ED Shift Card: Acute Anaphylaxis Protocol

A practical and academic emergency shift card for ED physicians, on-call doctors, ENT, anesthesia, and ICU teams. Anaphylaxis is not a condition that waits for laboratory confirmation or reassurance. If airway, breathing, or circulation are compromised, the practical question is not: “Can I prove the diagnosis?” The question is: “Have I given IM epinephrine now?”

Practical Overview

Anaphylaxis is a rapid, systemic, life-threatening hypersensitivity reaction. It may be IgE-mediated or non-IgE-mediated. The real danger is not the rash. The danger is upper airway obstruction, bronchospasm, vasodilation, capillary leak, circulatory collapse, and cardiac arrest.

Practical rule for the on-call physician

The absence of urticaria or rash does not exclude anaphylaxis. A patient with hypotension, dyspnea, stridor, hoarseness, tongue swelling, altered consciousness, or collapse after possible allergen exposure should be treated as anaphylaxis until proven otherwise.

Common triggers

• Food: peanuts, tree nuts, fish, shellfish, egg, milk, and age-specific food allergens.
• Insect venom: bee stings, wasp stings, and other Hymenoptera venom, especially in patients with previous reactions or elevated baseline tryptase.
• Medications: beta-lactam antibiotics, NSAIDs, anesthetic agents, neuromuscular blockers, contrast media, and some biologic therapies.
• Other triggers: latex, exercise, food-dependent exercise-induced anaphylaxis, cold exposure, and idiopathic anaphylaxis.

The treatment that must not be delayed

Intramuscular epinephrine into the anterolateral thigh is the first and decisive treatment. Antihistamines and corticosteroids do not treat airway obstruction, shock, or life-threatening bronchospasm. They must never be given before epinephrine when anaphylaxis is suspected.

Red Flags

These signs mean the patient is no longer presenting with “just an allergic reaction.” The patient has entered an emergency risk zone. One red flag is enough to escalate.

• Airway: new hoarseness, inspiratory stridor, swelling of the tongue, lips, pharynx, or floor of mouth, dysphagia, drooling, or a sensation of throat closing.
• Breathing: dyspnea, diffuse wheeze, bronchospasm, hypoxemia, respiratory fatigue, or a silent chest in a deteriorating patient.
• Circulation: hypotension, dizziness, syncope, pallor, sweating, tachycardia, cold extremities, or altered consciousness.
• Neurological status: sudden agitation, confusion, drowsiness, collapse, or the patient saying they feel they are going to die.
• Gastrointestinal involvement: repeated vomiting, severe abdominal cramps, or diarrhea, especially when combined with respiratory or circulatory symptoms.
• High risk for biphasic reaction: delayed epinephrine, need for more than one epinephrine dose, severe initial reaction, poorly controlled asthma, cardiac disease, pregnancy, or suspected mast cell disease.

Clinical trap

Do not wait for a rash. Some of the most dangerous anaphylaxis cases have few skin findings, especially in severe vascular collapse, perioperative reactions, older patients, or patients treated early.

Diagnostic Algorithm

Anaphylaxis is a clinical diagnosis. Laboratory tests are useful for documentation and later investigation, but they do not drive the first emergency decision.

Think anaphylaxis when acute deterioration follows possible exposure and includes one or more of the following

• Skin or mucosal involvement with respiratory or circulatory symptoms.
• Hypotension, syncope, or collapse after known or possible allergen exposure.
• Bronchospasm or laryngeal edema after food, medication, sting, injection, anesthesia, or contrast exposure.
• Repeated vomiting or severe abdominal pain after food exposure, especially in children or when associated with systemic symptoms.

Important differential diagnoses

• Severe asthma attack: may mimic anaphylaxis, but rash, angioedema, hypotension, or a clear exposure history favors anaphylaxis.
• Vasovagal reaction: bradycardia and pallor after injection or fear, usually without wheeze, angioedema, or generalized urticaria.
• Hereditary angioedema: swelling without urticaria, often with poor response to epinephrine compared with classic anaphylaxis.
• Foreign body aspiration or upper airway obstruction: sudden choking or stridor without a clear allergic context.
• Sepsis or septic shock: often slower in evolution, with fever or infectious focus, but this must not delay epinephrine if the clinical scenario suggests anaphylaxis.
• Myocardial infarction or arrhythmia: especially in older patients or patients with cardiac disease, and may coexist with anaphylaxis or occur after severe shock.
• Toxic or non-allergic drug reactions: such as opioid-related histamine release, scombroid poisoning, or infusion reactions.

Shift summary

When possible exposure intersects with acute respiratory or circulatory compromise, treat it as anaphylaxis. Differential diagnosis matters, but it does not replace epinephrine.

Investigations

Do not delay treatment for any test. Investigations are for documentation, severity assessment, complication screening, and follow-up planning.

Tryptase

• Take an acute tryptase sample as early as possible, ideally within the first 1–2 hours after symptom onset, without delaying epinephrine.
• Take a later baseline tryptase sample after recovery, when the patient is clinically stable.
• The commonly used mast-cell activation rule is: Peak Tryptase > (1.2 × Baseline Tryptase) + 2 ng/mL.
• A persistently elevated baseline tryptase, especially when associated with severe reactions or insect-sting anaphylaxis, should raise concern for mast-cell disorders such as systemic mastocytosis or hereditary alpha-tryptasemia.
• A normal tryptase does not exclude anaphylaxis, especially in some food-triggered reactions, early-treated cases, or samples taken outside the optimal time window.

Additional tests according to the clinical scenario

• Blood pressure, pulse, oxygen saturation, ECG, and continuous monitoring in moderate or severe cases.
• Blood gas if there is hypoxemia, respiratory fatigue, or suspected ventilatory failure.
• Glucose, creatinine, electrolytes, lactate, and CBC according to severity and clinical context.
• Troponin and ECG if there is chest pain, cardiac disease, older age, arrhythmia, or concern for ischemia after shock or epinephrine.
• Document the suspected trigger, timing, epinephrine doses, response, airway findings, and need for repeat treatment.

Management Plan

Emergency doctrine: Epinephrine early — airway always.

1. Stop exposure and call for help

• Stop the drug, infusion, food exposure, or suspected trigger if still ongoing.
• Activate the resuscitation team if respiratory or circulatory symptoms are present.
• Call anesthesia, ENT, and ICU early when there is stridor, tongue swelling, deteriorating ventilation, or a likely difficult airway.

2. Patient position

• Lay the patient flat with legs elevated if hypotensive.
• Do not allow the patient to stand or walk suddenly, even if they feel better.
• If severe dyspnea is dominant, a semi-sitting position may be used while closely monitoring blood pressure and consciousness.
• Pregnant patients should be positioned in the left lateral position when possible.

3. Rapid practical ABCDE

• A — Airway: prepare suction, oxygen, difficult airway equipment, and call anesthesia/ENT for any sign of upper airway obstruction.
• B — Breathing: give high-flow oxygen. Add nebulized salbutamol/albuterol for wheeze or bronchospasm, but never use it as a substitute for epinephrine.
• C — Circulation: insert two large-bore IV lines. Give rapid crystalloid fluids if hypotension or shock is present.
• D — Disability: monitor consciousness, glucose, cerebral hypoperfusion signs, and sudden agitation.
• E — Exposure: assess skin, urticaria, swelling, and sting site, but do not let absence of rash reassure you.

Drug Treatment

Intramuscular epinephrine

Give IM epinephrine into the anterolateral thigh. Do not use the upper arm as the first-choice site, and do not delay epinephrine while waiting for IV access.

• Adult: 0.5 mg IM using 1 mg/mL solution. A 0.3 mg auto-injector dose may be used when that is what is immediately available or according to local protocol.
• Child: 0.01 mg/kg IM, respecting local weight-based maximum doses.
• Repeat dosing: repeat every 5–15 minutes if airway, breathing, or circulation problems persist. In resuscitation protocols, repeating every 5 minutes while ABC compromise continues is practical and common.

Fluids

• If hypotension or shock is present, give rapid crystalloid boluses.
• Adults: commonly start with 500–1000 mL rapidly, then reassess blood pressure, pulse, urine output, work of breathing, and signs of overload.
• Children: 20 mL/kg as an initial bolus, with frequent reassessment.
• Severe anaphylactic shock may require large fluid volumes because of marked capillary leak.

Salbutamol / Albuterol

Use for wheeze or persistent bronchospasm. It does not treat laryngeal edema or hypotension, so it must never delay or replace epinephrine.

Antihistamines

Antihistamines may help itching and urticaria after the patient is stabilized. They do not treat shock, bronchospasm, or airway obstruction. Do not make them the center of the first minutes of management.

Corticosteroids

Corticosteroids may be used as adjunctive therapy in selected cases, especially with asthma or severe reactions, but their immediate emergency benefit is not reliable. They must not delay epinephrine, fluids, or airway management.

Refractory anaphylaxis

If airway, breathing, or circulation problems persist after two appropriate IM epinephrine doses with adequate resuscitation, treat the patient as refractory anaphylaxis.

• Call anesthesia, ICU, and an experienced emergency physician immediately.
• Start IV epinephrine infusion in a monitored setting using an infusion pump and experienced staff.
• Starting doses vary by local protocol, but often begin low, for example 0.05–0.1 mcg/kg/min, then titrate to blood pressure, perfusion, and adverse effects.
• Add noradrenaline/norepinephrine or vasopressin if shock persists despite epinephrine and fluids, in coordination with ICU.
• Avoid IV epinephrine boluses outside cardiac arrest or outside expert hands, because they may cause arrhythmia or myocardial ischemia.

Patient on beta-blockers

If the patient is taking beta-blockers and responds poorly to epinephrine, consider IV glucagon because it can partially bypass beta-receptor blockade.

• Glucagon: 1–5 mg IV slowly over 5–10 minutes, followed by infusion 5–15 mcg/min according to response.
• Monitor for vomiting, hyperglycemia, hypokalemia, and blood pressure changes.
• Glucagon does not replace epinephrine, fluids, airway management, or close monitoring.

Airway Procedures

The airway in anaphylaxis can move from “intubatable” to “cannot ventilate” within minutes. Do not wait until the space is gone.

When should anesthesia and ENT be called early?

• Inspiratory stridor or worsening hoarseness.
• Swelling of the tongue, floor of mouth, palate, pharynx, or a feeling of throat closure.
• Drooling or difficulty swallowing.
• Hypoxemia or respiratory fatigue despite oxygen.
• Repeated need for epinephrine or rapid clinical deterioration.
• Known difficult intubation, severe obesity, pregnancy, or difficult facial/neck anatomy.

Airway plan

• Prepare suction, non-rebreather mask, bag-valve-mask, intubation equipment, supraglottic airway, and a CICO plan.
• Early expert intubation may be safer than waiting for complete obstruction.
• Avoid agitating the patient or forcing a position that worsens breathing.
• If ventilation and intubation fail: cricothyrotomy is the rescue procedure in a CICO scenario.

Practical rescue point

If you have started thinking that the airway may become difficult, that is the time to call the expert — not the time to wait. In anaphylaxis, late airway escalation is more dangerous than early help.

Admission and Discharge

Admit to ICU or high-dependency monitoring

• Need for more than one IM epinephrine dose, especially two or more doses.
• Need for IV epinephrine infusion or vasopressors.
• Persistent hypotension or shock requiring large fluid volumes.
• Airway involvement or need for intubation/surgical airway.
• Severe asthma, cardiac disease, arrhythmia, pregnancy, or known/suspected mastocytosis.
• Severe, prolonged, refractory, idiopathic, or late-presenting reaction.
• Patient lives far from care or has no reliable adult observer after discharge.

Observation after improvement

Observe the patient for at least 4–6 hours after the last epinephrine dose in lower-risk cases. Observe longer, or overnight, in severe, prolonged, refractory, or high-risk cases. The aim is to detect biphasic reaction or recurrence before discharge.

Safe discharge requirements

• Clear respiratory and circulatory stability without recurrence during an appropriate observation period.
• No progressive airway swelling, persistent wheeze, or hypotension.
• Provide or prescribe two epinephrine auto-injectors when there is risk of re-exposure, unknown cause, or specialist recommendation.
• Teach the patient practically: when to use the injector, where to inject, and when to call emergency services.
• Provide a written allergen-avoidance plan and document suspected triggers.
• Arrange allergy/immunology follow-up for trigger assessment, baseline tryptase, and future prevention planning.
• Warn the patient that improvement of skin symptoms does not mean the danger is over if breathing difficulty, dizziness, collapse, or repeated vomiting returns.

Pitfalls and Pearls

• Pitfall 1: Giving antihistamine and corticosteroid first, then waiting. This wastes the minutes the patient needs for epinephrine.
• Pitfall 2: Being reassured because the rash is mild. Airway and circulation matter more than skin.
• Pitfall 3: Assuming early improvement means the story is over. Some patients return with biphasic anaphylaxis hours later.
• Pitfall 4: Making IV access a condition before epinephrine. IM epinephrine is given immediately and does not wait for a cannula.
• Pitfall 5: Letting the patient walk after improvement. Sudden standing can worsen venous return and trigger collapse.
• Pitfall 6: Forgetting that a patient on beta-blockers may need glucagon if the reaction is refractory.
• Pitfall 7: Taking acute tryptase but forgetting the later baseline sample. The comparison between peak and baseline is what gives true diagnostic value.
• Pitfall 8: Delaying anesthesia/ENT in a patient with hoarseness, stridor, and tongue swelling. The airway does not always give a second warning.

Practical pearl

In anaphylaxis, the correct early decision is often simple: lay the patient flat, give epinephrine into the thigh, start ABC, call for help, and watch the airway as if you may need it within minutes. The complexity usually comes from delay, not from epinephrine.

References

1. World Allergy Organization Anaphylaxis Guidance 2020.
2. Resuscitation Council UK. Emergency Treatment of Anaphylaxis Guidelines. 2021.
3. ASCIA Guidelines: Acute Management of Anaphylaxis. 2024.
4. AAAAI/ACAAI Joint Task Force. Anaphylaxis: A 2023 Practice Parameter Update.
5. Wang J, Lieberman JA, Wallace DV, Waserman S, Golden DBK. Anaphylaxis in Practice: A Guide to the 2023 Practice Parameter Update. J Allergy Clin Immunol Pract. 2024.
6. Whyte AF et al. Emergency treatment of anaphylaxis: concise clinical guidance. Clin Med. 2022.
7. Pouessel G et al. Management of Refractory Anaphylaxis: An Overview of Current Guidelines. J Clin Med. 2024.