Analysis of Inflammatory Mediator Profiles in Sepsis Patients Reveals That Extracellular Histones Are Strongly Elevated in Nonsurvivors.

The timely recognition of sepsis and the prediction of its clinical course are challenging due to the complex molecular mechanisms leading to organ failure and to the heterogeneity of sepsis patients. Treatment strategies relying on a "one-fits-all" approach have failed to reduce mortality, suggesting that therapeutic targets differ between patient subgroups and highlighting the need for accurate analysis of the molecular cascades to assess the highly variable host response. Here, we characterized a panel of 44 inflammatory mediators, including cytokines, chemokines, damage-associated molecular patterns, and coagulation-related factors, as well as markers of endothelial activation in 30 patients suffering from renal failure in the course of sepsis. All patients received continuous veno-venous hemodialysis with either high cut-off filters or with standard filters, and mediators were quantified for all patients at the initiation of dialysis and after 24 h and 48 h. Mediator concentrations in individual patients ranged widely, demonstrating the heterogeneity of sepsis patients. None of the mediators correlated with SAPS III or TISS scores. The overall in-hospital mortality of the study population was 56.7% (57.1% vs. 56.3% for high cut-off vs. standard filter). The two filter groups differed regarding most of the mediator levels at baseline, prohibiting conclusions regarding the effect of standard filters versus high cut-off filters on mediator depletion. The elevation and correlation of damage-associated molecular patterns and markers of endothelial activation gave evidence of severe tissue damage. In particular, extracellular histones were strongly increased and were almost 30-fold higher in nonsurvivors as compared to survivors, indicating their diagnostic and prognostic potential.

Clearance of Selected Plasma Cytokines with Continuous Veno-Venous Hemodialysis Using Ultraflux EMiC2 versus Ultraflux AV1000S.

BACKGROUND: High cutoff hemofilters might support the restoration of immune homeostasis in systemic inflammation by depleting inflammatory mediators from the circulation. METHODS: Interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha depletion was assessed in 30 sepsis patients with acute renal failure using continuous veno-venous hemodialysis with high cutoff versus standard filters (CVVHD-HCO vs. CVVHD-STD) over 48 h. RESULTS: The transfer of IL-6 and IL-8 was significantly higher for CVVHD-HCO, as shown by increased IL-6 and IL-8 effluent concentrations. The mean plasma cytokine concentrations decreased over time for all cytokines without detectable differences for the treatment modalities. No transfer of albumin was observed for either of the filters. C-reactive protein remained stable over time and did not differ between CVVHD-HCO and CVVHD-STD, while procalcitonin decreased significantly over 48 h for both treatment modalities. CONCLUSION: CVVHD-HCO achieved enhanced removal of IL-6 and IL-8 as compared to CVVHD-STD, without differentially reducing plasma cytokine levels.

Automated control of mechanical ventilation during general anaesthesia: study protocol of a bicentric observational study (AVAS).

INTRODUCTION: Automated control of mechanical ventilation during general anaesthesia is not common. A novel system for automated control of most of the ventilator settings was designed and is available on an anaesthesia machine. METHODS AND ANALYSIS: The 'Automated control of mechanical ventilation during general anesthesia study' (AVAS) is an international investigator-initiated bicentric observational study designed to examine safety and efficacy of the system during general anaesthesia. The system controls mechanical breathing frequency, inspiratory pressure, pressure support, inspiratory time and trigger sensitivity with the aim to keep a patient stable in user adoptable target zones. Adult patients, who are classified as American Society of Anesthesiologists physical status I, II or III, scheduled for elective surgery of the upper or lower limb or for peripheral vascular surgery in general anaesthesia without any additional regional anaesthesia technique and who gave written consent for study participation are eligible for study inclusion. Primary endpoint of the study is the frequency of specifically defined adverse events. Secondary endpoints are frequency of normoventilation, hypoventilation and hyperventilation, the time period between switch from controlled ventilation to assisted ventilation, achievement of stable assisted ventilation of the patient, proportion of time within the target zone for tidal volume, end-tidal partial pressure of carbon dioxide as individually set up for each patient by the user, frequency of alarms, frequency distribution of tidal volume, inspiratory pressure, inspiration time, expiration time, end-tidal partial pressure of carbon dioxide and the number of re-intubations. ETHICS AND DISSEMINATION: AVAS will be the first clinical study investigating a novel automated system for the control of mechanical ventilation on an anaesthesia machine. The study was approved by the ethics committees of both participating study sites. In case that safety and efficacy are acceptable, a randomised controlled trial comparing the novel system with the usual practice may be warranted. TRIAL REGISTRATION: DRKS DRKS00011025, registered 12 October 2016; clinicaltrials.gov ID. NCT02644005, registered 30 December 2015.