The Role of Endogenous Kallikrein Inhibition in Perioperative Transfusion and Adverse Outcome in Cardiac Surgical Patients

Objective: The goal of this study was to explore the relationship among endogenous plasma kallikrein inhibition (KI), perioperative bleeding, and adverse outcomes in cardiac surgery. Design: A prospective, observational study. Setting: University teaching hospitals. Participants: Cardiac surgical patients. Interventions: Endogenous plasma KI levels (%) and kallikrein-like activity (KKA) were measured preoperatively, 30 minutes into cardiopulmonary bypass, and at the end of surgery. Patients were divided into quartiles of preoperative KI. Data including risk factors, blood loss, transfusion requirements, and postoperative outcomes were collected. Measurements and Main Results: Preoperative endogenous KI ranged from 40% to 175%, where 100% represents the activity of pooled healthy volunteer plasma. The quartiles of KI levels were as follows: quartile 1, KI = 40% to 83.8% (n = 40); quartile 2, KI = 84% to 101.5% (n = 40); quartile 3, KI = 102% to 120% (n = 42); and quartile 4, KI = 121% to 175% (n = 38). The hematocrits on admission to the intensive care unit were as follows: quartile 1, 28% ± 4%; quartile 2, 26% ± 4%; quartile 3, 26% ± 4%; and quartile 4, 24% ± 4% (p = 0.009). Blood product use was similar among quartiles in the operating room. Quartiles 3 and 4 received more blood (p = 0.003) and platelet (p = 0.04) transfusions than quartiles 1 and 2 in the first 24 hours after surgery. More patients in quartile 4 were ventilated for more than 24 hours after surgery (p < 0.05). Hospital length of stay was longest in quartile 4 (p = 0.002). Conclusion: Contrary to expectation, higher endogenous KI levels were associated with more blood product transfusion, longer postoperative mechanical ventilation, and hospital length of stay. These findings raise questions as to the role of KI in postoperative outcomes.