How should intravenous immunoglobulin (IVIG) be administered, including appropriate dose, infusion rate, premedication, and monitoring?

How to Administer Intravenous Immunoglobulin (IVIG)

IVIG should be administered at 1-2 g/kg of ideal body weight (typically divided over 2 consecutive days for most autoimmune conditions, or as a single 2 g/kg infusion for Kawasaki disease), after screening for IgA deficiency, ensuring adequate hydration, and infusing at a slow initial rate (0.3-0.6 mL/kg/hr) with gradual titration to a maximum of 2-8 mL/kg/hr while monitoring vital signs continuously. 1

Pre-Administration Assessment

Before initiating IVIG therapy, critical safety screening must be performed:

• Screen for IgA deficiency before the first infusion to prevent potentially fatal anaphylactic reactions; if IgA deficiency is detected, use IgA-depleted IVIG preparations 1, 2
• Assess renal function including serum creatinine and hydration status, as impaired renal function increases risk of acute kidney injury, particularly with sucrose-containing products 1, 3
• Evaluate cardiac function and fluid status, especially in patients with heart disease or shock, as volume overload can precipitate cardiac decompensation 4
• Review thrombotic risk factors including advanced age (>65 years), previous thromboembolic events, immobilization, diabetes, hypertension, and dyslipidemia 3, 2

Dosing Guidelines by Indication

Autoimmune and Inflammatory Conditions

• Standard dose: 1-2 g/kg of ideal body weight divided over 2 consecutive days 1
• Immune Thrombocytopenic Purpura (ITP): 1 g/kg as a single dose, may repeat if insufficient response 1

Kawasaki Disease and MIS-C

• Standard dose: 2 g/kg as a single infusion over 10-12 hours 4, 1, 5
• Cardiac dysfunction present: Divide into 1 g/kg daily over 2 consecutive days to minimize fluid overload 4
• Critical consideration: Patients with ejection fraction <35% require close monitoring and may need concurrent diuretics 4

Immunodeficiency Replacement Therapy

• Maintenance dose: 300-400 mg/kg IV monthly, adjusted to maintain IgG trough levels >500 mg/dL 1
• Alternative dosing: 400 mg/kg every 2-4 weeks for hypogammaglobulinemia with recurrent infections 4

Obese Patients (BMI ≥30 kg/m²)

• Calculate dose using ideal body weight or adjusted body weight, not actual body weight, to avoid excessive dosing and adverse effects 1

Premedication Protocol

Premedication reduces the incidence of mild infusion reactions:

• Acetaminophen (paracetamol): Administer before infusion to reduce fever, headache, and myalgia 1, 2
• Diphenhydramine: Consider for patients with history of mild reactions 1
• Corticosteroids (e.g., 20 mg prednisone): Reserve for patients with documented history of infusion reactions or when using high-dose regimens 1
• Important caveat: Premedication necessity may diminish with repeated infusions as tolerance improves 1

Infusion Rate and Administration

Initial Setup

• Ensure adequate hydration before starting infusion, particularly in patients with renal or thrombotic risk factors 3, 2
• Starting rate: 0.3-0.6 mL/kg/hr 6
• Rate escalation: Increase every 15-30 minutes as tolerated 6
• Maximum rate: 2-8 mL/kg/hr, with lower maximum rates (2-4 mL/kg/hr) for high-risk populations including renal impairment, advanced age, or cardiac dysfunction 6, 3

Kawasaki Disease-Specific Timing

• Recommended infusion duration: 10-12 hours for the 2 g/kg dose 5
• Critical evidence: All coronary artery aneurysms in one retrospective study occurred in patients who received IVIG in <10 hours, supporting the 10-12 hour recommendation 5

Monitoring During Infusion

Continuous vigilance is essential throughout IVIG administration:

• Vital signs: Monitor blood pressure, heart rate, respiratory rate, and temperature continuously 1
• Anaphylaxis surveillance: Maintain heightened awareness in IgA-deficient patients; signs include flushing, facial swelling, dyspnea, cyanosis, hypotension, and loss of consciousness 1
• Renal monitoring: Track urine output and serum creatinine during and for 24-48 hours post-infusion 1, 3
• Timing of common reactions:
  • Within first 10 minutes: Back/abdominal pain, nausea, vomiting 1
  • End of infusion and several hours after: Chills, fever, headache, myalgia, fatigue 1

Management of Adverse Reactions

Immediate Reactions (During Infusion)

• Mild reactions (headache, flushing, myalgia): Slow or temporarily stop infusion; administer analgesics, NSAIDs, or antihistamines 2
• Severe reactions (anaphylaxis, severe hypotension): Immediately stop infusion, administer epinephrine, oxygen, IV antihistamines, IV corticosteroids, and provide cardiorespiratory support 1

Late Adverse Events (Hours to Days Post-Infusion)

Aseptic Meningitis Syndrome:

• Presents within hours to 2 days with severe headache, nuchal rigidity, fever, photophobia, nausea, vomiting 1
• More frequent with high-dose regimens (2 g/kg) 1
• Discontinuation leads to remission within days without sequelae 1

Hemolytic Anemia:

• Risk increases with repeated high-dose (2 g/kg) infusions, particularly in patients with AB blood type 1
• Monitor for Coombs-positive hemolytic anemia 1

Acute Renal Failure:

• Usually oliguric and transient, occurs primarily with sucrose-containing products due to osmotic injury 3, 2
• Prevention: Use non-sucrose products in high-risk patients, ensure hydration, use slow infusion rates, monitor urine output 2

Thromboembolic Events:

• Occur due to hyperviscosity, especially with rapid infusion rates or high doses in patients with risk factors 3, 2
• Prevention: Slow infusion rate, adequate hydration, avoid in patients with multiple thrombotic risk factors unless benefits clearly outweigh risks 3

Post-Infusion Monitoring

• Renal function: Continue monitoring for 24-48 hours to detect delayed nephrotoxic effects 1
• Clinical response assessment: Evaluate based on indication-specific parameters (e.g., platelet count in ITP, fever resolution in Kawasaki disease) 1
• Watch for delayed complications: Thromboembolism, aseptic meningitis, hemolytic anemia 1

Critical Pitfalls to Avoid

• Never administer a second high-dose IVIG course for refractory disease without considering alternatives, as repeated 2 g/kg doses markedly increase risk of volume overload and hemolytic anemia 4
• Do not use intramuscular immunoglobulin preparations intravenously—only IV-formulated products are safe for this route 1
• Avoid sucrose-containing IVIG products in patients with renal insufficiency due to osmotic renal injury risk 1, 3
• Do not give IVIG before therapeutic plasma exchange, as it will be removed; schedule IVIG after plasma exchange is completed 1

Vaccine Interactions

• Live-virus vaccines (measles, mumps, varicella): Administer ≥14 days before or 6 weeks to 3 months after IVIG 1
• High-dose IVIG: Defer measles, mumps, and varicella immunizations for 11 months; high-risk children may receive earlier vaccination with re-immunization after 11 months if serologic response is inadequate 1

Product Selection Considerations

The most commonly used IVIG formulations in neurocritical care and acute settings are Privigen® followed by Gammagard®, with Gamunex®-C used less frequently 6. Product selection should consider IgA content (use IgA-depleted products for IgA-deficient patients), stabilizer type (avoid sucrose in renal impairment), and osmolarity (lower osmolarity products may reduce adverse effects) 1, 3.