What is the recommended immediate management and workup for a patient presenting with an allergic reaction (possible anaphylaxis)?

Immediate Management and Workup for Allergic Reaction (Possible Anaphylaxis)

Administer intramuscular epinephrine immediately into the mid-anterolateral thigh as soon as anaphylaxis is suspected—this is the only first-line treatment that prevents death, and all other interventions are adjunctive. 1, 2, 3

Immediate Recognition and First Actions

Clinical Features to Recognize Anaphylaxis

Anaphylaxis typically develops within minutes but may be delayed up to one hour after allergen exposure. 1 Look for involvement of two or more organ systems:

• Cardiovascular: Hypotension (occurs in 74.7% of allergic anaphylaxis), cardiovascular collapse (50.8%), tachycardia, or bradycardia (10% of cases—do not rule out anaphylaxis based on heart rate alone) 1
• Respiratory: Bronchospasm (39.8%), stridor, throat tightness, difficulty breathing, or hypoxia 1, 3
• Cutaneous: Flushing, urticaria, or angioedema (71.9% of cases—but absence does not exclude anaphylaxis) 1, 3
• Gastrointestinal: Nausea, vomiting, crampy abdominal pain, or diarrhea 3
• Neurologic: Sense of doom, confusion, dizziness, or syncope 3

Critical pitfall: Hypotension may be the sole presenting feature in approximately 10% of patients, and cutaneous signs may be absent in nearly 30% of cases. 1 In nonverbal children, watch for subtle signs like ear picking, tongue rubbing, hand in mouth, or assuming the fetal position. 1

Immediate Epinephrine Administration

Do not delay epinephrine while considering other diagnoses, obtaining IV access, or waiting for symptoms to worsen. 4, 2

• Adults and adolescents ≥30 kg: 0.3–0.5 mg of 1:1000 (1 mg/mL) epinephrine intramuscularly 2, 3, 5
• Children <30 kg: 0.01 mg/kg intramuscularly (maximum 0.3 mg) 2, 3, 5
• Injection site: Mid-outer thigh (vastus lateralis)—this achieves peak plasma levels in 8±2 minutes versus 34±14 minutes with subcutaneous administration 1, 2, 3
• Repeat dosing: Every 5–15 minutes if symptoms persist or recur; 10–20% of patients require more than one dose 1, 2, 4

There are no absolute contraindications to epinephrine in anaphylaxis—the risk of death from untreated anaphylaxis outweighs any theoretical cardiac concerns, even in elderly patients with cardiovascular disease. 1, 2, 3

Simultaneous Supportive Measures (Do Not Delay Epinephrine)

ABC Approach

• Call for help immediately and activate emergency medical services while beginning treatment 1, 2, 4

• Remove all potential causative agents (IV colloids, latex, chlorhexidine, medications) 1, 4

• Position patient supine with legs elevated to increase venous return—up to 35% of intravascular volume can shift to extravascular space within minutes 1, 2, 4

  • Exception: If respiratory distress or vomiting is present, position for comfort 3
  • In pregnant women, perform left uterine displacement to avoid aortocaval compression 2
  • Never allow patient to stand, walk, or run—sudden postural changes can precipitate cardiovascular collapse 2, 3

• Administer 100% oxygen at 6–8 L/min for any patient with respiratory symptoms 1, 2, 4

• Maintain airway—intubate if necessary; prepare for emergency cricothyroidotomy if severe laryngeal edema prevents conventional intubation 1, 2

Aggressive Fluid Resuscitation

Establish IV access immediately and begin rapid crystalloid infusion (normal saline or lactated Ringer's solution). 1, 4

• Adults: 5–10 mL/kg in first 5 minutes (approximately 1–2 L total); up to 20–30 mL/kg may be required 2, 4
• Children: Up to 30 mL/kg in the first hour 2
• Grade II reactions: Initial bolus of 0.5 L 2
• Grade III reactions: Initial bolus of 1 L, repeated as needed based on clinical response 2

Fluid resuscitation is imperative because anaphylaxis causes massive vasodilation and capillary leak, with potential transfer of up to 35% of intravascular volume into extravascular space within minutes. 1, 2

Secondary (Adjunctive) Treatments—Only AFTER Epinephrine

These medications should never be given before or in place of epinephrine, as they have slow onset and do not treat life-threatening cardiovascular or airway compromise. 1, 2

H1 Antihistamines

• Diphenhydramine 25–50 mg IV/IM (or 1–2 mg/kg in children) for urticaria and itching only 1, 2, 4
• Chlorphenamine 10 mg IV (adults) 1, 4
• Oral liquid formulations are absorbed more rapidly than tablets 3

H2 Antihistamines

• Ranitidine 50 mg IV (adults) or famotidine 20 mg IV, given with H1 antihistamine 1, 2
• Evidence of benefit is minimal 2

Corticosteroids

• Hydrocortisone 200 mg IV (adults) or methylprednisolone 1–2 mg/kg/day IV every 6 hours 1, 2
• Critical limitation: Onset of action is 4–6 hours, so they have no immediate effect on acute anaphylaxis 2, 4
• Do not prevent biphasic reactions despite common practice 1, 2

Bronchodilators

• Albuterol 2.5–5 mg nebulized in 3 mL saline for persistent bronchospasm after epinephrine 1, 2
• Does not treat airway edema or cardiovascular collapse 2

Management of Refractory Anaphylaxis

When to Escalate

Consider refractory anaphylaxis if hypotension or bronchospasm persists despite:

• Multiple IM epinephrine doses (typically >3 doses) 2
• Adequate fluid resuscitation 2

IV Epinephrine

Only use in monitored settings with continuous cardiac monitoring. 1, 2

• Dilution: Use 1:10,000 concentration (0.1 mg/mL)—never use 1:1000 concentration IV, as it can cause fatal arrhythmias 2
• Bolus dosing:
  • Adults: 50–100 µg (0.5–1 mL of 1:10,000) IV slowly, titrated to response 1, 2
  • Children: 1 µg/kg IV 2
  • Repeat every 5–15 minutes as needed 2
• Continuous infusion: 0.05–0.1 µg/kg/min (approximately 1–4 µg/min in adults, maximum 10 µg/min) 1, 2, 4

Alternative Vasopressors

For persistent hypotension despite epinephrine and fluids, consider: 2, 3

• Norepinephrine
• Vasopressin
• Phenylephrine
• Metaraminol
• Dopamine

Special Populations

Patients on β-blockers may be resistant to epinephrine and develop refractory hypotension and bradycardia: 1, 2

• Glucagon 1–5 mg IV over 5 minutes (20–30 µg/kg in children, maximum 1 mg), followed by infusion of 5–15 µg/min
• Rapid administration can induce vomiting 1

Bradycardia: Administer atropine IV 1

Observation and Monitoring

Minimum Observation Period

• Standard: 4–6 hours after complete symptom resolution in a facility capable of managing anaphylaxis 1, 2, 4
• Extended observation (6+ hours) or admission is required for: 1, 2
  • Patients requiring >1 epinephrine dose (strongest predictor of biphasic reaction)
  • Severe initial presentation (hypotension, respiratory compromise)
  • Wide pulse pressure
  • Unknown trigger
  • Drug trigger in children
  • Cardiovascular comorbidity
  • Coexisting asthma (especially poorly controlled)
  • Refractory or protracted symptoms
  • Lack of access to epinephrine or emergency services

Biphasic Anaphylaxis

• Occurs in 1–20% of cases, typically around 8 hours after initial reaction but can occur up to 72 hours later 1, 2, 4
• Predictors include severe initial presentation, multiple epinephrine doses, wide pulse pressure, unknown trigger, and prominent skin/mucosal signs 1, 2
• Corticosteroids and antihistamines do not reliably prevent biphasic reactions 2

Diagnostic Workup

Serum Tryptase Sampling

Obtain when clinical diagnosis is unclear or for documentation: 2, 4, 6

• First sample: As soon as feasible after resuscitation starts (ideally 1 hour after reaction onset)
• Second sample: 2–4 hours after onset
• Baseline sample: At least 24 hours post-reaction for comparison

Mandatory Discharge Requirements

Before discharge, ensure: 1, 2, 3, 4

• Two epinephrine autoinjectors prescribed with hands-on training:
  • 0.15 mg for children 10–25 kg
  • 0.3 mg for individuals ≥25 kg
  • 0.1 mg for infants where available (if unavailable, 0.15 mg for infants >7.5 kg)
• Written anaphylaxis emergency action plan detailing:
  • Common symptoms and signs
  • Clear instructions for epinephrine use
  • List of known triggers
  • Instructions to seek emergency care after using epinephrine
• Education on:
  • Trigger avoidance
  • Signs/symptoms of anaphylaxis
  • Biphasic reaction risk
  • Proper epinephrine technique
  • Monitoring autoinjector expiration dates
• Referral to allergist-immunologist for comprehensive evaluation within 1–2 weeks

High-Risk Populations Requiring Heightened Vigilance

• Adolescents and young adults (higher likelihood of denying symptoms) 2, 3
• Patients with coexisting asthma, especially severe or poorly controlled 1, 2, 3
• Peanut or tree-nut allergy 2, 3
• Previous history of anaphylaxis 3
• Older adults or those with underlying cardiovascular disease 2

Critical Pitfalls to Avoid

• Never delay IM epinephrine while establishing IV access—IM injection achieves therapeutic levels faster 1, 2
• Do not rely on antihistamines or corticosteroids to treat airway obstruction or cardiovascular collapse 2
• Do not discharge based solely on symptom resolution—biphasic reactions may develop hours later 2
• Do not use 1:1000 epinephrine concentration for IV administration—use only 1:10,000 to avoid fatal arrhythmias 2
• Bradycardia does not rule out anaphylaxis—it occurs in 10% of cases 1
• Absence of cutaneous signs does not exclude anaphylaxis—nearly 30% lack skin findings 1