Shock, Sepsis & Multisystem · Topic 4 of 14

Anaphylaxis

Shock & resuscitation · anaphylaxis

Anaphylaxis

A rapid, life-threatening systemic allergic reaction. Give IM epinephrine 0.01 mg/kg (max 0.5 mg) in the thigh at once and repeat every 5–15 minutes.

Key numbers

IM epinephrine 0.01 mg/kg, max 0.5 mg0.01 mg/kg IM, max 0.5 mg

Biphasic reactions recur within 48 hoursBiphasic ≈ 6.5%

01 · GiveIM epinephrine 0.01 mg/kg, max 0.5 mg

Give epinephrine 0.01 mg/kg of the 1 mg/mL (1:1000) solution IM into the anterolateral thigh — maximum 0.5 mg in adults, 0.3 mg in prepubertal children — and repeat every 5–15 minutes as needed.

02 · Defined bySkin plus respiratory, BP or GI involvement

Anaphylaxis is a clinical diagnosis: acute skin or mucosal signs plus respiratory compromise, hypotension or severe GI symptoms — or, after a likely allergen, hypotension, bronchospasm or laryngeal involvement even without skin signs (WAO 2020).

03 · Watch forBiphasic reactions recur within 48 hours

Biphasic anaphylaxis recurs within 48 hours (median about 10 hours) after at least 1 symptom-free hour, without re-exposure; it affects about 6.5% of adults, more after severe reactions or more than 1 epinephrine dose.

What it is

Core idea

Refractory: persists after 3 epinephrine dosesRefractory anaphylaxis persists despite 3 or more appropriate epinephrine doses (or an IV infusion) plus symptom-directed care; it is rare (< 0.5% of severe cases), often drug-induced, and carries a high fatality rate.

Causes & risk factors

Why it happens

Triggers: drugs, foods, venom, latex, contrastCommon triggers: drugs (beta-lactams, NSAIDs, perioperative agents), foods (nuts, eggs, seafood), insect venom, latex and radiocontrast; some cases are idiopathic.

Diagnosis & monitoring

Work-up

Observe longer after severe or multidose reactionsObserve until symptoms fully resolve; a 1-hour symptom-free period has a 95% negative predictive value for biphasic anaphylaxis after nonsevere reactions, while severe or multidose reactions need longer monitoring.

Tryptase within 2 hours, compare with baselineDraw serum tryptase within 2 hours of onset and a baseline level later; an acute value above 1.2 × baseline + 2 ng/mL (the "20% + 2" rule) supports mast-cell activation; never delay treatment for it.

Do right now

In this order

First moves

IM epinephrine 0.01 mg/kg, max 0.5 mg0.01 mg/kg IM, max 0.5 mg

→

Intubate early for progressing airway edema

→

Refractory: IV fluids, then epinephrine infusion

Why each step

IM epinephrine 0.01 mg/kg, max 0.5 mgGive epinephrine 0.01 mg/kg of the 1 mg/mL (1:1000) solution IM into the anterolateral thigh — maximum 0.5 mg in adults, 0.3 mg in prepubertal children — and repeat every 5–15 minutes as needed.

Intubate early for progressing airway edemaStridor or wheeze not responding to epinephrine needs oxygen and early intubation; waiting can let upper-airway edema progress until only cricothyrotomy is possible.

Refractory: IV fluids, then epinephrine infusionIf hypotension persists after IM epinephrine, give rapid isotonic fluid boluses and an IV epinephrine infusion titrated to blood pressure (slow 0.05–0.1 mg IV bolus if the infusion is delayed); add vasopressors if still refractory.

Management

Orders

Do not wait for criteria to give epinephrineGive epinephrine at the first sign of suspected anaphylaxis — meeting diagnostic criteria is not required, serious adverse effects of IM epinephrine are rare, and a response to epinephrine does not itself prove anaphylaxis.

Antihistamines and steroids are adjuncts onlyH1 (± H2) antihistamines relieve itch and hives only, and glucocorticoids have no proven acute role; neither reliably prevents biphasic anaphylaxis, and neither replaces epinephrine.

On beta-blockers: add glucagon 1–5 mg IVBeta-blockers can blunt the response to epinephrine; still give epinephrine, then glucagon 1–5 mg IV over 5 minutes followed by a 5–15 mcg/min infusion (rapid injection causes vomiting).

Inhaled albuterol for persisting bronchospasmAdd an inhaled short-acting beta-agonist (albuterol) for bronchospasm that persists after epinephrine.

Anaphylaxis or bradykinin angioedema?

Commonly confused

Usual cause	Drugs, foods, venom, latex, contrast
Urticaria and itch	Usually present
Organ involvement	Skin plus airway, blood pressure or GI
Epinephrine	First-line, IM 0.01 mg/kg

Teach & follow up

Patient education

Discharge with autoinjectors and allergist referralBefore discharge prescribe epinephrine autoinjectors (0.3 mg for ≥ 30 kg; more than one after biphasic reactions or multiple doses), teach when and how to use them and trigger avoidance, and refer to an allergist.

More detail

Reference

Show 6 reference facts

For most indications the risk of stopping a beta-blocker or ACE inhibitor outweighs the added risk of more severe anaphylaxis, especially in insect-sting anaphylaxis; continue them with shared decision-making.

Non-IgE (anaphylactoid) reactions from direct mast-cell activation — radiocontrast, NSAIDs, opioids, monoclonal antibodies — need no prior sensitization and are treated the same way.

Persistent anaphylaxis is anaphylaxis lasting at least 4 hours.

With recurrent, idiopathic or severe anaphylaxis, check a baseline tryptase; > 8 ng/mL raises hereditary alpha-tryptasemia or a clonal mast-cell disorder (mastocytosis).

Intranasal epinephrine (2 mg spray for ≥ 30 kg, 1 mg for 15–30 kg) is an alternative to IM injection; repeat doses go in the same nostril after 5 minutes.

After home autoinjector use, emergency services may not be needed if the response is prompt, complete and durable; call them for severe, unresolved, recurring or worsening reactions.

Pearl

Thigh, now, and again in 5–15 minutes: IM epinephrine is first-line, and antihistamines or steroids never replace it.

Sources · Golden DBK et al. Anaphylaxis: A 2023 practice parameter update (AAAAI/ACAAI JTFPP). Ann Allergy Asthma Immunol 2024;132:124–176. doi:10.1016/j.anai.2023.09.015 (AAAAI open PDF) · Wang J et al. Anaphylaxis in Practice: A Guide to the 2023 Practice Parameter Update. J Allergy Clin Immunol Pract 2024;12:2325–2336 (AAAAI PDF) · Merck Manual Professional — Anaphylaxis (reviewed Sept 2026) · Shaker MS et al. Anaphylaxis — a 2020 practice parameter update, systematic review, and GRADE analysis. J Allergy Clin Immunol 2020;145:1082–1123 · Merck Manual Professional — Shock (reviewed Jun 2026) · Merck Manual Professional — Angioedema · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).