What are the common and serious side effects of intravenous immunoglobulin (IVIG) and how should they be managed?

IVIG Side Effects and Management

IVIG is generally safe but can cause both common mild reactions (headache, fever, chills) in 25-36% of patients and rare but serious complications including anaphylaxis, acute renal failure, thromboembolic events, and aseptic meningitis that require immediate recognition and intervention. 1, 2

Common Mild Side Effects (Occur in 25-36% of Patients)

Immediate reactions during or within 6 hours of infusion:

• Headache (most common), fever, chills, and fatigue 1, 2, 3
• Flushing, myalgia, back pain, and arthralgia 1, 3
• Nausea, vomiting, and diarrhea 1, 3
• Blood pressure changes (both hypertension and hypotension) and tachycardia 1, 2
• Chest tightness, dyspnea, and malaise 3
• Rash, pruritus, and local injection site reactions 1, 3

Management of mild reactions:

• Slow or temporarily stop the infusion immediately 4
• Administer acetaminophen for fever and headache 4
• Give antihistamines for urticaria or pruritus 4
• After symptom resolution, restart infusion at 50% of previous rate and titrate upward as tolerated 4
• For patients with prior reactions, premedicate with acetaminophen, antihistamines, and corticosteroids before future infusions 4

Serious Adverse Events (Rare but Life-Threatening)

Anaphylaxis and Anaphylactoid Reactions

Highest risk in IgA-deficient patients who may have anti-IgA antibodies: 1, 5

• Symptoms include flushing, facial swelling, dyspnea, cyanosis, anxiety, hypotension, loss of consciousness, and potentially death 1
• Onset ranges from seconds to hours after infusion 1

Immediate management protocol:

• Discontinue infusion immediately and maintain IV access 5
• Administer epinephrine 0.01 mg/kg IM (maximum 0.3-0.5 mg) in lateral thigh, repeat every 5-15 minutes if needed 5, 6
• Provide supplemental oxygen and aggressive fluid resuscitation with normal saline 1-2 L IV (5-10 mL/kg in first 5 minutes) 5, 6
• Give adjuvant therapy: diphenhydramine 50 mg IV and ranitidine 50 mg IV 5
• Administer methylprednisolone 1-2 mg/kg IV to prevent biphasic reactions 5
• Monitor for 24 hours after severe reactions due to biphasic response risk 5
• Never delay epinephrine while waiting for antihistamines or corticosteroids 5

Aseptic Meningitis Syndrome

• Occurs within hours to 2 days after treatment, more frequently with high-dose therapy (2 g/kg) 1
• Presents with severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea, and vomiting 1
• Discontinuation of IVIG results in remission within days without sequelae 1

Acute Renal Failure

Risk factors include:

• Pre-existing renal disease, dehydration, diabetes mellitus, advanced age, hypertension, or concurrent nephrotoxic medications 3, 7
• Use of sucrose-containing IVIG products (causes osmotic injury) 2, 3
• Usually presents as oliguric and transient renal failure 2, 3

Prevention strategies:

• Ensure adequate hydration before and during infusion 2, 3
• Use non-sucrose-containing products in high-risk patients 3
• Administer at low concentration and slow infusion rate 3
• Monitor urine output and kidney function 3

Thromboembolic Events (Stroke, Myocardial Infarction, Deep Vein Thrombosis)

High-risk patients include those with: 2, 3, 7

• Advanced age, previous thromboembolic events, immobilization 2, 3
• Diabetes mellitus, hypertension, dyslipidemia 2, 3
• Receiving high-dose IVIG at rapid infusion rate 2, 3

Prevention:

• Use slow infusion rates and ensure adequate hydration 2, 3
• Exercise particular caution in elderly patients with multiple cardiovascular risk factors 7

Hemolytic Anemia

• Particularly associated with anti-D immunoglobulin (not standard IVIG) 1
• Ranges from mild extravascular hemolysis to severe intravascular hemolysis with disseminated intravascular coagulation 1
• Black box warning exists for anti-D immunoglobulin related to fatal intravascular hemolysis, though this is rare 1

Special Populations

Pediatric patients:

• Immediate adverse events occur in approximately 25% of children receiving IVIG 8
• Most common reaction is fever/chills 8
• High doses, rapid infusion rates, and accompanying infection may worsen adverse effects, especially in primary immunodeficiency diseases 8
• Children with anaphylaxis may present differently than adults—behavior changes (becoming very quiet, irritable, or cranky) may be the primary sign 6

Elderly patients:

• Serious adverse reactions occur more frequently in elderly individuals with multiple cardiovascular risk factors 7
• Particular caution needed regarding thromboembolic complications 7

Prevention Strategies to Minimize All Adverse Events

• Monitor vital signs during and after infusion 5
• Use slow infusion rates, especially in first-time recipients or those with risk factors 2, 3
• Ensure adequate hydration before and during treatment 2, 3
• Avoid rapid infusion rates in high-risk patients 3
• Consider premedication with acetaminophen, antihistamines, and corticosteroids in patients with prior reactions 4
• Screen for IgA deficiency before first infusion in patients with history of severe allergic reactions 1

Important caveat: While IVIG is described as having lower infection risk compared to other immunosuppressive therapies, the theoretical risk of transmission of blood-borne infectious agents cannot be totally excluded, though manufacturing processes have been validated to inactivate and remove viruses 1