Prospective clinical study testing the efficacy and safety of a new formula to increase the precision of oxygen therapy in the initiation phase of cardiopulmonary bypass.

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 <79.9 mmHg, 31.25% between 80 and 149.9 mmHg, 38.75% between 150 and 249.9 mmHg and 21.25%>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.

Invasive aspergillosis in solid organ transplant patients: diagnosis, prophylaxis, treatment, and assessment of response.

BACKGROUND: Invasive aspergillosis (IA) is a rare complication in solid organ transplant (SOT) recipients. Although IA has significant implications on graft and patient survival, data on diagnosis and management of this infection in SOT recipients are still limited. METHODS: Discussion of current practices and limitations in the diagnosis, prophylaxis, and treatment of IA and proposal of means of assessing treatment response in SOT recipients. RESULTS: Liver, lung, heart or kidney transplant recipients have common as well as different risk factors to the development of IA, thus each category needs a separate evaluation. Diagnosis of IA in SOT recipients requires a high degree of awareness, because established diagnostic tools may not provide the same sensitivity and specificity observed in the neutropenic population. IA treatment relies primarily on mold-active triazoles, but potential interactions with immunosuppressants and other concomitant therapies need special attention. CONCLUSIONS: Criteria to assess response have not been sufficiently evaluated in the SOT population and CT lesion dynamics, and serologic markers may be influenced by the underlying disease and type and severity of immunosuppression. There is a need for well-orchestrated efforts to study IA diagnosis and management in SOT recipients and to develop comprehensive guidelines for this population.

Therapeutic drug monitoring-guided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience.

PURPOSE: Standard dosing and intermittent bolus application (IB) are important risk factors for pharmacokinetic (PK) target non-attainment during empirical treatment with ß-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. METHODS: 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)]. RESULTS: 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 < 0.0005), whereas high CrCL led to non-target attainment (p < 0.0005). Patients with target attainment (33-64 mg/L) within the first 24 h exhibited the lowest hospital mortality rates (13.9% [n = 23/166], p < 0.005). Those with target non-attainment demonstrated higher mortality rates (≤ 32 mg/L; 20.8% [n = 10/49] ≥ 64 mg/L; 29.4% [n = 79/269]). CONCLUSION: TDM-guided CI of PIP is safe in critically ill patients and improves PK-target attainment. Exposure to defined PK-targets impacts patient mortality while lower and higher than intended SCs may influence the outcome of critically ill patients. Renal function and renal replacement therapy are main determinants of PK-target attainment. These results are only valid for CI of PIP and not for prolonged or intermittent bolus administration of PIP.

Impact of a semi-structured briefing on the management of adverse events in anesthesiology: a randomized pilot study.

BACKGROUND: Human factors research has identified mental models as a key component for the effective sharing and organization of knowledge. The challenge lies in the development and application of tools that help team members to arrive at a shared understanding of a situation. The aim of this study was to assess the influence of a semi-structured briefing on the management of a simulated airway emergency. METHODS: 37 interprofessional teams were asked to perform a simulated rapid-sequence induction in the simulator. Teams were presented with a "cannot ventilate, cannot oxygenate" scenario that ultimately required a cricothyroidotomy. Study group (SG) teams were asked to perform a briefing prior to induction, while controls (CG) were asked to perform their usual routine. RESULTS: We observed no difference in the mean time until cricothyroidotomy (SG 8:31 CG 8:16, p = 0.36). There was a significant difference in groups' choice of alternative means of oxygenation: While SG teams primarily chose supraglottic airway devices, controls initially reverted to mask ventilation (p = 0.005). SG teams spent significantly less time with this alternative airway device and were quicker to advance in the airway algorithm. CONCLUSIONS: Our study addresses effects on team coordination through a shared mental model as effected by a briefing prior to anesthesia induction. We found measurable improvements in airway management during those stages of the difficult airway algorithm explicitly discussed in the briefing. For those, time spent was shorter and participants were quicker to advance in the airway algorithm.

Sepsis in mechanically ventilated patients with spinal cord injury: a retrospective analysis.

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.

Applying the human factors analysis and classification system to critical incident reports in anaesthesiology.

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.

Inflammation and Its Consequences After Surgical Versus Transcatheter Aortic Valve Replacement.

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.

Risk factors for early viral infections after liver transplantation.

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: DRKS00010672 on German Clinical Trial Register.

Advanced glycation endproducts induce self- and cross-tolerance in monocytes.

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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".

Plasma DNA and RNA differentially impact coagulation during abdominal sepsis-an explorative study.

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.

Anesthetic Management for Percutaneous Minimally Invasive Fetoscopic Surgery of Spina Bifida Aperta: A Retrospective, Descriptive Report of Clinical Experience.

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).

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

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

Cardiac Effects of Echinocandins in Endotoxemic Rats.

Echinocandins are known as effective and safe agents for the prophylaxis and treatment of different cohorts of patients with fungal infections. Recent studies revealed that certain pharmacokinetics of echinocandin antifungals might impact clinical efficacy and safety in special patient populations. The aim of our study was to evaluate echinocandin-induced aggravation of cardiac impairment in septic shock. Using an in vivo endotoxemic shock model in rats, we assessed hemodynamic parameters and time to hemodynamic failure (THF) after additional central-venous application of anidulafungin (2.5 mg/kg of body weight [BW]), caspofungin (0.875 mg/kg BW), micafungin (3 mg/kg BW), and control (0.9% sodium chloride). In addition, echinocandin-induced cytotoxicity was evaluated in isolated rat cardiac myocytes. THF of the animals in the caspofungin group (n = 7) was significantly reduced compared to that in the control (n = 6) (136 min versus 180 min; P = 0.0209). The anidulafungin group (n = 7) also showed a trend of reduced THF (136 min versus 180 min; log-rank test P = 0.0578). Animals in the micafungin group (n = 7) did not show significant differences in THF compared to those in the control. Control group animals and also micafungin group animals did not show altered cardiac output (CO) during our experiments. In contrast, administration of anidulafungin or caspofungin induced a decrease in CO. We also revealed a dose-dependent increase of cytotoxicity in anidulafungin- and caspofungin-treated cardiac myocytes. Treatment with micafungin did not cause significantly increased cytotoxicity. Further studies are needed to explore the underlying mechanism.

Cardiac effects of echinocandins after central venous administration in adult rats.

Echinocandins have become the agents of choice for early and specific antifungal treatment in critically ill patients. In vitro studies and clinical case reports revealed a possible impact of echinocandin treatment on cardiac function. The aim of our study was to evaluate echinocandin-induced cardiac failure. Using an in vivo rat model, we assessed hemodynamic parameters and time to hemodynamic failure after central venous application (vena jugularis interna) of anidulafungin (low-dose group, 2.5 mg/kg body weight [BW]; high-dose group, 25 mg/kg BW), caspofungin (low-dose group, 0.875 mg/kg BW; high-dose group, 8.75 mg/kg BW), micafungin (low-dose group, 3 mg/kg BW; high-dose group, 30 mg/kg BW), and placebo (0.9% sodium chloride). Left ventricular heart tissue was collected to determine mitochondrial enzyme activity via spectrophotometric measurements. mRNA expression of transcriptional regulators and primary mitochondrial transcripts, mitochondrial DNA (mtDNA) content, and citrate synthase activity were also explored. Animals receiving high-dose anidulafungin or caspofungin showed an immediate decrease in hemodynamic function. All of the subjects in these groups died during the observation period. Every animal in the untreated control group survived (P < 0.001). Hemodynamic failure was not noticed in the anidulafungin and caspofungin low-dose groups. Micafungin had no impact on cardiac function. In analyzing mitochondrial enzyme activity and mitochondrial transcripts, we found no association between echinocandin administration and the risk for hemodynamic failure. Further experimental studies are needed to elucidate the underlying mechanisms involved in cardiotoxic echinocandin effects. In addition, randomized controlled clinical trials are needed to explore the clinical impact of echinocandin treatment in critically ill patients.

Relevance of Candida and other mycoses for morbidity and mortality in severe sepsis and septic shock due to peritonitis.

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.

Role of the RAGE Axis during the Immune Response after Severe Trauma: A Prospective Pilot Study.

BACKGROUND: Severe traumatization induces a complex pathophysiology, driven by the patient's own immune system. The initial activation is a result of damage-associated molecular patterns, which are released from disrupted and dying cells and recognized by immune receptors, for example, RAGE. In this study we aimed to evaluate the contribution of the RAGE axis to early and late immune responses. METHODS: We enrolled 16 patients with severe trauma together with 10 patients after major abdominal surgery and 10 healthy volunteers. Blood samples were taken on admission and every 48 h for a total of 8 days. Plasma concentrations of various RAGE ligands as well as RAGE isoforms and IL-6 were measured by ELISA. Monocyte surface expression of RAGE and HLA-DR was assessed by flow cytometry. RESULTS: High and transient levels of IL-6 and methylglyoxal characterize the early immune response after trauma, whereas samples from later time points provide evidence for a secondary release of RAGE ligands. CONCLUSION: Our results provide evidence for a persisting activation of the RAGE axis while classical mediators like IL-6 disappear early. Considering the immunocompromised phenotype of the monocytes, the RAGE ligands might be substantial contributors to the well-known secondary stage of impaired immune responsiveness in trauma patients.

Prospective evaluation of regional oxygen saturation to estimate central venous saturation in sepsis.

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 ScvO2 >70% 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 ScvO2 <70% and lactate levels <2.5 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 lactate >2.5 mmol/l and ScvO2 >70 % is highly associated with poor outcome in ICU patients with sepsis, severe sepsis and septic shock.

[Pathophysiology of sepsis]. / Sepsis und Multiorganversagen - Pathophysiologie der Sepsis.

Our understanding of the causes and pathophysiological basis of sepsis has been subject to constant change over the last decades. In today's understanding, sepsis is primarily a pathology of the immune system, triggered by an underlying infection but perpetuated by the host's response itself. Thereby, sepsis should not be categorized to be either a sole pro- or anti-inflammatory syndrome, but rather as a variable continuum of overlaying immune mechanisms. While a overshooting immune reaction predominates in early sepsis, this reaction is rapidly compensated, often leading to a immune dysfunction, rendering the host susceptible for secondary infections. This review aims to provide the reader with an overview of the broad molecular mechanisms contributing to the clinical picture of sepsis.

Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.

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.

The early antibiotic therapy in septic patients--milestone or sticking point?

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.