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A number of studies performed in the operating room evaluated the hemodynamic effects of the fluid challenge (FC), solely considering the effect before and after the infusion. Few studies have investigated the pharmacodynamic effect of the FC on hemodynamic flow and pressure variables. We designed this trial aiming at describing the pharmacodynamic profile of two different FC infusion times, of a fixed dose of 4 ml kg-1. Forty-nine elective neurosurgical patients received two consecutive FCs of 4 ml kg-1 of crystalloids in 10 (FC10) or 20 (FC20) minutes, in a random order. Fluid responsiveness was defined as stroke volume index increase ≥ 10%. We assessed the net area under the curve (AUC), the maximal percentage difference from baseline (dmax), time when the dmax was observed (tmax), change from baseline at 1-min (d1) and 5-min (d5) after FC end. After FC10 and FC20, 25 (51%) and 14 (29%) of 49 patients were classified as fluid responders (p = 0.001). With the exception of the AUCs of SAP and MAP, the AUCs of all the considered hemodynamic variables were comparable. The dmax and the tmax were overall comparable. In both groups, the hemodynamic effects on flow variables were dissipated within 5 min after FC end. The infusion time of FC administration affects fluid responsiveness, being higher for FC10 as compared to FC20. The effect on flow variables of either FCs fades 5 min after the end of infusion.

Supplemental Digital Content is available in the text., OBJECTIVES: Critical care medicine is a natural environment for machine learning approaches to improve outcomes for critically ill patients as admissions to ICUs generate vast amounts of data. However, technical, legal, ethical, and privacy concerns have so far limited the critical care medicine community from making these data readily available. The Society of Critical Care Medicine and the European Society of Intensive Care Medicine have identified ICU patient data sharing as one of the priorities under their Joint Data Science Collaboration. To encourage ICUs worldwide to share their patient data responsibly, we now describe the development and release of Amsterdam University Medical Centers Database (AmsterdamUMCdb), the first freely available critical care database in full compliance with privacy laws from both the United States and Europe, as an example of the feasibility of sharing complex critical care data. SETTING: University hospital ICU. SUBJECTS: Data from ICU patients admitted between 2003 and 2016. INTERVENTIONS: We used a risk-based deidentification strategy to maintain data utility while preserving privacy. In addition, we implemented contractual and governance processes, and a communication strategy. Patient organizations, supporting hospitals, and experts on ethics and privacy audited these processes and the database. MEASUREMENTS AND MAIN RESULTS: AmsterdamUMCdb contains approximately 1 billion clinical data points from 23,106 admissions of 20,109 patients. The privacy audit concluded that reidentification is not reasonably likely, and AmsterdamUMCdb can therefore be considered as anonymous information, both in the context of the U.S. Health Insurance Portability and Accountability Act and the European General Data Protection Regulation. The ethics audit concluded that responsible data sharing imposes minimal burden, whereas the potential benefit is tremendous. CONCLUSIONS: Technical, legal, ethical, and privacy challenges related to responsible data sharing can be addressed using a multidisciplinary approach. A risk-based deidentification strategy, that complies with both U.S. and European privacy regulations, should be the preferred approach to releasing ICU patient data. This supports the shared Society of Critical Care Medicine and European Society of Intensive Care Medicine vision to improve critical care outcomes through scientific inquiry of vast and combined ICU datasets.

Background Survivors of severe COVID-19 are at risk of impaired health-related quality of life (HRQoL) and persistent physical and psychological disability after ICU and hospital discharge. The subsequent social burden is a major concern. We aimed to assess the short-term HRQoL, physical function and prevalence of post-traumatic stress symptoms of invasively mechanically ventilated COVID-19 patients treated in our ICU. Methods Prospective, observational cohort study in a follow-up clinic. Patients completed a 6-min walking test (6MWT) to assess their cardio-pulmonary function around 2 months (early follow-up) from hospital discharge, the EQ-5D-5L questionnaire for quality of life assessment around 2 months and at 6 months from hospital discharge and an anonymous web-based Impact of Event Scale-Revised (IES-R) questionnaire for Post-Traumatic Stress symptoms at 2 months. Results 47 patients attended our follow-up program, mean age 59 ± 10 years, median pre-morbid Clinical Frailty Scale (CFS) 2 [2–3]. The median distance walked in 6 min was 470 [406–516] m, 83 [67–99]% of the predicted value. Overall 1 out 3 patients and 4/18 (22%) among those with a good functional baseline prior to COVID-19 (CFS of 1 or 2) had lower (84%) than predicted 6MWT. EQ-5D-5L quality of life VAS was 80 [70–90] out of 100 at early follow-up with a slight improvement to 85 [77.5–90] at 6 months. Mobility, self-care and usual activities improved between the two timepoints, while pain/discomfort and depression/anxiety did not improve or got worse. The IES-R total score was greater than the threshold for concern of 1.6 in 27/41(66%) respondents. Conclusions Patients recovering from severe COVID-19 requiring invasive mechanical ventilation surviving hospital discharge present with early mild to moderate functional impairment, mildly reduced quality of life from hospital discharge with an overall improvement of mobility, self-care and the ability of performing usual activities, while a worsening of pain and depression/anxiety symptoms at 6 months and a large proportion of symptoms of post-traumatic distress soon after hospital discharge.

Objectives Joblessness is common in survivors from critical care. Our aim was to describe rates of return to work versus unemployment following coronavirus disease 2019 acute respiratory distress syndrome requiring intensive care admission. Design Single-center, prospective case series. Setting Critical Care Follow-Up Clinic, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. Patients One-hundred one consecutive laboratory-confirmed coronavirus disease 2019 patients were discharged from our hospital following an ICU stay between March 1, 2020, and June 30, 2020. Twenty-five died in the ICU. Seventy-six were discharged alive from hospital. Two patients refused participation, while three were unreachable. The remaining 71 were alive at 6 months and interviewed. Interventions Baseline and outcome healthcare data were extracted from the electronic patient records. Employment data were collected using a previously published structured interview instrument that included current and previous employment status, hours worked per week, and timing of return to work. Health-related quality of life status was assessed using the Italian EQ-5D-5L questionnaire. Measurements and main results Of the 71 interviewed patients, 45 (63%) were employed prior to coronavirus disease 2019, of which 40 (89%) of them worked full-time. Thirty-three (73%) of the previously employed survivors had returned to work by 6 months, 10 (22%) were unemployed, and 2 (5%) were newly retired. Among those who returned to work, 20 (85%) of them reported reduced effectiveness at work. Those who did not return to work were either still on sick leave or lost their job as a consequence of coronavirus disease 2019. Reported quality of life of survivors not returning to work was worse than of those returning to work. Conclusions The majority of coronavirus disease 2019 survivors following ICU in our cohort had returned to work by 6 months of follow-up. However, most of them reported reduced work effectiveness. Prolonged sick leave and unemployment were common findings in those not returning.

The Lombardy SARS-CoV-2 outbreak in February 2020 represented the beginning of COVID-19 epidemic in Italy. Hospitals were flooded by thousands of patients with bilateral pneumonia and severe respiratory, and vital sign derangements compared to the standard hospital population. We propose a new visual analysis technique using heat maps to describe the impact of COVID-19 epidemic on vital sign anomalies in hospitalized patients. We conducted an electronic health record study, including all confirmed COVID-19 patients hospitalized from February 21st, 2020 to April 21st, 2020 as cases, and all non-COVID-19 patients hospitalized in the same wards from January 1st, 2018 to December 31st, 2018. All data on temperature, peripheral oxygen saturation, respiratory rate, arterial blood pressure, and heart rate were retrieved. Derangement of vital signs was defined according to predefined thresholds. 470 COVID-19 patients and 9241 controls were included. Cases were older than controls, with a median age of 79 vs 76 years in non survivors (p =

BackgroundAppropriate perioperative fluid management is of pivotal importance to reduce postoperative complications, which impact on early and long-term patient outcome. The so-called perioperative goal-directed therapy (GDT) approach aims at customizing perioperative fluid management on the individual patients’ hemodynamic response. Whether or not the overall amount of perioperative volume infused in the context of GDT could influence postoperative surgical outcomes is unclear.MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of GDT approach between study population and control group in reducing postoperative complications and perioperative mortality, using MEDLINE, EMBASE and the Cochrane Controlled Clinical trials register. The enrolled studies were grouped considering the amount infused intraoperatively and during the first 24 h after the admission in the critical care unit (perioperative fluid).ResultsThe metanalysis included 21 RCTs enrolling 2729 patients with a median amount of perioperative fluid infusion of 4500 ml. In the studies reporting an overall amount below or above this threshold, the differences in postoperative complications were not statically significant between controls and GDT subgroup [43.4% vs. 34.2%,pvalue = 0.23 and 54.8% vs. 39.8%;pvalue = 0.09, respectively].Overall, GDT reduced the overall rate of postoperative complications, as compared to controls [pooled risk difference (95% CI) = − 0.10 (− 0.14, − 0.07); Chi2 = 30.97;pvalue pvalue = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal (pvalue = 0.52) nor cardiovascular (pvalue = 0.86) or pulmonary (pvalue = 0.14) or neurological (pvalue = 0.44) or infective (pvalue = 0.12) complications.ConclusionsIrrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality.Trial RegistrationCRD42020168866; Registration: February 2020https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=168866

The current coronavirus pandemic has impacted heavily on ICUs worldwide. Although many hospitals and healthcare systems had plans in place to manage multiple casualties as a result of major natural disasters or accidents, there was insufficient preparation for the sudden, massive influx of severely ill patients with COVID-19. As a result, systems and staff were placed under immense pressure as everyone tried to optimize patient management. As the pandemic continues, we must apply what we have learned about our response, both good and bad, to improve organization and thus patient care in the future., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. Methods: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. Findings: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33–52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25–43]; p

The diffusion of electronic health records collecting large amount of clinical, monitoring, and laboratory data produced by intensive care units (ICUs) is the natural terrain for the application of artificial intelligence (AI). AI has a broad definition, encompassing computer vision, natural language processing, and machine learning, with the latter being more commonly employed in the ICUs. Machine learning may be divided in supervised learning models (i.e., support vector machine [SVM] and random forest), unsupervised models (i.e., neural networks [NN]), and reinforcement learning. Supervised models require labeled data that is data mapped by human judgment against predefined categories. Unsupervised models, on the contrary, can be used to obtain reliable predictions even without labeled data. Machine learning models have been used in ICU to predict pathologies such as acute kidney injury, detect symptoms, including delirium, and propose therapeutic actions (vasopressors and fluids in sepsis). In the future, AI will be increasingly used in ICU, due to the increasing quality and quantity of available data. Accordingly, the ICU team will benefit from models with high accuracy that will be used for both research purposes and clinical practice. These models will be also the foundation of future decision support system (DSS), which will help the ICU team to visualize and analyze huge amounts of information. We plea for the creation of a standardization of a core group of data between different electronic health record systems, using a common dictionary for data labeling, which could greatly simplify sharing and merging of data from different centers.

Background The COVID-19 pandemic has resulted in an unprecedented healthcare crisis with a high prevalence of psychological distress in healthcare providers. We sought to document the prevalence of burnout syndrome amongst intensivists facing the COVID-19 outbreak. Methods Cross-sectional survey among intensivists part of the European Society of Intensive Care Medicine. Symptoms of severe burnout, anxiety and depression were collected. Factors independently associated with severe burnout were assessed using Cox model. Results Response rate was 20% (1001 completed questionnaires were returned, 45 years [39–53], 34% women, from 85 countries, 12 regions, 50% university-affiliated hospitals). The prevalence of symptoms of anxiety and depression or severe burnout was 46.5%, 30.2%, and 51%, respectively, and varied significantly across regions. Rating of the relationship between intensivists and other ICU stakeholders differed significantly according to the presence of anxiety, depression, or burnout. Similar figures were reported for their rating of the ethical climate or the quality of the decision-making. Factors independently associated with anxiety were female gender (HR 1.85 [1.33–2.55]), working in a university-affiliated hospital (HR 0.58 [0.42–0.80]), living in a city of > 1 million inhabitants (HR 1.40 [1.01–1.94]), and clinician’s rating of the ethical climate (HR 0.83 [0.77–0.90]). Independent determinants of depression included female gender (HR 1.63 [1.15–2.31]) and clinician’s rating of the ethical climate (HR 0.84 [0.78–0.92]). Factors independently associated with symptoms of severe burnout included age (HR 0.98/year [0.97–0.99]) and clinician’s rating of the ethical climate (HR 0.76 [0.69–0.82]). Conclusions The COVID-19 pandemic has had an overwhelming psychological impact on intensivists. Follow-up, and management are warranted to assess long-term psychological outcomes and alleviate the psychological burden of the pandemic on frontline personnel.

Mortality after liver surgery reduced during the last three decades to less than 2%, but post-operative morbidity occurs in 20–50% of cases. Patients are often considered eligible for post-operative intensive-care unit (ICU) admission. Predicting which patients that are at higher risk could lead to a more precise perioperative management. We investigated whether renal resistive index (RRI), alone or along with other items, can predict post-operative complication after hepatic resection. All consecutive patients undergoing hepatectomy for primary or metastatic neoplasm at our Institution between February 2015 and March 2017 were enrolled. They received RRI measurement before entering in operative room and after awakening from general anesthesia. 183 Patients were enrolled. High surgical invasiveness, surgery time > 360 min, pre-operative RRI and postoperative serum lactate clearance

Postoperative C-reactive protein (CRP) level allows to rule out infectious complications ensuring safe hospital discharge in colorectal cancer surgery. Since its clinical significance in Crohn’s disease (CD) has not been studied yet, we investigated whether CRP can guide decision-making on hospital discharge in this population. Only consecutive CD patients undergoing resections with primary anastomosis and without covering stoma (2013–2017) were analysed. Pre- and post-operative CRP values, measured daily until discharge, were correlated with postoperative complications including anastomotic leakage (AL), infectious and non-infectious complications. The diagnostic accuracy of CRP in predicting AL was evaluated according to the area under the curve (AUC), using the receiver-operating characteristic (ROC) methodology. Two-hundred and fifty-one consecutive patients undergoing elective surgery for CD were selected. AL was diagnosed in 10 patients (4%). High CRP level was associated with AL on postoperative day (POD) 3–5 (p = 0.002, AUC 0.825) with a positive predictive value of 60%. CRP linear difference of 140 between POD 1 and 3 (AUC 0.800) maximizes sensitivity and specificity with a NPV of 98.6%. CRP trend, measured with the linear difference between POD 1 and 3, is able to rule out anastomotic complications with a high NPV and may allow a safe early hospital discharge after surgery for CD.

The first person-to-person transmission of the 2019 novel coronavirus in Italy on 21 February 2020 led to an infection chain that represents one of the largest known COVID-19 outbreaks outside Asia. In northern Italy in particular, we rapidly experienced a critical care crisis due to a shortage of intensive care beds, as we expected according to data reported in China. Based on our experience of managing this surge, we produced this review to support other healthcare services in preparedness and training of hospitals during the current coronavirus outbreak. We had a dedicated task force that identified a response plan, which included: (1) establishment of dedicated, cohorted intensive care units for COVID-19-positive patients; (2) design of appropriate procedures for pre-triage, diagnosis and isolation of suspected and confirmed cases; and (3) training of all staff to work in the dedicated intensive care unit, in personal protective equipment usage and patient management. Hospital multidisciplinary and departmental collaboration was needed to work on all principles of surge capacity, including: space definition; supplies provision; staff recruitment; and ad hoc training. Dedicated protocols were applied where full isolation of spaces, staff and patients was implemented. Opening the unit and the whole hospital emergency process required the multidisciplinary, multi-level involvement of healthcare providers and hospital managers all working towards a common goal: patient care and hospital safety. Hospitals should be prepared to face severe disruptions to their routine and it is very likely that protocols and procedures might require re-discussion and updating on a daily basis.

Background Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19. Methods We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020–10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC). Results We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%–11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 h of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients. Conclusions The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients., Highlights • COVID-19 is characterized by coagulation activation and endothelial dysfunction. Few data are available on thromboembolic complications. • We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020). • Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission. • Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications. • There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

PURPOSE OF REVIEW The availability of large datasets and computational power has prompted a revolution in Intensive Care. Data represent a great opportunity for clinical practice, benchmarking, and research. Machine learning algorithms can help predict events in a way the human brain can simply not process. This possibility comes with benefits and risks for the clinician, as finding associations does not mean proving causality. RECENT FINDINGS Current applications of Data Science still focus on data documentation and visualization, and on basic rules to identify critical lab values. Recently, algorithms have been put in place for prediction of outcomes such as length of stay, mortality, and development of complications. These results have begun being implemented for more efficient allocation of resources and in benchmarking processes, to allow identification of successful practices and margins for improvement. In parallel, machine learning models are increasingly being applied in research to expand medical knowledge. SUMMARY Data have always been part of the work of intensivists, but the current availability has not been completely exploited. The intensive care community has to embrace and guide the data science revolution in order to decline it in favor of patients' care.

Objective To develop evidence-based clinical practice recommendations regarding transfusion practices in non-bleeding, critically ill adults. Design A task force involving 13 international experts and three methodologists used the GRADE approach for guideline development. Methods The task force identified four main topics: red blood cell transfusion thresholds, red blood cell transfusion avoidance strategies, platelet transfusion, and plasma transfusion. The panel developed structured guideline questions using population, intervention, comparison, and outcomes (PICO) format. Results The task force generated 16 clinical practice recommendations (3 strong recommendations, 13 conditional recommendations), and identified five PICOs with insufficient evidence to make any recommendation. Conclusions This clinical practice guideline provides evidence-based recommendations and identifies areas where further research is needed regarding transfusion practices and transfusion avoidance in non-bleeding, critically ill adults. Electronic supplementary material The online version of this article (10.1007/s00134-019-05884-8) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text., Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. Methods: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. Results: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. Conclusion: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

BACKGROUND Tracheostomy is performed in patients expected to require prolonged mechanical ventilation, but to date optimal timing of tracheostomy has not been established. The evidence concerning tracheostomy in COVID-19 patients is particularly scarce. We aimed to describe the relationship between early tracheostomy (���10 days since intubation) and outcomes for patients with COVID-19. METHODS This was a prospective cohort study performed in 152 centres across 16 European countries from February to December 2020. We included patients aged ���70 yr with confirmed COVID-19 infection admitted to an intensive care unit, requiring invasive mechanical ventilation. Multivariable analyses were performed to evaluate the association between early tracheostomy and clinical outcomes including 3-month mortality, intensive care length of stay, and duration of mechanical ventilation. RESULTS The final analysis included 1740 patients with a mean age of 74 yr. Tracheostomy was performed in 461 (26.5%) patients. The tracheostomy rate varied across countries, from 8.3% to 52.9%. Early tracheostomy was performed in 135 (29.3%) patients. There was no difference in 3-month mortality between early and late tracheostomy in either our primary analysis (hazard ratio [HR]=0.96; 95% confidence interval [CI], 0.70-1.33) or a secondary landmark analysis (HR=0.78; 95% CI, 0.57-1.06). CONCLUSIONS There is a wide variation across Europe in the timing of tracheostomy for critically ill patients with COVID-19. However, we found no evidence that early tracheostomy is associated with any effect on survival amongst older critically ill patients with COVID-19. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov NCT04321265.

Background\ud Sepsis poses a global threat to millions of lives. The Surviving Sepsis Campaign (SSC) guidelines provide evidence-based recommendations on the recognition and management of sepsis and its complications.\ud Methods\ud We formed a panel of 60 experts from 22 countries and 11 members of the public. The panel prioritized questions that are relevant to the recognition and management of sepsis and septic shock in adults. New questions and sections were addressed, relative to the previous guidelines. These questions were grouped under 6 subgroups (screening and early treatment, infection, hemodynamics, ventilation, additional therapies, and long-term outcomes and goals of care). With input from the panel and methodologists, professional medical librarians performed the search strategy tailored to either specific questions or a group of relevant questions. A dedicated systematic review team performed screening and data abstraction when indicated. For each question, the methodologists, with input from panel members, summarized the evidence assessed and graded the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. The panel generated recommendations using the evidence-to-decision framework. Recommendations were either strong or weak, or in the form of best practice statements. When evidence was insufficient to support a recommendation, the panel was surveyed to generate “in our practice” statements.\ud Results\ud The SSC panel issued 93 statements: 15 best practice statements, 15 strong recommendations, and 54 weak recommendations and no recommendation was provided for 9 questions. The recommendations address several important clinical areas related to screening tools, acute resuscitation strategies, management of fluids and vasoactive agents, antimicrobials and diagnostic tests and the use of additional therapies, ventilation management, goals of care, and post sepsis care.\ud Conclusion\ud The SSC panel issued evidence-based recommendations to help support key stakeholders caring for adults with sepsis or septic shock and their families.

More than a year after the onset of the SARS-Cov-2 pandemic, treating patients with COVID-19 remains a challenge. By contrast to the rapid development of effective vaccines against SARS-Cov-2, the development of specific and effective therapeutics against COVID-19 remains largely unresolved., This secondary analysis of the COVIP study shows a higher 30-day-mortality in critically ill elderly COVID-19 patients who received steroids as part of their treatment.

Background International guidelines suggest using a higher (>10 cmH2O) positive end-expiratory pressure (PEEP) in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) due to the novel coronavirus disease (COVID-19). However, even if oxygenation generally improves with a higher PEEP, compliance and arterial carbon dioxide tension (PaCO2) frequently do not, as if recruitment was small. Research question Is the potential for lung recruitment small in patients with early ARDS due to COVID-19? Study design and methods Forty patients with ARDS due to COVID-19 were studied in the supine position within three days of endotracheal intubation. They all underwent a PEEP trial, where oxygenation, compliance, and PaCO2 were measured with 5, 10, and 15 cmH2O of PEEP and all other ventilatory settings unchanged. Twenty underwent a whole-lung static computed tomography at 5 and 45 cmH2O, and the other twenty at 5 and 15 cmH2O of airway pressure. Recruitment and hyperinflation were defined as a decrease in the volume of the non-aerated (density above -100 HU) and an increase in the volume of the over-aerated (density below -900 HU) lung compartments, respectively. Results From 5 to 15 cmH2O, oxygenation improved in thirty-six (90%) patients but compliance only in eleven (28%) and PaCO2 only in fourteen (35%). From 5 to 45 cmH2O, recruitment was 351 (161-462) ml and hyperinflation 465 (220-681) ml. From 5 to 15 cmH2O, recruitment was 168 (110-202) ml and hyperinflation 121 (63-270) ml. Hyperinflation variably developed in all patients and exceeded recruitment in more than half of them. Interpretation Patients with early ARDS due to COVID-19, ventilated in the supine position, present with a large potential for lung recruitment. Even so, their compliance and PaCO2 do not generally improve with a higher PEEP, possibly due to hyperinflation.

BackgroundQuantitative CT (QCT) analysis is an invaluable diagnostic tool to assess lung injury and predict prognosis of patients affected by COVID-19 pneumonia. PTX3 was recently described as one of the most reliable serological predictors of clinical deterioration and short-term mortality. The present study was designed to evaluate a correlation between serological biomarkers of inflammation and lung injury measured by QCT.MethodsThis retrospective monocentric study analysed a cohort of patients diagnosed with COVID-19 and admitted because of respiratory failure, or significant radiological involvement on chest CT scan. All patients, males and non-pregnant females older than 18 years, underwent chest CT scan and laboratory testing at admission. Exclusion criteria were defined by concurrent acute pathological processes and ongoing specific treatments which could interfere with immune activity. The cohort was stratified based on severity in mild and severe forms. Compromised lung at QCT was then correlated to serological biomarkers representative of SARS-CoV-2. We further developed a multivariable logistic model to predict CT data and clinical deterioration based on a specific molecular signature. Internal cross-validation led to evaluate discrimination, calibration, and clinical utility of the tool that was provided by a score to simplify its application.Findings592 patients were recruited between March 19th and December 1st, 2020. Applying exclusion criteria which consider confounders, the cohort resulted in 366 individuals characterized by 177 mild and 189 severe forms. In our predictive model, blood levels of PTX3, CRP and LDH were found to correlate with QCT values in mild COVID-19 disease. A signature of these three biomarkers had a high predictive accuracy in detecting compromised lungs as assessed by QCT. The score was elaborated and resulted representative of lung CT damage leading to clinical deterioration and oxygen need in mild disease.InterpretationThe LDH, PTX3, CRP blood signature can serve as a strong correlate of compromised lung in COVID-19, possibly integrating cellular damage, systemic inflammation, myeloid and endothelial cell activation.FundingThis work was supported by a philanthropic donation by Dolce & Gabbana fashion house (to A.M., C.G.) and by a grant from Italian Ministry of Health for COVID-19 (to A.M. and C.G.).Research in contextEvidence before this studyBesides nasopharyngeal swab and serological test, chest CT scan represents one of the most useful tools to confirm COVID-19 diagnosis; moreover, QCT has been demonstrated to foresee oxygen need as well as deterioration of health status. Several clinical and serological parameters have been studied alone or combined in scores to be applied as prognostic tools of SARS-CoV-2 pneumonia; however, no one has yet reached the everyday practice. Recently, our group has investigated the expression and clinical significance of PTX3 in COVID-19 demonstrating the correlation with short-term mortality independently of confounders. The result was confirmed by other studies in different settings increasing evidence of PTX3 as a strong biomarker of severity; noteworthy, a recent report analysed proteomic data with a machine learning approach identifying age with PTX3 or SARS-CoV-2 RNAemia as the best binary signatures associated to 28-days mortality.Added value of this studyThe present study was designed to investigate associations between markers of damage and the CT extension of SARS-CoV-2 pneumonia in order to provide a biological footprint of radiological results in paucisymptomatic patients. QCT data were considered in a binary form identifying a threshold relevant for clinical deterioration, as already proved by literature. Our findings demonstrate a significant correlation with three peripheral blood proteins (PTX3, LDH and CRP) which result representative of COVID-19 severity. The study presents a predictive model of radiological lung involvement which performs with a high level of accuracy (cvAUC of 0·794±0·107; CI 95%: 0·74–0·87) and a simple score was provided to simplify the interpretation of the three biomarkers. Besides additional finding on PTX3 role in SARS-CoV2 pathology, its prognostic value was confirmed by data on clinical deterioration; indeed, paucisymptomatic subjects showed a 11·9% deaths. The model offers the possibility to quickly assess patients resulted positive for SARS-CoV-2 and estimate people at risk of deterioration despite normal clinical and blood gases analysis, with potential to identify those who need better clinical monitoring and interventions.Implications of all the available evidencePredicting the extension, severity, and clinical deterioration in COVID-19 patients its pivotal to allocate enough resources in emergency and to avoid health system burden. Despite the urgent clinical need of biomarkers, SARS-CoV-2 pneumonia still lacks something able to provide an easy measure of its severity. Some multiparametric scores have been proposed for severe COVID-19 and rely on deep assessment of patients status (clinical, serological, and radiological data). Our model represents an unprecedented effort to provide a tool which could predict CT pneumonia extension, oxygen requirement and clinical deterioration in mild COVID-19. Based on the measurement of three proteins on peripheral blood, this score could improve early assessment of asymptomatic patients tested positive by SARS-CoV2 specifically in first level hospitals as well in developing countries.

Background Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear. Objective To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function. Design Prospective cohort study. Setting 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019. Subjects Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2. Methods Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients’ characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected. Results Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09–1.25, P 4): HR, 1.34 (95% CI, 1.18–1.51, P Conclusions There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.

BACKGROUND COVID-19 patients developing the acute respiratory distress syndrome (ARDS) show increased production of pro-inflammatory cytokines, including interleukin-6 (IL-6). The use of humanized monoclonal antibody against interleukin-6 receptor (IL-6R) may represent a potential treatment strategy. We analyzed the effects of compassionate use of tocilizumab and sarilumab on clinical outcome of patients affected by ARDS due COVID-19. METHODS This single-center, observational, exploratory study was performed during the acute phase of COVID-19 outbreak, between March 7th and April 21st, 2020 in a University Hospital in Rome, Italy. All consecutive adult patients admitted to the intensive care unit with laboratory-confirmed COVID-19 and fulfilling ARDS criteria were enrolled. Patients who were treated with anti-IL-6R therapy were compared to those who were not, as per clinical decision. Inverse probability weights were applied to weight individual's contribution to survival curves and in the multivariate regression model. RESULTS Among 105 ARDS patients, 65 received compassionate treatment with anti-IL-6R therapy (43 [66%] Tocilizumab [Hoffmann-La Roche, Basel, Switzerland] and 22 [34%] Sarilumab, respectively], with oxygenation improvement. In the multivariable Cox proportional regression hazards model with propensity score inverse probability weighting, patients who received anti-IL-6R treatment had lower risk of death compared to those who did not, with a hazard ration of 0.34 [95% confidence interval 0.17-0.74], P=0.001. CONCLUSIONS Our data suggested that immune modulator therapy based on anti-human IL-6 receptor monoclonal antibodies might lead to improved outcome in patients with ARDS due to COVID-19. These data support the need for confirmatory randomized trials to assess the effect of immune modulator therapies on mortality.

Background Fluid boluses are administered to septic shock patients with the purpose of increasing cardiac output as a means to restore tissue perfusion. Unfortunately, fluid therapy has a narrow therapeutic index, and therefore, several approaches to increase safety have been proposed. Fluid responsiveness (FR) assessment might predict which patients will effectively increase cardiac output after a fluid bolus (FR+), thus preventing potentially harmful fluid administration in non-fluid responsive (FR−) patients. However, there are scarce data on the impact of assessing FR on major outcomes. The recent ANDROMEDA-SHOCK trial included systematic per-protocol assessment of FR. We performed a post hoc analysis of the study dataset with the aim of exploring the relationship between FR status at baseline, attainment of specific targets, and clinically relevant outcomes. Methods ANDROMEDA-SHOCK compared the effect of peripheral perfusion- vs. lactate-targeted resuscitation on 28-day mortality. FR was assessed before each fluid bolus and periodically thereafter. FR+ and FR− subgroups, independent of the original randomization, were compared for fluid administration, achievement of resuscitation targets, vasoactive agents use, and major outcomes such as organ dysfunction and support, length of stay, and 28-day mortality. Results FR could be determined in 348 patients at baseline. Two hundred and forty-two patients (70%) were categorized as fluid responders. Both groups achieved comparable successful resuscitation targets, although non-fluid responders received less resuscitation fluids (0 [0–500] vs. 1500 [1000–2500] mL; p 0.0001), exhibited less positive fluid balances, but received more vasopressor testing. No difference in clinically relevant outcomes between FR+ and FR− patients was found, including 24-h SOFA score (9 [5–12] vs. 8 [5–11], p = 0.4), need for MV (78% vs. 72%, p = 0.16), need for RRT (18% vs. 21%, p = 0.7), ICU-LOS (6 [3–11] vs. 6 [3–16] days, p = 0.2), and 28-day mortality (40% vs. 36%, p = 0.5). Only thirteen patients remained fluid responsive along the intervention period. Conclusions Systematic assessment allowed determination of fluid responsiveness status in more than 80% of patients with early septic shock. Fluid boluses could be stopped in non-fluid responsive patients without any negative impact on clinical relevant outcomes. Our results suggest that fluid resuscitation might be safely guided by FR assessment in septic shock patients. Trial registration ClinicalTrials.gov identifier, NCT03078712. Registered retrospectively on March 13, 2017.

Background Pulse pressure variation (PPV) and stroke volume variation (SVV) do not predict fluid responsiveness when using a protective ventilation strategy: the use of functional haemodynamic tests can be useful to overcome this limitation. Objectives We tested the use of a tidal volume challenge (VTC), during 6 ml kg [predicted body weight (PBW)] ventilation, and the end-expiratory occlusion test (EEOT) for prediction of fluid responsiveness. Design An interventional prospective study. Setting Supine elective neurosurgical patients. Interventions The study protocol was, first, the initial EEOT test was performed during baseline 6 ml kg PBW ventilation; second, VTC was performed by increasing the VT up to 8 ml kg PBW and PPV and SVV changes were recorded after 1 min; third, a second EEOT was performed during 8 ml kg PBW ventilation; and VT was reduced back to 6 ml kg PBW and a third EEOT was performed. Finally, a 250 ml fluid challenge was administered over 10 min to identify fluid responders (increase in stroke volume index ≥10%). Results In the 40 patients analysed, PPV and SVV values at baseline and EEOT performed at 6 ml kg PBW did not predict fluid responsiveness. A 13.3% increase in PPV after VTC predicted fluid responsiveness with a sensitivity of 94.7% and a specificity of 76.1%, while a 12.1% increase in SVV after VTC predicted fluid responsiveness with a sensitivity of 78.9% and a specificity of 95.2%. After EEOT performed at 8 ml kg PBW, a 3.6% increase in cardiac index predicted fluid responsiveness with a sensitivity of 89.4% and a specificity of 85.7%, while a 4.7% increase in stroke volume index (SVI) with a sensitivity of 89.4% and a specificity of 85.7%. Conclusion The changes in PPV and SVV obtained after VTC are reliable and comparable to the changes in CI and SVI obtained after EEOT performed at 8 ml kg PBW in predicting fluid responsiveness in neurosurgical patients. Trial registration ACTRN12618000351213.

The monitoring and optimization of cardiac output (CO) are central components of perioperative hemodynamic management in patients undergoing cardiothoracic surgery. Until recently, echocardiography and invasive indicator dilution methods have been the mainstays of CO monitoring in these patients. However, completely noninvasive methods to estimate CO have become available during recent years. In this review, the physical measurement principles, limitations, and measurement performance of the different techniques for continuous noninvasive CO estimation in the setting of cardiothoracic surgery are described. Methods to estimate CO in a completely noninvasive manner include noninvasive pulse wave analysis (using a finger cuff method or automated radial artery applanation tonometry), thoracic electrical bioimpedance and bioreactance, pulse wave transit time, and partial carbon dioxide rebreathing. All these technologies have been evaluated in cardiothoracic surgery patients, but the validation studies describing the measurement performance in comparison with invasive reference methods have shown inconsistent and, in part, contradictory results. In addition, all technologies have major limitations with regard to the applicability during routine clinical care in the operating room or the intensive care unit. Therefore, the methods for noninvasive CO estimation described in this review still require technological improvements with regard to measurement performance and clinical applicability before they can be recommended for routine perioperative hemodynamic management of cardiothoracic surgery patients outside of studies.

Background Perioperative arterial blood pressure management is a physiologically complex challenge influenced by multiple factors. Methods A multidisciplinary, international working subgroup of the Third Perioperative Quality Initiative (POQI) consensus meeting reviewed the (patho)physiology and measurement of arterial pressure as applied to perioperative medicine. We addressed predefined questions by undertaking a modified Delphi analysis, in which primary clinical research and review articles were identified using MEDLINE. Strength of recommendations, where applicable, were graded by National Institute for Health and Care Excellence (NICE) guidelines. Results Multiple physiological factors contribute to the perioperative physiological importance of arterial pressure: (i) arterial pressure is the input pressure to organ blood flow, but is not the sole determinant of perfusion pressure; (ii) blood flow is often independent of changes in perfusion pressure because of autoregulatory changes in vascular resistance; (iii) microvascular dysfunction uncouples microvascular blood flow from arterial pressure (haemodynamic incoherence). From a practical clinical perspective, we identified that: (i) ambulatory measurement is the optimal method to establish baseline arterial pressure; (ii) automated and invasive arterial pressure measurements have inherent physiological and technical limitations; (iii) individualised arterial pressure targets may change over time, especially in the perioperative period. There remains a need for research in non-invasive, continuous arterial pressure measurements, macro- and micro-circulatory control, regional perfusion pressure measurement, and the development of sensitive, specific, and continuous measures of cellular function to evaluate blood pressure management in a physiologically coherent manner. Conclusion The multivariable, complex physiology contributing to dynamic changes in perioperative arterial pressure may be underappreciated clinically. The frequently unrecognised dissociation between arterial pressure, organ blood flow, and microvascular and cellular function requires further research to develop a more refined, contextualised clinical approach to this routine perioperative measurement.

Background A multidisciplinary international working subgroup of the third Perioperative Quality Initiative consensus meeting appraised the evidence on the influence of preoperative arterial blood pressure and community cardiovascular medications on perioperative risk. Methods A modified Delphi technique was used, evaluating papers published in MEDLINE on associations between preoperative numerical arterial pressure values or cardiovascular medications and perioperative outcomes. The strength of the recommendations was graded by National Institute for Health and Care Excellence guidelines. Results Significant heterogeneity in study design, including arterial pressure measures and perioperative outcomes, hampered the comparison of studies. Nonetheless, consensus recommendations were that (i) preoperative arterial pressure measures may be used to define targets for perioperative management; (ii) elective surgery should not be cancelled based solely upon a preoperative arterial pressure value; (iii) there is insufficient evidence to support lowering arterial pressure in the immediate preoperative period to minimise perioperative risk; and (iv) there is insufficient evidence that any one measure of arterial pressure (systolic, diastolic, mean, or pulse) is better than any other for risk prediction of adverse perioperative events. Conclusions Future research should define which preoperative arterial pressure values best correlate with adverse outcomes, and whether modifying arterial pressure in the preoperative setting will change the perioperative morbidity or mortality. Additional research should define optimum strategies for continuation or discontinuation of preoperative cardiovascular medications.

The aim of this study was to quantify the impact of different cardiovascular factors on left ventricular ejection fraction (LVEF) and test a novel LVEF calculation considering these factors. 10 pigs were studied. The experimental protocol consisted of sequentially changing afterload, preload and contractility. LV pressure–volume (PV) loops and peripheral arterial pressure were obtained before and after each intervention. LVEF was calculated as stroke volume (SV)/end-diastolic volume (EDV). We studied global cardiac function variables: LV end-systolic elastance (Ees), effective arterial elastance (Ea), end-diastolic volume and heart rate. Diastolic function was evaluated by means of the ventricular relaxation time (τ) and ventricular stiffness constant (β) obtained from the end-diastolic PV relationship. Ventriculo-arterial coupling (VAC), an index of cardiovascular performance, was calculated as Ea/Ees. LV mechanical efficiency (LVeff) was calculated as the ratio of stroke work to LV pressure–volume area. A linear mixed model was used to determine the impact of cardiac factors (Ees, Ea, EDV and heart rate), VAC and LVeff on LVEF during all experimental conditions. LVEF was mainly related to Ees and Ea. There was a strong relationship between LVEF and both VAC and LVeff (r2 = 0.69 and r2 = 0.94, respectively). The relationship between LVEF and Ees was good (r2 = 0.43). Adjusting LVEF to afterload ( $${\text{LVEF}}_{\rm EA} = {\text{EF}} \times \sqrt {\text{Ea}}$$ ) performed better for estimating Ees (r2 = 0.75) and improved the tracking of LV contractility changes, even when a peripheral Ea was used as surrogate (Ea = radial MAP/SV; r2 = 0.73). LVEF was mainly affected by contractility and afterload changes and was strongly related to VAC and LVeff. An adjustment to LVEF that considers the impact of afterload provided a better assessment of LV contractility.

During the COVID-19 pandemic, a shortage of mechanical ventilators was reported and ventilator sharing between patients was proposed as an ultimate solution. Two lung simulators were ventilated by one anesthesia machine connected through two respiratory circuits and T-pieces. Five different combinations of compliances (30–50 mL × cmH2O−1) and resistances (5–20 cmH2O × L−1 × s−1) were tested. The ventilation setting was: pressure-controlled ventilation, positive end-expiratory pressure 15 cmH2O, inspiratory pressure 10 cmH2O, respiratory rate 20 bpm. Pressures and flows from all the circuit sections have been recorded and analyzed. Simulated patients with equal compliance and resistance received similar ventilation. Compliance reduction from 50 to 30 mL × cmH2O−1 decreased the tidal volume (VT) by 32% (418 ± 49 vs. 285 ± 17 mL). The resistance increase from 5 to 20 cmH2O × L−1 × s−1 decreased VT by 22% (425 ± 69 vs. 331 ± 51 mL). The maximal alveolar pressure was lower at higher compliance and resistance values and decreased linearly with the time constant (r² = 0.80, p &lt, 0.001). The minimum alveolar pressure ranged from 15.5 ± 0.04 to 16.57 ± 0.04 cmH2O. Cross-flows between the simulated patients have been recorded in all the tested combinations, during both the inspiratory and expiratory phases. The simultaneous ventilation of two patients with one ventilator may be unable to match individual patient’s needs and has a high risk of cross-interference.

Background Postoperative complications impact on early and long-term patients’ outcome. Appropriate perioperative fluid management is pivotal in this context; however, the most effective perioperative fluid management is still unclear. The enhanced recovery after surgery pathways recommend a perioperative zero-balance, whereas recent findings suggest a more liberal approach could be beneficial. We conducted this trial to address the impact of restrictive vs. liberal fluid approaches on overall postoperative complications and mortality. Methods Systematic review and meta-analysis, including randomised controlled trials (RCTs). We performed a systematic literature search using MEDLINE (via Ovid), EMBASE (via Ovid) and the Cochrane Controlled Clinical trials register databases, published from 1 January 2000 to 31 December 2019. We included RCTs enrolling adult patients undergoing elective abdominal surgery and comparing the use of restrictive/liberal approaches enrolling at least 15 patients in each subgroup. Studies involving cardiac, non-elective surgery, paediatric or obstetric surgeries were excluded. Results After full-text examination, the metanalysis finally included 18 studies and 5567 patients randomised to restrictive (2786 patients; 50.0%) or liberal approaches (2780 patients; 50.0%). We found no difference in the occurrence of severe postoperative complications between restrictive and liberal subgroups [risk difference (95% CI) = 0.009 (− 0.02; 0.04); p value = 0.62; I2 (95% CI) = 38.6% (0–66.9%)]. This result was confirmed also in the subgroup of five studies having a low overall risk of bias. The liberal approach was associated with lower overall renal major events, as compared to the restrictive [risk difference (95% CI) = 0.06 (0.02–0.09); p value = 0.001]. We found no difference in either early (p value = 0.33) or late (p value = 0.22) postoperative mortality between restrictive and liberal subgroups Conclusions In major abdominal elective surgery perioperative, the choice between liberal or restrictive approach did not affect overall major postoperative complications or mortality. In a subgroup analysis, a liberal as compared to a restrictive perioperative fluid policy was associated with lower overall complication renal major events, as compared to the restrictive. Trial Registration CRD42020218059; Registration: February 2020, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=218059.

This is the twelfth version (eleventh update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline.What is the role of drugs in the treatment of patients with covid-19?The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and under way. The emerging SARS-CoV-2 variants (such as omicron) and subvariants are also changing the role of therapeutics. This update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers, and janus kinase (JAK) inhibitors in patients with severe or critical covid-19, and modifies previous recommendations for the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe covid-19.• Remdesivir: a conditional recommendation for its use in patients with severe covid-19; and a conditional recommendation against its use in patients with critical covid-19. • Concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab) and the JAK inhibitor baricitinib: these drugs may now be combined, in addition to corticosteroids, in patients with severe or critical covid-19. • Sotrovimab and casirivimab-imdevimab: strong recommendations against their use in patients with covid-19, replacing the previous conditional recommendations for their use.When moving from new evidence to updated recommendations, the Guideline Development Group (GDG) considered a combination of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. For remdesivir, new trial data were added to a previous subgroup analysis and provided sufficiently trustworthy evidence to demonstrate benefits in patients with severe covid-19, but not critical covid-19. The GDG considered benefits of remdesivir to be modest and of moderate certainty for key outcomes such as mortality and mechanical ventilation, resulting in a conditional recommendation. For baricitinib, the GDG considered clinical trial evidence (RECOVERY) demonstrating reduced risk of death in patients already receiving corticosteroids and IL-6 receptor blockers. The GDG acknowledged that the clinical trials were not representative of the world population and that the risk-benefit balance may be less advantageous, particularly in patients who are immunosuppressed at higher risk of opportunistic infections (such as serious fungal, viral, or bacteria), those already deteriorating where less aggressive or stepwise addition of immunosuppressive medications may be preferred, and in areas where certain pathogens such as HIV or tuberculosis, are of concern. The panel anticipated that there would be situations where clinicians may opt for less aggressive immunosuppressive therapy or to combine medications in a stepwise fashion in patients who are deteriorating. The decision to combine the medications will depend on their availability, and the treating clinician's perception of the risk-benefit balance associated with combination immunosuppressive therapy, particularly in patient populations at risk of opportunistic infections who may have been under-represented in clinical trials. When making a strong recommendation against the use of monoclonal antibodies for patients with covid-19, the GDG considered in vitro neutralisation data demonstrating that sotrovimab and casirivimab-imdevimab evaluated in clinical trials have meaningfully reduced neutralisation activity of the currently circulating variants of SARS-CoV-2 and their subvariants. There was consensus among the panel that the absence of in vitro neutralisation activity strongly suggests absence of clinical effectiveness of these monoclonal antibodies. However, there was also consensus regarding the need for clinical trial evidence in order to confirm clinical efficacy of new monoclonal antibodies that reliably neutralise the circulating strains in vitro. Whether emerging new variants and subvariants might be susceptible to sotrovimab, casirivimab-imdevimab, or other anti-SARS-CoV-2 monoclonal antibodies cannot be predicted.• Recommended for patients with severe or critical covid-19—strong recommendations for systemic corticosteroids; IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids; and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation—a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19—a conditional recommendation against systemic corticosteroids; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial; and a strong recommendation against colchicine. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation—a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19—a recommendation against convalescent plasma except in the context of a clinical trial; and a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity—a strong recommendations against hydroxychloroquine and against lopinavir/ritonavir; and a recommendation against ivermectin except in the context of a clinical trial.This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF, with a summary version here in The BMJ. These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact.Recommendations on anticoagulation are planned for the next update to this guideline.

Dunbar Syndrome (DS), also known as Median Arcuate Ligament (MAL) syndrome, is a rare disease in which the celiac trunk is compressed by a fibrous attachment at the diaphragmatic crura causing abdominal angina with a large spectrum of symptoms including nausea, vomiting, weight loss, and postprandial epigastric pain.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) outbreak, a critical care outreach team was implemented in our hospital to guarantee multidisciplinary patient assessment at admission and prompt ICU support in medical wards. In this paper, we report the activity plan results and describe the baseline characteristics of the referred subjects. METHODS: We retrospectively evaluated data from 125 subjects referred to the critical care outreach team from March 22 to April 22, 2020. We considered subjects with a ceiling of care decision, with those deemed eligible assigned to level 3 care (ward subgroup), and those deemed ineligible admitted to the ICU (ICU subgroup). Quality indicators of the outreach team plan delivery included number of cardiac arrest calls, number of intubations in level 2 areas, and ineffective palliative support. RESULTS: We enrolled 125 consecutive adult subjects with a confirmed diagnosis of COVID-19. We did not report any emergency endotracheal intubations in the clinical ward. In the care ceiling subgroup, we had 2 (3.3%) emergency calls for cardiac arrest, whereas signs of ineffective palliative support were reported in 5 subjects (12.5%). Noninvasive forms of respiratory assistance were delivered to 40.0% of subjects in the ward subgroup (median 3 d [interquartile range (IQR) 2–5]), to 45.9% of subjects in the care ceiling subgroup (median 5 d [IQR 3–7]), and to 64.7% of subjects in the ICU subgroup (median 2.5 d [IQR 1–3]). Thirty of the 31 ward subjects (96.7%), 26 of the 34 ICU subjects, (76.4%), and 19 of the 61 ceiling of care subjects (31.1%) were discharged. CONCLUSIONS: In the context of a hospital and ICU surge, a multidisciplinary daily plan supported by a dedicated critical care outreach team was associated with a low rate of cardiac arrest calls, no emergency intubations in the ward, and appropriate palliative care support for subjects with a ceiling of care decision.

Background Despite growing controversies around Hydroxychloroquine's effectiveness, the drug is still widely prescribed by clinicians to treat COVID19 patients. Therapeutic judgment under uncertainty and imperfect information may be influenced by personal preference, whereby individuals, to confirm a-priori beliefs, may propose drugs without knowing the clinical benefit. To estimate this disconnect between available evidence and prescribing behavior, we created a Bayesian model analyzing a-priori optimistic belief of physicians in Hydroxychloroquine's effectiveness. Methodology: We created a Bayesian model to simulate the impact of different a-priori beliefs related to Hydroxychloroquine's effectiveness on clinical and economic outcome. Results: Our hypothetical results indicate no significant difference in treatment effect (combined survival benefit and harm) up to a presumed drug's effectiveness level of 20%, with younger individuals being negatively affected by the treatment (RR 0.82, 0.55–1.2; (0.95 (1.1) % expected adverse events versus 0.05 (0.98) % expected death prevented). Simulated cost data indicate overall hospital cost (medicine, hospital stay, complication) of 18.361,41€ per hospitalized patient receiving Hydroxychloroquine treatment. Conclusion: Off-label use of Hydroxychloroquine needs a rational, objective and datadriven evaluation, as personal preferences may be flawed and cause harm to patients and to society., Highlights • Hydroxychloroquine has been widely used as an off-label drug during the COVID-19 pandemic despite accumulating evidence showing limited clinical effectiveness • Subjective preference during emergencies may skew clinical judgment about benefit versus harm in prescribing Hydroxychloroquine • We have quantified the internal belief of “optimistic believers in the effectiveness of the drug” to be around or above 20% • Increasing awareness of personal bias may reduce waste and improve the quality of informed prescribing

Background Novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines have been approved recently, and public concern regarding the risk of anaphylactic reactions arose after a few cases during the first days of mass vaccination. Polyethylene glycol (PEG) has been suggested as the most probable culprit agent for allergic reactions. Objective We describe the allergy work-up protocol implemented for the vaccination campaign in our Center, aiming to allow the greatest number of people to be vaccinated safely. Methods The protocol included the self-report of a history of suspected drug or vaccine allergies, and subsequent teleconsultation and allergometric tests for PEG and Polysorbate 80 (PS80). A desensitizing protocol of vaccine administration was applied to patients sensitized only to PS80, and to those with a suspect allergic reaction after the first vaccine dose. Results 10.2% (414 out of 4042) of the entire vaccine population have been screened: only one patient resulted allergic to PEG and therefore excluded from the vaccination. Another patient was sensitized to PS80 only and safely vaccinated applying the desensitizing protocol. Seven subjects without a previous history of allergic disease experienced suspect hypersensitivity reactions to the first administered dose: one of them resulted allergic to PEG and was excluded from the second dose, while the others safely completed the vaccination with the desensitizing protocol. Conclusion A careful allergological risk-assessment protocol significantly reduces the number of patients who would have avoided SARS-CoV-2 vaccination for their allergies and to effectively identify and manage those rare patients with sensitization to PEGs and/or PS80.

BackgroundChronic obstructive pulmonary disease (COPD) exacerbation and protective mechanical ventilation of acute respiratory distress syndrome (ARDS) patients induce hypercapnic respiratory acidosis.Main textExtracorporeal carbon dioxide removal (ECCO2R) aims to eliminate blood CO2to fight against the adverse effects of hypercapnia and related acidosis. Hypercapnia has deleterious extrapulmonary consequences, particularly for the brain. In addition, in the lung, hypercapnia leads to: lower pH, pulmonary vasoconstriction, increases in right ventricular afterload, acute cor pulmonale. Moreover, hypercapnic acidosis may further damage the lungs by increasing both nitric oxide production and inflammation and altering alveolar epithelial cells. During an exacerbation of COPD, relieving the native lungs of at least a portion of the CO2could potentially reduce the patient's respiratory work, Instead of mechanically increasing alveolar ventilation with MV in an already hyperinflated lung to increase CO2removal, the use of ECCO2R may allow a decrease in respiratory volume and respiratory rate, resulting in improvement of lung mechanic. Thus, the use of ECCO2R may prevent noninvasive ventilation failure and allow intubated patients to be weaned off mechanical ventilation. In ARDS patients, ECCO2R may be used to promote an ultraprotective ventilation in allowing to lower tidal volume, plateau (Pplat) and driving pressures, parameters that have identified as a major risk factors for mortality. However, although ECCO2R appears to be effective in improving gas exchange and possibly in reducing the rate of endotracheal intubation and allowing more protective ventilation, its use may have pulmonary and hemodynamic consequences and may be associated with complications.ConclusionIn selected patients, ECCO2R may be a promising adjunctive therapeutic strategy for the management of patients with severe COPD exacerbation and for the establishment of protective or ultraprotective ventilation in patients with ARDS without prognosis-threatening hypoxemia.

Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients. ispartof: INTENSIVE CARE MEDICINE vol:47 issue:3 pages:282-291 ispartof: location:United States status: published

Since December 2019, the world has been devastated by the Coronavirus Disease 2019 (COVID-19) pandemic. Emergency Departments have been experiencing situations of urgency where clinical experts, without long experience and mature means in the fight against COVID-19, have to rapidly decide the most proper patient treatment. In this context, we introduce an artificially intelligent tool for effective and efficient Computed Tomography (CT)-based risk assessment to improve treatment and patient care. In this paper, we introduce a data-driven approach built on top of volume-of-interest aware deep neural networks for automatic COVID-19 patient risk assessment (discharged, hospitalized, intensive care unit) based on lung infection quantization through segmentation and, subsequently, CT classification. We tackle the high and varying dimensionality of the CT input by detecting and analyzing only a sub-volume of the CT, the Volume-of-Interest (VoI). Differently from recent strategies that consider infected CT slices without requiring any spatial coherency between them, or use the whole lung volume by applying abrupt and lossy volume down-sampling, we assess only the “most infected volume” composed of slices at its original spatial resolution. To achieve the above, we create, present and publish a new labeled and annotated CT dataset with 626 CT samples from COVID-19 patients. The comparison against such strategies proves the effectiveness of our VoI-based approach. We achieve remarkable performance on patient risk assessment evaluated on balanced data by reaching 88.88%, 89.77%, 94.73% and 88.88% accuracy, sensitivity, specificity and F1-score, respectively.

Since the lockdown because of the pandemic, family members have been prohibited from visiting their loved ones in hospital. While it is clearly complicated to implement protocols for the admission of family members, we believe precise strategic goals are essential and operational guidance is needed on how to achieve them. Even during the pandemic, we consider it a priority to share strategies adapted to every local setting to allow family members to enter intensive care units and all the other hospital wards. Supplementary Information The online version contains supplementary material available at 10.1186/s13054-021-03608-3.

Background There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. Of note, ACE2 is responsible for the host cell entry of the virus. Method We extracted data on 575 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the Emergency Department (ED) of Humanitas Center, between February 21 and April 14, 2020. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients. Results Multivariate analysis showed that a chronic intake of ACE-I was associated with a trend in reduction of mortality (OR: 0.53; 95% CI: 0.27–1.03; p = 0.06). Increased age (ORs ranging from 3.4 to 25.2 and to 39.5 for 60–70, 70–80 and > 80 years vs 50% of total Italian deaths. Based on our findings, we support that daily intake of antihypertensive medications in the setting of COVID-19 should not be discontinued and that a timely LMWH administration in ED has shown to decrease in-hospital mortality., Highlights • This is a retrospective study on 575 consecutive patients with laboratory-confirmed SARS-CoV-2 infection from a center in Northern Italy, whose in hospital mortality was 20.9%. • According to multivariate analysis, chronic treatment with angiotensin converting enzyme inhibitors (ACE—I) in COVID-19 patients is associated with a decrease and a significant delay in in-hospital mortality, differently from the chronic use of angiotensin II receptor blockers (ARBs). • As previously shown by other studies on COVID-19 patients, increasing age and cardiovascular comorbidities are important risk factors for Covid-19 mortality, while an early introduction of LMWH in the setting of Covid-19 leads to a better prognosis.

BACKGROUND: The aim was to describe the incidence and risk factors of barotrauma in patients with the Coronavirus disease 2019 (COVID-19) on invasive mechanical ventilation, during the outbreak in our region (Lombardy, Italy). METHODS: The study was an electronic survey open from March 27th to May 2nd, 2020. Patients with COVID-19 who developed barotrauma while on invasive mechanical ventilation from 61 hospitals of the COVID-19 Lombardy Intensive Care Unit network were involved. RESULTS: The response rate was 38/61 (62%). The incidence of barotrauma was 145/2041 (7.1%; 95%-CI: 6.1-8.3%). Only a few cases occurred with ventilatory settings that may be considered non-protective such as a plateau airway pressure >35 cmH2O (2/113 [2%]), a driving airway pressure >15 cmH2O (30/113 [27%]), or a tidal volume >8 mL/kg of ideal body weight and a plateau airway pressure >30 cmH2O (12/134 [9%]). CONCLUSIONS: Within the limits of a survey, patients with COVID-19 might be at high risk for barotrauma during invasive (and allegedly lung-protective) mechanical ventilation.