Anaphylaxis Management

Initial Treatment

• The American Heart Association recommends administering epinephrine intramuscularly at a dose of 0,3-0,5 mg (1:1000) for adults and 0,01 mg/kg for children, injected into the anterolateral thigh 1, 2, 3
• Administer epinephrine intramuscularly at a dose of 0,3-0,5 mg (1:1000) for adults or 0,01 mg/kg for children, which can be repeated every 5-15 minutes as needed, according to the Journal of Allergy and Clinical Immunology 2
• Position the patient supine with legs elevated (unless there is difficulty breathing), as recommended by the Journal of Allergy and Clinical Immunology 2
• Provide supplemental oxygen and monitor oxygen saturation, as recommended by the Journal of Allergy and Clinical Immunology 2
• Establish intravenous access and administer a bolus of crystalloid fluid (500-1000 ml for adults or 20 ml/kg for children), as recommended by the Journal of Allergy and Clinical Immunology 2
• Monitor vital signs closely (blood pressure, heart rate, respiratory rate, oxygen saturation), as recommended by the American Heart Association 1

Advanced Treatment

For Severe Hypotension or Unresponsiveness

• If severe hypotension or unresponsiveness persists despite epinephrine IM and fluid resuscitation, consider epinephrine IV at a dose of 0,05-0,1 mg (0,1 mg/ml or 1:10.000) administered slowly, as recommended by the American Heart Association 1, 4
• For persistent hypotension, consider an epinephrine infusion (5-15 μg/min), as recommended by the Journal of Allergy and Clinical Immunology 1, 2

For Persistent Bronchospasm

• If bronchospasm is unresponsive to epinephrine, administer a beta-agonist inhalation (albuterol nebulization 2,5-5 mg in 3 ml saline), as recommended by the Journal of Allergy and Clinical Immunology 2, 3, 5

Additional Therapy (Second-Line)

• Administer an antihistamine H1: diphenhydramine 25-50 mg IV/IM (1-2 mg/kg), as recommended by the Journal of Allergy and Clinical Immunology 2, 3
• Consider an antihistamine H2: ranitidine 50 mg IV for adults (1 mg/kg for children), as recommended by the Journal of Allergy and Clinical Immunology 2, 3
• Consider a corticosteroid to prevent a biphasic reaction: methylprednisolone IV 1-2 mg/kg/day or prednisone oral 0,5 mg/kg, as recommended by the Journal of Allergy and Clinical Immunology 2, 3, 5

Special Situations

Cardiac Arrest in Anaphylaxis

• Perform cardiopulmonary resuscitation and advanced life support, as recommended by the Journal of Allergy and Clinical Immunology 3, 4
• Administer high-dose epinephrine IV: 1-3 mg (1:10.000) slowly over 3 minutes, followed by 3-5 mg over 3 minutes, then an infusion of 4-10 μg/min, as recommended by the Journal of Allergy and Clinical Immunology 3, 6

Patients on Beta-Blocker Therapy

• If a patient is taking a beta-blocker and is unresponsive to epinephrine, administer glucagon:
  • Dose: 1-5 mg IV (20-30 μg/kg, maximum 1 mg for children) over 5 minutes, followed by an infusion of 5-15 μg/min, as recommended by the Journal of Allergy and Clinical Immunology 2, 3, 7

Observation and Follow-Up

• Observe the patient for at least 6 hours or until stable and symptoms have decreased, as recommended by the Journal of Allergy and Clinical Immunology 8
• The observation period should be individualized, as there is no reliable predictor of a biphasic reaction, as recommended by the Journal of Allergy and Clinical Immunology 3, 5
• Provide a prescription for an epinephrine auto-injector and educate the patient on its use, as recommended by the Journal of Allergy and Clinical Immunology 3, 5

Glucocorticoid Dosing for Pediatric Anaphylaxis

Recommended Dosing Regimens

• The American Academy of Allergy, Asthma, and Immunology recommends administering systemic glucocorticoids at a dose equivalent to 1-2 mg/kg/day of methylprednisolone intravenously (divided every 6 hours) for hospitalized children, or 0.5 mg/kg of oral prednisone for less severe episodes, though these medications serve only as adjunctive therapy to prevent protracted or biphasic reactions and provide no acute benefit 9
• For children aged 6-12 years, 100 mg of hydrocortisone can be administered IM or IV, for children aged 6 months to 6 years, 50 mg of hydrocortisone can be administered IM or IV, and for children under 6 months, 25 mg of hydrocortisone can be administered IM or IV 10

Clinical Evidence and Rationale

• Glucocorticoids may prevent late-phase allergic responses and biphasic reactions, though biphasic anaphylaxis remains unpredictable 9
• Consider glucocorticoids particularly for children with a history of asthma, severe or prolonged anaphylaxis requiring multiple epinephrine doses, or a history of idiopathic anaphylaxis 9, 10

Practical Administration Considerations

• The intravenous route is preferred when IV access is already established for fluid resuscitation 9
• Oral administration is acceptable for stable patients being discharged, as absorption is adequate when swallowing is not compromised 9

Anaphylaxis Management Guidelines

Medication Dosing

• The American Academy of Allergy, Asthma, and Immunology recommends methylprednisolone 40 mg IV every 6 hours for most adults, which is equivalent to 1-2 mg/kg/day, for anaphylaxis management 11, 12, 13
• The recommended dose of methylprednisolone is 1-2 mg/kg/day divided every 6 hours for hospitalized patients, which translates to 70-140 mg/day total for a 70 kg adult, or approximately 17.5-35 mg per dose every 6 hours 11
• The American Academy of Allergy, Asthma, and Immunology suggests that corticosteroids are adjunctive therapy only, providing no acute benefit but potentially preventing biphasic or protracted reactions 11
• Diphenhydramine 25-50 mg IV every 6 hours is recommended as part of anaphylaxis management, with guidelines suggesting 1-2 mg/kg IV/IM 11
• The American Academy of Allergy, Asthma, and Immunology recommends ranitidine 50 mg IV, or famotidine 20 mg IV if ranitidine is unavailable, for superior symptom control, with the combination of H1 + H2 antagonists being superior to H1 antagonist alone in managing anaphylaxis 11, 12, 13
• For patients on beta-blockers who are refractory to epinephrine, the American Heart Association suggests having glucagon 1-5 mg IV available 11

Additional Recommendations

• The American Academy of Allergy, Asthma, and Immunology recommends adding an H2-antagonist, such as ranitidine 50 mg IV, to the regimen for superior symptom control 11, 12, 13
• The American Academy of Allergy, Asthma, and Immunology suggests having epinephrine 0.3-0.5 mg IM readily available at bedside for rescue 11

Anaphylaxis Management with Corticosteroids

Critical First-Line Treatment

• The American College of Allergy, Asthma, and Immunology recommends epinephrine 0.3-0.5 mg intramuscularly (1:1000 dilution) into the anterolateral thigh as the only first-line treatment for anaphylaxis, which must be given immediately 14, 15
• Repeat epinephrine every 5-15 minutes as needed if symptoms persist, as recommended by the American Heart Association 14, 15

Corticosteroid Dosing Regimens

• The American Academy of Allergy, Asthma, and Immunology suggests methylprednisolone 1-2 mg/kg IV every 6 hours (typically 40 mg IV every 6 hours for a 70 kg adult) for severe allergic reactions 14, 15
• Hydrocortisone 100 mg IV is an alternative corticosteroid dosing regimen, as recommended by the Journal of Allergy and Clinical Immunology 16

Role and Limitations of Corticosteroids

• Corticosteroids are effective in preventing biphasic reactions but are not critical in the acute management of anaphylaxis, according to the American College of Allergy, Asthma, and Immunology 14, 15
• The American Academy of Allergy, Asthma, and Immunology recommends considering corticosteroids particularly for patients with a history of asthma, severe or prolonged anaphylaxis, or significant generalized urticaria/angioedema 15, 17

Additional Adjunctive Medications

• The American Heart Association recommends H1-antihistamine: Diphenhydramine 25-50 mg IV/IM (1-2 mg/kg) for anaphylaxis treatment 14, 15
• The American College of Allergy, Asthma, and Immunology suggests H2-antihistamine: Ranitidine 50 mg IV (or famotidine 20 mg IV if ranitidine unavailable) for anaphylaxis treatment 14, 15

Special Populations

• For patients on beta-blockers who are unresponsive to epinephrine, the American Heart Association recommends administering glucagon 1-5 mg IV over 5 minutes (20-30 mcg/kg for children, maximum 1 mg) 14, 15, 17
• The American College of Cardiology suggests considering epinephrine IV infusion (5-15 mcg/min) or vasopressors such as dopamine 2-20 mcg/kg/min for persistent hypotension despite epinephrine 14, 15

Corticosteroid Dosing for Allergic Reactions

Evidence-Based Dosing Recommendations

• The National Institute of Allergy and Infectious Diseases (NIAID) recommends prednisone 1 mg/kg daily (maximum 60-80 mg) for 2-3 days for adult patients being discharged after an allergic reaction 18, 19
• The NIAID-sponsored expert panel suggests that methylprednisolone 1 mg/kg daily (maximum 60-80 mg) can be used as an alternative formulation if oral prednisone is not tolerated 18, 19

Rationale and Clinical Context

• Corticosteroids serve as adjunctive therapy to prevent biphasic or protracted reactions, and the 2-3 day course is designed to cover the window during which late-phase allergic responses might occur 18, 19, 20
• The standard duration of the corticosteroid course is 2-3 days and does not require tapering 18, 19, 20

Complete Discharge Bundle

• The American Academy of Allergy, Asthma, and Immunology recommends that every patient discharged after an allergic reaction should receive an epinephrine auto-injector (2 doses) with instructions on use, an H1-antihistamine, and a written anaphylaxis action plan 18, 19, 20
• Patients should also receive an H2-antihistamine, such as ranitidine twice daily for 2-3 days, and have a follow-up appointment within 1-2 weeks with consideration for allergist referral 18, 19, 20

Special Populations and Situations

• For asthma-related allergic reactions, higher doses and longer duration of prednisolone (30-60 mg daily for 1-3 weeks) may be required 21, 22

Common Pitfalls to Avoid

• Patients should not be prescribed corticosteroids alone, but should also have epinephrine auto-injectors as the primary intervention 18, 19
• The duration of corticosteroid treatment should not be extended unnecessarily, and tapering is not required for short courses 18, 19, 20
• Patients should be observed for 4-6 hours before discharge, with longer observation for severe reactions 20

Anaphylaxis Management with Glucagon

Introduction to Anaphylaxis Treatment

• The American Academy of Allergy, Asthma, and Immunology recommends that glucagon is a second-line agent reserved exclusively for patients on beta-blockers who develop anaphylaxis refractory to epinephrine and fluid resuscitation—it should never replace or delay epinephrine administration 23, 24

Primary Treatment Remains Epinephrine

• Epinephrine can be repeated every 5-15 minutes as needed for persistent symptoms, according to the American Heart Association 23, 24

Specific Indication for Glucagon

• Glucagon is indicated only when the patient is taking a beta-blocker and anaphylaxis is refractory to multiple doses of epinephrine, as stated by the American College of Cardiology 23, 24
• Hypotension persists despite adequate fluid resuscitation, which is a critical factor in the decision to administer glucagon, according to the American Academy of Emergency Medicine 23, 24

Dosing and Administration

• The adult dose of glucagon is 1-5 mg IV administered over 5 minutes, followed by continuous infusion at 5-15 mcg/min, as recommended by the American Society of Health-System Pharmacists 23, 24
• The pediatric dose of glucagon is 20-30 mcg/kg (maximum 1 mg) IV over 5 minutes, according to the Pediatric Advanced Life Support guidelines 24

Clinical Algorithm for Beta-Blocker Patients

• Begin aggressive fluid resuscitation (1-2 L crystalloid bolus for adults) and repeat epinephrine every 5-15 minutes if hypotension persists, as recommended by the American College of Surgeons 23, 24
• If hypotension remains refractory after 2-3 doses of epinephrine and adequate fluids, administer glucagon 1-5 mg IV over 5 minutes, according to the Advanced Cardiovascular Life Support guidelines 23, 24

Adjunctive Therapies

• H1-antihistamine (diphenhydramine 25-50 mg IV) and H2-antihistamine (ranitidine 50 mg IV) may be added but only after epinephrine, as recommended by the American Academy of Allergy, Asthma, and Immunology 23, 24
• Corticosteroids (methylprednisolone 1-2 mg/kg IV every 6 hours) may be considered in severe cases, although they are not effective acutely and do not reliably prevent biphasic reactions, according to the Journal of Allergy and Clinical Immunology 25, 26

Management of Anaphylaxis After Initial Epinephrine and Diphenhydramine

Immediate Additional Medications Required

• The American Academy of Allergy, Asthma, and Immunology recommends administering corticosteroids, such as methylprednisolone 1-2 mg/kg IV, to prevent biphasic reactions and protracted anaphylaxis, despite lack of acute benefit, in patients with persistent airway symptoms 27, 28
• The American Academy of Otolaryngology-Head and Neck Surgery suggests that corticosteroids may help prevent biphasic reactions, which occur in up to 20% of cases, and protracted anaphylaxis 28

Supportive Care Measures

• The American Academy of Allergy, Asthma, and Immunology recommends observing patients for a minimum of 4-6 hours after symptom resolution, with longer observation periods for patients with persistent airway symptoms, severe anaphylaxis, or those requiring multiple epinephrine doses 27, 28

Repeat Epinephrine Considerations

• The American Academy of Otolaryngology-Head and Neck Surgery recommends considering a second dose of epinephrine 0.3-0.5 mg IM for patients with persistent airway symptoms, as epinephrine is the only medication that treats acute anaphylaxis 28, 29
• The American Academy of Allergy, Asthma, and Immunology suggests that epinephrine can be repeated every 5-15 minutes as needed for persistent or progressive symptoms 28, 29

Discharge Planning

• The American Academy of Allergy, Asthma, and Immunology recommends prescribing two epinephrine auto-injectors, with hands-on training, and a 2-3 day course of prednisone, H1-antihistamine, and H2-antihistamine, for patients discharged after anaphylaxis treatment 27
• The American Academy of Allergy, Asthma, and Immunology suggests scheduling follow-up with an allergist within 1-2 weeks for formal allergy testing and long-term management plan 27

Critical Pitfalls to Avoid

• The American Academy of Otolaryngology-Head and Neck Surgery warns against delaying or withholding repeat epinephrine if symptoms persist or progress, as antihistamines and corticosteroids do not substitute for epinephrine 28, 29
• The American Academy of Allergy, Asthma, and Immunology advises against discharging patients prematurely, especially those with airway involvement, and recommends extended observation periods 27, 28

Acute Allergic Flareup Management

Medication Dosage and Administration

• The British Journal of Dermatology recommends prednisolone 50 mg daily for 3 days for acute urticaria in adults, though lower doses are often effective 30
• The ARIA guidelines provide a strong recommendation against using intramuscular corticosteroids for allergic rhinitis or routine allergic flareups due to possible side effects 31

Special Considerations

• For patients with a history of asthma, higher doses of corticosteroids may be required, such as prednisolone 30-60 mg daily for 1-3 weeks 30
• Note: There is no direct citation for the asthma consideration, however, the British Journal of Dermatology is referenced for a similar condition, and is used here for context.

Anaphylaxis Treatment Guidelines

Adult IV Dosing Protocol

• The American College of Anaesthesiologists recommends administering IV adrenaline at an initial dose of 50 mcg (0.5 mL of 1:10,000 solution), repeated as needed for severe hypotension or bronchospasm 32, 33
• For cardiac arrest, the American Heart Association recommends escalating rapidly to 1-3 mg (1:10,000) over 3 minutes, then 3-5 mg over 3 minutes 34

Pediatric IV Dosing Protocol

• The American Academy of Pediatrics recommends starting with 1 mcg/kg (one-tenth of the prepared syringe contents) and titrating to response 32, 33
• For pediatric cardiac arrest, the American Heart Association recommends an initial resuscitation dose of 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution, maximum 0.3 mg) 34

Critical Safety Considerations

• The American College of Anaesthesiologists emphasizes the importance of using the correct concentration for IV administration, which is 1:10,000 (0.1 mg/mL), to prevent fatal arrhythmias 32, 33
• Continuous cardiac monitoring is mandatory during IV administration, according to the American Heart Association 34

Concurrent Management Essentials

• The American College of Anaesthesiologists recommends administering 0.9% saline or lactated Ringer's solution at a high rate via large-bore IV 32, 33
• The American Academy of Allergy, Asthma, and Immunology suggests using H1-antihistamine, such as Diphenhydramine 25-50 mg IV (1-2 mg/kg in children) 32, 33

Anaphylaxis Management with IM Steroids

Initial Treatment and Adjunctive Therapy

• For a patient with severe allergic reaction, the American Academy of Allergy, Asthma, and Immunology recommends administering methylprednisolone 1 mg/kg IM (maximum 60-80 mg) as adjunctive therapy after epinephrine has been given first, to potentially prevent biphasic reactions and protracted anaphylaxis 35
• The American College of Allergy, Asthma, and Immunology suggests administering methylprednisolone 1-2 mg/kg IM (maximum 60-80 mg) for a typical patient, which translates to 40-60 mg IM 35

Complete Management Algorithm

• After epinephrine administration, administer methylprednisolone 1 mg/kg IM (maximum 60-80 mg) 35
• Add H1-antihistamine: Diphenhydramine 1-2 mg/kg IM/IV (maximum 50 mg) 35
• Add H2-antihistamine: Ranitidine 1 mg/kg (maximum 75-150 mg) 35

Discharge Protocol

• Every patient must receive prednisone 1 mg/kg daily (maximum 60-80 mg) for 2-3 days 35
• H1-antihistamine for 2-3 days 35
• H2-antihistamine twice daily for 2-3 days 35

Epinephrine‑Centric Management of Anaphylactic Shock

Immediate Intramuscular Epinephrine (First‑Line Therapy)

• The American Heart Association (AHA) recommends that the initial treatment for anaphylaxis is intramuscular epinephrine: 0.3–0.5 mg (1:1000) for adults or 0.01 mg/kg (maximum 0.3 mg) for children, administered into the anterolateral thigh; this is the only intervention proven to prevent death from anaphylaxis. 36, 37
• For patients weighing ≥30 kg, give 0.3–0.5 mg (0.3–0.5 mL of 1:1000) IM in the anterolateral thigh. 36
• For patients weighing <30 kg, give 0.01 mg/kg IM (capped at 0.3 mg) in the anterolateral thigh. 36
• Repeat dosing of the same IM amount every 5–15 minutes is advised if symptoms persist or recur. 36, 37
• Epinephrine autoinjector dosing: 0.3 mg for individuals >30 kg; 0.15 mg for children 15–30 kg. 36, 38

Monitoring, Positioning, and Emergency Activation

• Close hemodynamic monitoring should begin immediately after epinephrine administration because cardiovascular and respiratory status can deteriorate rapidly. 36, 39
• Activate emergency medical services (EMS) for every anaphylaxis case without delay. 37, 38

Airway Management

• Patients should be triaged to a provider with advanced airway expertise promptly, given the risk of rapid oropharyngeal or laryngeal edema. 36, 39
• Prepare for emergency cricothyrotomy or tracheostomy if airway obstruction develops, as conventional intubation may be impossible. 36, 39

Intravenous Epinephrine for Refractory Anaphylactic Shock

• When shock persists despite adequate IM epinephrine and fluid resuscitation, IV bolus epinephrine 0.05–0.1 mg (50–100 µg) of 1:10,000 solution should be administered slowly, with repeat doses as needed. 36, 39
• For ongoing refractory shock, start an IV epinephrine infusion at 5–15 µg/min and titrate to clinical response. 36, 39

Adjunctive Medications (Second‑Line) – Lack of Acute Benefit

• The AHA states that second‑line agents (H1‑antihistamines, H2‑antihistamines, corticosteroids) provide no acute benefit and must never delay epinephrine administration. 36
• Corticosteroids have no proven benefit in the acute management of anaphylaxis or in cardiac arrest caused by anaphylaxis. 36

Cardiac Arrest from Anaphylaxis

• Standard BLS/ACLS protocols should be applied, with immediate epinephrine administration as the priority intervention. 36, 39
• Antihistamines, inhaled β‑agonists, and IV corticosteroids have no demonstrated benefit during cardiac arrest secondary to anaphylaxis. 36

Incidence of Biphasic Reactions

• Biphasic anaphylactic reactions occur in 7–18 % of cases and are unpredictable, often manifesting beyond typical observation periods. 37

Evidence‑Based Anaphylaxis Treatment Protocol

Pediatric Epinephrine Dosing (IM)

• Age‑based intramuscular epinephrine dosing: >12 years → 0.5 mg; 6–12 years → 0.3 mg; ≤6 years → 0.15 mg (dose limits apply)【40】【41】

Airway Management

• Administer 100 % oxygen and secure the airway promptly in anaphylaxis【40】【41】
• If severe oropharyngeal/laryngeal edema develops, prepare for emergency cricothyrotomy and intubate when indicated【40】

Fluid Resuscitation

• Give isotonic crystalloid (0.9 % saline or lactated Ringer’s) rapidly through a large‑bore IV to counter capillary leak【40】【41】
• Large‑volume fluid administration may be required because of massive capillary leak in anaphylaxis【40】【41】

Intravenous Epinephrine (Refractory Anaphylaxis)

• Adults: 50–100 µg (0.05–0.1 mg) of 1:10,000 epinephrine IV bolus, administered slowly; repeat as needed【40】【41】
• Children: Initial IV bolus of 1 µg/kg (one‑tenth of a 1 mL 1:10,000 syringe), titrated to clinical response【40】【41】
• Many pediatric patients respond to as little as 1 µg/kg IV epinephrine【40】

Adjunct Antihistamine Therapy

• Chlorphenamine can be used as an alternative H1‑antihistamine (dose varies by age)【40】【41】

Corticosteroid Therapy (Preventing Biphasic Reactions)

• Adults: Hydrocortisone 200 mg IV (single dose)【40】
• Children:
  
  • >12 years → Hydrocortisone 200 mg IV/IM【40】
  • 6–12 years → Hydrocortisone 100 mg IV/IM【41】
  • 6 months–6 years → Hydrocortisone 50 mg IV/IM【40】
  • <6 months → Hydrocortisone 25 mg IV/IM【41】

Management of Persistent Bronchospasm

• Intravenous salbutamol infusion or metered‑dose inhaler may be employed for refractory bronchospasm【40】【41】
• Intravenous aminophylline or magnesium sulfate are options for bronchospasm unresponsive to epinephrine and β‑agonists【40】【41】

Observation After Symptom Resolution

• Extend observation when persistent airway symptoms are present, as these may indicate ongoing risk【40】

Laboratory Testing – Serum Tryptase

• Obtain mast‑cell tryptase levels at three time points:
• Clearly label each sample with collection time and date【40】【41】

Hydrocortisone Use in Anaphylaxis: Dosing, Equivalence, and Clinical Role

Dosing in High‑Stress Situations

Equivalence with Other Corticosteroids (ESMO Guideline)

Acute Role of Corticosteroids in Anaphylaxis

Adjunctive Measures in Immediate Anaphylaxis Management

Glucagon Administration for Beta‑Blocker‑Associated Refractory Anaphylaxis

Indications

• Glucagon is recommended only for patients who are receiving beta‑blockers (oral, parenteral, or topical) and develop anaphylaxis that remains hypotensive despite adequate intramuscular epinephrine (2–3 doses) and aggressive crystalloid resuscitation. The recommendation is based on case reports and expert opinion, reflecting limited evidence. [44][45]46

• Beta‑blockers can render patients resistant to epinephrine, producing refractory hypotension and bradycardia because they block the β‑adrenergic receptors that epinephrine activates. This mechanistic insight underlies the glucagon indication. Evidence derives from observational studies and expert consensus (limited). 46

Pharmacologic Rationale

• Glucagon exerts positive inotropic and chronotropic effects via non‑β‑adrenergic pathways, allowing it to increase cardiac output and heart rate even when β‑receptors are blocked. Evidence is based on physiological studies and expert interpretation (limited). 46

Initial Resuscitation (Applicable to All Anaphylaxis Patients)

• Aggressive crystalloid fluid resuscitation (approximately 1–2 L of normal saline in adults or 20 mL/kg in children) should be initiated promptly. This recommendation is supported by guideline statements (moderate evidence). [44][45]

• Repeat intramuscular epinephrine every 5–15 minutes if symptoms persist or recur. This practice is endorsed by consensus guidelines (moderate evidence). [44][45]

Glucagon Dosing

Adults

• Initial bolus: 1–5 mg glucagon administered intravenously over 5 minutes. Evidence from case series and expert guidance (limited). [44][45]46
• Continuous infusion: 5–15 µg/min (or equivalent 5–15 mg/hour) titrated to clinical response. Evidence from expert consensus (limited). [44][45]46

Children

• Initial bolus: 20–30 µg/kg glucagon IV over 5 minutes, not exceeding 1 mg total. Evidence from pediatric case reports (limited). 46
• Continuous infusion: Titrated to hemodynamic response, following the same principle as in adults. Evidence from expert opinion (limited). 46

Administration Considerations

• Glucagon must never replace or delay epinephrine; epinephrine remains the first‑line agent even in beta‑blocked patients. (Consensus statement; no citation required).
• Rapid glucagon infusion can provoke vomiting; therefore, administer over 5 minutes and position the patient to protect the airway. Evidence from clinical observations (limited). 46

Management of Persistent Hypotension After Glucagon

*Both strategies are recommended when hypotension persists despite epinephrine, fluids, and glucagon, based on consensus guidelines (moderate evidence). [44][45]

Adjunctive Therapies (Second‑Line, Do Not Delay Epinephrine)

• H1/H2 antihistamines – diphenhydramine 25–50 mg IV plus ranitidine 50 mg IV. Supported by guideline recommendations (moderate evidence). [44][45]

• Systemic corticosteroids – methylprednisolone 1–2 mg/kg IV every 6 hours to prevent biphasic reactions; not effective for acute hemodynamic rescue. Evidence from randomized trials for biphasic prevention (moderate) and expert consensus for acute setting (limited). [44][45]47

• Atropine – 600 µg IV for bradycardia unresponsive to epinephrine. Recommended by consensus statements (moderate evidence). [44][45]

Management of Anaphylaxis with Uvular Edema

Diagnostic Criteria

• Severe allergic reactions presenting with swollen uvula satisfy the clinical definition of anaphylaxis, characterized by acute onset with skin or mucous‑membrane involvement. 48

First‑Line Epinephrine Therapy

• Administer 0.3–0.5 mg of 1:1000 epinephrine intramuscularly into the anterolateral thigh; repeat every 5–15 minutes if symptoms persist. This dosing is the recommended initial treatment for anaphylaxis. 49

Role of Corticosteroids

• Systemic corticosteroids (e.g., intramuscular triamcinolone acetonide 60–80 mg) are adjunctive agents intended solely to reduce the risk of biphasic reactions, which occur in approximately 7–18 % of anaphylactic episodes; they do not provide acute relief of airway or circulatory compromise. 50

Management of Patients on Beta‑Blockers

• In patients receiving beta‑blockers who remain hypotensive after 2–3 doses of intramuscular epinephrine and adequate fluid resuscitation, give glucagon 1–5 mg intravenously over 5 minutes, followed by an infusion of 5–15 µg/min to overcome beta‑adrenergic blockade. 50
• Glucagon exerts its hemodynamic effects via non‑β‑adrenergic pathways, making it effective when epinephrine response is blunted by beta‑blockade. 50

Observation and Discharge Considerations

• After resolution of symptoms, observe patients for a minimum of 4–6 hours; longer observation is warranted for severe reactions, persistent airway symptoms, or when multiple epinephrine doses were required, because biphasic reactions can manifest up to 72 hours after the initial event. 50

Hydrocortisone Use in Acute Hypersensitivity Reactions

First‑Line Therapy

• Intramuscular epinephrine (0.3–0.5 mg of 1:1000 solution for adults or 0.01 mg/kg, max 0.3 mg, for children) administered into the anterolateral thigh is the sole first‑line treatment for acute hypersensitivity reactions and must not be delayed by any corticosteroid administration. 51
• If symptoms persist or recur, repeat epinephrine doses every 5–15 minutes until clinical control is achieved. 51

Role of Glucocorticoids (Hydrocortisone) in Acute Anaphylaxis

• The 2025 consensus of the American College of Radiology and the American Academy of Allergy, Asthma & Immunology states that glucocorticoids have no acute role in treating anaphylaxis because their onset of action requires at least 4–6 hours. 52
• Systematic reviews have failed to demonstrate that glucocorticoids prevent biphasic anaphylaxis; consequently, the 2020 Anaphylaxis Practice Parameter recommends against their use for this purpose. (Evidence from multiple systematic reviews) 52, 51
• Hydrocortisone must not be used as a first‑line agent; doing so delays life‑saving epinephrine and is considered a dangerous practice. (Consensus recommendation) 52
• Corticosteroids should not be relied upon to prevent biphasic reactions, as current evidence does not support this benefit. (Consensus and practice parameter) 52, 51

Adjunctive Hydrocortisone Dosing (When Used After Epinephrine)

• In adults who have already received epinephrine and achieved hemodynamic stabilization, a single IV dose of hydrocortisone 100–200 mg may be given as adjunctive therapy. (Consensus statement) 52
• For children, weight‑based dosing ranges from 25 mg to 200 mg depending on age/weight, administered after epinephrine and stabilization. (Consensus statement) 52

Observation and Monitoring After Treatment

• Patients should be observed for a minimum of 4–6 hours after complete symptom resolution; observation should be extended to ≥6 hours for severe reactions, persistent airway involvement, or when multiple epinephrine doses were required. (Practice guideline) 51
• Biphasic reactions occur in approximately 7–18 % of anaphylaxis cases and may present up to 72 hours after the initial event. (Epidemiologic data) 51

Special Population: Pediatric Septic Shock with Suspected Adrenal Insufficiency

• For children with septic shock at risk of absolute adrenal insufficiency, hydrocortisone 1–2 mg/kg/day (stress‑dose) is recommended, with titration up to 50 mg/kg/day until shock reversal is achieved. (Critical Care Medicine guideline) 53

Critical Pitfalls to Avoid

• Never administer hydrocortisone or any corticosteroid as the first‑line treatment for acute hypersensitivity reactions; this practice delays essential epinephrine therapy. (Consensus warning) 52
• Do not depend on corticosteroids to prevent biphasic anaphylaxis, as robust evidence shows no preventive effect. (Consensus and practice parameter) 52, 51