What is the treatment for anaphylaxis?

Treatment of Anaphylaxis

Intramuscular epinephrine administered immediately into the anterolateral thigh is the first-line treatment for anaphylaxis and should never be delayed or substituted with antihistamines or corticosteroids. 1

Immediate First-Line Treatment: Epinephrine

Epinephrine is the only medication that counteracts the life-threatening effects of anaphylaxis and has no absolute contraindications, even in patients with cardiac disease, advanced age, or frailty. 1

Dosing and Administration

• Administer 0.01 mg/kg of 1:1000 concentration (1 mg/mL) intramuscularly into the vastus lateralis (anterolateral thigh) 1, 2
• Maximum single dose: 0.5 mg for adults >50 kg; 0.3 mg for children 1, 2
• Autoinjector dosing: 0.3 mg for patients >30 kg; 0.15 mg for children 10-25 kg; 0.1 mg for infants where available 1, 3, 2
• Repeat every 5-15 minutes if symptoms persist or recur 1, 3, 2
• The intramuscular route in the lateral thigh achieves peak plasma concentrations in 8 minutes compared to 34 minutes with subcutaneous injection 2, 4

Critical Timing

Delayed epinephrine administration is directly associated with anaphylaxis fatalities and increased risk of biphasic reactions. 1, 3 Epinephrine must be given immediately upon recognition of anaphylaxis—before any other interventions. 1, 3, 2

Supportive Measures (After Epinephrine)

Patient Positioning and Oxygen

• Position patient supine with legs elevated (unless respiratory distress present) 3
• In pregnant women, perform left uterine displacement to avoid aortocaval compression 3
• Administer supplemental oxygen for respiratory symptoms 1, 3

Fluid Resuscitation

Fluid resuscitation is imperative for hypotension due to vasodilation and capillary leak. 3

• Grade II reactions: initial bolus 0.5 L crystalloids 3
• Grade III reactions: initial bolus 1 L crystalloids 3
• Repeat boluses as needed up to 20-30 mL/kg based on clinical response 3, 2

Management of Refractory Anaphylaxis

If symptoms persist after 2-3 doses of intramuscular epinephrine, escalate to intravenous epinephrine or continuous infusion. 1, 3, 2

Intravenous Epinephrine (1:10,000 concentration)

• Grade II reactions: 20 μg IV bolus 3, 2
• Grade III reactions: 50-100 μg IV bolus 3, 2
• Grade IV reactions (cardiac arrest): 1 mg IV following ACLS guidelines 3, 2
• Continuous infusion: 0.05-0.1 μg/kg/min when >3 boluses have been administered 3, 2

Alternative Vasopressors

For persistent hypotension despite epinephrine and fluids, consider norepinephrine (0.05-0.5 μg/kg/min), vasopressin (1-2 IU bolus or 2 units/hour infusion), phenylephrine, or metaraminol. 3, 2

Special Populations

Patients on beta-blockers may be unresponsive to epinephrine and require glucagon 1-2 mg IV (20-30 μg/kg in children, maximum 1 mg) administered over 5 minutes. 3, 2

Second-Line Adjunctive Therapies (Never Before Epinephrine)

Antihistamines

H1 antihistamines (diphenhydramine 25-50 mg IV or chlorphenamine) are adjunctive only for cutaneous symptoms and should never be administered before or instead of epinephrine. 1, 3, 2 These medications have slow onset (≥1 hour), address only non-life-threatening skin manifestations, and do not relieve respiratory symptoms or shock. 1, 2

H2 antihistamines (ranitidine 50 mg IV) have only indirect evidence supporting their use and should be considered after adequate epinephrine and fluid resuscitation. 1, 3

Corticosteroids

Glucocorticoids have no role in treating acute anaphylaxis due to slow onset of action and should not be administered to prevent biphasic anaphylaxis, as multiple systematic reviews have not demonstrated clear evidence of benefit. 1 Consider only for patients with history of idiopathic anaphylaxis, asthma, or severe/prolonged reactions. 2

Bronchodilators

Inhaled albuterol may provide adjunctive therapy for wheezing in patients with preexisting asthma but does not replace epinephrine. 2

Post-Anaphylaxis Observation and Monitoring

Observe patients in a monitored area for a minimum of 6 hours or until stable and symptoms are regressing. 3, 2 High-risk patients (Grade III-IV reactions, required >1 dose of epinephrine, severe initial presentation) may require extended observation or ICU admission. 3

Biphasic Reactions

Biphasic anaphylaxis occurs in 7-18% of cases, with symptoms recurring up to 72 hours later (mean 11 hours) without re-exposure to the allergen. 1 Risk factors include severe initial reaction and requirement of multiple epinephrine doses (odds ratio 4.82). 1

Tryptase Sampling

Obtain mast cell tryptase samples to confirm diagnosis: 3, 2

• First sample: 1 hour after reaction onset
• Second sample: 2-4 hours after onset
• Baseline sample: at least 24 hours post-reaction for comparison

Discharge Planning

All patients must be discharged with two epinephrine autoinjectors and a written personalized anaphylaxis emergency action plan. 3, 2

Autoinjector Prescription

• 0.15 mg for children 10-25 kg 3, 2
• 0.3 mg for individuals ≥25 kg 3, 2
• 0.1 mg for infants >7.5 kg (where available); if unavailable, 0.15 mg is appropriate 3, 2

Patient Education

Train patients and caregivers on autoinjector use, anaphylaxis recognition, and the critical importance of administering epinephrine first at the earliest sign of symptoms. 3, 2 Emphasize that patients must seek emergency care after using epinephrine, even if symptoms improve, due to risk of biphasic reactions. 3, 2

Refer all patients to an allergist for trigger identification and consideration of allergen immunotherapy (e.g., venom immunotherapy). 2

Critical Pitfalls to Avoid

• Never substitute antihistamines, corticosteroids, or bronchodilators for epinephrine as first-line treatment 1, 3, 2
• Do not use subcutaneous or deltoid routes—intramuscular injection in the anterolateral thigh is superior 3, 2, 4
• Avoid premature discharge without adequate observation for biphasic reactions 2
• Do not prescribe ampule/syringe/needle for home use due to 40-fold variation in dosing accuracy and significant delays 2
• Recognize that adolescents and patients with severe uncontrolled asthma are at particularly high risk for fatal anaphylaxis 2