Should the second day of Intravenous Immunoglobulin (IVIG) infusion be delayed if the patient develops a fever?

Management of Fever During IVIG Infusion

The second day of IVIG infusion should be delayed if the patient develops a fever on the morning of day two, with treatment focused on addressing the fever before proceeding with the infusion.

Understanding Fever as an Adverse Reaction to IVIG

Fever is one of the most common adverse reactions associated with IVIG therapy:

• Fever occurs in approximately 30.6% of adverse reactions to IVIG 1
• Most adverse reactions to IVIG occur within 1-6 hours from the onset of infusion 2, 1
• Fever is typically considered an immediate-type reaction rather than a delayed reaction 2

Management Algorithm for Fever During IVIG Treatment

1. When Fever Develops Before Starting Day 2 Infusion:

• Delay the infusion until the patient is afebrile
• Administer antipyretics (e.g., paracetamol/acetaminophen) 2
• Ensure proper hydration before attempting to restart infusion 3
• Monitor vital signs closely

2. When Fever Develops During Infusion:

• Temporarily discontinue the infusion 3
• Administer antipyretics (paracetamol/acetaminophen) 2
• Consider antihistamines if accompanied by other symptoms like rash 2
• For more severe reactions, consider steroids 2
• Once fever resolves, consider restarting at a slower infusion rate 2, 1

Rationale for Delaying Infusion

Delaying the second day of IVIG when fever is present is recommended because:

1. Fever may indicate an adverse reaction to the previous day's infusion
2. Continuing infusion during fever may worsen the reaction
3. Slower infusion rates are associated with fewer adverse reactions 2, 3
4. Proper hydration before restarting reduces risk of adverse events 3

Risk Factors for Adverse Reactions

Be particularly cautious with patients who have:

• Previous history of adverse reactions to IVIG
• IgA deficiency (risk of anaphylaxis) 4
• Renal impairment
• Advanced age
• Cardiovascular risk factors 5
• Dehydration 3

Prevention of Recurrent Reactions

For subsequent infusions after a fever reaction:

• Use slower infusion rates (less than 1.5 ml/kg/hour) 2
• Consider premedication with antipyretics and antihistamines 6
• Ensure adequate hydration before and during infusion 3
• Consider switching to a different IVIG product if reactions persist 1

Special Considerations for Kawasaki Disease

For patients receiving IVIG for Kawasaki disease (a common indication):

• Fever may be part of the disease process rather than solely an adverse reaction
• However, safety principles still apply - delay infusion until fever is controlled
• The American Heart Association recommends instituting IVIG as early as possible within the first 10 days of illness onset 6
• If fever persists or recurs after initial IVIG treatment, a second dose of IVIG (2 g/kg) may be considered for patients with persistent or recrudescent fever at least 36 hours after the end of the first IVIG infusion 7

Monitoring During Resumed Infusion

When restarting IVIG after fever resolution:

• Begin at a slower infusion rate than previously used
• Monitor vital signs frequently, especially temperature
• Be prepared to discontinue again if fever recurs
• Assess for other potential adverse reactions (rash, headache, chills, etc.)

By delaying the second day of IVIG infusion when fever is present, addressing the fever appropriately, and resuming with caution, the risk of more serious adverse reactions can be minimized while still providing the necessary treatment.