Guidelines for Managing Fever and Severe Reactions During IVIG Infusion

1. Grading of Infusion‑Related Fever

• Mild to moderate fever (Grade 1‑2) – characterized by fever with or without chills, headache, myalgia, or fatigue that begins at the end of the infusion or within a few hours and is usually self‑limited. 1
• Severe fever (Grade 3‑4) – fever accompanied by hypotension, anaphylaxis, bronchospasm, cyanosis, or loss of consciousness, indicating a systemic reaction that requires immediate intervention. 1
• Serious adverse events may also include renal dysfunction and aseptic meningitis syndrome in addition to hypotension and anaphylaxis. 1

2. Management of Mild‑to‑Moderate Reactions (Grade 1‑2)

• Immediately stop or slow the infusion rate when fever or associated symptoms appear. 3
• Provide symptomatic treatment:
  
  • Administer acetaminophen for fever. 1
  • Give antihistamines if urticaria or pruritus is present. 3
• After symptom resolution, restart the infusion at 50 % of the previous rate and then titrate upward as tolerated. 3
• Continue close monitoring of vital signs throughout the restart phase. (Monitoring recommendation derived from the same source as the rate‑adjustment guidance.) 3

3. Management of Severe Reactions (Grade 3‑4)

• Discontinue the infusion immediately at the first sign of severe reaction. 1
• Administer aggressive supportive therapy:
  
  • Epinephrine 0.01 mg/kg of 1:1000 solution (maximum 0.3–0.5 mg) for anaphylaxis. 2
  • Provide supplemental oxygen. 1
  • Give intravenous antihistamines. 1
  • Give intravenous corticosteroids. 1
  • Initiate cardiorespiratory support as needed. 1
• Fluid resuscitation with normal saline 1–2 L (5–10 mL/kg in the first 5 minutes) for hypotension. 2
• Do not attempt to restart the infusion after a severe reaction. 3

4. Premedication for Future Infusions

• If a prior infusion reaction occurred, pre‑medicate the next dose with acetaminophen, antihistamines, and corticosteroids. 5
• For patients with recurrent mild reactions, consider a regimen of corticosteroids (e.g., methylprednisolone 1 g) plus antihistamines before the infusion. 5

5. Distinguishing Fever During Infusion from IVIG Resistance (Kawasaki Disease Context)

• Fever that occurs during the infusion is an infusion reaction, not IVIG resistance. 6
• IVIG resistance is defined as persistent or recrudescent fever lasting ≥36 hours after completion of the initial 2 g/kg IVIG course. 6
• A new rash without accompanying fever does not meet criteria for IVIG resistance. 6
• Do not give additional IVIG solely because of fever that arises during the infusion; first manage it as an infusion reaction. 6

6. Post‑Reaction Observation

• After treating an anaphylactic reaction, observe the patient for several hours to detect possible biphasic reactions. 3
• Biphasic reactions are more likely in patients who presented initially with severe symptoms. 3
• When epinephrine has been administered, an emergency‑department assessment is recommended to determine whether further interventions are required. 2

All facts are presented in English, with patient‑specific details replaced by generic descriptors. Each bullet point includes the citation(s) from which the information was derived.