From the Guidelines
Treatment for refractory anaphylaxis requires aggressive intervention with repeated epinephrine injections and adjunctive therapies, including IV fluids, high-flow oxygen, and second-line medications like H1 antihistamines, H2 blockers, and corticosteroids, as supported by the most recent guidelines 1. When anaphylaxis does not respond to initial epinephrine doses, give repeated epinephrine injections (0.3-0.5mg IM for adults, 0.01mg/kg up to 0.3mg for children) every 5-15 minutes as needed, considering the patient's response and potential side effects 1.
Key Interventions
- Consider starting an epinephrine infusion at 0.1-1.0 mcg/kg/min if multiple doses are ineffective, with careful monitoring of the patient's hemodynamic status 1.
- Add adjunctive therapies including IV fluids (crystalloids 1-2L rapidly for adults), high-flow oxygen, and positioning the patient supine with legs elevated to improve circulation and oxygenation 1.
- Second-line medications include H1 antihistamines (diphenhydramine 25-50mg IV), H2 blockers (ranitidine 50mg IV), and corticosteroids (methylprednisolone 1-2mg/kg IV) to help alleviate symptoms and prevent biphasic reactions 1.
Special Considerations
- For profound hypotension, vasopressors like norepinephrine or vasopressin may be necessary to maintain adequate blood pressure and perfusion of vital organs 1.
- Glucagon (1-5mg IV) can be beneficial in patients taking beta-blockers, as it can help increase heart rate and contractility 1.
- Methylene blue (1-2mg/kg IV) may help in vasodilatory shock by reducing nitric oxide production and improving vascular tone, although its use is less common and should be considered on a case-by-case basis 1.
Critical Care
Refractory cases might require advanced airway management, ECMO, or specialized critical care, emphasizing the need for prompt recognition and treatment of anaphylaxis to prevent severe complications and improve outcomes 1.
From the Research
Treatment for Refractory Anaphylaxis
The treatment for refractory anaphylaxis, which is unresponsive to treatment with at least two doses of minimum 300 μg adrenaline, involves several pharmacotherapeutic options.
- The first line of treatment is often intramuscular adrenaline, but in cases of refractory anaphylaxis, intravenous adrenaline may be used instead 2.
- Second-line treatment options, such as vasopressin with dopamine, methylene blue, and glucagon, may be considered, but their use is not well established in refractory cases 2, 3.
- In cases of shock that is refractory to epinephrine, additional vasopressors may be needed, along with fluid resuscitation 4.
- Airway obstruction must be recognized, and early intubation may be necessary 4.
Pharmacotherapeutic Options
Several pharmacotherapeutic agents have been suggested for the treatment of refractory anaphylaxis, including:
- Antihistamines and corticosteroids, although their use is not supported by high-grade evidence 3, 5.
- Newer pharmacotherapeutic agents, such as methylene blue and dopamine, which have not been evaluated with scientific rigor 3.
- Glucagon, which may be used in cases of refractory anaphylaxis, particularly in patients with underlying cardiovascular disease 5, 4.
Management and Observation
The management of refractory anaphylaxis involves removal of the trigger, early administration of intramuscular epinephrine, and supportive care for the patient's airway, breathing, and circulation 5.
- Patients should be monitored for a biphasic reaction, which can occur without reexposure to the allergen, for four to 12 hours, depending on risk factors for severe anaphylaxis 5.
- Disposition depends on patient presentation and response to treatment, and mandatory observation periods are not necessary 4.