Can Therapeutic Plasma Exchange (TPE) worsen the inflammation process in septic patients?

Can Therapeutic Plasma Exchange Worsen Inflammation in Septic Patients?

No, therapeutic plasma exchange (TPE) does not worsen inflammation in septic patients, but it also does not improve mortality and may prolong ICU stay, making it generally not recommended for sepsis without specific indications like thrombocytopenia-associated multiple organ failure (TAMOF). 1

Current Guideline Recommendations

The most authoritative guidance comes from major sepsis guidelines:

• The 2016 WSES consensus states there is currently insufficient evidence supporting the use of any adjunctive therapy, including plasma exchange, in patients with septic shock due to intra-abdominal infection (No Recommendation). 1

• The 2020 Surviving Sepsis Campaign pediatric guidelines suggest against using plasma exchange in children with septic shock or other sepsis-associated organ dysfunction without TAMOF (weak recommendation, very low quality of evidence). 1

• The rationale for TPE in sepsis is to modulate the immune response by removing both pro- and anti-inflammatory cytokines, as mortality is higher when both cytokine levels are elevated. 1

Evidence on Safety and Efficacy

Does TPE Worsen Inflammation?

TPE does not worsen the inflammatory process itself. The mechanism involves:

• Removal of pathologically elevated cytokines (both pro-inflammatory and anti-inflammatory mediators) 2
• Simultaneous replacement of protective plasma factors that may be depleted in sepsis 2, 3
• No evidence in the literature suggests TPE exacerbates the inflammatory cascade 1, 4

Clinical Outcomes

The most recent and highest quality evidence shows:

• A 2023 propensity score-matched analysis of 742 septic patients found no significant difference in organ failure improvement (delta SOFA score) or 28-day mortality between TPE and control groups. However, TPE was associated with significantly shorter ICU-free and alive days, suggesting prolonged ICU stay. 4

• A 2019 pediatric multicenter study found that TPE requirement was not associated with mortality (p = 0.124), though it did not demonstrate decreased mortality with TPE use. 5

• Historical meta-analysis data showed that when trials using polymyxin B hemoperfusion were excluded, blood purification techniques (including plasma exchange) were no longer associated with lower mortality. 1

Specific Clinical Context: TAMOF

The one exception where TPE may be considered is in children with septic shock and thrombocytopenia-associated multiple organ failure (TAMOF):

• The 2020 pediatric sepsis guidelines state they cannot suggest for or against TPE in this specific population, acknowledging insufficient evidence. 1
• The rationale is that plasma contains protein C, antithrombin III, and other anticoagulant proteins that may be critically consumed in progressive purpura. 1
• Large volumes of plasma require concomitant use of diuretics or continuous renal replacement therapy to prevent >10% fluid overload. 1

Safety Concerns

The primary risks of TPE in sepsis are procedural and infectious, not worsening inflammation:

• Increased infection risk when combined with immunosuppressants (which are typically used concurrently in autoimmune conditions but not routinely in sepsis). 6, 7
• One randomized trial reported four deaths from sepsis in the plasma exchange group, though this was in newly diagnosed pemphigus patients receiving concurrent immunosuppression. 1
• Removal of clotting factors can result in coagulation defects. 7
• Hemodynamic shifts and thrombosis risk. 7
• Mortality associated with plasmapheresis itself is estimated at 0.05%. 7

Clinical Algorithm for Decision-Making

When considering TPE in septic patients:

1. First-line management remains: source control, antimicrobial therapy, and supportive care (fluid resuscitation, vasopressors). 1

2. Do NOT use TPE routinely for septic shock - insufficient evidence of benefit and potential for prolonged ICU stay. 1, 4

3. Consider TPE only in highly specific scenarios:

   • Pediatric septic shock with TAMOF and progressive purpura despite rapid shock resuscitation 1
   • As part of research protocols or clinical trials 1

4. If TPE is used in sepsis (off-guideline):

   • Ensure adequate source control and antimicrobial therapy are established first 1
   • Monitor for fluid overload (use diuretics/CRRT as needed) 1
   • Recognize this will likely prolong ICU stay without mortality benefit 4
   • Do not expect improvement in organ failure scores 4

Common Pitfalls to Avoid

• Do not use TPE thinking it will "reset" the immune system in sepsis - while it removes cytokines, this has not translated to improved outcomes. 1, 4

• Do not delay definitive sepsis management (antibiotics, source control, hemodynamic support) to pursue TPE. 1

• Avoid fluid overload - aggressive crystalloid resuscitation combined with large plasma volumes can worsen gut edema and increase intra-abdominal pressure, potentially leading to abdominal compartment syndrome. 1

• Do not confuse sepsis indications with autoimmune disease indications - TPE has established roles in ANCA vasculitis, Guillain-Barré syndrome, and other autoimmune conditions, but these protocols do not apply to sepsis. 6, 7