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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.

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 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).

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).

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.

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.

Intra-abdominal infections represent a subgroup of septic syndromes with high death rates and the need for prompt and appropriate antimicrobial therapy. Conventional culture-based microbial identification has notable shortcomings in the diagnostics of polymicrobial infections. Modern culture-independent molecular methods may represent a new diagnostic approach. The current study aimed to compare the results obtained from the denaturing high-performance liquid chromatography WAVEThe study included 42 samples of pathologic intra-abdominal fluids, collected from 37 patients with intra-abdominal sepsis. Micro-organisms grown in culture and detected by the WAVE system were compared. Further, we recorded clinical data including baseline characteristics and the use of antibiotic agents.In 38.1% of the analyzed samples, the classic, culture-based methods showed no bacterial growth on agar plates, in comparison with the microbiomic analysis in which the proportion of samples with negative signal was 31%. In about 40% of the patients, both methods detected one microbiologic agent, whereas in approximately one quarter of the samples, two or more agents were identified. The detection rate of certain bacteria such as Enterobacteriacae or Enterococcus faecium was significantly higher using the microbiomic analysis. Bacteria such as Haemophilus, Lactobacillus, Clostridium, Methylobacterium, Collinsella aerofaciens, and Solobacterium moorei were detected exclusively using microbiomic analysis.The culture independent molecular WAVE system provided additional information, especially concerning unusual, fastidious bacteria in patients with intra-abdominal infections. Further, it has a higher detection rate for polymicrobial infection and delivers results much sooner than conventional microbiologic methods.

Minimally invasive fetoscopic surgery for spina bifida aperta is a new therapeutic approach to preserve neurologic function by protecting exposed neural tissue. The anesthetic management is of paramount importance for the success of the procedure. Therefore, our protocol was developed with particular attention to safe and adequate maternal and fetal anesthesia, sufficient uterine relaxation as well as prevention of pulmonary edema, placental abruption, and spontaneous labor. As illustrated by this retrospective analysis of 61 cases, these goals can be reliably achieved. The clinical protocol is presented as a supplemental digital content to this manuscript (Supplemental Digital Content 1, http://links.lww.com/AA/B733).

Die Sepsis ist das Krankheitsbild, das aus einer schweren systemischen Immunreaktion des Korpers auf eine Infektion unterschiedlicher Ursache resultiert. Initial reagiert das Immunsystem mit einer uberschiesenden Aktivierung von Entzundungszellen und der Ausschuttung proinflammatorischer Zytokine. Gleichzeitig wirken korpereigene Mechanismen durch antiinflammatorische Mediatoren und Immunzellen dieser generalisierten Entzundungsreaktion als Gegenregulation entgegen. Auch diese kompensatorische antiinflammatorische Immunantwort kann entsprechend der proinflammatorischen Reaktion ubersteigert sein und resultiert dann in einer prolongierten sepsisinduzierten Immunsuppression. Die Grunde fur eine solche persistierende antiinflammatorische Reaktion und die daraus folgende Vulnerabilitat sind unklar. Allerdings gibt es Hinweise, dass ein septisches Ereignis die Grundeigenschaften der Immunzellen durch epigenetische Modifikation verandert. Veranderungen von Histonmodifikationen und Anderungen der Aktivierungsmechanismen von Transkriptionsfaktoren scheinen dabei in vielen Zellen des Immunsystems, wie Makrophagen, wichtige Rollen zu spielen sowie dadurch die Genregulation und Transkriptionsmechanismen der Zelle zu beeinflussen. Dieser Beitrag gibt einen Uberblick uber den aktuellen Stand der epigenetischen Sepsisforschung und uber bisherige Erkenntnisse zu den langfristigen Auswirkungen der Sepsis auf das Immunsystem.

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 fluconazol 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.

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.

Background In the pathogenesis of sepsis, inflammation-induced changes in coagulation play a pivotal role. Methods In total, 90 patients (30 patients with septic shock, 30 surgical patients following major abdominal surgery and 30 healthy volunteers) were enrolled. Blood samples from patients with septic shock were collected at the time of sepsis diagnosis as well as 24 h, 4 days, 7 days, 14 days and 28 days later. Samples from surgical patients with a post-surgical inflammatory response were collected three times (before surgery, immediately after surgery and 24 h after surgery) and once from healthy volunteers. Thromboelastometry (ROTEM ®), as well as whole blood impedance aggregometry (Multiplate®) were performed. Additionally, plasma concentrations of interleukin-6 and tumour necrosis factor-alpha were measured using enzyme-linked immunosorbent assay kits. Results Thromboelastometry lysis index was shown to be a reliable biomarker for septic shock. Furthermore, in septic patients with overt disseminated intravascular coagulation, thromboelastometry revealed signs indicating a hypocoagulable status, whereas patients without overt disseminated intravascular coagulation were found to be hypercoagulable. Platelet aggregation capability, as assessed by whole blood impedance aggregometry, was significantly reduced in septic patients with overt disseminated intravascular coagulation, whereas it was comparable with healthy volunteers and in septic patients without overt disseminated intravascular coagulation. Conclusion Viscoelastic and aggregometric point-of-care testing was shown to be potentially useful for bedside diagnosis of sepsis. Moreover, viscoelastic and aggregometric point-of-care testing was able to determine the phase of septic coagulopathy (hypercoagulability vs. hypocoagulability) and therefore identified patients at high risk for overt disseminated intravascular coagulation.

Proopiomelanocortin (POMC) derivatives and mRNA of POMC have been detected in cardiomyocytes and vascular smooth muscle cells. Increased plasma levels of POMC derivatives have been found in septic patients during cardiovascular deregulation; therefore, we evaluated whether corticotroph-type (ACTH, β-endorphin, β-lipotropin) or melanotroph-type (α-melanocyte-stimulating hormone and N-acetyl-β-END) POMC derivatives have influences on patients' hemodynamics during sepsis. Seventeen septic patients were monitored by pulmonary artery catheter and corticotropin-releasing hormone (CRH) tests were performed by intravenous administration of 100 μg CRH. Before, 15, 30, 45, and 60 minutes after CRH administration, hemodynamic variables were measured, and plasma concentrations of POMC derivatives were determined. After CRH administration, heart rate, cardiac index, and stroke index increased, and the systemic vascular resistance index decreased; moreover, a correlation between ACTH concentration and stroke index as well as an inverse correlation between (α-melanocyte-stimulating hormone concentration and systemic vascular resistance index was observed. CRH and ACTH may have opposite effects on the blood pressure (mean arterial pressure). Immediately after CRH injection mean arterial pressure decreased. ACTH (in contrast to β-endorphin or β-lipotropin), released into the cardiovascular compartment 15 minutes after CRH injection, might have raised mean arterial pressure as compatible with the correlation between ACTH levels and stroke index. (α-melanocyte-stimulating hormone appears to have a vasodilative effect during sepsis.

The authors describe two cases of successful and safe posaconazole use in patients of a surgical intensive care unit of a university hospital.

Urosepsis is one of the most frequent sepsis entities. Mortality from urosepsis is nowadays mostly lower than from other entities. Sepsis syndrome is pathophysiologically characterized by a generalized infection and immune dysregulation. Exogenous microbiological and active or passive endogenous factors released from body cells initiate and accompany the immune dysregulation. Diagnosis and therapy of urosepsis need to be instigated as early as possible (within the first hour), in order to prevent cell and tissue damage in the early phase. For this reason a series of measures is started, aimed at achieving early control of the focus of infection, providing antibiotic treatment, and stabilizing respiratory and cardiovascular function in order to optimize tissue oxygenation. A significant clinical problem ensues due to increasing antibiotic resistance mainly of enterobacteria. The choice of antibiotic therefore is made on the basis of local antibiotic resistance statistics. Dosage is determined on an individual basis, as well as according to current pharmacokinetic/pharmacodynamic knowledge. The intensive care of the septic patient needs to be started as early as on patient admission and, where necessary, continued on the intensive care ward.

Background: Considering the complexity of diagnosis, high costs of therapy and high morbidity and mortality of systemic fungal infections, antifungal therapy of intensive care patients should follow clearly defined guidelines. We outline the impact of a standardised practice of antifungal treatment in an interdisciplinary surgical intensive care unit of a university hospital. Methods: Therapy was intended to be optimised by implementation of standardised practice guidelines supported by the clinical pharmacist. Costs for antifungal agents during a period of 18 months before and after implementation of the practice guidelines were compared, respectively. Results: The intervention was associated with a significant decrease in use of antifungal agents. Analysis of data revealed a reduction in costs by 50%. This could substantially be attributed to the implementation of the practice guidelines. Conclusion: The implementation of standardised practice guidelines for antifungal therapy in intensive care units decreased the use of selected antifungal agents and resulted in substantial reduction in expenditure on antifungal agents.

Candida species constitute the majority of nosocomial fungal pathogens in non-neutropenic patients. Candida infections are still connected with substantial mortality. Recent epidemiological observations indicate a shift to non-albicans species, especially because of a rise of infections caused by C. glabrata, which frequently shows fluconazole-resistance. New therapeutic options like caspofungin, as the first licensed echinocandin, new broad-spectrum azoles, and lipid preparations of amphotericin B emerged in the last decade as efficient alternatives to fluconazole and amphotercin B deoxycholate. In invasive candidiasis, a delayed treatment initiation is associated with an increased mortality, thus risk stratification and empirical therapy strategies become vitally important. This review reflects the efficacy of caspofungin in the treatment of Candida infections, especially in the setting of empirical therapy in critically ill patients, and considers the option of de-escalation to fluconazole.

Critically ill patients after extended surgical procedures are at high risk for postoperative infections. The overall incidence of sepsis increased constantly over the last decade, whereas sepsis-related mortality decreased, due to new intensive care options. After extended intra-abdominal surgery the abdomen is the predominant focus of sepsis, followed by respiratory tract infections. Unspecific clinical signs lead to the diagnosis of postoperative sepsis. Early focus identification by clinical, laboratory and radiologic examination is of major importance for a promising therapy, followed by immediately initiated procedures for source control and an adequate anti-infective drug therapy. For nosocomial sepsis, the use of antimicrobial regimens with extended spectra and potent activity against both Gram-negative and Gram-positive bacterial pathogens are warranted. Fungal infections play a great role for immunocompromized patients, e.g. after solid organ transplantation or under chronic corticoid therapy. An increasing incidence of multi-drug resistance in bacterial and fungal isolates has been observed in the last years. This is becoming a growing problem also for critically ill patients after abdominal surgery. Standardized treatment protocols including supportive and adjunctive therapy and the use of modern anti-infective agents may lead to a decrease in postoperative mortality due to sepsis.

Critically ill patients in intensive-care units are at high risk for pulmonary embolism (PE). As a result of modern multi-detector computed tomographic angiography (MDCT) increased visualization of peripheral pulmonary arteries, isolated subsegmental pulmonary embolisms (ISSPE) are increasingly being detected. The aim of this study was to investigate the rate, impact on treatment, and outcome of unsuspected ISSPE in critically ill patients receiving MDCT. The secondary aim was to investigate the potential impact of contrast media-induced nephropathy (CIN) in our cohort. We conducted a retrospective single-centre analysis on critically ill adult patients treated between January 2009 and December 2012 who underwent a contrast-enhanced chest MDCT. We excluded patients with clinical suspicion of PE/ISSPE prior to CT and patients with MDCT confirmed central PE. Clinical findings, laboratory parameters, and outcome data were recorded. We identified 240 ICU patients not suspected for PE receiving MDCT. A total of 12 Patients (5 %) showed unexpected ISSPE representing increased 24 h mortality (16.7 vs. 3.5 %; p = 0.026) compared to non-ISPPE/non-PE patients. A 30-days mortality did not differ between the groups (33.3 vs. 33.8 %; p = 0.53). Highest mean creatinine serum level in our cohort (n = 240) was found before MDCT with a significant decrease to day 5 (1.4 ± 1.1 vs. 1.1 ± 0.9 mg/dl: p

Abdominal surgery may affect intestinal absorption and the resulting levels of posaconazole in the blood. We measured plasma posaconazole levels in surgical intensive care unit (SICU) patients and tried to develop a predictive population pharmacokinetics model. A total of 270 samples from 15 patients receiving posaconazole via nasogastric tube were measured by high-performance liquid chromatography (HPLC). SICU patients showed lower plasma drug concentrations, a higher apparent clearance, and a higher volume of distribution than those in hematology patients, possibly due to poor absorption.

BackgroundCiliary beating by respiratory epithelial cells continuously purges pathogens from the lower airways. Here we investigated the effect of the fungal cell wall polysaccharides Galactomannan (GM) and Zymosan (Zym) on the adrenergic activated particle transport velocity (PTV) of tracheal epithelium.MethodsExperiments were performed using tracheae isolated from male C57BL/6J mice. Transport velocity of the cilia bearing epithelial cells was measured by analysing recorded image sequences. Generation of reactive oxygen species (ROS) were determined using Amplex Red reagents. PCR experiments were performed on isolated tracheal epithelium to identify adrenergic receptor mRNA.ResultsThe adrenergic receptors α1D, α2A, β1 and β2 have been identified in isolated tracheal epithelium. We found epinephrine responsible for an increase in PTV, which could only be reduced by selective β-receptor-inhibition. In addition, either GM or Zym prevented the epinephrine induced PTV increase. Furthermore, we observed a strong ROS generation evoked by GM or Zym. However, epinephrine induced increase in PTV recovered in the presence of GM and Zym after application of ROS scavengers.ConclusionBoth GM or Zym trigger reversible ROS generation in tracheal tissue leading to inhibition of the β-adrenergic increase in PTV.

Sepsis is one of the oldest and most elusive syndromes in medicine. Every effort should be made to treat these patients with the best available evidence. As a milestone, empiric antimicrobial therapy is essential in order to reduce morbidity and mortality of septic patients. As a sticking point, the use of broad-spectrum antimicrobial agents may be associated with induction of resistance among common pathogens.

Life-threatening traumatic injuries lead to a complex inflammation-driven pathophysiology. Receptor of advanced glycation end product (RAGE) is a multiligand receptor of several endogenous alarmins, while cytokeratin 18 is a structural component of the filament of epithelial cells. Both proteins can be frequently found in plasma of patients with different diseases, whereby they have distinct underlying mechanism of formation. In this prospective observational study, we wanted to shed light on the kinetic of plasmatic RAGE and cytokeratin 18 isoforms after severe trauma, thereby also addressing the association of these markers with inflammation and their potential use as biomarkers.Plasma samples of 77 patients with severe multiple trauma as defined by an Injury Severity Score (ISS) 16 or greater were obtained from a local repository and levels of soluble RAGE, endogenous secretory RAGE, cytokeratin 18, cleaved cytokeratin 18, and interleukin 6 by enzyme-linked immunosorbent assay. Demographic and routine parameters of the cohort were extracted from an electronic patient data management system.Both RAGE isoforms were transiently increased in plasma within 24 hours after trauma, while cytokeratin 18 levels were unchanged. Moreover, soluble RAGE concentrations in patients with thoracic injuries were higher compared with patients without injury, and both isoforms of RAGE discriminated between patients with most severe adult respiratory distress syndrome and patients with milder forms. In addition, cleaved and total cytokeratin 18 levels differ between patients with hepatic dysfunction and normal function, without possessing discriminatory power. RAGE and cytokeratin 18 isoforms correlated significantly but to a low extent with interleukin 6, while the isoforms of both parameters correlated to a high extent with one another.The release of RAGE (but not cytokeratin 18) isoforms occurs early and transiently after trauma and is associated with the extent of injury and inflammatory response. RAGE and cytokeratin 18 isoforms have the potential to act as diagnostic or prognostic biomarkers of lung and hepatic dysfunction.Epidemiologic/prognostic study, level IV.

Background During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus , has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N . vagus , there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function. Materials and methods We performed stimulation of the right cervical branch of the N . vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure–volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N . vagus was enough during initial LPS infusion. Conclusions Overall, the N . vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock.

Urosepsis is defined as sepsis caused by a urogenital tract infection. Urosepsis in adults comprises approximately 25% of all sepsis cases, and is in most cases due to complicated urinary tract infections. The urinary tract is the infection site of severe sepsis or septic shock in approximately 10-30% of cases. Severe sepsis and septic shock is a critical situation, with a reported mortality rate nowadays still ranging from 30% to 40%. Urosepsis is mainly a result of obstructed uropathy of the upper urinary tract, with ureterolithiasis being the most common cause. The complex pathogenesis of sepsis is initiated when pathogen or damage-associated molecular patterns recognized by pattern recognition receptors of the host innate immune system generate pro-inflammatory cytokines. A transition from the innate to the adaptive immune system follows until a T(H2) anti-inflammatory response takes over, leading to immunosuppression. Treatment of urosepsis comprises four major aspects: (i) early diagnosis; (ii) early goal-directed therapy including optimal pharmacodynamic exposure to antimicrobials both in the plasma and in the urinary tract; (iii) identification and control of the complicating factor in the urinary tract; and (iv) specific sepsis therapy. Early adequate tissue oxygenation, adequate initial antibiotic therapy, and rapid identification and control of the septic focus in the urinary tract are critical steps in the successful management of a patient with urosepsis, which includes early imaging, and an optimal interdisciplinary approach encompassing emergency unit, urological and intensive-care medicine specialists.

BACKGROUND Valid prognostic factors for early identification of a complicated course after orthotopic liver transplantation from deceased donors are rare. The aim of this study was to investigate the prognostic value of different cell death biomarkers and inflammatory markers in patients after orthotopic liver transplantation from deceased donors. METHODS In total, 100 patients were evaluated for short-term complications within 10 days after orthotopic liver transplantation from deceased donors. Blood samples were collected before surgery, immediately after the end of the surgical procedure, and 1 day and 3, 5, and 7 days later. Plasma levels of total keratin 18, keratin 18 fragments, interleukin 6, tumor necrosis factor α, and soluble intercellular adhesion molecule 1 were measured. RESULTS Total keratin 18 was demonstrated to be favorable in its prognostic value for early identification of a complicated course in comparison to routine markers of liver impairment (e.g., aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase). In contrast, inflammation markers (e.g., interleukin 6, tumor necrosis factor α and soluble intercellular adhesion molecule 1) were unsuitable for predicting early complications after liver transplantation from deceased donors. CONCLUSIONS For early identification of patients at high risk for complications, the implementation of total keratin 18 measurements in routine diagnostics after orthotopic liver transplantation from deceased donors should be taken into consideration.

Background. Redox active substances (e.g., Thioredoxin-1, Macrophage Migration Inhibitory Factor) seem to be central hubs in the septic inflammatory process.Materials and Methods. Blood samples from patients with severe sepsis or septic shock (n=15) were collected at the time of sepsis diagnosis (t0), and 24 (t24) and 48 (t48) hours later; samples from healthy volunteers (n=18) were collected once; samples from postoperative patients (n=28) were taken one time immediately after surgery. In all patients, we measured plasma levels of IL-6, TRX1 and MIF.Results. The plasma levels of MIF and TRX1 were significantly elevated in patients with severe sepsis or septic shock. Furthermore, TRX1 and MIF plasma levels showed a strong correlation (t0:rsp=0.720,ρ=0.698/t24:rsp=0.771,ρ=0.949).Conclusions. Proinflammatory/~oxidative and anti-inflammatory/~oxidative agents show a high correlation in order to maintain a redox homeostasis and to avoid the harmful effects of an excessive inflammatory/oxidative response.