What is the management for hypersensitivity reactions?

Management of Hypersensitivity Reactions

Epinephrine 0.3-0.5 mg intramuscularly into the anterolateral thigh is the immediate first-line treatment for anaphylaxis and must be administered without delay—antihistamines and corticosteroids are adjunctive only and provide no acute benefit. 1, 2, 3

Immediate Recognition and Treatment

First-Line: Epinephrine Administration

• Administer epinephrine 0.3-0.5 mg (1:1000 concentration) intramuscularly into the vastus lateralis muscle immediately upon recognition of anaphylaxis in adults, or 0.01 mg/kg (maximum 0.5 mg) in children 1, 2, 3
• Repeat every 5-15 minutes if symptoms persist or worsen 1, 2
• Never delay epinephrine while administering antihistamines or corticosteroids first—this delay is directly associated with increased mortality 1, 4
• Stop any ongoing infusion of the causative agent immediately 1, 4

Patient Positioning and Supportive Care

• Position patient supine with legs elevated unless respiratory distress is present (then sit upright) 2, 5
• Establish large-bore IV access and administer normal saline bolus 500-1000 mL for adults or 10-20 mL/kg for children 2, 5
• Provide supplemental oxygen and monitor oxygen saturation continuously 2, 5
• Monitor vital signs every 15 minutes: blood pressure, heart rate, respiratory rate, oxygen saturation 2, 5

Second-Line Adjunctive Medications

Antihistamines

• H1-antagonist: Diphenhydramine 25-50 mg IV/IM (1-2 mg/kg) 1, 2
• H2-antagonist: Ranitidine 50 mg IV (or famotidine 20 mg IV if ranitidine unavailable) 1, 2
• The combination of H1 + H2 antagonists provides superior symptom control compared to H1 alone 2

Corticosteroids

• Methylprednisolone 1-2 mg/kg IV every 6 hours (typically 40 mg IV every 6 hours for a 70 kg adult) 1, 2
• Alternative: Hydrocortisone 100 mg IV 2
• Corticosteroids may prevent biphasic reactions but provide no acute benefit in anaphylaxis management 1, 2
• Evidence for preventing biphasic anaphylaxis is unclear, with some studies suggesting worse outcomes when glucocorticoids are used with epinephrine 1

Advanced Management for Refractory Cases

Persistent Hypotension Despite Epinephrine

• Consider epinephrine IV infusion at 5-15 μg/min (1:10,000 concentration, 4.0 μg/mL at 1-4 μg/min, maximum 10 μg/min) 2, 4
• For severe hypotension unresponsive to epinephrine IM and fluids, administer epinephrine 0.05-0.1 mg IV (1:10,000) slowly 2
• Vasopressors: Dopamine 400 mg in 500 mL at 2-20 μg/kg/min titrated to clinical response 1, 2
• Vasopressin 25 units in 250 mL (0.1 U/mL) at 0.01-0.04 U/min may be used for refractory hypotension 1

Persistent Bronchospasm

• Albuterol nebulization 2.5-5 mg in 3 mL saline if bronchospasm is unresponsive to epinephrine 2

Patients on Beta-Blockers

• Glucagon 1-5 mg IV over 5 minutes (20-30 μg/kg for children, maximum 1 mg), followed by infusion of 5-15 μg/min if patient is unresponsive to epinephrine 1, 2, 4
• Atropine 600 μg IV if bradycardia develops 1

Cardiac Arrest in Anaphylaxis

• Perform cardiopulmonary resuscitation and advanced life support 2
• High-dose epinephrine IV: 1-3 mg (1:10,000) slowly over 3 minutes, followed by 3-5 mg over 3 minutes, then infusion of 4-10 μg/min 2

Observation and Monitoring

Duration of Observation

• Minimum 6-hour observation period after symptom resolution to monitor for biphasic reactions 2, 5
• Extended observation warranted for severe anaphylaxis or patients requiring more than one dose of epinephrine 4, 5
• Monitor vital signs every 30-60 minutes during observation period after initial stabilization 5
• No reliable predictor exists for biphasic reactions, which can occur in up to 20% of cases 2, 5

Continuous Assessment

• Continuously monitor for signs of airway compromise: voice changes, difficulty swallowing, stridor, throat tightness, respiratory distress 5
• Have intubation equipment immediately available at bedside, as laryngeal angioedema can progress rapidly to complete airway obstruction 5

Discharge Planning and Prevention

Prescriptions and Education

• Prescribe two epinephrine auto-injectors (0.3 mg each) for patients >25 kg with hands-on training before discharge 2, 5
• Prescribe oral prednisone 40-60 mg daily for 2-3 days (or 0.5 mg/kg for children) to prevent biphasic reactions 2, 6
• Provide written emergency action plan detailing when and how to use epinephrine auto-injector, with explicit instructions to call 911 immediately after self-administration 2, 5
• Refer to allergist for evaluation and identification of safe alternatives 4

Context-Specific Management

Radiocontrast Media Hypersensitivity

• For mild immediate reactions: premedication is NOT recommended; switching contrast agents is preferred when the inciting agent is known 1
• For severe immediate reactions: consider alternative imaging first; if no alternative exists, premedication is recommended and the study should be performed in a hospital setting with rapid response team available 1
• No premedication necessary for chemotoxic reactions, physiologic reactions, or isolated shellfish/iodine allergy 1

Infusion Reactions to Systemic Anticancer Therapy

• Grade 1 reactions: slow infusion rate 1
• Grade 2 reactions: slow rate or short-term cessation, treat with H1/H2 antagonists and corticosteroids, restart at 50% rate and titrate to tolerance 1
• Grade 3/4 reactions: stop infusion permanently, treat with antihistamines and corticosteroids, rechallenge discouraged 1

Critical Pitfalls to Avoid

• Never delay epinephrine administration—it is the only medication proven to prevent mortality in anaphylaxis 2, 4, 5
• Never rely on antihistamines alone to treat cardiovascular collapse or respiratory distress 4
• Never assume "no respiratory distress" means low risk—laryngeal edema can progress from minimal symptoms to complete airway obstruction within minutes 5
• Never discharge without prescribing epinephrine auto-injectors and providing hands-on training 5
• Do not use subcutaneous epinephrine—intramuscular administration into the anterolateral thigh provides optimal absorption 1, 2
• Recognize that ACE inhibitor-induced angioedema and hereditary angioedema will not respond to standard anaphylaxis treatment 5