Continuous renal replacement therapy in cytokine release syndrome following immunotherapy or cellular therapies?

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadRecently, an increasing number of novel drugs were approved in oncology and hematology. Nevertheless, pharmacology progress comes with a variety of side effects, of which cytokine release syndrome (CRS) is a potential complication of some immunotherapies that can lead to multiorgan failure if not diagnosed and treated accordingly. CRS generally occurs with therapies that lead to highly activated T cells, like chimeric antigen receptor T cells or in the case of bispecific T-cell engaging antibodies. This, in turn, leads to a proinflammatory state with subsequent organ damage. To better manage CRS there is a need for specific therapies or to repurpose strategies that are already known to be useful in similar situations. Current management strategies for CRS are represented by anticytokine directed therapies and corticosteroids. Based on its pathophysiology and the resemblance of CRS to sepsis and septic shock, as well as based on the principles of initiation of continuous renal replacement therapy (CRRT) in sepsis, we propose the rationale of using CRRT therapy as an adjunct treatment in CRS where all the other approaches have failed in controlling the clinically significant manifestations.School of Doctoral Studies - Iuliu Hatieganu University Romanian Government Ion Chiricuta Oncology Institute Cluj Napoca Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca European Economic Spac

Sepsis-Associated Coagulopathy

Systemic inflammatory activation in sepsis often leads to coagulation activation, but the relationship is bilateral, as coagulation also modulates the inflammatory response. This close associate has significant consequences for the pathogenesis of microvascular thrombosis and organ dysfunction in sepsis. While coagulation activation can be beneficial for immune defense, it can also be detrimental once it becomes widespread and uncontrolled. The knowledge of the pathophysiologic mechanisms involved in the interaction between infection and coagulation may lead to the better timing for the administration of targeted antithrombotic therapies in septic patients. This brief review highlights the pathophysiologic pathways leading to the prothrombotic state in sepsis and the mechanisms that play a role in the interaction between infection and coagulation

The current status of viscoelastic testing in septic coagulopathy

Sepsis can be associated with different degrees of coagulopathy, ranging from a mild activation of the coagulation system to disseminated intravascular coagulation (DIC). The evaluation of haemostasis in the context of sepsis is important since it has been shown that anticoagulant therapies were beneficial mainly in patients with sepsis-induced DIC, but not in the general population of septic patients. Sepsis-induced haemostatic disturbances are not adequately reflected by standard coagulation tests (SCTs) which only consider the plasmatic components of the haemostatic system and not the cellular components. In addition, SCTs only assess the initiation phase of coagulation and reflect the activity of pro-coagulant factors, but lack sensitivity for the anticoagulant drive and the fibrinolytic activity. Viscoelastic tests (VET) are whole-blood tests which can assess clot formation and dissociation, and the contribution of both plasmatic and cellular components with a shorter turnaround time compared to SCTs. The use of VET in septic patients has proved useful for the assessment of the fibrinolytic activity, detecting hypercoagulable status and for the diagnosis of DIC and mortality risk prediction. While having relevant advantages over SCTs, the VET also present some blind spots or limitations leaving space for future improvement by the development of new reagents or new viscoelastic parameters

Intraoperative transfusion practices and perioperative outcome in the European elderly: A secondary analysis of the observational ETPOS study

The demographic development suggests a dramatic growth in the number of elderly patients undergoing surgery in Europe. Most red blood cell transfusions (RBCT) are administered to older people, but little is known about perioperative transfusion practices in this population. In this secondary analysis of the prospective observational multicentre European Transfusion Practice and Outcome Study (ETPOS), we specifically evaluated intraoperative transfusion practices and the related outcomes of 3149 patients aged 65 years and older. Enrolled patients underwent elective surgery in 123 European hospitals, received at least one RBCT intraoperatively and were followed up for 30 days maximum. The mean haemoglobin value at the beginning of surgery was 108 (21) g/l, 84 (15) g/l before transfusion and 101 (16) g/l at the end of surgery. A median of 2 [1–2] units of RBCT were administered. Mostly, more than one transfusion trigger was present, with physiological triggers being preeminent. We revealed a descriptive association between each intraoperatively administered RBCT and mortality and discharge respectively, within the first 10 postoperative days but not thereafter. In our unadjusted model the hazard ratio (HR) for mortality was 1.11 (95% CI: 1.08–1.15) and the HR for discharge was 0.78 (95% CI: 0.74–0.83). After adjustment for several variables, such as age, preoperative haemoglobin and blood loss, the HR for mortality was 1.10 (95% CI: 1.05–1.15) and HR for discharge was 0.82 (95% CI: 0.78–0.87). Preoperative anaemia in European elderly surgical patients is undertreated. Various triggers seem to support the decision for RBCT. A closer monitoring of elderly patients receiving intraoperative RBCT for the first 10 postoperative days might be justifiable. Further research on the causal relationship between RBCT and outcomes and on optimal transfusion strategies in the elderly population is warranted. A thorough analysis of different time periods within the first 30 postoperative days is recommended

Intraoperative transfusion practices in Europe

© 2016 The Author. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.Background: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. Methods: We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. Results: The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl-1 and increased to 9.8 (1.8) g dl-1 after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Conclusions: Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl-1), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold