The use of angiotensin II for the management of distributive shock: expert consensus statements.

BACKGROUND: Despite the growing body of evidence supporting the use of angiotensin II (ATII) in distributive shock, its integration into existing treatment algorithms requires careful consideration of factors related to patient comorbidities, hemodynamic parameters, cost-effectiveness, and risk-benefit balance. Moreover, several questions regarding its use in clinical practice warrant further investigations. To address these challenges, a group of Italian intensive care specialists (the panel) developed a consensus process using a modified Delphi technique. METHODS: The panel defined five clinical questions during an online scoping workshop and then provided a short list of statements related to each clinical question based on literature review and clinical experience. A total of 20 statements were collected. Two coordinators screened and selected the final list of statements to be included in the online survey, which consisted of 17 statements. The consensus was reached when ≥ 75% of respondents assigned a score within the 3-point range of 1-3 (disagreement) or 7-9 (agreement). RESULTS: Overall, a consensus on agreement was reached on 13 statements defining the existing gaps in scientific evidence, the possibility of evaluating the addition of drugs with different mechanisms of action for the treatment of refractory shock, the utility of ATII in reducing the catecholamine requirements in the treatment of vasopressor-resistant septic shock, and the effectiveness of ATII in treating patients in whom angiotensin-converting enzyme activity is reduced or pharmacologically blocked. It was widely shared that renin concentration can be used to identify patients who most likely benefit from ATII to restore vascular tone. Thus, the patients who might benefit most from using ATII were defined. Lastly, some potential barriers to the use of ATII were described. CONCLUSIONS: ATII was recognized as a useful treatment to reduce catecholamine requirements in treating vasopressor-resistant septic shock. At the same time, the need for additional clinical trials to further elucidate the efficacy and safety of ATII, as well as investigations into potential mechanisms of action and optimization of treatment protocols in patients with refractory distributive shock, emerged.

Long-term outcomes in critically ill patients with acute respiratory failure.

PURPOSE OF REVIEW: This review aims to explore the latest evidence on long-term outcomes in patients admitted to the ICU because of acute respiratory failure (ARF). RECENT FINDINGS: As the survival rate of critically ill patients with acute respiratory failure improves, long-term mortality and disability still influence the quality of life of survivors and their caregivers. Patients admitted to the ICU because of ARF are at risk of developing the postintensive care syndrome, which presents with physical, cognitive and mental symptoms, all of which may impair their quality of life. Caregivers seem to be affected as well, which may lead to intergenerational trauma. The need for more care, including prone positioning, invasive support (e.g. mechanical ventilation, ECMO) and deep sedation are probably adjunctive risk factors for poor long-term outcomes. SUMMARY: There is not much data on the long-term outcomes of patients who have survived ARF. More follow-up studies should be conducted, especially in centers providing higher levels of costly care (e.g. ECMO). Randomized controlled trials on interventions for ARF should include patient-centered long-term outcomes in addition to mortality rates. The high mortality rates associated with ARF mandate collaboration among multiple centers to achieve an adequate sample size for studying the long-term outcomes of survivors.

Effects of high-flow nasal therapy on swallowing function: a scoping review.

Background: High-flow nasal therapy is widely used in patients with respiratory failure in different clinical settings, but the effect of high-flow nasal therapy on respiratory-swallow coordination is unknown. Understanding this relationship is crucial, considering the necessity for patients to maintain adequate nutrition during daytime high-flow nasal therapy. This scoping review aims to synthesise available data on the effects of high-flow nasal therapy flow rates on swallowing function and the possible risk of aspiration during treatment, focusing on knowledge and evidence gaps. Methods: PubMed, Scopus, Web of Science and Google Scholar databases were searched from inception to 30 May 2023 for studies reporting data on swallowing assessment in healthy adults or patients with acute or chronic respiratory failure receiving high-flow nasal therapy. Data on study design, patients' characteristics and quality outcomes were extracted. Results: Eight studies were included, four including cohorts of healthy volunteers (n=148) and four including patients with acute or chronic respiratory failure (n=151). Study designs, patient populations and quality outcome measures were heterogeneous. Two studies indicated improvement while four articles showed impairment in swallowing function during high-flow nasal therapy; two studies showed that patients' overall clinical picture and underlying medical conditions influenced swallowing-breathing coordination rather than high-flow nasal therapy per se. Conclusion: This scoping review found limited and controversial evidence on the impact of high-flow nasal therapy on swallowing function. Remarkably, methods for swallowing function assessment were quite heterogeneous. Additional research is required to test the effect of high-flow nasal therapy on respiratory-swallowing coordination.

Teaching team competencies within resuscitation training: A systematic review.

Objectives: To evaluate the effectiveness of life support training with specific emphasis on team competencies on clinical and educational outcomes. Methods: This systematic review was prospectively registered (PROSPERO CRD42023473154) and followed the PICOST (population, intervention, comparison, outcome, study design, timeframe) format. All randomized controlled trials and non-randomized studies evaluating learners undertaking life support training with specific emphasis on team competencies in any setting (actual and simulated resuscitations) were included. Unpublished studies were excluded. Medline, Embase and Cochrane databases as well as trial registries were searched from inception to August 2023 (updated January 18, 2024). Two researchers performed title and abstract screening, full-text screening, data extraction, assessment of risk of bias (using RoB2 and ROBINS-I) and certainty of evidence (using GRADE). PRISMA reporting checklist was used to report the results. No funding was obtained to perform this systematic review. Results: The literature search identified 5470 manuscripts. After the removal of 2073 duplicates, reviewing the remaining articles' titles and abstracts yielded 31 articles for full-text review. Of these, 17 studies were finally included. The studies involved the following training levels: basic life support, adult advanced life support, paediatric and neonatal resuscitations. Most studies (n = 16) evaluated outcomes in simulated, and only one study in actual resuscitations. Studies included in all training contexts showed either neutrality and/or benefits of life support training with specific emphasis on team competencies. Team competencies training improved CPR skill performance and CPR quality. Specific team competencies that improved included leadership, communication, decision-making and task management. No undesirable effects were observed. Meta-analysis was not possible due to significant methodological heterogeneity. Sub-group analysis was impossible due to lack of data. Risk of bias assessment ranged from some concerns to serious. Overall certainty of evidence was rated as low to very low due to risk of bias and imprecision. Conclusion: This systematic review identified very low and low certainty evidence, almost entirely derived from simulation studies. The studies and their findings were heterogenous but suggest that teaching team competencies can improve resuscitation skills performance and CPR quality, as well as improve team competencies, specifically leadership, communication, decision-making, and task management. Further research is required to understand optimal configuration of team competencies training interventions and to understand the effect on clinical outcomes and cost-effectiveness.

Use of Cefiderocol in Adult Patients: Descriptive Analysis from a Prospective, Multicenter, Cohort Study.

INTRODUCTION: Cefiderocol is a siderophore cephalosporin showing activity against various carbapenem-resistant Gram-negative bacteria (CR-GNB). No data currently exist about real-world use of cefiderocol in terms of types of therapy (e.g., empirical or targeted, monotherapy or combined regimens), indications, and patient characteristics. METHODS: In this multicenter, prospective study, we aimed at describing the use of cefiderocol in terms of types of therapy, indications, and patient characteristics. RESULTS: Cefiderocol was administered as empirical and targeted therapy in 27.5% (55/200) and 72.5% (145/200) of cases, respectively. Overall, it was administered as monotherapy in 101/200 cases (50.5%) and as part of a combined regimen for CR-GNB infections in the remaining 99/200 cases (49.5%). In multivariable analysis, previous isolation of carbapenem-resistant Acinetobacter baumannii odds ratio (OR) 2.56, with 95% confidence interval (95% CI) 1.01-6.46, p = 0.047] and previous hematopoietic stem cell transplantation (OR 8.73, 95% CI 1.05-72.54, p = 0.045) were associated with administration of cefiderocol as part of a combined regimen, whereas chronic kidney disease was associated with cefiderocol monotherapy (OR 0.38 for combined regimen, 95% CI 0.16-0.91, p = 0.029). Cumulative 30-day mortality was 19.8%, 45.0%, 20.7%, and 22.7% in patients receiving targeted cefiderocol for infections by Enterobacterales, A. baumannii, Pseudomonas aeruginosa, and any metallo-ß-lactamase producers, respectively. CONCLUSIONS: Cefiderocol is mainly used for targeted treatment, although empirical therapies account for more than 25% of prescriptions, thus requiring dedicated standardization and guidance. The almost equal distribution of cefiderocol monotherapy and cefiderocol-based combination therapies underlines the need for further study to ascertain possible differences in efficacy between the two approaches.

Association Between Spontaneous Breathing Trial Methods and Reintubation in Adult Critically Ill Patients: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Reintubation is associated with higher risk of mortality. There is no clear evidence on the best spontaneous breathing trial (SBT) method to reduce the risk of reintubation. RESEARCH QUESTION: Are different methods of conducting SBTs in critically ill patients associated with different risk of reintubation compared with T-tube? STUDY DESIGN AND METHODS: We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials investigating the effects of different SBT methods on reintubation. We surveyed PubMed, MEDLINE, CINAHL, and Cochrane Central Register of Controlled Trials databases from inception to January 26, 2024. The surface under the cumulative ranking curve (SUCRA) was used to determine the likelihood that an intervention was ranked as the best. Pairwise comparisons were also investigated by frequentist meta-analysis. Certainty of the evidence was assessed according to the Grading of Recommendations, Assessment, Development, and Evaluations approach. RESULTS: A total of 22 randomized controlled trials were included, for a total of 6,196 patients. The network included nine nodes, with 13 direct pairwise comparisons. About 71% of the patients were allocated to T-tube and pressure support ventilation with positive end-expiratory pressure, with 2,135 and 2,101 patients, respectively. The only intervention with a significantly lower risk of reintubation compared with T-tube was high flow oxygen (HFO) (risk ratio, 0.23; 95% credibility interval, 0.09-0.51; moderate quality evidence). HFO was associated with the highest probability of being the best intervention for reducing the risk of reintubation (81.86%; SUCRA, 96.42), followed by CPAP (11.8%; SUCRA, 76.75). INTERPRETATION: HFO SBT was associated with a lower risk of reintubation in comparison with other SBT methods. The results of our analysis should be considered with caution due to the low number of studies that investigated HFO SBTs and potential clinical heterogeneity related to cointerventions. Further trials should be performed to confirm the results on larger cohorts of patients and assess specific subgroups. TRIAL REGISTRATION: PROSPERO; No.: CRD42023449264; URL: https://www.crd.york.ac.uk/prospero/.

Factors affecting mortality in COVID-19-associated pulmonary aspergillosis: An international ID-IRI study.

Background: This study aimed to identify factors that influence the mortality rate of patients with coronavirus disease (COVID-19)-associated pulmonary aspergillosis (CAPA). Methods: In this cross-sectional study, data from 23 centers across 15 countries, spanning the period of March 2020 to December 2021, were retrospectively collected. The study population comprised patients who developed invasive pulmonary aspergillosis while being treated for COVID-19 in the intensive care unit. Cox regression and decision tree analyses were used to identify factors associated with mortality in patients with CAPA. Results: A total of 162 patients (males, 65.4 %; median age: 64 [25th-75th: 54.0-73.8] years) were included in the study, of whom 113 died during the 90-day follow-up period. The median duration from CAPA diagnosis to death was 12 (25th-75th: 7-19) days. In the multivariable Cox regression model, an age of ≥65 years (hazard ratio [HR]: 2.05, 95 % confidence interval [CI]: 1.37-3.07), requiring vasopressor therapy at the time of CAPA diagnosis (HR: 1.80, 95 % CI: 1.17-2.76), and receiving renal replacement therapy at the time of CAPA diagnosis (HR: 2.27, 95 % CI: 1.35-3.82) were identified as predictors of mortality. Decision tree analysis revealed that patients with CAPA aged ≥65 years who received corticosteroid treatment for COVID-19 displayed higher mortality rates (estimated rate: 1.6, observed in 46 % of patients). Conclusion: This study concluded that elderly patients with CAPA who receive corticosteroids are at a significantly higher risk of mortality, particularly if they experience multiorgan failure.

End-of-life Care in the Intensive Care Unit and Ethics of Withholding/Withdrawal of Life-sustaining Treatments.

The medical progress has produced improvements in critically ill patients' survival to early phases of life-threatening diseases, thus producing long intensive care stays and persisting disability, with uncertain long-term survival rates and quality of life. Thus, compassionate end-of-life care and the provision of palliative care, even overlapping with the most aggressive of curative intensive care unit (ICU) care has become crucial. Moreover, withdrawal or withholding of life-sustaining treatment may be adopted, allowing unavoidable deaths to occur, without prolonging agony or ICU stay. Our aim was to summarize the key element of end-of-life care in the ICU and the ethics of withholding/withdrawal life-sustaining treatments.

Clinical usefulness of presepsin and monocyte distribution width (MDW) kinetic for predicting mortality in critically ill patients in intensive care unit.

Background: In this study, we explored the accuracy of two new sepsis biomarkers, monocyte distribution width (MDW) and presepsin (PSP), compared to traditional ones, C-reactive protein (CRP) and Procalcitonin (PCT), to identify sepsis and predict intra-hospital mortality by analyzing their kinetic at different time points during hospitalization stay. Methods: We enrolled 104 patients admitted to the intensive care unit (ICU) of University Hospital "Paolo Giaccone", Palermo. Among these, 30 (29%) had a clinical diagnosis of sepsis. MDW, PCT, CRP, and PSP were evaluated at admission (T0), after 24 h (T24), 48 h (T48), 72 h (T72), at day 5 (T5), and at discharge (TD). Results: Patients with sepsis displayed higher levels of PCT and PSP than patients without sepsis at each timepoint; differently, CRP displayed statistically significant differences only at T0, while MDW only at T0 and T24. Patients with increasing levels of PSP displayed lower median survival time than patients with decreasing levels; differences reached statistical significance only at 48 h (20 vs. 29 days, log rank test, p = 0.046). Interestingly, PSP was an independent predictor of ICU mortality at 48 and 72 h after hospital admission. Also, the kinetic of PSP had prognostic value, with increased values at 48 h after admission being associated with reduced survival. Conclusion: Our findings support the role of PSP and its kinetic as a predictor of ICU mortality.

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.

A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Stress-strain curve and elastic behavior of the fibrotic lung with usual interstitial pneumonia pattern during protective mechanical ventilation.

Patients with acute exacerbation of lung fibrosis with usual interstitial pneumonia (EUIP) pattern are at increased risk for ventilator-induced lung injury (VILI) and mortality when exposed to mechanical ventilation (MV). Yet, lack of a mechanical model describing UIP-lung deformation during MV represents a research gap. Aim of this study was to develop a constitutive mathematical model for UIP-lung deformation during lung protective MV based on the stress-strain behavior and the specific elastance of patients with EUIP as compared to that of acute respiratory distress syndrome (ARDS) and healthy lung. Partitioned lung and chest wall mechanics were assessed for patients with EUIP and primary ARDS (1:1 matched based on body mass index and PaO2/FiO2 ratio) during a PEEP trial performed within 24 h from intubation. Patient's stress-strain curve and the lung specific elastance were computed and compared with those of healthy lungs, derived from literature. Respiratory mechanics were used to fit a novel mathematical model of the lung describing mechanical-inflation-induced lung parenchyma deformation, differentiating the contributions of elastin and collagen, the main components of lung extracellular matrix. Five patients with EUIP and 5 matched with primary ARDS were included and analyzed. Global strain was not different at low PEEP between the groups. Overall specific elastance was significantly higher in EUIP as compared to ARDS (28.9 [22.8-33.2] cmH2O versus 11.4 [10.3-14.6] cmH2O, respectively). Compared to ARDS and healthy lung, the stress/strain curve of EUIP showed a steeper increase, crossing the VILI threshold stress risk for strain values greater than 0.55. The contribution of elastin was prevalent at lower strains, while the contribution of collagen was prevalent at large strains. The stress/strain curve for collagen showed an upward shift passing from ARDS and healthy lungs to EUIP lungs. During MV, patients with EUIP showed different respiratory mechanics, stress-strain curve and specific elastance as compared to ARDS patients and healthy subjects and may experience VILI even when protective MV is applied. According to our mathematical model of lung deformation during mechanical inflation, the elastic response of UIP-lung is peculiar and different from ARDS. Our data suggest that patients with EUIP experience VILI with ventilatory setting that are lung-protective for patients with ARDS.

Rapid cycle deliberate practice approach on resuscitation training: A systematic review.

Aim: To evaluate the effectiveness of Rapid Cycle Deliberate Practice (RCDP) compared to traditional instruction or other forms of learning on resuscitation training outcomes and on clinical and/or patient-related outcomes. Methods: As part of the continuous evidence evaluation process of the International Liaison Committee on Resuscitation it was conducted this review and searched Medline, Embase and Cochrane from inception to Feb 12th, 2024. Risk of bias assessment was performed with the Risk of Bias in Non-randomized Studies of Interventions assessment tool and the Revised Cochrane risk-of-bias tool for randomized trials. The GRADE approach was used to evaluate the overall certainty of evidence for each outcome. Results: 4420 abstracts were retrieved by the initial search and 10 additional studies were identified through other resources. Sixty-five studies were selected for eligibility and nine simulated studies met the inclusion criteria. A meta-analysis was performed on three outcomes: time to chest compressions, time to defibrillation and time to first epinephrine given, which showed that RCDP had significantly shorter time to defibrillation and time to administration of epinephrine than controls. The overall certainty of evidence was very low across all outcomes due to risk of bias, inconsistency, indirectness, and imprecision. Conclusion: It may be reasonable to include RCDP as an instructional design feature of basic and advanced life support training. However, substantial variations of delivering RCDP exist and there is no uniform use of RCDP. Further research is necessary on medium/long-term effects of RCDP training, and on the effects on different target groups of training.

Exploring European Consensus About the Remaining Treatment Challenges and Subsequent Opportunities to Improve the Management of Invasive Fungal Infection (IFI) in the Intensive Care Unit.

BACKGROUND: The global prevalence of invasive fungal infections (IFI) is increasing, particularly within Intensive Care Units (ICU), where Candida spp. and Aspergillus spp. represent the most important pathogens. Diagnosis and management of IFIs becomes progressively challenging, with increasing antifungal resistance and the emergence of rare fungal species. Through a consensus survey focused on assessing current views on how IFI should be managed, the aim of this project was to identify challenges around diagnosing and managing IFIs in the ICU. The current status in different countries and perceived challenges to date amongst a multidisciplinary cohort of healthcare professionals involved in the care of IFI in the ICU was assessed. METHODS: Using a modified Delphi approach, an expert panel developed 44 Likert-scale statements across 6 key domains concerning patient screening and minimal standards for diagnosis of IFIs in ICU; initiation and termination of antifungal treatments and how to minimise their side effects and insights for future research on this topic. These were used to develop an online survey which was distributed on a convenience sampling basis utilising the subscriber list held by an independent provider (M3 Global). This survey was distributed to intensivists, infectious disease specialists, microbiologists and antimicrobial/ICU pharmacists within the UK, Germany, Spain, France and Italy. The threshold for consensus was set at 75%. RESULTS: A total of 335 responses were received during the five-month collection period. From these, 29/44 (66%) statements attained very high agreement (≥ 90%), 11/44 (25%) high agreement (< 90% and ≥ 75%), and 4/44 (9%) did not meet threshold for consensus (< 75%). CONCLUSION: The results outline the need for physicians to be aware of the local incidence of IFI and the associated rate of azole resistance in their ICUs. Where high clinical suspicion exists, treatment should start immediately and prior to receiving the results from any diagnostic test. Beta-D-glucan testing should be available to all ICU centres, with results available within 48 h to inform the cessation of empirical antifungal therapy. These consensus statements and proposed measures may guide future areas for further research to optimise the management of IFIs in the ICU.

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.

Intentional interruptions during compression only CPR: A scoping review.

Introduction: Out of hospital cardiac arrest (OHCA) remains one of the main causes of death among industrialized countries. The initiation of cardiopulmonary resuscitation (CPR) by laypeople before the arrival of emergency medical services improves survival. Mouth-to-mouth ventilation may constitute a hindering factor to start bystander CPR, while during continuous chest compressions (CCC) CPR quality decreases rapidly. The aim of this scoping review is to examine the existing literature on strategies that investigate the inclusion of intentional pauses during compression-only resuscitation (CO-CPR) to improve the performance in the context of single lay rescuer OHCA. Methods: The protocol of this Scoping review was prospectively registered in Open Science Framework (https://osf.io/rvn8j). A systematic search of PubMed, Scopus, EMBASE, CINAHL was performed. Results: Six articles were included. All studies were carried out on simulation manikins and involved a total of 1214 subjects. One study had a multicenter design. Three studies were randomized controlled simulation trials, the rest were prospective randomized crossover studies. The tested protocols were heterogeneous and compared CCC to CO-CPR with intentional interruptions of various length. The most common primary outcome was compressions depth. Compression rate, rescuers' perceived exertion and composite outcomes were also evaluated. Compressions depth and perceived exertion improved in most study groups while compression rate and chest compression fraction remained within guidelines indications. Conclusions: In simulation studies, the inclusion of intentional interruptions during CO-CPR within the specific scenario of single rescuer bystander CPR during OHCA may improve the rate of compressions with correct depth and lower rate of perceived exertion. Further high-quality research and feasibility and safety of protocols incorporating intentional interruptions during CO-CPR may be justified.

Effects of fatigue on anaesthetist well-being and patient safety: a narrative review.

The elements that render anaesthesia a captivating profession can also foster stress and fatigue. Professionals considering anaesthesia as a career choice should have a comprehensive understanding of the negative consequences of fatigue and its implications for clinical performance and of the available preventive measures. Available evidence suggests that factors unrelated to patient characteristics or condition can affect clinical outcomes where anaesthetists are involved. Workload, nighttime work, and fatigue are persistent issues in anaesthesia and are perceived as presenting greater perioperative risks to patients. Fatigue seems to negatively affect both physical and mental health of anaesthetists. Existing evidence justifies specific interventions by institutions, stakeholders, and scientific societies to address the effects of anaesthetist fatigue. This narrative review summarises current knowledge regarding the effects of fatigue on anaesthetist well-being and patient safety, and discusses potential preventive solutions.

Home Respiratory Strategies in Patients With COPD With Chronic Hypercapnic Respiratory Failure.

BACKGROUND: Home noninvasive ventilation (NIV) may improve chronic hypercarbia in COPD and patient-important outcomes. The efficacy of home high-flow nasal cannula (HFNC) as an alternative is unclear. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL, Scopus, and ClinicalTrials.gov for randomized trials of subjects from inception to March 31, 2023, and updated the search on July 14, 2023. We performed a frequentist network meta-analysis and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We analyzed randomized controlled trials (RCTs) comparing NIV, HFNC, or standard care in adult subjects with COPD with chronic hypercapnic respiratory failure. Outcomes included mortality, COPD exacerbations, hospitalizations, and quality of life (St George Respiratory Questionnaire [SGRQ]). RESULTS: We analyzed 24 RCTs (1,850 subjects). We found that NIV may reduce the risk of death compared to standard care (relative risk 0.82 [95% CI 0.66-1.00]) and probably reduces exacerbations (relative risk 0.71 [95% CI 0.58-0.87]). HFNC probably reduces exacerbations compared to standard care (relative risk 0.77 [0.68-0.88]), but its effect on mortality is uncertain (relative risk 1.20 [95% CI 0.63-2.28]). HFNC probably improves SGRQ scores (mean difference -7.01 [95% CI -12.27 to -1.77]) and may reduce hospitalizations (relative risk 0.87 [0.69-1.09]) compared to standard care. No significant difference was observed between HFNC and NIV in reducing exacerbations. CONCLUSIONS: Both NIV and HFNC reduce exacerbation risks in subjects with COPD compared to standard care. HFNC may offer advantages in improving quality of life.

Monocyte distribution width (MDW) kinetic for monitoring sepsis in intensive care unit.

OBJECTIVES: Monocyte distribution width (MDW) is a measure of monocyte anisocytosis. In this study, we assessed the role of MDW, in comparison to C-reactive protein (CRP), procalcitonin (PCT), and lactate, as a screening and prognostic biomarker of sepsis in intensive care unit (ICU) by longitudinally measuring it in the first 5 days of hospital stay. METHODS: We considered all consecutive patients admitted to the ICU. At admission, patients were classified as septic or not according to Sepsis-3 criteria. MDW, CRP, PCT, and lactate were measured daily in the first 5 days of hospitalization. ICU mortality was also recorded. RESULTS: We included 193 patients, 62 with sepsis and 131 without sepsis (controls). 58% and 26 % of the patients, with and without sepsis respectively, died during ICU stay. MDW showed the highest accuracy for sepsis detection, superior to CRP, PCT, and lactate (AUC of 0.840, 0.755, 0.708, 0.622, respectively). At admission, no biomarker predicts ICU mortality in patients with sepsis. The kinetic of all biomarkers during the first 5 days of hospitalization was associated with ICU mortality. Noteworthy, above all, the kinetic of MDW showed the best accuracy. Specifically, an increase or decrease in MDW from day 1-4 and 5 was significantly associated with mortality or survival, respectively. CONCLUSIONS: MDW is a reliable diagnostic and prognostic sepsis biomarker, better than traditional biomarkers.