Overview
Definition:
Anaphylaxis is a severe, potentially life-threatening systemic hypersensitivity reaction characterized by rapid onset and progression of symptoms
Refractory anaphylaxis refers to cases that do not adequately respond to initial intramuscular (IM) epinephrine administration, necessitating alternative treatment strategies, most notably intravenous (IV) epinephrine infusion
This is particularly concerning in pediatric patients due to unique physiological considerations.
Epidemiology:
Anaphylaxis occurs in approximately 0.05-2% of the population
While rare, refractory cases represent a significant challenge in emergency care
Pediatric anaphylaxis is often triggered by food allergens, insect stings, and medications
The incidence of biphasic or protracted anaphylaxis, which may be misidentified as refractory, is estimated to be between 4-20% of cases.
Clinical Significance:
Failure to adequately manage refractory anaphylaxis can lead to cardiovascular collapse, refractory hypotension, airway compromise, and death
Prompt recognition and appropriate escalation of therapy, including IV epinephrine, are critical for improving outcomes in these critically ill pediatric patients
Understanding the nuances of IV infusion protocols is paramount for pediatric residents preparing for DNB and NEET SS examinations.
Clinical Presentation
Symptoms:
Rapid onset after allergen exposure
Pruritus, urticaria, angioedema
Dyspnea, wheezing, cough
Hoarseness, stridor
Nausea, vomiting, abdominal pain, diarrhea
Dizziness, syncope, feeling of impending doom
Hypotension, weak pulse.
Signs:
Tachycardia or bradycardia
Hypotension (systolic BP < 70 + [2x age in years] mmHg in children < 10 years, or < 90 mmHg in older children)
Tachypnea, diffuse wheezing, stridor
Cyanosis
Urticarial rash or angioedema
Altered mental status.
Diagnostic Criteria:
Diagnosis is primarily clinical, based on the occurrence of acute onset of symptoms involving the skin/mucosa (e.g., urticaria, angioedema) OR airway compromise (e.g., dyspnea, wheezing) with at least one of the following: 1
Respiratory compromise (e.g., bronchospasm, stridor)
2
Reduced blood pressure or collapse
3
Persistent gastrointestinal symptoms
4
Sudden onset of hypotension
Anaphylaxis is considered refractory if symptoms persist or recur despite prompt administration of IM epinephrine and other standard measures.
Diagnostic Approach
History Taking:
Detailed allergen exposure history (food, insect sting, medication, latex)
Timeline of symptom onset
Previous anaphylactic reactions and their management
History of atopy, asthma, or other allergic diseases
Family history of anaphylaxis
Current medications.
Physical Examination:
Rapid assessment of airway, breathing, and circulation (ABCs)
Vital signs monitoring (BP, HR, RR, SpO2, temperature)
Full skin examination for urticaria, angioedema
Pulmonary examination for wheezing or stridor
Abdominal examination for tenderness or distension
Neurological assessment for altered mental status or syncope.
Investigations:
Not typically required for diagnosis but can be supportive
Serum tryptase levels (elevated 1-2 hours after reaction onset, useful for retrospective diagnosis)
Arterial blood gases (ABGs) to assess oxygenation and ventilation
Chest X-ray if pneumonia or other respiratory cause suspected
Electrocardiogram (ECG) if cardiac involvement suspected.
Differential Diagnosis:
Vasovagal syncope
Sepsis
Asthma exacerbation
Anaphylactoid reactions (non-IgE mediated)
Laryngeal edema from other causes
Panic attacks
Food intolerances.
Management
Initial Management:
Immediate discontinuation of the suspected trigger (if ongoing)
ABC assessment and stabilization
Administration of IM epinephrine (1:1000 solution, 0.01 mg/kg/dose, max 0.3-0.5 mg per dose, every 5-15 minutes as needed)
If refractory to IM epinephrine, transition to IV epinephrine infusion
Place patient in supine position with legs elevated (Trendelenburg if hypotensive)
Secure IV access (large bore)
Administer supplemental oxygen
Establish cardiac monitoring.
Medical Management:
IV Epinephrine Infusion Protocol for Refractory Anaphylaxis (Pediatrics):
Preparation: Dilute 1 mg (1 mL of 1:1000 solution) of epinephrine in 250 mL of Normal Saline (NS) or 5% Dextrose in Water (D5W) to create a concentration of 4 mcg/mL
Concentration can be adjusted based on weight and local protocols (e.g., 1 mg in 100 mL NS for 10 mcg/mL)
Start infusion at 0.05-0.1 mcg/kg/minute (e.g., for a 10 kg child, start at 0.5-1 mcg/min)
Titrate infusion rate every 5-10 minutes to maintain adequate blood pressure and clinical improvement
Typical maintenance doses range from 0.05 to 0.4 mcg/kg/minute
Higher doses may be required in severe cases
Monitor BP closely
Consider adjunctive medications: H1-antihistamines (e.g., diphenhydramine 1 mg/kg/dose, max 50 mg IV/IM, every 6 hours)
H2-antihistamines (e.g., ranitidine or famotidine) may be considered
Corticosteroids (e.g., methylprednisolone 1-2 mg/kg/dose, max 125 mg IV, every 6-12 hours or hydrocortisone) are typically given after initial stabilization to prevent prolonged or biphasic reactions
Bronchodilators (e.g., albuterol nebulized) for bronchospasm
Glucagon may be considered for patients on beta-blockers with refractory hypotension.
Surgical Management:
Not applicable for anaphylaxis itself, but immediate airway management (e.g., intubation) may be required if severe upper airway obstruction is present and unresponsive to medical management
Surgical cricothyroidotomy or tracheostomy is a last resort for intractable airway obstruction.
Supportive Care:
Continuous cardiac and pulse oximetry monitoring
Frequent vital sign assessment, especially blood pressure
Close monitoring for signs of recurrence
Maintain airway patency and adequate ventilation
Strict fluid balance monitoring
Provide emotional support to the child and family
Educate family on allergen avoidance and emergency action plan.
Complications
Early Complications:
Cardiovascular collapse
Refractory hypotension
Hypoxic brain injury
Laryngeal edema and airway obstruction
Acute respiratory distress syndrome (ARDS)
Myocardial infarction (rare)
Stroke (rare)
Gastrointestinal ischemia.
Late Complications:
Prolonged hypotension
Biphasic or protracted anaphylaxis
Anxiety and post-traumatic stress disorder
Development of new allergies.
Prevention Strategies:
Strict allergen avoidance
Carrying epinephrine auto-injectors and knowing how to use them
Wearing medical alert jewelry
Comprehensive education on recognizing and managing anaphylaxis
Prompt recognition and aggressive initial management of anaphylactic reactions
Consideration for early IV epinephrine in patients with concerning features or poor response to IM epinephrine.
Prognosis
Factors Affecting Prognosis:
Rapidity of onset and severity of initial symptoms
Promptness and adequacy of initial treatment
Presence of comorbidities (e.g., asthma, cardiovascular disease)
Development of refractory hypotension or severe airway compromise
Response to IV epinephrine infusion.
Outcomes:
With prompt and aggressive management, including appropriate use of IV epinephrine infusion, most pediatric patients with refractory anaphylaxis can recover
However, severe cases can lead to significant morbidity or mortality
Long-term prognosis depends on avoiding future exposures and effective management of underlying allergic predispositions.
Follow Up:
Close monitoring in an intensive care setting until vital signs are stable and the risk of biphasic reaction has passed (typically 24-48 hours)
Referral to an allergist/immunologist for comprehensive evaluation, allergy testing, and development of a long-term management plan
Education on allergen avoidance and emergency preparedness
Provision of multiple epinephrine auto-injectors with instructions on their use.
Key Points
Exam Focus:
Recognizing anaphylaxis refractory to IM epinephrine
Understanding the rationale and components of the IV epinephrine infusion protocol
Knowing the starting infusion rate and titration parameters
Differentiating anaphylaxis from other conditions
Identifying pediatric-specific BP targets.
Clinical Pearls:
Always reassess the patient after IM epinephrine
If no improvement or deterioration, consider refractory anaphylaxis and IV epinephrine
Start IV epinephrine at a low dose and titrate upwards gradually based on hemodynamic response
Do not underestimate the need for airway management in severe cases
Multidisciplinary approach involving pediatrics, emergency medicine, and allergy is crucial.
Common Mistakes:
Delaying administration of IM epinephrine
Inadequate dosing or frequency of IM epinephrine
Hesitation in escalating to IV epinephrine for refractory cases
Incorrect preparation or administration of IV epinephrine infusion
Failure to monitor vital signs closely during IV infusion
Inadequate follow-up and patient education.