Human cytomegalovirus seropositivity is associated with reduced patient survival during sepsis.

BACKGROUND: Sepsis is one of the leading causes of death. Treatment attempts targeting the immune response regularly fail in clinical trials. As HCMV latency can modulate the immune response and changes the immune cell composition, we hypothesized that HCMV serostatus affects mortality in sepsis patients. METHODS: We determined the HCMV serostatus (i.e., latency) of 410 prospectively enrolled patients of the multicenter SepsisDataNet.NRW study. Patients were recruited according to the SEPSIS-3 criteria and clinical data were recorded in an observational approach. We quantified 13 cytokines at Days 1, 4, and 8 after enrollment. Proteomics data were analyzed from the plasma samples of 171 patients. RESULTS: The 30-day mortality was higher in HCMV-seropositive patients than in seronegative sepsis patients (38% vs. 25%, respectively; p = 0.008; HR, 1.656; 95% CI 1.135-2.417). This effect was observed independent of age (p = 0.010; HR, 1.673; 95% CI 1.131-2.477). The predictive value on the outcome of the increased concentrations of IL-6 was present only in the seropositive cohort (30-day mortality, 63% vs. 24%; HR 3.250; 95% CI 2.075-5.090; p < 0.001) with no significant differences in serum concentrations of IL-6 between the two groups. Procalcitonin and IL-10 exhibited the same behavior and were predictive of the outcome only in HCMV-seropositive patients. CONCLUSION: We suggest that the predictive value of inflammation-associated biomarkers should be re-evaluated with regard to the HCMV serostatus. Targeting HCMV latency might open a new approach to selecting suitable patients for individualized treatment in sepsis.

A double-blind randomised feasibility trial of angiotensin-2 in cardiac surgery.

Acute kidney injury is common after cardiac surgery. Vasoplegic hypotension may contribute to kidney injury, and different vasopressors may have variable effects on kidney function. We conducted a double-blind, randomised feasibility trial comparing peri-operative angiotensin-2 with noradrenaline. We randomly allocated 60 patients at two centres to a blinded equipotent angiotensin-2 or noradrenaline infusion intra-operatively and for up to 48 h postoperatively, titrated to mean arterial pressure of 70-80 mmHg. Primary feasibility outcomes included consent rate, protocol adherence, infusion duration, mean arterial pressure maintenance in the target range and major adverse outcomes. Secondary outcomes included kidney injury rate. The consent rate was 47%. Protocol adherence was 100% in the angiotensin-2 group and 94% in the noradrenaline group. Study drug duration was median (IQR [range]) 217 (160-270 [30-315]) vs. 185 (135-301 [0-480]) min (p = 0.78) min intra-operatively, and 5 (0-16 [0-48]) vs. 14.5 (4.8-29 [0-48]) hours (p = 0.075) postoperatively for angiotensin-2 and noradrenaline, respectively. The mean arterial pressure target was achieved postoperatively in 25 of 28 (89%) of the angiotensin-2 group and 27 of 32 (84%) of the noradrenaline group. One participant had a stroke, one required extracorporeal support and three required renal replacement therapy, all in the noradrenaline group (p = 0.99, p = 0.99 and p = 0.1). Acute kidney injury occurred in 7 of 28 in the angiotensin-2 group vs. 12 of 32 patients in the noradrenaline group (p = 0.31). This pilot study suggests that a trial comparing angiotensin-2 with noradrenaline is feasible. Its findings justify further investigations of angiotensin-2 in cardiac surgery.

Report of the first AKI Round Table meeting: an initiative of the ESICM AKI Section.

PURPOSE: Critical Care Nephrology is an emerging sub-specialty of Critical Care. Despite increasing awareness about the serious impact of acute kidney injury (AKI) and renal replacement therapy (RRT), important knowledge gaps persist. This report represents a summary of a 1-day meeting of the AKI section of the European Society of Intensive Care Medicine (ESICM) identifying priorities for future AKI research. METHODS: International Members of the AKI section of the ESICM were selected and allocated to one of three subgroups: "AKI diagnosis and evaluation", "Medical management of AKI" and "Renal Replacement Therapy for AKI." Using a modified Delphi methodology, each group identified knowledge gaps and developed potential proposals for future collaborative research. RESULTS: The following key research projects were developed: Systematic reviews: (a) epidemiology of AKI with stratification by patient cohorts and diagnostic criteria; (b) role of higher blood pressure targets in patients with hypertension admitted to the Intensive Care Unit, and (c) specific clearance characteristics of different modalities of continuous renal replacement therapy (CRRT). Observational studies: (a) epidemiology of critically ill patients according to AKI duration, and (b) current clinical practice of CRRT. Intervention studies:( a) Comparison of different blood pressure targets in critically ill patients with hypertension, and (b) comparison of clearance of solutes with various molecular weights between different CRRT modalities. CONCLUSION: Consensus was reached on a future research agenda for the AKI section of the ESICM.

[Perioperative inflammation]. / Perioperative Inflammation.

BACKGROUND: Surgical interventions and invasive procedures can trigger an inflammatory reaction in patients. This inflammatory reaction is an inherent response by the body and can be triggered by different stimuli, including the surgical tissue trauma itself and also by the administration of drugs commonly used for the induction and maintenance of general anesthesia. OBJECTIVE: Immune system activation is mostly beneficial for the host defense against various exogenous pathogens during infectious disorders; however, if uncontrolled and overshooting or in the case of excessive immune system activation as a consequence of sterile inflammation, the inflammatory host response may also carry the risk for tissue and organ damage, which might severely threaten the patient. The aim of this article is to identify the causal factors of a perioperative immune reaction and to present interventional options. MATERIAL AND METHODS: An extensive MEDLINE search was carried out on the perioperative and postoperative inflammatory response in the field of clinical and basic research. RESULTS: Current publications provide essential information on how surgical patients may be affected by overshooting inflammatory responses. Thus, the choice of administered anesthetic agent and the surgical trauma itself in addition to a supportive therapy may modulate perioperative inflammation in the perioperative phase. The effects on the patient can be multifarious. CONCLUSION: This article discusses the causes and effects of inflammatory processes in the perioperative phase. Additionally, it highlights the immunomodulatory effects of perioperatively administered therapeutics and anesthetics. Knowledge of this topic enables the reader to make qualified decisions in the perioperative setting to improve the individual patient outcome.

[Renal replacement therapy in acute kidney injury : From the indications to cessation]. / Nierenersatzverfahren bei akuter Nierenschädigung : Von der Indikation bis zur Beendigung.

BACKGROUND: The incidence of acute kidney injury (AKI) has increased over the last decades. Renal replacement therapy (RRT) is increasingly being used. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines define AKI by serum creatinine (SCr) elevation and decrease in urinary output (UO) and suggest prevention strategies and recommendations on the management of RRT. Treatment options are limited and RRT remains the gold standard as supportive treatment but implies a substantial escalation of treatment. With respect to the indications and management of RRT, there are only a few evidence-based recommendations. OBJECTIVE: This review summarizes the clinical relevance of AKI and presents the most important aspects on the indications and implementation of RRT. MATERIAL AND METHODS: The available evidence is summarized based on the current literature. RESULTS: Implementation of the KDIGO bundles to prevent AKI in high-risk patients reduces the incidence of AKI. In the absence of absolute indications, the evidence-based recommendations on when to initiate RRT are limited and controversial. Intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) procedures can be considered as complementary therapeutic strategies. The CRRT is recommended in hemodynamically unstable patients. Regional citrate anticoagulation is the recommended anticoagulation in CRRT. The optimal effluent dose is effectively 20-25 ml/kg body weight and hour. Spontaneous diuresis is a best predictor of successful cessation of RRT. CONCLUSION: Risk identification and prevention of AKI are essential. In the absence of absolute indications, initiation and accomplishment of RRT should be patient-adapted and carried out in the clinical context. Newly developed biomarkers could be helpful in the future for a better estimation of the prognosis and for a more precise definition of therapeutic strategies of RRT.

[Non-cardiac surgery in adults with congenital heart defects : Most important parameters in anesthesia management]. / Nichtkardiale Eingriffe bei Erwachsenen mit angeborenen Herzfehlern : Wichtigste Parameter des anästhesiologischen Managements.

BACKGROUND: Adults with congenital heart disease (CHD) represent an increasing proportion of patients undergoing non-cardiac surgery. OBJECTIVE: To identify the most important parameters for management of anesthesia. MATERIAL AND METHODS: Evaluation and discussion of the current original research and guideline recommendations. RESULTS: There are approximately 300,000 patients with CHD living in Germany. The preoperative evaluation is an important influencing factor affecting perioperative morbidity and mortality. Echocardiography is the key instrument for identifying cardiac conditions predisposing to adverse events. The subdivision of CHD into lesions with left-to-right shunt, obstructive lesions and complex congenital heart diseases facilitates the classification of the pathophysiology. CONCLUSION: Decisive for the perioperative outcome of patients with CHD are the identification of high-risk patients, understanding of the individual situation with respect to the underlying pathophysiology and the intraoperative maintenance of cardiac output.

[Metabolic management and nutrition in critically ill patients with renal dysfunction : Recommendations from the renal section of the DGIIN, ÖGIAIN, and DIVI]. / Metabolische Führung und Ernährung von Intensivpatienten mit renaler Dysfunktion : Empfehlungen der Sektionen Niere der DGIIN, ÖGIAIN und DIVI.

BACKGROUND: Intensive care patients with renal failure or insufficiency comprise a heterogeneous group of subjects with widely differing metabolic patterns and nutritional requirements. They include subjects with various stages of acute kidney injury (AKI), acute-on-chronic renal failure (A-CKD), without/with renal replacement therapy (RRT), chronic kidney disease (CKD), and subjects on regular hemodialysis or peritoneal dialysis therapy (HD/PD). GOALS: Development of recommendations by the renal section of DGIIN (Deutsche Gesellschaft für Internistische Intensivmedizin und Notfallmedizin), ÖGIAIN (Österreichische Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) for the metabolic management and the planning, indication, implementation, and monitoring of nutrition therapy in this heterogeneous group of patients. MATERIALS AND METHODS: The recommendations are based on recent evidence and current recommendations of DGEM (Deutsche Gesellschaft für Ernährungsmedizin), ASPEN (American Society for Parenteral and Enteral Nutrition) and ESPEN (European Society for Clinical Nutrition and Metabolism) and also the KDGIO (Kidney Disease: Improving Global Outcomes) clinical practice guidelines for AKI and the expert knowledge and clinical experience of the authors. RESULTS: Nutrition support in these patient groups is not fundamentally different from that in other disease states but must consider the multiple variations in metabolism and nutrient requirements. Nutrition therapy must be adapted to the stage of disease and especially, in those patients on RRT. Nutritional needs can differ widely between patients but also in the same patient during the course of the disease. CONCLUSIONS: Thus, the patient with renal failure requires an individualized approach in nutrition support and because of the altered metabolism of many nutrients and intolerances for electrolytes and fluids, the nutrition support in patients with renal insufficiency requires close clinical and laboratory monitoring.

[Regional citrate anticoagulation in renal replacement therapy in the intensive care station : Recommendations from the renal section of the DGIIN, ÖGIAIN and DIVI]. / Regionale Zitratantikoagulation bei Nierenersatzverfahren auf der Intensivstation : Empfehlungen der Sektionen Niere der DGIIN, ÖGIAIN und DIVI.

BACKGROUND: Regional citrate anticoagulation (RCA) in continuous renal replacement therapy can effectively anticoagulate dialysis circuits without having adverse effects on systemic heparin application. In particular, in continuous renal replacement therapy RCA is well established and represents a safe procedure with longer filter lifetimes and fewer bleeding complications. OBJECTIVES: To provide guidance on the indications, advantages and disadvantages, and use of RCA, current recommendations from the renal section of the DGIIN (Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin), ÖGIAIN (Österreichischen Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin) and DIVI (Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin) are stated. MATERIALS AND METHODS: The recommendations in this paper are based on the current KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, other published guidelines and protocols as well as the expert knowledge and clinical experience of the authors. RESULTS: The use of commercially available machines with coupled pumps and integrated safety features, effective personal training and standardized protocols for clinical usage (SOP) is particularly important for the safe clinical use of RCA in renal replacement therapy. Contrary to previous recommendations, even liver failure or shock with lactic acidosis may no longer be an absolute contra-indication for RCA. However, these particular patients have to be carefully monitored for signs of citrate accumulation.

Bystander-witnessed cardiac arrest is associated with reported agonal breathing and leads to less frequent bystander CPR.

AIM: Although the importance of bystander cardiopulmonary resuscitation has been shown in multiple studies, the rate of bystander cardiopulmonary resuscitation is still relatively low in many countries. Little is known on bystanders' perceptions influencing the decision to start cardiopulmonary resuscitation. Our study aims to determine such factors. MATERIALS AND METHODS: Semi-structured telephone interviews with bystanders of out-of-hospital cardiac arrests between December 2014 and April 2016 were performed in a prospective manner. This single-center survey was conducted in the city of Münster, Germany. The bystander's sex and age, the perception of the victim's breathing and initial condition were correlated with the share of bystander cardiopulmonary resuscitation in the corresponding group. RESULTS: 101 telephone interviews were performed with 57 male and 44 female participants showing a mean age of 52.7 (SD ±â€¯16.3). In case of apnoea 38 out of 46 bystanders (82.6%) started cardiopulmonary resuscitation; while in case of descriptions indicating agonal breathing 19 out of 35 bystanders (54.3%) started cardiopulmonary resuscitation (p = .007). If the patient was found unconscious 47 out of 63 bystanders (74.7%) performed cardiopulmonary resuscitation, while in cases of witnessed cardiac arrest 19 out of 38 bystanders (50%) attempted cardiopulmonary resuscitation (p = .012). Witnessed change of consciousness is an independent factor significantly lowering the probability of starting cardiopulmonary resuscitation (regression coefficient -1.489, p < .05). CONCLUSION: The witnessed loss of consciousness was independently associated with a significant reduction in the likelihood that bystander-CPR was started. These data reinforce the importance of teaching the recognition of early cardiac arrest.

[Extracorporeal renal replacement therapy in acute kidney injury : Recommendations from the renal section of the DGIIN, ÖGIAIN and DIVI]. / Extrakorporale Nierenersatztherapie bei akuter Nierenschädigung : Empfehlungen der Sektionen "Niere" der DGIIN, ÖGIAIN und DIVI.

BACKGROUND: Acute kidney injury (AKI) is a common complication in intensive care unit (ICU) patients. The incidence of AKI in ICU patients exceeds 50% and the associated morbidity and mortality rates increase with severity of AKI. In addition, long-term consequences of AKI are underestimated and several studies show impaired long-term outcome after AKI. In about 5-25% of ICU patients with AKI renal replacement therapy (RRT) is required. OBJECTIVES: To assist in indication, timing, modality and application of renal replacement therapy of adult patients, current recommendations from the renal sections of the DGIIN (Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin), ÖGIAIN (Österreichischen Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin) and DIVI (Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin) are stated. MATERIALS AND METHODS: The recommendations stated in this paper are based on the current KDIGO (Kidney Disease: Improving Global Outcomes) guidelines, recommendations from the 17th Acute Disease Quality Initiative (ADQI) Consensus Group, the French Intensive Care Society (SRLF) with the French Society of Anesthesia Intensive Care (SFAR) and the expert knowledge and clinical experience of the authors. RESULTS: Today, different treatment modalities for RRT are available. Although continuous RRT and intermittent dialysis therapy as well as continuous dialysis therapy have comparable outcomes, differences exist with respect to practical application as well as health-economic aspects. Individualized risk stratification might be helpful to choose the right time to start and the right treatment modality for patients.

[Dose adjustment of anti-infective drugs in patients with renal failure and renal replacement therapy in intensive care medicine : Recommendations from the renal section of the DGIIN, ÖGIAIN and DIVI]. / Dosierung von Antiinfektiva bei Nierenversagen und Nierenersatztherapie in der Intensivmedizin : Empfehlungen der Sektionen Niere der DGIIN, ÖGIAIN und DIVI.

BACKGROUND: Many anti-infective drugs require dose adjustments in critically ill patients with acute kidney injury (AKI) and renal replacement therapy, in order to achieve adequate therapeutic drug concentrations. OBJECTIVES: The fundamental pharmacokinetic and pharmacodynamic principles of drug dose adjustment are presented. Recommendations on anti-infective drug dosage in intensive care are provided. MATERIALS AND METHODS: We established dose recommendations of selected anti-infective drugs based on information in the summary of product characteristics, published studies and recommendations, pharmacokinetic and pharmacodynamic considerations, and the experience and expert opinion of the authors. RESULTS: Out of a total of 37 anti-infective drugs (31 antibiotics, 2 antivirals, 4 antifungals) 8 can be administered independent of renal function. For 29 anti-infective drugs, a specific recommendation on drug dosage could be made in case of intermittent hemodialysis and for 24 anti-infective drugs in case of continuous hemo(dia)filtration. CONCLUSIONS: Recommendations on dosing of important anti-infective drugs in critically ill patients with AKI and renal replacement therapy are provided.

[Prevention of acute kidney injury in critically ill patients : Recommendations from the renal section of the DGIIN, ÖGIAIN and DIVI]. / Prävention der akuten Nierenschädigung beim kritisch kranken Patienten : Empfehlungen der Sektionen Niere der DGIIN, ÖGIAIN und DIVI.

BACKGROUND: Acute kidney injury (AKI) has both high mortality and morbidity. OBJECTIVES: To prevent the occurrence of AKI, current recommendations from the renal section of the DGIIN (Deutschen Gesellschaft für Internistische Intensivmedizin und Notfallmedizin), ÖGIAIN (Österreichischen Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin) and DIVI (Deutschen Interdisziplinären Vereinigung für Intensiv- und Notfallmedizin) are stated. MATERIALS AND METHODS: The recommendations stated in this paper are based on the current Kidney Disease Improving Global Outcomes (KDIGO) guidelines, the published statements of the "Working Group on Prevention, AKI section of the European Society of Intensive Care Medicine" and the expert knowledge and clinical experience of the authors. RESULTS: Currently there are no approved clinically effective drugs for the prevention of AKI. Therefore the mainstay of prevention is the optimization of renal perfusion by improving the mean arterial pressure (>65 mm Hg, higher target may be considered in hypertensive patients). This can be done by vasopressors, preferably norepinephrine and achieving or maintaining euvolemia. Hyperhydration that can lead to AKI itself should be avoided. In patients with maintained diuresis this can be done by diuretics that are per se no preventive drug for AKI. Radiocontrast enhanced imaging should not be withheld from patients at risk for AKI; if indicated, however, the contrast media should be limited to the smallest possible volume.

Hydroxyethyl starch 130/0.4 decreases inflammation, neutrophil recruitment, and neutrophil extracellular trap formation.

BACKGROUND: During systemic inflammation, leucocytes are activated and extravasate into damaged tissue. Activation and recruitment are influenced by different mechanisms, including the interaction of leucocytes with platelets and neutrophil extracellular traps (NET) formation. Here, we investigated the molecular mechanism by which hydroxyethyl starch (HES 130/0.4) dampens systemic inflammation in vivo. METHODS: Systemic inflammation was induced in C57Bl/6 wild-type mice by caecal ligation and puncture and cytokine concentrations in the blood, neutrophil recruitment, platelet-neutrophil aggregates, and NET formation were investigated in vivo. Intravascular adherent and transmigrated neutrophils were analysed by intravital microscopy (IVM) of the cremaster muscle and the kidneys. Flow chamber assays were used to investigate the different steps of the leucocyte recruitment cascade. RESULTS: By using flow cytometry, we demonstrated that HES 130/0.4 reduces neutrophil recruitment into the lung, liver, and kidneys during systemic inflammation (n=8 mice per group). IVM revealed a reduced number of adherent and transmigrated neutrophils in the cremaster and kidney after HES 130/0.4 administration (n=8 mice per group). Flow chamber experiments showed that HES 130/0.4 significantly reduced chemokine-induced neutrophil arrest (n=4 mice per group). Furthermore, HES 130/0.4 significantly reduced the formation of platelet-neutrophil aggregates, and NET formation during systemic inflammation (n=8 mice per group). CONCLUSIONS: Our findings suggest that HES 130/0.4 significantly reduces neutrophil-platelet aggregates, NET formation, chemokine-induced arrest, and transmigration of neutrophils under inflammatory conditions.

Platelets in inflammation and immunity.

The paradigm of platelets as mere mediators of hemostasis has long since been replaced by a dual role: hemostasis and inflammation. Now recognized as key players in innate and adaptive immune responses, platelets have the capacity to interact with almost all known immune cells. These platelet-immune cell interactions represent a hallmark of immunity, as they can potently enhance immune cell functions and, in some cases, even constitute a prerequisite for host defense mechanisms such as NETosis. In addition, recent studies have revealed a new role for platelets in immunity: They are ubiquitous sentinels and rapid first-line immune responders, as platelet-pathogen interactions within the vasculature appear to precede all other host defense mechanisms. Here, we discuss recent advances in our understanding of platelets as inflammatory cells, and provide an exemplary review of their role in acute inflammation.