Is there a risk of sepsis associated with therapeutic plasma exchange?

Risk of Sepsis with Plasma Exchange

Yes, plasma exchange carries a documented increased risk of serious infections, including sepsis, with moderate certainty evidence showing a 19% relative increase in serious infection risk. 1

Magnitude of Infection Risk

The infection risk associated with plasma exchange is clinically significant and well-established across multiple high-quality guidelines:

• Absolute risk increase of 6.8% to 12.8% in serious infections when plasma exchange is added to standard immunosuppressive therapy over one year 1
• Relative risk of 1.19 (95% CI 0.99-1.42) for severe infections based on pooled data from four trials, with moderate certainty evidence 1, 2
• In one large retrospective analysis of 883 plasma exchange procedures, sepsis occurred in 0.3% of procedures (3 cases), representing one of the most severe life-threatening complications 3

Mechanisms of Infection Risk

The increased sepsis risk stems from multiple procedural factors:

• Central venous catheter requirement creates a direct portal for bacterial entry, with line-related bacteremia being a recognized complication 1, 2
• Removal of immunoglobulins and complement proteins during plasma removal temporarily impairs immune function 4
• Concurrent immunosuppressive therapy compounds the infection risk, particularly in patients with ANCA-associated vasculitis receiving cyclophosphamide or rituximab 1, 2
• Removal of clotting factors can necessitate fresh frozen plasma replacement, which carries additional infectious disease transmission risk 2, 5

Clinical Context: Risk-Benefit Analysis

The 2022 BMJ guidelines explicitly acknowledge that infection risk is the primary harm driving recommendations against routine plasma exchange in low-risk patients:

• For patients with low or low-moderate risk of end-stage kidney disease, the panel concluded that "the harms of serious infections outweighed the benefits" 1
• The guideline panel noted that patients "would place a high value on reduction in ESKD, and less value on avoiding serious infections," yet still recommended against routine plasma exchange in low-risk groups due to unfavorable risk-benefit balance 1
• Only in high-risk patients (serum creatinine >500 μmol/L or >5.8 mg/dL) does the benefit potentially outweigh the increased infection risk 1

Specific Sepsis Considerations

Plasma exchange is explicitly not recommended for treatment of sepsis itself:

• The World Society of Emergency Surgery recommends against using plasma exchange in septic shock due to insufficient evidence of benefit 6
• The Surviving Sepsis Campaign suggests against plasma exchange in pediatric septic shock (weak recommendation, very low quality evidence) 1, 6
• The only potential exception is pediatric septic shock with thrombocytopenia-associated multiple organ failure (TAMOF), though evidence remains insufficient 6

Risk Mitigation Strategies

When plasma exchange is deemed necessary despite infection risk:

• Use albumin replacement rather than fresh frozen plasma when possible to minimize transfusion-related infectious complications 2, 5
• Employ pathogen-inactivated plasma when fresh frozen plasma is required 2
• Optimize peripheral venous access when feasible to avoid central line placement and associated catheter-related bacteremia 7, 8
• Maintain continuous monitoring for early signs of infection, particularly in patients on concurrent immunosuppression 2, 3
• Consider prophylactic antimicrobial measures in high-risk immunosuppressed patients 5

Common Pitfalls

• Underestimating cumulative risk: The infection risk compounds with each procedure and is additive with immunosuppressive medications 1, 2
• Ignoring baseline patient risk: Patients with neurological diseases have significantly higher complication rates (P=0.013) compared to those with internal medicine conditions 3
• Failing to account for catheter duration: Central venous catheters required for plasma exchange create ongoing infection risk beyond the procedure itself 1

The evidence consistently demonstrates that plasma exchange increases serious infection risk, including sepsis, and this harm must be carefully weighed against potential benefits in each clinical scenario.