Epinephrine Infusion for Refractory Anaphylaxis
Immediate Answer
For this 18-year-old male weighing 125 pounds (56.8 kg) with anaphylaxis refractory to 3 IM epinephrine doses, start a continuous IV epinephrine infusion at 0.05-0.1 mcg/kg/min (approximately 3-6 mcg/min), titrating up to a maximum of 10 mcg/min based on blood pressure response. 1
Preparation of Epinephrine Infusion
Standard Concentration
- Add 1 mg (1 mL) of 1:1000 epinephrine to 250 mL of D5W to yield a concentration of 4 mcg/mL 1
- This solution is infused intravenously at a rate of 1 to 4 mcg/min (15 to 60 drops per minute with a microdrop apparatus), increasing to a maximum of 10 mcg/min for adults and adolescents 1
Alternative Concentration (If Infusion Pump Available)
- Prepare a 1:100,000 solution by adding 1 mg (1 mL) of epinephrine to 100 mL of saline (yields 10 mcg/mL) 1, 2
- Administer at an initial rate of 30 to 100 mL/h (5-15 mcg/min), titrated up or down depending on clinical response or epinephrine side effects 1, 2
Weight-Based Dosing for This Patient
Initial Dose Calculation
- For a 56.8 kg patient, start at 0.05-0.1 mcg/kg/min = 2.8-5.7 mcg/min (round to 3-6 mcg/min) 1
- Using the 4 mcg/mL concentration: start at 45-90 mL/h 1
- Using the 10 mcg/mL concentration: start at 18-36 mL/h 1, 2
Titration Protocol
- Titrate every 10-15 minutes in increments of 0.05-0.2 mcg/kg/min to achieve adequate blood pressure and tissue perfusion 3
- Maximum dose: 10 mcg/min (or up to 2 mcg/kg/min = 114 mcg/min in severe cases per FDA labeling, though this is rarely needed) 3
- Monitor blood pressure and heart rate every 5-15 minutes during initial titration 2
Critical Concurrent Management
Fluid Resuscitation
- Administer aggressive IV fluid resuscitation with normal saline: 1-2 L rapidly in adults (5-10 mL/kg in first 5 minutes) 1
- Large volumes of crystalloid may be required (up to 30 mL/kg in the first hour) due to profound intravascular volume depletion characteristic of anaphylaxis 1, 4
- Fluid resuscitation must not be delayed—it is essential alongside epinephrine infusion 1, 5
Airway Management
- Establish and maintain airway immediately; consider early intubation if upper airway obstruction is present or worsening 1, 5
- Endotracheal intubation or cricothyrotomy may be necessary if clinicians are adequately trained 1
- Administer supplemental oxygen at 6-8 L/min 1
Patient Positioning
- Place patient in recumbent position with lower extremities elevated 1
- Exception: if respiratory distress is prominent, patient should be sitting up 1
When to Escalate to IV Epinephrine
Clear Indications
- IV epinephrine infusion is indicated after failure to respond to repeated IM epinephrine injections (typically 2-3 doses given 5 minutes apart) 1, 4, 5
- Patients with cardiovascular collapse or profound hypotension unresponsive to IM epinephrine and IV fluids require IV epinephrine 5, 6
- Continuous infusion is preferred over IV boluses due to better control and lower risk of adverse effects 1, 5
Additional Vasopressor Considerations
Refractory Hypotension
- If hypotension persists despite epinephrine infusion and adequate fluid resuscitation, add vasopressin 0.01-0.04 U/min 1
- Prepare as 25 units in 250 mL of D5W or normal saline (0.1 U/mL) 1
- Alternatively, norepinephrine may be used for refractory cases 2
- Prepare as 1 mg in 100 mL saline, administered at 30-100 mL/h (5-15 mcg/min) 2
Special Consideration: Beta-Blocker Use
- If patient is on beta-blockers, glucagon 1-5 mg IV infusion over 5 minutes should be administered 1
- Beta-blockers may blunt the response to epinephrine, making glucagon essential 1
Adjunctive Medications (Secondary Priority)
Antihistamines
- H1 antagonist: diphenhydramine 50 mg IV 1
- H2 antagonist: ranitidine 50 mg IV 1
- These should never delay epinephrine administration 4, 6
Corticosteroids
- Methylprednisolone 1-2 mg/kg IV every 6 hours 1
- May help prevent biphasic reactions, but are not critical in acute management 1
- Should not be given prior to epinephrine 4
Monitoring and Observation
Vital Sign Monitoring
- Monitor blood pressure, heart rate, and oxygen saturation every 5-15 minutes during infusion titration 2, 3
- Assess for signs of adequate tissue perfusion: mental status, urine output, capillary refill 1
Duration of Observation
- After severe anaphylaxis requiring IV epinephrine, close observation for 24 hours is recommended 1
- Biphasic reactions occur in 1-7% of patients and may happen outside typical observation periods 5, 6
- Risk factors for biphasic reaction include severe initial presentation and repeated doses of epinephrine 6
Critical Pitfalls to Avoid
Administration Errors
- Never administer 1:1000 epinephrine IV—this concentration is 10 times too strong and can cause fatal arrhythmias 7, 8
- Only use properly diluted epinephrine (1:10,000 or 1:100,000) for IV administration 1, 7
- Do not mix epinephrine with sodium bicarbonate or other alkaline solutions in the IV line, as they inactivate the medication 2, 9
Delayed Treatment
- Failure to inject epinephrine promptly contributes to anaphylaxis fatalities 8, 10
- Antihistamines and corticosteroids should never be given in lieu of, or prior to, epinephrine 4
- Do not delay epinephrine infusion while waiting for central venous access—peripheral IV is acceptable initially 2
Inadequate Fluid Resuscitation
- Epinephrine alone without aggressive fluid resuscitation is insufficient 1, 5
- Anaphylaxis causes profound intravascular volume depletion requiring large volumes of crystalloid 1, 4