← EMA Topics
EMA Topics · Allergy · Resuscitation

Anaphylaxis

Updated Oct 16, 2026Adults · ED management9 sources · 5 checked in PubMed1 figureAAAAI/ACAAI 2023 · WAO 2020 · RCUK 2021

Bottom line

  • IM epinephrine first. Give 0.01 mg/kg of 1 mg/mL solution, up to 0.5 mg in adults, into the anterolateral thigh.1,2 Repeat after 5 minutes if there is no improvement.3
  • Don't wait for the criteria to be met. You don't need to meet diagnostic criteria before giving epinephrine. A response to epinephrine does not prove the diagnosis either.1
  • Minutes matter. In UK deaths from anaphylaxis, the median time to arrest was 5 minutes for drug reactions, 15 for venom and 30 for food. Only 14% got epinephrine before arrest.4
  • Avoid IV bolus epinephrine. In an ED cohort, IV boluses caused cardiovascular events in 10% of doses vs 1.3% for IM, and caused every overdose.5 If two IM doses fail, start a low-dose epinephrine infusion.3
  • Antihistamines and steroids are not rescue drugs. They do not reliably prevent biphasic reactions.3,6

Recognize

Under the 2020 World Allergy Organization (WAO) criteria, anaphylaxis is highly likely when either of these is met:1,2

CriterionFindings
1. Skin or mucosa, plus one more systemAcute onset (minutes to hours) of hives, itch, flushing or lip-tongue-uvula swelling, and at least one of: respiratory compromise, low BP or end-organ dysfunction (collapse, syncope, incontinence), or severe GI symptoms (especially after non-food allergens)
2. No skin signs neededAcute hypotension, bronchospasm or laryngeal involvement (stridor, voice change, painful swallowing) after exposure to a known or highly probable allergen
  • Hypotension in adults: systolic BP under 90 mm Hg, or a drop of more than 30% from baseline.1
  • The older 2006 NIAID criteria were 95% sensitive and 71% specific in a prospective ED validation.1
  • Mimics include vasovagal reactions, flushing syndromes (carcinoid, pheochromocytoma), scombroid, panic, vocal cord dysfunction, hereditary angioedema and vancomycin infusion reaction.1
  • Severe anaphylaxis is more likely in older patients, those with heart or lung disease, and drug-triggered reactions.1

Tryptase

  • Draw an acute tryptase as early as possible, ideally within 2 hours of onset, and a later baseline for comparison (conditional, moderate certainty).1 Never delay treatment to draw it.3
  • Tryptase may not rise until 30 minutes or more after onset, and peaks at 1–2 hours.3
  • A normal tryptase does not exclude anaphylaxis, especially from food.3 An acute level at least 20% plus 2 ng/mL above baseline supports mast cell activation.1

First 10 minutes

  1. Remove the trigger if you can (stop the infusion or drug) and call for help.2
  2. IM epinephrine 0.5 mg (0.5 mL of 1 mg/mL) into the anterolateral mid-thigh. Use a needle long enough to reach muscle.3
  3. Position: supine, or sitting up if breathing is hard. Pregnant patients lie semi-recumbent on the left side, and unconscious patients go in the recovery position.2
  4. Monitor pulse oximetry, BP and ECG as soon as you can, to judge the response.3
  5. High-flow oxygen for respiratory distress or anyone needing further epinephrine. Place large-bore IV access.2
  6. IV crystalloid for cardiovascular instability: 20 mL/kg2, or 500–1,000 mL boluses in adults titrated to response.3
  7. No improvement after 5 minutes? Repeat IM epinephrine.3 Peak absorption is around 5–10 minutes after IM injection.3
  8. Still no improvement in breathing or circulation after 2 IM doses: treat as refractory (below).3

Treatment

DrugAdult doseNotes
First line
Epinephrine IM (1 mg/mL)0.5 mg (0.5 mL); 0.01 mg/kg, max 0.5 mgAnterolateral thigh. Repeat after 5 min if no improvement. Not subcutaneous or inhaled.1,2,3
Crystalloid500–1,000 mL IV per bolusFor shock. Large volumes (3–5 L) may be needed in refractory cases.3
Refractory (no improvement after 2 IM doses)
Epinephrine infusion, low dose, peripheral1 mg in 100 mL 0.9% saline (10 µg/mL); start at 0.5–1.0 mL/kg/hInfusion pump, dedicated line, not on the BP cuff arm. Continuous monitoring. Give IM doses every 5 min until it runs.3
Nebulized epinephrine (1 mg/mL)5 mLAdjunct for upper airway obstruction, after IM epinephrine, never instead of it.3
Second vasopressorPer local protocolNorepinephrine, vasopressin or metaraminol if refractory to the epinephrine infusion.3
GlucagonDose per institutional protocol and labelConsider for patients on beta-blockers who respond poorly. Evidence is very limited.2,3
Not for rescue
H1 antihistamineNon-sedating oral (e.g. cetirizine) once stableSkin symptoms only. No role for airway or circulation. Rapid IV chlorphenamine can cause hypotension.2,3
CorticosteroidNot routineConsider after resuscitation for refractory reactions or ongoing asthma or shock. Never before epinephrine.3

Unreviewed doses. Verify against the current label and your institution's protocol before giving anything.

IV epinephrine

IV epinephrine is for experienced specialists in a monitored setting. Excess doses can cause tachyarrhythmias, severe hypertension, MI and stroke, and dilution errors are a known cause of harm.3 In an ED cohort, all 4 overdoses occurred with IV boluses (4 of 30 IV bolus doses vs 0 of 316 IM).5 A markedly raised BP suggests epinephrine overdose.3

Refractory anaphylaxis

  • Definition: anaphylaxis that continues despite appropriate epinephrine and symptom-directed treatment, after 3 or more epinephrine doses or once an infusion has started.1
  • It accounts for under 0.5% of severe cases, most often drug-triggered and perioperative. Fatality was 26.2% vs 0.35% for other reactions in a 2019 European registry.1
  • Get expert help early. Critical care support is essential. Prioritize oxygenation over intubation. For severe bronchospasm use nebulized salbutamol (albuterol) and ipratropium.3
  • Cardiac arrest: follow advanced life support, with IV or IO epinephrine boluses, aggressive fluids, and consider prolonged CPR or extracorporeal CPR.3

Beta-blockers and ACE inhibitors

Both have been linked to more severe anaphylaxis. For most indications, the risk of stopping or switching them may outweigh that risk, so decide with the patient.1 For poor response to epinephrine in a patient on a beta-blocker, consider glucagon.2,3

Sources disagree

Steroids: EM Cases describes them as standard care alongside epinephrine, while noting little evidence that they reduce mortality or prevent biphasic reactions.9 The UK Resuscitation Council no longer advises routine steroids, and cites data linking early steroid use to more ICU admission.3 The 2020 US practice parameter found steroids and antihistamines unreliable for preventing biphasic reactions.6

Observation and biphasic reactions

  • Biphasic anaphylaxis: symptoms return 1–48 hours after complete resolution, with no new exposure to the trigger.1 It occurs in about 5% of patients.3
  • Risk factors: a more severe first reaction, needing more than one epinephrine dose, and epinephrine delayed more than 30–60 minutes.3 Others are wide pulse pressure, unknown trigger and, in children, drug triggers.1
  • In a meta-analysis of 27 observational studies, hypotension at presentation (OR 2.18) and an unknown trigger (OR 1.72) raised the risk, and a food trigger lowered it (OR 0.62). Median onset was 11 hours.7
  • Persistent anaphylaxis means symptoms lasting at least 4 hours.1
FIG 1How long to observe. Minimum observation after symptoms have fully resolved, from the UK Resuscitation Council's risk-stratified approach. The warning band shows when biphasic reactions occur; their median onset was about 11–12 hours in pooled studies.3,7 Drawn for this page.
Sources disagree

How long to watch: the UK Resuscitation Council uses 2, 6 or 12 hours by risk (Figure 1).3 The US practice parameter says a biphasic reaction is unlikely when anaphylaxis was not severe and the patient stays symptom-free for 1 hour.1 In 2,819 ED encounters for allergic reactions or anaphylaxis, clinically important biphasic reactions occurred in 0.18% (0.40% after anaphylaxis), with no deaths.8 EM Cases notes that the traditional 4–6 hours has no supporting literature.9

Discharge

  • Before leaving: consider having the patient eat at least an hour before discharge, and stand them up to check for dizziness.3
  • Warn about biphasic reactions and give clear instructions to return.3
  • Epinephrine autoinjectors: counsel high-risk patients to always carry one (strong recommendation).1 UK guidance advises two devices.3 The US parameter suggests more than one for patients who needed multiple doses or had a biphasic reaction.1
  • Teach the device and when to use it: at the first sign of suspected anaphylaxis, not preemptively without symptoms.1 Serious adverse effects of IM epinephrine are very rare.1
  • Refer to an allergist, and teach trigger avoidance.3,6

Pitfalls

  • Reaching for diphenhydramine or steroids while epinephrine waits.3,4
  • Giving 1 mg/mL epinephrine IV, or any IV bolus outside a monitored specialist setting.3,5
  • Missing anaphylaxis without hives. Hypotension, bronchospasm or laryngeal involvement after a likely allergen is enough.1
  • Mistaking post-epinephrine pallor for ongoing shock and overdosing.3
  • Using a subcutaneous injection, which is less effective than IM.3
  • Discharging without an autoinjector, training, and an allergy referral.1,3

How strong is the evidence?

There are no randomized trials of epinephrine in anaphylaxis. The doses are based on what is safe and practical, and have been used for decades.3 Most US recommendations are consensus-based, with low or very low certainty.1 The case for early IM epinephrine rests on fatality series and observational safety data.4,5 Steroid and observation advice is also very low certainty.3

On-shift teaching

Questions to ask a learner at the bedside. Tap a question to see the answer. Every answer uses facts cited above.

Q1A patient stung by a bee has a BP of 80/50 and no rash. Is this anaphylaxis?
Yes. Under the WAO criteria, acute hypotension after exposure to a known or highly probable allergen is enough, even without skin signs.1,2
Q2What is the adult IM epinephrine dose, where does it go, and when do you repeat it?
0.5 mg (0.5 mL of 1 mg/mL) into the anterolateral mid-thigh. Repeat after 5 minutes if there is no improvement.2,3
Q3Two IM doses haven't helped. What now?
Treat as refractory: get expert help, give fluid boluses, and start a low-dose epinephrine infusion (1 mg in 100 mL saline, starting at 0.5–1.0 mL/kg/h), giving IM doses every 5 minutes until it runs.3
Q4Why is IV bolus epinephrine risky?
In an ED cohort, cardiovascular events followed 10% of IV bolus doses vs 1.3% of IM doses, and all 4 overdoses were IV boluses.5
Q5Do steroids prevent biphasic reactions?
Not reliably. The 2020 US parameter found steroids and antihistamines unreliable for this.6 The UK guideline no longer advises routine steroids.3
Q6Who should you watch longer for a biphasic reaction?
Patients with a severe first reaction, those who needed more than one dose of epinephrine, those treated late (more than 30–60 minutes),3 and those with hypotension or an unknown trigger.7

References

  1. 1
    Golden DBK, Wang J, Waserman S, et al. Anaphylaxis: a 2023 practice parameter update (AAAAI/ACAAI Joint Task Force on Practice Parameters). Ann Allergy Asthma Immunol. 2024;132(2):124–176.GuidelinePMID 38108678aaaai.org (PDF)Full text read (AAAAI site)
  2. 2
    Cardona V, Ansotegui IJ, Ebisawa M, et al. World Allergy Organization anaphylaxis guidance 2020. World Allergy Organ J. 2020;13(10):100472.GuidelinePMID 33204386PMCFull text read (PMC)
  3. 3
    Resuscitation Council UK. Emergency treatment of anaphylaxis: guidelines for healthcare providers, and refractory anaphylaxis algorithm. May 2021.Guidelineresus.org.ukFull text read
  4. 4
    Pumphrey RS. Lessons for management of anaphylaxis from a study of fatal reactions. Clin Exp Allergy. 2000;30(8):1144–1150.RegistryPMID 10931122PubMed
  5. 5
    Campbell RL, Bellolio MF, Knutson BD, et al. Epinephrine in anaphylaxis: higher risk of cardiovascular complications and overdose after administration of intravenous bolus epinephrine compared with intramuscular epinephrine. J Allergy Clin Immunol Pract. 2015;3(1):76–80.CohortPMID 25577622PubMed
  6. 6
    Shaker MS, Wallace DV, Golden DBK, et al. Anaphylaxis: a 2020 practice parameter update, systematic review, and GRADE analysis. J Allergy Clin Immunol. 2020;145(4):1082–1123.GuidelinePMID 32001253PubMed record; full text not openly accessible
  7. 7
    Lee S, Bellolio MF, Hess EP, et al. Time of onset and predictors of biphasic anaphylactic reactions: a systematic review and meta-analysis. J Allergy Clin Immunol Pract. 2015;3(3):408–416.Meta-analysisPMID 25680923PubMed
  8. 8
    Grunau BE, Li J, Yi TW, 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.CohortPMID 24239340PubMed
  9. 9
    Helman A. Episode 78: Anaphylaxis and anaphylactic shock. Emergency Medicine Cases; March 2016.FOAMemergencymedicinecases.comPage read
How this page was made
  • Written from scratch. No source text was copied; facts are restated and cited.
  • The 2023 US practice parameter was read in full from the AAAAI site. It focuses on diagnosis, tryptase, autoinjectors and prevention, so acute ED treatment and doses come from the WAO 2020 guidance (full text in PMC) and the Resuscitation Council UK 2021 guideline and refractory algorithm (full text read). The 2020 US parameter was available only as its PubMed abstract.
  • Study results were checked against their PubMed abstracts. No FDA epinephrine label could be matched by the DailyMed search, so doses come from guideline text only. No glucagon dose is given because none of the guidelines read states one.
  • Adults only. Children need weight- or age-based epinephrine doses; see the cited guidelines.
  • Figure 1 was drawn for this page from the UK guideline's observation tiers. No openly licensed image clearly showing acute allergic skin signs without identifying the patient was found.
  • Not for clinical use until physician review.
Not for clinical use

AI-generated draft. Not reviewed by a physician. This page is for education only and may contain errors, including in doses. Do not use it to diagnose, treat or make decisions about any patient. Rely on your own clinical judgment, your institution's protocols and current drug labeling. Reading this page does not create a physician-patient relationship. Full terms