From the Guidelines
Yes, Soliris-like drugs (complement inhibitors) have been used to mitigate complement activation during cardiopulmonary bypass (CPB). Specifically, eculizumab (Soliris) and other terminal complement inhibitors have been studied in this context. During CPB, blood contact with the artificial circuit surfaces triggers massive complement activation, contributing to systemic inflammatory response syndrome, which can lead to organ dysfunction. Eculizumab works by blocking C5 activation, preventing formation of the membrane attack complex (C5b-9) and reducing inflammation.
Key Points
- Typical dosing for cardiac surgery applications ranges from 600-900 mg IV administered shortly before CPB initiation.
- Other complement inhibitors studied include pexelizumab (a short-acting C5 inhibitor) and ravulizumab (Ultomiris, a longer-acting eculizumab alternative) 1.
- These drugs are particularly beneficial for patients at high risk for complement-mediated complications, such as those undergoing complex procedures or with pre-existing inflammatory conditions.
- The rationale is that by blocking the terminal complement pathway, these medications reduce neutrophil activation, endothelial damage, and subsequent organ injury that commonly occurs during CPB.
Complement Activation Mitigation
The use of heparin-coated CPB circuits has also been explored 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 the focus has shifted towards the use of complement inhibitors like eculizumab to mitigate complement activation during CPB.
Clinical Application
In clinical practice, the use of Soliris-like drugs during CPB has shown promise in reducing morbidity and mortality associated with complement-mediated complications. The most recent and highest quality study supports the use of eculizumab in this context, although the exact dosing and patient selection criteria may vary depending on the specific clinical scenario 1.
From the Research
Complement Activation During Cardiopulmonary Bypass
- Complement activation plays a significant role in tissue damage associated with trauma and ischemia 2.
- During cardiopulmonary bypass (CPB), complement activation occurs, leading to an inflammatory response that may cause post-operative complications 3, 4, 5, 6.
- The activation of the complement system during CPB is triggered by various factors, including the contact system, endotoxemia, ischemia, and reperfusion injury, as well as surgical trauma 4.
Therapeutic Interventions to Reduce Complement Activation
- Inhibiting complement activation may be a therapeutic intervention to reduce post-operative blood loss in patients undergoing CPB 5.
- Soluble complement receptor 1 has been used to intervene with complement activation in experimental models, providing evidence for the importance of complement in tissue damage 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.