Anaphylaxis

Anaphylaxis is a systemic allergic or hypersensitivity reaction. Onset is rapid, and it can be fatal. Mast cells and basophils release histamine, tryptase and leukotrienes. Vessels dilate and leak plasma. The bronchi constrict and the mucosa swells.

• Common triggers: foods (peanut, tree nut, shellfish), stinging insects, drugs (β-lactam antibiotics, NSAIDs, neuromuscular blockers, contrast), latex and exercise
• Mechanism: most cases are IgE-mediated. Some triggers hit mast cells directly, with no IgE involved. Treatment is the same for both.
• Biphasic course: a second phase can start after apparent recovery. About half of biphasic reactions occur within the first 6–12 hours after the reaction, per WAO 2020.

The diagnosis is clinical. The 2023 AAAAI/ACAAI practice parameter update revised the diagnostic criteria and defines the reaction patterns. The core picture is skin or mucosal involvement with respiratory or circulatory compromise. Or hypotension and bronchospasm after a known exposure.

Likely Anaphylaxis

• Skin or mucosa plus one more system: generalized hives, pruritus, flushing, or lip, tongue or uvula swelling, together with respiratory compromise, hypotension or persistent severe GI symptoms
• After a known or highly probable allergen: hypotension, bronchospasm or laryngeal involvement, even without typical skin findings
• Timing: minutes to several hours after exposure per WAO 2020

Red Flags

• Stridor, hoarse voice, drooling or inability to swallow (upper-airway involvement)
• Wheeze, falling SpO₂ or a silent chest
• Hypotension: systolic BP under 90 mmHg in adults and children over 10 years, or a systolic fall of more than 30% from the patient's baseline (baseline is often unknown in the field). Children under 10 years: systolic BP under 70 mmHg plus twice the age in years (pediatric vital signs); WAO 2020 criteria
• Syncope or altered mental status

Anaphylaxis is a clinical diagnosis. Treat first. Labs come afterward and support the diagnosis.

• Acute asthma: wheeze without skin, GI or circulatory findings after an exposure
• Angioedema without urticaria or itch: hereditary angioedema or ACE-inhibitor angioedema, both in the WAO 2020 differential. A localized swelling pattern often points here.
• Syncope: vasovagal or cardiac. Bradycardia, pallor and sweating, without respiratory or skin involvement
• Anxiety or panic: no objective hypoxia, hypotension, hives or swelling

1. Remove the trigger when it is safe and quick (stinger, infusion, allergen on skin).
2. Position: supine if circulation is compromised; sitting up if breathing is hard; semi-recumbent on the left side if pregnant; recovery position if unconscious. Never let the patient walk or stand.
3. Epinephrine autoinjector: help the patient use their own device, or the unit's autoinjector, into the anterolateral thigh, through clothing if necessary per the FDA label. Choose the strength by weight: adult or 30 kg or more, 0.3 mg; 15 to 30 kg, 0.15 mg. Do not use the 0.3 mg device in a child under 30 kg unless protocol directs. Under 15 kg, follow protocol and medical direction (see Special Populations).
4. Oxygen at high flow for respiratory distress or any patient who has received epinephrine.
5. Reassess every 5 minutes: airway, breathing, BP, mental status. If the response is incomplete, a second dose is given 5–15 minutes after the last one, per protocol.
6. Call for ALS early and report the allergen, time of exposure, time and dose of each epinephrine injection, and response.

Doses here follow the 2025 AHA Guidelines where they give one, then NASEMSO v3.0 and WAO 2020 for IM epinephrine, and the FDA label for autoinjectors. Local protocol governs scope. IM epinephrine is the first-line drug, so give it as soon as you suspect anaphylaxis. Reassess every 5 minutes. If the response is incomplete, repeat IM epinephrine 5–15 minutes after the last dose.

• IM epinephrine (Paramedic/RN/CCT): adult 0.3–0.5 mg (1 mg/mL, 0.3–0.5 mL) IM, outer mid-thigh, every 5–15 min if refractory (max 0.5 mg/dose). Child under 25 kg: 0.15 mg (0.15 mL of 1 mg/mL) IM, every 5–15 min if refractory (NASEMSO v3.0, Anaphylaxis p. 66). Differs from FDA label: the 0.15 mg autoinjector is labeled for 15–30 kg, and the label advises another injectable form for doses under 0.15 mg. WAO 2020 Table 6 gives 0.01 mg/kg (max 0.5 mg), which is lower for infants under 10 kg. The 0.5 mg teen or adult dose is drawn from a 1 mg/mL vial, because the FDA EpiPen label lists only 0.3 mg and 0.15 mg devices. See Epinephrine IM
• Refractory anaphylaxis (Paramedic/RN/CCT): no response after 2 IM doses and fluids: start a low-dose IV infusion in a monitored patient, about 0.1 mcg/kg/min (0.6 mL/kg/h of a 10 mcg/mL infusion), and titrate to response. This low-dose rate is institution-specific practice, not in AHA 2025 or WAO 2020 (WAO names the Brown protocol but gives no rate). NASEMSO v3.0 (p. 67) gives 0.5 mcg/kg/min when collapse persists after repeated IM doses and at least 60 mL/kg of fluid, a higher starting point. Keep giving IM doses every 5 min until the infusion is running. Check mcg/kg/min against mcg/min on the pump. See Epinephrine IV
• IV epinephrine bolus: not recommended for initial treatment. The risk is fatal arrhythmia, per WAO 2020. Use it only as a specialist, protocol-directed push dose.
• Cardiac arrest from anaphylaxis (Paramedic/RN/CCT): start CPR and follow the standard ACLS or PALS arrest algorithm: epinephrine 1 mg IV/IO every 3–5 min in adults, or 0.01 mg/kg IV/IO (0.1 mg/mL arrest syringe; max 1 mg per dose) in children (2025 AHA ACLS and PALS cardiac arrest algorithms). For fluid resuscitation, isotonic IV fluids are reasonable (2025 AHA Guidelines for CPR and ECC, Part 10, COR 2a, LOE C-EO). The effectiveness of the standard IM epinephrine dose in arrest from anaphylaxis is uncertain and may be insufficient (2025 AHA Guidelines for CPR and ECC, Part 10, COR 2b, LOE C-EO). See Epinephrine IV
• No absolute contraindication: WAO 2020 finds no absolute contraindication to epinephrine for anaphylaxis. Don't withhold it because of age or heart disease. Monitor the rhythm and BP instead (see Special Populations).
• Crystalloid bolus: 20 mL/kg IV or IO for cardiovascular instability. WAO 2020 gives this figure for adults and children. Reassess after each bolus for response and for signs of fluid overload (lung sounds, SpO₂, work of breathing). Rate and any further volume per protocol.
• IV or IO access: two large-bore IVs if possible. IO access if IV fails (IO access)
• Bronchodilator: inhaled albuterol for residual wheeze. Albuterol does not replace IM epinephrine, per WAO 2020. See Albuterol
• Airway (Paramedic/RN/CCT): get an early advanced airway for stridor, drooling or rising airway obstruction (intubation, supraglottic airway). Don't delay for drugs.
• Adjuncts: antihistamines relieve hives and itch. They do not treat the airway or circulation. Glucocorticoids have no proven benefit in the acute phase, and they are not a substitute for epinephrine, per WAO 2020. See Diphenhydramine and Methylprednisolone
• Monitoring: continuous ECG, BP every 5 min and after each dose, SpO₂, EtCO₂ when airway is secured

• Refractory anaphylaxis: keep giving IM epinephrine and the low-dose IV infusion. Titrate to the lowest effective rate. Adjust by BP, heart rate and perfusion. If hypotension persists on the infusion, add a second vasopressor per protocol (for example norepinephrine or vasopressin). In cardiac arrest from anaphylaxis refractory to drugs, extracorporeal CPR is reasonable (2025 AHA Guidelines for CPR and ECC, Part 10, COR 2a, LOE C-EO), where available.
• Beta-blocker exposure with refractory anaphylaxis: glucagon IV may be considered for refractory anaphylaxis with β-blocker exposure (limited evidence). The 2025 AHA Guidelines for CPR and ECC, Part 10 gives 1–5 mg IV in adults and 20–30 mcg/kg IV push, up to 1 mg, in children (supportive text). The same part rates glucagon in cardiac arrest from anaphylaxis with suspected β-blocker use as COR 2b, LOE C-EO. Glucagon is off-label for anaphylaxis. It often causes vomiting, so watch for it, position for airway protection and keep suction ready. See the Glucagon page
• Airway: anticipate loss of the airway. Prepare a surgical airway for progressive upper-airway obstruction, per the airway team (cricothyrotomy)
• Perioperative or drug-induced anaphylaxis: stop the suspected drug or agent, call anesthesia, and treat with the same algorithm. Per WAO 2020, the triggers include neuromuscular blockers, contrast and other perioperative drugs
• Discharge and prevention: before release, prescribe one or more epinephrine autoinjectors with training on use, give a written personalized anaphylaxis action plan and a medical identification method, refer to allergy or immunology to confirm the trigger, and advise trigger avoidance, per WAO 2020 and the AAAAI 2023 update
• Consults and workup: serum tryptase per lab protocol, allergy or immunology follow-up, and monitoring for biphasic reactions
• Disposition: observe severe reactions and any patient needing more than one epinephrine dose. WAO 2020 guidance says there is no consensus on how long observation should last

• EMS: transport any patient who has received epinephrine. AAAAI 2023 notes that EMS activation may not be needed after a prompt, complete and durable response to epinephrine. Release and observation rules are set by local protocol and medical direction.
• Transport: continue monitoring, keep IM and IV epinephrine doses and times on the handoff, and carry a second autoinjector and an infusion pump. Pack a rescue plan for stridor (airway kit, suction, BVM, surgical airway tools).
• ED/ICU handoff: include the allergen, total epinephrine (mg and mL) with times, any infusion rate and concentration, fluids given, and the response.

• Pediatrics: IM epinephrine 0.15 mg for children under 25 kg, repeated every 5–15 min if refractory (NASEMSO v3.0, Anaphylaxis p. 66). The dose is fixed, not weight-based. Differs from FDA label: the autoinjector is labeled for 15–30 kg (0.15 mg) and 30 kg or more (0.3 mg), and the label advises another injectable form for doses under 0.15 mg. Under 15 kg, draw up 0.15 mg from a 1 mg/mL vial rather than using an autoinjector. WAO 2020 Table 6 gives 0.01 mg/kg (max 0.5 mg), which is lower for infants under 10 kg, and 0.3 mg for ages 6–12 years. Infants and toddlers can present with age-specific symptoms. Per AAAAI 2023, anaphylaxis is unlikely to be the first reaction to a new allergen. Use weight-based dosing and pediatric vital signs.
• Pregnancy: give epinephrine as you would for any adult. WAO 2020 finds no absolute contraindication to IM epinephrine. Place the patient semi-recumbent on the left side. Notify obstetrics early.
• Older Adults: IM epinephrine is generally well tolerated. The bigger risk is arrhythmia and ischemia, with IV bolus doses. The FDA label notes that older patients may be particularly sensitive to epinephrine. Start infusions at the low end of the range and monitor on a cardiac monitor.
• Heart Disease: give epinephrine when it is indicated. The FDA label advises caution in heart disease because of arrhythmia risk. WAO 2020 finds no absolute contraindication. Monitor the rhythm and BP.
• Patients on Beta-Blockers: anaphylaxis may be more severe and less responsive in these patients. Glucagon may be considered for refractory cases (limited evidence): 1–5 mg IV in adults and 20–30 mcg/kg IV, up to 1 mg, in children (2025 AHA Guidelines for CPR and ECC, Part 10, supportive text). See ED & ICU Management. For most indications, stopping a beta-blocker or ACE inhibitor to lower anaphylaxis risk may do more harm than continuing it, per AAAAI 2023.
• Renal Impairment and Hepatic Impairment: no specific adjustment is established for IM epinephrine. Titrate infusions to perfusion and monitor for arrhythmia.

• Error: mixing up concentrations. IM and autoinjector use 1 mg/mL (1:1,000). IV infusion uses a diluted, institution-specified concentration, for example about 10 mcg/mL (1 mg in 100 mL). The 0.1 mg/mL (100 mcg/mL) arrest syringe is not an infusion concentration. Never push undiluted 1 mg/mL IV. Check mcg/min against mcg/kg/min on the pump. IV epinephrine is a high-alert medication. Confirm concentration, mg and mL on every dose.
• Error: antihistamines or steroids first, or instead of epinephrine. Epinephrine is the only first-line drug. Epinephrine first, then everything else.
• Error: an inhaled bronchodilator for wheeze as the primary treatment. It does not treat the systemic reaction, per WAO 2020.
• Error: an IV epinephrine bolus for a non-arrest patient. That risks fatal arrhythmia. Use the IM route first.
• Error: stopping at one dose when the response is incomplete. Reassess at 5 minutes, and repeat IM epinephrine if the response is incomplete. An infusion comes only after 2 IM doses and fluids have failed.
• Error: discharging or releasing after one good response, with no observation or biphasic plan, per WAO 2020.
• Error: missing an airway threat. Stridor and voice change are signs of progressive obstruction. Prepare for airway management early.