Blood Loss after Cardiopulmonary Bypass, Standard vs Titrated Protamine: A Meta-Analysis

Background: The aim of this meta-analysis was to determine whether standard or titrated dosing of protamine is more effective in facilitating haemostasis after cardiac surgery with cardiopulmonary bypass (CPB). Methods: We searched MEDLINE, and Biomedical Central using the terms ‘cardiopulmonary bypass and heparin and protamine’. Studies were included in the meta-analysis if they were randomised controlled trials (RCTs), controlled clinical studies, or cohort studies with designs comparing the postoperative volume of bleeding between the study group (titrated dose) and the control group (standard dose) for protamine reversal of surgical anticoagulation in CPB procedures. The primary outcome of interest was postoperative blood loss. Results: There were 219 studies identified in the initial search; four of these were included in the meta-analysis. All studies were RCTs, involving a total of 507 patients. Postoperative blood loss was lower in the study group (range: 625-839 ml) compared with the control group (range: 765-995 ml) in all four studies. Transfusion of packed red blood cells was also lower in the study group compared with the control group in all four studies. There was no evidence of significant heterogeneity in postoperative blood loss among the four studies (Q=4.224, I2=28.98%, p=0.238); hence, a fixed-effects model of analysis was used. The overall÷combined standardised difference in means of postoperative blood loss volume significantly favoured study treatment over control treatment (-0.562±0.322, p.