[Perioperative fluid management in major abdominal surgery]. / Perioperatives Flüssigkeitsmanagement bei großen viszeralchirurgischen Eingriffen.

Intravascular fluid administration belongs to the cornerstones of perioperative treatment with a substantial impact on surgical outcome especially with respect to major abdominal surgery. By avoidance of hypovolemia and hypervolemia, adequate perioperative fluid management significantly contributes to the reduction of insufficient tissue perfusion as a determinant of postoperative morbidity and mortality. The effective use of intravascular fluids requires detailed knowledge of the substances as well as measures to guide fluid therapy. Fluid management already starts preoperatively and should be continued in the postoperative setting (recovery room, peripheral ward) considering a patient-adjusted and surgery-adjusted hemodynamic monitoring. Communication between all team members participating in perioperative care is essential to optimize fluid management.

Bacterial sepsis : Diagnostics and calculated antibiotic therapy.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of ß­lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).

The impact of real life treatment strategies for Candida peritonitis-A retrospective analysis.

Candida species are commonly detected isolates from abdominal foci. The question remains as to who would benefit from early empiric treatment in cases of Candida peritonitis. This study collected real-life data on critically ill patients with Candida peritonitis to estimate the relevance of the chosen treatment strategy on the outcome of these patients. One hundred and thirty-seven surgical intensive care unit (ICU) patients with intra-abdominal invasive Candidiasis were included in the study. Fifty-six patients did not get any antifungal agent. Twenty-nine patients were empirically treated, and 52 patients were specifically treated. In the group without, with empiric and with specific antifungal treatment, the 30-day mortality rate was 33.9, 48.3 and 44.2 respectively. Candida albicans was the most frequently found species. Seven patients in the specific treatment group and one patient in the empiric treatment group emerged with candidaemia. Age, leucocyte count, APACHE II Score and acute liver failure were independent predictors of 30-day mortality in patients with Candida peritonitis. Not all patients with Candida peritonitis received antifungal treatment in real clinical practice. Patients with higher morbidity more often got antifungals. Early empirical therapy has not been associated with a better 30-day mortality.

[Bacterial sepsis : Diagnostics and calculated antibiotic therapy]. / Bakterielle Sepsis : Diagnostik und kalkulierte Antibiotikatherapie.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).

Sepsis-induced long-term immune paralysis--results of a descriptive, explorative study.

BACKGROUND: Long-lasting impairment of the immune system is believed to be the underlying reason for delayed deaths after surviving sepsis. We tested the hypothesis of persisting changes to the immune system in survivors of sepsis for the first time. METHODS: In our prospective, cross-sectional pilot study, eight former patients who survived catecholamine-dependent sepsis and eight control individuals matched for age, sex, diabetes and renal insufficiency were enrolled. Each participant completed a questionnaire concerning morbidities, medications and infection history. Peripheral blood was collected for determination of i) immune cell subsets (CD4(+), CD8(+) T cells; CD25(+) CD127(-) regulatory T cells; CD14(+) monocytes), ii) cell surface receptor expression (PD-1, BTLA, TLR2, TLR4, TLR5, Dectin-1, PD-1 L), iii) HLA-DR expression, and iv) cytokine secretion (IL-6, IL10, TNF-α, IFN-γ) of whole blood stimulated with either α-CD3/28, LPS or zymosan. RESULTS: After surviving sepsis, former patients presented with increased numbers of clinical apparent infections, including those typically associated with an impaired immune system. Standard inflammatory markers indicated a low-level inflammatory situation in former sepsis patients. CD8(+) cell surface receptor as well as monocytic HLA-DR density measurements showed no major differences between the groups, while CD4(+) T cells tended towards two opposed mechanisms of negative immune cell regulation via PD-1 and BTLA. Moreover, the post-sepsis group showed alterations in monocyte surface expression of distinct pattern recognition receptors; most pronouncedly seen in a decrease of TLR5 expression. Cytokine secretion in response to important activators of both the innate (LPS, zymosan) and the adaptive immune system (α-CD3/28) seemed to be weakened in former septic patients. CONCLUSIONS: Cytokine secretion as a reaction to different activators of the immune system seemed to be comprehensively impaired in survivors of sepsis. Among others, this could be based on trends in the downregulation of distinct cell surface receptors. Based on our results, the conduct of larger validation studies seems feasible, aiming to characterize alterations and to find potential therapeutic targets to engage.

[Complex control of the source of infection in sepsis : Extracorporeal membrane oxygenation (ECMO) as a bridging concept for tracheal fistula repair in sepsis-associated ARDS]. / Komplexe Fokussanierung in der Sepsis : Extrakorporale Membranoxygenierung (ECMO) als Bridging-Konzept zur trachealen Fistelsanierung bei sepsisassoziiertem ARDS.

Here, we present a case of a tracheal fistula due to an anastomotic insufficiency following abdominothoracic esophageal resection. Despite immediate discontinuity resection, the tracheal fistula could not be surgically closed, resulting in incomplete control of the source of infection and an alternative treatment concept in the form of interventional fistula closure using a Y-tracheal stent. However, owing to existing severe acute respiratory distress syndrome (ARDS), which is associated with a considerable risk of peri-interventional hypoxia, a temporary bridging concept using venovenous extracorporeal membrane oxygenation (ECMO) was implemented successfully.

[Epigenetic regulation in sepsis : current state of knowledge]. / Epigenetische Regulation in der Sepsis : Aktueller Wissensstand.

Sepsis is known to be a severe systemic immune reaction based on an infection of various origins. The initial immune response is accompanied by excess activation of immune cells and release of proinflammatory cytokines. Simultaneously initiated compensatory mechanisms lead to high levels of anti-inflammatory mediators to counterbalance the generalized inflammatory reaction; however, the compensatory immunoreaction itself equally overreacts and results in a prolonged sepsis-induced immunosuppression. The underlying mechanisms for these exaggerated immune responses and the resulting global immunosuppression that increase the risk for secondary infection are still unknown. Recent findings indicate that epigenetic mechanisms change basic properties of important immune cells by mechanisms leading to changes in gene expression. Dynamic exchanges of histone modifications result in a variation of transcription and seem to play a key role in cell function of macrophages and other immune cells. This article provides a current overview of epigenetic sepsis research and the sepsis-induced effects on the immune system.

[Use of biomarkers in sepsis. Update and perspectives]. / Einsatz von Biomarkern in der Sepsis. Update und Ausblick.

Sepsis and related complications are a challenge for intensive care medicine. Despite many advances in antibiotic therapy sepsis remains one of the most common diseases of patients in intensive care units and is designated as the main cause of death in critically ill patients. Persisting sepsis leads to impaired immunity, resulting in immunosuppression. Unspecific predictive signs complicate an early diagnosis; however, an early initiation of adequate therapy is of crucial importance for the prognosis. Scoring systems can be applied for the initial evaluation but are controversially discussed concerning the monitoring of disease progression and therapy as well as outcome prediction. Biomarkers are considered as a complementary approach.

Effects of echinocandin preparations on adult rat ventricular cardiomyocytes. Preliminary results of an in vitro study.

BACKGROUND: Candida infections represent a relevant risk for patients in intensive care units resulting in increased mortality. Echinocandins have become the agents of choice for early and specific antifungal treatment in critically ill patients. Due to cardiac effects following echinocandin administration seen in intensive care unit (ICU) patients the in vitro effects of echinocandins and fluconazole on isolated cardiomyocytes of the rat were examined. AIM: The study was designed to investigate a possible impact of echinocandins and fluconazole in clinically relevant concentrations on the in vitro contractile responsiveness and shape of isolated rat cardiomyocytes. MATERIAL AND METHODS: Ventricular cardiomyocytes were isolated from Lewis rats. Cardiomyocytes were cultured in the presence of all licensed echinocandin preparations and fluconazole at concentrations of 0 (control), 0.1, 1, 3.3, 10, 33 and 100 µg/ml for 90 min. Cells were stimulated by biphasic electrical stimuli and contractile responsiveness was measured as shortening amplitude. Additionally, the ratio of rod-shaped to round cells was determined. RESULTS: Anidulafungin concentrations of 3.3 and 10 µg/ml caused a significant increase in contractile responsiveness, caspofungin showed a significant decrease at 10 µg/ml and micafungin concentrations of 3.3-33 µg/ml led to a significant increase in cell shortening. Measurement was not possible at 33 µg/ml for anidulafungin and caspofungin and at 100 µg/ml for all echinocandins due to a majority of round-shaped, non-contracting cardiomyocytes. Fluconazole showed no significant effect on cell shortening at all concentrations tested. For the three echinocandins the ratio of round-shaped, non-contracting versus rod-shaped normal contracting cardiomyocytes increased in a dose-dependent manner. CONCLUSIONS: Echinocandins impact the in vitro contractility of isolated cardiomyocytes of rats. This observation could be of great interest in the context of antifungal treatment.

Cardiac effects of echinocandin preparations - three case reports.

WHAT IS KNOWN AND OBJECTIVE: Echinocandins are antifungal agents, routinely used in invasive candida infections in critically ill patients. Their excellent anticandidal activity and their low frequency of reported adverse events and drug interactions make them first-line guideline treatments of candidiasis especially in intensive care units (ICU). We report on three ICU patients who developed cardiac insufficiency and hemodynamic instability during administration of loading doses of an echinocandin. CASE SUMMARY: Three ICU patients showed a substantial drop in their cardiac index or a deterioration of the mean arterial pressure following start of echinocandin administration. The patients were 75 years (female), 71 years (male) and 66 years (male) old. One patient received caspofungin, and two patients received anidulafungin as empirical antifungal treatment for severe sepsis. WHAT IS NEW AND CONCLUSION: Our cases suggest that the observed cardiac impairment could be associated with echinocandin administration. Therefore, we recommend close hemodynamic monitoring of critically ill patients receiving echinocandins.

[Antibiotic treatment of nosocomial pneumonia]. / Antibiotikatherapie der nosokomialen Pneumonie.

Nosocomial pneumonia is one of the most common infectious diseases acquired in hospital and is often caused by resistant pathogens. For treatment of nosocomial pneumonia an appropriate initial antibiotic therapy is essential and exact knowledge of the specific pathogen spectrum is essential for the correct choice of the empirically calculated antibiotics. In line with a critical reevaluation of the primary treatment, pathogen-specific de-escalation therapy, a diagnosis of possible pulmonary complications (e. g. pleural empyema) and the identification and appropriate rehabilitation measures of non-pulmonary infections are necessary. To attain the best possible outcome the respective therapy concept needs to be adjusted to the individual risk characteristics. Appropriate initial antibiotic therapy, duration of mechanical ventilation and comorbidities are the key factors for patient outcome. This approach helps to avoid the development of resistant pathogens and saves economic resources.