Key result
High-dose unfractionated heparin (600 U/kg) during cardiopulmonary bypass reduced thrombin-antithrombin complex (P=0.04) and platelet factor 4 levels (P=0.04) compared to a 300 U/kg dose.
Why the study?
Does high-dose unfractionated heparin improve inflammatory and coagulation parameters compared to low-dose heparin in patients undergoing elective coronary artery bypass surgery requiring cardiopulmonary bypass?
RCT (n=40)
randomized
Does high-dose unfractionated heparin improve inflammatory and coagulation parameters compared to low-dose heparin in patients undergoing elective coronary artery bypass surgery requiring cardiopulmonary bypass?
p-value: p=0.04
High-dose heparin during cardiopulmonary bypass better preserves the coagulation system by reducing thrombin formation and platelet activation, without significantly affecting systemic inflammation or increasing postoperative bleeding.
High-dose heparin attenuates thrombin generation and platelet activation during CPB; extends biomarker evidence for dosing optimization in cardiac surgery.
Systemic inflammation and the activation of the coagulation system following cardiopulmonary bypass (CPB) may contribute to postoperative complications. In vitro studies have demonstrated that heparin possesses anti-inflammatory properties. To ascertain the relative benefits of high versus low heparin doses, we studied the impact of varying heparin doses on the inflammatory response and coagulation system during and following CPB. Forty patients scheduled for elective coronary artery bypass surgery requiring CPB were randomized to either a low dose (300 U/kg) (Group L) or a high dose of unfractionated heparin (600 U/kg) (Group H). To evaluate the inflammatory response, proinflammatory cytokines [tumor necrosis factor-alpha and interleukin-6 (IL-6)] were measured at four different times: before CPB (T0), 30 min after the institution of CPB (T1), 30 min after cross-clamp release (T2), and 4 h after the end of CPB (T3). Thrombin-antithrombin complex, platelet factor 4 and anti-activated factor X heparin concentrations were also measured. Patients in Group H received greater heparin (44.934 U versus 27.741 U, P<0.001) and protamine (P=0.003) doses. Postoperative blood loss and blood products transfusions were not significantly different in the groups. At T1, mean heparin plasma concentration was higher in Group H (P<0.001). IL-6 was significantly lower in Group H compared with Group L (P=0.01) only at T1. Using a mixed-effects statistical model, tumor necrosis factor-alpha and IL-6 levels were comparable regardless of the heparin dose. Thrombin-antithrombin complex levels were lower in Group H (P=0.04) and platelet factor 4 levels were significantly lower in Group H at T2 (P=0.04). Higher heparin doses were associated with higher heparin concentrations during CPB. A high heparin dose achieved a better preservation of the coagulation system with less thrombin formation and platelet activation. The heparin dose had small influence on proinflammatory cytokines release.
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Paparella et al. (2005) conducted an RCT in elective coronary artery bypass surgery requiring CPB (n=40). Unfractionated heparin vs. Low dose unfractionated heparin (300 U/kg) was evaluated on Inflammatory response (TNF-alpha, IL-6) and coagulation system parameters (TAT, PF4) (p=0.04). High-dose unfractionated heparin (600 U/kg) during cardiopulmonary bypass reduced thrombin-antithrombin complex (P=0.04) and platelet factor 4 levels (P=0.04) compared to a 300 U/kg dose.
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