title: The effects of high-dose heparin on inflammatory and coagulation parameters following cardiopulmonary bypass.
abstract: 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.
authors.affiliation: Henderson Research Centre, McMaster University, Hamilton, Ontario, Canada. paparella@tin.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Paparella
authors.forename: Osman O
authors.initials: OO
authors.lastname: Al Radi
authors.forename: Qing H
authors.initials: QH
authors.lastname: Meng
authors.forename: Thomas
authors.initials: T
authors.lastname: Venner
authors.forename: Kevin
authors.initials: K
authors.lastname: Teoh
authors.forename: Edward
authors.initials: E
authors.lastname: Young
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D000990:Antithrombin III; D001777:Blood Coagulation / Q000187:drug effects*; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000097:blood; D010978:Platelet Factor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C046193:antithrombin III-protease complex; D010978:Platelet Factor 4; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases