD).

In patients prescribed beta-blockers for CAD, both the medication and the underlying comorbidity complicate the treatment of severe anaphylaxis. The beta-blocker counteracts epinephrine by limiting heart rate and compromising cardiac output. CAD limits cardiac reserve, which might compound the hypotension occurring due to the release of vasoactive mediators. The stresses of hypotension, tachycardia, and endogenous or iatrogenic adrenergic agents may cause myocardial ischemia by reducing perfusion during diastole. Glucagon may be used to overcome beta blockade, but the resulting tachycardia can be detrimental in patients with severe CAD.[6][53][55] Therefore, early consultation of a cardiologist may be considered.

Other treatments in acute phase

Inhaled beta agonists are indicated if patients have persistent respiratory symptoms (wheeze, dyspnea) despite epinephrine, but should not be used as an alternative to the repeated administration of intramuscular epinephrine.[53] Supplemental oxygen should continue in these patients.

Use of H1 and H2 antagonists is limited to relief of itching, hives, and rhinorrhea. Their use should never delay or replace the use of intramuscular epinephrine.[92][93] Most antihistamines can be given intravenously, intramuscularly, or orally. In perioperative anaphylaxis, no evidence for harm in the administration of antihistamines was reported in a large UK audit.[27] Oral administration may be sufficient for very mild allergic reactions but not anaphylaxis.

Post-emergency stabilization

Corticosteroids may be prescribed as adjunctive therapy after the administration of epinephrine.[1][12] Corticosteroids may decrease the risk of symptoms associated with anaphylaxis, including urticaria.

Guidelines published in 2020 advise against administering corticosteroids to prevent biphasic anaphylaxis. This is based on limited evidence suggesting that there is no clear benefit in terms of risk reduction.[12]

Although corticosteroids are not routinely recommended for the acute management of anaphylaxis, they may be considered after the administration of epinephrine for refractory reactions or where an acute asthma exacerbation may have contributed to the severity of anaphylaxis.[94]

Treatment of the underlying etiology - immunotherapy

After resolution of signs and symptoms of anaphylaxis, efforts should be made to treat the underlying cause. Refer the patient to an allergy/immunology specialist, who can play a uniquely important role in preparing the patient for self-treatment in the community, confirmation of the trigger of an anaphylactic episode, education regarding allergen avoidance, and immune modulation.[53]

Venom immunotherapy may be recommended for prevention of systemic reactions in patients with a history of anaphylaxis subsequent to insect sting.[74] [ ] The treatment is highly effective at preventing these systemic reactions.[95] Venom immunotherapy increases the risk of adverse systemic reactions during treatment.[95]

Avoidance of food allergens remains the preventive mainstay of food-induced anaphylaxis.[12][96] Subcutaneous, epicutaneous (via absorbed patch), oral, and sublingual immunotherapy routes have been assessed. Studies suggest that while treatment may lead to desensitization, few patients attain tolerance.[96] Food-allergy-specific immunotherapy continues to be researched; it has historically been associated with adverse reactions, including anaphylaxis.[96] Currently, oral immunotherapy is approved for use under specialist supervision by the Food and Drug Administration (FDA) for the mitigation of allergic reactions including anaphylaxis, which may occur with exposure to peanuts.[97] See Food allergy for further information.

Drug desensitization may be considered to induce temporary drug tolerance in patients with immunoglobulin E-mediated drug-induced anaphylaxis who require the causal drug, and where there is no effective alternative option.[12][74] Drug desensitization should be performed by experienced clinicians in an appropriate setting.

Central venous catheter insertion: animated demonstration

Ultrasound-guided insertion of a non-tunnelled central venous catheter (CVC) into the right internal jugular vein using the Seldinger insertion technique.

Peripheral intravascular catheter: animated demonstration

How to insert a peripheral intravascular catheter into the dorsum of the hand.

Nasopharyngeal airway: animated demonstration

How to select the correct size naspharyngeal airway and insert the airway device safely.

Oropharyngeal airway: animated demonstration

How to size and insert an oropharygeal airway.

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