Has Eculizumab (Soliris) been used to mitigate complement activation during cardiopulmonary bypass (CPB)?

From the Guidelines

Yes, Soliris-like drugs (complement inhibitors) have been used to mitigate complement activation during cardiopulmonary bypass (CPB). Eculizumab (Soliris), a terminal complement inhibitor that blocks C5 activation, has been studied in this context, though it is not yet standard practice 1. Other complement inhibitors investigated include pexelizumab (a short-acting C5 inhibitor) and various C1 esterase inhibitors. These medications work by preventing the inflammatory cascade triggered by CPB, which involves complement activation leading to systemic inflammatory response syndrome. During CPB, blood contact with the artificial circuit surfaces activates complement proteins, particularly through the alternative pathway, causing inflammation, tissue damage, and potential organ dysfunction. Some key points to consider when using these medications include:

• Complement inhibition may be particularly beneficial for high-risk patients undergoing complex cardiac procedures or those with pre-existing inflammatory conditions.
• These therapies come with significant concerns about increased infection risk and high cost.
• Currently, their use remains primarily investigational rather than routine clinical practice, with ongoing trials evaluating their safety and efficacy in cardiac surgery settings. Additionally, heparin-coated CPB circuits have been developed to reduce the systemic inflammatory response associated with CPB, as measured by less complement activation, less leukocyte activation, a reduction in the release of cytokines, and the need for less systemic anticoagulation therapy 1. However, the reported results have been mixed, and more research is needed to fully understand the benefits and limitations of these interventions.

From the Research

Complement Activation During Cardiopulmonary Bypass

• Complement activation plays a significant role in tissue damage associated with trauma and ischemia, including cardiopulmonary bypass 2.
• The activation of the complement system induces an inflammatory reaction, which may lead to harmful effects on the host, either as local tissue damage or as breakdown of homeostatic mechanisms 2.
• Cardiopulmonary bypass induces an acute phase reaction that has been implicated in the pathogenesis of several postoperative complications, including inflammation and endothelial dysfunction 3, 4.

Mitigating Complement Activation

• Inhibiting complement activation may be a therapeutic intervention to reduce post-operative blood loss in patients undergoing cardiopulmonary bypass 5.
• Soluble complement receptor 1 has been used to intervene with complement activation, providing direct evidence for the importance of complement in tissue damage in various experimental models 2.
• However, there is no direct evidence in the provided studies that a Soliris-like drug has been used to mitigate complement activation during cardiopulmonary bypass.

Cardiopulmonary Bypass-Induced Inflammation

• Cardiac surgery with cardiopulmonary bypass induces an acute phase reaction, which is responsible for cell dysfunction in different organs 3.
• The inflammatory response to cardiopulmonary bypass involves the activation of leukocytes and endothelial cells, leading to the release of pro- and anti-inflammatory mediators 3, 4.
• Different pharmacological, technical, and surgical strategies have been used to reduce the effects of cardiopulmonary bypass-induced inflammation, including the use of heparin, glycosaminoglycans, phosphodiesterase inhibitors, and protease inhibitors 3.