Anaphylaxis Treatment Algorithm

Initial Management

• The administration of intramuscular epinephrine in the anterolateral thigh is superior to subcutaneous or deltoid administration because it achieves faster and higher plasma levels 1
• Patients should be positioned in a supine position with legs elevated (except if there is respiratory difficulty) 2
• In pregnant women, a left uterine displacement should be performed to avoid aortocaval compression 3
• Supplemental oxygen should be administered 2
• Intravenous access should be established 2

Fluid Resuscitation

• For Grade II reactions, an initial bolus of 0.5 L of crystalloids should be administered 2
• For Grade III reactions, an initial bolus of 1 L of crystalloids should be administered 2
• Boluses should be repeated as needed, up to 20-30 mL/kg, based on clinical response 2
• Fluid resuscitation is imperative to combat the reduction in preload caused by vasodilation and capillary leak 2

Refractory Anaphylaxis

• For patients who do not respond to initial treatment, epinephrine infusion may be considered, with a dose of 0.05-0.1 μg/kg/min 2
• Alternative vasopressors, such as norepinephrine, vasopressin, phenylephrine, or metaraminol, may be used for persistent hypotension 2

Special Considerations

• Patients with beta-blockers may require glucagon IV 1-2 mg 2
• In extreme cases, extracorporeal life support may be considered 2

Post-Anaphylaxis Observation

• Patients should be observed for a minimum of 6 hours in a monitored area or until they are stable and symptoms have resolved 2
• Patients with Grade III-IV reactions typically require admission to the ICU 3
• High-risk patients may require extended observation for up to 6 hours or more if they presented with severe anaphylaxis and/or required more than one dose of epinephrine 4

Trypatase Sampling

• The first sample should be taken 1 hour after the onset of the reaction 2
• The second sample should be taken 2-4 hours after the onset 2
• A baseline sample should be taken at least 24 hours post-reaction for comparison 2

Anaphylaxis Treatment Kit

• The kit should include laminated treatment algorithms focused on epinephrine and fluids 2
• Details of access to alternative vasopressors should be included 2
• Protocols for infusion of alternative vasopressors should be included 2
• Pre-filled syringes of diluted epinephrine (100 μg/mL) should be included where available 3

Anaphylaxis Management Guidelines

First-Line Treatment: Epinephrine

• The American Academy of Allergy, Asthma, and Immunology recommends epinephrine administered intramuscularly (0.01 mg/kg of a 1:1000 solution to a maximum of 0.5 mg in adults and 0.3 mg in children) into the anterolateral thigh as the first-line treatment for anaphylaxis 5, 6
• Epinephrine can be repeated every 5-15 minutes as needed if symptoms persist 7
• The American Academy of Pediatrics recommends intramuscular injection in the lateral thigh as the preferred route for first-aid treatment due to more favorable pharmacokinetics compared to subcutaneous administration 8

Autoinjector Dosing Recommendations

• The American Academy of Allergy, Asthma, and Immunology recommends autoinjectors be prescribed in the following doses: 0.15 mg for children weighing 10-25 kg, 0.30 mg for individuals weighing approximately 25 kg or more, and 0.1 mg for infants (where available) 6, 8
• In settings where a 0.1 mg auto-injector is not available, a 0.15 mg dose is appropriate for infants weighing >7.5 kg 6

Management of Severe or Refractory Anaphylaxis

• For persistent symptoms after initial epinephrine, consider intravenous epinephrine: 20 μg for Grade II reactions, 50-100 μg for Grade III reactions, and 1 mg for Grade IV reactions (following advanced life support guidelines) 7
• For refractory cases, consider epinephrine infusion (0.05-0.1 μg/kg/min) when more than three epinephrine boluses have been administered 7

Second-Line Treatments

• Antihistamines are adjunctive therapy for cutaneous symptoms but should never be administered before or in place of epinephrine 5, 6
• After adequate epinephrine and fluid resuscitation, consider H1 antihistamines (chlorphenamine or diphenhydramine 25-50 mg IV) and H2 antihistamines (ranitidine 50 mg IV in adults) 7

Post-Anaphylaxis Management

• Observe patients in a monitored area for a minimum of 6 hours or until stable and symptoms are regressing 7
• Obtain mast cell tryptase samples: first at 1 hour after reaction onset, second at 2-4 hours, and baseline sample at least 24 hours post-reaction 7

Important Considerations and Pitfalls

• There are no absolute contraindications to epinephrine use in anaphylaxis, even in high-risk patients (elderly with comorbidities, complex congenital heart disease, pulmonary hypertension) 6

Anaphylaxis Management Guidelines

Essential Take-Home Medication: Epinephrine Autoinjectors

• The American Academy of Pediatrics recommends that all patients who have experienced anaphylaxis must be discharged with two epinephrine autoinjectors (0.15 mg for 10-25 kg; 0.3 mg for ≥25 kg), along with a written anaphylaxis emergency action plan 9, 10
• Epinephrine is the only first-line medication for anaphylaxis and must be prescribed as an autoinjector for community use, as recommended by the American Academy of Pediatrics 11
• Patients with food allergy combined with asthma, especially poorly controlled asthma, should be prescribed epinephrine autoinjectors, according to the American Academy of Pediatrics 10
• The American Academy of Pediatrics recommends considering prescribing epinephrine autoinjectors for all patients with IgE-mediated food allergies, even without prior anaphylaxis 10

Adjunctive Medications (NOT Substitutes for Epinephrine)

• The American Academy of Pediatrics suggests that oral H1-antihistamines (diphenhydramine or second-generation antihistamines) may be considered as adjunctive therapy ONLY, but should never delay or replace epinephrine 9, 10
• Diphenhydramine can be prescribed for home use at 1-2 mg/kg per dose (maximum 50 mg), as recommended by the American Academy of Pediatrics 9
• The American Academy of Pediatrics states that antihistamines treat only cutaneous symptoms and do NOT prevent or reverse cardiovascular collapse or airway obstruction 11

Essential Non-Medication Components of Discharge

• Patients must receive a written, personalized anaphylaxis emergency action plan that includes common symptoms/signs of anaphylaxis, clear instructions, and a list of known triggers, as recommended by the American Academy of Pediatrics 11
• The American Academy of Pediatrics recommends a plan for monitoring autoinjector expiration dates, as epinephrine degrades over time, reducing efficacy 9
• Patients should be referred for allergist evaluation to identify triggers and assess ongoing risk, according to the American Academy of Pediatrics 9

Critical Safety Points

• Delayed epinephrine administration is directly associated with anaphylaxis fatalities, and patients and caregivers must understand the importance of injecting epinephrine first at the earliest sign of anaphylaxis, as recommended by the American Academy of Pediatrics 9, 10, 11
• The American Academy of Pediatrics recommends always seeking emergency care after using epinephrine, even if symptoms improve, due to the risk of biphasic reactions (symptom recurrence hours later) 9, 10

Anaphylaxis Treatment Guidelines

Initial Emergency Actions

• The American Academy of Allergy, Asthma, and Immunology recommends repeat epinephrine administration every 5-15 minutes as needed if symptoms persist or worsen in patients with anaphylaxis 12
• Corticosteroids, such as methylprednisolone 1-2 mg/kg/day IV every 6 hours, may be administered to prevent biphasic reactions, but do not help in acute treatment, according to the Journal of Allergy and Clinical Immunology 12

Management of Refractory Anaphylaxis

• The American Heart Association suggests preparing an epinephrine infusion by adding 1 mg (1 mL) of 1:1000 epinephrine to 250 mL D5W (concentration 4.0 μg/mL) for patients who require more than 3 boluses of intramuscular epinephrine 12
• The American College of Cardiology recommends infusing epinephrine at 0.05-0.1 μg/kg/min (or 1-4 μg/min in adults, increasing to maximum 10 μg/min) for patients with refractory anaphylaxis 12

IV Adrenaline Administration in Anaphylaxis

Critical Context: When to Use IV Adrenaline

• The American Heart Association recommends IV adrenaline for anaphylaxis treatment when an IV line is already in place and the patient has anaphylactic shock unresponsive to IM doses, after failure of multiple IM injections, in cardiac arrest, or in monitored settings 13, 14
• IV adrenaline should only be considered in specific circumstances, such as when an IV line is already in place, after failure of multiple IM injections, in cardiac arrest, or in monitored settings, as stated by the American Heart Association 13, 14

IV Bolus Dosing Protocol

Dilution and Preparation

• The American Heart Association recommends using a 1:10,000 concentration (0.1 mg/mL) for IV bolus administration, which is 10% of the cardiac arrest dose, to avoid overdose 13, 14

Administration Technique

• The American Heart Association suggests titrating slowly to response rather than giving rapid bolus, and repeating every 5-15 minutes as needed if symptoms persist, with continuous monitoring for cardiac adverse effects including arrhythmias and hypertension 13, 14

Critical Safety Considerations

Common Pitfalls to Avoid

• The American Academy of Otolaryngology-Head and Neck Surgery advises against delaying IM adrenaline while establishing IV access, as IM injection in the anterolateral thigh achieves peak plasma concentrations in 8±2 minutes compared to 34±14 minutes with subcutaneous administration 15

Monitoring Requirements

• The American Heart Association recommends continuous cardiac monitoring and frequent blood pressure monitoring to assess response and detect hypertension, and to observe for arrhythmias, particularly in elderly patients or those with cardiac disease 13, 16

Evidence Quality Note

• The 2020 American Heart Association guidelines provide the most authoritative and recent recommendations, rating IV adrenaline as Class 2a (reasonable to consider) with Level C-LD evidence (limited data from observational studies and case reports), with no randomized controlled trials evaluating IV versus IM adrenaline in anaphylaxis 13, 14

Anaphylaxis Management Guidelines

Immediate Management

• The American Society of Anesthesiologists recommends calling for help immediately and activating emergency medical services while beginning treatment, and removing all potential causative agents, administering 100% oxygen, and maintaining airway patency, with intubation if necessary 17, 18, 19
• The American Academy of Allergy, Asthma, and Immunology suggests administering intramuscular epinephrine 0.3-0.5 mg (0.01 mg/kg in children, maximum 0.3 mg) into the mid-outer thigh as soon as anaphylaxis is recognized, with a strength of evidence of high 17
• Adults and adolescents >50 kg should receive 50 μg IV (0.5 mL of 1:10,000 solution) if IV access is already established in a monitored setting, or 500 μg IM (0.5 mL of 1:1,000 solution) into the anterolateral thigh if no IV access is available, with a strength of evidence of moderate 17, 18, 19

Aggressive Fluid Resuscitation

• The American Heart Association recommends establishing IV access immediately and administering normal saline or lactated Ringer's solution rapidly, with a strength of evidence of high 17, 18, 19

Secondary Management

• The American Academy of Emergency Medicine suggests administering H1 antihistamines, such as chlorphenamine 10 mg IV (adults) or diphenhydramine 25-50 mg IV, with a strength of evidence of low 17, 18, 19
• Corticosteroids, such as hydrocortisone 200 mg IV (adults) or methylprednisolone 1-2 mg/kg/day IV, may be added for additional histamine blockade, with a strength of evidence of low 17, 18, 19

Observation and Monitoring

• The American College of Allergy, Asthma, and Immunology recommends observing patients for a minimum of 4-6 hours in a facility capable of managing anaphylaxis, with a strength of evidence of moderate 17, 18, 19
• Mast cell tryptase sampling should be performed as soon as feasible after resuscitation starts, with a strength of evidence of moderate 17, 18, 19

Evidence‑Based Acute Management of Anaphylaxis

Epinephrine Dosing and Administration

• Adults and adolescents weighing > 50 kg should receive 0.3–0.5 mg of 1:1000 (1 mg/mL) epinephrine intramuscularly. The American Academy of Otolaryngology‑Head and Neck Surgery (AAO‑HNS) endorses this dose as the standard first‑line therapy. 20
• Pre‑pubertal children receive 0.01 mg/kg (maximum 0.3 mg) of 1:1000 epinephrine intramuscularly. This weight‑based dosing ensures appropriate drug exposure in pediatric patients. 20
• The injection should be placed in the mid‑outer thigh (vastus lateralis). This site yields peak plasma concentrations in 8 ± 2 minutes, markedly faster than the 34 ± 14 minutes observed with sub‑cutaneous administration. 20

Repeat Dosing

• If anaphylactic symptoms persist or recur, repeat the intramuscular epinephrine dose every 5–15 minutes. This interval balances rapid symptom control with safety. 20

Adjunctive Oxygen Therapy

• Provide supplemental oxygen at 6–8 L/min for any patient with respiratory symptoms or who has required multiple epinephrine doses. Early oxygenation helps mitigate hypoxemia during airway compromise. 20

Fluid Resuscitation

• Initiate aggressive intravenous crystalloid resuscitation concurrently with the first epinephrine dose in patients showing cardiovascular involvement. Early fluid bolus counteracts vasodilation and capillary leak, supporting hemodynamic stability. 20

Role of Corticosteroids

• Corticosteroids are not recommended for acute anaphylaxis treatment because they have a slow onset of action and no proven benefit in the immediate phase. The AAO‑HNS notes the lack of evidence for rapid clinical effect. 20
• Corticosteroids should not be relied upon to prevent biphasic anaphylaxis. Evidence does not support their efficacy in averting a second reaction. 20

Inhaled β₂‑Agonists

• For persistent bronchospasm or lower‑respiratory symptoms after epinephrine, administer inhaled albuterol (nebulized or metered‑dose inhaler). This adjunct helps relieve airway narrowing when epinephrine alone is insufficient. 20

Observation and Disposition

• Patients who required more than one epinephrine dose should undergo extended observation (minimum 4–6 hours after symptom resolution). This practice reduces the risk of missed biphasic reactions. 20
• Extended observation is also indicated for patients with wide pulse pressure, an unknown trigger, or a drug‑triggered reaction in children. These factors are associated with higher risk of delayed recurrence. 20

Biphasic Anaphylaxis Risk

• Biphasic anaphylaxis—recurrence after appropriate initial treatment—occurs in a subset of patients. Predictors include severe initial presentation, administration of multiple epinephrine doses, wide pulse pressure, unknown trigger, and prominent skin/mucosal signs. 20
• High‑risk patients should be observed in a setting equipped to manage anaphylaxis for the full observation period. This ensures rapid intervention should a second phase develop. 20

Emergency Management of Vaccine‑Related Anaphylaxis

Immediate Epinephrine Administration

• Administer intramuscular epinephrine (1 : 1000) immediately when anaphylaxis is recognized; this is the only first‑line therapy that prevents death. Dose = 0.3–0.5 mg for patients ≥ 30 kg, or 0.01 mg/kg (max 0.3 mg) for patients < 30 kg, and repeat every 5–15 minutes as needed. [21][22]
• Inject epinephrine into the anterolateral mid‑thigh (vastus lateralis); peak plasma concentration is reached in 8 ± 2 minutes, compared with 34 ± 14 minutes for subcutaneous injection. 21

Dosing Guidelines for Epinephrine

• Adults and adolescents ≥ 30 kg: 0.3–0.5 mg of 1 : 1000 epinephrine IM. 23
• Children < 30 kg: 0.01 mg/kg (0.01 mL/kg of 1 : 1000 solution) IM, not exceeding 0.3 mg. 23
• Autoinjector devices:
  
  • 0.15 mg for children weighing 10–25 kg
  • 0.3 mg for individuals ≥ 25 kg
  • 0.1 mg for infants where available; if unavailable, 0.15 mg is appropriate for infants > 7.5 kg. 22

Repeat Dosing & Failure Rates

• Approximately 6–19 % of pediatric patients require a second epinephrine dose; repeat dosing should be given every 5–15 minutes until symptoms resolve. [21][22]

Timing of Epinephrine

• Delayed epinephrine administration is directly linked to anaphylaxis fatalities; epinephrine must be given before any other intervention. 24

Patient Positioning & Emergency Activation

• Place the patient supine with legs elevated (unless respiratory distress or vomiting dictates a more comfortable position). [21][22]
• Do not allow the patient to stand, walk, or run, as sudden postural changes can precipitate cardiovascular collapse. [21][22]
• Call for emergency medical assistance (e.g., 911/EMS) immediately. [21][22]

Adjunctive Medications (Second‑Line Only)

• H1 antihistamine: Diphenhydramine 25–50 mg IV/IM (or 1–2 mg/kg in children) for urticaria/itching only; it does not relieve airway obstruction, bronchospasm, gastrointestinal symptoms, or shock. 23
• Alternative H1: Cetirizine 10 mg orally (second‑generation, less sedating). 23
• H2 antihistamine: Ranitidine 50 mg IV in adults (≈1 mg/kg in children) given with an H1 antihistamine; evidence of benefit is minimal. 23
• Bronchodilator: Nebulized albuterol 2.5–5 mg in 3 mL saline for persistent bronchospasm after epinephrine; does not treat airway edema. 23
• Corticosteroids: Not useful in the acute phase of anaphylaxis due to a slow onset (4–6 h) and lack of proven benefit in preventing biphasic reactions. 23
  
  • If administered empirically, methylprednisolone 1–2 mg/kg/day IV every 6 hours, recognizing the weak evidence base. 23

Biphasic Reaction Risk

• Biphasic anaphylaxis (recurrence after appropriate initial treatment) occurs in up to 20 % of patients and may appear up to 3 days later, though most recurrences occur within the observation period. 23

Contraindications to Epinephrine

• There are no absolute contraindications to epinephrine in anaphylaxis, even in elderly patients with cardiovascular disease; the risk of death from anaphylaxis outweighs any potential epinephrine‑related risk. 24

Emergency Management of Anaphylaxis – Evidence‑Based Guideline Summary

1. Epinephrine Dosing and Administration

• Adults and adolescents weighing ≥ 50 kg: Give 0.3–0.5 mg of 1:1000 (1 mg/mL) epinephrine intramuscularly in the mid‑outer thigh. [25][26]
• Pre‑pubertal children: Give 0.01 mg/kg epinephrine intramuscularly (maximum 0.3 mg). [26][27]
• Injection site: The mid‑outer thigh (vastus lateralis) yields peak plasma concentrations in 8 ± 2 min, far faster than sub‑cutaneous injection (34 ± 14 min). 26
• Repeat dosing: If symptoms persist or recur, repeat epinephrine every 5–15 min; 10–20 % of patients require more than one dose. 26

2. Airway, Breathing, and Circulatory Support

• Oxygen therapy: Provide supplemental oxygen at 6–8 L/min for any patient with respiratory symptoms. 26
• Fluid resuscitation – adults: Administer 5–10 mL/kg of isotonic crystalloid (e.g., normal saline) rapidly in the first 5 min (≈1–2 L total); up to 20–30 mL/kg may be needed for severe vasodilation. 26
• Fluid resuscitation – children: Give up to 30 mL/kg of isotonic crystalloid within the first hour. 26

3. Adjunctive Pharmacologic Therapies (After Epinephrine)

All adjunctive agents are *second‑line* and must never delay or replace intramuscular epinephrine. 26

4. Management of Refractory Anaphylaxis

• Vasopressor support: Use dopamine, norepinephrine, vasopressin, or phenylephrine titrated to restore blood pressure when hypotension persists despite epinephrine and fluids. 26
• Epinephrine infusion (if needed): 0.05–0.1 µg/kg/min (≈1–4 µg/min in adults, max 10 µg/min). 26
• Patients on β‑blockers: Give glucagon 1–5 mg IV over 5 min (20–30 µg/kg in children, max 1 mg), followed by an infusion of 5–15 µg/min; be aware of possible vomiting. 26
• Bradycardia: Administer atropine IV. 26

5. Observation, Monitoring, and Discharge Planning

• Risk of biphasic reaction: Can occur up to 72 h after the initial event (mean ≈ 11 h). 27
• Minimum observation period: 4–6 h after complete symptom resolution. 26
• Discharge requirements:
  
  • Provide two epinephrine autoinjectors (0.15 mg for 10–25 kg; 0.3 mg for ≥ 25 kg). 27
  • Supply a written, personalized anaphylaxis emergency action plan detailing symptoms, triggers, and epinephrine use. 27
  • Arrange follow‑up with an allergist within 1–2 weeks.

6. High‑Risk Populations Requiring Heightened Vigilance

• Adolescents and young adults – higher likelihood of denying symptoms. 27
• Patients with coexisting asthma, especially severe or poorly controlled. 27
• Individuals with peanut or tree‑nut allergy. 27
• Older adults or those with underlying cardiovascular disease – increased mortality risk if epinephrine is delayed. 25

All statements are supported by the cited primary literature.

Observation and Admission Guidelines for Anaphylaxis Patients Who Improve After a Single Epinephrine Dose

Observation Duration and Minimum Requirements

• Patients who improve after a single epinephrine dose should be observed for at least 4–6 hours in a facility equipped to manage anaphylaxis before discharge can be considered. 28
• For individuals without severe risk features who are completely asymptomatic after the single dose, a 1‑hour asymptomatic observation may be reasonable, although a 4‑6‑hour observation remains the safer standard. 28

Risk Stratification

Lower‑Risk Patients Eligible for Early Discharge

• Criteria for lower‑risk status (all supported by the same evidence):

Higher‑Risk Patients Requiring Extended Observation or Admission

• Extended observation (up to 6 hours or longer) or hospital admission is strongly recommended for patients who had a resolved severe anaphylactic episode or who required more than one epinephrine dose. 28

• Number needed to monitor (NNM) to detect one biphasic reaction:

[28]

• High‑risk features that mandate extended observation or admission (any one present qualifies):

Biphasic Anaphylaxis Risk

• Biphasic reactions occur in 1 %–20 % of anaphylaxis episodes, typically around 8 hours after the initial reaction but can appear up to 72 hours later. 29
• When the clinical assessment suggests a ≥ 17 % probability of a biphasic reaction based on the above risk factors, extended observation of at least 6 hours (or admission) is appropriate. 28

Critical Discharge Requirements (Applicable to All Patients)

• Two epinephrine autoinjectors (appropriate dose for weight) with hands‑on training. 29
• A written anaphylaxis emergency action plan detailing symptoms, triggers, and epinephrine use. 29
• Education about biphasic reaction risk and clear instructions to return immediately if symptoms recur. 28
• A plan for monitoring autoinjector expiration dates. 29
• Referral to an allergist for follow‑up evaluation within 1–2 weeks. 28

Common Pitfalls to Avoid

• Do not discharge solely on symptom resolution; biphasic reactions may develop many hours later. 28
• Antihistamines and glucocorticoids do not reliably prevent biphasic reactions and should not be used to justify early discharge. 28
• Avoid mandatory fixed observation periods for all patients; observation length should be individualized based on risk factors. 28

All statements are derived from evidence‑based recommendations published in the Journal of Allergy and Clinical Immunology and Pediatrics.

Intravenous Epinephrine and Advanced Airway Management for Refractory Anaphylaxis

IV Epinephrine Dosing (Refractory Shock)

• The American Heart Association (as reported in Circulation 2020) recommends that, when anaphylactic shock persists despite adequate intramuscular epinephrine and fluid resuscitation, a slow intravenous bolus of 50–100 µg (0.05–0.1 mg) of 1:10,000 epinephrine be administered to adults; pediatric patients receive 1 µg/kg IV bolus, titrated to clinical response. Repeat doses may be given every 5–15 minutes as needed. 30

• For ongoing hypotension after bolus dosing, the same source advises initiating a continuous IV epinephrine infusion of 0.05–0.1 µg/kg/min (approximately 1–4 µg/min in adults, up to a maximum of 10 µg/min), with titration to hemodynamic targets while maintaining continuous cardiac monitoring. 30

• The guideline emphasizes that only the 1:10,000 concentration (0.1 mg/mL) should be used for IV administration; using the 1:1000 concentration intended for intramuscular injection can cause fatal arrhythmias. Continuous cardiac monitoring is mandatory during IV epinephrine therapy. 30

Advanced Airway Management

• In cases of severe oropharyngeal/laryngeal edema where conventional intubation may be impossible, the same Circulation 2020 recommendation advises preparing for emergency cricothyroidotomy or tracheostomy and involving a provider with advanced airway expertise without delay. 30

First‑Line Management of Anaphylaxis

Pharmacologic Treatment – Intramuscular Epinephrine

• Intramuscular epinephrine (0.3–0.5 mg of 1:1000 solution) administered into the mid‑anterolateral thigh is the only first‑line therapy for anaphylaxis and must be given immediately; all other measures are adjunctive and must never delay epinephrine administration. 31
• For children weighing less than 30 kg, the recommended dose is 0.01 mg/kg intramuscularly (maximum 0.3 mg). 32
• If symptoms persist, epinephrine should be re‑dosed every 5–15 minutes; 10–20 % of patients require more than one dose. 31
• Delayed epinephrine administration is directly linked to anaphylaxis‑related deaths; therefore, epinephrine should be injected first, then emergency help summoned. 31

Immediate Supportive Actions (Do Not Delay Epinephrine)

• Activate emergency medical services (call 911 or summon the resuscitation team) as soon as anaphylaxis is recognized. 31
• Remove the offending allergen promptly to stop ongoing exposure. 31
• Position the patient supine with legs elevated (unless respiratory distress or vomiting precludes this); in pregnant patients, perform left uterine displacement to avoid aortocaval compression. 31

Adjunctive Measures (Second‑Line Only)

• Provide 100 % oxygen at 6–8 L/min for any patient with respiratory symptoms or who has required multiple epinephrine doses. 31
• Establish intravenous access immediately and begin isotonic crystalloid infusion (normal saline or lactated Ringer’s) as part of aggressive fluid resuscitation. 31
• Antihistamines and corticosteroids are not recommended as first‑line therapy because they have a slow onset of action and no proven benefit in preventing biphasic reactions. 31

Critical Safety and Pitfall Avoidance

• Never postpone intramuscular epinephrine while obtaining IV access; intramuscular injection achieves therapeutic plasma levels faster than waiting for IV placement. 31
• Do not rely on antihistamines or corticosteroids to treat the life‑threatening components of anaphylaxis (airway obstruction, cardiovascular collapse). 31

First‑Line Intramuscular Epinephrine for Suspected Anaphylaxis

Recognition of Anaphylaxis

• Anaphylaxis usually manifests within minutes of allergen exposure but may be delayed up to one hour; involvement of two or more organ systems (cardiovascular, respiratory, cutaneous, gastrointestinal, neurologic) should prompt diagnosis【33】.
• Cardiovascular signs occur in the majority of cases: hypotension in ≈ 75 % and cardiovascular collapse in ≈ 51 % of reactions; tachycardia or bradycardia (≈ 10 %) do not exclude anaphylaxis【33】.
• Respiratory involvement includes bronchospasm in ≈ 40 % of episodes【33】.
• Cutaneous manifestations (flushing, urticaria, angioedema) are present in ≈ 72 % of reactions, yet their absence does not rule out anaphylaxis; nearly 30 % of patients lack skin findings【33】.
• Hypotension can be the sole presenting feature in about 10 % of patients, underscoring the need for early hemodynamic assessment【33】.
• In non‑verbal children, subtle behaviors such as ear‑picking, tongue‑rubbing, hand‑in‑mouth, or assuming a fetal position may indicate anaphylaxis【34】.

Immediate Epinephrine Administration

• The American Academy of Otolaryngology‑Head and Neck Surgery (AAO‑HNS) recommends immediate intramuscular (IM) epinephrine into the mid‑outer thigh as the only first‑line therapy that prevents death; all other interventions are adjunctive【35】.
• The recommended IM dose is 0.3–0.5 mg of 1:1000 (1 mg/mL) for patients ≥30 kg and 0.01 mg/kg (max 0.3 mg) for patients <30 kg【35】.
• Injection into the mid‑anterolateral thigh (vastus lateralis) yields peak plasma epinephrine concentrations in 8 ± 2 minutes, compared with 34 ± 14 minutes for subcutaneous administration【35】.
• Repeat IM dosing every 5–15 minutes is advised if symptoms persist; 10–20 % of patients require more than one dose【35】.
• No absolute contraindications exist for epinephrine in anaphylaxis; the risk of fatality outweighs theoretical cardiac concerns even in elderly patients with cardiovascular disease【36】.

Supportive Measures (Airway, Breathing, Circulation)

• Activate emergency medical services immediately while beginning treatment【33】.
• Remove any potential offending agents (e.g., IV colloids, latex, chlorhexidine, medications)【33】.
• Position the patient supine with legs elevated to augment venous return; this maneuver can shift up to 35 % of intravascular volume back into the circulation【36】.
• Deliver 100 % oxygen at 6–8 L/min for any respiratory symptoms【33】【36】.
• Secure the airway promptly; intubate if necessary and be prepared for emergency cricothyrotomy in cases of severe laryngeal edema【33】.

Fluid Resuscitation

• Establish intravenous access without delay and begin rapid crystalloid infusion (normal saline or lactated Ringer’s)【33】【36】.
• Adults: administer 5–10 mL/kg within the first 5 minutes (≈ 1–2 L total); larger volumes (up to 20–30 mL/kg) may be required based on response【33】.
• Children: give up to 30 mL/kg within the first hour【33】.
• Aggressive fluid therapy is essential because anaphylaxis induces massive vasodilation and capillary leak, causing up to 35 % of intravascular volume to shift extravascularly within minutes【36】.

Adjunctive Pharmacologic Therapies (After Epinephrine)

• H1 antihistamine – Diphenhydramine 25–50 mg IV/IM (or 1–2 mg/kg in children) is indicated only for urticaria and itching【35】.
• H2 antihistamine – Ranitidine 50 mg IV or famotidine 20 mg IV may be added to H1 blockade, but evidence of clinical benefit is minimal【35】.
• Corticosteroids – Hydrocortisone 200 mg IV (adults) or methylprednisolone 1–2 mg/kg IV q6h have a delayed onset of 4–6 hours and do not prevent biphasic reactions【33】【35】.
• Bronchodilator – Albuterol 2.5–5 mg nebulized in 3 mL saline can treat persistent bronchospasm after epinephrine, but does not address airway edema or cardiovascular collapse【35】.

Management of Refractory Anaphylaxis

• Consider refractory anaphylaxis when hypotension or bronchospasm persists despite ≥3 IM epinephrine doses and adequate fluid resuscitation【35】.
• Intravenous epinephrine should be administered only in a monitored setting with continuous cardiac monitoring; use a 1:10,000 (0.1 mg/mL) dilution, never the 1:1000 concentration【35】.
  
  • Adults: 50–100 µg IV bolus (0.5–1 mL of 1:10,000), titrated to effect【33】.
  • Children: 1 µg/kg IV bolus【35】.
  • Continuous infusion: 0.05–0.1 µg/kg/min (≈ 1–4 µg/min in adults, max 10 µg/min)【36】.
• Patients on β‑blockers may be refractory to epinephrine; administer glucagon 1–5 mg IV (20–30 µg/kg in children, max 1 mg) followed by an infusion of 5–15 µg/min【36】【34】.
• Treat bradycardia with IV atropine【36】【34】.

Observation and Monitoring

• Minimum observation period after complete symptom resolution is 4–6 hours in a facility capable of managing anaphylaxis【35】【34】.
• Extended observation (≥6 hours) or admission is advised for patients who:
• Biphasic anaphylaxis occurs in 1–20 % of cases, typically around 8 hours after the initial reaction but may appear up to 72 hours later【35】.
• Predictors of biphasic response include severe initial presentation, multiple epinephrine doses, wide pulse pressure, unknown trigger, and prominent skin/mucosal signs【35】.

Discharge Planning and Patient Education

• Prior to discharge, prescribe two epinephrine autoinjectors with hands‑on training (dose appropriate for weight categories)【35】.
• Provide a written anaphylaxis emergency action plan detailing common symptoms, clear epinephrine administration instructions, known triggers, and the need to seek emergency care after use【35】.
• Educate patients on trigger avoidance, recognition of anaphylaxis signs, biphasic reaction risk, proper autoinjector technique, and monitoring of device expiration dates【35】.
• Arrange referral to an allergist‑immunologist for comprehensive evaluation within 1–2 weeks of the event【35】.

Critical Pitfalls to Avoid

• Do not delay IM epinephrine while establishing IV access; IM injection achieves therapeutic levels more rapidly【35】.
• Do not rely on antihistamines or corticosteroids to treat airway obstruction or cardiovascular collapse【35】.
• Do not discharge a patient solely based on symptom resolution, as biphasic reactions can develop hours later【35】.
• Do not use 1:1000 epinephrine concentration for IV administration; only 1:10,000 is safe【35】.
• Recognize that bradycardia occurs in about 10 % of anaphylactic episodes and does not exclude the diagnosis【33】.
• Understand that the absence of cutaneous signs does not rule out anaphylaxis, given that nearly 30 % of patients lack skin findings【33】.

Management and Observation of Anaphylaxis

Pharmacokinetics of Epinephrine

• Intramuscular epinephrine administered in the anterolateral thigh reaches peak plasma concentrations in 8 ± 2 minutes, producing rapid relief of anaphylactic symptoms. 37

Incidence and Predictors of Bifasic Anaphylactic Reactions

• Bifasic reactions occur in 1 %–20 % of anaphylaxis episodes, most often about 8 hours after the initial event but may appear as late as 72 hours. 38
• The strongest predictor of a bifasic reaction is the need for more than one dose of epinephrine (Odds Ratio = 4.82; 95 % CI 2.70–8.58). 38
• Additional predictors include:
  
  • Unknown trigger of the initial anaphylaxis. 37
  • Prominent cutaneous manifestations (e.g., extensive urticaria). 39

Standard Observation Requirements

• All patients who experience anaphylaxis should be observed for a minimum of 4–6 hours in a facility equipped to manage anaphylaxis, even if symptoms have resolved. 40

Criteria for Extended Observation or Hospital Admission

Post‑Observation Pharmacologic Management

• Glucocorticoids do not prevent bifasic reactions and therefore have no proven role in this context. [40][39]
• Antihistamines (H1/H2) also lack evidence for preventing bifasic reactions; their routine use for this purpose is not supported. [40][39]

Practices Not Supported by Evidence

• Discharging patients solely based on symptom resolution is unsafe because bifasic reactions can develop many hours later. (Evidence cited above).
• Relying on antihistamines or glucocorticoids to avert bifasic reactions is not evidence‑based. [40][39]