Post-operative iron in cardiac surgery trial - a protocol for a randomised controlled trial.

INTRODUCTION: Anaemia is common after cardiac surgery and has a negative impact on rehabilitation and patient well-being. We aim to compare the efficacy of single, high-dose intravenous iron therapy versus oral iron supplementation to correct anaemia following open cardiac surgery. METHODS: We present a randomised, active-control superiority trial. Adult patients with moderate anaemia (haemoglobin 5.0-6.8 mmol/l) on the first post-operative day after first-time, non-emergent cardiac surgery are eligible. After stratification by gender, 110 patients are randomised 1:1 to either single, high-dose intravenous iron therapy (20 mg/kg ferric derisomaltose) or oral iron supplementation (100 mg ferrous sulphate orally twice daily). The primary outcome measure at the four-week follow-up is the proportion of participants who are neither anaemic (haemoglobin less-than 8.1 mmol/l in men and less-than 7.5 mmol/l in women) nor have received allogeneic red blood cells since randomisation. Secondary outcome measures include changes in haemoglobin and iron biomarkers, exercise capacity, patient-reported outcome measures and cost of care at the four-week follow-up. CONCLUSION: The results of the PICS trial may fundamentally alter future management of anaemia following cardiac surgery. FUNDING: The study is supported by Aarhus University Hospital, an unrestricted research grant by Pharmacosmos A/S (Holbæk, Denmark) and an independent grant from the Health Research Foundation of the Central Denmark Region (ISM). TRIAL REGISTRATION: EudraCT number: 2020-001389-12; Clinical Trials ID: NCT04608539.

Impact of minimally invasive extracorporeal circulation on coagulation-a randomized trial.

OBJECTIVES: Minimally invasive extracorporeal circulation (MiECC) is suggested to have favourable impact on blood loss compared to conventional extracorporeal circulation. We aimed to compare the impact of both systems on coagulation. METHODS: Randomized trial comparing endogenous thrombin-generating potential early after elective coronary surgery employing either MiECC group (n = 30) or conventional extracorporeal circulation group (n = 30). Secondary outcomes were in vivo thrombin generation, bleeding end points and haemodilution, as well as morbidity and mortality up to 30-day follow-up. RESULTS: Compared to the conventional extracorporeal circulation group, the MiECC group showed (i) a trend towards a higher early postoperative endogenous thrombin-generating potential (P = 0.06), (ii) lower intraoperative levels of thrombin-antithrombin complex and prothrombin fragment 1 + 2 (P < 0.001), (iii) less haemodilution early postoperatively as measured by haematocrit and weight gain, but without correlation to coagulation factors or bleeding end points. Moreover, half as many patients required postoperative blood transfusion in the MiECC group (17% vs 37%, P = 0.14), although postoperative blood loss did not differ between groups (P = 0.84). Thrombin-antithrombin complex levels (rs = 0.36, P = 0.005) and prothrombin fragment 1 + 2 (rs = 0.45, P < 0.001), but not early postoperative endogenous thrombin-generating potential (rs = 0.05, P = 0.72), showed significant correlation to increased transfusion requirements. The MiECC group demonstrated significantly lower levels of creatine kinase-MB, lactate dehydrogenase and free haemoglobin indicating superior myocardial protection, less tissue damage and less haemolysis, respectively. Perioperative morbidity and 30-day mortality did not differ between groups. CONCLUSIONS: Conventional but not MiECC is associated with significant intraoperative thrombin generation despite full heparinization. No correlation between coagulation factors or bleeding end points with the degree of haemodilution could be ascertained. CLINICALTRIALS.GOV IDENTIFIER: NCT03216720.

The association between a three-day ticagrelor discontinuation and perioperative bleeding complications.

OBJECTIVES: Dual antiplatelet therapy at the time of cardiac surgery is associated with excessive perioperative bleeding. International guidelines, therefore, recommended discontinuing oral adenosine diphosphate receptor antagonists prior to non-emergency surgery. In this study, we analysed whether a 3-day ticagrelor discontinuation was sufficient to avoid major bleeding complications. METHODS: This study is a retrospective cohort analysis of 3377 patients undergoing coronary artery bypass or single-valve surgery from January 2013 to September 2017. Patients exposed to ticagrelor prior to surgery were compared with control patients exposed to aspirin only. Outcome measures included transfusion requirements, bleeding volumes, the need for re-exploration and the composite outcome major bleeding complication. Data were retrieved from the the Western Denmark Heart Registry. RESULTS: During the study period, 101 patients were preoperatively exposed to ticagrelor, whereas 3276 patients were exposed to aspirin only. Propensity-score matching resulted in 90 pairs of patients. Overall, ticagrelor exposure was associated with a greater risk of major bleeding complications compared with control patients [31 vs 12%, relative risk 2.6, 95% confidence interval (CI) 1.4-4.8]. While ticagrelor exposure within 0-72 h before surgery (n = 42) was associated with a substantially increased risk of major bleeding complications (48 vs 10%, relative risk 5.0, 95% CI 1.9-13.4), ticagrelor exposure 72-120 h before surgery (n = 48) showed no statistically significant association (17 vs 15%, relative risk 1.1, 95% CI 0.4-2.9). CONCLUSIONS: In our historical cohort, ticagrelor exposure 0-72 h prior to cardiac surgery was associated with an increased risk of major bleeding complications. On the other hand, ticagrelor exposure 72-120 h prior to surgery was not associated with a clinically relevant increase in major bleeding complications.

The association between platelet transfusion and adverse outcomes after coronary artery bypass surgery.

OBJECTIVES: Previous research suggests that platelet transfusion is associated with adverse events after coronary artery bypass grafting (CABG). The aim of the current analysis was to verify this hypothesis. METHODS: Data from 6745 consecutive patients undergoing CABG from 2006 through 2012 were collected. Patients receiving platelet transfusions intraoperatively or postoperatively in the intensive care unit were compared with control patients. To adjust for possible confounders, propensity score matching and conditional regression analyses were performed. Short-term outcomes were 30-day mortality, in-hospital myocardial infarction and stroke. Mid-term outcomes were 6-month mortality, and need for coronary angiography or repeat coronary revascularization within 6 months after surgery. Data were retrieved from the Western Denmark Heart Registry. RESULTS: Using propensity scores, 982 patients exposed to platelets were matched with 982 control patients. Platelet transfusion was associated with a higher rate of postoperative coronary angiography (adjusted odds ratio 2.34, 95% confidence interval 1.15-4.76). There was no significant association between platelet transfusion and postoperative mortality, myocardial infarction, stroke and need for repeat coronary revascularization. CONCLUSIONS: Platelet transfusion at the time of CABG is not associated with increased postoperative mortality, in-hospital myocardial infarction, stroke or need for repeat coronary revascularization.

Autotransfusion of a restricted volume of shed mediastinal blood does not affect the haemostatic capacity in patients following cardiac surgery.

UNLABELLED: The aim was to investigate the haemostatic capacity after autotransfusion of shed mediastinal blood in patients following cardiac surgery. Fifteen cardiac surgery patients with a chest tube drainage ≥ 300 mL blood within the first 6 hours postoperatively were included. The haemostatic capacity was evaluated using whole blood thromboelastometry (ROTEM(®)), impedance aggregometry (Multiplate(®)) and conventional coagulation tests. Measurements were carried out in (1) mediastinal blood, and in blood samples obtained, (2) before autotransfusion, and (3) after autotransfusion of mediastinal blood. In shed mediastinal blood, ROTEM(®) analyses showed reduced clot firmness in the EXTEM (p < 0.001), INTEM (p < 0.001), and FIBTEM assay (p = 0.002). Platelet function and conventional coagulation parameters were significantly impaired (p < 0.001). However, ROTEM(®), platelet function and conventional coagulation tests remained unchanged after autotransfusion. CONCLUSION: Shed mediastinal blood has a substantially reduced haemostatic capacity, but autotransfusion of an average of 350 mL did not affect the overall haemostatic capacity.

Antiplatelet therapy at the time of coronary artery bypass grafting: a multicentre cohort study.

OBJECTIVES: The purpose of this multicentre cohort study was to examine the relationship between antiplatelet therapy (APT) at the time of coronary artery bypass grafting (CABG) and postoperative bleeding complications, transfusion requirements and adverse cardiovascular events. METHODS: A matched-pair analysis was carried out on 6350 consecutive patients undergoing CABG at the three university hospitals in Western Denmark. Patients exposed to aspirin or clopidogrel within 5 days before surgery were compared with those not exposed to these drugs. The data used in the study were retrieved from the Western Denmark Heart Registry. RESULTS: Of the 6350 patients enrolled, 1846 (29%) had been exposed to aspirin or clopidogrel within 5 days prior to CABG (the APT group). Matching with the remaining 4504 (71%) patients of the control group resulted in 1132 pairs of patients. Patients in the APT group had greater mean chest tube drainage volumes (946 vs 775 ml; P < 0001) and greater transfusion requirements (ranging from 37.4-57.5 vs 29.8%; P < 0.0001) than control group patients. Preoperative aspirin therapy was not associated with greater reoperation rates (4.0 vs 3.9%; P = 0.005); nor was it an independent risk factor for severe postoperative bleeding >1000 ml (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.55-1.34). Preoperative clopidogrel use, on the other hand, was associated with greater reoperation rates (10.2 vs 3.9% in the control group; P = 0.005) and was an independent predictor of severe postoperative bleeding (OR: 2.08, 95% CI: 1.55-2.80). Overall, preoperative APT had no significant effect on postoperative 30-day mortality, incidence of myocardial infarction, stroke or need for dialysis. CONCLUSIONS: Preoperative APT is associated with increased bleeding and greater transfusion requirements after CABG. Clopidogrel exposure is associated with greater reoperation rates and is an independent risk factor for severe postoperative bleeding.