Anaphylaxis

Quick Answer

One-liner: Anaphylaxis is a severe, life-threatening systemic hypersensitivity reaction requiring immediate intramuscular adrenaline (0.5mg IM lateral thigh) as first-line treatment.

Anaphylaxis is a rapid-onset, IgE or non-IgE mediated systemic allergic reaction affecting multiple organ systems. It affects 30-60 per 100,000 people annually, with mortality of 0.05-0.51 per million. The three cardinal features are cutaneous manifestations (urticaria, angioedema), respiratory compromise (wheeze, stridor, dyspnoea), and/or cardiovascular collapse (hypotension, syncope). Immediate IM adrenaline (0.5mg in adults; 0.01mg/kg in children up to 0.5mg) into the lateral thigh is life-saving and must not be delayed. Biphasic reactions occur in 2-20% of cases 4-8 hours later, requiring prolonged observation.

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ACEM Exam Focus

Primary Exam Relevance

• Anatomy: Upper airway structures (larynx, vocal cords, epiglottis), bronchial tree, cardiovascular system, dermatological structures
• Physiology: Mast cell degranulation and mediator release (histamine, tryptase, leukotrienes), complement activation, systemic vasodilation, increased vascular permeability, bronchoconstriction mechanisms
• Pharmacology: Adrenaline (α1-adrenergic vasoconstriction, β1-inotropic/chronotropic, β2-bronchodilation, mast cell stabilisation), antihistamines (H1/H2 receptors), corticosteroids (mechanism, onset delay)

Fellowship Exam Relevance

• Written: Adrenaline dose and route (IM vs IV), biphasic reaction incidence and observation period, serum tryptase timing (1-4 hours post-onset), discharge criteria, EpiPen prescription and education
• OSCE: Anaphylaxis recognition and immediate management, communication with distressed patient/family, EpiPen training, breaking bad news (severe allergy diagnosis), allergy action plan counselling
• Key domains tested: Medical Expert (immediate recognition and treatment), Communicator (family education, EpiPen training), Health Advocate (allergy referral, action plan), Leader (team coordination in resuscitation)

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Key Points

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Epidemiology

Australian/NZ Specific

• Anaphylaxis presentations to Australian EDs increased 350% from 1998 to 2012 (PMID: 25737977).
• Food triggers dominate in children (90%), while medications (40%) and insect stings (25%) dominate in adults (Australian Resuscitation Council data).
• Indigenous Australians may have higher rates of insect-sting anaphylaxis in remote areas but lower recognition of food allergies due to access barriers (PMID: 23244543).
• New Zealand has high rates of wasp and bee sting anaphylaxis in rural areas, particularly summer months (ANZCOR data).
• Australian peanut and tree nut allergy prevalence: 3% in children, highest in developed world (PMID: 25737977).

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Pathophysiology

Mechanism

Anaphylaxis can occur via IgE-mediated (Type I hypersensitivity) or non-IgE-mediated mechanisms:

IgE-Mediated (Most Common)

1. Sensitisation: Prior allergen exposure → antigen-presenting cells process allergen → Th2 lymphocytes stimulate B cells → production of allergen-specific IgE antibodies → bind to high-affinity FcεRI receptors on mast cells and basophils.
2. Re-exposure: Allergen cross-links two adjacent IgE molecules on mast cell surface → triggers intracellular signalling cascade (phospholipase C, calcium influx).
3. Degranulation: Mast cells and basophils release preformed mediators (histamine, tryptase, heparin) within seconds to minutes.
4. Mediator synthesis: Newly synthesized lipid mediators (leukotrienes C4/D4/E4, prostaglandin D2, platelet-activating factor) released over 6-8 hours.

Non-IgE-Mediated Mechanisms

• Direct mast cell activation: Medications (opioids, radiocontrast, vancomycin), physical triggers (exercise, cold, heat)
• Complement activation: Immunoglobulin aggregates, transfusion reactions
• Idiopathic: No identifiable trigger despite investigation (10-20% of cases)

Pathological Progression

Allergen exposure → Mast cell/basophil degranulation (seconds to 30 minutes)
    ↓
Histamine + Tryptase + Leukotrienes release
    ↓
1. Increased vascular permeability → angioedema, urticaria
2. Systemic vasodilation → hypotension, distributive shock
3. Bronchoconstriction → wheeze, respiratory distress
4. Gastrointestinal smooth muscle contraction → cramping, vomiting, diarrhoea
    ↓
Cardiovascular collapse + Respiratory failure → Cardiac arrest (if untreated)

Biphasic Reaction Mechanism: Unclear. Hypotheses include incomplete initial mediator clearance, ongoing allergen absorption (especially ingested), secondary mediator synthesis, or inflammatory cell recruitment. Does NOT correlate with corticosteroid administration.

Why It Matters Clinically

• Rapid progression: Symptoms can progress from mild to life-threatening within minutes (median time to cardiac arrest: 30 minutes for foods, 15 minutes for IV medications, 10 minutes for insect stings).
• Adrenaline mechanism: α1-adrenergic vasoconstriction reverses distributive shock; β2-agonism reverses bronchoconstriction; β1-inotropy/chronotropy improves cardiac output; mast cell stabilisation prevents further mediator release.
• Tryptase elevation: Peaks 1-2 hours post-onset (half-life 2 hours), useful for retrospective diagnosis. Normal tryptase does NOT exclude anaphylaxis (sensitivity only 50-70% in food-triggered anaphylaxis).

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Clinical Approach

Recognition

Anaphylaxis is highly likely when any ONE of the following criteria is met:

Criterion 1: Acute onset (below 2 hours) of skin/mucosal involvement (urticaria, angioedema, flushing, pruritus) PLUS at least one of:

• Respiratory compromise (dyspnoea, wheeze, stridor, hypoxaemia)
• Reduced blood pressure or end-organ hypoperfusion (syncope, collapse)

Criterion 2: Two or more of the following occurring rapidly after likely allergen exposure (below 2 hours):

• Skin/mucosal involvement
• Respiratory compromise
• Reduced blood pressure or end-organ hypoperfusion
• Gastrointestinal symptoms (cramping abdominal pain, vomiting, diarrhoea)

Criterion 3: Reduced blood pressure after exposure to known allergen:

• Infants/children: Low systolic BP (age-specific) or greater than 30% decrease from baseline
• Adults: Systolic BP below 90 mmHg or greater than 30% decrease from baseline

Initial Assessment

Primary Survey

A - Airway

• Look for: Angioedema (lips, tongue, uvula, posterior pharynx), drooling, inability to swallow, stridor (inspiratory = supraglottic, biphasic = subglottic)
• Action: Sit patient upright if airway compromise, prepare for intubation if stridor (difficult airway), call for senior help early
• Red Flag: Stridor indicates greater than 70% narrowing of laryngeal inlet – imminent complete obstruction

B - Breathing

• Look for: Wheeze (expiratory polyphonic), tachypnoea, accessory muscle use, hypoxia (SpO2 below 92%), inability to speak full sentences
• Action: High-flow oxygen (15L/min via non-rebreather mask), continuous SpO2 monitoring, prepare nebulised adrenaline if severe wheeze
• Red Flag: Silent chest = near-complete obstruction, pre-arrest

C - Circulation

• Look for: Tachycardia, hypotension (SBP below 90), cool peripheries, delayed capillary refill (greater than 2 seconds), altered consciousness
• Action: Lie patient flat (or reclined if dyspnoeic, never fully upright), wide-bore IV access x2, rapid IV fluid bolus (20mL/kg crystalloid)
• Red Flag: Sudden standing/sitting after lying down → cardiac arrest ("empty ventricle syndrome" from venous pooling in vasodilated periphery)

D - Disability

• Look for: Agitation (hypoxia), confusion (hypotension), syncope, seizure (severe hypoxia/hypotension)
• Action: Maintain supine position, avoid sudden position changes
• Red Flag: Reduced GCS indicates severe anaphylaxis with end-organ hypoperfusion

E - Exposure

• Look for: Urticaria (raised, erythematous, pruritic wheals), angioedema (non-pitting oedema of face/hands/genitalia), generalised erythema/flushing
• Action: Full skin examination (rash may be absent in 10-20% of anaphylaxis, especially hypotensive presentations)
• Pitfall: Absence of rash does NOT exclude anaphylaxis

History

Key Questions

Red Flag Symptoms

Examination

General Inspection

• Patient position: Reluctant to lie flat (respiratory distress) vs syncope/collapse (hypotension). Never force upright if hypotensive.
• Distress level: Severe anxiety, agitation (hypoxia), confusion (hypoperfusion), altered consciousness (pre-arrest)
• Work of breathing: Tachypnoea, accessory muscles, nasal flaring (children), tripod position
• Colour: Pallor (shock), cyanosis (hypoxia), flushing/erythema (histamine release)

Specific Findings

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Investigations

Immediate (Resus Bay)

Standard ED Workup

Advanced/Specialist

Point-of-Care Ultrasound

• Cardiac POCUS: Assess ventricular function (hyperdynamic in distributive shock), exclude tamponade (if chest pain), assess volume status (IVC collapsibility) to guide fluid resuscitation
• Lung POCUS: Differentiate wheeze (A-lines, no B-lines) from pulmonary oedema (B-lines) if diagnostic uncertainty
• Rarely indicated in anaphylaxis – diagnosis is clinical, and POCUS should not delay treatment

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Management

Immediate Management (First 10 minutes)

1. CALL FOR HELP – Activate resuscitation team/MET call if severe
2. ADRENALINE 0.5mg IM (0.5mL of 1:1,000) into LATERAL THIGH immediately
   - Children: 0.01mg/kg (max 0.5mg), use 1:1,000 concentration IM
   - Repeat every 5 minutes if no improvement or deterioration
3. POSITION patient supine (lie flat) – critical to prevent cardiac arrest
   - If dyspnoeic, recline but do NOT sit fully upright
   - NEVER allow patient to stand or walk
4. HIGH-FLOW OXYGEN 15L/min via non-rebreather mask
5. IV ACCESS x2 (wide-bore 16-18G) + FLUID BOLUS 20mL/kg crystalloid (1-2L adult) rapidly
6. REMOVE TRIGGER if identifiable and still present (e.g. stop IV infusion, remove bee sting)

Resuscitation (if applicable)

Airway

Approach:

• If stridor or angioedema: Sit patient upright, call senior anaesthetist/ENT immediately
• Nebulised adrenaline: 5mg (5mL of 1:1,000) nebulised while preparing for intubation – may temporise but NOT definitive
• Intubation: Anticipated difficult airway (oedematous, distorted anatomy). Use video laryngoscopy, prepare bougie, have surgeon ready for emergency front-of-neck airway (cricothyroidotomy)
• RSI drugs: Avoid histamine-releasing drugs (morphine, atracurium). Use fentanyl, rocuronium, ketamine (supports BP)
• Post-intubation: Large ETT (≥7.5mm) to allow for airway oedema. Consider dexamethasone 8mg IV (may reduce oedema duration).

Pitfall: Intubation can precipitate cardiovascular collapse in underfilled, vasodilated patient. Optimise preload with IV fluids and IM adrenaline before induction if time permits.

Breathing

Targets:

• SpO2 ≥94% on high-flow oxygen
• Respiratory rate below 25/min
• No accessory muscle use

Interventions:

• Bronchodilators: Salbutamol 10mg nebulised continuously (via oxygen-driven nebuliser) if wheeze persists despite adrenaline. Ipratropium bromide 500mcg nebulised may be added.
• Magnesium sulfate: 2g IV over 20 minutes if severe bronchospasm (PMID: 24011763) – smooth muscle relaxant
• Mechanical ventilation (if intubated): Lung-protective ventilation (Vt 6-8mL/kg, plateau pressure below 30 cmH2O). Prolonged expiratory time for bronchospasm. High PEEP may worsen haemodynamics in vasodilated patient.

Circulation

Targets:

• SBP ≥90 mmHg (or MAP ≥65 mmHg)
• Heart rate below 110 bpm
• Urine output ≥0.5 mL/kg/h

Haemodynamic Management:

1. IV Fluid Resuscitation:

   • First-line: 0.9% sodium chloride or Hartmann's solution
   • Dose: 20 mL/kg bolus (1-2L adult), repeat as needed – patients may require 4-6L in first hour due to massive capillary leak
   • Monitoring: Reassess BP, heart rate, perfusion after each bolus. If no response after 2-3L, consider IV adrenaline infusion

2. IV Adrenaline Infusion (if refractory hypotension despite IM adrenaline + fluids):

   • Indication: Ongoing hypotension after 2-3 doses IM adrenaline + adequate fluid resuscitation
   • Dose: 1mg adrenaline in 100mL 0.9% saline (10 mcg/mL), start at 1-10 mcg/min, titrate to BP
   • Monitoring: Continuous ECG, arterial line desirable, regular BP (every 2-5 min)
   • Environment: ICU or resus bay with senior clinician (ED consultant, ICU, anaesthetics)
   • Risk: Arrhythmias (VT/VF), myocardial ischaemia, especially in elderly or beta-blocker patients

3. Alternative Vasopressors (if IV adrenaline fails):

   • Noradrenaline: 0.05-0.5 mcg/kg/min – more potent α-agonist, less tachycardia
   • Metaraminol: 0.5-1mg IV bolus, repeat as needed – pure α-agonist, temporising measure
   • Vasopressin: 0.01-0.04 units/min – non-adrenergic vasoconstrictor, useful if adrenergic receptors desensitised

Medications

Paediatric Dosing

Ongoing Management

After Initial Stabilisation:

1. Continue monitoring: Continuous ECG, SpO2, automated BP every 5-15 minutes for first 2 hours, then hourly
2. Repeat adrenaline: Most patients respond to 1-2 doses IM. If requiring ≥3 doses, consider IV infusion and ICU admission
3. Wean oxygen: Once stable SpO2 ≥94% on lower FiO2, wean to target SpO2 92-96%
4. Observation period:
   • Minimum 4 hours: Mild anaphylaxis, single IM adrenaline dose, rapid complete resolution
   • 12-24 hours: Severe anaphylaxis, multiple adrenaline doses, poor initial response, severe asthma, remote location, patient lives alone, no adult supervision
5. Monitor for biphasic reaction: Peak incidence 4-8 hours (median 7-10 hours), can occur up to 72 hours. Symptoms identical to initial reaction. Treat with repeat IM adrenaline.

Definitive Care

• ICU admission criteria: Refractory hypotension requiring IV adrenaline infusion, intubation, refractory bronchospasm, cardiac arrest, severe comorbidities (severe asthma, coronary disease)
• Ward admission criteria: Moderate anaphylaxis requiring multiple adrenaline doses, significant comorbidities, inadequate home supervision
• Allergy clinic referral: All patients must be referred to clinical immunologist/allergist for trigger identification (skin prick testing, specific IgE), venom immunotherapy (if insect), oral immunotherapy (emerging for food allergies)

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Disposition

Admission Criteria

• Severe anaphylaxis (requiring ≥2 doses IM adrenaline)
• Refractory hypotension or bronchospasm despite treatment
• Comorbidities (severe asthma, coronary disease, age greater than 60 years)
• Inadequate home supervision (lives alone, no reliable adult)
• Remote location (greater than 1 hour from hospital)
• Patient on beta-blocker or ACE inhibitor (higher risk of refractory/biphasic reaction)
• Previous severe or biphasic reaction

ICU/HDU Criteria

• IV adrenaline infusion required
• Intubation and mechanical ventilation
• Refractory shock (SBP below 90 despite IM adrenaline + 4L fluids)
• Cardiac arrest or severe arrhythmia
• Severe bronchospasm requiring continuous nebulisation

Discharge Criteria

All of the following must be met:

• Observation period complete (minimum 4 hours, 12-24 hours if severe)
• Complete resolution of symptoms for ≥2 hours
• Vital signs normal and stable (BP, HR, SpO2, RR)
• Able to tolerate oral fluids and mobilise without symptoms
• Discharge safety net (4 essentials):
  1. EpiPen provided or prescription given (EpiPen 0.3mg for adults/children greater than 20kg; EpiPen Jr 0.15mg for children below 20kg)
  2. ASCIA Anaphylaxis Action Plan (red plan) completed by doctor, given to patient
  3. Education provided on EpiPen use (demonstrate on trainer device), trigger avoidance, when to use (early administration at first sign of anaphylaxis)
  4. Referral to clinical immunologist/allergist (urgent if severe, routine if mild)

Follow-up

• General Practitioner: Within 1-2 weeks with ED discharge summary, ASCIA Action Plan, and EpiPen
• Clinical Immunologist/Allergist: Urgent referral (within 4 weeks) for skin prick testing, serum specific IgE, trigger identification, consideration of venom immunotherapy (if insect sting) or emerging oral immunotherapy (for food allergies)
• GP letter requirements: Document allergen (if known), time to onset, symptoms, treatment (adrenaline doses, fluids), response, observation period, discharge medications, EpiPen supplied
• MedicAlert bracelet: Recommend for all patients with confirmed anaphylaxis

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Special Populations

Paediatric Considerations

• Presentation differences: Abdominal pain and vomiting may be dominant features before cardiovascular collapse (absence of urticaria in 20-30% of children)
• Dose calculation: IM adrenaline 0.01mg/kg of 1:1,000 (max 0.5mg). Use paediatric pre-filled syringes (EpiPen Jr 0.15mg for below 20kg, EpiPen 0.3mg for ≥20kg) to avoid dose errors
• Common triggers: Food allergies dominate (peanut, tree nuts, egg, cow's milk, sesame). Insect stings second most common.
• EpiPen storage: Schools and childcare centres must have EpiPen available and staff trained in use (Australian state legislation mandates)
• Asthma: Strong risk factor for severe/fatal anaphylaxis in children (PMID: 31577820). Optimise asthma control post-discharge.

Pregnancy

• Adrenaline is safe: IM adrenaline at standard doses is safe and necessary. Risk of fetal hypoxia from untreated anaphylaxis far exceeds theoretical risk of adrenaline-induced uterine vasoconstriction.
• Positioning: Left lateral tilt after 20 weeks gestation to avoid aortocaval compression
• Monitoring: Continuous CTG (cardiotocography) if viable fetus (≥24 weeks) to monitor fetal wellbeing
• Triggers: Antibiotic allergy, latex (especially at delivery), food, insect stings
• IV access and fluids: As per standard management. Avoid histamine-releasing drugs (morphine, atracurium) if anaesthesia required.

Elderly

• Cardiovascular risk: Elderly patients with pre-existing coronary disease may develop myocardial ischaemia (demand ischaemia, Takotsubo cardiomyopathy, or Kounis syndrome – allergic coronary vasospasm) during anaphylaxis or from adrenaline. Monitor ECG, troponin post-resuscitation.
• Medications: High prevalence of beta-blockers, ACE inhibitors (worsen angioedema), aspirin (may mask tachycardia). Beta-blockers blunt adrenaline response; glucagon may be needed.
• Polypharmacy: Medication allergies common (antibiotics, NSAIDs, opioids). Detailed drug history essential.
• Comorbidities: COPD, heart failure, chronic kidney disease complicate fluid resuscitation and interpretation of clinical signs.

Indigenous Health

Important Note: Aboriginal, Torres Strait Islander, and Māori considerations:

• Higher rates of insect sting allergy in remote areas (Australian bush, rural NZ) due to increased exposure to wasps, bees, jack jumper ants (Tasmania)
• Access barriers: Remote communities may be greater than 4 hours from hospital. EpiPens and community education critical. Telehealth consultation for management advice if unsure.
• Lower rates of food allergy recognition: Peanut/tree nut allergy prevalence lower in Indigenous populations but may be under-recognised due to access barriers to allergy testing and specialist services (PMID: 23244543)
• Cultural safety: Ensure interpreter services if language barrier. Involve Aboriginal Health Workers, Māori health practitioners. Explain importance of allergen avoidance and EpiPen in culturally appropriate manner.
• RFDS retrieval: Royal Flying Doctor Service provides aeromedical retrieval for severe anaphylaxis in remote Australia. Early contact if patient in remote area requires transfer.
• Medication access: PBS-subsidised adrenaline autoinjectors (EpiPen) available but may require travel to pharmacy. Consider providing EpiPen from ED stock as "bridge" if remote patient unable to fill prescription immediately.

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Pitfalls & Pearls

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Viva Practice

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OSCE Scenarios

Station 1: Anaphylaxis Recognition and Management

Format: Resuscitation station Time: 11 minutes Setting: ED resuscitation bay

Candidate Instructions:

You are the emergency registrar. A 28-year-old woman has just arrived to the resuscitation bay. She was stung by a bee 10 minutes ago while gardening. The triage nurse reports she is short of breath and has a rash. You have a resuscitation nurse available. Assess and manage the patient.

Examiner Instructions: The patient is a 28-year-old woman with anaphylaxis following bee sting. Initial observations: HR 120, BP 85/50, RR 28, SpO2 88% on room air, GCS 15. She has urticaria on torso and limbs, audible wheeze, and appears anxious.

Expected progression:

• Candidate should recognise anaphylaxis immediately
• Call for help, administer IM adrenaline 0.5mg (0.5mL 1:1,000) into lateral thigh within 2 minutes
• Position patient supine, apply high-flow oxygen
• Obtain IV access x2, administer rapid crystalloid bolus
• Reassess at 5 minutes
• If candidate performs correctly, patient improves: HR 100, BP 100/60, SpO2 95% on oxygen, wheeze reduced
• Candidate should observe patient, consider second-line medications, arrange tryptase sample

Actor/Patient Brief: You are a 28-year-old woman who was stung by a bee on your arm 10 minutes ago while gardening. You have never been stung before. Within 5 minutes you developed tingling of your lips and tongue, generalised itching, and difficulty breathing. You feel like your throat is swelling and you are scared you are going to die. You are cooperative but very anxious. If candidate asks about medications, you take oral contraceptive pill only. No medical history. After receiving IM adrenaline and fluids (if managed correctly), you start to feel better – breathing easier, less anxious.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: IM adrenaline given within 2 minutes (critical action), correct dose and site, patient positioned supine

Fail Criteria:

• Fails to administer adrenaline within 5 minutes
• Gives antihistamine or steroid before adrenaline
• Gives adrenaline subcutaneously or IV bolus (undiluted)
• Allows patient to sit upright despite hypotension

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Station 2: EpiPen Education and Discharge Planning

Format: Communication station Time: 11 minutes Setting: ED consultation room

Candidate Instructions:

You are the emergency registrar. You have just successfully treated a 35-year-old man for anaphylaxis following peanut exposure at a restaurant. He is now well and ready for discharge. His observations are normal. He has never had an allergic reaction before and does not have an EpiPen. Educate him on EpiPen use and complete a discharge plan. You have an EpiPen trainer device available.

Examiner Instructions: The patient is a 35-year-old man who had anaphylaxis (urticaria, wheeze, hypotension) after eating satay chicken containing peanut sauce. He was treated with IM adrenaline x1, IV fluids, and second-line medications. He has been asymptomatic for 4 hours. Observations are now normal (HR 72, BP 125/75, SpO2 98% RA). He is ready for discharge. Assess the candidate's ability to educate on EpiPen use and provide a comprehensive discharge plan.

Actor/Patient Brief: You are a 35-year-old office worker who has never had an allergic reaction before. You have eaten peanut products many times in the past without issue. You are surprised and scared by today's event. You have never heard of an EpiPen and don't understand why you need one or how to use it. You are receptive to education but ask questions: "Will this happen again? How do I avoid peanuts? What if I use the EpiPen by accident?" You live with your wife. No children. You are compliant and want to stay safe.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: EpiPen demonstration with patient repeating, emphasis on early use, clear discharge plan (EpiPen + action plan + allergy referral)

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Station 3: Breaking Bad News – Severe Peanut Allergy in Child

Format: Communication station Time: 11 minutes Setting: ED relatives room

Candidate Instructions:

You are the emergency registrar. You have just treated a 4-year-old boy for severe anaphylaxis (requiring 2 doses IM adrenaline) after eating a peanut butter sandwich at preschool. He is now stable and admitted to the ward for observation. His mother is waiting in the relatives' room. She is unaware of any food allergies and is very anxious. Break the news to her and discuss the implications.

Examiner Instructions: The patient is a 4-year-old boy with severe anaphylaxis (urticaria, stridor, hypotension) requiring 2 doses IM adrenaline, IV fluids, and admission for 24-hour observation. This is his first known allergic reaction. He has no prior history of allergies or eczema. His mother is anxious and upset. Assess the candidate's ability to break bad news and explain the implications of severe peanut allergy in a child.

Actor/Patient Brief: You are a 35-year-old mother of a 4-year-old boy. You are shocked and terrified by what has happened. You brought peanut butter sandwiches to preschool today as they are his favourite. Within 10 minutes he developed facial swelling, couldn't breathe, and collapsed. Preschool staff called an ambulance. You are crying and blame yourself. You ask: "Will he be OK? Is it my fault? Can he ever eat peanuts again? What do I do if it happens again? Can he go back to preschool?" You are a concerned, loving parent seeking reassurance and guidance.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators: Empathy and acknowledgment of distress, clear explanation of future management (strict avoidance, EpiPen, action plan), addresses guilt ("not your fault")

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SAQ Practice

Question 1 (6 marks, 8 minutes)

Stem: A 22-year-old woman presents to ED with anaphylaxis. She has been treated with IM adrenaline, IV fluids, and is now stable. You are preparing to discharge her.

Question: List SIX essential components of a safe discharge plan for a patient with anaphylaxis. (1 mark each)

Model Answer:

1. EpiPen provided or prescription given (EpiPen 0.3mg for adults, 0.15mg for children below 20kg) (1 mark)
2. ASCIA Anaphylaxis Action Plan (red plan) completed by doctor and provided to patient (1 mark)
3. Education on EpiPen use – demonstrate on trainer device, have patient repeat, explain when to use (at first sign of anaphylaxis) (1 mark)
4. Trigger identification and avoidance advice – explain allergen (if known), how to avoid exposure (food label reading, restaurant disclosure, etc.) (1 mark)
5. Referral to clinical immunologist/allergist – for formal testing (skin prick test, specific IgE), trigger confirmation, consideration of immunotherapy (if venom) (1 mark)
6. GP follow-up within 1-2 weeks – with discharge summary, ASCIA Action Plan, documentation of allergen and treatment (1 mark)

Examiner Notes:

• Accept: MedicAlert bracelet, provision of second EpiPen (backup), observation period completed (4 hours minimum), advice to avoid NSAIDs/beta-blockers (if relevant)
• Do not accept: Antihistamine prescription, steroid prescription (these are not essential for discharge safety)

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Question 2 (8 marks, 10 minutes)

Stem: A 45-year-old man presents with anaphylaxis following a wasp sting. He has received one dose of IM adrenaline 0.5mg and 2L IV fluids. His BP is now 110/65 (was 80/50), HR 100 (was 130), SpO2 96% on 6L oxygen (was 88% on RA). Urticaria has resolved. He feels much better and is requesting immediate discharge.

Question: Outline your approach to observation and discharge planning for this patient, including timing and rationale. (8 marks)

Model Answer:

1. Observation period: Minimum 4 hours from symptom resolution (1 mark)

   • Rationale: Biphasic reactions occur in 2-20% (average 5%) of anaphylaxis, typically 4-8 hours post-initial reaction (median 7-10 hours), but can occur up to 72 hours later (1 mark)

2. Consider extended observation (12-24 hours) if:

   • Severe initial anaphylaxis (required ≥2 doses adrenaline, prolonged hypotension) (0.5 marks)
   • Poor initial response to treatment (0.5 marks)
   • History of severe asthma (risk factor for fatal anaphylaxis) (0.5 marks)
   • Remote location (lives greater than 1 hour from hospital) (0.5 marks)
   • Patient lives alone or no adult supervision at home (0.5 marks)
   • Previous biphasic reaction (0.5 marks)

3. During observation: Continuous monitoring of vital signs (HR, BP, SpO2, RR) every 15-30 minutes initially, then hourly once stable. Patient remains in ED or short-stay unit with IV access in situ and resuscitation equipment nearby (1 mark)

4. Discharge criteria (all must be met):

   • Complete resolution of symptoms for ≥2 hours (1 mark)
   • Vital signs normal and stable (0.5 marks)
   • Able to tolerate oral fluids and mobilise without symptoms (0.5 marks)
   • Discharge safety net completed: EpiPen provided, ASCIA Action Plan, education, allergy referral (1 mark)

Examiner Notes:

• Accept: Serum tryptase collection (1-4 hours post-onset) as part of workup, second-line medications (antihistamine, corticosteroid) given but not required for discharge
• Common mistakes: Discharging after 1-2 hours (insufficient observation), failing to mention biphasic reaction risk, not providing EpiPen or action plan

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Question 3 (6 marks, 8 minutes)

Stem: A 6-year-old child (weight 20kg) presents with anaphylaxis after eating cashew nuts. You are preparing to administer adrenaline.

Question: (a) State the correct dose, concentration, and route of adrenaline for this child. (3 marks) (b) Explain the rationale for this route over alternative routes. (3 marks)

Model Answer:

(a) Dose, concentration, route:

• Dose: 0.2mg (or 0.01mg/kg, max 0.5mg) (1 mark)
• Concentration: 1:1,000 (1mg/mL) adrenaline (1 mark)
• Route: Intramuscular (IM) into lateral thigh (vastus lateralis muscle) (1 mark)

(b) Rationale for IM route:

• Faster absorption: IM lateral thigh reaches peak plasma concentration at 8 minutes, faster than IM deltoid (13 min) or subcutaneous (34 min) (1 mark)
• More reliable: Vastus lateralis is a large muscle with good blood supply. Subcutaneous route has slow, erratic absorption due to vasoconstriction in anaphylaxis (1 mark)
• Safer than IV: IV adrenaline requires dilution (1mg in 100mL), cardiac monitoring, infusion pump, and ICU/senior supervision due to risk of arrhythmias, severe hypertension, myocardial ischaemia if given as undiluted bolus. IM is safe, effective, and standard of care in ED (1 mark)

Examiner Notes:

• Accept: Volume = 0.2mL of 1:1,000 adrenaline
• Do not accept: Subcutaneous route, IM deltoid (inferior to lateral thigh), IV bolus

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Question 4 (8 marks, 10 minutes)

Stem: A 55-year-old man with ischaemic heart disease (on bisoprolol 5mg daily) presents with anaphylaxis. Despite 3 doses of IM adrenaline and 3L IV fluids, his BP remains 75/45.

Question: (a) Explain why this patient is refractory to standard treatment. (2 marks) (b) Outline your management plan for refractory anaphylaxis in this patient. (6 marks)

Model Answer:

(a) Pathophysiology of refractory anaphylaxis in beta-blocker patient:

• Beta-blockers (bisoprolol) competitively antagonise β-adrenergic receptors, blunting both endogenous and exogenous adrenaline effects (1 mark)
• This reduces the β1-inotropic/chronotropic response (reduced cardiac output) and β2-bronchodilator effect. The α1-vasoconstrictor effect is preserved but insufficient to maintain BP in severe anaphylaxis (1 mark)

(b) Management plan for refractory anaphylaxis:

1. IV adrenaline infusion: 1mg adrenaline in 100mL 0.9% saline (10 mcg/mL), start at 1-10 mcg/min, titrate to BP. Requires continuous ECG monitoring, senior clinician supervision (ED consultant/ICU/anaesthetics), arterial line desirable (2 marks)

2. Glucagon: 1-2mg IV bolus, then 1-5mg/hour infusion. Bypasses blocked β-receptors by directly activating adenylyl cyclase, increasing cAMP → inotropy and bronchodilation. Side effect: nausea/vomiting (2 marks)

3. Alternative vasopressor: If inadequate response, add noradrenaline infusion (0.05-0.5 mcg/kg/min) for potent α-agonist vasoconstriction, or vasopressin (0.01-0.04 units/min) as non-adrenergic vasoconstrictor (1 mark)

4. ICU transfer: This patient requires ICU admission for ongoing vasopressor support and monitoring (1 mark)

Examiner Notes:

• Accept: Continued aggressive fluid resuscitation (may need 4-6L total), methylene blue (rescue therapy in extreme refractory cases), ECMO (case reports in severe refractory anaphylactic shock)
• Do not accept: Higher doses of IM adrenaline alone (inadequate for refractory shock), stopping bisoprolol acutely (takes hours to days to reverse effect)

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Australian Guidelines

ARC/ANZCOR

• ANZCOR Guideline 9.2.7 (2023): Anaphylaxis

  • "Adrenaline 0.5mg (0.5mL of 1:1,000) IM into lateral thigh (vastus lateralis) is first-line treatment"
  • Repeat every 5 minutes if no improvement or deterioration
  • Position patient supine (or reclined if dyspnoeic) – NEVER allow patient to sit upright or stand if hypotensive
  • IV adrenaline reserved for refractory cases with senior supervision
  • Observation minimum 4 hours, extend to 12-24 hours if severe
  • "Available: https://www.anzcor.org"

• Key differences from AHA/ERC guidelines:

  • ARC/ANZCOR specifies lateral thigh (vastus lateralis) as preferred IM site (AHA/ERC allow deltoid)
  • ARC/ANZCOR emphasizes patient positioning (supine) more strongly than AHA
  • Observation periods slightly longer in ARC/ANZCOR (minimum 4 hours vs 4-6 hours in AHA)

Therapeutic Guidelines

• Therapeutic Guidelines: Antibiotic (eTG) – Allergy and Adverse Reactions
  • Distinguishes between immunological (IgE-mediated anaphylaxis, T-cell mediated delayed reactions) and non-immunological (direct histamine release, idiosyncratic) adverse drug reactions
  • "Beta-lactam allergy: Cross-reactivity between penicillins and cephalosporins is low (below 5%) for 2nd/3rd generation cephalosporins. Can use cephalosporins if penicillin allergy history is vague or remote, but avoid if prior anaphylaxis."
  • Recommends allergy testing (skin prick, intradermal, drug challenge) before labeling patient as "penicillin allergic" – 90% of patient-reported penicillin allergies are not confirmed on testing

State-Specific

• NSW Health Policy Directive PD2024_020: Adrenaline for Anaphylaxis

  • All NSW Health facilities must have adrenaline autoinjectors (EpiPens) available in resuscitation areas, EDs, operating theatres, and high-risk areas (radiology for contrast reactions)
  • Staff must be trained annually in anaphylaxis recognition and EpiPen use
  • Mandatory reporting of anaphylaxis events to Clinical Excellence Commission

• Victorian Department of Health: Anaphylaxis Guidelines for Schools

  • All Victorian schools must have anaphylaxis management policy
  • Staff trained in EpiPen use, ASCIA Action Plans for all students with known allergies
  • EpiPens stored in unlocked, easily accessible location (not locked first aid room)

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Remote/Rural Considerations

Pre-Hospital

• Ambulance protocols: Paramedics carry adrenaline autoinjectors (adult and paediatric) and 1:1,000 ampoules for IM administration. Protocols allow multiple doses (typically up to 3) before hospital arrival.
• Bystander EpiPens: Encourage bystanders to use patient's own EpiPen if available while waiting for ambulance. Good Samaritan laws protect bystanders who use EpiPen in emergency.
• Delayed presentations: Patients in remote areas may delay presentation due to distance from hospital. Telephone triage should advise immediate IM adrenaline (if EpiPen available) and urgent ambulance, NOT "wait and see" approach.

Resource-Limited Setting

Modified approach when resources limited:

• No EpiPen available: Draw up 0.5mL of 1:1,000 adrenaline from ampoule into 1mL syringe, administer IM into lateral thigh. Repeat from fresh ampoule every 5 min if needed.
• No IV access: IM adrenaline + oral/IM antihistamine + IM corticosteroid can temporise. Continue attempts at IV access for fluid resuscitation.
• No oxygen: Position patient to optimise airway (sit upright if wheeze, supine if hypotensive). Open windows for air circulation. Prepare for bag-valve-mask ventilation if deteriorates.
• Limited monitoring: Manually check pulse, BP, respiratory rate, conscious state every 5 minutes. Use patient's mobile phone to call retrieval service for guidance.

Retrieval

Criteria for retrieval (RFDS or road ambulance):

• Refractory anaphylaxis (requiring ≥3 doses IM adrenaline or IV adrenaline infusion)
• Significant comorbidities (severe asthma, coronary disease, elderly, pregnancy)
• Remote location with limited resources (no ICU, no senior medical staff)
• Paediatric anaphylaxis in rural hospital without paediatric experience
• Biphasic reaction requiring ongoing observation beyond capability of local facility

RFDS considerations:

• Telephone advice available 24/7 for remote clinicians managing anaphylaxis
• Aeromedical retrieval can take 2-6 hours depending on distance and weather
• Local clinician may need to manage patient for several hours before team arrives – ensure adequate adrenaline supply, IV fluids, oxygen
• RFDS carries advanced airway equipment, vasoactive medications, ventilator for in-flight management

Telemedicine

Remote consultation approach:

• Video link (if available): Visual assessment of urticaria, angioedema, work of breathing, conscious state
• Audio only: Detailed verbal description from on-site clinician or patient. Ask about timing from exposure, progression of symptoms, vital signs.
• Decision support: Guide local clinician through ABCDE approach, adrenaline dose calculation (especially paediatrics), fluid resuscitation, when to repeat adrenaline
• Retrieval coordination: Early activation if severe or poor response to initial treatment
• Documentation: Remote consultant should document advice given, patient details, and retrieval decisions for medicolegal record

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References

Guidelines

1. Australian Resuscitation Council. ANZCOR Guideline 9.2.7: Anaphylaxis. 2023. Available from: https://www.anzcor.org
2. Australasian Society of Clinical Immunology and Allergy (ASCIA). ASCIA Guidelines: Acute Management of Anaphylaxis. 2023. Available from: https://www.allergy.org.au
3. Australasian Society of Clinical Immunology and Allergy (ASCIA). ASCIA Action Plan for Anaphylaxis (Red). 2023. Available from: https://www.allergy.org.au
4. Therapeutic Guidelines Limited. eTG complete: Antibiotic – Allergy and Adverse Reactions. 2024. Available from: https://www.tg.org.au
5. World Allergy Organization. WAO Anaphylaxis Guidance 2020. World Allergy Organ J. 2020;13(10):100472. PMID: 33204386

Key Evidence

6. Sampson HA, et al. Second symposium on the definition and management of anaphylaxis: summary report—Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006;117(2):391-397. PMID: 16461139
7. Simons FE, et al. World Allergy Organization anaphylaxis guidelines: 2013 update of the evidence base. Int Arch Allergy Immunol. 2013;162(3):193-204. PMID: 24008815
8. Turner PJ, et al. Fatal anaphylaxis: mortality rate and risk factors. J Allergy Clin Immunol Pract. 2017;5(5):1169-1178. PMID: 28888247
9. Shaker MS, et al. Anaphylaxis—a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol. 2020;145(4):1082-1123. PMID: 32001253
10. Cardona V, et al. World Allergy Organization Anaphylaxis Guidance 2020. World Allergy Organ J. 2020;13(10):100472. PMID: 33204386

Epidemiology

11. Pouessel G, et al. The epidemic of anaphylaxis: what is the true frequency of anaphylaxis? Curr Opin Allergy Clin Immunol. 2018;18(5):435-441. PMID: 29956664
12. Wood RA, et al. Anaphylaxis in America: the prevalence and characteristics of anaphylaxis in the United States. J Allergy Clin Immunol. 2014;133(2):461-467. PMID: 24144575
13. Mullins RJ, et al. Increases in anaphylaxis fatalities in Australia from 1997 to 2013. Clin Exp Allergy. 2016;46(8):1099-1110. PMID: 27027880
14. Poulos LM, et al. Trends in hospitalizations for anaphylaxis, angioedema, and urticaria in Australia, 1993-1994 to 2004-2005. J Allergy Clin Immunol. 2007;120(4):878-884. PMID: 17931562
15. Jerschow E, et al. Fatal anaphylaxis in the United States, 1999-2010: temporal patterns and demographic associations. J Allergy Clin Immunol. 2014;134(6):1318-1328. PMID: 25280385

Adrenaline Pharmacology and Routes

16. Simons FE, et al. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol. 1998;101(1 Pt 1):33-37. PMID: 9449498
17. Simons FE, et al. Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol. 1998;101(1 Pt 1):33-37. PMID: 9449498
18. Simons KJ, et al. Epinephrine dispensed for self-administration in anaphylaxis: absorption kinetics and patient self-administration techniques. J Allergy Clin Immunol. 2000;106(6):1184-1185. PMID: 11112908
19. Campbell RL, et al. Epinephrine in anaphylaxis: higher risk without benefit - biphasic anaphylaxis study. J Allergy Clin Immunol Pract. 2015;3(1):76-80. PMID: 25577622

Biphasic Reactions

20. Shaker M, et al. Incidence and characteristics of biphasic reactions in prospective studies of anaphylaxis. J Allergy Clin Immunol Pract. 2020;8(4):1228-1235. PMID: 31877391
21. Lee S, et al. Biphasic anaphylactic reactions in pediatrics. Pediatr Emerg Care. 2000;16(5):376-380. PMID: 11063370
22. Grunau BE, et al. Incidence of clinically important biphasic reactions in emergency department patients with allergic reactions or anaphylaxis. Ann Emerg Med. 2014;63(6):736-744. PMID: 24262144
23. Rohacek M, et al. Biphasic anaphylactic reactions: occurrence and mortality. Allergy. 2014;69(6):791-797. PMID: 24725292

Serum Tryptase

24. Valent P, et al. Serum tryptase as a diagnostic marker in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am. 2006;26(3):451-463. PMID: 16931287
25. Triggiani M, et al. Differentiation between allergic and non-allergic anaphylaxis by measurement of serum tryptase. J Investig Allergol Clin Immunol. 2009;19 Suppl 2:23-28. PMID: 19530415
26. Edston E, van Hage-Hamsten M. Beta-tryptase measurements post-mortem in anaphylactic deaths and in controls. Forensic Sci Int. 1998;93(2-3):135-142. PMID: 9717192
27. Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am. 2006;26(3):451-463. PMID: 16931287

Beta-Blockers and Refractory Anaphylaxis

28. Toogood JH. Risk of anaphylaxis in patients receiving beta-blocker drugs. J Allergy Clin Immunol. 1988;81(1):1-5. PMID: 2892872
29. Lang DM. Anaphylactoid and anaphylactic reactions: hazards of beta-blockers. Drug Saf. 1995;12(5):299-304. PMID: 7669261
30. Hepner DL, Castells MC. Anaphylaxis during the perioperative period. Anesth Analg. 2003;97(5):1381-1395. PMID: 14570656
31. Mink SN, et al. Refractory anaphylactic shock: a role for combined α- and β-adrenergic agonist therapy. Can J Anaesth. 2006;53(1):78-84. PMID: 16371613

Indigenous Health and Access

32. Koplin JJ, et al. Epidemiology of food allergy and food-induced anaphylaxis: is there really a Western lifestyle? Curr Opin Allergy Clin Immunol. 2008;8(6):522-526. PMID: 18978467
33. Mullins RJ, et al. Adrenaline auto-injector prescription and use in Australia: a population-based study. Med J Aust. 2013;199(4):266-269. PMID: 23984783
34. Osborne NJ, et al. Prevalence of challenge-proven IgE-mediated food allergy using population-based sampling and predetermined challenge criteria in infants. J Allergy Clin Immunol. 2011;127(3):668-676. PMID: 21377036
35. Holt PG, et al. Environmental factors and primary prevention of allergy and asthma. Curr Opin Allergy Clin Immunol. 2007;7(1):76-81. PMID: 17218815

Paediatric Anaphylaxis

36. Pumphrey RS, Gowland MH. Further fatal allergic reactions to food in the United Kingdom, 1999-2006. J Allergy Clin Immunol. 2007;119(4):1018-1019. PMID: 17349682
37. Bock SA, et al. Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol. 2001;107(1):191-193. PMID: 11150010
38. Lieberman P, et al. Biphasic anaphylactic reactions. Ann Allergy Asthma Immunol. 2005;95(3):217-226. PMID: 16200811
39. Ben-Shoshan M, et al. A population-based study on peanut, tree nut, fish, shellfish, and sesame allergy prevalence in Canada. J Allergy Clin Immunol. 2010;125(6):1327-1335. PMID: 20451985

Venom Immunotherapy

40. Golden DB, et al. Stinging insect hypersensitivity: a practice parameter update 2016. Ann Allergy Asthma Immunol. 2017;118(1):28-54. PMID: 28007086
41. Boyle RJ, et al. Venom immunotherapy for preventing allergic reactions to insect stings. Cochrane Database Syst Rev. 2012;10:CD008838. PMID: 23076950

Kounis Syndrome

42. Kounis NG. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med. 2016;54(10):1545-1559. PMID: 27071153

Food-Induced Anaphylaxis

43. Sicherer SH, Sampson HA. Food allergy: recent advances in pathophysiology and treatment. Annu Rev Med. 2009;60:261-277. PMID: 18729730
44. Lieberman JA, et al. Epidemiology of food allergy. Immunol Allergy Clin North Am. 2021;41(2):157-171. PMID: 33863467
45. Muraro A, et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy. 2014;69(8):1008-1025. PMID: 24909706
46. Yu JE, et al. Biphasic reactions in food-triggered anaphylaxis in children and adolescents. Ann Allergy Asthma Immunol. 2012;108(5):321-324. PMID: 22541401

Drug-Induced Anaphylaxis

47. Demoly P, et al. International Consensus on drug allergy. Allergy. 2014;69(4):420-437. PMID: 24697291
48. McNeil BD, et al. Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions. Nature. 2015;519(7542):237-241. PMID: 25517090
49. Thong BY, et al. Drug allergy in a general hospital: results of a novel 10-year survey. Ann Allergy Asthma Immunol. 2010;104(4):331-336. PMID: 20408344

Anaphylaxis in Pregnancy

50. Simons FE, et al. Anaphylaxis: the acute episode and beyond. BMJ. 2013;346:f602. PMID: 23335853
51. Chaudhuri K, et al. Anaphylaxis in pregnancy: a case series and review. J Obstet Gynaecol Can. 2013;35(11):988-993. PMID: 24246398

Exercise-Induced Anaphylaxis

52. Shadick NA, et al. The natural history of exercise-induced anaphylaxis: survey results from a 10-year follow-up study. J Allergy Clin Immunol. 1999;104(1):123-127. PMID: 10400849
53. Feldweg AM. Exercise-induced anaphylaxis. Immunol Allergy Clin North Am. 2015;35(2):261-275. PMID: 25841551

Mastocytosis and Elevated Baseline Tryptase

54. Bonadonna P, et al. Clonal mast cell disorders in patients with systemic reactions to Hymenoptera stings and increased serum tryptase levels. J Allergy Clin Immunol. 2009;123(3):680-686. PMID: 19135713

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Differential Diagnosis

When evaluating a patient with suspected anaphylaxis, consider the following differential diagnoses:

Conditions that Mimic Anaphylaxis

Vasovagal Syncope

• Similarities: Sudden collapse, pallor, loss of consciousness, hypotension
• Differences: Bradycardia (not tachycardia), NO urticaria/wheeze/angioedema, responds to supine positioning alone, no exposure history
• Key discriminator: Heart rate. Vasovagal causes bradycardia; anaphylaxis causes compensatory tachycardia (unless terminal).

Acute Asthma

• Similarities: Wheeze, dyspnoea, hypoxia, tachypnoea
• Differences: No urticaria, no hypotension (initially), gradual onset (hours), personal history of asthma
• Key discriminator: Multi-system involvement in anaphylaxis. Asthma affects respiratory system only.

Panic Attack/Hyperventilation

• Similarities: Dyspnoea, anxiety, tachycardia, sense of "impending doom"
• Differences: No urticaria, no hypotension, no wheeze, carpopedal spasm (respiratory alkalosis), emotional trigger
• Key discriminator: Allergen exposure history absent. Vital signs normal (BP, SpO2). Perioral tingling from hyperventilation (not anaphylaxis).

Septic Shock

• Similarities: Hypotension, tachycardia, altered consciousness, fever (occasionally in anaphylaxis)
• Differences: Gradual onset (hours), fever more prominent, source of infection, elevated lactate and WCC
• Key discriminator: Time course. Anaphylaxis onset within minutes; sepsis over hours to days.

Carcinoid Crisis

• Similarities: Flushing, hypotension, wheeze, diarrhoea
• Differences: Rare, history of carcinoid tumour, flushing lasts hours (not minutes), elevated urinary 5-HIAA
• Key discriminator: History of neuroendocrine tumour. Flushing is prolonged. No urticaria.

Hereditary Angioedema

• Similarities: Angioedema (face, lips, tongue, larynx), abdominal pain
• Differences: NO urticaria, NO wheeze, NO hypotension, family history, episodes last 24-72 hours, C1-esterase inhibitor deficiency
• Key discriminator: Absence of urticaria/wheeze/hypotension. Does NOT respond to adrenaline. Requires C1-INH concentrate or icatibant.

Scombroid Poisoning

• Similarities: Flushing, urticaria, headache, abdominal pain, hypotension (histamine from decomposed fish)
• Differences: Occurs after eating dark-flesh fish (tuna, mackerel, mahi-mahi), multiple people affected if shared meal, responds to antihistamines alone
• Key discriminator: Food history (fish). Multiple cases if shared meal. Normal tryptase (histamine from fish, not mast cell degranulation).

Pheochromocytoma Crisis

• Similarities: Hypertension (rarely hypotension), tachycardia, flushing, anxiety
• Differences: HYPERTENSION (not hypotension in most cases), headache, sweating, elevated catecholamines
• Key discriminator: Hypertension. No urticaria. Urinary metanephrines elevated.

Systemic Mastocytosis

• Similarities: Flushing, hypotension, GI symptoms (chronic diarrhoea, abdominal pain), anaphylaxis episodes
• Differences: Chronic/recurrent symptoms, urticaria pigmentosa (skin lesions), elevated baseline tryptase (greater than 11.4 μg/L), bone marrow biopsy shows mast cell infiltration
• Key discriminator: Recurrent episodes. Elevated baseline tryptase (not just acute elevation). Darier's sign (urtication on stroking skin lesions).

Approach to Diagnosis

Clinical Diagnosis: Anaphylaxis is a clinical diagnosis. Do NOT delay treatment waiting for tryptase results or other investigations.

Criteria for Anaphylaxis (reproduced for emphasis):

• Criterion 1: Skin/mucosal involvement + respiratory OR cardiovascular compromise
• Criterion 2: Two or more systems involved (skin, respiratory, cardiovascular, GI) after allergen exposure
• Criterion 3: Hypotension after known allergen exposure

Post-Resuscitation Evaluation:

1. Serum tryptase: 1-4 hours post-onset (ideally 1-2 hours), then baseline ≥24 hours later
2. Specific IgE (at allergy clinic): Identifies suspected allergen (food, venom, medication)
3. Skin prick testing (at allergy clinic): Gold standard for allergen identification
4. Challenge testing (specialist setting only): If diagnosis uncertain

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Common Triggers

Understanding common triggers helps predict and prevent anaphylaxis.

Food Allergens

Children

Adults

Insect Stings

Venom Immunotherapy: Highly effective (90-95% protection). Indicated after systemic reaction. Administered over 3-5 years. Near-curative.

Medications

Penicillin Allergy: 90% of patients reporting "penicillin allergy" are NOT truly allergic on formal testing. Many report childhood rash (viral exanthem, not allergy). Delabeling via allergy clinic testing is important to avoid unnecessary broad-spectrum antibiotics (resistance risk, C. difficile).

Other Triggers

Latex

• Prevalence: 1-6% general population, 10-17% healthcare workers
• Cross-reactivity: Banana, avocado, kiwi fruit, chestnut ("latex-fruit syndrome")
• Exposure: Gloves, catheters, condoms, balloons
• Prevention: Latex-free gloves in healthcare. Preoperative screening.

Seminal Fluid

• Rare: below 100 cases reported worldwide
• Presentation: Anaphylaxis after sexual intercourse (local or systemic)
• Diagnosis: Skin prick testing with partner's seminal plasma
• Management: Barrier contraception, desensitisation protocols available

Excipients

• Gelatin: Vaccines (MMR, varicella), IV fluids
• Polysorbate 80: Vaccines (influenza, HPV), medications
• Carboxymethylcellulose: Eye drops, laxatives
• Significance: Often overlooked. Consider in anaphylaxis with "no identifiable trigger" after medication/vaccine.

Idiopathic Anaphylaxis

• Definition: Recurrent anaphylaxis (≥2 episodes) with no identifiable trigger despite thorough investigation
• Prevalence: 10-20% of anaphylaxis cases
• Management: Chronic antihistamine prophylaxis (cetirizine or fexofenadine daily), omalizumab (anti-IgE monoclonal antibody) in severe cases, always carry two EpiPens
• Prognosis: Spontaneous remission in 50% over 5-10 years

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Severity Grading

While all anaphylaxis requires immediate IM adrenaline, grading severity helps predict outcomes and guide disposition.

Ring and Messmer Classification (Modified)

Predictors of Severe Anaphylaxis:

• Rapid onset (below 10 minutes from exposure)
• Route of exposure: IV > IM > ingestion
• Severe asthma (strongest risk factor for fatal anaphylaxis)
• Cardiovascular disease
• Beta-blocker or ACE inhibitor use
• Mastocytosis (elevated baseline tryptase)
• Prior severe reaction

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Controversies and Grey Zones

Corticosteroids: Do They Prevent Biphasic Reactions?

Current Evidence: No.

• Multiple studies (including PMID: 24262144, PMID: 31877391) show NO reduction in biphasic reaction incidence with corticosteroid administration
• Mechanism: Corticosteroids have 4-6 hour onset of action (too slow for immediate effect), primarily anti-inflammatory (not anti-histamine or anti-mediator)
• Current practice: Still widely given (hydrocortisone 200mg IV in adults) as adjunct for potential benefit in reducing protracted urticaria or late-phase reactions, but NOT relied upon to prevent biphasic reactions

ACEM Position: Corticosteroids are second-line adjuncts. They do NOT replace adrenaline or observation period.

Antihistamines: Are They Necessary?

H1-blockers (promethazine, cetirizine):

• Benefit: Reduce urticaria and pruritus (itch)
• No benefit: Airway obstruction, bronchospasm, hypotension
• Sedation risk: Promethazine causes drowsiness → may mask deterioration or delay recognition of biphasic reaction

H2-blockers (ranitidine, famotidine):

• Theoretical benefit: Histamine acts on both H1 (vasodilation, pruritus) and H2 (gastric acid, some vasodilation) receptors. Combination H1+H2 blockade may be superior to H1 alone.
• Evidence: Limited. Small studies show faster resolution of urticaria with H1+H2 vs H1 alone. No mortality benefit.

ACEM Position: Antihistamines are adjuncts. They should never delay adrenaline. Consider H1-blocker (promethazine 25mg IM/IV or cetirizine 10mg PO) + H2-blocker (ranitidine 50mg IV or famotidine 20mg IV) after adrenaline administration.

IV Adrenaline: When is it Appropriate?

IM vs IV Debate:

• IM adrenaline: Safe, effective, rapid absorption (8 min to peak), standard of care, minimal adverse effects, no cardiac monitoring required
• IV adrenaline infusion: Faster onset, titratable, but requires dilution (1mg in 100mL), infusion pump, continuous ECG monitoring, senior supervision, ICU-level care. Risk of arrhythmias, severe hypertension, myocardial ischaemia if undiluted bolus given.
• IV bolus (undiluted 1mg): Causes VT/VF, severe hypertension. ONLY indicated in cardiac arrest (not anaphylaxis without arrest).

Indications for IV Adrenaline Infusion:

1. Refractory hypotension despite ≥2-3 IM adrenaline doses + adequate IV fluids (≥2-3L)
2. Cardiac arrest (give 1mg IV boluses as per ALS protocol)
3. Peri-arrest (severe hypotension SBP below 70, altered GCS, pre-arrest rhythm)

ACEM Position: IM adrenaline is first-line in almost all cases. IV infusion only for refractory shock with senior clinician (ED consultant, ICU, anaesthetics) and continuous monitoring.

Observation Period: How Long is Enough?

Biphasic Reaction Timing:

• 2-20% incidence (average 5%)
• Median time to biphasic reaction: 7-10 hours (range: 30 min to 72 hours)
• Most occur within 12 hours

Observation Recommendations:

• Minimum 4 hours: Mild anaphylaxis (Grade I), single IM adrenaline dose, rapid complete resolution, no comorbidities, adequate home supervision
• 12-24 hours: Severe anaphylaxis (Grade II-III), ≥2 adrenaline doses, poor initial response, severe asthma, beta-blocker/ACE inhibitor, remote location, lives alone, prior biphasic reaction

Risk Factors for Biphasic Reactions (inconsistently reported across studies):

• Delayed initial adrenaline (greater than 30 min from symptom onset)
• Severe initial reaction
• Food allergen (slower absorption from GI tract)
• Unknown allergen (ongoing exposure)

ACEM Position: Minimum 4 hours for all patients. Extend to 12-24 hours if any risk factors present. Corticosteroids do NOT shorten observation period.

Intubation in Anaphylaxis: Friend or Foe?

Risks of Intubation:

• Precipitation of cardiac arrest (loss of sympathetic tone from induction agents + reduced preload from positive pressure ventilation in underfilled, vasodilated patient)
• Difficult airway (angioedema distorts anatomy, tongue oedema, laryngeal oedema)
• Worsening hypotension from sedation

When to Intubate:

• Absolute indications: Cardiac/respiratory arrest, severe hypoxia (SpO2 below 85% despite high-flow oxygen), complete airway obstruction
• Relative indications: Rapidly progressive stridor, inability to protect airway (reduced GCS), severe hypoxia despite NIV

How to Intubate Safely:

1. Optimise first: IM adrenaline x2-3, IV fluids ≥2L, nebulised adrenaline 5mg (temporising measure)
2. Senior help: Call most experienced airway clinician (anaesthetics, ED consultant)
3. Preparation: Video laryngoscopy, bougie, larger ETT (≥7.5mm), emergency front-of-neck airway kit ready (scalpel-bougie-tube technique)
4. Drug choice: Avoid histamine-releasing drugs (morphine, atracurium). Use ketamine (maintains BP), rocuronium (no histamine release), fentanyl.
5. Positioning: Ramped position (head-up), consider awake fibreoptic intubation if time permits

ACEM Position: Intubation is high-risk in anaphylaxis. Avoid if possible. Optimise with adrenaline and fluids first. If intubation necessary, most experienced clinician + full preparation for difficult airway.

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Quality Improvement and Audit

Anaphylaxis management is a key quality indicator in emergency medicine. Audit the following metrics:

Process Measures

Outcome Measures

Discharge Quality Measures

Common Errors to Audit

1. Antihistamine or steroid given before adrenaline → Delays definitive treatment
2. Subcutaneous adrenaline → Slow, unreliable absorption
3. IV adrenaline bolus (undiluted) → Arrhythmias, hypertension, myocardial ischaemia
4. Patient allowed to stand/sit upright when hypotensive → "Empty ventricle syndrome" → cardiac arrest
5. Discharge before 4-hour observation → Missed biphasic reactions
6. Discharge without EpiPen or action plan → High-risk if recurrence

Morbidity & Mortality Review: All anaphylaxis cases requiring intubation, ICU admission, or with biphasic reactions should be reviewed at departmental M&M meetings to identify system improvements.

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Case-Based Learning

Case 1: Classic Food Anaphylaxis

Presentation: 19-year-old university student presents 10 minutes after eating pad Thai at a restaurant. Reports lip tingling, throat tightness, difficulty breathing. On arrival: HR 125, BP 88/55, SpO2 90% RA, diffuse expiratory wheeze, urticarial rash on torso.

Key Learning Points:

• Rapid onset (below 30 min) after ingestion suggests anaphylaxis
• Multi-system involvement (skin + respiratory + cardiovascular) = Grade II-III severity
• Immediate IM adrenaline 0.5mg lateral thigh is first-line
• Peanuts in pad Thai (satay sauce) are common hidden allergens in Asian cuisine
• Patient will need allergy testing to confirm trigger, EpiPen for future, dietary education

Management: IM adrenaline 0.5mg → improved to BP 105/65, HR 100, SpO2 96% on 6L O2. Given IV fluids 2L, promethazine 25mg IV, hydrocortisone 200mg IV. Observed 4 hours, discharged with EpiPen, ASCIA plan, allergy referral.

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Case 2: Biphasic Reaction

Initial Presentation: 8-year-old boy stung by bee while playing in backyard. Developed facial angioedema, wheeze, urticaria. Given IM adrenaline 0.3mg by paramedics, improved en route to hospital. In ED: vital signs normal, urticaria resolved. Observed for 3 hours, parents request discharge.

6 hours post-initial reaction: While still in ED (family delayed leaving), child suddenly develops recurrent urticaria, wheeze, BP drops to 80/50.

Key Learning Points:

• Biphasic reactions occur in 2-20% of cases, typically 4-8 hours after initial reaction
• No reliable predictors - observation is only safeguard
• Minimum 4-hour observation for mild cases, 12-24 hours for severe
• Second reaction treated identically to first: IM adrenaline 0.3mg, IV fluids
• After biphasic reaction, extended observation (24 hours) and consider admission

Outcome: Second dose of IM adrenaline, IV fluids, admitted for 24-hour observation. Discharged next day with TWO EpiPens (one may be insufficient if biphasic), urgent allergy referral for bee venom immunotherapy.

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Case 3: Refractory Anaphylaxis in Beta-Blocker Patient

Presentation: 72-year-old man with ischaemic heart disease (on bisoprolol 5mg daily, aspirin, atorvastatin) presents 5 minutes after IV ceftriaxone for community-acquired pneumonia. Developed urticaria, wheeze, hypotension.

Initial Management: IM adrenaline 0.5mg x3 doses (at 0, 5, 10 min), IV fluids 3L. BP remains 75/45.

Key Learning Points:

• Beta-blockers blunt response to adrenaline (β1-inotropic and β2-bronchodilator effects antagonised)
• Refractory anaphylaxis defined as inadequate response to ≥2-3 IM adrenaline doses + adequate fluids
• Glucagon bypasses blocked β-receptors: 1-2mg IV bolus, then 1-5mg/h infusion
• May require IV adrenaline infusion (1mg in 100mL, start 1-10 mcg/min)
• ICU admission required

Management: Glucagon 2mg IV bolus → BP improved to 95/60. Started IV adrenaline infusion at 5 mcg/min, admitted to ICU. Weaned off infusion over 6 hours. Cardiology consultation for myocardial ischaemia risk (troponin mildly elevated, no ECG changes). Discharged day 3 with EpiPen, advised to carry two given refractory reaction, drug allergy clinic referral to confirm ceftriaxone as trigger.

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