What is the emergency management of a systemic hypersensitivity reaction (anaphylaxis)?

Emergency Management of Anaphylaxis

Intramuscular epinephrine 0.3-0.5 mg (1:1000 concentration) injected into the mid-outer thigh is the immediate, life-saving first-line treatment that must be administered as soon as anaphylaxis is recognized—delays in epinephrine administration are directly associated with fatal outcomes. 1, 2, 3

Immediate Recognition and First Actions

Call for emergency medical services immediately while simultaneously beginning treatment. 2, 3 Do not delay epinephrine administration while waiting for help or establishing IV access. 3

Epinephrine Administration (First-Line Treatment)

• Adults and adolescents ≥50 kg: Administer 0.3-0.5 mg of 1:1000 (1 mg/mL) epinephrine intramuscularly. 4, 2, 3, 5
• Prepubertal children: Administer 0.01 mg/kg intramuscularly (maximum 0.3 mg). 4, 2, 3
• Injection site: Mid-outer thigh (vastus lateralis muscle)—this achieves peak plasma concentrations in 8±2 minutes compared to 34±14 minutes with subcutaneous administration. 4, 2, 3
• Repeat dosing: Repeat epinephrine every 5-15 minutes if symptoms persist or recur; approximately 10-20% of patients require multiple doses. 4, 1, 2, 3

There are no absolute contraindications to epinephrine in anaphylaxis, even in elderly patients with cardiovascular disease—the risk of death from untreated anaphylaxis far outweighs any theoretical epinephrine-related risk. 3

Critical Patient Positioning

• Position the patient supine with legs elevated unless respiratory distress or vomiting is present. 1, 2, 3
• Never allow the patient to stand, walk, or run—sudden postural changes can precipitate cardiovascular collapse. 1, 2, 3
• In pregnant women, perform left uterine displacement to avoid aortocaval compression. 3

Supportive Measures (Concurrent with Epinephrine)

Oxygen and Airway Management

• Administer supplemental oxygen at 6-8 L/min for any patient with respiratory symptoms. 4, 1, 2, 3
• Maintain airway patency; consider endotracheal intubation or cricothyrotomy if airway obstruction develops. 3

Aggressive Fluid Resuscitation

• Establish IV access immediately and administer normal saline or lactated Ringer's solution rapidly. 4, 3
• Adults: 5-10 mL/kg in the first 5 minutes (1-2 L total); up to 20-30 mL/kg may be needed. 4, 1, 3
• Children: Up to 30 mL/kg in the first hour. 4, 1
• Fluid resuscitation is imperative to combat vasodilation and capillary leak. 3

Adjunctive Medications (ONLY After Epinephrine)

These medications are second-line treatments that address specific symptoms but do NOT treat the life-threatening components of anaphylaxis and should NEVER substitute for or delay epinephrine. 4, 1, 2

H1 Antihistamines

• Diphenhydramine 25-50 mg IV/IM (or 1-2 mg/kg in children) for urticaria and itching only. 4, 1, 3
• Alternative: Cetirizine 10 mg orally (less sedating, second-generation). 4
• Important caveat: Antihistamines do NOT relieve stridor, bronchospasm, gastrointestinal symptoms, or shock. 4, 1

H2 Antihistamines

• Ranitidine 50 mg IV or famotidine 20 mg IV in adults; may be given with H1 antihistamines. 4, 1
• Minimal evidence supports their use, but some clinicians use them concurrently with H1 antihistamines. 4

Bronchodilators

• Albuterol nebulizer (2.5-5 mg in 3 mL saline) or MDI for persistent bronchospasm after epinephrine. 4, 1, 3
• Bronchodilators treat bronchospasm but do NOT address airway edema or cardiovascular collapse. 3

Corticosteroids: NOT Recommended for Acute Treatment or Biphasic Prevention

Corticosteroids have no role in treating acute anaphylaxis due to their slow onset of action (4-6 hours) and should NOT be relied upon to prevent biphasic reactions—multiple systematic reviews have found no clear evidence that glucocorticoids prevent biphasic anaphylaxis. 4, 1, 3

• If administered empirically (despite weak evidence), use methylprednisolone 1-2 mg/kg/day IV every 6 hours or hydrocortisone 200 mg IV. 4, 3
• Stop treatment within 2-3 days, as all reported biphasic reactions have occurred within 3 days. 4

Management of Refractory Anaphylaxis

Persistent Hypotension Despite Epinephrine and Fluids

• Administer vasopressor medications (dopamine, norepinephrine, vasopressin, phenylephrine) titrated to restore blood pressure. 4, 3
• Consider epinephrine infusion: 0.05-0.1 μg/kg/min (1-4 μg/min in adults, maximum 10 μg/min). 3
• Patients requiring vasopressors should be transferred to a hospital setting with continuous hemodynamic monitoring. 4, 3

Patients on Beta-Blockers

• Glucagon 1-5 mg IV over 5 minutes (20-30 μg/kg in children, maximum 1 mg) for patients resistant to epinephrine due to beta-blocker use. 4, 1, 3
• Follow with infusion at 5-15 μg/min. 4, 1
• Important caveat: Rapid glucagon administration can induce vomiting. 4

Bradycardia

• Consider atropine IV for patients with bradycardia. 4

Observation and Monitoring Requirements

All patients must be transferred to an emergency department for extended observation, even if symptoms resolve completely—biphasic anaphylaxis (recurrence without re-exposure) can occur up to 72 hours later (mean 11 hours). 4, 1, 2, 6, 7

• Minimum observation: 4-6 hours after complete symptom resolution. 4, 1, 2, 3, 6
• Extended observation (6-12 hours or hospital admission): Required for severe anaphylaxis, patients requiring multiple epinephrine doses, wide pulse pressure, unknown trigger, or drug-triggered reactions. 1, 2, 3, 7
• Patients requiring >1 dose of epinephrine have significantly higher risk of biphasic reaction (odds ratio = 4.82). 1

Mast Cell Tryptase Sampling

• First sample: 1 hour after onset of reaction. 3, 7
• Second sample: 2-4 hours after onset. 3, 7
• Baseline sample: At least 24 hours post-reaction for comparison. 3, 7

Discharge Planning

Before discharge, patients must receive:

• Two epinephrine autoinjectors with hands-on training on proper use (0.15 mg for 10-25 kg; 0.3 mg for ≥25 kg). 4, 1, 2, 3
• Written, personalized anaphylaxis emergency action plan listing symptoms, triggers, and instructions for epinephrine use. 4, 1, 2
• Referral to an allergist for evaluation within 1-2 weeks. 1, 2
• Education on trigger avoidance and recognition of biphasic reaction risk. 1, 2

Common Pitfalls to Avoid

• Never substitute antihistamines or corticosteroids for epinephrine—they are not effective for acute anaphylaxis treatment. 1, 2, 3
• Do not delay repeat epinephrine if symptoms persist or progress—early epinephrine administration reduces risk of subsequent biphasic reactions. 1, 3
• Do not discharge patients prematurely—biphasic reactions can occur many hours after initial resolution. 1, 2
• Do not rely on glucocorticoids to prevent biphasic reactions—the evidence does not support this practice despite historical use. 1, 3
• Do not delay IM epinephrine while establishing IV access—IM injection achieves therapeutic levels much faster. 3

High-Risk Populations Requiring Heightened Vigilance

• Adolescents and young adults (more likely to engage in risky behaviors and deny symptoms). 4, 2
• Patients with coexisting asthma, especially severe or poorly controlled. 4, 2, 6
• Previous history of anaphylaxis. 2, 6
• Peanut or tree nut allergies. 4, 6
• Underlying cardiovascular disease or older age. 4, 6