From the Guidelines
Cardiopulmonary bypass (CPB) triggers a more robust complement activation compared to hemodialysis, leading to significant increases in C3a, C5a, and terminal complement complex (TCC) formation, which contributes to systemic inflammatory response syndrome and potentially causes organ dysfunction. The complement activation during CPB peaks within 1-2 hours of initiation, primarily occurring via the alternative and classical pathways 1. In contrast, hemodialysis induces a milder complement activation, mainly through the alternative pathway when blood contacts the dialyzer membrane, with modern biocompatible dialysis membranes reducing but not eliminating this activation 1.
The clinical impact of complement activation can be mitigated in both procedures through the use of biocompatible materials, heparin coating, and complement inhibitors like C1 esterase inhibitors, though these strategies are more commonly employed in CPB than in routine hemodialysis 1. Key differences in complement activation between CPB and hemodialysis include:
- Mechanism: CPB triggers complement activation through blood contact with the extracorporeal circuit, surgical trauma, ischemia-reperfusion injury, and endotoxemia, while hemodialysis induces complement activation mainly through the alternative pathway when blood contacts the dialyzer membrane.
- Intensity: CPB leads to more robust complement activation, with significant increases in C3a, C5a, and TCC formation, while hemodialysis induces a milder complement activation with modest increases in C3a and C5a.
- Duration: Complement activation during CPB peaks within 1-2 hours of initiation, while hemodialysis-related complement activation is characterized by levels typically returning to baseline between sessions.
Overall, understanding the differences in complement activation between CPB and hemodialysis is crucial for developing strategies to mitigate the clinical impact of complement activation and improve patient outcomes 1.
From the Research
Complement Activation Comparison
- Complement activation during cardiopulmonary bypass (CPB) and hemodialysis can be compared in terms of the effects of methylprednisolone on complement activation.
- A study published in the Journal of cardiovascular pharmacology 2 found that methylprednisolone pretreatment affected complement activation during heparin-protamine interaction after termination of CPB, with significantly lower C3a and C4a levels in the methylprednisolone group.
- Another study published in EJHaem 3 found that CPB surgery and protamine sulphate had significant effects on complement activation, with increases in alternative and classical pathways activation markers during CPB.
Effects of Methylprednisolone on Complement Activation
- Methylprednisolone has been shown to inhibit complement activation during CPB, with decreased C3a and C4a levels after protamine administration 2.
- However, a review article published in Chest 4 suggested that corticosteroids, including methylprednisolone, may not offer clinical benefits to patients undergoing cardiac surgery with CPB and may even be detrimental.
- An earlier study published in The Journal of thoracic and cardiovascular surgery 5 found that massive doses of methylprednisolone during CPB improved perfusion flows and reduced vasoconstriction.
Clinical Outcomes and Complement Activation
- A study published in EJHaem 3 found a moderate inverse correlation between post-protamine C3 and C4 levels and total drain volume 24 hours after surgery, suggesting that inhibition of complement activation may be a therapeutic intervention to reduce post-operative blood loss in patients undergoing CPB.
- The same study found a moderate positive correlation between post-protamine C3a, C5a, and SC5b-9 levels and total drain volume 24 hours after surgery, indicating that complement activation may play a role in post-operative blood loss 3.