Anaphylaxis: workup and management
Anaphylaxis is a severe, rapid-onset systemic allergic reaction. Intramuscular epinephrine is the first and most important treatment and should not be delayed for antihistamines or steroids. Observe for biphasic reactions and discharge with epinephrine auto-injectors.
Working diagnosis
Adult · US guidelines
Draft · awaiting physician review
01Orient
What's new in the evidence
- Intranasal epinephrine (2 mg) was FDA-approved in 2024 for people ≥30 kg; IM and intranasal doses can be repeated every 5–15 minutes
- 2023 practice parameter: glucocorticoids and antihistamines do not prevent biphasic reactions and should not delay epinephrine
- Prepare an epinephrine infusion after 2 doses and start it if a third is needed
Differential diagnoses
- Anaphylaxis (food, drug, insect sting, contrast) (can't miss)
- ACE-inhibitor or hereditary angioedema (bradykinin-mediated; no urticaria, poor epinephrine response)
- Asthma exacerbation
- Vasovagal reaction (bradycardia, pallor, no urticaria)
- Septic shock, scombroid poisoning
- Panic attack, vocal cord dysfunction
02Assess
Risk scores and decision tools
- Clinical criteria for anaphylaxis (WAO 2020)
- Serum tryptase 30 min–2 h after onset and a baseline ≥24 h later
- Biphasic risk: severe initial reaction, >1 epinephrine dose needed
Key history questions
- Exposure and timing: foods, drugs, stings, latex, contrast
- Symptoms: skin, airway, breathing, GI, dizziness
- Prior reactions; epinephrine use before arrival
- Beta-blockers or ACE inhibitors
- Asthma (higher risk of fatal reaction)
Examination findings
- Airway: stridor, hoarseness, tongue or lip swelling
- Wheeze, hypoxia
- Hypotension, tachycardia
- Urticaria, flushing (may be absent in up to 10–20%)
03Investigate
Initial investigations
- Clinical diagnosis; treat immediately
- Serum tryptase ideally 30 minutes to 2 hours after onset (supports diagnosis later)
Advanced investigations
- Baseline tryptase at least 24 hours later
- Allergy testing as an outpatient
04Treat
Immediate management
- Epinephrine 0.5 mg IM (1 mg/mL) into the anterolateral thigh; repeat every 5–15 minutes as needed
- Lie flat with legs raised (sit up if breathing difficulty); high-flow oxygen
- IV crystalloid bolus 1–2 L for hypotension
- Refractory after 2–3 IM doses: epinephrine infusion with monitoring, ICU
First-line treatment
- Nebulized albuterol for persistent bronchospasm
- Glucagon 1–5 mg IV for refractory hypotension on beta-blockers
- H1/H2 antihistamines for skin symptoms only (adjunct)
- Glucocorticoids are not first-line and do not prevent biphasic reactions reliably
Second-line treatment
- Difficult airway: early expert intubation or surgical airway
- Bradykinin angioedema: icatibant or C1-esterase inhibitor; epinephrine is less effective
Specialist referrals
- Allergy/immunology after discharge
- ICU for refractory anaphylaxis or airway involvement
05Disposition
Admission criteria
- Needed more than one epinephrine dose or an infusion
- Airway involvement, persistent hypotension
- Severe asthma, poor access to care
Safe discharge criteria
- Symptoms resolved after observation (often 4–6 hours; longer if severe)
- Two epinephrine auto-injectors prescribed and use taught
- Written anaphylaxis action plan
Follow-up timing
- Allergy referral; primary care within 1–2 weeks
Patient instructions
- Use your auto-injector at the first sign of a reaction, then call 911
- Avoid the trigger; wear a medical alert
Monitoring
- Continuous monitoring during observation
- Watch for biphasic reaction
Clinical pearls and pitfalls
- There is no absolute contraindication to IM epinephrine in anaphylaxis
- Delayed epinephrine is the main risk factor for death
- Stop or switch ACE inhibitors after angioedema
RefGuidelines and landmark evidence
For education only. Typical adult starting points; confirm doses against renal function, allergies, interactions and your institution's protocols. Not a substitute for clinical judgment or senior review.