Anaphylaxis Treatment Guidelines

Immediate Recognition and First-Line Treatment

The American Academy of Pediatrics recommends administering intramuscular epinephrine immediately into the anterolateral thigh at 0.01 mg/kg (maximum 0.3 mg in children, 0.5 mg in adolescents) as soon as anaphylaxis is recognized 1, 2
Inject epinephrine 0.01 mg/kg of 1:1000 solution intramuscularly into the mid-outer thigh immediately upon recognition of anaphylaxis 1, 3
Repeat epinephrine every 5-15 minutes as needed if symptoms persist or recur 3, 4
The intramuscular route in the lateral thigh provides superior pharmacokinetics compared to subcutaneous administration 1, 3

Establish IV access, provide supplemental oxygen, and continuously monitor vital signs 4
Administer crystalloid fluid bolus: 500 mL for moderate reactions, 1 L for severe reactions, escalating to 20-30 mL/kg for refractory cases 4

If inadequate response after 10 minutes, double the epinephrine bolus dose 4
Consider IV epinephrine for severe reactions: 20 μg for Grade II, 50-100 μg for Grade III, 1 mg for Grade IV (cardiac arrest) 3, 4
Start epinephrine infusion (0.05-0.1 μg/kg/min) when more than three boluses have been administered 3, 4
For persistent hypotension despite epinephrine, add norepinephrine infusion (0.05-0.5 μg/kg/min) 4
Consider vasopressin 1-2 IU bolus with or without infusion (2 units/h) for refractory hypotension 4
For patients on beta-blockers with refractory symptoms, administer IV glucagon 1-2 mg 4

H1 antihistamines (diphenhydramine 25-50 mg IV or chlorphenamine) are adjunctive only for cutaneous symptoms—never administer before or instead of epinephrine 3, 4
H1 antihistamines have slow onset (≥1 hour) and do not relieve respiratory symptoms or shock 5
Inhaled albuterol may provide adjunctive therapy for wheezing in patients with preexisting asthma but does not replace epinephrine 5
Consider systemic glucocorticosteroids for patients with history of idiopathic anaphylaxis, asthma, or severe/prolonged reactions to potentially prevent biphasic reactions 4

Observe in a monitored area for minimum 6 hours or until stable and symptoms are regressing 3, 4
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 3, 4
Prescribe epinephrine autoinjector before discharge 1
Provide written personalized anaphylaxis emergency action plan 1
Train patient/family on autoinjector use and anaphylaxis recognition 1, 2
Arrange allergist referral for trigger identification and consideration of allergen immunotherapy (e.g., venom immunotherapy) 1, 4

Delayed epinephrine administration is associated with fatalities—administer immediately when anaphylaxis is suspected 5
Never substitute antihistamines or corticosteroids for epinephrine as first-line treatment 3, 4
Do not administer IV epinephrine in non-arrest situations without appropriate monitoring 4
Avoid premature discharge without adequate observation for biphasic reactions 4
Patients with preexisting severe uncontrolled asthma are at higher risk for fatal anaphylaxis 5
Adolescents have particularly high risk for fatal anaphylaxis 5
Patients on beta-blockers may have refractory symptoms requiring glucagon 4

Intravenous epinephrine should be reserved exclusively for children with cardiac arrest or profound hypotension unresponsive to multiple intramuscular epinephrine doses and aggressive fluid resuscitation, administered at 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution; maximum 0.3 mg) given slowly over several minutes with continuous hemodynamic monitoring, as recommended by the Journal of Allergy and Clinical Immunology 6
The American Heart Association emphasizes that intramuscular administration into the lateral thigh remains the preferred route for anaphylaxis treatment, achieving peak plasma concentrations in 8 ± 2 minutes compared to 34 ± 14 minutes with subcutaneous injection 7

For severe hypotension, a slow IV bolus administration of 0.01 mg/kg (maximum 0.3 mg) of 1:10,000 solution should be given slowly over several minutes, as recommended by the Journal of Allergy and Clinical Immunology 6
For continuous infusion, 1 mg (1 mL of 1:1000) epinephrine can be added to 250 mL D5W, resulting in a 4 μg/mL concentration, with an infusion rate of 1-4 μg/min (15-60 drops/min with microdrop apparatus), as recommended by the Journal of Allergy and Clinical Immunology 6

Continuous hemodynamic monitoring is mandatory when administering IV epinephrine, including continuous electrocardiographic monitoring, blood pressure measurement every minute, and heart rate monitoring, as recommended by the Journal of Allergy and Clinical Immunology 6

Children on beta-blockers may be unresponsive to epinephrine, and glucagon can be administered at 1-5 mg IV (20-30 μg/kg, maximum 1 mg for children) over 5 minutes, as recommended by the Journal of Allergy and Clinical Immunology 6

For persistent hypotension despite epinephrine and fluids, dopamine can be infused at 2-20 μg/kg/min, titrated to maintain systolic BP >90 mmHg, as recommended by the Journal of Allergy and Clinical Immunology 6

The American Academy of Pediatrics recommends that for infants <7.5 kg, the 0.15 mg autoinjector is still preferable to ampule/syringe/needle methods, which carry a 40-fold variation in dosing accuracy and significant delays 8
The American Academy of Pediatrics advises against prescribing ampule/syringe/needle for home use due to the risk of dosing errors and delays outweighing theoretical overdosing concerns 8

The American Academy of Pediatrics states that IV epinephrine should only be used for cardiac arrest or profound hypotension unresponsive to multiple IM doses, and carries significant risk of dilution and dosing errors, reserving it for hospital settings only 8