What is the role of Intravenous Immunoglobulin (IVIG) in the treatment of Acute Respiratory Distress Syndrome (ARDS)?

Role of IVIG in Acute Respiratory Distress Syndrome (ARDS)

IVIG is not recommended as a standard treatment for ARDS but may be considered as an adjunct therapy in specific circumstances such as ARDS associated with rapidly progressive interstitial lung disease (RP-ILD) in systemic autoimmune rheumatic diseases. 1

Current Evidence for IVIG in ARDS

• Standard therapies for ARDS include lung-protective ventilation strategies, higher PEEP in moderate-to-severe ARDS, prone positioning in severe ARDS, consideration of VV-ECMO in selected severe cases, and corticosteroids for patients with poor oxygenation 1
• IVIG is not recommended as a first-line treatment option for general ARDS cases due to limited efficacy data and potential risks 1
• A retrospective cohort study found that IVIG therapy in mechanically ventilated patients with COVID-19 related moderate-to-severe ARDS was associated with higher ICU mortality (36.4% vs. 15.3%) 2

Specific Indications for IVIG in ARDS

• IVIG may be considered in ARDS specifically associated with rapidly progressive interstitial lung disease (RP-ILD) in systemic autoimmune rheumatic diseases 3, 1
• For people with idiopathic inflammatory myopathy-associated ILD (IIM-ILD) and mixed connective tissue disease-associated ILD (MCTD-ILD) progression despite first-line ILD treatment, the American College of Rheumatology conditionally recommends adding IVIG as a treatment option 3
• IVIG is particularly useful when rapid onset of action is desired, such as in the presence of severe respiratory muscle weakness in IIM-ILD 3

Timing and Administration

• Early administration of IVIG appears to be more beneficial if considered for RP-ILD in systemic autoimmune conditions 1
• A small retrospective study of COVID-19 patients suggested that those who received IVIG within the first 4 days of admission demonstrated a shorter length of hospital stay compared to those who received it later 4
• IVIG is typically administered with pulse methylprednisolone in the context of RP-ILD in systemic autoimmune rheumatic diseases 1

Limitations and Risks

• IVIG carries risks of complications, including renal failure 1
• A retrospective cohort study found that IVIG therapy in COVID-19 related ARDS was associated with higher incidence of acute kidney injury (85.6% vs. 67.8%) 2
• IVIG should not be used long-term without clear clinical need due to limited supply and high cost 1, 5
• The quality of evidence for IVIG in ARDS is generally low to very low 6

Treatment Algorithm for ARDS with Consideration of IVIG

1. Implement standard ARDS management strategies first:

   • Lung-protective ventilation
   • Prone positioning in severe ARDS
   • Consider neuromuscular blockade and corticosteroids 1

2. Consider IVIG only in specific circumstances:

   • ARDS due to rapidly progressive interstitial lung disease in systemic autoimmune rheumatic diseases 3, 1
   • As part of combination therapy with pulse methylprednisolone 1
   • When infection risk is a particular concern 1
   • In IIM-ILD and MCTD-ILD with progression despite first-line treatment 3

3. IVIG is conditionally ranked below rituximab and cyclophosphamide in the treatment hierarchy for RP-ILD 1

4. Monitor closely for adverse effects, particularly renal function 1, 2

Conclusion

While IVIG may have a role in specific cases of ARDS associated with autoimmune conditions, the current evidence does not support its routine use in general ARDS cases. Further randomized clinical trials are needed to definitively establish its efficacy and safety profile in ARDS.