Effect of Methylprednisolone on Complement Activation During Heparin Neutralization

Abstract

During cardiac surgery, steroids are frequently administered before the initiation of cardiopulmonary bypass (CPB), termed "pre-treatment," to reduce "first phase" complement activation during cardiopulmonary bypass (CPB). "Second phase" complement activation also occurs during heparin neutralization with protamine, although the effects of steroid pretreatment on such activation are unknown. This study was performed in patients undergoing coronary artery bypass graft surgery to determine whether high-dose methylprednisolone pretreatment affected complement activation during heparin-protamine interaction after termination of CPB. In eight patients (group MP), methylprednisolone, 30 mg/kg, was administered before CPB commencement, whereas another eight patients received placebo (group C). By using 125I des Arg radioimmunoassay, C3a, C4a, and C5a were measured in the arterial blood samples drawn before and 10 min after administration of protamine. An increase in C3a and C4a was observed in both groups after protamine, suggesting classic pathway activation (delta C3a: group C, 4,484 +/- 3,320; group MP, 1,394 +/- 1,653; delta C4a: group C, 1,810 +/- 731; group MP, 717 +/- 580). C3a and C4a levels were significantly lower in group MP patients after protamine compared with controls [delta C3a, 3,499 +/- 1,826 (p < 0.05); delta C4a, 1,241 +/- 232 (p < 0.05)]. C5a was not detected in any samples. These results demonstrate that the effect of pretreatment persists beyond the period of CPB and that methylprednisolone inhibits second-phase complement activation during heparin-protamine interaction. These findings have implication for patients with severe anaphylactoid reactions to protamine.