Pre-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. To 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. A 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). Overall, 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. We 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.

Background: Pseudomonas aeruginosa has recently shown to be one of the most important strains of bacteria and alert pathogens in Europe among Intensive Care Unit patients that provide serious therapeutic problems because of its multidrug resistance. Methods: The purpose of this microbiological study was data analysis of device associated- healthcare associated infections (DA-HAIs) in an ICU in terms of the incidents of P.aeruginosa strain infections and its susceptibility within an 8.5-year observation. Results: Among 919 isolated strains responsible for 799 DA-HAIs (17,62 ± 1,98/1000 patient-days) in 4010 ICU patients P.aeruginosa was the pathogen in 108/799 (13.52%) cases. Incidence rate (density) of: VAP/1000 MV- days, UTI /1000 UC- days and CLA-BSI/1000 CL- days were 11,15 ± 2.5, 6.82 ± 0.81, 2.35 ± 1.54.respectivelly. P.aeruginosa was the pathogen most frequently responsible for VAP 69/108 (63.88%). Mean frequency of VAP, UTI and CLA-BSI with P.aeruginosa etiology was 69/493 (14.28%), 32/299 (11.1%) and 7/127 (5.77%) respectively. The mean density of P.aeruginosa infection amounted to 2.43/1000 patient-days. The decrease was observed in the total number of DA-HAIs caused by the P.aeruginosa from 15.75% and 3.23/1000 patient-days in 2011 to 5.0% and 1.17/1000 in 2016 (p = 0.0104, p = 0.0348). Starting from 2016 to 2019 incidence and density of P.aeruginosa DA-HAIs increased to 12.33% and 2.63/1000 (p = 0.1388, p = 0.0818). P.aeruginosa was susceptible to ceftazidime, cefepime, amikacin, meropenem, ciprofloxacin, colistin, in 55.55, 58.33, 70.37, 53.73, 50, and 100% respectively. MDR characterised it in 40% in 2011 and 66.7% in 2019, (p = 0.177). Conclusions: The study revealed a changeable prevalence of P. aeruginosa strain infections; however their frequency was never highest in our ICU patients as it presented in the last years in Europe. The study showed a significant decrease in 2016 and increase in 2019, a nearly 3-fold increase of P.aeruginosa infections among Gram-negative strain infections, and a 2-fold increase of the P.aeruginosa DA-HAIs frequency between 2016 and 2019 as well as an increased resistance. Microbiological analysis of DA-HAIs in each hospital should be a standard method used in hospital infection control and antibiotic policy. In the case of P.aeruginosa, in order to minimize transmission, preventive infection methods should be assessed mainly in case of VAP.

Gastrointestinal (GI) failure can be both a cause of sepsis and a consequence of the systemic pro-inflammatory response in sepsis. Changes in biomarkers of enterocyte damage, citrulline and I-FABP (intestinal fatty acid binding protein), may indicate altered intestinal permeability and damage. The study group consisted of patients with sepsis (N = 28) and septic shock (N = 30); the control group included patients without infection (N = 10). Blood samples were collected for citrulline and I-FABP and a 4-point AGI score (acute GI injury score) was calculated to monitor GI function on days 1, 3, 5, 7, and 10. Citrulline concentrations in the study group were lower than in the control. Lower values were also noted in septic patients with shock when compared to the non-shock group throughout the study period. I-FABP was higher in the septic shock group than in the sepsis group only on days 1 and 3. Citrulline was lower in patients with GI failure (AGI III) when compared to AGI I/II, reaching significance on days 7 (p = 0.034) and 10 (p = 0.015); moreover, a higher AGI score was associated with an increased 28 day mortality (p = 0.038). The results indicate that citrulline measurements, along with the AGI assessment, have clinical potential in monitoring GI function and integrity in sepsis.

The Nutrition Risk in Critically Ill score (NUTRIC) is an important nutritional risk assessment instrument for patients in the intensive care unit (ICU). The purpose of this study was to evaluate the power of the score to predict mortality in patients treated for sepsis and to forecast increased resource utilization and nursing workload in the ICU. The NUTRIC score predicted mortality (AUC 0.833, p < 0.001) with the optimal cut-off value of 6 points. Among patients with a score ≥ 6 on ICU admission, the 28-day mortality was 61%, and 10% with a score < 6 (p < 0.001). In addition, a NUTRIC score of ≥6 was associated with a more intense use of ICU resources, as evidenced by a higher proportion of patients requiring vasopressor infusion (98 vs. 82%), mechanical ventilation (99 vs. 87%), renal replacement therapy (54 vs. 26%), steroids (68 vs. 31%), and blood products (60 vs. 43%); the nursing workload was also significantly higher in this group. In conclusion, the NUTRIC score obtained at admission to the ICU provided a good discriminative value for mortality and makes it possible to identify patients who will ultimately require intense use of ICU resources and an associated increase in the nursing workload during treatment.

Gastrointestinal symptoms are common in critically ill COVID-19 patients. There is currently no generally recognized method of assessing gastrointestinal injury in unconscious or sedated intensive care unit (ICU) patients. I-FABP (intestinal fatty acid binding protein) and citrulline have previously been studied as potential biomarkers of enterocyte damage in various gastrointestinal tract diseases, and changes in the levels of these markers may reflect intestinal wall damage in COVID-19. Patients with critical COVID-19, with diagnosed sepsis, or septic shock requiring ICU treatment were included in the study. Blood samples for citrulline and I-FABP were taken daily from day 1 to 5. I-FABP levels were significantly higher in patients who eventually died from COVID-19 than in survivors, and the optimal I-FABP cut-off point for predicting 28-day mortality was 668.57 pg/mL (sensitivity 0.739, specificity 0.765). Plasma levels of I-FABP, but not citrulline, were associated with significantly higher mortality and appeared to be a predictor of poor outcome in multivariate logistic regression analysis. In conclusion, I-FABP seems to be an effective prognostic marker in critically ill COVID-19 patients. Assessing mortality risk based on intestinal markers may be helpful in making clinical decisions regarding the management of intestinal injury, imaging diagnostics, and potential surgical interventions.

Given the rising rate of opioid-related adverse drug events during postsurgical pain management, a nonpharmacologic therapy that could decrease analgesic medication requirements would be of immense value. We designed a prospective, placebo-and-randomized controlled trial to assess the clinical effect of transcutaneous acupoint electrical stimulation (TEAS) on the postoperative patient-controlled analgesia (PCA) requirement for morphine, as well as side effects and recovery profile after inguinal hernia repair. Seventy-one subjects undergoing inguinal hernia repair with a standardized anesthetic technique were randomly assigned to one of three analgesic treatment regimens: PCA + TEAS (n = 24); PCA + sham-TEAS (no electrical stimulation) (n = 24), and PCA only (n = 23). The postoperative PCA requirement, pain scores, opioid-related side effects, and blood cortisol levels were recorded. TEAS treatment resulted in a twofold decrease in the analgesic requirement and decreased pain level reported by the patients. In addition, a significant reduction of cortisol level was reported in the TEAS group at 24 h postoperatively compared to the sham and control groups. We conclude that TEAS is a safe and effective option for reducing analgesic consumption and postoperative pain following inguinal hernia repair.