How should a child with Kawasaki disease be managed if they develop shivering during intravenous immunoglobulin (IVIG) infusion?

Management of Shivering During IVIG Infusion in Kawasaki Disease

Slow or temporarily stop the IVIG infusion immediately, then resume at a slower rate once symptoms resolve 1. Shivering during IVIG infusion represents a hypersensitivity or infusion-related reaction that requires immediate rate adjustment rather than discontinuation of therapy.

Immediate Management Steps

1. Infusion Rate Modification

• Stop or slow the infusion as soon as shivering develops 1
• Monitor vital signs continuously during the reaction
• Once symptoms subside, resume infusion at a lower rate that is comfortable for the patient 1
• The standard initial rate is 0.01 mL/kg/min (0.5 mg/kg/min), gradually increasing to maximum 0.10 mL/kg/min (5 mg/kg/min) if tolerated 1

2. Supportive Measures

• Ensure adequate hydration before and during infusion 1
• Consider premedication with antipyretics (acetaminophen) or antihistamines for subsequent infusions if shivering recurs
• Warm the patient if hypothermic
• Monitor for progression to more severe hypersensitivity reactions (hypotension, respiratory distress, anaphylaxis)

Key Clinical Distinctions

Shivering vs. Rigors vs. Anaphylaxis:

• Shivering alone = infusion rate-related reaction → slow/stop and resume slower
• Rigors with fever/chills = cytokine-mediated reaction → slow rate, consider antipyretics
• Hypotension, bronchospasm, angioedema = anaphylaxis → discontinue immediately and treat with epinephrine 1

Important Caveats

Do NOT Abandon IVIG Therapy

The 2017 AHA guidelines emphasize that IVIG at 2 g/kg remains the cornerstone of Kawasaki disease treatment 2. Shivering is a manageable infusion reaction, not a contraindication to completing therapy. Failure to complete IVIG significantly increases coronary artery aneurysm risk.

True Contraindications Are Rare

IVIG is only contraindicated in 1:

• History of anaphylaxis to human immune globulin
• IgA-deficient patients with anti-IgA antibodies AND prior hypersensitivity

Monitor for Serious Complications

While managing the infusion reaction, remain vigilant for 1:

• Renal dysfunction (especially in volume-depleted patients)
• Thrombosis (ensure adequate hydration)
• Hemolysis (monitor for jaundice, dark urine)
• Aseptic meningitis (severe headache, neck stiffness within hours to 2 days post-infusion)

Practical Algorithm

1. Shivering develops → Immediately slow or stop infusion
2. Assess severity → Check vital signs, look for progression
3. Symptoms resolve → Resume at 50% of previous rate
4. Gradually increase → If tolerated, slowly advance rate over 30-60 minutes
5. Complete full dose → Ensure patient receives entire 2 g/kg over extended time if needed
6. Document reaction → Note for future infusions; consider premedication next time

If IVIG Resistance Develops

Should the patient remain febrile ≥36 hours after completing IVIG (separate from the infusion reaction), the AHA recommends 2:

• Second IVIG dose (2 g/kg) as first-line (Class IIa)
• High-dose methylprednisolone (20-30 mg/kg IV × 3 days) as alternative (Class IIb)
• Infliximab (5 mg/kg) as alternative to second IVIG (Class IIb)

The infusion reaction itself does not constitute IVIG resistance—resistance is defined by persistent or recrudescent fever after completing the full therapeutic dose.