Management of intra-abdominal infections: recommendations by the Italian council for the optimization of antimicrobial use.

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.

Blood Purification in Hepatic Dysfunction after Liver Transplant or Extensive Hepatectomy: Far from the Best-Case Scenarios.

Background: Hepatic dysfunction (HD) after liver transplantation (LT) or extended hepatic resection (EHR) is associated with graft failure and high short-term mortality. We evaluated the safety and depurative efficacy of CytoSorb® in these settings. The primary endpoint was the change in serum total bilirubin at the end of the treatment compared to the baseline value. The secondary endpoint was to evaluate the trend of serum total bilirubin and coagulation parameters up to 72 h after discontinuation of CytoSorb®. The effects of CytoSorb® therapy on the degree of hepatic encephalopathy (HE), Sequential Organ Failure Assessment (SOFA), and Model for End-Stage Liver Disease (MELD) scores as well as the hemodynamic status compared to baseline were also assessed. Methods: Adult patients with a serum total bilirubin level > 10 mg/dL admitted to the Intensive Care Unit were included. Exclusion criteria were hemodynamic instability, postoperative bleeding and platelet count < 20,000/mm3. Results: Seven patients were treated. Serum total bilirubin was significantly reduced at the end of treatment. However, seventy-two hours after the discontinuation of extracorporeal therapy, bilirubin levels returned to baseline levels in four patients. A decrease in platelet count was found during therapy, and platelet transfusion was required in six cases. A significant increase in D-dimer at the end of treatment was detected. HE degree, SOFA and MELD scores remained stable, while a deterioration in hemodynamic status was observed in two cases. Conclusions: Our preliminary findings did not show the possible benefits of CytoSorb® in rebalancing clinical and laboratory parameters in patients with HD after LT or EHR.

Antimicrobial De-Escalation in Critically Ill Patients.

Antimicrobial de-escalation (ADE) is defined as the discontinuation of one or more antimicrobials in empirical therapy, or the replacement of a broad-spectrum antimicrobial with a narrower-spectrum antimicrobial. The aim of this review is to provide an overview of the available literature on the effectiveness and safety of ADE in critically ill patients, with a focus on special conditions such as anti-fungal therapy and high-risk categories. Although it is widely considered a safe strategy for antimicrobial stewardship (AMS), to date, there has been no assessment of the effect of de-escalation on the development of resistance. Conversely, some authors suggest that prolonged antibiotic treatment may be a side effect of de-escalation, especially in high-risk categories such as neutropenic critically ill patients and intra-abdominal infections (IAIs). Moreover, microbiological documentation is crucial for increasing ADE rates in critically ill patients with infections, and efforts should be focused on exploring new diagnostic tools to accelerate pathogen identification. For these reasons, ADE can be safely used in patients with infections, as confirmed by high-quality and reliable microbiological samplings, although further studies are warranted to clarify its applicability in selected populations.

Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23.

BACKGROUND: In the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies. METHODS: A panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method. RESULTS: The consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions. CONCLUSIONS: Although clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.

Severe Community-Acquired Pneumonia: Noninvasive Mechanical Ventilation, Intubation, and HFNT.

Severe acute respiratory failure (ARF) is a major issue in patients with severe community-acquired pneumonia (CAP). Standard oxygen therapy is the first-line therapy for ARF in the less severe cases. However, respiratory supports may be delivered in more severe clinical condition. In cases with life-threatening ARF, invasive mechanical ventilation (IMV) will be required. Noninvasive strategies such as high-flow nasal therapy (HFNT) or noninvasive ventilation (NIV) by either face mask or helmet might cover the gap between standard oxygen and IMV. The objective of all the supporting measures for ARF is to gain time for the antimicrobial treatment to cure the pneumonia. There is uncertainty regarding which patients with severe CAP are most likely to benefit from each noninvasive support strategy. HFNT may be the first-line approach in the majority of patients. While NIV may be relatively contraindicated in patients with excessive secretions, facial hair/structure resulting in air leaks or poor compliance, NIV may be preferable in those with increased work of breathing, respiratory muscle fatigue, and congestive heart failure, in which the positive pressure of NIV may positively impact hemodynamics. A trial of NIV might be considered for select patients with hypoxemic ARF if there are no contraindications, with close monitoring by an experienced clinical team who can intubate patients promptly if they deteriorate. In such cases, individual clinician judgement is key to choose NIV, interface, and settings. Due to the paucity of studies addressing IMV in this population, the protective mechanical ventilation strategies recommended by guidelines for acute respiratory distress syndrome can be reasonably applied in patients with severe CAP.

Predictors of Mortality and Orotracheal Intubation in Patients with Pulmonary Barotrauma Due to COVID-19: An Italian Multicenter Observational Study during Two Years of the Pandemic.

Introduction: Coronavirus disease 2019 (COVID-19) is a significant and novel cause of acute respiratory distress syndrome (ARDS). During the COVID-19 pandemic, there has been an increase in the incidence of cases involving pneumothorax and pneumomediastinum. However, the risk factors associated with poor outcomes in these patients remain unclear. Methods: This observational study collected clinical and imaging data from COVID-19 patients with PTX and/or PNM across five tertiary hospitals in central Italy between 1 March 2020 and 1 March 2022. This study also calculated the incidence of PTX and PNM and utilized multivariable regression analysis and Kaplan-Meier curve analysis to identify predictor factors for 28-day mortality and 3-day orotracheal intubation after PTX/PNM. This study also considered the impact of the three main variants of concern (VoCs) (alfa, delta, and omicron) circulating during the study period. Results: During the study period, a total of 11,938 patients with COVID-19 were admitted. This study found several factors independently associated with a higher risk of death in COVID-19 patients within 28 days of pulmonary barotrauma. These factors included a SOFA score ≥ 4 (OR 3.22, p = 0.013), vasopressor/inotropic therapy (OR 11.8, p < 0.001), hypercapnia (OR 2.72, p = 0.021), PaO2/FiO2 ratio < 150 mmHg (OR 10.9, p < 0.001), and cardiovascular diseases (OR 7.9, p < 0.001). This study also found that a SOFA score ≥ 4 (OR 3.10, p = 0.015), PCO2 > 45 mmHg (OR 6.0, p = 0.003), and P/F ratio < 150 mmHg (OR 2.9, p < 0.042) were factors independently associated with a higher risk of orotracheal intubation (OTI) within 3 days from PTX/PNM in patients with non-invasive mechanical ventilation. SARS-CoV-2 VoCs were not associated with 28-day mortality or the risk of OTI. The estimated cumulative probability of OTI in patients after pneumothorax was 44.0% on the first day, 67.8% on the second day, and 68.9% on the third day, according to univariable survival analysis. In patients who had pneumomediastinum only, the estimated cumulative probability of OTI was 37.5%, 46.7%, and 57.7% on the first, second, and third days, respectively. The overall incidence of PTX/PNM among hospitalized COVID-19 patients was 1.42%, which increased up to 4.1% in patients receiving invasive mechanical ventilation. Conclusions: This study suggests that a high SOFA score (≥4), the need for vasopressor/inotropic therapy, hypercapnia, and PaO2/FiO2 ratio < 150 mmHg in COVID-19 patients with pulmonary barotrauma are associated with higher rates of intubation, ICU admission, and mortality. Identifying these risk factors early on can help healthcare providers anticipate and manage these patients more effectively and provide timely interventions with appropriate intensive care, ultimately improving their outcomes.

Lung microbiota composition, respiratory mechanics, and outcomes in COVID-19-related ARDS.

Few data are available on the lung microbiota composition of patients with coronavirus disease 2019-related acute respiratory distress syndrome (C-ARDS) receiving invasive mechanical ventilation (IMV). Moreover, it has never been investigated whether there is a potential correlation between lung microbiota communities and respiratory mechanics. We performed a prospective observational study in two intensive care units of a university hospital in Italy. Lung microbiota was investigated by bacterial 16S rRNA gene sequencing, performed on bronchoalveolar lavage fluid samples withdrawn after intubation. The lung bacterial communities were analyzed after stratification by respiratory system compliance/predicted body weight (Crs) and ventilatory ratio (VR). Weaning from IMV and hospital survival were assessed as secondary outcomes. In 70 C-ARDS patients requiring IMV from 1 April through 31 December 2020, the lung microbiota composition (phylum taxonomic level, permutational multivariate analysis of variance test) significantly differed between who had low Crs vs those with high Crs (P = 0.010), as well as in patients with low VR vs high VR (P = 0.012). As difference-driving taxa, Proteobacteria (P = 0.017) were more dominant and Firmicutes (P = 0.040) were less dominant in low- vs high-Crs patients. Similarly, Proteobacteria were more dominant in low- vs high-VR patients (P = 0.013). After multivariable regression analysis, we further observed lung microbiota diversity as a negative predictor of weaning from IMV and hospital survival (hazard ratio = 3.31; 95% confidence interval, 1.52-7.20, P = 0.048). C-ARDS patients with low Crs/low VR had a Proteobacteria-dominated lung microbiota. Whether patients with a more diverse lung bacterial community may have more chances to be weaned from IMV and discharged alive from the hospital warrants further large-scale investigations. IMPORTANCE: Lung microbiota characteristics were demonstrated to predict ventilator-free days and weaning from mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). In this study, we observed that in severe coronavirus disease 2019 patients with ARDS who require invasive mechanical ventilation, lung microbiota characteristics were associated with respiratory mechanics. Specifically, the lung microbiota of patients with low respiratory system compliance and low ventilatory ratio was characterized by Proteobacteria dominance. Moreover, after multivariable regression analysis, we also found an association between patients' microbiota diversity and a higher possibility of being weaned from mechanical ventilation and discharged alive from the hospital. For these reasons, lung microbiota characterization may help to stratify patient characteristics and orient the delivery of target interventions. (This study has been registered at ClinicalTrials.gov on 17 February 2020 under identifier NCT04271345.).Registered at ClinicalTrials.gov, 17 February 2020 (NCT0427135).

Complicated Falciparum Malarial ARDS Requiring Noninvasive Support.

Severe plasmodium falciparum infection can induce respiratory distress and clinical ARDS in children, requiring intensive care admission and respiratory support. We present 3 cases of imported malarial acute respiratory distress syndrome requiring noninvasive ventilation in the pediatric intensive care unit, in the absence of any cerebral involvement. Radiological features and their relationship with severe hematological complications are also illustrated.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society and the European Society of Intensive Care Medicine. Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

Successful Versus Failed Transition From Controlled Ventilation to Pressure Support Ventilation in COVID-19 Patients: A Retrospective Cohort Study.

OBJECTIVES: In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient's respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN: Retrospective observational cohort study. SETTING: Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS: Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION: The transition period from CMV to PSV was evaluated. We defined it as "failure of assisted breathing" if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS: Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99-1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42-3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS: Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

Dyspnoea in acutely ill mechanically ventilated adult patients: an ERS/ESICM statement.

This statement outlines a review of the literature and current practice concerning the prevalence, clinical significance, diagnosis and management of dyspnoea in critically ill, mechanically ventilated adult patients. It covers the definition, pathophysiology, epidemiology, short- and middle-term impact, detection and quantification, and prevention and treatment of dyspnoea. It represents a collaboration of the European Respiratory Society (ERS) and the European Society of Intensive Care Medicine (ESICM). Dyspnoea ranks among the most distressing experiences that human beings can endure. Approximately 40% of patients undergoing invasive mechanical ventilation in the intensive care unit (ICU) report dyspnoea, with an average intensity of 45 mm on a visual analogue scale from 0 to 100 mm. Although it shares many similarities with pain, dyspnoea can be far worse than pain in that it summons a primal fear response. As such, it merits universal and specific consideration. Dyspnoea must be identified, prevented and relieved in every patient. In the ICU, mechanically ventilated patients are at high risk of experiencing breathing difficulties because of their physiological status and, in some instances, because of mechanical ventilation itself. At the same time, mechanically ventilated patients have barriers to signalling their distress. Addressing this major clinical challenge mandates teaching and training, and involves ICU caregivers and patients. This is even more important because, as opposed to pain which has become a universal healthcare concern, very little attention has been paid to the identification and management of respiratory suffering in mechanically ventilated ICU patients.

Vaccines and Myocardial Injury in Patients Hospitalized for COVID-19 Infection: the CardioCOVID-Gemelli Study.

BACKGROUND: Myocardial injury is prevalent among patients hospitalized for COVID-19. However, the role of COVID-19 vaccines in modifying the risk of myocardial injury is unknown. OBJECTIVES: To assess the role of vaccines in modifying the risk of myocardial injury in COVID-19. METHODS: We enrolled COVID-19 patients admitted from March 2021 to February 2022 with known vaccination status and ≥1 assessment of hs-cTnI within 30 days from the admission. The primary endpoint was the occurrence of myocardial injury (hs-cTnI levels >99th percentile upper reference limit). RESULTS: 1019 patients were included (mean age 67.7±14.8 years, 60.8% male, 34.5% vaccinated against COVID-19). Myocardial injury occurred in 145 (14.2%) patients. At multivariate logistic regression analysis, advanced age, chronic kidney disease and hypertension, but not vaccination status, were independent predictors of myocardial injury. In the analysis according to age tertiles distribution, myocardial injury occurred more frequently in the III tertile (≥76 years) compared to other tertiles (I tertile:≤60 years;II tertile:61-75 years) (p<0.001). Moreover, in the III tertile, vaccination was protective against myocardial injury (OR 0.57, CI 95% 0.34-0.94; p=0.03), while a previous history of coronary artery disease was an independent positive predictor. In contrast, in the I tertile, chronic kidney disease (OR 6.94, 95% CI 1.31-36.79, p=0.02) and vaccination (OR 4.44, 95% CI 1.28-15.34, p=0.02) were independent positive predictors of myocardial injury. CONCLUSIONS: In patients ≥76 years, COVID-19 vaccines were protective for the occurrence of myocardial injury, while in patients ≤60 years, myocardial injury was associated with previous COVID-19 vaccination. Further studies are warranted to clarify the underlying mechanisms.

Surviving Sepsis Campaign Research Priorities 2023.

OBJECTIVES: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. DESIGN: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. METHODS: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. RESULTS: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? CONCLUSIONS: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

Follow-up short and long-term mortalities of tracheostomized critically ill patients in an Italian multi-center observational study.

The effects of tracheostomy on outcome as well as on intra or post-operative complications is yet to be defined. Admission of patients with tracheostomy to rehabilitation facility is at higher risk of suboptimal care and increased mortality. The aim of the study was to investigate ICU mortality, clinical outcome and quality of life up to 12 months after ICU discharge in tracheostomized critically ill patients. This is a prospective, multi-center, cohort study endorsed by Italian Society of Anesthesia, Analgesia, Reanimation, and Intensive Care (SIAARTI Prot. n° 643/13) registered in Clinicaltrial.gov (NCT01899352). Patients admitted to intensive care unit (ICU) and requiring elective tracheostomy according to physician in charge decision were included in the study. The primary outcome was ICU mortality. Secondary outcomes included risk factors for ICU mortality, prevalence of mortality at follow-up, rate of discharge from the hospital and rehabilitation, quality of life, performance status, and management of tracheostomy cannula at 3-, 6, 12-months from the day of tracheostomy. 694 critically ill patients who were tracheostomized in the ICU were included. ICU mortality was 15.8%. Age, SOFA score at the day of the tracheostomy, and days of endotracheal intubation before tracheostomy were risk factors for ICU mortality. The regression tree analysis showed that SOFA score at the day of tracheostomy and age had a preeminent role for the choice to perform the tracheostomy. Of the 694 ICU patients with tracheostomy, 469 completed the 12-months follow-up. Mortality was 33.51% at 3-months, 45.30% at 6-months, and 55.86% at 12-months. Patients with tracheostomy were less likely discharged at home but at hospital facilities or rehabilitative structures; and quality of life of patients with tracheostomy was severely compromised at 3-6 and 12 months when compared with patients without tracheostomy. In patients admitted to ICU, tracheostomy is associated with high mortality, difficult rehabilitation, and decreased quality of life. The choice to perform a tracheostomy should be carefully weighed on family burden and health-related quality of life.Clinical trial registration: Clinicaltrial.gov (NCT01899352).

Epidemiology and risk factors for mortality in critically ill patients with pancreatic infection.

Background: The AbSeS-classification defines specific phenotypes of patients with intra-abdominal infection based on the (1) setting of infection onset (community-acquired, early onset, or late-onset hospital-acquired), (2) presence or absence of either localized or diffuse peritonitis, and (3) severity of disease expression (infection, sepsis, or septic shock). This classification system demonstrated reliable risk stratification in intensive care unit (ICU) patients with intra-abdominal infection. This study aimed to describe the epidemiology of ICU patients with pancreatic infection and assess the relationship between the components of the AbSeS-classification and mortality. Methods: This was a secondary analysis of an international observational study ("AbSeS") investigating ICU patients with intra-abdominal infection. Only patients with pancreatic infection were included in this analysis (n=165). Mortality was defined as ICU mortality within 28 days of observation for patients discharged earlier from the ICU. Relationships with mortality were assessed using logistic regression analysis and reported as odds ratio (OR) and 95% confidence interval (CI). Results: The overall mortality was 35.2% (n=58). The independent risk factors for mortality included older age (OR=1.03, 95% CI: 1.0 to 1.1 P=0.023), localized peritonitis (OR=4.4, 95% CI: 1.4 to 13.9 P=0.011), and persistent signs of inflammation at day 7 (OR=9.5, 95% CI: 3.8 to 23.9, P<0.001) or after the implementation of additional source control interventions within the first week (OR=4.0, 95% CI: 1.3 to 12.2, P=0.013). Gram-negative bacteria were most frequently isolated (n=58, 49.2%) without clinically relevant differences in microbial etiology between survivors and non-survivors. Conclusions: In pancreatic infection, a challenging source/damage control and ongoing pancreatic inflammation appear to be the strongest contributors to an unfavorable short-term outcome. In this limited series, essentials of the AbSeS-classification, such as the setting of infection onset, diffuse peritonitis, and severity of disease expression, were not associated with an increased mortality risk.ClinicalTrials.gov number: NCT03270345.

High vs Low PEEP in Patients With ARDS Exhibiting Intense Inspiratory Effort During Assisted Ventilation: A Randomized Crossover Trial.

BACKGROUND: Positive end-expiratory pressure (PEEP) can potentially modulate inspiratory effort (ΔPes), which is the major determinant of self-inflicted lung injury. RESEARCH QUESTION: Does high PEEP reduce ΔPes in patients with moderate-to-severe ARDS on assisted ventilation? STUDY DESIGN AND METHODS: Sixteen patients with Pao2/Fio2 ≤ 200 mm Hg and ΔPes ≥ 10 cm H2O underwent a randomized sequence of four ventilator settings: PEEP = 5 cm H2O or PEEP = 15 cm H2O + synchronous (pressure support ventilation [PSV]) or asynchronous (pressure-controlled intermittent mandatory ventilation [PC-IMV]) inspiratory assistance. ΔPes and respiratory system, lung, and chest wall mechanics were assessed with esophageal manometry and occlusions. PEEP-induced alveolar recruitment and overinflation, lung dynamic strain, and tidal volume distribution were assessed with electrical impedance tomography. RESULTS: ΔPes was not systematically different at high vs low PEEP (pressure support ventilation: median, 20 cm H2O; interquartile range (IQR), 15-24 cm H2O vs median, 15 cm H2O; IQR, 13-23 cm H2O; P = .24; pressure-controlled intermittent mandatory ventilation: median, 20; IQR, 18-23 vs median, 19; IQR, 17-25; P = .67, respectively). Similarly, respiratory system and transpulmonary driving pressures, tidal volume, lung/chest wall mechanics, and pendelluft extent were not different between study phases. High PEEP resulted in lower or higher ΔPes, respiratory system driving pressure, and transpulmonary driving pressure according to whether this increased or decreased respiratory system compliance (r = -0.85, P < .001; r = -0.75, P < .001; r = -0.80, P < .001, respectively). PEEP-induced changes in respiratory system compliance were driven by its lung component and were dependent on the extent of PEEP-induced alveolar overinflation (r = -0.66, P = .006). High PEEP caused variable recruitment and systematic redistribution of tidal volume toward dorsal lung regions, thereby reducing dynamic strain in ventral areas (pressure support ventilation: median, 0.49; IQR, 0.37-0.83 vs median, 0.96; IQR, 0.62-1.56; P = .003; pressure-controlled intermittent mandatory ventilation: median, 0.65; IQR, 0.42-1.31 vs median, 1.14; IQR, 0.79-1.52; P = .002). All results were consistent during synchronous and asynchronous inspiratory assistance. INTERPRETATION: The impact of high PEEP on ΔPes and lung stress is interindividually variable according to different effects on the respiratory system and lung compliance resulting from alveolar overinflation. High PEEP may help mitigate the risk of self-inflicted lung injury solely if it increases lung/respiratory system compliance. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04241874; URL: www. CLINICALTRIALS: gov.