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This paper discusses the use of Artificial Intelligence Chatbot in scientific writing. ChatGPT is a type of chatbot, developed by OpenAI, that uses the Generative Pre-trained Transformer (GPT) language model to understand and respond to natural language inputs. AI chatbot and ChatGPT in particular appear to be useful tools in scientific writing, assisting researchers and scientists in organizing material, generating an initial draft and/or in proofreading. There is no publication in the field of critical care medicine prepared using this approach; however, this will be a possibility in the next future. ChatGPT work should not be used as a replacement for human judgment and the output should always be reviewed by experts before being used in any critical decision-making or application. Moreover, several ethical issues arise about using these tools, such as the risk of plagiarism and inaccuracies, as well as a potential imbalance in its accessibility between high- and low-income countries, if the software becomes paying. For this reason, a consensus on how to regulate the use of chatbots in scientific writing will soon be required. [ABSTRACT FROM AUTHOR] more...

The p-value has changed from a versatile tool for scientific reasoning to a strict judge of medical information, with the usual 0.05 cutoff frequently deciding a study's significance and subsequent clinical use. Through an examination of five critical care interventions that demonstrated meaningful treatment effects yet narrowly missed conventional statistical significance, this paper illustrates how rigid adherence to p-value thresholds may obscure therapeutically beneficial findings. By providing a clear, step-by-step illustration of a basic Bayesian calculation, we demonstrate that clinical importance can remain undetected when relying solely on p-values. These observations challenge current statistical paradigms and advocate for hybrid approaches—including both frequentist and Bayesian methodologies—to provide a more comprehensive understanding of clinical data, ultimately leading to better-informed medical decisions. [ABSTRACT FROM AUTHOR] more...

Mitigating environmental impacts is an urgent challenge supported by (scientific) intensive care societies worldwide. However, making green choices without compromising high-quality care for critically ill patients may be challenging. The current paper describes a three-step approach towards green intensive care units. Starting with the measurement of environmental sustainability, intensive care units can identify hotspots, quantify the environmental impacts of products and procedures, and monitor sustainable progress. Subsequently, a multidisciplinary approach is proposed to improve environmental sustainability, including a collaboration of procurement specialists and healthcare professionals, using co-creation and green teams as efficient grassroots change agents. A context-specific approach for enhancing sustainable healthcare practices is key in order to fit local regulatory requirements and create support of professionals. A final step is to share results and create momentum, including publishing initiatives and participating in online (inter)national networks. Based on the core sustainability principles, this three-step approach towards green ICUs provides a valuable tool to professionals worldwide to facilitate change towards environmentally responsible intensive care units. [ABSTRACT FROM AUTHOR] more...

Assessing and quantifying recruitability are important for characterizing ARDS severity and for reducing or preventing the atelectrauma caused by the cyclic opening and closing of pulmonary units. Over the years, several methods for recruitment assessment have been developed, grouped into three main approaches: 1) Quantitative CT Scanning: This method accurately measures the amount of atelectatic lung tissue that regains aeration; 2) Regional Gas Volume Measurement: Based on anatomical markers, this approach assesses gas volume within a specified lung region; 3) Compliance-Based Gas Volume Measurement: This technique compares actual gas volume at a given pressure to expected values, assuming respiratory system compliance is constant within the explored pressure range. Additional methods, such as lung ultrasonography and electrical impedance variation, have also been explored. This paper details the distribution of opening and closing pressures throughout the lung parenchyma, which underpin the concept of recruitability. The distribution of recruitable regions corresponds to atelectasis distribution, with the pressure needed for recruitment varying according to whether the atelectasis is "loose" or "sticky." We also discuss the effects of different PEEP levels on preventing atelectrauma, the importance of keeping some lung areas closed throughout the respiratory cycle, and briefly cover the roles of sigh ventilation, prone positioning, and the closed lung approach. [ABSTRACT FROM AUTHOR] more...

This narrative review provides an overview of the evolving significance of lymphopenia in sepsis, emphasizing its critical function in this complex and heterogeneous disease. We describe the causal relationship of lymphopenia with clinical outcomes, sustained immunosuppression, and its correlation with sepsis prediction markers and therapeutic targets. The primary mechanisms of septic lymphopenia are highlighted. In addition, the paper summarizes various attempts to treat lymphopenia and highlights the practical significance of promoting lymphocyte proliferation as the next research direction. [ABSTRACT FROM AUTHOR] more...

Despite significant progress in our understanding of the pathophysiology of sepsis and extensive clinical research, there are few proven therapies addressing the underlying immune dysregulation of this life-threatening condition. The aim of this scoping review is to describe the literature evaluating immunotherapy in adult patients with sepsis, emphasizing on methods providing a "personalized immunotherapy" approach, which was defined as the classification of patients into a distinct subgroup or subphenotype, in which a patient's immune profile is used to guide treatment. Subgroups are subsets of sepsis patients, based on any cut-off in a variable. Subphenotypes are subgroups that can be reliably discriminated from other subgroup based on data-driven assessments. Included studies were randomized controlled trials and cohort studies investigating immunomodulatory therapies in adults with sepsis. Studies were identified by searching PubMed, Embase, Cochrane CENTRAL and ClinicalTrials.gov, from the first paper available until January 29th, 2024. The search resulted in 15,853 studies. Title and abstract screening resulted in 1409 studies (9%), assessed for eligibility; 771 studies were included, of which 282 (37%) were observational and 489 (63%) interventional. Treatment groups included were treatments targeting the innate immune response, the complement system, coagulation and endothelial dysfunction, non-pharmalogical treatment, pleiotropic drugs, immunonutrition, concomitant treatments, Traditional Chinese Medicine, immunostimulatory cytokines and growth factors, intravenous immunoglobulins, mesenchymal stem cells and immune-checkpoint inhibitors. A personalized approach was incorporated in 70 studies (9%). Enrichment was applied using cut-offs in temperature, laboratory, biomarker or genetic variables. Trials often showed conflicting results, possibly due to the lack of patient stratification or the potential influence of severity and timing on immunomodulatory therapy results. When a personalized approach was applied, trends of clinical benefit for several interventions emerged, which hold promise for future clinical trials using personalized immunotherapy. [ABSTRACT FROM AUTHOR] more...

Background: Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage in the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly in conditions such as acute respiratory distress syndrome (ARDS). This review discusses the detailed structure of the ECM in healthy and ARDS-affected lungs under mechanical ventilation, aiming to bridge the gap between experimental insights and clinical practice by offering a thorough understanding of lung ECM organization and the dynamics of its alteration during mechanical ventilation. Main text: Focusing on the clinical implications, we explore the potential of precise interventions targeting the ECM and cellular signaling pathways to mitigate lung damage, reduce inflammation, and ultimately improve outcomes for critically ill patients. By analyzing a range of experimental studies and clinical papers, particular attention is paid to the roles of matrix metalloproteinases (MMPs), integrins, and other molecules in ECM damage and VILI. This synthesis not only sheds light on the structural changes induced by mechanical stress but also underscores the importance of cellular responses such as inflammation, fibrosis, and excessive activation of MMPs. Conclusions: This review emphasizes the significance of mechanical cues transduced by integrins and their impact on cellular behavior during ventilation, offering insights into the complex interactions between mechanical ventilation, ECM damage, and cellular signaling. By understanding these mechanisms, healthcare professionals in critical care can anticipate the consequences of mechanical ventilation and use targeted strategies to prevent or minimize ECM damage, ultimately leading to better patient management and outcomes in critical care settings. Key points: Question: How does mechanical ventilation affect the lung's interstitial extracellular matrix (ECM), with a specific focus on ECM organization in healthy lungs and those affected by acute respiratory distress syndrome (ARDS). Findings: The narrative review reveals that mechanical ventilation induces stress on the interstitial ECM, leading to inflammation, fibrogenesis, elastogenesis, and matrix metalloproteinase hyperactivity. Matrix metalloproteinase and integrin involvement in ECM damage are emphasized. Our findings are based on a narrative review of studies of mechanical ventilation-induced alterations of interstitial ECM organization and cellular response. Meaning: The key conclusion is that understanding the intricate processes of interstitial ECM damage, as well as cell signaling and communication related to ventilation-induced lung injury, can pave the way for more targeted interventions that have the potential to mitigate lung damage and improve outcomes for patients in critical care settings. [ABSTRACT FROM AUTHOR] more...

Surface electromyography (sEMG) can be used to measure the electrical activity of the respiratory muscles. The possible applications of sEMG span from patients suffering from acute respiratory failure to patients receiving chronic home mechanical ventilation, to evaluate muscle function, titrate ventilatory support and guide treatment. However, sEMG is mainly used as a monitoring tool for research and its use in clinical practice is still limited—in part due to a lack of standardization and transparent reporting. During this round table meeting, recommendations on data acquisition, processing, interpretation, and potential clinical applications of respiratory sEMG were discussed. This paper informs the clinical researcher interested in respiratory muscle monitoring about the current state of the art on sEMG, knowledge gaps and potential future applications for patients with respiratory failure. [ABSTRACT FROM AUTHOR] more...

Background: Regardless of the available antifungals, intraabdominal candidiasis (IAC) mortality continues to be high and represents a challenge for clinicians. Main body: This opinion paper discusses alternative antifungal options for treating IAC. This clinical entity should be addressed separately from candidemia due to the peculiarity of the required penetration of antifungals into the peritoneal cavity. Intraabdominal concentrations may be further restricted in critically ill patients where pathophysiological facts alter normal drug distribution. Echinocandins are recommended as first-line treatment in guidelines for invasive candidiasis. However, considering published data, our pharmacodynamic analysis suggests the required increase of doses, postulated by some authors, to attain adequate pharmacokinetic (PK) levels in peritoneal fluid. Given the limited evidence in the literature on PK/PD-based treatments of IAC, an algorithm is proposed to guide antifungal treatment. Liposomal amphotericin B is advocated as first-line therapy in patients with sepsis/septic shock presenting candidemia or endophthalmitis, or with prior exposure to echinocandins and/or fluconazole, or with infections by Candida glabrata. Other situations and alternatives, such as new compounds or combination therapy, are also analysed. Conclusion: There is a critical need for more robust clinical trials, studies examining patient heterogeneity and surveillance of antifungal resistance to enhance patient care and optimise treatment outcomes. Such evidence will help refine the existing guidelines and contribute to a more personalised and effective approach to treating this serious medical condition. Meanwhile, it is suggested to broaden the consideration of other options, such as liposomal amphotericin B, as first-line treatment until the results of the fungogram are available and antifungal stewardship could be implemented to prevent the development of resistance. [ABSTRACT FROM AUTHOR] more...

Background: The timely integration of palliative care is important for patients suffering from various advanced diseases with limited prognosis. While a German S-3-guideline on palliative care exists for patients with incurable cancer, a recommendation for non-oncological patients and especially for integration of palliative care into intensive care medicine is missing to date. Method: Ten German medical societies worked on recommendations on palliative care aspects in intensive care in a consensus process from 2018 to 2023. Results: Based on the german consensus paper, the palliative care aspects of the respective medical disciplines concerning intensive care are addressed. The recommendations partly refer to general situations, but also to specific aspects or diseases, such as geriatric issues, heart or lung diseases, encephalopathies and delirium, terminal renal diseases, oncological diseases and palliative emergencies in intensive care medicine. Measures such as non-invasive ventilation for symptom control and compassionate weaning are also included. Conclusion: The timely integration of palliative care into intensive care medicine aims to improve quality of life and symptom control and also takes into acccount the often urgently needed support for patients' highly stressed relatives. [ABSTRACT FROM AUTHOR] more...

COVID-19 patients with acute hypoxemic respiratory failure (AHRF) benefit from high flow nasal cannula (HFNC) oxygen therapy. However, delays in initiating invasive ventilation after HFNC failure are associated with poorer outcomes. The respiratory oxygenation (ROX) index, combining SpO2/FiO2 and respiratory rate, can predict HFNC failure. This meta-analysis evaluated the optimal ROX index cut-offs in predicting HFNC failure among COVID-19 patients at different measurement timings and clinical settings. Three databases were searched for eligible papers. From each study, we reconstructed the confusion matrices at different cut-offs, fitted linear mixed models to estimate the ROX index distribution function, and derived the area under the summary receiver operator characteristic curve (sAUC) and optimal cut-offs to predict HFNC failure. 24 studies containing 4790 patients were included. Overall sAUC was 0.771 (95% CI: 0.666–0.847) (optimal cut-off: 5.23, sensitivity: 0.732, specificity: 0.690). The cut-off values to achieve 80%, 90% sensitivity, 80%, 90% specificity were 5.70, 6.69, 4.45, 3.37, respectively. We stratified the analysis by ROX measurement time and estimated optimal cut-offs and cut-offs to achieve 80% sensitivity and specificity. For 2–6 h and 6–12 h post-HFNC initiation, we propose the use of 80% specific cut-offs to rule in HFNC failure of < 5.33 and < 3.69, respectively. For 12–24 h post-HFNC initiation, we propose the use of the 80% sensitive cut-off of > 6.07 to rule out HFNC failure. Our analysis confirms the overall utility of the ROX index in risk stratification of COVID-19 patients with AHRF receiving HFNC and provides potentially useful cut-offs for different times from HFNC initiation. [ABSTRACT FROM AUTHOR] more...

Critical illness is a continuum, but patient care is often fragmented. Value-based critical care focuses on the overall health of the patient, not on an episode of care. The "ICU without borders" model incorporates a concept where members of the critical care team are involved in the management of patients from the onset of critical illness until recovery and beyond. In this paper, we summarise the potential benefits and challenges to patients, families, staff and the wider healthcare system and list some essential requirements, including a tight governance framework, advanced technologies, investment and trust. We also argue that "ICU without borders" should be viewed as a bi-directional model, allowing extended visiting hours, giving patients and families direct access to experienced critical care staff and offering mutual aid when needed. [ABSTRACT FROM AUTHOR] more...

Use of extracorporeal membrane oxygenation (ECMO) in cardiopulmonary resuscitation, termed eCPR, offers the prospect of improving survival with good neurological function after cardiac arrest. After death, ECMO can also be used for enhanced preservation of abdominal and thoracic organs, designated normothermic regional perfusion (NRP), before organ recovery for transplantation. To optimize resuscitation and transplantation outcomes, healthcare networks in Portugal and Italy have developed cardiac arrest protocols that integrate use of eCPR with NRP. Similar dissemination of eCPR and its integration with NRP in the USA raise novel ethical issues due to a non-nationalized health system and an opt-in framework for organ donation, as well as other legal and cultural factors. Nonetheless, eCPR investigations are ongoing, and both eCPR and NRP are selectively employed in clinical practice. This paper delineates the most pressing relevant ethical considerations and proposes recommendations for implementation of protocols that aim to promote public trust and reduce conflicts of interest. Transparent policies should rely on protocols that separate lifesaving from organ preservation considerations; robust, centralized eCPR data to inform equitable and evidence-based allocations; uniform practices concerning clinical decision-making and resource utilization; and partnership with community stakeholders, allowing patients to make decisions about emergency care that align with their values. Proactively addressing these ethical and logistical challenges could enable eCPR dissemination and integration with NRP protocols in the USA, with the potential to maximize lives saved through both improved resuscitation with good neurological outcomes and increased organ donation opportunities when resuscitation is unsuccessful or not in accordance with individuals' wishes. [ABSTRACT FROM AUTHOR] more...

Background: Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI.Methods: In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence.Results: We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1-25.9), urinary NGAL (DOR 13.8, 95% CI 10.2-18.8), and serum NGAL (DOR 12.6, 95% CI 9.3-17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively.Conclusions: Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020. [ABSTRACT FROM AUTHOR] more...

Early haemorrhage control and minimizing the time to definitive care have long been the cornerstones of therapy for patients exsanguinating from non-compressible haemorrhage (NCH) after penetrating injuries, as only basic treatment could be provided on scene. However, more recently, advanced on-scene treatments such as the transfusion of blood products, resuscitative thoracotomy (RT) and resuscitative endovascular balloon occlusion of the aorta (REBOA) have become available in a small number of pre-hospital critical care teams. Although these advanced techniques are included in the current traumatic cardiac arrest algorithm of the European Resuscitation Council (ERC), published in 2021, clear guidance on the practical application of these techniques in the pre-hospital setting is scarce. This paper provides a scoping review on how these advanced techniques can be incorporated into practice for the resuscitation of patients exsanguinating from NCH after penetrating injuries, based on available literature and the collective experience of several helicopter emergency medical services (HEMS) across Europe who have introduced these advanced resuscitation interventions into routine practice. [ABSTRACT FROM AUTHOR] more...

Background: The ratio of pulse-oximetric peripheral oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) has been proposed as additional hypoxemia criterion in a new global definition of acute respiratory distress syndrome (ARDS). This study aims to evaluate the clinical and theoretical limitations of the SpO2/FiO2-ratio when using it to classify patients with ARDS and to follow disease progression. Methods: Observational cohort study of ARDS patients from three high-resolution Intensive Care Unit databases, including our own database ICU Cockpit, MIMIC-IV (Version 3.0) and SICdb (Version 1.0.6). Patients with ARDS were identified based on the Berlin criteria or ICD 9/10-codes. Time-matched datapoints of SpO2, FiO2 and partial pressure of oxygen in arterial blood (PaO2) were created. Severity classification followed the thresholds for SpO2/FiO2 and PaO2/FiO2 of the newly proposed global definition. Results: Overall, 708 ARDS patients were included in the analysis. ARDS severity was misclassified by SpO2/FiO2 in 33% of datapoints, out of which 84% were classified as more severe. This can be partially explained by imprecision of SpO2 measurement and equation used to transform SpO2/FiO2 to PaO2/FiO2. A high dependence of SpO2/FiO2-ratio on FiO2 settings was found, leading to major treatment effect and limited capability for tracking change in ARDS severity, which was achieved in less than 20% of events. Conclusions: The use of SpO2/FiO2 interchangeably with PaO2/FiO2 for severity classification and monitoring of ARDS is limited by its inadequate trending ability and high dependence on FiO2 settings, which may influence treatment decisions and patient selection in clinical trials. [ABSTRACT FROM AUTHOR] more...

Background: Serum cardiac troponin (cTn) elevation is a well-established phenomenon in sepsis. However, the clinical significance of this phenomenon with high-sensitivity (hs) assays and the current sepsis definition needs to be settled. Research Question: What is the association between early serum cTn levels measured by hs-assays and the risk of short-term mortality in septic patients? Study Design and Methods: We conducted a systematic review using a comprehensive PubMed, Scopus, and Embase search. Studies were eligible if they reported association data on early hs-cTn and mortality in an adult sample with sepsis that met the Sepsis-3 definition. For the synthesis of the effect of hs-cTn on mortality, we applied random effect models on the pooled unadjusted and adjusted odds ratio (OR and aOR, respectively) of elevated vs. normal hs-cTn serum values, and on the crude standardized mean difference (SMD) of hs-cTn between survivors and non-survivors. Results: In total, 6242 patients from 17 studies were included, with short-term mortality rates ranging from 16.9% to 53.8%. Using a crude analysis, non-survivor patients showed higher hs-cTn than survivors (SMD of 0.87, 95%CI: 0.41–1.33). Elevated hs-cTn was associated with increased mortality (OR = 1.78, 95% CI: 1.41–2.25). However, this prognostic effect was absent in studies that adjusted for different confounders (aOR = 1.06, 95% CI: 0.99–1.14). Discussion and Conclusions: Non-survivors of sepsis exhibited significantly elevated hs-cTn levels. While elevated hs-cTn levels are associated with an increased risk of mortality, they are not independently associated with this outcome in sepsis. [ABSTRACT FROM AUTHOR] more...

Background: Although potent P2Y12 inhibitors, such as ticagrelor and prasugrel, are standard treatment in patients with acute myocardial infarction (AMI), evidence for their efficacy and safety compared with clopidogrel is limited in patients with AMI complicated by cardiogenic shock. Methods: Among 28,949 patients from the nationwide pooled registry of KAMIR-NIH and KAMIR-V, a total of 1482 patients (5.1%) with AMI and cardiogenic shock who underwent percutaneous coronary intervention of the culprit vessel were selected. Primary outcome was major adverse cardiovascular event (MACE, a composite of cardiac death, MI, repeat revascularization and definite stent thrombosis) and major secondary outcome was Bleeding Academic Research Consortium (BARC) type 2 or greater bleeding at 2 years. Results: Among the study population, 537 patients (36.2%) received potent P2Y12 inhibitors and 945 patients (63.8%) received clopidogrel after index procedure. The risk of MACE was significantly lower in the potent P2Y12 inhibitors group than in the clopidogrel group (16.6% versus 24.7%; adjusted hazard ratio [HR], 0.76 [95% CI 0.59–0.99]; P = 0.046). Regarding BARC type 2 or greater bleeding, there was no significant difference between the potent P2Y12 inhibitors group and the clopidogrel group (12.5% versus 10.7%; adjusted HR, 1.36 [95% CI 0.98–1.88]; P = 0.064). Significant interaction was observed in patients aged ≥ 75 years (interaction P = 0.021) or venoarterial extracorporeal membrane oxygenator (VA-ECMO) use (interaction P = 0.015) for significantly increased risk of BARC type 2 or greater bleeding following the use of potent P2Y12 inhibitors. Conclusions: In patients with AMI complicated by cardiogenic shock, the use of potent P2Y12 inhibitors was associated with a lower risk of MACE compared with clopidogrel, without an increased risk of BARC type 2 or greater bleeding. The current data supports the use of potent P2Y12 inhibitors in patients with AMI and cardiogenic shock, except in patients aged ≥ 75 years or receiving VA-ECMO support. [ABSTRACT FROM AUTHOR] more...

Background: Relatives of intensive care unit (ICU) patients often endure symptoms of post-traumatic stress, anxiety, and depression during and after treatment of a family member's hospitalization. The aim of this study was to evaluate the effect of ICU-specific virtual reality (ICU-VR) on mental health among relatives, 6 months after patient's ICU discharge. Methods: This multicenter, randomized controlled trial included relatives of ICU patients who were assigned to receive either standard care or standard care plus ICU-VR, by randomizing the ICU patients. Relatives were assessed up to 6 months after patient discharge from the ICU for post-traumatic stress, anxiety, depression, quality of life, relatives' understanding of ICU care, and appreciation of ICU-VR. Results: One hundred relatives of 81 patients and 89 relatives of 80 patients were randomized to the intervention and control groups, respectively. Relatives' median age was 48 years and 53% were female. Compared to the control group, relatives who received ICU-VR did not experience a decrease in post-traumatic stress (23% vs. 18%; p = 0.99), anxiety (22% vs. 30%; p = 0.35), or depression (17% vs. 23%; p = 0.44). There was no significant difference between median mental quality of life (50.2 vs. 52.6; p = 0.51), physical quality of life (56.1 vs. 54.3; p = 0.16), or understanding of ICU care between groups. Patients in the intervention group highly endorsed ICU-VR (90%), favoring it over traditional informational brochures and the majority (82%) stated it improved their understanding of ICU treatment. Conclusion: ICU-VR did not significantly improve mental health distress symptoms among relatives 6-months after a patient's discharge. Relatives highly endorsed ICU-VR and self-reported that it improved their understanding of ICU treatment. [ABSTRACT FROM AUTHOR] more...

Background: Critical care nurses are vulnerable to depression, which not only lead to poor well-being and increased turnover intention, but also affect their working performances and organizational productivity as well. Work related factors are important drivers of depressive symptoms. However, the non-liner and multi-directional relationships between job demands-resources and depressive symptoms in critical care nurses has not been adequately analyzed. Understanding these relationships would be helpful for reducing depression, increasing nurses' well-being and retain healthcare forces. Methods: This was a cross-sectional study using baseline data from the Nurses' mental health study (NMHS), a prospective cohort study on nurses from 67 tertiary hospitals in 31 province-level administrative regions in China. Only clinical nurses working in the ICU were included (n = 13,745). Data were collected using online questionnaires, and analyzed using network analysis and structural equation model. Job demands (average working hours per week, average number of night shifts per month, paperwork burden and work-life balance), job resources (supervisor support, co-worker support, leader justice, organizational climate satisfaction, work meaning, and career prospect), personal resource (resilience) and depressive symptoms were main variables in the networks, while demographic data and social health (social-emotional support and loneliness) were covariates. Results: The prevalence of severe, moderately severe, moderate, mild, and none or minimum depressive symptoms in critical care nurses of this study were 1.21, 3.42, 9.76, 42.88, and 42.07% respectively. In the final network, 132 of 210 possible edges (62.8%) were not zero. "Fatigue" had the highest expected influence, followed by "Motor", and "Appetite". Meanwhile, in terms of job demands-resources and personal resources, the node with the highest expected influence was "Supervisor support", followed by "Work meaning" and "Co-worker support". Three bridge variables were identified: "Resilience-adaptation", "Average working hours per week", and "Co-worker support". The final structural equation model basically supported the results of network analysis with an acceptable model-fit (GFI = 0.918, AGFI = 0.896, PCFI = 0.789, PNFI = 0.788, NFI = 0.909, IFI = 0.911, CFI = 0.911, SRMR = 0.040, and RMSEA = 0.064). Conclusions: There was a rather strong interconnectedness between depressive symptoms and job demands-resources. Fatigue, motor, and appetite were core depressive symptoms of critical care nurses. Close attention to those symptoms could help recognize depression in critical care nurses. Supervisor support, work meaning, and co-worker support played vital roles as job resources in reducing depression, while negative impact of long average working hours per week were more contagious. Resilience, as personal resources, could help mediate the associations between job demands-resources and depression. In clinical practice, it's recommended for nursing managers to (1) encourage critical care nurses to find their "meaning in work", (2) implement resilience enhancing programs for nurse, (3) build and maintain meaningful relationships with nurses and support them in daily work, and (4) create a harmonious and dedicated working environment where co-workers are willing to help and support each other. Improvements in those modifiable aspects could help reduce risk and prevent exacerbations of depressive symptoms in critical care nurses. [ABSTRACT FROM AUTHOR] more...

Background: Ulinastatin (UTI), recognized for its anti-inflammatory properties, holds promise for patients undergoing cardiac surgery. This study aimed to investigate the relationship between intraoperative UTI administration and the incidence of delirium following cardiac surgery. Methods: A retrospective analysis was performed on a retrospective cohort of 6,522 adult cardiac surgery patients to evaluate the relationship between UTI treatment and the incident of postoperative delirium (POD) in patients ongoing cardiac surgery. This was followed by a prospective observational cohort study of 241 patients and an in vitro study to explore the findings and the potential role of UTI in preventing cardiac ischemia–reperfusion induced glycocalyx degradation. Results: Both univariate and multivariate logistic regression analyses in retrospective cohort indicated that intraoperative administration of UTI was associated with a significant lower risk of POD among cardiac surgery patients, a finding confirmed through employing propensity score matching. The subsequent prospective observational cohort further supported these findings (adjusted Odds Ratio = 0.392, 95% CI: 0.157–0.977, P = 0.044). Furthermore, UTI mitigated glycocalyx degradation, as demonstrated by in vitro study. Conclusions: UTI administration may mitigate glycocalyx degradation, potentially lowering the risk of POD in cardiac surgery patients, offering valuable insights for future interventions to prevent POD and enhance patient outcomes. Trial registration number ClinicalTrials.gov (No. NCT06268249). Retrospectively registered 4 February 2024. [ABSTRACT FROM AUTHOR] more...

Background: In-hospital cardiac arrest (IHCA) poses a considerable threat to hospitalized patients, leading to high mortality rates and severe neurological deficits among survivors. Despite the advancements in resuscitation practices, the prognosis of IHCA remains poor, and comprehensive studies exploring nationwide trends and long-term survival are scarce, particularly in the Asian populations. Methods: Utilizing data from the Taiwan National Health Insurance Research Database, we conducted a nationwide cohort study to analyze the IHCA events among adult patients between 2003 and 2020. The outcomes of interest in this study included the temporal trend in the IHCA incidence, in-hospital mortality, and median survival after discharge for overall hospitalizations. Results: Over the 18-year period, the IHCA incidence in Taiwan declined by 70%, from an annual incidence of 7.1 per 1,000 admissions to a lower rate in 2020, accompanied by a 14% reduction in the in-hospital mortality rate, with an average of 86.5%. The overall long-term survival rate for discharged survivors was 63.9%. We observed a substantial 125% increase in the median survival duration of discharged survivors, rising from 1.56 years in 2003 to 3.51 years in 2015. Favorable in-hospital survival rates and extended life expectancy were notably seen in the patients with shockable rhythms, those with a cardiac primary diagnosis, women, and younger patients. Conclusions: Our study data revealed significant declines in the IHCA incidence and in-hospital mortality in Taiwan, along with improved long-term survival among survivors, particularly among specific subgroups. Women exhibited significantly better long-term survival as compared to men, underscoring the need to avoid sex-based treatment biases. Improvements in discharge survival rates and life expectancy were less pronounced in older survivors, indicating that age alone may not be sufficient to guide IHCA management decisions. Proactive resuscitation should be carefully considered for older patients, particularly those with mild frailty and potentially reversible conditions. Trial registration the institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (Registration number: 202301625B0, Registered 7 November 2023) [ABSTRACT FROM AUTHOR] more...

Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Interleukin 40 (IL-40), a novel cytokine with immune regulatory functions in human diseases, was elevated at admission in two independent cohorts of patients with sepsis. High levels of secreted IL-40 in septic patients were positively correlated with PCT, CRP, lactate (LDH), and Sequential Organ Failure Assessment (SOFA) scores, in which IL-40 levels were used to stratify the early death of critically ill patients with sepsis. Moreover, genetic knockout of IL-40 (IL-40−/−) improved outcomes in mice with experimental sepsis, as evidenced by attenuated cytokine storm, multiple-organ failure, and early mortality, compared with those of wild-type (WT) mice. Mechanistically, single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) have revealed that S100A8/9hi neutrophil influx into the peritoneal cavity along with neutrophil extracellular trap (NETs) formation accounts predominantly for the IL-40-mediated worsening of sepsis outcomes. Clinically, the IL-40 level was positively correlated with the NET-related MPO/dsDNA ratio in septic patients. Finally, with antibiotics (gentamycin), genetic knockout of IL-40 prevented polymicrobial sepsis fatalities more efficiently than without gentamycin treatment. In summary, these data reveal a novel prognostic strategy for sepsis and that IL-40 may serve as a novel therapeutic target for sepsis. [ABSTRACT FROM AUTHOR] more...

Background: Pulse pressure variation (PPV) is limited in low tidal volume mechanical ventilation. We conducted this systematic review and meta-analysis to evaluate whether passive leg raising (PLR)-induced changes in PPV can reliably predict preload/fluid responsiveness in mechanically ventilated patients with low tidal volume in the intensive care unit. Methods: PubMed, Embase, and Cochrane databases were screened for diagnostic research relevant to the predictability of PPV change after PLR in low-tidal volume mechanically ventilated patients. The QUADAS-2 scale was used to assess the risk of bias of the included studies. In-between study heterogeneity was assessed through the I2 indicator. Publication bias was assessed by the Deeks' funnel plot asymmetry test. Summary receiving operating characteristic curve (SROC), pooled sensitivity, and specificity were calculated. Results: Five studies with a total of 474 patients were included in this meta-analysis. The SROC of the absolute PPV change resulted in an area under the curve of 0.91 (95% CI 0.88–0.93), with overall pooled sensitivity and specificity of 0.88 (95% CI 0.82–0.91) and 0.83 (95% CI 0.76–0.89), respectively. The diagnostic odds ratio was 35 (95% CI 19–67). The mean and median cutoff values of PLR-induced absolute change in absolute PPV were both -2 points and ranged from -2.5 to -1 points. Overall, there was no significant heterogeneity with I2 = 0%. There was no significant publication bias. Fagan's nomogram showed that with a pre-test probability of 50%, the post-test probability reached 84% and 17% for the positive and negative tests, respectively. Conclusions: PLR-induced change in absolute PPV has good diagnostic performance in predicting preload/fluid responsiveness in ICU patients on mechanical ventilation with low tidal volume. Trial registration PROSPERO (CRD42024496901). Registered on 15 January 2024. [ABSTRACT FROM AUTHOR] more...

Background: Continuous electroencephalography (cEEG) has been recommended in critically ill patients although its efficacy for improving patients' functional status remains unclear. This study aimed to compare the efficacy of Tele-cEEG with Tele-routine EEG (Tele-rEEG), in terms of seizure detection rate, mortality and functional outcomes. Methods: This study is a 3-year randomized, controlled, parallel, multicenter trial, conducted in eight regional hospitals across Thailand. Eligible participants were critically ill patients aged ≥ 15 years and at-risk for developing nonconvulsive seizure (NCS)/nonconvulsive status epilepticus (NCSE). Study interventions were 24–72 h Tele-cEEG versus 30-min Tele-rEEG. Study outcomes were seizure detection rate, mortality and functional outcomes (mRS), assessed at hospital discharge, ≤ 7 days, 3-, 6-, 9-months and 1 year. Results: Two hundred and fifty-four patients were randomized, 128 and 126 patients received Tele-cEEG and Tele-rEEG, respectively. NCS/NCSE were detected more commonly in the Tele-cEEG (21.88%) than Tele-rEEG arm (14.29%) but this was not statistically significant (p = 0.116). Intention-to-treat, per-protocol and as-treated analysis showed non-significant differences in mortality at all assessment periods, with corresponding mortality rates of 10.03% (Tele-cEEG) versus 10.10% (Tele-rEEG) (p = 0.894), 9.67% versus 9.06% (p = 0.833) and 10.34% versus 9.06% (p = 0.600), respectively. Functional outcome was also not significantly different in all analyses. Conclusions: Both Tele-cEEG and Tele-rEEG are feasible, although Tele-EEG requires additional EEG specialists, budget, and computational resources. While Tele-cEEG may help detect NCS/NCSE, this study had limited power to detect its efficacy in reducing mortality or improving functional outcomes. In limited-resource settings, Tele-rEEG approximating 30 min or longer offers a feasible and potentially valuable initial screening tool for critically ill patients at-risk of seizures. However, where Tele-cEEG is readily available, it remains the recommended approach. Trial registration Thai Clinical Trials Registry (TTCTR20181022002); Registered 22 October 2018. [ABSTRACT FROM AUTHOR] more...

Background: Management of bleeding trauma patients is still a difficult challenge. Massive transfusion (MT) requires resources to ensure the safety and timely delivery of blood products. Early prediction of MT need may be useful to shorten the time process of blood product preparation. The primary aim of this study was to assess the accuracy of shock index to predict the need for MT in adult patients with trauma. For the same population, we also assessed the accuracy of SI to predict mortality. Methods: This systematic review and meta-analysis was performed in accordance with the PRISMA guidelines. We performed a systematic search on MEDLINE, Scopus, and Web of Science from inception to March 2022. Studies were included if they reported MT or mortality with SI recorded at arrival in the field or the emergency department. The risk of bias was assessed using the QUADAS-2. Results: Thirty-five studies were included in the systematic review and meta-analysis, for a total of 670,728 patients. For MT the overall sensibility was 0.68 [0.57; 0.76], the overall specificity was 0.84 [0.79; 0.88] and the AUC was 0.85 [0.81; 0.88]. Positive and Negative Likelihood Ratio (LR+; LR−) were 4.24 [3.18–5.65] and 0.39 [0.29–0.52], respectively. For mortality the overall sensibility was 0.358 [0.238; 0.498] the overall specificity 0.742 [0.656; 0.813] and the AUC 0.553 (confidence region for sensitivity given specificity: [0.4014; 0.6759]; confidence region for specificity given sensitivity: [0.4799; 0.6332]). LR+ and LR− were 1.39 [1.36–1.42] and 0.87 [0.85–0.89], respectively. Conclusions: Our study demonstrated that SI may have a limited role as the sole tool to predict the need for MT in adult trauma patients. SI is not accurate to predict mortality but may have a role to identify patients with a low risk of mortality. [ABSTRACT FROM AUTHOR] more...

Background: Megakaryocytes are traditionally recognized as cells responsible for platelet production. However, beyond their role in thrombopoiesis, megakaryocytes also participate in inflammatory responses and regulate immune system functions. Sepsis, characterized by life-threatening organ dysfunction due to a dysregulated response to infection, prominently features coagulopathy, severe inflammation, and immune dysfunction as key pathophysiological aspects. Aim of review: Given the diverse functions of megakaryocytes, we explore their roles in coagulation in the context of sepsis, and also in inflammatory and immune regulation. We try to infer future research directions and potential strategies for sepsis prevention and treatment based on the properties of megakaryocytes. Key scientific concepts of review: The purpose of this review is to both highlight and provide an update on the functions of megakaryocytes and pathophysiological changes in sepsis. Specific emphasis is given to the role of megakaryocytes in sepsis, which suggests value of future research and clinical application. [ABSTRACT FROM AUTHOR] more...

Background: An increasing number of patients requires extracorporeal membrane oxygenation (ECMO) for life support. This supportive modality is associated with nosocomial infections (NIs). This systematic review and meta-analysis aim to assess the incidence and risk factors of NIs in adult. Methods: We searched PubMed, Scopus, Web of Science, and ProQuest databases up to 2022. The primary endpoint was incidence of NI. Secondary endpoints included time to infection, source of infection, ECMO duration, Intensive care and hospital length of stay (LOS), ECMO survival and overall survival. Incidence of NI was reported as pooled proportions and 95% confidence intervals (CIs), while dichotomous outcomes were presented as risk ratios (RR) as the effective index and 95% CIs using a random-effects model. Results: Among the 4,733 adult patients who received ECMO support in the 30 included studies, 1,249 ECMO-related NIs per 1000 ECMO-days was observed. The pooled incidence of NIs across 18 studies involving 3424 patients was 26% (95% CI 14–38%).Ventilator-associated pneumonia (VAP) and bloodstream infections (BSI) were the most common NI sources. Infected patients had lower ECMO survival and overall survival rates compared to non-infected patients, with risk ratio values of 0.84 (95% CI 0.74–0.96, P = 0.01) and 0.80 (95% CI 0.71–0.90, P < 0.001), respectively. Conclusion: Results showed that 16% and 20% lower of ECMO survival and overall survival in patients with NI than patients without NI, respectively. However, NI increased the risk of in-hospital mortality by 37% in infected patients compared with non-infected patients. In addition, this study identified the significant positive correlation between ECMO duration and ECMO-related NI. [ABSTRACT FROM AUTHOR] more...

Rapid multiplex molecular syndromic panels (RMMSP) (3 or more pathogens and time-to-results < 6 h) allow simultaneous detection of multiple pathogens and genotypic resistance markers. Their implementation has revolutionized the clinical landscape by significantly enhancing diagnostic accuracy and reducing time-to-results in different critical conditions. The current revision is a comprehensive but not systematic review of the literature. We conducted electronic searches of the PubMed, Medline, Embase, and Google Scholar databases to identify studies assessing the clinical performance of RMMSP in critically ill patients until July 30, 2024. A multidisciplinary group of 11 Spanish specialists developed clinical questions pertaining to the indications and limitations of these diagnostic tools in daily practice in different clinical scenarios. The topics covered included pneumonia, sepsis/septic shock, candidemia, meningitis/encephalitis, and off-label uses of these RMMSP. These tools reduced the time-to-diagnosis (and therefore the time-to-appropriate treatment), reduced inappropriate empiric treatment and the length of antibiotic therapy (which has a positive impact on antimicrobial stewardship and might be associated with lower in-hospital mortality), may reduce the length of hospital stay, which could potentially lead to cost savings. Despite their advantages, these RMMSP have limitations that should be known, including limited availability, missed diagnoses if the causative agent or resistance determinants are not included in the panel, false positives, and codetections. Overall, the implementation of RMMSP represents a significant advancement in infectious disease diagnostics, enabling more precise and timely interventions. This document addresses relevant issues related to the use of RMMSP on different critically ill patient profiles, to standardize procedures, assist in making management decisions and help specialists to obtain optimal outcomes. [ABSTRACT FROM AUTHOR] more...

Background: Excessive exposure to adrenergic vasopressors may be harmful. Non-adrenergic vasopressors may spare adrenergic agents and potentially improve outcomes. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of non-adrenergic vasopressors in adult patients receiving vasopressor therapy for vasodilatory shock or perioperative vasoplegia. Methods: We searched PubMed, Embase, and Cochrane Library for RCTs comparing non-adrenergic vasopressors with adrenergic vasopressors alone or placebo in critically ill or perioperative patients. Each eligible study was categorized into septic shock, cardiac surgery, or non-cardiac surgery. Non-adrenergic vasopressors included vasopressin, terlipressin, selepressin, angiotensin II, methylene blue, and hydroxocobalamin. The primary outcome was mortality at longest follow-up. We conducted a random-effects meta-analysis. We registered the protocol in PROSPERO International Prospective Register of Systematic Reviews (CRD42024505039). Results: Among 51 eligible RCTs totaling 5715 patients, the predominant population was septic shock in 30 studies, cardiac surgery in 11 studies, and non-cardiac surgery in 10 studies. Cochrane risk-of-bias tool for randomized trials version 2 identified 17 studies as low risk of bias. In septic shock, mortality was significantly lower in the non-adrenergic group (960/2232 [43%] vs. 898/1890 [48%]; risk ratio [RR], 0.92; 95% confidence interval [95% CI], 0.86–0.97; P = 0.03; I2 = 0%), with none of the individual non-adrenergic vasopressors showing significant survival benefits. No significant mortality difference was observed in patients undergoing cardiac surgery (34/410 [8.3%] vs. 47/412 [11%]; RR, 0.82; 95% CI, 0.55–1.22; P = 0.32; I2 = 12%) or those undergoing non-cardiac surgery (9/388 [2.3%] vs. 18/383 [4.7%]; RR, 0.66; 95% CI, 0.31–1.41; P = 0.28; I2 = 0%). Conclusions: Administration of non-adrenergic vasopressors was significantly associated with reduced mortality in patients with septic shock. However, no single agent achieved statistical significance in separate analyses. Although the pooled effects of non-adrenergic vasopressors on survival did not reach statistical significance in patients undergoing cardiac or non-cardiac surgery, the confidence intervals included the possibility of both no effect and a clinically important benefit from non-adrenergic agents. These findings justify the conduct of further RCTs comparing non-adrenergic vasopressors to usual care based on noradrenaline alone. [ABSTRACT FROM AUTHOR] more...

Background: Listening and responding to family concerns in organ and tissue donation is generally considered important, but has never been researched in real time. We aimed to explore in real time, (a) which family concerns emerge in the donation process, (b) how these concerns manifest during and after the donor conversation, and (c) how clinicians respond to the concerns during the donor conversation. Methods: A qualitative embedded multiple-case study in eight Dutch hospitals was conducted. Thematic analysis was performed based on audio recordings and direct observations of 29 donor conversations and interviews with the family members involved (n = 24). Results: Concerns clustered around six topics: 1) Life-event of a relative's death, 2) Dying well, 3) Tensions and fears about donation, 4) Experiences of time, 5) Procedural clarity, and 6) Involving (non-)present family. Most concerns occurred in topics 1 and 2. Clinicians mostly responded to concerns by providing information or immediate solutions, while sometimes acknowledgement sufficed. When concerns were highly charged with emotion, the clinicians' responses were less frequently attuned to families' needs. Cues of less clearly articulated concerns gained less follow-up. Then, concerns often remained or reappeared. Conclusion: The identified concerns and the distinction between clearly and less clearly articulated concerns may prove valuable for clinicians to improve family support. We advise clinicians to engage with a curious, probing attitude to enhance the dialogue around concerns, elaborate on less clearly articulated concerns and identify the informational needs of the family. [ABSTRACT FROM AUTHOR] more...

Background: Cardiopulmonary bypass (CPB) triggers marked cytokine release often followed by a systemic inflammatory response syndrome, associated with adverse postoperative outcomes. This trial investigates the intraoperative use of haemoadsorption (HA) during cardiac surgery with CPB to assess its impact on postoperative systemic inflammatory response. Methods: In this prospective randomised controlled trial (ethics approval no. 5094-14DRKS00007928), patients (> 65 years) undergoing elective on-pump cardiac surgery were randomised to intraoperative HA (CytoSorb) during CPB or standard care without HA. Primary outcome was the difference in mean interleukin (IL)-6 serum concentrations between groups on intensive care unit (ICU) admission. The secondary outcomes included various clinical and biochemical endpoints. Statistical methods included paired and unpaired t-tests, Wilcoxon, Mann–Whitney U-tests, and chi-square tests. Results: Thirty-eight patients were allocated to receive either intraoperative HA (n = 19) or standard care (n = 19). The primary outcome, IL-6 levels on ICU admission, did not differ between the study group and controls (214.4 ± 328.8 vs. 155.8 ± 159.6 pg/ml, p = 0.511). During surgery pre- versus post-adsorber IL-2, IL-6, IL-8, IL-10, heparan sulfate and myoglobin post- levels were reduced. Furthermore, IL-6 levels did not differ between the study groups on day 1 and 2 in the ICU. While sequential organ failure assessment scores, lactate levels, and C-reactive protein and procalcitonin (PCT) showed no statistically significant differences. Regarding haemodynamic stability in the treatment group the cardiac index (3.2 ± 0.7 vs. 2.47 ± 0.47 l/min/m2, p = 0.012) on ICU day 2 increased, and lower fluid requirements as well as decreased fibrinogen requirement were observed. Need for renal replacement therapy did not differ though a shorter duration was observed in the treatment group. Time on ventilator, respiratory parameters, infectious complications, delirium scores, ICU and hospital lengths of stay, and mortality did not differ between groups. Conclusion: HA did not reduce the IL-6 level on ICU admission or afterwards. Even though HA reduced cytokine load during cardiac surgery in the treatment group. There were no significant differences between groups in the postoperative course of other cytokine concentrations, organ dysfunction, ICU and hospital lengths of stay and mortality rates. Trial registration prospectively DRKS00007928 and published under: Baumann A, Buchwald D, Annecke T, Hellmich M, Zahn PK, Hohn A. RECCAS - REmoval of Cytokines during Cardiac Surgery: study protocol for a randomised controlled trial. Trials. 2016;17: 137. [ABSTRACT FROM AUTHOR] more...

Background: Continuous waveform monitoring is standard-of-care for patients at risk for or with critically illness. Derived from waveforms, heart rate, respiratory rate and blood pressure variability contain useful diagnostic and prognostic information; and when combined with machine learning, can provide predictive indices relating to severity of illness and/or reduced physiologic reserve. Integration of predictive models into clinical decision support software (CDSS) tools represents a potential evolution of monitoring. Methods: We perform a review and analysis of the multidisciplinary steps required to develop and rigorously evaluate predictive clinical decision support tools based on monitoring. Results: Development and evaluation of waveform-based variability-derived predictive models involves a multistep, multidisciplinary approach. The stepwise processes involves data science (data collection, waveform processing, variability analysis, statistical analysis, machine learning, predictive modelling), CDSS development (iterative research prototype evolution to commercial tool), and clinical research (observational and interventional implementation studies, followed by feasibility then definitive randomized controlled trials), and poses unique challenges (including technical, analytical, psychological, regulatory and commercial). Conclusions: The proposed roadmap provides guidance for the development and evaluation of novel predictive CDSS tools with potential to help transform monitoring and improve care. [ABSTRACT FROM AUTHOR] more...

Dysregulation of the renin–angiotensin–aldosterone-system (RAAS) in sepsis is a complex and early phenomenon with a likely significant contribution to organ failure and patient outcomes. A better understanding of the pathophysiology and intricacies of the RAAS in septic shock has led to the use of exogenous angiotensin II as a new therapeutic agent. In this review, we report a multinational and multi-disciplinary expert panel discussion on the role and implications of RAAS modulation in sepsis and the use of exogenous angiotensin II. The panel proposed guidance regarding patient selection and treatment options with exogenous angiotensin II which should trigger further research. [ABSTRACT FROM AUTHOR] more...