What is the recommended immediate management of anaphylaxis, including epinephrine dosing, patient positioning, airway and circulatory support, adjunctive medications, observation duration, and discharge instructions?

Immediate Management of Anaphylaxis

Administer intramuscular epinephrine 0.3–0.5 mg (1:1000 concentration) into the mid-outer thigh immediately upon recognizing anaphylaxis in adults, or 0.01 mg/kg (maximum 0.3 mg) in children—this is the only first-line treatment that prevents death and must never be delayed. 1, 2

Initial Actions (First 60 Seconds)

• Call for help immediately and activate emergency medical services while beginning treatment 2, 3
• Remove any potential causative agents (stop infusions, remove stingers) 2
• Position the patient supine with legs elevated unless respiratory distress or vomiting is present, in which case position for comfort 1, 2, 3
  • Never allow the patient to stand, walk, or run—sudden postural changes can precipitate cardiovascular collapse 2, 3
  • In pregnant women, perform left uterine displacement to avoid aortocaval compression 2

Epinephrine Administration: The Critical Intervention

Dosing and Route

• Adults and adolescents ≥50 kg: 0.3–0.5 mg of 1:1000 (1 mg/mL) epinephrine intramuscularly 1, 2
• Children <50 kg: 0.01 mg/kg intramuscularly (maximum 0.3 mg for prepubertal children) 1, 2, 3
• Injection site: Mid-outer thigh (vastus lateralis muscle)—this achieves peak plasma concentrations in 8±2 minutes compared to 34±14 minutes with subcutaneous administration 1, 2, 3
• Autoinjector dosing: 0.15 mg for 10–25 kg, 0.3 mg for ≥25 kg, 0.1 mg for infants where available 2

Repeat Dosing

• Repeat epinephrine every 5–15 minutes as needed if symptoms persist or recur 1, 2
• Approximately 6–19% of patients require a second dose 2, 3
• Delayed epinephrine administration is directly associated with anaphylaxis fatalities—do not hesitate 2, 3

Intravenous Epinephrine (Refractory Cases Only)

IV epinephrine should only be considered when an IV line is already in place and the patient has anaphylactic shock unresponsive to multiple IM doses. 1, 2

• Dilution: Use 1:10,000 concentration (0.1 mg/mL) for IV bolus 1, 2
• Dosing: 0.05–0.1 mg (50–100 μg) IV bolus, titrated slowly to response 1, 2
• Infusion: For patients requiring >3 IM doses, prepare epinephrine infusion at 0.05–0.1 μg/kg/min (or 5–15 μg/min in adults) 1, 2
• Critical safety: Requires continuous cardiac monitoring; risk of arrhythmias and hypertension with IV route 1, 2

Airway and Circulatory Support

Oxygen and Airway Management

• Administer 100% oxygen at 6–8 L/min to all patients with respiratory symptoms 1, 2, 3
• Prepare for advanced airway management if oropharyngeal or laryngeal edema develops 1
• Emergency cricothyroidotomy or tracheostomy may be required for obstructive airway edema 1
• Immediate referral to a provider with expertise in surgical airway management is recommended given the potential for rapid airway deterioration 1

Fluid Resuscitation

Establish IV access immediately and administer aggressive crystalloid resuscitation concurrently with epinephrine. 1, 2, 3

• Grade II reactions: Initial bolus of 0.5 L crystalloid (normal saline or lactated Ringer's) 2
• Grade III reactions: Initial bolus of 1 L crystalloid 2
• Repeat boluses as needed: Up to 20–30 mL/kg based on clinical response 2
• Pediatric dosing: 5–10 mL/kg in first 5 minutes, up to 30 mL/kg in first hour 3
• Fluid resuscitation is imperative to combat vasodilation and capillary leak 2

Hemodynamic Monitoring

• Close hemodynamic monitoring is mandatory for all patients in anaphylactic shock 1
• Cardiovascular and respiratory status can change rapidly 1

Adjunctive Medications (Second-Line Only)

These medications are adjuncts only and should NEVER delay or replace epinephrine. 2, 3

H1 Antihistamines

• Diphenhydramine 25–50 mg IV/IM (or 1–2 mg/kg in children, maximum 50 mg) for urticaria and pruritus 1, 2, 3
• Chlorphenamine 10 mg IV (adults) as alternative 2
• Antihistamines treat only cutaneous symptoms and do NOT prevent or reverse cardiovascular collapse or airway obstruction 2, 3

H2 Antihistamines

• Ranitidine 50 mg IV in adults (≈1 mg/kg in children) may be added for additional histamine blockade 1, 2
• Evidence of benefit is minimal 2

Bronchodilators

• Albuterol 2.5–5 mg nebulized for persistent bronchospasm after epinephrine 1, 2, 3
• Does NOT treat airway edema 2

Corticosteroids

Corticosteroids are NOT recommended for acute anaphylaxis treatment because they have a slow onset of action (4–6 hours) and no proven benefit in the immediate phase. 2, 3

• No evidence supports their use in preventing biphasic reactions 1, 2
• If administered empirically: methylprednisolone 1–2 mg/kg/day IV every 6 hours or hydrocortisone 200 mg IV (adults), recognizing the weak evidence base 1, 2

Management of Refractory Anaphylaxis

Vasopressor Support

• Dopamine 2–20 μg/kg/min IV titrated to maintain systolic blood pressure >90 mm Hg if epinephrine and fluids fail 1, 2
• Alternative vasopressors (norepinephrine, vasopressin, phenylephrine, metaraminol) may be used for persistent hypotension 2

Beta-Blocker Patients

• Glucagon 1–2 mg IV over 5 minutes for patients on beta-blockers who are resistant to epinephrine 2, 3
• Follow with infusion of 5–15 μg/min titrated to response 3
• Note: Rapid glucagon administration can induce vomiting 3

Extreme Cases

• Extracorporeal life support may be considered in refractory cardiac arrest 2

Cardiac Arrest from Anaphylaxis

In cardiac arrest secondary to anaphylaxis, standard BLS and ACLS measures with immediate epinephrine administration take priority. 1

• Use standard cardiac arrest epinephrine dosing: 1 mg IV/IO every 3–5 minutes 1
• There is no proven benefit from antihistamines, inhaled beta-agonists, or IV corticosteroids during anaphylaxis-induced cardiac arrest 1

Observation Duration

All patients must be observed for a minimum of 6 hours in a monitored area or until stable and symptoms have resolved. 2, 3

Extended Observation Criteria

• Patients requiring >1 dose of epinephrine should undergo extended observation (minimum 4–6 hours after symptom resolution) 2, 3
• High-risk factors requiring prolonged observation:
  • Severe initial presentation 2, 4
  • Wide pulse pressure 2
  • Unknown trigger 2
  • Drug-triggered reaction in children 2
  • Grade III–IV reactions (typically require ICU admission) 2

Biphasic Reaction Risk

• Biphasic anaphylaxis (recurrence after appropriate initial treatment) occurs in 1–20% of patients and may appear up to 3 days later, though most occur within the observation period 2, 4
• Predictors include severe initial presentation, multiple epinephrine doses, wide pulse pressure, unknown trigger, and prominent skin/mucosal signs 2

Tryptase Sampling

• First sample: 1 hour after onset of reaction 2
• Second sample: 2–4 hours after onset 2
• Baseline sample: At least 24 hours post-reaction for comparison 2

Discharge Instructions

Mandatory Prescriptions

All patients who have experienced anaphylaxis must be discharged with two epinephrine autoinjectors. 2, 3

• Dosing: 0.15 mg for 10–25 kg; 0.3 mg for ≥25 kg 2, 3
• For patients ≥45 kg: Consider prescribing 0.5 mg autoinjector based on shared decision-making 5

Written Action Plan

• Provide a written, personalized anaphylaxis emergency action plan that includes:
  • Common symptoms/signs of anaphylaxis 2, 3
  • Clear instructions to inject epinephrine first at earliest sign 2, 3
  • List of known triggers 2, 3
  • Instructions to call 911 immediately after epinephrine use 2, 3

Critical Education Points

• Always seek emergency care after using epinephrine, even if symptoms improve, due to risk of biphasic reactions 2, 3
• Delayed epinephrine administration is directly associated with anaphylaxis fatalities—inject first, call 911 second 2, 3
• Monitor autoinjector expiration dates, as epinephrine degrades over time 2
• Do not allow patient to stand, walk, or run after reaction—maintain supine position during transport 2, 3

Follow-Up

• Refer to allergist for evaluation to identify triggers and assess ongoing risk 2, 3

High-Risk Populations

Patients at increased risk for severe/fatal anaphylaxis include: 2, 3

• Adolescents and young adults 2, 3
• Those with coexisting asthma, especially poorly controlled 2, 3
• Previous history of anaphylaxis 2, 3
• Peanut/tree nut allergies 2, 3

Common Pitfalls to Avoid

• Never delay epinephrine while establishing IV access—IM injection achieves therapeutic levels faster 2
• Never substitute antihistamines or corticosteroids for epinephrine—they are not effective for life-threatening manifestations 2, 3
• Never use IV epinephrine without continuous cardiac monitoring—risk of fatal arrhythmias 1, 2
• Never discharge without two autoinjectors and written action plan—this is a critical safety measure 2, 3
• There are no absolute contraindications to epinephrine in anaphylaxis, even in elderly patients with cardiovascular disease—the risk of death from anaphylaxis outweighs any epinephrine-related risk 2, 3