From the Guidelines
Cardiopulmonary bypass (CPB) during cardiac surgery is the medical procedure that causes the most complement activation. This is due to the contact of blood with the artificial surfaces of the bypass circuit, which triggers the alternative pathway of complement 1. The foreign surfaces of the CPB machine, including tubing, oxygenator membranes, and filters, lack the regulatory proteins that normally inhibit complement activation on human cells.
Key Points
- During CPB, complement proteins C3a and C5a increase dramatically within minutes of initiating bypass, peaking at levels 10-20 times above baseline.
- This massive complement activation contributes to systemic inflammatory response syndrome (SIRS) that many cardiac surgery patients experience, characterized by increased vascular permeability, leukocyte activation, and potential organ dysfunction.
- Other procedures that significantly activate complement include hemodialysis, extracorporeal membrane oxygenation (ECMO), and plasmapheresis, but none match the magnitude seen with CPB.
- The use of heparin-coated CPB circuits has been shown to reduce the systemic inflammatory response associated with CPB, including less complement activation 1.
Clinical Implications
- The complement activation during CPB explains many post-cardiac surgery complications including lung injury, renal dysfunction, and neurological effects.
- Reducing complement activation during CPB, such as through the use of biocompatible coatings or heparin-coated circuits, may help to minimize these complications and improve patient outcomes.
From the Research
Medical Procedures and Complement Activation
- Cardiopulmonary bypass (CPB) is a medical procedure that can cause significant complement activation, leading to a systemic inflammatory response syndrome (SIRS) 2, 3, 4.
- The contact of blood with the artificial surfaces of the CPB, mechanical stress, and surgical trauma are the main inducers of SIRS 2, 4.
- The magnitude of the inflammatory reaction varies, but the persistence of any degree of inflammation may be considered potentially harmful to the cardiac patient 3.
Reducing Complement Activation
- Minimized systems with biocompatible surfaces have been shown to be effective in attenuating the inflammatory response to CPB 2.
- Alternative procedures such as off-pump surgery may help to avoid CPB-associated complications, but due to specific limitations, will not replace conventional bypass surgery 2, 5.
- Various therapeutic strategies, including pharmacologic and immunomodulatory agents, have been examined in clinical studies to modulate the systemic inflammatory response following cardiac surgery 3, 5.
Clinical Investigations
- Corticosteroids have been administered to patients undergoing cardiac surgery with CPB to ward off detrimental physiologic alterations associated with activation of the systemic inflammatory response, but their use remains controversial 6.
- A critical review of the evidence base found that no single intervention was supported by strong level A evidence for clinical benefit in attenuating the systemic inflammatory response to cardiopulmonary bypass 5.