Despite current recommendations on the management of severe peri-operative bleeding, there is no pragmatic guidance for the peri-operative monitoring and management of cardiac surgical patients taking direct oral anticoagulants. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology, of their own volition, performed an independent systematic review of peerreviewed original research, review articles and case reports and developed the following consensus statement. This has been endorsed by the European Association of Cardiothoracic Anaesthesiology. In our opinion, most patients on direct oral anticoagulant therapy presenting for elective cardiac surgery can be safely managed in the peri-operative period if the following conditions are fulfilled: direct oral anticoagulants have been discontinued two days before cardiac surgery, corresponding to five elimination half-live periods; in patients with renal or hepatic impairment or a high risk of bleeding, a pre-operative plasma level of direct oral anticoagulants has been determined and found to be below 30 ng.ml À1 (currently only valid for dabigatran, rivaroxaban and apixaban). In cases where plasma level monitoring is not possible (e.g. assay was not available), discontinuation for 10 elimination half-live periods (four days) is required. For FXa inhibitors, a standard heparin-calibrated anti-Xa level of < 0.1 IU.ml À1 should be measured, indicating sufficient reduction in the anticoagulant effect. Finally, short-term bridging with heparin is not required in the pre-operative period.

Background Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients. Methods A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival. Results In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline. Conclusions Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline. Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).

Summary Modern four‐factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist‐related bleeding vary greatly. They include INR and bodyweight‐related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four‐factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four‐factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four‐factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg‐1. This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half‐dose bolus (12.5 IU.kg‐1) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue‐factor‐activated, factor VII‐dependent and heparin insensitive point‐of‐care tests may be used for peri‐operative monitoring and guiding of prothrombin complex concentrate therapy.

Objective: Ischemia and reperfusion injury (IRI) in cardiac arrest patients after return to spontaneous circulation causes dysfunctions in multiple organs. Kidney injury is generally transient but in some patients persists and contributes both to mortality and increased resource utilisation. Ongoing shock may compound renal injury from IRI, resulting in persistent dysfunction. We tested whether cardiac dysfunction was associated with the development of persistent acute kidney injury (PAKI) in the first 72 hours after cardiac arrest. Methods: We performed an observational retrospective study from January 2013 to April 2017. We included consecutive patients treated after out-of-hospital cardiac arrest at a single academic medical center with renal function measured and immediately and for 48 hours post arrest. We also recorded each patient's pre arrest baseline creatinine, demographic and clinical characteristics. Our primary outcome of interest was PAKI, defined as acute kidney injury (AKI) on at least 2 measurements 24 hours apart. We compared demographics and outcomes between patients with PAKI and those without, and used logistic regression to identify independent predictors of PAKI. Results: Of 98 consecutive patients, we excluded 24 for missing data. AKI was present in 75% of subjects on arrival. PAKI developed in 35% of patients. PAKI patients had a longer hospital length of stay (median 21 vs 11 days) and lower hospital survival (47% vs 71%). Serum lactate levels, dosage of adrenaline during resuscitation and days of dobutamine infusion strongly predicted PAKI. Conclusions: Among patient who survive cardiac arrest, acute AKI is common and PAKI occurs in more than one third. PAKI is associated both with survival and with length of stay at the hospital. High doses of adrenaline, high serial serum lactate levels, and dose of dobutamine predict

Body mass index (BMI) and specifically overweight and obesity have been associated with an increased platelet reactivity in different series of patients. This information is derived by different laboratory platelet function tests (PFTs) like mean platelet volume (MPV), platelet microparticles, thromboxane B2 metabolites, and others. Point-of-care PFT, which are often used in cardiac surgery, are rarely addressed. The present study aims to verify platelet reactivity using multiple-electrode aggregometry (MEA) as a function of BMI in cardiac surgery patients. One-hundred ninety-eight cardiac surgery patients free from the effects of drugs acting on the P2Y receptor and undergoing cardiac surgery received MEA-PFT immediately before surgery. Platelet reactivity was compared between normal weight and overweight-obese subjects. There were 99 underweight/normal (BMI < 25), 60 overweight (BMI ≥ 25) and 39 obese (BMI ≥ 30) patients. Overweight-obese patients did not show higher platelet counts nor a clear platelet hyper-reactivity, when tested with MPV and MEA ADP test. At TRAPtest, the overweight/obese patients had a significantly (P = 0.011) higher platelet reactivity (median 118, interquartile range 106-136) than controls (median 112, interquartile range 101-123) and a higher rate of platelet hyper-reactivity (odds ratio 2.19, 95% confidence interval 1.15-4.16, P = 0.016) in a multivariable model. A minor association was found between the BMI and platelet reactivity at TRAPtest, with a higher degree of activity for increasing BMI. The BMI determines an increased thrombin-dependent platelet reactivity in cardiac surgery patients. Thrombin is extensively formed during cardiac surgery, and this may explain the lower postoperative bleeding observed in obese patients in previous studies.