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Prolonged invasive mechanical ventilation (IMV) influences patient outcome in multiple ways. In this regard the early weaning from IMV is a major goal to be achieved in the treatment of ICU patients. Adopting a weaning protocol that incorporates a Spontaneous Awakening Trial (SAT) and a Spontaneous Breathing Trial (SBT) seems to be essential to reach this goal. Most studies investigating the effectiveness of SAT/SBT protocols in ICU patients' outcomes have focused mainly on medical or mixed (medical and surgical), but not on exclusively surgical patient populations. Surgical patients usually experience more complications and often undergo revision surgeries, therefore needing longer sedation periods and adequate analgo-sedation therapy. Moreover, the longer IMV times make the weaning process more arduous.Our retrospective data analysis therefore investigates the effectiveness of a SAT/SBT protocol implementation in the surgical ICU of Heidelberg University Hospital, focusing exclusively on surgical patients and their outcome related to the weaning process. The SAT/SBT protocol was adopted in Heidelberg ICU starting from 05/2019. We therefore analyzed the time period before and after the implementation between 03/2018 and 08/2020. Adult patients who required invasive ventilation for at least 48 hours were screened for study entry. Demographic data, clinical data and SOFA Score on admission, were collected to define the baseline characteristics of the two groups. Only patients with full adherence to the protocol were included. The primary outcome was defined as the successful extubation, intended as an extubation not followed by successive re-intubations until discharge from the ICU. We performed an univariate analysis to evaluate the rate of successful extubations between the two groups.In total, 199 patients were included in the analysis, 98 of which before the SAT/SBT protocol implementation (control group) and 101 after the SAT/SBT protocol implementation (intervention group). The successful extubation rate in the intervention group resulted in 82% (83/101 patients) compared to 64% (63/98 patients) in the control group (P0.004).We conclude that even for an exclusively surgical patient population, the implementation of a SAT/SBT protocol could result in a higher rate of successful extubation.

Background: Critically ill patients, especially those who have undergone solid organ transplantation (SOT), are at risk of invasive pulmonary aspergillosis (IPA). The outcome relevance of adequately treated putative IPA (pIPA) is a matter of debate. The aim of this study is to assess the outcome relevance of pIPA in a cohort of critically ill patients with and without SOT. Methods: Data from 121 surgical critically ill patients with pIPA (n = 30) or non-pIPA (n = 91) were included. Cox regression analysis was used to identify risk factors for mortality and unfavourable outcomes after 28 and 90 days. Results: Mortality rates at 28 days were similar across the whole cohort of patients (pIPA: 31% vs. non-pIPA: 27%) and did not differ in the subgroup of patients after SOT (pIPA: 17% vs. non-pIPA: 22%). A higher Sequential Organ Failure Assessment (SOFA) score and evidence of bacteraemia were identified as risk factors for mortality and unfavourable outcome, whereas pIPA itself was not identified as an independent predictor for poor outcomes. Conclusions: Adequately treated pIPA did not increase the risk of death or an unfavourable outcome in this mixed cohort of critically ill patients with or without SOT, whereas higher disease severity and bacteraemia negatively affected the outcome. OA Förderung 2023

ZusammenfassungDie Gabe intravasaler Flüssigkeiten gehört zu den Grundpfeilern der perioperativen Therapie und nimmt insbesondere bei großen viszeralchirurgischen Eingriffen maßgeblichen Einfluss auf das chirurgische Behandlungsergebnis. Ein adäquates perioperatives Flüssigkeitsmanagement kann durch Vermeidung von Hypo- und Hypervolämie dazu beitragen, das Risiko einer unzureichenden Gewebeperfusion als Treiber postoperativer Morbidität und Letalität signifikant zu reduzieren. Der effektive Umgang mit intravasal zugeführten Flüssigkeiten setzt dabei die Kenntnis der Substanzen sowie Maßnahmen zur Therapiesteuerung voraus. Das Flüssigkeitsmanagement beginnt bereits präoperativ und sollte – unter Nutzung einer an die Bedürfnisse des Patienten angepassten und dem Eingriff entsprechenden hämodynamischen Überwachung – auch postoperativ im Aufwachraum und auf Station fortgesetzt werden. Der Kommunikation aller an der perioperativen Versorgung Beteiligten kommt im Sinne eines optimalen Flüssigkeitsmanagements eine entscheidende Bedeutung zu.

Zusammenfassung Hintergrund „Critical-incident-reporting“-Systeme (CIRS) dienen dazu, Organisationen und Individuen für bislang unbekannte und sicherheitsrelevante Ereignisse zu sensibilisieren und dadurch Veränderungen herbeiführen zu können. In den letzten Jahren häufen sich allerdings kritische Stimmen, die Einsatz und Nutzen von CIRS in der Medizin hinterfragen, u. a. aufgrund unklarer bzw. zu allgemeiner inhaltlicher Kriterien für die Aufnahme einer Meldung in ein System. Ziel der Arbeit ist die Auswertung und Analyse aller Fälle aus CIRSmedical Anästhesiologie (CIRS-AINS) als Grundlage weiterer, differenzierter Betrachtungen. Methode In einer retrospektiven Datenbankanalyse wurden alle Fälle aus CIRS-AINS (April 2010–Juni 2019) inhaltlich analysiert. Ergebnisse Die gemeldeten 6013 Fälle setzen sich aus 3492 „incidents“ (58,1 %), 1734 „near-misses“ (28,8 %) und 787 sonstigen Meldungen (13,1 %) zusammen. Unter Letztere fielen 21 Konfliktmeldungen (0,4 %), 102 Beschwerden (1,7 %), 89 Überlastungsanzeigen (1,5 %) sowie 575 sonstige Meldungen, die keine CIRS-Fälle darstellen (9,6 %). Seit 2015 zeigt sich eine stetige Zunahme der sonstigen Meldungen um das 2,8-Fache von 7,4 % auf 20,8 %. In 20,1 % der Meldungen wurde Technik, in 27,7 % Medizinprodukte erwähnt. Medikamente waren in 10,7 % der Meldungen Gegenstand der Zwischenfälle. Aus dem perioperativen Umfeld wurden 47,8 % der stationären Zwischenfälle berichtet, 24,6 % aus den Bereichen Intensivstation/Aufwachraum. Das CIRS-Team des BDA analysierte und kommentierte 36,1 % der Fälle . Schlussfolgerung Die Analyse liefert Erkenntnisse für die Gestaltung zukünftiger Melderichtlinien und Anwenderschulungen. Insbesondere der Häufung „sonstiger“ Meldungen, welche nicht den Kriterien einer CIRS-Meldung entsprechen, sollte künftig Rechnung getragen werden.

Seit 2016 praktiziert das Universitätsklinikum Heidelberg die offene fetalchirurgische Defektdeckung der Myelomeningocele (MMC). Ein großer Vorteil der Methode gegenüber der postpartalen Behandlung ist die Reduzierung der Shunt-Pflicht und die Verbesserung der motorisch-neurologischen Funktion der Hüfte und der unteren Extremität. Dieser Beitrag beschreibt Diagnostik, Beratung und Operation anhand eines Fallbeispiels und erläutert die Möglichkeiten sowie Grenzen des Eingriffs.

Background Echinocandins are well-established agents for the treatment of patients with fungal infections, but growing evidence questions their safety in special patient populations prone to systemic inflammatory responses. Objective The study aimed to analyse early hemodynamic changes during echinocandin therapy in critically ill surgical patients. Setting The study was conducted at the surgical intensive care unit at the University Hospital of Giessen, Germany. Methods This single-centre retrospective study includes data from critically ill patients who underwent primary antifungal treatment during 2009–2013. Main outcome measures Hemodynamic parameters, need for vasopressor/inotropic therapy, and dose of vasopressor/inotropic therapy were recorded 2 h before and 2 h after the onset of antifungal treatment. Comparisons of echinocandins to azoles and analysis of a combined endpoint (decrease of mean arterial pressure ≥ 10 mmHg and/or new or increased dosages of norepinephrine, epinephrine, or dobutamine) were performed. Results We found 342 episodes of intravenous antifungal treatment (33 [9.6%] anidulafungin, 116 [33.9%] caspofungin, 132 [38.6%] fluconazole, 17 [5%] micafungin, 44 [12.9%] voriconazole). Group comparisons revealed no significant differences of hemodynamic parameters, need for vasopressor/inotropic therapy, and dose of vasopressor/inotropic therapy, expect for a decreased dose of norepinephrine in the fluconazole group (p

Introduction During cardiopulmonary bypass (CPB), supranormal concentrations of oxygen are routinely administered with the intention to prevent cellular hypoxia. However, hyperoxemia may have adverse effects on patient outcome. Oxygen settings are based on the perfusionist’s individual work experience rather than profound recommendations and studies analyzing the effect of oxygen levels are in need of methodological improvement. We aimed to advance perfusion technique by developing and clinically applying a formula for tailored oxygen therapy in CPB. Methods A formula to precalculate the oxygenator setting before CPB was developed. The newly-derived formula was then evaluated in a prospective, single-center pilot study to test whether a predefined arterial partial oxygen pressure (PaO2) of 150–250 mmHg could be reached. 80 patients were enrolled in the study between April and September 2021. Results The mean oxygen fraction calculated for the setting of the gas blender was 52% ±0,12. The mean PaO2 after initiation of the CPB was 193 ± 99 mmHg (min-max: 61-484, median 163 mmHg). 38.75% of the values were in the desired PaO2 corridor of 150 to 250 mmHg. 8.75% of all PaO2 values were below 250 mmHg. Conclusions Conceptually, perfusion technique should be goal-directed, guided by objective parameters and formulas. Although the optimal CPB oxygenation target remains unknown, it is nevertheless important to develop strategies to tailor oxygen therapy to aid in creating evidence as to what level of oxygen is best for patients during CPB. The formula we derived needs further adjustments to increase results in the target range.

Aims Upon suspicion of infective endocarditis, the causative microorganism must be identified to optimize treatment. Blood cultures and culturing of removed valves are the mainstay of this diagnosis and should be complemented by growth-independent methods. We assessed the diagnostic benefit of examining removed endocarditis valves by broad-range bacterial PCR to detect causative bacteria in cases where culturing was not available, negative, or inconclusive because a skin commensal was detected, in patients from our clinical routine practice. Methods and results Patients from Heidelberg University Hospital with suspicion of endocarditis, followed by valve replacement and analysis by 16S rDNA PCR, between 2015 and 2018, were evaluated. 146 patients with definite infective endocarditis, confirmed by the valve macroscopics and/or histology, were included. Valve PCRs were compared to corresponding blood and valve culture results. Overall, valve PCR yielded an additional diagnostic benefit in 34 of 146 cases (23%) and was found to be more sensitive than valve culture. In 19 of 38 patients with both negative blood and valve cultures, valve PCR was the only method rendering a pathogen. In 23 patients with positive blood cultures detecting skin commensals, 4 patients showed discordant valve PCR results, detecting a more plausible pathogen, and in 11 of 23 cases, valve PCR confirmed commensals in blood culture as true pathogens. Only the remaining 8 patients had negative valve PCRs. Conclusion Valve PCR was found to be a valuable diagnostic tool in surgical endocarditis cases with negative blood cultures or positive blood cultures of unknown significance. Trial registration S-440/2017 on 28.08.2017 retrospectively registered. Graphic abstract Subdividing of all infective endocarditis patients in this study, showing that valve PCR yields valuable information for patients with skin commensals in blood cultures, which were either confirmed by the same detection in valve PCR or refuted by the detection of a different and typical pathogen in valve PCR. Additionally, benefit was determined in patients with negative or not available blood cultures and only positive detection in valve PCR. +: Positive; −: negative; n/a: not available results

Study Design Retrospective analysis. Objectives Sepsis, one of the most frequent and life-threatening complications on intensive care units (ICUs), is associated with a need for mechanical ventilation (MV) as well as adverse respiratory outcomes in hospitalized individuals. However, it has poorly been investigated in patients with spinal cord injury (SCI); a population at high risk for pulmonary and infectious complications. Setting Spinal Cord Injury Center, Heidelberg University Hospital. Methods Over a 5-year period, 182 individuals with SCI requiring MV during their ICU stay were analyzed. Data assessment included demographics, medical characteristics, focus and causative pathogen of sepsis, length of stay, weaning outcomes, and mortality. Results Sepsis was recorded in 28 patients (15%), containing a subgroup of individuals suffering from infectious SCI and co-occurring primary sepsis with Staphylococcus aureus as the predominant microorganism. In most individuals, sepsis was found as secondary complication, which was associated with pulmonary foci, Gram-negative bacteria, and high mortality. More than 80% of individuals with secondary sepsis required induction of MV due to respiratory failure. Furthermore, respiratory failure was found to be independent of sepsis focus, spectrum of causative pathogens, SCI etiology, or severity of injury. Subsequent weaning from the respirator was prolonged in more than 90% with a high proportion of weaning failure. Conclusions Sepsis predominantly occurs as a secondary complication after SCI and is associated with detrimental outcomes. Although the lung is frequently affected as a failing organ, not all sepsis foci are pulmonary. Awareness of both actual sepsis focus and causative pathogen is central to initiate an adequate sepsis treatment.

Viral infections represent a serious threat for patients after liver transplantation (LT). The identification of risk factors during the early post-transplant period might help to improve prevention of viral infections after LT. Between 2004 and 2010, 530 adult patients underwent LT at a large university hospital serving a metropolitan region in Europe. This retrospective single-centre study analysed putative risk factors for early viral infections with herpes simplex virus-1 (HSV-1), varicella-zoster virus (VZV), Epstein-Barr virus (EBV), hepatitis A/B/C (HAV/HBV/HCV) and cytomegalovirus (CMV) in the first 3 months after LT. The final analysis included 501 patients of whom 126 (25.1%) had documented viral infections after LT. No significant differences could be detected between patients with or without viral infections concerning 30- and 90-day mortality. Risk factors in the early post-transplant period identified by multivariate analysis included female gender (CMV, HSV-1), the post-operative need for continuous veno-venous hemofiltration (CMV), septic shock (CMV), detection of fungi (CMV) and the intraoperative amount of transfused blood (EBV). Enhanced vigilance regarding opportunistic infections is crucial in the management of this high-risk population of immunocompromised patients. In particular, attention should be paid to avoidable conditions that increase the risk of renal replacement therapies in the post-LT setting, especially among women. DRKS00010672 on German Clinical Trial Register

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 β‑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 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 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).

Advanced glycation endproducts (AGEs) are well-known inflammatory mediators, which are recognized by immune cells through their corresponding receptor RAGE and have been shown to participate in the pathophysiology of a variety of acute as well as chronic inflammatory diseases. Nevertheless, no data are available on the aftermath of AGE recognition on immune cells. We used the monocytic cell line MonoMac6 as well as primary human monocytes for double stimulation experiments. We measured secreted as well as intracellular levels of TNF-α using ELISA and flow cytometry. In addition, gene expression of surface receptors (RAGE and TLR4) and TNF were measured by qPCR. Stimulation with AGE leads to a dose-dependent induction of self- and cross-tolerance in both primary monocytes as well as the MonoMac6 cell line. The AGE tolerance depended neither on a decreased expression of RAGE or TLR4, nor on a decrease of TNF-α expression. Nevertheless, intracellular TNF-α was decreased, hinting towards a posttranscriptional regulation. High levels of AGEs are capable to activate immune cells at first, but induce a secondary state of hypo-responsiveness in these cells. Based on the origin of its causal agent, we propose this phenomenon to be “metabolic tolerance”.

Background Cell-free DNA (cfDNA) and extracellular RNA (exRNA) are both suspected to activate coagulation cascades in sepsis. Therefore, our study investigated the influence of plasmatic nucleic acids on coagulation in septic patients in comparison to patients after major abdominal surgery. Materials and methods A total of 15 patients with sepsis, 10 postoperative patients, and 10 healthy volunteers were included in this longitudinal study. Blood was collected at sepsis onset and after surgery respectively, as well as after 24, 72 and 168 h. Levels of cfDNA and exRNA were measured by quantitative probe-based polymerase chain reaction. In addition, thromboelastography for coagulation as well as thromboaggregometry for platelet function was conducted. Results Both cfDNA and exRNA were elevated in patients with sepsis compared with postoperative patients and healthy volunteers. While higher exRNA levels correlated with a faster clotting time and more stable clots, cfDNA correlated with a shorter clotting time but also less fibrinolysis. In addition, higher cfDNA seems to be associated with kidney dysfunction as well as with general markers of cell damage (lactate dehydrogenase and lactate). Conclusions Both nucleic acid species might be associated with different effects on coagulation during sepsis, with an overall procoagulatory influence. For this reason, individualized therapeutic approaches in patients suffering from coagulation-associated organ dysfunction might be feasible.

Opportunistic bacterial infections are dreaded risks in patients following liver transplantation (LTX), even though patients receive an antibiotic prophylaxis. The timely recognition of such an infection may be delayed, as culture-based diagnostic methods are linked with a relevant gap in performance. We measured plasma concentrations of Delta-like canonical Notch ligand 1 (DLL1) in 93 adult patients at seven consecutive time points after liver transplantation and correlated the results to the occurrence of culture-proven bacterial infection or a complicated clinical course (composite endpoint of two or more complications: graft rejection or failure, acute kidney failure, acute lung injury, or 90-day mortality). Patients exhibited elevated plasma concentrations after liver transplantation over the whole 28 d observation time. Patients with bacterial infection showed increased DLL1 levels compared to patients without infection. Persistent elevated levels of DLL1 on day 7 and afterward following LTX were able to indicate patients at risk for a complicated course. Plasma levels of DLL1 following LTX may be useful to support an earlier detection of bacterial infections in combination with C-reactive protein (CRP) and procalcitonin (PCT), or they may lead to risk stratification of patients as a single marker for post-operative complications. (Clinical Trial Notation. German Clinical Trials Register: DRKS00005480).

Standard dosing and intermittent bolus application (IB) are important risk factors for pharmacokinetic (PK) target non-attainment during empirical treatment with β-lactams in critically ill patients, particularly in those with sepsis and septic shock. We assessed the effect of therapeutic drug monitoring-guided (TDM), continuous infusion (CI) and individual dosing of piperacillin/tazobactam (PIP) on PK-target attainment in critically ill patients. This is a retrospective, single-center analysis of a database including 484 patients [933 serum concentrations (SC)] with severe infections, sepsis and septic shock who received TDM-guided CI of PIP in the intensive care unit (ICU) of an academic teaching hospital. The PK-target was defined as a PIP SC between 33 and 64 mg/L [fT > 2–4 times the epidemiological cutoff value (ECOFF) of Pseudomonas aeruginosa (PSA)]. PK-target attainment with standard dosing (initial dose) was observed in 166 patients (34.3%), whereas only 49 patients (10.1%) demonstrated target non-attainment. The minimum PK-target of ≥ 33 mg/L was overall realized in 89.9% (n = 435/484) of patients after the first PIP dose including 146 patients (30.2%) with potentially harmful SCs ≥ 100 mg/L. Subsequent TDM-guided dose adjustments significantly enhanced PK-target attainment to 280 patients (62.4%) and significantly reduced the fraction of potentially overdosed (≥ 100 mg/L) patients to 4.5% (n = 20/449). Renal replacement therapy (RRT) resulted in a relevant reduction of PIP clearance (CLPIP): no RRT CLPIP 6.8/6.3 L/h (median/IQR) [SCs n = 752, patients n = 405], continuous veno-venous hemodialysis (CVVHD) CLPIP 4.3/2.6 L/h [SCs n = 160, n = 71 patients], intermittent hemodialysis (iHD) CLPIP 2.6/2.3 L/h [SCs n = 21, n = 8 patients]). A body mass index (BMI) of > 40 kg/m2 significantly increased CLPIP 9.6/7.7 L/h [SC n = 43, n = 18 patients] in these patients. Age was significantly associated with supratherapeutic PIP concentrations (p

Hintergrund Personaleinsatzplanung (PEP) befasst sich mit der Planung und Verteilung von personellen Ressourcen. Dabei sollen sowohl Mitarbeiterwunsche, als auch Planungsvorstellungen wie kompetenzbasierte Einteilung und wirtschaftliche Ziele Berucksichtigung finden. In der Anasthesie stellen eine Vielzahl von Dienststrukturen und eine hohe Zahl an Teilzeitkraften Herausforderungen an die PEP dar.

Im ursprunglich veroffentlichten Beitrag wurden 3 Antibiotikumdosierungen in Tab. 1 falsch angegeben. Korrekt muss es in Tab. 1 „Therapieoptionen bei Infektionen durch Methicillin-resistente Staphylokokken (MRSA)“ bei den „Skin and soft tissue infections“ (SSTI) heisen

Background In nonneutropenic intensive care unit (ICU) patients, current risk stratification scores lack specificity to reliably predict the risk of a prospective invasive candidiasis (IC). We aimed to explore possible associations of distinct immunological markers with different degrees of Candida affection in patients with abdominal sepsis. Methods The presented explorative, noninterventional diagnosis study recruited patients admitted to the surgical ICU at Heidelberg University Hospital with abdominal sepsis. Over 5 days, we determined white blood cell count, 1,3-β-D-glucan, and HLA-DR expression; the amount of Th1, Th17, regulatory T, T helper, and cytotoxic T cells; Dectin-1 and TLR2-expression; the amount of T, B, and NK cells; the ex vivo secretion of IL-8 upon stimulation with LPS, flagellin, and zymosan; and the distribution of distinct T-cell cytokines in a daily manner. On day 21, patients' Candida infection status was stratified in no colonization or IC, colonization or IC. Results A total of 26 patients were included. On day 21, five patients showed no colonization or IC, in 13 patients a colonization was detected, and eight patients were diagnosed with IC. On study inclusion, the stratification groups showed comparable values in standard laboratory parameters and morbidity scores. Decreased B and NK cell counts, as well as reduced IL-8 secretion after ex vivo stimulation with LPS or flagellin seemed to be associated with a higher risk of subsequent Candida colonization. Even lower values could distinguish the therapy-relevant difference between prospective IC from colonization alone. Conclusions We were able to show distinct immune system impairments in early abdominal sepsis by specific immune-based measurements. A possible association of these impairments with a subsequent Candida affection is shown.

Purpose: The soluble receptor for advanced glycation end-products (sRAGE) is a marker of lung epithelial injury and alveolar fluid clearance (AFC), with promising values for assessing prognosis and lung injury severity in acute respiratory distress syndrome (ARDS). Because AFC is impaired in most patients with ARDS and is associated with higher mortality, we hypothesized that baseline plasma sRAGE would predict mortality, independently of two key mediators of ventilator-induced lung injury. Methods: We conducted a meta-analysis of individual data from 746 patients enrolled in eight prospective randomized and observational studies in which plasma sRAGE was measured in ARDS articles published through March 2016. The primary outcome was 90-day mortality. Using multivariate and mediation analyses, we tested the association between baseline plasma sRAGE and mortality, independently of driving pressure and tidal volume. Results: Higher baseline plasma sRAGE [odds ratio (OR) for each one-log increment, 1.18; 95% confidence interval (CI) 1.01–1.38; P = 0.04], driving pressure (OR for each one-point increment, 1.04; 95% CI 1.02–1.07; P = 0.002), and tidal volume (OR for each one-log increment, 1.98; 95% CI 1.07–3.64; P = 0.03) were independently associated with higher 90-day mortality in multivariate analysis. Baseline plasma sRAGE mediated a small fraction of the effect of higher ΔP on mortality but not that of higher VT. Conclusions: Higher baseline plasma sRAGE was associated with higher 90-day mortality in patients with ARDS, independently of driving pressure and tidal volume, thus reinforcing the likely contribution of alveolar epithelial injury as an important prognostic factor in ARDS. Registration: PROSPERO (ID: CRD42018100241). © 2018, The Author(s).

Background The Human Factors Analysis and Classification System (HFACS) was developed as a practical taxonomy to investigate and analyse the human contribution to accidents and incidents. Based on Reason's "Swiss Cheese Model", it considers individual, environmental, leadership and organizational contributing factors in four hierarchical levels. The aim of this study was to assess the applicability of a modified HFACS taxonomy to incident reports from a large, anonymous critical incident database with the goal of gaining valuable insight into underlying, more systemic conditions and recurring schemes that might add important information for future incident avoidance. Methods We analysed 50 reports from an anonymous, anaesthesiologic, single-centre Critical Incident Reporting System using a modified HFACS-CIRS taxonomy. The 19 HFACS categories were further subdivided into a total of 117 nanocodes representing specific behaviours or preconditions for incident development. Results On an individual level, the most frequent contributions were decision errors, attributed to inadequate risk assessment or critical-thinking failure. Communication and Coordination, mostly due to inadequate or ineffective communication, was contributory in two-thirds of reports. Half of the reports showed contributory complex interactions in a sociotechnical environment. Ratability scores were noticeably lower for categories evaluating leadership and organizational influences, necessitating careful interpretation. Conclusions We applied the HFACS taxonomy to the analysis of CIRS reports in anaesthesiology. This constitutes a structured approach that, especially when applied to a large data set, might help guide future mitigation and intervention strategies to reduce critical incidents and improve patient safety. Improved, more structured reporting templates could further optimize systematic analysis.

Erratum zu: Der Anaesthesist 2019 https://doi.org/10.1007/s00101-019-00645-0 Im ursprunglich veroffentlichten Beitrag wurden 2 Antibiotikumdosierungen in Tab. 1 falsch angegeben. Korrekt muss es in Tab. 1 „Therapieoptionen bei Infektionen durch Methicillin-resistente Staphylokokken (MRSA)“ bei den …

Right ventricular failure (RVF) is an unfortunate complication that continues to limit outcomes following durable left ventricular assist device (LVAD) implantation. Despite several ‘RVF risk scores’ having been proposed, preoperative prediction of post-LVAD RVF remains a guesstimate at best. Current strategies for institution of temporary RVAD support are invasive, necessitate additional re-thoracotomy, restrict postoperative mobilization, and/or entail prolonged retention of prosthetic material in-situ. The authors propose a novel surgical strategy comprising simultaneous implantation of a permanent LVAD and percutaneous TandemHeart® plus ProtekDuo® to provide temporary RVAD support and preempt RVF in patients with impaired RV function.

Epidemiologische Studien der letzten Jahre belegen sowohl eine steigende Inzidenz invasiver Pilzinfektionen als auch ein zunehmendes Problem mit Therapieversagen auf Intensivstationen. In bis zu 70 % der Falle zeigt sich ein Nichtansprechen der primaren antimykotischen Therapie abhangig von der auslosenden Spezies bzw. von vorliegenden Grunderkrankungen. Der vorliegende Review-Beitrag soll fur das Thema des Therapieversagens sensibilisieren, die klinischen Umstande des Therapieversagens beschreiben sowie ein systematisches Vorgehen bei Verdacht auf ein Scheitern der primaren antimykotischen Therapie vorschlagen.

This single-centre retrospective cohort study evaluated the incidence and outcome of mycoses in critical ill patients (n = 283) with sepsis due to peritonitis. Overall mortality was 41.3%, and the 28-day mortality was 29.3%. Fungal pathogens were found in 51.9%. The common first location was the respiratory tract (66.6%), followed by the abdominal site (19.7%). Candida colonisation was found in 64.6%, and invasive Candida infection in 34.0%. Identified fungi were Candida spp. in 98.6% and Aspergillus spp. in 6.1%. Patients with fungal pathogens showed a higher rate of postoperative peritonitis, APACHE II and tracheotomy. In comparison to patients without fungal pathogens, these patients showed a longer duration on mechanical ventilation, and a higher overall mortality. Patients with Candida-positive swabs from abdominal sites had more fascia dehiscence and anastomosis leakage. Seventy-two patients (48.9%) received antifungal therapy, 26 patients were treated empirically. Antifungal therapy was not associated with a decrease in mortality. Age and renal replacement therapy were associated with mortality. In conclusion, fungi are common pathogens in critically ill patients with peritonitis, and detection of fungi is associated with an increase in overall mortality. Particularly, Candida-positive abdominal swabs are associated with an increase in morbidity. However, we were not able to demonstrate a survival benefit for antifungal therapy in peritonitis patients.

Current treatment guidelines for sepsis claim an early goal-directed hemodynamic optimization including fluid resuscitation, use of vasopressors and inotropic agents. We investigated the correlation between the prominent treatment goal central venous saturation (ScvO2) and the frontal and the thenar regional oxygen saturation (rSO2) measured by near infrared spectroscopy. Secondary, we examined the value of ScvO2, lactate levels and rSO2 as surrogate markers of an impaired tissue oxygenation for outcome prediction in sepsis. This prospective, observational study was performed at the surgical intensive care unit of the University Hospital Giessen. A total of 50 patients with sepsis, severe sepsis or septic shock were included. ScvO2, rSO2 and lactate were measured at sepsis diagnosis (baseline), 24 and 48 h, thereafter. We investigated the predictive value of frontal and thenar rSO2 for a decreased SvcO2 under 70%. For survivor and non-survivors ScvO2, rSO2 and lactate were analysed. Patients with ScvO270% showed a trend to higher levels of fontal rSO2 (62.81 ± 8.06 vs. 53.54 ± 15.48; p = 0.058). ROC-analysis revealed a minor prediction of a decreased ScvO2 by frontal rSO2 levels at baseline (AUC = 0.687; 95% CI 0.511-0.863; p = 0.047). Combined measurements of lactate and ScvO2 showed significantly elevated mortality for patients with ScvO2 ≥70% and lactate levels ≥2.5 mmol/l (log rank test p = 0.004). In the group with ScvO270% and lactate levels2.5 mmol/l no patients died during the observation period. Frontal rSO2 correlates with ScvO2 but both frontal and thenar rSO2 do not exactly discriminate between patients with high or low ScvO2 in sepsis. The combination of elevated lactate2.5 mmol/l and ScvO270 % is highly associated with poor outcome in ICU patients with sepsis, severe sepsis and septic shock.

Unser Verstandnis der Ursachen und pathophysiologischen Grundlagen der Sepsis war im Laufe der Zeit einem stetigen Wandel unterworfen. Nach heutigem Verstandnis handelt es sich bei der Sepsis um eine Immunpathologie, die zwar durch eine Infektion ausgelost wird, deren klinisches Bild jedoch masgeblich von der Reaktion des Wirtsorganismus bestimmt wird. Die Sepsis ist daher weder als rein pro-, noch als anti-inflammatorisches Syndrom zu verstehen. Vielmehr kommt es im Verlauf zu einer Uberlagerung verschiedener Mechanismen des Immunsystems. Wahrend in einer fruhen Phase der Sepsis die uberschiesende (proinflammatorische) Immunreaktion dominiert, kommt es schnell zu einer antiinflammatorischen Kompensation dieser Reaktion, welche oftmals in einer Immundysfunktion mit konsekutiver Anfalligkeit fur Sekundarinfektionen resultiert. Die vorliegende Ubersichtsarbeit soll einen Uberblick uber die breite Palette an molekularen Mechanismen geben, die dem klinischen Bild der Sepsis zugrunde liegen.

Study background: The purpose of this study was to evaluate recent strategies for anti-infective treatment in patients suffering from ventilator-associated respiratory infections caused by P. aeruginosa and to assess the riskbenefit profile of inhaled tobramycin.Methods: Electronic health records of patients suffering from respiratory infections caused by P. aeruginosa from 2011-2014 were retrospectively screened.Results: In 81 patients, P. aeruginosa was found in respiratory secretions, of which 26 patients suffered from ventilator-associated pneumonia (VAP), whereas 55 patients only fulfilled criteria of ventilator-associated tracheitis (VAT). Inhaled tobramycin was used in 14 patients with VAP and 31 patients with VAT. In this context, inhaled tobramycin was shown to be safe (e.g. no bronchoconstriction or systemic toxicity) and did not result in an increase of tobramycin resistant strains in respiratory secretions at 90 days following study inclusion. However, a clear clinical benefit (e.g. reduced need for i.v. antibiotics) could not be shown.\Conclusion: Inhaled tobramycin was shown to be a suitable approach with a favorable risk profile to treat patients suffering from respiratory infections (VAP, VAT) caused by P. aeruginosa. The clinical benefit needs to be reevaluated in a larger prospective investigation.

Symptomatic aortic stenosis can be treated by surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR), the latter of which is regarded as a minimally invasive procedure. Differences between these procedures regarding immune responses or changes in coagulation and neurocognitive function have thus far been evaluated only sparsely. We carried out a prospective, single-center, nonrandomized explorative study with 38 patients. Thirteen patients were subjected to either SAVR or transfemoral (TF-) TAVR, and 12 patients underwent transapical (TA-) TAVR. Plasma cytokines (IL-6, -8, -18, presepsin) and acute-phase proteins (C-reactive protein, procalcitonin), markers of coagulation and platelet function, and neurocognitive function (via various standard tests) were assessed before and at five-time points during a 72-h follow-up after surgery. SAVR and TA-TAVR patients responded similarly to the procedure in terms of C-reactive protein, leukocyte numbers, and IL-6, whereas these responses were substantially lower in TF-TAVR patients. Only SAVR patients showed measurable IL-10 levels. SAVR patients without prior anticoagulation experienced a robust and transient restoration of platelet function after surgery, with no hypercoagulation observable in functional coagulation assays. None of the procedures led to an immediate improvement of hand and leg coordination, but patients after TA-TAVR had decreased neurocognitive function. Patients after SAVR or TA-TAVR exhibit a robust pro-inflammatory response, which is-on the cytokine level-counterbalanced only in SAVR patients. Our results point toward a greater impact of TA-TAVR on neurocognitive function and indicate a potentially detrimental activation of platelets in some patients after SAVR.

BACKGROUND The use of perioperative checklists has generated a growing body of evidence pointing toward reduction of mortality and morbidity, improved compliance with guidelines, reduction of adverse events, and improvements in human factor-related areas. Usual quality management metrics generally fall short in assessing compliance with their perioperative application. Our study assessed application attitudes and compliance with safety measures centered around the World Health Organization (WHO) "Safe Surgery Saves Lives" campaign as perceived by anesthesia professionals in Germany. METHODS Three hundred sixteen physicians and nurses participated in our cross-sectional survey, and 304 completed all 35 questions. RESULTS Only 59.5% of participants had knowledge of the theoretical framework behind the WHO campaign. During the "sign-in," patient ID and surgical site were checked in 99.6% and 95.1% as recommended by the WHO. Allergies were addressed by 89.2%, expected difficult airway by 65.7%, and the availability of blood products by 70.5%. A total of 84.9% of participants advocated for the time-out to include all persons present in the operating room, which was the case in 57.0%. A total of 40.8% stated that the time-out was only performed between anesthetist and surgeon; in 17.0% of cases, the patient was simultaneously draped and/or surgically scrubbed. No significant differences between hospital types were observed. CONCLUSIONS Our study paints a heterogeneous picture of the implementation, usage, and safety attitudes concerning the Safe Surgery Checklist as promoted by the WHO. The lack of standardized execution and team-mindedness can be taken as further evidence for the importance of interdisciplinary training focusing on human factors, communication, and collaboration rather than the mere implementation by decree.