What is the management of anaphylaxis?

Anaphylaxis Management

Administer intramuscular epinephrine 0.01 mg/kg (1:1000 concentration) into the mid-outer thigh immediately upon recognition of anaphylaxis—this is the only first-line treatment and delays in administration are associated with fatality. 1, 2

Immediate First-Line Treatment: Epinephrine

• Inject epinephrine 0.01 mg/kg of 1:1000 solution intramuscularly into the anterolateral thigh as soon as anaphylaxis is suspected—maximum dose is 0.3 mg in prepubertal children and 0.5 mg in adults 3, 1, 2

• For children, use epinephrine auto-injector 0.15 mg if weight is 10-25 kg or 0.3 mg if ≥25 kg 1

• Repeat epinephrine every 5-15 minutes if symptoms persist or progress—there are no absolute contraindications to epinephrine in anaphylaxis 1, 2

• The intramuscular route in the lateral thigh achieves peak plasma concentrations in 8 minutes compared to 34 minutes with subcutaneous injection 2

• If there is any doubt about the diagnosis, administer epinephrine—it is better to give epinephrine than to delay 3

Immediate Supportive Measures (Concurrent with Epinephrine)

• Call emergency services immediately and activate emergency medical response 1

• Position patient supine with elevated lower extremities to prevent orthostatic hypotension and improve circulation to vital organs—this slows progression of hemodynamic compromise 3, 1

• Establish intravenous access and administer supplemental oxygen—oxygen is particularly important for prolonged reactions, pre-existing hypoxemia, or patients requiring multiple epinephrine doses 3, 1

• Maintain airway patency—consider endotracheal intubation or cricothyroidotomy if laryngeal edema is severe and clinicians are adequately trained 3, 1

Fluid Resuscitation

• Administer normal saline rapidly: 1-2 L in adults at 5-10 mL/kg in the first 5 minutes; up to 30 mL/kg in the first hour for children 3, 1

• Up to 7 L of crystalloid may be necessary because increased vascular permeability can transfer 50% of intravascular fluid to extravascular space within 10 minutes 3, 1

• Avoid lactated Ringer's solution as it may contribute to metabolic acidosis; dextrose is rapidly extravasated from intravascular circulation 3

• Patients with congestive heart failure or chronic renal disease require cautious monitoring to prevent volume overload 3

Management of Refractory Anaphylaxis

Escalating Epinephrine Therapy

• If inadequate response after 10 minutes, double the epinephrine bolus dose 1, 2

• Consider epinephrine infusion (0.05-0.1 μg/kg/min) when more than three boluses have been administered 1, 2

• For IV epinephrine infusion: add 1 mg (1 mL of 1:1000) to 250 mL D5W yielding 4 μg/mL concentration, infuse at 1-4 μg/min (15-60 drops/min with microdrop apparatus), titrating up to maximum 10 μg/min based on clinical response 3

Additional Vasopressors for Persistent Hypotension

• For hypotension refractory to epinephrine and fluids, add norepinephrine infusion (0.05-0.5 μg/kg/min) or dopamine 2-20 μg/kg/min titrated to maintain systolic BP >90 mmHg 1, 2

• Consider vasopressin 1-2 IU bolus with or without infusion (2 units/h) for refractory hypotension 2

Special Consideration: Beta-Blocker Patients

• For patients on beta-blockers with refractory symptoms, administer IV glucagon 1-2 mg (20-30 μg/kg in children, maximum 1 mg) over 5 minutes 2

Cardiopulmonary Arrest During Anaphylaxis

• Initiate CPR and advanced cardiac life support immediately 1

• Administer high-dose IV epinephrine rapidly: 1-3 mg (1:10,000 dilution) over 3 minutes, then 3-5 mg over 3 minutes, followed by 4-10 μg/min infusion 1

Second-Line Adjunctive Therapies (NEVER Before Epinephrine)

Antihistamines

• Administer H1-antihistamine diphenhydramine 1-2 mg/kg or 25-50 mg parenterally ONLY AFTER epinephrine—antihistamines have slow onset (≥1 hour) and do not relieve respiratory symptoms or shock 1, 2

• Consider H2-antihistamine ranitidine 50 mg IV in adults (1 mg/kg in children) diluted in 5% dextrose over 5 minutes 1

• Never substitute antihistamines for epinephrine as first-line treatment—this is a critical pitfall associated with fatalities 2

Bronchodilators

• For bronchospasm resistant to adequate epinephrine doses: administer nebulized albuterol 2.5-5 mg in 3 mL saline, repeat as necessary 1

• Albuterol may provide adjunctive therapy for wheezing in patients with preexisting asthma but does not replace epinephrine 2

Corticosteroids

• Consider systemic corticosteroids for patients with history of idiopathic anaphylaxis, asthma, or severe/prolonged anaphylaxis 1, 2

• Corticosteroids are not helpful acutely but may prevent biphasic or protracted reactions 1

Observation and Monitoring

• Observe all patients for minimum 6 hours in a monitored setting—there are no reliable predictors of biphasic reactions 1, 2

• Biphasic reactions (recurrence without re-exposure) can occur in up to 20% of cases 1

• Obtain mast cell tryptase samples: first at 1 hour after reaction onset, second at 2-4 hours, and baseline at least 24 hours post-reaction 2

Post-Event Management and Discharge

• Provide patient with two epinephrine auto-injectors and comprehensive training on self-administration 1, 2

• Provide written personalized anaphylaxis emergency action plan 2

• Refer all patients to an allergist-immunologist for diagnostic evaluation, identification of triggers, and long-term management 1, 2

• Instruct patient to wear and/or carry identification denoting their condition (e.g., Medic Alert jewelry) 3

Critical Pitfalls to Avoid

• Delayed epinephrine administration is the most common cause of preventable anaphylaxis deaths—the more rapidly anaphylaxis develops, the more likely it is to be severe and life-threatening 3, 2

• Never administer antihistamines or corticosteroids before or instead of epinephrine 2

• Do not administer IV epinephrine in non-arrest situations without continuous hemodynamic monitoring 2

• Avoid premature discharge without adequate observation for biphasic reactions 2

• Recognize that cutaneous findings (urticaria/angioedema) may be delayed or absent in rapidly progressive anaphylaxis 3

• Patients with preexisting severe uncontrolled asthma, adolescents, and those with peanut/tree nut allergies are at particularly high risk for fatal anaphylaxis 2