Refractory Anaphylaxis: Definition and Management
Refractory anaphylaxis is defined as persistent anaphylactic symptoms despite adequate initial treatment with epinephrine and fluids, requiring additional management strategies beyond standard protocols. 1, 2
Definition and Characteristics
- Refractory anaphylaxis indicates insufficient response to standard treatment, typically identified after 10 minutes of sustained inadequate response despite appropriate epinephrine dosing and fluid resuscitation 1
- It can result from the pathological process alone or be compounded by underlying medical conditions, surgical factors, or anesthesia 1
- Refractory anaphylaxis represents a severe end of the anaphylaxis spectrum that requires escalated interventions beyond initial epinephrine treatment 2
- While standard anaphylaxis typically responds to intramuscular epinephrine, refractory cases persist despite this intervention 3
Epidemiology and Risk Factors
- In a study of 145 patients with ICM (iodinated contrast media) anaphylaxis, 4.1% developed refractory anaphylaxis 1
- Risk factors for developing refractory anaphylaxis include:
Clinical Presentation
- Persistent life-threatening hypotension despite adequate epinephrine and fluid administration 1
- Ongoing severe bronchospasm unresponsive to initial treatments 1
- Cardiovascular collapse requiring advanced interventions 1
- Symptoms that continue or worsen despite standard anaphylaxis management 2
Management Protocol for Refractory Anaphylaxis
Initial Recognition and Assessment
- Re-evaluate after 10 minutes of standard anaphylaxis treatment if symptoms persist 1
- Confirm adequate dosing of epinephrine and volume resuscitation 1
- Assess for complicating factors (e.g., beta-blocker use, underlying cardiac disease) 4
Escalated Epinephrine Administration
- Double the initial bolus dose of epinephrine 1
- Start an epinephrine infusion after a total of three bolus doses 1
- Consider intravenous epinephrine administration in severe cases under appropriate monitoring 3, 5
Advanced Cardiovascular Support
- Ensure adequate volume replacement with crystalloids or colloids 1
- Consider alternative vasopressors such as vasopressin, norepinephrine, metaraminol, or phenylephrine 1
- For patients taking beta-adrenergic receptor blockers, administer IV glucagon 1-2 mg 1
- Consider extracorporeal life support in facilities where skills and equipment are available 1
Respiratory Management
- Add inhaled bronchodilators for persistent bronchospasm 1
- Consider adding intravenous bronchodilators if respiratory symptoms persist 1
- Secure the airway early if there are signs of upper airway compromise 5
Additional Interventions
- Corticosteroids may be given after adequate resuscitation, though they have no immediate role in acute management 1
- Antihistamines can be administered after adequate resuscitation but are not a priority 1
- Position the patient supine or in Trendelenburg position to improve venous return 1
- Provide supplemental oxygen 1
Post-Crisis Management
- Extended observation period (minimum 6 hours) is recommended for patients who experienced refractory anaphylaxis 1
- Hospital admission should be considered for patients with severe or refractory reactions 6
- Obtain serum tryptase samples at 1 hour and 2-4 hours after reaction onset, with a baseline sample at least 24 hours post-reaction 1
- All patients should receive education on anaphylaxis management and be referred to an allergist 1
Important Distinctions and Considerations
- Refractory anaphylaxis differs from biphasic anaphylaxis, which occurs when symptoms resolve completely but then recur up to 72 hours later (mean 11 hours) 1
- Sugammadex has no immediate role in the resuscitation of suspected anaphylaxis 1
- The absence of cutaneous symptoms does not rule out anaphylaxis, particularly in rapidly progressive cases 7
- Bradycardia can occasionally occur in anaphylaxis due to the Bezold-Jarisch reflex, despite tachycardia being more common 1, 7
Understanding and promptly recognizing refractory anaphylaxis is crucial for implementing appropriate escalated interventions to prevent morbidity and mortality in these severe cases.