136 research outputs found
Hypercoagulopathy in Severe COVID-19: Implications for Acute Care.
No full textCOVID-19 was first described in late 2019 and has since developed into a pandemic affecting more than 21 million people worldwide. Of particular relevance for acute care is the occurrence of COVID-19-associated coagulopathy (CAC), which is characterised by hypercoagulability, immunothrombosis and venous thromboembolism, and contributes to hypoxia in a significant proportion of patients. This review describes diagnosis and treatment of CAC in the emergency department and in intensive care. We summarise the pathological mechanisms and common complications of CAC such as pulmonary thrombosis and venous thromboembolic events and discuss current strategies for thromboprophylaxis and therapeutic anti-coagulation in the acute care setting
Can Beta-D-Glucan testing as part of the diagnostic pathway for invasive fungal infection reduce anti-fungal treatment costs?
No full textWe performed a cost comparison of the current diagnostic and treatment pathway for invasive fungal infection (IFI) versus a proposed pathway that incorporates Beta-D-Glucan (BDG) testing from the NHS perspective. A fungal pathogen was identified in 58/107 (54.2%) patients treated with systemic anti-fungals in the Critical Care Department. Mean therapy duration was 23 days (standard deviation [SD] = 22 days), and cost was £5590 (SD = £7410) per patient. Implementation of BDG tests in the diagnostic and treatment pathway of patients with suspected IFI could result in a mean saving of £1643 per patient should a result be returned within 2 days. Lay Summary: Invasive fungal infection increases the risk of death in very sick people. So, treatment is started before test results are known. Beta-D-Glucan (BDG) test is faster than standard blood culture tests. We estimate that using BDG tests in how patients are diagnosed could save about £1643 per patient
Study protocol: A systematic review and meta-analysis regarding the influence of coagulopathy and immune activation on new onset atrial fibrillation in patients with sepsis.
No full textBackgroundNew onset atrial fibrillation (NOAF) is the most common arrhythmia affecting critically ill patients with sepsis. NOAF is associated with increased intensive care unit mortality, increased hospital mortality, development of heart failure and increased risk of permanent atrial fibrillation and thromboembolic events such as stroke. The pathophysiology of NOAF has been outlined, however, a knowledge gap exists regarding the association between abnormalities in coagulation and immune biomarkers, and the risk of developing NOAF in patients with sepsis.Methods and analysisThis protocol describes a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guideline (PRISMA-P) and the Meta-Analyses and Systematic Reviews of Observational Studies guideline (MOOSE). We will conduct the literature search in Medline, Scopus and Cochrane Library. We will include studies that report data in adult patients (>18 years) with sepsis that develop NOAF. We will extract data from studies that report at least one coagulation or immune biomarker. Risk of bias will be assessed by using the Newcastle Ottawa Scale (NOS) and Risk of Bias 2 tool (RoB2) for non-randomized and randomized trials respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be utilized in assessing the quality of evidence.DiscussionThis systematic review and meta-analysis will explore the scientific literature regarding the association between coagulation and immune activation in critically ill patients with sepsis, who develop NOAF. The findings will add to the existing knowledge base of NOAF in sepsis, highlight areas of uncertainty and identify future areas of interest to guide and improve management strategies for NOAF.Trial registrationRegistration details. CRD42022385225 (PROSPERO)
Development of a Risk Prediction Model for New Episodes of Atrial Fibrillation in Medical-Surgical Critically Ill Patients Using the AmsterdamUMCdb.
No full textThe occurrence of atrial fibrillation (AF) represents clinical deterioration in acutely unwell patients and leads to increased morbidity and mortality. Prediction of the development of AF allows early intervention. Using the AmsterdamUMCdb, clinically relevant variables from patients admitted in sinus rhythm were extracted over the full duration of the ICU stay or until the first recorded AF episode occurred. Multiple logistic regression was performed to identify risk factors for AF. Input variables were automatically selected by a sequential forward search algorithm using cross-validation. We developed three different models: For the overall cohort, for ventilated patients and non-ventilated patients. 16,144 out of 23,106 admissions met the inclusion criteria. 2,374 (12.8%) patients had at least one AF episode during their ICU stay. Univariate analysis revealed that a higher percentage of AF patients were older than 70 years (60% versus 32%) and died in ICU (23.1% versus 7.1%) compared to non-AF patients. Multivariate analysis revealed age to be the dominant risk factor for developing AF with doubling of age leading to a 10-fold increased risk. Our logistic regression models showed excellent performance with AUC.ROC > 0.82 and > 0.91 in ventilated and non-ventilated cohorts, respectively. Increasing age was the dominant risk factor for the development of AF in both ventilated and non-ventilated critically ill patients. In non-ventilated patients, risk for development of AF was significantly higher than in ventilated patients. Further research is warranted to identify the role of ventilatory settings on risk for AF in critical illness and to optimise predictive models
In-Hospital Mortality of Sepsis Differs Depending on the Origin of Infection: An Investigation of Predisposing Factors.
No full textSepsis is a heterogeneous syndrome characterized by a variety of clinical features. Analysis of large clinical datasets may serve to define groups of sepsis with different risks of adverse outcomes. Clinical experience supports the concept that prognosis, treatment, severity, and time course of sepsis vary depending on the source of infection. We analyzed a large publicly available database to test this hypothesis. In addition, we developed prognostic models for the three main types of sepsis: pulmonary, urinary, and abdominal sepsis. We used logistic regression using routinely available clinical data for mortality prediction in each of these groups. The data was extracted from the eICU collaborative research database, a multi-center intensive care unit with over 200,000 admissions. Sepsis cohorts were defined using admission diagnosis codes. We used univariate and multivariate analyses to establish factors relevant for outcome prediction in all three cohorts of sepsis (pulmonary, urinary and abdominal). For logistic regression, input variables were automatically selected using a sequential forward search algorithm over 10 dataset instances. Receiver operator characteristics were generated for each model and compared with established prognostication tools (APACHE IV and SOFA). A total of 3,958 sepsis admissions were included in the analysis. Sepsis in-hospital mortality differed depending on the cause of infection: abdominal 18.93%, pulmonary 19.27%, and renal 12.81%. Higher average heart rate was associated with increased mortality risk. Increased average Mean Arterial Pressure (MAP) showed a reduced mortality risk across all sepsis groups. Results from the LR models found significant factors that were relevant for specific sepsis groups. Our models outperformed APACHE IV and SOFA scores with AUC between 0.63 and 0.74. Predictive power decreased over time, with the best results achieved for data extracted for the first 24 h of admission. Mortality varied significantly between the three sepsis groups. We also demonstrate that factors of importance show considerable heterogeneity depending on the source of infection. The factors influencing in-hospital mortality vary depending on the source of sepsis which may explain why most sepsis trials have failed to identify an effective treatment. The source of infection should be considered when considering mortality risk. Planning of sepsis treatment trials may benefit from risk stratification based on the source of infection
Impact of prolonged elevated heart rate on incidence of major cardiac events in critically ill patients with a high risk of cardiac complications*
No full textLipopolysaccharide induces a downregulation of adiponectin receptors in-vitro and in-vivo
No full textBackground. Adipose tissue contributes to the inflammatory response through production of cytokines, recruitment of macrophages and modulation of the adiponectin system. Previous studies have identified a down-regulation of adiponectin in pathologies characterised by acute (sepsis and endotoxaemia) and chronic inflammation (obesity and type-II diabetes mellitus). In this study, we investigated the hypothesis that LPS would reduce adiponectin receptor expression in a murine model of endotoxaemia and in adipoocyte and myocyte cell cultures.Methods. 25 mg/kg LPS was injected intra-peritoneally into C57BL/6J mice, equivalent volumes of normal saline were used in control animals. Mice were killed at 4 or 24 h post injection and tissues harvested. Murine adipocytes (3T3-L1) and myocytes (C2C12) were grown in standard culture, treated with LPS (0.1 µg/ml–10 µg/ml) and harvested at 4 and 24 h. RNA was extracted and qPCR was conducted according to standard protocols and relative expression was calculated.Results. After LPS treatment there was a significant reduction after 4 h in gene expression of adipo R1 in muscle and peri-renal fat and of adipo R2 in liver, peri-renal fat and abdominal wall subcutaneous fat. After 24 h, significant reductions were limited to muscle. Cell culture extracts showed varied changes with reduction in adiponectin and adipo R2 gene expression only in adipocytes.Conclusions. LPS reduced adiponectin receptor gene expression in several tissues including adipocytes. This reflects a down-regulation of this anti-inflammatory and insulin-sensitising pathway in response to LPS. The trend towards base line after 24 h in tissue depots may reflect counter-regulatory mechanisms. Adiponectin receptor regulation differs in the tissues investigated
Development of Core Outcome Sets for trials on the management of Atrial fiBrillAtion in Critically Unwell patientS (COS-ABACUS): a protocol
No full textIntroduction Atrial fibrillation (AF) is the most common cardiac arrhythmia in critically unwell patients. New-onset AF (NOAF) affects 5%–11% of all admissions and up to 46% admitted with septic shock. NOAF is associated with increased morbidity, mortality and healthcare costs. Existing trials into the prevention and management of NOAF suffer from significant heterogeneity making comparisons and inferences limited. Core outcome sets (COS) aim to standardise outcome reporting, reduce inconsistency between trials and reduce outcome reporting bias. We aim to develop an internationally agreed COS for trials of interventions on the management of NOAF during critical illness.Methods and analysis Stakeholders including intensive care physicians, cardiologists and patients will be recruited from national and international critical care organisations. COS development will occur in five stages: (1) Outcomes included in trials, recent systematic reviews and surveys of clinician practice and patient focus groups will be extracted. (2) Extracted outcomes will inform a two-stage e-Delphi process and consensus meeting using Grading of Recommendations Assessment, Development and Evaluation methodology. (3) Outcome measurement instruments (OMIs) will be identified from the literature and a consensus meeting held to agree OMI for core outcomes. (4) Nominal group technique will be used in a final consensus meeting to the COS. (5) The findings of our COS will be published in peer-reviewed journals and implemented in future guidelines and intervention trials.Ethics and dissemination The study has been approved by the University of Liverpool ethics committee (Ref: 11 256, 21 June 2022), with a formal consent waiver and assumed consent. We will disseminate the finalised COS via national and international critical care organisations and publication in peer-reviewed journals
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