Preclinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of preclinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on preclinical sepsis modeling was held in Vienna in May, 2017. The goal of the conference was to identify limitations of preclinical sepsis models and to propose a set of guidelines, defined as the “Minimum Quality Threshold in Preclinical Sepsis Studies” (MQTiPSS), to enhance translational value of these models. A total of 31 experts from 13 countries participated and were divided into six thematic Working Groups: Study Design, Humane modeling, Infection types, Organ failure/dysfunction, Fluid resuscitation, and Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002–2013). Overall, the participants reached consensus on 29 points; 20 at “recommendation” and nine at “consideration” strength. This Executive Summary provides a synopsis of the MQTiPSS consensus. We believe that these recommendations and considerations will serve to bring a level of standardization to preclinical models of sepsis and ultimately improve translation of preclinical findings. These guideline points are proposed as “best practices” for animal models of sepsis that should be implemented. To encourage its wide dissemination, this article is freely accessible on the Intensive Care Medicine Experimental and Infection journal websites. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection, and Intensive Care Medicine Experimental.

BackgroundPre-clinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking.ObjectiveTo address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May 2017. The goal of the conference was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the “Minimum Quality Threshold in Pre-Clinical Sepsis Studies” (MQTiPSS), to enhance translational value of these models.MethodsA total of 31 experts from 13 countries participated and were divided into 6 thematic working groups (WG): (1) study design, (2) humane modeling, (3) infection types, (4) organ failure/dysfunction, (5) fluid resuscitation, and (6) antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002–2013).ResultsOverall, the participants reached consensus on 29 points; 20 at “recommendation” (R) and 9 at “consideration” (C) strength. This executive summary provides a synopsis of the MQTiPSS consensus (Tables 1, 2, and 3). Detailed commentaries to all Rs and Cs are simultaneously published in three separate full-length papers.ConclusionsWe believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as “best practices” for animal models of sepsis that should be implemented. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.

PurposePre-clinical animal studies precede the majority of clinical trials. While the clinical sepsis definitions and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May, 2017. The conference goal was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the “Minimum Quality Threshold in Pre-Clinical Sepsis Studies” (MQTiPSS), to enhance translational value of these models.Methods31 experts from 13 countries participated and were divided into 6 thematic Working Groups (WG): (1) Study Design, (2) Humane modeling, (3) Infection types, (4) Organ failure/dysfunction, (5) Fluid resuscitation and (6) Antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002–2013).ResultsOverall, the participants reached consensus on 29 points; 20 at “recommendation” (R) and 9 at “consideration” (C) strength. This Executive Summary provides a synopsis of the MQTiPSS consensus (Tables 1, 2 and 3).ConclusionsWe believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as “best practices” that should be implemented for animal sepsis models. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.

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Objective and DesignThe soluble urokinase plasminogen activator receptor (suPAR) has been recently recognized as a potential biological marker of various disease states, but the impact of a major surgical intervention on the suPAR level has not yet been established. The aim of our study was to investigate if the induction of a systemic inflammatory reaction in response to cardiopulmonary bypass would be accompanied by an increase in the plasma suPAR level.Methods and SubjectsPatients undergoing coronary artery bypass grafting under cardiopulmonary bypass (CPB) were added. Based on the baseline suPAR level, patients were divided into group 1 (suPAR within normal range) or group 2 (suPAR above range). Blood was collected before the induction of anesthesia and 6 and 24 hours after surgery. Plasma suPAR, IL-6, IL-8, TNF-α, troponin I, NT-proBNP, and NGAL were quantified to assess the impact of surgical trauma on these markers.ResultsThe baseline suPAR level was within the normal range in 31 patients (3.3 ng/mL), and elevated in 29 (5.1 ng/mL) (p<0.001). Baseline mediators of systemic inflammatory reaction concentrations (IL-6, TNF-α, and IL-8) and organ injury indices (troponin I, NT-proBNP, and NGAL) were low and increased after surgery in all patients (p<0.05). The surgery did not cause significant changes in the suPAR level either at 6 or 24 hours after, however the difference between groups observed at baseline remained substantial during the postoperative period.ConclusionsThere was no change in the suPAR level observed in patients subjected to elective cardiac coronary artery bypass surgery and CPB, despite activation of a systemic inflammatory reaction.

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As outlined in the “International Guidelines for Management of Sepsis and Septic Shock: 2016,” initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part III report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen (s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as “best practices” for animal models of sepsis that should be implemented.

Background In Poland, the clinical characteristics and outcomes of patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) remain unknown. This study aimed to answer these unknowns by analyzing data collected from high-volume ECMO centers willing to participate in this project. Methods This retrospective, multicenter cohort study was completed between March 1, 2020, and May 31, 2021 (15 months). Data from all patients treated with ECMO for COVID-19 were analyzed. Pre-ECMO laboratory and treatment data were compared between non-survivors and survivors. Independent predictors for death in the intensive care unit (ICU) were identified. Results There were 171 patients admitted to participating centers requiring ECMO for refractory hypoxemia due to COVID-19 during the defined time period. A total of 158 patients (mean age: 46.3 ± 9.8 years) were analyzed, and 13 patients were still requiring ECMO at the end of the observation period. Most patients (88%) were treated after October 1, 2020, 77.8% were transferred to ECMO centers from another facility, and 31% were transferred on extracorporeal life support. The mean duration of ECMO therapy was 18.0 ± 13.5 days. The crude ICU mortality rate was 74.1%. In the group of 41 survivors, 37 patients were successfully weaned from ECMO support and four patients underwent a successful lung transplant. In-hospital death was independently associated with pre-ECMO lactate level (OR 2.10 per 1 mmol/L, p = 0.017) and BMI (OR 1.47 per 5 kg/m2, p = 0.050). Conclusions The ICU mortality rate among patients requiring ECMO for COVID-19 in Poland was high. In-hospital death was independently associated with increased pre-ECMO lactate levels and BMI.