Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU.

BACKGROUND: Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear. METHODS: In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization. RESULTS: A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups. CONCLUSIONS: Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621 .).

Changes in thrombin generation in children after cardiac surgery and ex-vivo response to blood products and haemostatic agents.

Impaired haemostasis has been reported in children with congenital heart disease undergoing cardiopulmonary bypass. As thrombin generation encompasses all phases of the coagulation process, this analysis might provide the best assessment of global haemostasis. A prospective study was undertaken to test the hypothesis that thrombin generation reveals an impaired haemostasis after paediatric cardiac surgery and that ex-vivo addition of platelet concentrate and haemostatic agents improves thrombin generation. The study comprised 29 children with congenital heart disease, who underwent corrective surgery including cardiopulmonary bypass. Thrombin generation was analysed both in platelet-poor plasma and platelet-rich plasma. Analysis of the thrombin generation showed a significantly prolonged lag time (Pplatelet-poorandplatelet-richplasma < 0.001), decreased peak thrombin generation (Pplatelet-poorplasma = 0.013; Pplatelet-richplasma < 0.001) as well as a decreased endogenous thrombin generation potential (Pplatelet-poorandplatelet-richplasma < 0.001) after cardiopulmonary bypass compared to baseline. Ex-vivo addition of platelet concentrate, fibrinogen concentrate and recombinant factor VIIa improved thrombin generation significantly (all P < 0.001). Changes were most pronounced after addition of platelet concentrate. The present study showed that thrombin generation was significantly reduced after cardiopulmonary bypass in children, both when analysed in platelet-poor and platelet-rich plasma. The impaired haemostasis was not only restored after ex-vivo addition of platelet concentrate but also rVIIa improved the haemostatic capacity.

Ex-vivo response to blood products and haemostatic agents after paediatric cardiac surgery.

Bleeding complications after cardiac surgery are of particular importance in children because they are more prone to volume overload. To optimize haemostatic intervention, the coagulopathy has to be characterized, and knowledge about the effect of blood products and haemostatic agents is needed. The aims of the present study were to investigate changes in coagulation profiles after paediatric cardiac surgery and the effect after ex-vivo addition of blood products and haemostatic agents. Coagulation profiles were evaluated by thromboelastometry (ROTEM) in 54 children before and immediately after cardiac surgery. The haemostatic potential of various factor concentrates (fibrinogen concentrate, recombinant factor VIIa and factor XIII), fresh frozen plasma (FFP), pooled platelets and tranexamic acid was investigated. After surgery, the coagulation profiles revealed significantly prolonged clotting time (P=0.008), and reduced clot propagation (P<0.001) as well as reduced whole blood clot stability (P<0.001). Ex-vivo addition of pooled platelets fully reversed the postoperative coagulopathy; this was also seen after addition of recombinant factor VIIa although less pronounced. Finally, addition of fibrinogen concentrate, FFP or tranexamic acid improved clot stability significantly. Whole blood coagulation was significantly impaired after cardiac surgery in children. Ex-vivo studies showed a total reversal of the coagulopathy after addition of pooled platelets and significantly improved clot stability after addition of fibrinogen concentrate, FFP and tranexamic acid, respectively.