What are the recommended steps to monitor for and manage infusion‑related reactions in a patient receiving intravenous immunoglobulin (IVIG)?

Management of IVIG Infusion Reactions

Stop the IVIG infusion immediately at the first sign of any reaction, maintain IV access with normal saline, and implement graded management based on reaction severity—mild reactions require rate reduction to 50% with monitoring, moderate reactions need temporary cessation plus combined H1/H2 antihistamines and corticosteroids, while severe reactions demand permanent discontinuation with intramuscular epinephrine 0.3-0.5 mg for anaphylaxis. 1

Immediate Recognition and Initial Response

At the very first sign of a reaction—including vague discomfort, urgency to void, headache, flushing, or vital sign changes—stop the infusion immediately and keep the IV line patent with normal saline. 1, 2 Call for medical assistance and assess airway, breathing, circulation, and level of consciousness. 3

Position the patient appropriately: 3, 1, 2

• Trendelenburg position for hypotension
• Upright/sitting for respiratory distress
• Recovery position if unconscious

Provide supplemental oxygen when clinically indicated. 1, 2

Graded Management by Reaction Severity

Grade 1 (Mild): Headache, Flushing, Mild Fever, Fatigue, Myalgia

Reduce the infusion rate to 50% of the current rate. 1 Once symptoms completely resolve, resume the infusion at 50% of the original rate and titrate upward as tolerated. 1, 4 Most mild reactions are rate-related and resolve with slowing. 5, 6

Grade 2 (Moderate): Moderate Headache, Chills, Nausea, Vomiting, Urticaria, Blood Pressure Changes, Tachycardia

Stop the infusion temporarily. 1 Administer combined H1 + H2 antihistamines (diphenhydramine 25-50 mg IV plus ranitidine 50 mg IV), which is superior to H1 antagonists alone. 1 Consider a single dose of IV corticosteroid (methylprednisolone 40-100 mg) for persistent symptoms. 1, 4

Monitor vital signs continuously until complete symptom resolution. 1 Once resolved, restart the infusion at 50% of the previous rate. 1 If symptoms recur, discontinue the infusion permanently for that session. 1

Grade 3 (Severe): Symptomatic Bronchospasm, Marked Dyspnea, Hypoxia, Severe Hypotension, Chest Pain

Permanently stop the infusion for that session. 1 Provide aggressive symptomatic treatment: 1

• Intramuscular epinephrine 0.3-0.5 mg (1:1000) if anaphylaxis criteria are met (see below)
• Rapid fluid resuscitation with 1-2 L normal saline (5-10 mL/kg in first 5 minutes)
• Combined H1/H2 antihistamines (diphenhydramine 25-50 mg IV + ranitidine 50 mg IV)
• IV corticosteroids (methylprednisolone 1-2 mg/kg IV every 6 hours) 3, 1
• Bronchodilators for bronchospasm 1
• Atropine 0.6 mg IV for bradycardia 1
• If hypotension persists despite epinephrine and fluids, start vasopressor infusion (dopamine 2-20 µg/kg/min) 1

Do not rechallenge during the same session; future IVIG may require desensitization at a specialized center. 1

Grade 4 (Life-Threatening): Anaphylaxis, Severe Respiratory Failure, Cardiovascular Collapse

Permanently discontinue IVIG. 1 Administer intramuscular epinephrine 0.3-0.5 mg immediately into the lateral thigh; repeat every 5-15 minutes as needed. 3, 1, 2 If inadequate response, initiate IV epinephrine infusion. 1

Give aggressive crystalloid/colloid boluses (20 mL/kg). 1, 2 Follow full anaphylaxis resuscitation protocols, including glucagon 1-5 mg IV over 5 minutes (followed by infusion) for patients on β-blockers. 1, 2 Never attempt rechallenge without formal desensitization protocol. 1

Anaphylaxis Criteria Requiring Immediate Epinephrine

Administer epinephrine immediately when any of the following is present: 1

1. Acute onset with skin/mucosal involvement (urticaria or angioedema) PLUS respiratory compromise OR hypotension
2. Isolated hypotension after IVIG exposure (systolic <90 mmHg or >30% drop from baseline)

Symptoms of classic anaphylaxis include flushing, facial swelling, dyspnea, cyanosis, anxiety, nausea, vomiting, malaise, hypotension, loss of consciousness, and potentially death, appearing from seconds to hours after infusion. 3

Post-Reaction Monitoring

Continuously monitor vital signs until complete symptom resolution. 1, 7 Observe patients for a minimum of 24 hours after severe (Grade 3-4) reactions to detect biphasic anaphylaxis. 1, 2 Most postinfusion reactions occur within 24 hours and consist mainly of headaches, fatigue, and nausea. 7

Document reaction grade, specific symptoms, time of onset, interventions performed, and response to treatment. 3, 1

Special Populations and Risk Factors

Patients with diabetes mellitus, hypertension, cardiovascular disease, and those receiving concurrent nephrotoxic medications have increased risk of IVIG-related complications. 1, 6, 8 A history of prior thromboembolic events or prolonged immobilization further elevates risk. 1, 6, 8

Patients with selective IgA deficiency may have anti-IgA antibodies and risk anaphylactic reactions, though this is extremely rare. 3 Some IgA-deficient patients have tolerated subcutaneous IgG infusions without reactions even after anaphylaxis with IVIG. 3

Critical Pitfalls to Avoid

Do NOT delay epinephrine administration when anaphylaxis is suspected—it is the only life-saving medication in true anaphylaxis. 1, 2, 9 After any reaction, never restart the infusion at the full original rate; always resume at 50% of the previous rate. 1, 2

Do NOT discharge patients prematurely after severe reactions; a 24-hour observation period is mandatory to capture possible biphasic events. 1, 2 Corticosteroids provide no acute benefit in anaphylaxis but may help prevent biphasic reactions; they should not be used as sole therapy. 1, 9

Avoid infusion rates >1.5 mL/kg/h, as higher rates significantly increase reaction frequency. 1, 4 Ensure adequate hydration before and during infusion, especially with sucrose-containing IVIG products, to reduce renal complications. 1, 6, 8

Prevention Strategies

Premedication with acetaminophen, antihistamines, or steroids reduces but does not eliminate infusion reactions; vigilance must be maintained. 3, 1 High doses, high infusion rates, and accompanying infection may worsen adverse effects, especially in primary immunodeficiency diseases. 5

Slow infusion rate of low concentration IVIG products and hydration, especially in high-risk patients, may prevent renal failure, thromboembolic events, and aseptic meningitis. 6, 8

Delayed Adverse Events

Aseptic meningitis syndrome can occur from within hours to 2 days after treatment, characterized by severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting—discontinuation results in remission within days without sequelae. 3 Hemolytic anemia may occur days after infusion; monitor for jaundice, dark urine, and falling hemoglobin levels. 1