What is the recommended dose and administration of intravenous (IV) epinephrine for pediatric anaphylaxis?

Intravenous Epinephrine for Pediatric Anaphylaxis

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. 1

Critical Context: When IV Epinephrine is Indicated

IV epinephrine carries significant risks of dilution errors, dosing errors, and potentially lethal arrhythmias, and should never be used as first-line therapy 1. The indication is narrow and specific:

• Cardiac arrest from anaphylaxis 2, 3
• Profound hypotension that has failed to respond to:
  • Multiple intramuscular epinephrine injections (typically ≥3 doses) 1, 3
  • Aggressive IV fluid resuscitation (up to 30 mL/kg in the first hour for children) 1

The American Heart Association and Journal of Allergy and Clinical Immunology emphasize 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 1, 4.

Dosing Regimens for IV Epinephrine

For Severe Hypotension (Non-Arrest)

Slow IV bolus administration:

• Dose: 0.01 mg/kg (maximum 0.3 mg) 1
• Preparation: 0.1 mL/kg of 1:10,000 solution 1
• Alternative preparation: 0.1-0.3 mL of 1:1000 epinephrine diluted in 10 mL normal saline 1
• Administration: Given slowly over several minutes 1
• Repeat: As necessary based on clinical response 1

The American Heart Association recommends 0.05-0.1 mg (1:10,000) administered slowly for severe hypotension 2.

For Cardiac Arrest

High-dose IV epinephrine:

• Initial dose: 1 mg (1:10,000) slowly over 3 minutes 2
• Escalation: 3-5 mg over 3 minutes if no response 2
• Maintenance: Continuous infusion at 4-10 μg/min 2

Alternatively, for Grade IV anaphylaxis with cardiac arrest, 1 mg bolus is recommended 3.

Continuous Infusion (Refractory Cases)

When more than three boluses have been required, transition to continuous infusion 3:

Standard preparation:

• Add 1 mg (1 mL of 1:1000) epinephrine to 250 mL D5W = 4 μg/mL concentration 1
• Infusion rate: 1-4 μg/min (15-60 drops/min with microdrop apparatus) 1
• Maximum rate: 10 μg/min 1
• Titrate: Based on clinical response and adverse effects 1

Alternative preparation with infusion pump:

• 1 mg (1 mL) in 100 mL saline = 1:100,000 solution 1
• Initial rate: 30-100 mL/h (5-15 μg/min) 1
• Pediatric weight-based: 0.05-0.1 μg/kg/min 2, 3

Pediatric "Rule of 6" method:

• 0.6 × body weight (kg) = mg of epinephrine diluted to 100 mL saline 1
• Then 1 mL/h delivers 0.1 μg/kg/min 1

Essential Monitoring Requirements

Continuous hemodynamic monitoring is mandatory when administering IV epinephrine 1, 2. This includes:

• Continuous electrocardiographic monitoring 1
• Blood pressure measurement every minute 1
• Pulse oximetry 2
• Heart rate monitoring 1

If formal hemodynamic monitoring is unavailable but IV epinephrine is deemed essential after failure of multiple IM injections, monitor by all available means including every-minute vital signs and ECG if available 1.

Critical Pitfalls and Safety Considerations

Concentration Confusion

The most dangerous error involves confusing 1:1000 (1 mg/mL) with 1:10,000 (0.1 mg/mL) concentrations 5. Always verify concentration before administration - using 1:1000 IV instead of 1:10,000 results in a 10-fold overdose with potentially fatal arrhythmias 1.

Delayed Administration

Fatal anaphylaxis is associated with delayed epinephrine use 6. However, the delay that matters most is delay in giving intramuscular epinephrine - not delay in escalating to IV 3. Do not withhold IM epinephrine while attempting IV access.

Special Population: Beta-Blocker Therapy

Children on beta-blockers may be unresponsive to epinephrine 1, 3. In these cases:

• Glucagon: 1-5 mg IV (20-30 μg/kg, maximum 1 mg for children) over 5 minutes 1, 2
• Maintenance infusion: 5-15 μg/min 1, 2

Adjunctive Vasopressors

For persistent hypotension despite epinephrine and fluids 1, 2:

• Dopamine: 400 mg in 500 mL D5W, infused at 2-20 μg/kg/min, titrated to maintain systolic BP >90 mmHg 1
• Norepinephrine: 0.05-0.5 μg/kg/min infusion 3
• Vasopressin: 1-2 IU bolus with or without 2 units/h infusion 3

Why Intramuscular Remains First-Line

The evidence strongly favors IM over IV for initial treatment 1, 4:

• Faster peak concentrations: IM achieves therapeutic levels in 8 minutes vs. 34 minutes for subcutaneous 1, 4
• Safety profile: Serious adverse effects from epinephrine have predominantly followed large IV overdoses 1
• Practical considerations: No need for IV access, which may be difficult in a hypotensive, edematous child 1
• Effective outcomes: Most anaphylaxis responds to IM epinephrine with supportive care 3

The 2007 Pediatrics guidelines explicitly state that IV administration should be reserved for hospital settings with appropriate monitoring capabilities 1.

Post-Resuscitation Management

After stabilization with IV epinephrine 2, 3:

• Observe minimum 6 hours in monitored setting 2, 3
• Obtain mast cell tryptase at 1 hour, 2-4 hours, and >24 hours post-reaction 3
• Prescribe epinephrine autoinjector before discharge 3
• Provide written anaphylaxis action plan 3
• Arrange allergist referral 3