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  • Aslam, Tayyba N., et al. (author)
  • A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure
  • 2023
  • In: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 67:10, s. 1383-1394
  • Journal article (peer-reviewed)abstract
    • BackgroundWhen caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers.MethodsWe distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice.ResultsThe survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF.ConclusionsThe responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.
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  • Granholm, Anders, et al. (author)
  • Long-term outcomes of dexamethasone 12 mg versus 6 mg in patients with COVID-19 and severe hypoxaemia
  • 2022
  • In: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 580-589
  • Journal article (peer-reviewed)abstract
    • Purpose We assessed long-term outcomes of dexamethasone 12 mg versus 6 mg given daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. Methods We assessed 180-day mortality and health-related quality of life (HRQoL) using EuroQoL (EQ)-5D-5L index values and EQ visual analogue scale (VAS) in the international, stratified, blinded COVID STEROID 2 trial, which randomised 1000 adults with confirmed COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 26 hospitals in Europe and India. In the HRQoL analyses, higher values indicated better outcomes, and deceased patients were given a score of zero. Results We obtained vital status at 180 days for 963 of 982 patients (98.1%) in the intention-to-treat population, EQ-5D-5L index value data for 922 (93.9%) and EQ VAS data for 924 (94.1%). At 180 days, 164 of 486 patients (33.7%) had died in the 12 mg group versus 184 of 477 (38.6%) in the 6 mg group [adjusted risk difference - 4.3%; 99% confidence interval (CI) - 11.7-3.0; relative risk 0.89; 0.72-1.09; P = 0.13]. The adjusted mean differences between the 12 mg and the 6 mg groups in EQ-5D-5L index values were 0.06 (99% CI - 0.01 to 0.12; P = 0.10) and in EQ VAS scores 4 (- 3 to 10; P = 0.22). Conclusion Among patients with COVID-19 and severe hypoxaemia, dexamethasone 12 mg compared with 6 mg did not result in statistically significant improvements in mortality or HRQoL at 180 days, but the results were most compatible with benefit from the higher dose.
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  • Huang, Stephen, et al. (author)
  • Echocardiography findings in COVID-19 patients admitted to intensive care units: a multi-national observational study (the ECHO-COVID study)
  • 2022
  • In: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 667-678
  • Journal article (peer-reviewed)abstract
    • Purpose Severely ill patients affected by coronavirus disease 2019 (COVID-19) develop circulatory failure. We aimed to report patterns of left and right ventricular dysfunction in the first echocardiography following admission to intensive care unit (ICU). Methods Retrospective, descriptive study that collected echocardiographic and clinical information from severely ill COVID-19 patients admitted to 14 ICUs in 8 countries. Patients admitted to ICU who received at least one echocardiography between 1st February 2020 and 30th June 2021 were included. Clinical and echocardiographic data were uploaded using a secured web-based electronic database (REDCap). Results Six hundred and seventy-seven patients were included and the first echo was performed 2 [1, 4] days after ICU admission. The median age was 65 [56, 73] years, and 71% were male. Left ventricle (LV) and/or right ventricle (RV) systolic dysfunction were found in 234 (34.5%) patients. 149 (22%) patients had LV systolic dysfunction (with or without RV dysfunction) without LV dilatation and no elevation in filling pressure. 152 (22.5%) had RV systolic dysfunction. In 517 patients with information on both paradoxical septal motion and quantitative RV size, 90 (17.4%) had acute cor pulmonale (ACP). ACP was associated with mechanical ventilation (OR > 4), pulmonary embolism (OR > 5) and increased PaCO2. Exploratory analyses showed that patients with ACP and older age were more likely to die in hospital (including ICU). Conclusion Almost one-third of this cohort of critically ill COVID-19 patients exhibited abnormal LV and/or RV systolic function in their first echocardiography assessment. While LV systolic dysfunction appears similar to septic cardiomyopathy, RV systolic dysfunction was related to pressure overload due to positive pressure ventilation, hypercapnia and pulmonary embolism. ACP and age seemed to be associated with mortality in this cohort.
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  • Myatra, Sheila Nainan, et al. (author)
  • Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline
  • 2023
  • In: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 67:5, s. 569-575
  • Journal article (peer-reviewed)abstract
    • This rapid practice guideline provides evidence-based recommendations for the use of awake proning in adult patients with acute hypoxemic respiratory failure due to COVID-19. The panel included 20 experts from 12 countries, including one patient representative, and used a strict conflict of interest policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the guidelines in intensive care, development, and evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation (GRADE) method we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. We conducted an electronic vote, requiring >80% agreement amongst the panel for a recommendation to be adopted. The panel made a strong recommendation for a trial of awake proning in adult patients with COVID-19 related hypoxemic acute respiratory failure who are not invasively ventilated. Awake proning appears to reduce the risk of tracheal intubation, although it may not reduce mortality. The panel judged that most patients would want a trial of awake proning, although this may not be feasible in some patients and some patients may not tolerate it. However, given the high risk of clinical deterioration amongst these patients, awake proning should be conducted in an area where patients can be monitored by staff experienced in rapidly detecting and managing clinical deterioration. This RPG panel recommends a trial of awake prone positioning in patients with acute hypoxemic respiratory failure due to COVID-19.
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  • Arnaud, Alexis P, et al. (author)
  • SARS-CoV-2 infection and venous thromboembolism after surgery : an international prospective cohort study
  • 2022
  • In: Anaesthesia. - : Wiley. - 0003-2409 .- 1365-2044. ; 77:1, s. 28-39
  • Journal article (peer-reviewed)abstract
    • SARS-CoV-2 has been associated with an increased rate of venous thromboembolism in critically ill patients. Since surgical patients are already at higher risk of venous thromboembolism than general populations, this study aimed to determine if patients with peri-operative or prior SARS-CoV-2 were at further increased risk of venous thromboembolism. We conducted a planned sub-study and analysis from an international, multicentre, prospective cohort study of elective and emergency patients undergoing surgery during October 2020. Patients from all surgical specialties were included. The primary outcome measure was venous thromboembolism (pulmonary embolism or deep vein thrombosis) within 30 days of surgery. SARS-CoV-2 diagnosis was defined as peri-operative (7 days before to 30 days after surgery); recent (1-6 weeks before surgery); previous (≥7 weeks before surgery); or none. Information on prophylaxis regimens or pre-operative anti-coagulation for baseline comorbidities was not available. Postoperative venous thromboembolism rate was 0.5% (666/123,591) in patients without SARS-CoV-2; 2.2% (50/2317) in patients with peri-operative SARS-CoV-2; 1.6% (15/953) in patients with recent SARS-CoV-2; and 1.0% (11/1148) in patients with previous SARS-CoV-2. After adjustment for confounding factors, patients with peri-operative (adjusted odds ratio 1.5 (95%CI 1.1-2.0)) and recent SARS-CoV-2 (1.9 (95%CI 1.2-3.3)) remained at higher risk of venous thromboembolism, with a borderline finding in previous SARS-CoV-2 (1.7 (95%CI 0.9-3.0)). Overall, venous thromboembolism was independently associated with 30-day mortality (5.4 (95%CI 4.3-6.7)). In patients with SARS-CoV-2, mortality without venous thromboembolism was 7.4% (319/4342) and with venous thromboembolism was 40.8% (31/76). Patients undergoing surgery with peri-operative or recent SARS-CoV-2 appear to be at increased risk of postoperative venous thromboembolism compared with patients with no history of SARS-CoV-2 infection. Optimal venous thromboembolism prophylaxis and treatment are unknown in this cohort of patients, and these data should be interpreted accordingly.
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  • Chew, Michelle S, 1969- (author)
  • Right ventricular function
  • 2020
  • In: Oxford Textbook of Advanced Critical Care Echocardiography. - : Oxford University Press. - 9780198749288
  • Book chapter (other academic/artistic)abstract
    • The right ventricle (RV) has historically been given less importance than the left. There are important anatomical differences, including several intracardiac structures that may complicate echocardiographic assessments. The right heart is sensitive to changes in pressure and its function is affected by common interventions in critical care such as fluid loading and positive pressure ventilation. Right and left ventricular functions are inextricably linked, and both systolic and diastolic ventricular interdependence occur. The echocardiographic examination of the RV includes an assessment of size and dimensions, systolic and diastolic function, estimation of intracardiac and pulmonary pressures. These should be interpreted in the context of the clinical interventions that the patient was subjected to at the time of imaging, as well as left ventricular function. RV failure is associated with poorer outcomes in several disease states including congestive cardiac failure and acute myocardial infarction. In critically ill patients, acute respiratory distress syndrome (ARDS) has significant implications for right heart function, where there is a necessary balance between respiratory mechanics and haemodynamics.
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  • Chew, Michelle S, 1969- (author)
  • Sedation and analgesia
  • 2022
  • In: The Very Old Critically Ill Patients. - Cham : Springer. - 9783030941321 - 9783030941338 ; , s. 319-333
  • Book chapter (peer-reviewed)abstract
    • The main objective of this chapter is to obtain an understanding of the interaction between pain, sedation, and delirium. Specifically, the reader should be able to identify the unique challenges for their management taking into account that the very old are a particularly vulnerable group with often conflicting treatment priorities. This chapter will discuss implications for short- and long-term ICU outcomes including mortality, time on mechanical ventilation, and increased ICU and hospital lengths of stay, as well long-term cognitive impairment. Finally, the reader should be able to formulate a plan for sedation, pain, and delirium management for the very old ICU patient using ABCDEF principles.
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  • Chew, Michelle S, 1969- (author)
  • Septic shock
  • 2020
  • In: Oxford Textbook of Advanced Critical Care Echocardiography. - : Oxford University Press. - 9780198749288
  • Book chapter (other academic/artistic)abstract
    • Failure or dysfunction of the cardiovascular system is the defining feature of septic shock. While there is now evidence for the central role of the heart in the pathophysiology of septic shock, it is important to remember that it is only one component of the cardiovascular system. Thus, it is often impossible to distinguish between the direct effects of sepsis on the heart and its responses to other changes in the cardiovascular system. Systolic, diastolic, left, and right heart functions are variably affected and are not mutually exclusive. They may be associated with rises in cardiac troponins and may be associated with underlying cardiovascular disease. Current evidence suggests left ventricular systolic dysfunction (assessed as reduced ejection fraction) is not associated with increased mortality, while diastolic dysfunction seems to be more predictive. Right heart failure occurs commonly, even with lung-protective ventilation strategies. Echocardiography is currently the only bedside technique providing comprehensive information regarding heart function during sepsis. In combination with information obtained with pulmonary arterial catheterization, it may be used to monitor the effects of fluid loading, mechanical ventilation, and vasopressor/inotropic therapy in the patient with septic shock. Future areas of research include (1) the development of a universal definition for septic cardiomyopathy; (2) investigating methods for distinguishing sepsis-specific changes from underlying disease; (3) investigating the relationship between cardiac biomarkers and echocardiographic changes; (4) investigating new echocardiographic markers of systolic and diastolic function; (5) integration of lung-protective mechanical ventilation and haemodynamic management strategies guided by echocardiographic findings.
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  • De Backer, Daniel, et al. (author)
  • How can assessing hemodynamics help to assess volume status?
  • 2022
  • In: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 11482-1494
  • Research review (peer-reviewed)abstract
    • In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.
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  • Dhanani, Jayesh A, et al. (author)
  • A research pathway for the study of the delivery and disposition of nebulised antibiotics: an incremental approach from in vitro to large animal models
  • 2018
  • In: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 6:1
  • Journal article (peer-reviewed)abstract
    • Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic.
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  • Dhanani, Jayesh A, et al. (author)
  • Recovery rates of combination antibiotic therapy using in vitro microdialysis simulating in vivo conditions
  • 2018
  • In: Journal of pharmaceutical analysis. - : Elsevier BV. - 2214-0883 .- 2095-1779. ; 8:6, s. 407-412
  • Journal article (peer-reviewed)abstract
    • Microdialysis is a technique used to measure the unbound antibiotic concentration in the interstitial spaces, the target site of action. In vitro recovery studies are essential to calibrating the microdialysis system for in vivo studies. The effect of a combination of antibiotics on recovery into microdialysate requires investigation. In vitro microdialysis recovery studies were conducted on a combination of vancomycin and tobramycin, in a simulated in vivo model. Comparison was made between recoveries for three different concentrations and three different perfusate flow rates. The overall relative recovery for vancomycin was lower than that of tobramycin. For tobramycin, a concentration of 20µg/mL and flow rate of 1.0µL/min had the best recovery. A concentration of 5.0µg/mL and flow rate of 1.0µL/min yielded maximal recovery for vancomycin. Large molecular size and higher protein binding resulted in lower relative recoveries for vancomycin. Perfusate flow rates and drug concentrations affected the relative recovery when a combination of vancomycin and tobramycin was tested. Low perfusate flow rates were associated with higher recovery rates. For combination antibiotic measurement which includes agents that are highly protein bound, in vitro studies performed prior to in vivo studies may ensure the reliable measurement of unbound concentrations.
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  • Granholm, Anders, et al. (author)
  • Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis
  • 2021
  • In: Acta Anaesthesiologica Scandinavica. - : WILEY. - 0001-5172 .- 1399-6576. ; 65:5, s. 702-710
  • Journal article (peer-reviewed)abstract
    • Background Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.
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  • Huang, Stephen, et al. (author)
  • Echocardiography phenotypes of right ventricular involvement in COVID-19 ARDS patients and ICU mortality: post-hoc (exploratory) analysis of repeated data from the ECHO-COVID study
  • 2023
  • In: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 49:8, s. 946-956
  • Journal article (peer-reviewed)abstract
    • PurposeExploratory study to evaluate the association of different phenotypes of right ventricular (RV) involvement and mortality in the intensive care unit (ICU) in patients with acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19).MethodsPost-hoc analysis of longitudinal data from the multicenter ECHO-COVID observational study in ICU patients who underwent at least two echocardiography examinations. Echocardiography phenotypes were acute cor pulmonale (ACP, RV cavity dilatation with paradoxical septal motion), RV failure (RVF, RV cavity dilatation and systemic venous congestion), and RV dysfunction (tricuspid annular plane systolic excursion & LE; 16 mm). Accelerated failure time model and multistate model were used for analysis.ResultsOf 281 patients who underwent 948 echocardiography studies during ICU stay, 189 (67%) were found to have at least 1 type of RV involvements during one or several examinations: ACP (105/281, 37.4%), RVF (140/256, 54.7%) and/or RV dysfunction (74/255, 29%). Patients with all examinations displaying ACP had survival time shortened by 0.479 [0.284-0.803] times when compared to patients with all examinations depicting no ACP (P = 0.005). RVF showed a trend towards shortened survival time by a factor of 0.642 [0.405-1.018] (P = 0.059), whereas the impact of RV dysfunction on survival time was inconclusive (P = 0.451). Multistate analysis showed that patients might transit in and out of RV involvement, and those who exhibited ACP in their last critical care echocardiography (CCE) examination had the highest risk of mortality (hazard ratio (HR) 3.25 [2.38-4.45], P < 0.001).ConclusionRV involvement is prevalent in patients ventilated for COVID-19 ARDS. Different phenotypes of RV involvement might lead to different ICU mortality, with ACP having the worst outcome.
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  • Jansson, Saga, et al. (author)
  • Incidence of acute myocardial injury and its association with left and right ventricular systolic dysfunction in critically ill COVID-19 patients
  • 2022
  • In: Annals of Intensive Care. - Heidelberg, Germany : Springer. - 2110-5820. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Background: Previous studies have found an increase in cardiac troponins (cTns) and echocardiographic abnormalities in patients with COVID-19 and reported their association with poor clinical outcomes. Whether acute injury occurs during the course of critical care and if it is associated with cardiac function is unknown.The purpose of this study was to document the incidence of acute myocardial injury (AMInj) and echocardiographically defined left ventricular (LV) and right ventricular (RV) systolic dysfunction in consecutive patients admitted to an intensive care unit (ICU) for COVID-19. The relationship between AMInj and echocardiographic abnormalities during the first 14 days of ICU admission was studied. Finally, the association between echocardiographic findings, AMInj and clinical outcome was evaluated.Methods: Seventy-four consecutive patients (≥18 years) admitted to the ICU at Linköping University Hospital between 19 Mar 2020 and 31 Dec 2020 for COVID-19 were included. High-sensitivity troponin-T (hsTnT) was measured daily for up to 14 days. Transthoracic echocardiography was conducted within 72 h of ICU admission. Acute myocardial injury was defined as an increased hsTnT > 14ng/l and a > 20% absolute change with or without ischaemic symptoms. LV and RV systolic dysfunction was defined as at least 2 abnormal indicators of systolic function specified by consensus guidelines.Results: Increased hsTnT was observed in 59% of patients at ICU admission, and 82% developed AMInj with peak levels at 8 (3–13) days after ICU admission. AMInj was not statistically significantly associated with 30-day mortality but was associated with an increased duration of invasive mechanical ventilation (10 (3–13) vs. 5 days (0–9), p=0.001) as well as ICU length of stay (LOS) (19.5 (11–28) vs. 7 days (5–13), p=0.015). After adjustment for SAPS-3 and admission SOFA score, the effect of AMInj was significant only for the duration of mechanical ventilation (p=0.030).The incidence of LV and RV dysfunction was 28% and 22%, respectively. Only indices of LV and RV longitudinal contractility (mitral and tricuspid annular plane systolic excursion) were associated with AMInj. Echocardiographic parameters were not associated with clinical outcome.Conclusions: Myocardial injury is common in critically ill patients with COVID-19, with AMInj developing in more than 80% after ICU admission. In contrast, LV and RV dysfunction occurred in approximately one-quarter of patients. AMInj was associated with an increased need for mechanical ventilation and ICU LOS but neither AMInj nor ventricular dysfunction was significantly associated with mortality.
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  • Lipcsey, Miklós, et al. (author)
  • Endotoxin removal in septic shock with the Alteco LPS adsorber was safe but showed no benefit compared to placebo in the double-blind randomized controlled trial-the asset study
  • 2020
  • In: Shock. - : Ovid Technologies (Wolters Kluwer Health). - 1073-2322 .- 1540-0514. ; 54:2, s. 224-231
  • Journal article (peer-reviewed)abstract
    • Purpose: Lipopolysaccharides (LPS) are presumed to contribute to the inflammatory response in sepsis. We investigated if extracorporeal Alteco LPS Adsorber for LPS removal in early gram-negative septic shock was feasible and safe. Also, effects on endotoxin level, inflammatory response, and organ function were assessed.Methods: A pilot, double-blinded, randomized, Phase IIa, feasibility clinical investigation was undertaken in six Scandinavian intensive care units aiming to allocate 32 septic shock patients with abdominal or urogenital focus on LPS Adsorber therapy or a Sham Adsorber, therapy without active LPS binding. The study treatment was initiated within 12 h of inclusion and given for 6 h daily on first 2 days. LPS was measured in all patients.Results: The investigation was terminated after 527 days with eight patients included in the LPS Adsorber group and seven in the Sham group. Twenty-one adverse effects, judged not to be related to the device, were reported in three patients in the LPS Adsorber group and two in the Sham group. Two patients in the Sham group and no patients in the LPS Adsorber group died within 28 days. Plasma LPS levels were low without groups differences during or after adsorber therapy. The changes in inflammatory markers and organ function were similar in the groups.Conclusions: In a small cohort of patients with presumed gram-negative septic shock, levels of circulating endotoxin were low and no adverse effects within 28 days after LPS adsorber-treatment were observed. No benefit compared with a sham device was seen when using a LPS adsorber in addition to standard care.
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  • Lundquist, Hans, et al. (author)
  • The Olfactomedin-4-Defined Human Neutrophil Subsets Differ in Proteomic Profile in Healthy Individuals and Patients with Septic Shock
  • 2023
  • In: Journal of Innate Immunity. - : Karger. - 1662-811X .- 1662-8128. ; 15:1, s. 351-364
  • Journal article (peer-reviewed)abstract
    • The specific granule glycoprotein olfactomedin-4 (Olfm4) marks a subset (1-70%) of human neutrophils and the Olfm4-high (Olfm4-H) proportion has been found to correlate with septic shock severity. The aim of this study was to decipher proteomic differences between the subsets in healthy individuals, hypothesizing that Olfm4-H neutrophils have a proteomic profile distinct from that of Olfm4 low (Olfm4-L) neutrophils. We then extended the investigation to septic shock. A novel protocol for the preparation of fixed, antibody-stained, and sorted neutrophils for LC-MS/MS was developed. In healthy individuals, 39 proteins showed increased abundance in Olfm4-H, including the small GTPases Rab3d and Rab11a. In Olfm4-L, 52 proteins including neutrophil defensin alpha 4, CXCR1, Rab3a, and S100-A7 were more abundant. The data suggest differences in important neutrophil proteins that might impact immunological processes. However, in vitro experiments revealed no apparent difference in the ability to control bacteria nor produce oxygen radicals. In subsets isolated from patients with septic shock, 24 proteins including cytochrome b-245 chaperone 1 had significantly higher abundance in Olfm4-H and 30 in Olfm4-L, including Fc receptor proteins. There was no correlation between Olfm4-H proportion and septic shock severity, but plasma Olfm4 concentration was elevated in septic shock. Thus, the Olfm4-H and Olfm4-L neutrophils have different proteomic profiles, but there was no evident functional significance of the differences in septic shock.
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  • Mayo, Paul H., et al. (author)
  • Machines that save lives in the intensive care unit: the ultrasonography machine
  • 2022
  • In: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 1429-1438
  • Research review (peer-reviewed)abstract
    • This article highlights the ultrasonography machine as a machine that saves lives in the intensive care unit. We review its utility in the limited resource intensive care unit and some elements of machine design that are relevant to both the constrained operating environment and the well-resourced intensive care unit. As the ultrasonography machine can only save lives, if is operated by a competent intensivist; we discuss the challenges of training the frontline clinician to become competent in critical care ultrasonography followed by a review of research that supports its use.
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