[Basics for the Use of Andexanet]. / Grundlagen zur Anwendung von Andexanet.

BACKGROUND: For life-threatening or uncontrollable bleeding in association with the thrombin inhibitor dabigatran, the monoclonal antibody fragment idarucizumab is available, and for bleeding in association with the direct factor Xa inhibitors rivaroxaban or apixaban, the modified recombinant FXa protein andexanet is available for reversal. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures. METHODS: An interdisciplinary group of experienced experts in the fields of angiology, hematology, internal medicine, clinical pharmacology, laboratory medicine, transfusion medicine, anesthesiology, intensive care, and hemostaseology developed recommendations relevant to daily clinical practice based on the current scientific evidence. RESULTS: Reversal of oral anticoagulants should be considered for severe bleeding in the following situations: (1) life-threatening bleeding or refractory hemorrhagic shock, (2) intracerebral bleeding, or (3) endoscopically unstoppable gastrointestinal bleeding. After successful hemostasis, anticoagulation (e.g., direct oral anticoagulant, vitamin K antagonist, and heparin) should be resumed promptly, taking into account individual bleeding and thromboembolic risk. DISCUSSION: This article aims to facilitate the management of patients with andexanet by all medical disciplines involved, thereby ensuring optimal care of patients during bleeding episodes.

[Surviving Sepsis Campaign update 2018: the 1 h bundle : Background to the new recommendations]. / Surviving Sepsis Campaign Update 2018: das 1­h-Bundle : Hintergrund zu den neuen Empfehlungen.

A new update of the sepsis bundle was published by the Surviving Sepsis Campaign (SSC) in April 2018. The original 3 h and 6 h bundles have been restructured and combined into a 1­h bundle. The recommendations comprehensively focus on diagnostic and therapeutic measures which should be carried out within 1 h after recognition of sepsis. This article presents the background and discusses criticisms of the new recommendations.

MicroRNAs 143 and 150 in whole blood enable detection of T-cell immunoparalysis in sepsis.

BACKGROUND: Currently, no suitable clinical marker for detection of septic immunosuppression is available. We aimed at identifying microRNAs that could serve as biomarkers of T-cell mediated immunoparalysis in sepsis. METHODS: RNA was isolated from purified T-cells or from whole blood cells obtained from septic patients and healthy volunteers. Differentially regulated miRNAs were identified by miRNA Microarray (n = 7). Validation was performed via qPCR (n = 31). RESULTS: T-cells of septic patients revealed characteristics of immunosuppression: Pro-inflammatory miR-150 and miR-342 were downregulated, whereas anti-inflammatory miR-15a, miR-16, miR-93, miR-143, miR-223 and miR-424 were upregulated. Assessment of T-cell effector status showed significantly reduced mRNA-levels of IL2, IL7R and ICOS, and increased levels of IL4, IL10 and TGF-ß. The individual extent of immunosuppression differed markedly. MicroRNA-143, - 150 and - 223 independently indicated T-cell immunoparalysis and significantly correlated with patient's IL7R-/ICOS-expression and SOFA-scores. In whole blood, composed of innate and adaptive immune cells, both traits of immunosuppression and hyperinflammation were detected. Importantly, miR-143 and miR-150 - both predominantly expressed in T-cells - retained strong power of discrimination also in whole blood samples. CONCLUSIONS: These findings suggest miR-143 and miR-150 as promising markers for detection of T-cell immunosuppression in whole blood and may help to develop new approaches for miRNA-based diagnostic in sepsis.

[When A is not A anymore: problems and pitfalls with blood group typing]. / Wenn A nicht mehr A ist: Schwierigkeiten und Fallstricke bei der Blutgruppenbestimmung.

Correct blood group typing is a prerequisite for transfusion. In most cases blood group determination is without problems; however, in individual cases various factors can complicate blood group determination and sometimes lead to confusing findings. For a better understanding the clinician should have basic knowledge of blood typing. Blood group determination usually covers the AB0 blood groups, Rhesus and Kell systems; in addition, a direct Coombs test and an antibody screening test for the detection of irregular antibodies in the recipient are performed. Confusion of patients, blood samples, results or preparations can lead to severe consequences due to incompatible transfusion and must be prevented. In this context, bedside blood type testing before transfusion is of utmost importance. Problems in laboratory analysis as well as patient-related factors, such as the existence of irregular antibodies against red blood cells can complicate the immunohematology diagnostics. Certain medications, such as daratumumab, lead to a significantly increased complexity in laboratory analyses. Massive transfusions can lead to chimerism with more than one population of circulating red blood cells. Hematopoetic stem cell transplantation can also lead to a change in blood groups as well as chimerism. In addition, there are various other rare causes that can result in difficulties in blood group determination, such as rare blood groups or rare disease-associated phenomena. In the case of problems in blood group determination, early and close cooperation with transfusion medicine is essential for the clinician.

[Novel aspects of the guidelines for hemotherapy 2017 : Implications for anesthesiology]. / Novelle der Hämotherapierichtlinien 2017 : Implikationen für die Anästhesiologie.

Based on the German Transfusion Law, the periodically updated guidelines "Richtlinien zur Gewinnung von Blut und Blutbestandteilen und zur Anwendung von Blutprodukten" ("Hämotherapierichtlinien") are intended to provide the current knowledge and state of the art of blood transfusion practice in Germany. The novel update 2017 contains relevant changes for blood donation, especially the extension of the exclusion period of persons at risk for sexually transmitted HBV, HCV and HIV diseases to 12 months. Moreover, the guidelines provide several changes relevant to blood transfusion practice in anesthesiology, such as: all autologous hemotherapy procedures including normovolemic hemodilution, cell saver, and autologous blood donation and transfusion require formal registration at the regulatory authority. A special detailed protocol is required for every cell saver use. A formal quality control procedure for cell saver use is necessary at least every 3 months. Retransfusion of unprocessed shed blood is generally not permitted. Guidance is provided for the clinical situation of lacking consent for blood transfusion in emergency situations (under certain circumstances blood transfusion may still be allowed). For the first time, the concept of "patient blood management" is explicitly mentioned and recommended in the guidelines. Especially the novel regulations regarding autologous blood use impose new challenges in clinical practice in anesthesiology.

[International guidelines from the Surviving Sepsis Campaign : 2016 update]. / Internationale Leitlinien der Surviving Sepsis Campaign : Update 2016.

An update to the international guidelines for sepsis therapy was published by the Surviving Sepsis Campaign (SSC) in March 2017. The guidelines have been completely restructured and comprehensively deal with new evidence. The guidelines discuss sepsis-specific therapeutic measures and provide detailed recommendations on general intensive care measures for sepsis. This article summarizes the most important amendments and suggests delving deeper into the guidelines.

[International guidelines of the Surviving Sepsis Campaign : update 2012]. / Internationale Leitlinien der Surviving Sepsis Campaign : Update 2012.

An update of the international guidelines for therapy of sepsis was published in February 2012 by the Surviving Sepsis Campaign (SSC). The update includes a further development of the guidelines from 2004 and 2008. The guidelines are divided into three sections, sepsis-specific therapeutic measures, recommendations on general intensive care measures for sepsis and finally special features of sepsis in pediatric intensive care medicine are presented in detail. This article discusses the most important amendments in the first two sections and delving deeper into the guidelines.

[Corticosteroid administration for acute respiratory distress syndrome : therapeutic option?]. / Kortikosteroidgabe beim schweren akuten Lungenversagen : Sinnvolle Therapieoption?

Despite a number of clinical trials there is still controversy about the role of corticosteroid therapy in acute respiratory distress syndrome (ARDS). In addition recent meta-analyses differed markedly in the conclusions. This review is intended to provide a short practical guide for the clinician. Based on the available literature, high-dose and pre-emptive administration of corticosteroids is hazardous and not indicated. A low-dose corticosteroid regime given for 4 weeks may potentially be helpful and can be considered in acute or unresolved ARDS in less than 14 days after onset of ARDS, if a close infection surveillance program is available, if neuromuscular blockade can be avoided and if a stepwise dose reduction of corticosteroids is performed. The total daily dose at the beginning of treatment should not exceed 2 mg/kg body weight (BW) methylprednisolone.

Indocyanine green clearance after cardiac surgery: the impact of cardiopulmonary bypass.

Plasma clearance of indocyanine green has recently been established as a tool to monitor hepatic function and perfusion non-invasively. Reduced indocyanine green clearance has been associated with adverse outcome in cardiac surgery patients, and cardiopulmonary bypass has been hypothesized to be one important triggering factor. We performed a prospective observational study comparing the influence of off-pump and on-pump coronary surgery on perioperative indocyanine green clearance. Twenty-five consecutive adult patients without known pre-existing hepatic diseases scheduled for off-pump coronary artery bypass grafting were evaluated for hepatic dysfunction pre- and postoperatively with serial measurements of indocyanine green plasma clearance, specific laboratory values and liver function scores. Twenty-five matched patients who underwent coronary artery bypass grafting surgery with cardiopulmonary bypass in the same period served as controls. Parameters of postoperative hepatic function, including measurements of indocyanine green plasma clearance and specific laboratory values and scores, did not differ significantly between patients undergoing off-pump coronary artery bypass grafting and patients undergoing coronary artery bypass grafting with extracorporeal circulation. In patients without pre-existing hepatic diseases, a significant influence of cardiopulmonary bypass on perioperative indocyanine green plasma clearance as well as on liver specific laboratory parameters and scores cannot be proven.

Determinants of cerebral oxygenation during cardiac surgery.

BACKGROUND: Neuropsychological deficits after cardiac surgery are attributed to the side effects of cardiopulmonary bypass (CPB). To protect the brain from ischemic damage, the influences of temperature, blood pressure, blood gases, acid-base status, and hemodilution on cerebral oxygenation have to be elucidated and quantified. METHODS: Forty-one consecutive patients were investigated during cardiac surgery while on CPB. Operative management included moderate hypothermia of 26 degrees C and the alpha-stat pH management. With near-infrared spectrophotometry, changes in oxygenated hemoglobin (HbO2, representing oxygen delivery) and oxidized cytochrome a,a3 (CtO2, cellular oxygenation) in brain tissue were obtained noninvasively. In addition, venous saturation of the brain was measured via a catheter in the jugular bulb (SBJO2). The influence of operative management parameters on cerebral oxygenation was calculated by univariate and multiple regression analyses. RESULTS: Before and after CPB there was no significant multivariate determinant of cerebral oxygenation. During CPB, HbO2 depended solely on PCO2 (P < .01; r = .89). CtO2 was determined by pH (P < .01), esophageal temperature (P < .01), PCO2 (P < .01), and Hb (P < .01). These parameters explained nearly all changes of the cytochrome measurements during CPB (r = .99). Arterial PCO2 (P < .01) and pH (P < .01) influenced brain venous oxygen saturation (SBJO2; r = .98). CONCLUSIONS: Cerebral oxygenation is autoregulated during cardiac surgery before and after CPB. During CPB, Hb, temperature, pH, and PCO2 determined at least 85% of all changes in cerebral oxygenation. The main causes of impaired cerebral oxygenation are the decrease in Hb with hemodilution, vasoconstriction due to hypocapnia, and the leftward shift of the Hb binding curve in alkalosis and hypothermia.

Postoperative neuropsychological dysfunction and cerebral oxygenation during cardiac surgery.

In 41 patients undergoing cardiac operations with extracorporeal circulation, oxidized cytochrome a,a3(CtO2), deoxygenated hemoglobin (Hb), and oxygenated hemoglobin (HbO2) were measured in brain tissue by near-infrared spectrophotometry (NIRS) intraoperatively. Monitoring also included electroencephalography (EEG) and jugular-bulb venous saturation (SBJO2). All operations were performed using membrane oxygenators, moderate hypothermia (26-28 degrees C) and pH alpha-stat management. During cardiopulmonary bypass (CPB) CtO2 and HbO2) were reduced, reaching minimal values when rewarming was instituted. At the end of the operation CtO2 and HbO2 had regained initial levels. During CPB, arterial PCO2, pH, and temperature were closely related to CtO2 (r = 1000, r = -0.964 and 0.929 respectively; p < 0.001, p < 0.001, and p < 0.003 respectively). Neuropsychological testing by the Mini-Mental-State Test indicated reversible postoperative neuropsychological deficits in four patients. There patients had a lower CtO2 minimum compared to those without these deficits (-4.5 mumol/L v. -0.7 mumol/L; p = 0.036). These findings support the hypothesis that neuropsychological deficits in patients after cardiac surgery can be caused by intraoperative cerebral hypoxia.