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Background: The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline "ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation." The guideline can provide guidance to Nordic anaesthesiologists on the perioperative use of cardiac biomarkers in patients undergoing non-cardiac surgery., Funding Agencies|Scandinavian Society of Anaesthesiology and Intensive Care Medicine and institutional and/or departmental sources

Background An increasing number of patients undergo surgical procedures worldwide each year, and despite advances in quality and care, morbidity and mortality rates remain high. Perioperative hypotension is a well-described condition, and is associated with adverse outcomes. Both fluids and vasoactive agents are commonly used to treat hypotension, however, whether one vasoactive agent is preferable over another has yet to be explored. Methods In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) statement, we plan to conduct a scoping review of studies assessing the use of vasoactive agents in patients undergoing non-cardiac surgery. We will provide an overview of indications, agents used and outcomes assessed. We will assess and report the certainty of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results We will provide descriptive analyses of the included studies accompanied by tabulated results. Conclusion The outlined scoping review will provide a summary of the body of evidence on the use of vasoactive agents in the non-cardiac surgical population.

Background: Acute or new-onset atrial fibrillation (NOAF) is the most common cardiac arrhythmia in critically ill adult patients, and observational data suggests that NOAF is associated to adverse outcomes. Methods: We prepared this guideline according to the Grading of Recommendations Assessment, Development and Evaluation methodology. We posed the following clinical questions: (1) what is the better first-line pharmacological agent for the treatment of NOAF in critically ill adult patients?, (2) should we use direct current (DC) cardioversion in critically ill adult patients with NOAF and hemodynamic instability caused by atrial fibrillation?, (3) should we use anticoagulant therapy in critically ill adult patients with NOAF?, and (4) should critically ill adult patients with NOAF receive follow-up after discharge from hospital? We assessed patient-important outcomes, including mortality, thromboembolic events, and adverse events. Patients and relatives were part of the guideline panel. Results: The quantity and quality of evidence on the management of NOAF in critically ill adults was very limited, and we did not identify any relevant direct or indirect evidence from randomized clinical trials for the prespecified PICO questions. We were able to propose one weak recommendation against routine use of therapeutic dose anticoagulant therapy, and one best practice statement for routine follow-up by a cardiologist after hospital discharge. We were not able to propose any recommendations on the better first-line pharmacological agent or whether to use DC cardioversion in critically ill patients with hemodynamic instability induced by NOAF. An electronic version of this guideline in layered and interactive format is available in MAGIC: https://app.magicapp.org/#/guideline/7197. Conclusions: The body of evidence on the management of NOAF in critically ill adults is very limited and not informed by direct evidence from randomized clinical trials. Practice variation appear, Funding Agencies|Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI)

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the ISTH guidelines for antithrombotic treatment in COVID-19. This evidence-based guideline serves as a useful decision aid for Nordic anaesthesiologists caring for patients with COVID-19., Funding Agencies|Scandinavian Society of Anaesthesiology and Intensive Care Medicine

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine. This clinical practice guideline serves as a useful decision aid for Nordic anaesthesiologists managing adult trauma patients in the operating room and in the intensive care unit., Funding Agencies|Scandinavian Society of Anaesthesiology and Intensive Care Medicine

Background: The Nordic perioperative and intensive care registries have been built up during the last 25 years to improve quality in intensive and perioperative care. We aimed to describe the Nordic perioperative and intensive care registries and to highlight possibilities and challenges in future research collaboration between these registries.Material and method: We present an overview of the following Nordic registries: Swedish Perioperative Registry (SPOR), the Danish Anesthesia Database (DAD), the Finnish Perioperative Database (FIN-AN), the Icelandic Anesthesia Database (IS-AN), the Danish Intensive Care Database (DID), the Swedish Intensive Care Registry (SIR), the Finnish Intensive Care Consortium, the Norwegian Intensive Care and Pandemic Registry (NIPaR), and the Icelandic Intensive Care Registry (IS-ICU).Results: Health care systems and patient populations are similar in the Nordic countries. Despite certain differences in data structure and clinical variables, the perioperative and intensive care registries have enough in common to enable research collaboration. In the future, even a common Nordic registry could be possible.Conclusion: Collaboration between the Nordic perioperative and intensive care registries is both possible and likely to produce research of high quality. Research collaboration between registries may have several add-on effects and stimulate international standardization regarding definitions, scoring systems, and benchmarks, thereby improving overall quality of care.

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., Funding Agencies|Fisher & Paykel Healthcare

Background Trials in critically ill patients increasingly focus on days alive without life support (DAWOLS) or days alive out of hospital (DAOOH) and health-related quality of life (HRQoL). DAWOLS and DAOOH convey more information than mortality and are simpler and faster to collect than HRQoL. However, whether these outcomes are associated with HRQoL is uncertain. We thus aimed to assess the associations between DAWOLS and DAOOH and long-term HRQoL. Methods Secondary analysis of the COVID STEROID 2 trial including adults with COVID-19 and severe hypoxaemia and the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial including adult intensive care unit patients with acute hypoxaemic respiratory failure. Associations between DAWOLS and DAOOH at day 28 and 90 and long-term HRQoL (after 6 or 12 months) using the EuroQol 5-dimension 5-level survey (EQ VAS and EQ-5D-5L index values) were assessed using flexible models and evaluated using measures of fit and prediction adequacy in both datasets (comprising internal performance and external validation), non-parametric correlation coefficients and graphical presentations. Results We found no strong associations between DAWOLS or DAOOH and HRQoL in survivors at HRQoL-follow-up (615 and 1476 patients, respectively). There was substantial variability in outcomes, and predictions from the best fitted models were poor both internally and externally in the other trial dataset, which also showed inadequate calibration. Moderate associations were found when including non-survivors, although predictions remained uncertain and calibration inadequate. Conclusion DAWOLS and DAOOH were poorly associated with HRQoL in adult survivors of severe or critical illness included in the COVID STEROID 2 and HOT-ICU trials., Background: Trials in critically ill patients increasingly focus on days alive without life support (DAWOLS) or days alive out of hospital (DAOOH) and health-related quality of life (HRQoL). DAWOLS and DAOOH convey more information than mortality and are simpler and faster to collect than HRQoL. However, whether these outcomes are associated with HRQoL is uncertain. We thus aimed to assess the associations between DAWOLS and DAOOH and long-term HRQoL.Methods: Secondary analysis of the COVID STEROID 2 trial including adults with COVID-19 and severe hypoxaemia and the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial including adult intensive care unit patients with acute hypoxaemic respiratory failure. Associations between DAWOLS and DAOOH at day 28 and 90 and long-term HRQoL (after 6 or 12 months) using the EuroQol 5-dimension 5-level survey (EQ VAS and EQ-5D-5L index values) were assessed using flexible models and evaluated using measures of fit and prediction adequacy in both datasets (comprising internal performance and external validation), non-parametric correlation coefficients and graphical presentations.Results: We found no strong associations between DAWOLS or DAOOH and HRQoL in survivors at HRQoL-follow-up (615 and 1476 patients, respectively). There was substantial variability in outcomes, and predictions from the best fitted models were poor both internally and externally in the other trial dataset, which also showed inadequate calibration. Moderate associations were found when including non-survivors, although predictions remained uncertain and calibration inadequate.Conclusion: DAWOLS and DAOOH were poorly associated with HRQoL in adult survivors of severe or critical illness included in the COVID STEROID 2 and HOT-ICU trials.

Critically ill patients are at risk of gastrointestinal (GI) bleeding. Counter measures to minimise this risk include the use of pharmacological stress ulcer prophylaxis (SUP). The effect of enteral nutrition as SUP on GI bleeding event rates is unknown. There are conflicting data describing the effect of co-administration of enteral nutrition with pharmacological SUP, and there is substantial variation in practice. We aim to conduct an exploratory post hoc analysis to evaluate the association of enteral nutrition with clinically important GI bleed rates in ICU patients included in the SUP-ICU trial, and to explore any interactions between enteral nutrition and pharmacologic SUP on patient outcomes. The SUP-ICU trial dataset will be used to assess if enteral nutrition is associated with the outcomes of interest. Extended Cox models will be used considering relevant competing events, including treatment allocation (SUP or placebo) and enteral nutrition as a daily time-varying covariate, with additional adjustment for severity of illness (SAPS II). Results will be presented as adjusted hazard ratios for treatment allocation and enteral nutrition, and for treatment allocation and enteral nutrition considering potential interactions with the other variable, all with 95% confidence intervals and p-values for the tests of interaction. All results will be considered as exploratory only. This post hoc analysis may yield important insights to guide practice and inform the design of future randomised clinical trial investigating the effect of enteral nutrition on GI bleeding., Critically ill patients are at risk of gastrointestinal (GI) bleeding. Counter measures to minimise this risk include the use of pharmacological stress ulcer prophylaxis (SUP). The effect of enteral nutrition as SUP on GI bleeding event rates is unknown. There are conflicting data describing the effect of co-administration of enteral nutrition with pharmacological SUP, and there is substantial variation in practice. We aim to conduct an exploratory post hoc analysis to evaluate the association of enteral nutrition with clinically important GI bleed rates in ICU patients included in the SUP-ICU trial, and to explore any interactions between enteral nutrition and pharmacologic SUP on patient outcomes. The SUP-ICU trial dataset will be used to assess if enteral nutrition is associated with the outcomes of interest. Extended Cox models will be used considering relevant competing events, including treatment allocation (SUP or placebo) and enteral nutrition as a daily time-varying covariate, with additional adjustment for severity of illness (SAPS II). Results will be presented as adjusted hazard ratios for treatment allocation and enteral nutrition, and for treatment allocation and enteral nutrition considering potential interactions with the other variable, all with 95% confidence intervals and p-values for the tests of interaction. All results will be considered as exploratory only. This post hoc analysis may yield important insights to guide practice and inform the design of future randomised clinical trial investigating the effect of enteral nutrition on GI bleeding.

Background: Awake proning in spontaneously breathing patients with hypoxemic acute respiratory failure was applied during the coronavirus disease 2019 (COVID-19) pandemic to improve oxygenation while avoiding tracheal intubation. An updated systematic review and meta-analysis on the topic was published.Methods: The Clinical practice committee (CPC) of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine (SSAI) assessed the clinical practice guideline "Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline" for possible endorsement. The Appraisal of Guidelines for REsearch and Evaluation (AGREE) II tool was used.Results: Four out of six SSAI CPC members completed the appraisal. The individual domain totals were: Scope and Purpose 90%; Stakeholder Involvement 89%; Rigour of Development 74%; Clarity of Presentation 85%; Applicability 75%; Editorial Independence 98%; Overall Assessment 79%.Conclusion: The SSAI CPC endorses the clinical practice guideline "Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline". This guideline serves as a useful decision aid for clinicians caring for critically ill patients with COVID-19-related acute hypoxemic respiratory failure and can be used to provide guidance on use of prone positioning in this group of patients., Funding Agencies|Scandinavian Society of Anaesthesiology and Intensive Care Medicine

Objective To identify PaCO2 trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) during the first and second waves of the pandemic in Denmark. Design A population-based cohort study with retrospective data collection. Patients All COVID-19 patients were treated in eight intensive care units (ICUs) in the Capital Region of Copenhagen, Denmark, between March 1, 2020 and March 31, 2021. Measurements Data from the electronic health records were extracted, and latent class analyses were computed based on up to the first 3 weeks of mechanical ventilation to depict trajectories of PaCO2 levels. Multivariable Cox regression analyses were used to calculate adjusted hazard ratios (aHRs) for Simplified Acute Physiology Score 3, sex and age with 95% confidence intervals (CIs) for death according to PaCO2 trajectories. Main results In latent class trajectory models, including 25,318 PaCO2 measurements from 244 patients, three PaCO2 latent class trajectories were identified: a low isocapnic (Class I; n = 130), a high isocapnic (Class II; n = 80), as well as a progressively hypercapnic (Class III; n = 34) trajectory. Mortality was higher in Class II [aHR: 2.16 {1.26–3.68}] and Class III [aHR: 2.97 {1.63–5.40}]) compared to Class I (reference). Conclusion Latent class analysis of arterial blood gases in mechanically ventilated COVID-19 patients identified distinct PaCO2 trajectories, which were independently associated with mortality., Objective: To identify PaCO2 trajectories and assess their associations with mortality in critically ill patients with coronavirus disease 2019 (COVID-19) during the first and second waves of the pandemic in Denmark. Design: A population-based cohort study with retrospective data collection.Patients: All COVID-19 patients were treated in eight intensive care units (ICUs) in the Capital Region of Copenhagen, Denmark, between March 1, 2020 and March 31, 2021. Measurements: Data from the electronic health records were extracted, and latent class analyses were computed based on up to the first 3 weeks of mechanical ventilation to depict trajectories of PaCO2 levels. Multivariable Cox regression analyses were used to calculate adjusted hazard ratios (aHRs) for Simplified Acute Physiology Score 3, sex and age with 95% confidence intervals (CIs) for death according to PaCO2 trajectories. Main results: In latent class trajectory models, including 25,318 PaCO2 measurements from 244 patients, three PaCO2 latent class trajectories were identified: a low isocapnic (Class I; n = 130), a high isocapnic (Class II; n = 80), as well as a progressively hypercapnic (Class III; n = 34) trajectory. Mortality was higher in Class II [aHR: 2.16 {1.26-3.68}] and Class III [aHR: 2.97 {1.63-5.40}]) compared to Class I (reference). Conclusion: Latent class analysis of arterial blood gases in mechanically ventilated COVID-19 patients identified distinct PaCO2 trajectories, which were independently associated with mortality.

Background The "Large observational study to understand the global impact of severe acute respiratory failure" (LUNG SAFE) study described the worldwide epidemiology and management of patients with acute hypoxaemic respiratory failure (AHRF). Here, we present the Nordic subset of data from the LUNG SAFE cohort. Methods We extracted LUNG SAFE data for adults fulfilling criteria for AHRF in intensive care units (ICU) in Denmark, Norway and Sweden, including demographics, co-morbidities, clinical assessment and management characteristics, 90-day survival and length-of-stay (LOS). We analysed ICU LOS with linear regression, and associations between risk factors and mortality were quantified using Cox regression. Results We included 192 patients, with a median age of 64 years (IQR 55, 72), and a male-to-female ratio of 2:1. The majority had one or more co-morbidities, and clinicians identified pneumonia as the primary cause of respiratory failure in 56% and acute respiratory distress syndrome (ARDS) in 21%. Median ICU LOS and duration of invasive mechanical ventilation (IMV) were 5 and 3 days. Tidal volumes (TV) were frequently larger than that supported by evidence and IMV allowing for spontaneous ventilation was common. Younger age, co-morbidity, surgical admission and ARDS were associated with ICU LOS. Sixty-one patients (32%) were dead at 90 days. Age and a non-surgical cause of admission were associated with death. Conclusions In this subset of LUNG SAFE, ARDS was often not recognised in patients with AHRF and management frequently deviated from evidence-based practices. ICU LOS was generally short, and mortality was attributable to known risk factors.

The 2021 Surviving Sepsis Campaign Guidelines provided evidence-based recommendations for adult patients with sepsis and septic shock. This iteration of the guidelines placed increased emphasis on a diverse, global perspective, as well as on the long-term sequelae of sepsis experienced by patients and their families. The guidelines encompassed the following sections: 1) screening and early treatment; 2) infection; 3) hemodynamic management; 4) ventilation; 5) additional therapies; and 6) goals of care and long-term outcomes. In this review, we provide a summary of key recommendations of interest to the practicing clinician, which are either novel or require a change in practice, as well as those for which the evidence has substantially evolved in the 5 years since the 2016 iteration of the Guidelines. Rather than reviewing the underlying evidence, we emphasize the practical aspects of interpretation, dissemination, and implementation of these recommendations in the clinical setting.

Introduction Thrombocytopenia is frequent in intensive care unit (ICU) patients and has been associated with worse outcome. Platelet transfusions are often used in the management of ICU patients with severe thrombocytopenia. However, the reported frequencies of thrombocytopenia and platelet transfusion practices in the ICU vary considerably. Therefore, we aim to provide contemporary epidemiological data on thrombocytopenia and platelet transfusion practices in the ICU. Methods We will conduct an international inception cohort, including at least 1000 acutely admitted adult ICU patients. Routinely available data will be collected at baseline (ICU admission), and daily during ICU stay up to a maximum of 90 days. The primary outcome will be the number of patients with thrombocytopenia (a recorded platelet count < 150 x 10(9)/L) at baseline and/or during ICU stay. Secondary outcomes include mortality, days alive and out of hospital, days alive without life-support, the number of patients with at least one bleeding episode, at least one thromboembolic event and at least one platelet transfusion in the ICU, the number of platelet transfusions and the indications for transfusion. The primary and secondary outcomes will be presented descriptively. In addition, we will assess risk factors for developing thrombocytopenia during ICU stay and the association between thrombocytopenia at baseline and 90-day mortality using logistic regression analyses. Conclusion The outlined international PLOT-ICU cohort study will provide contemporary epidemiological data on the burden and clinical significance of thrombocytopenia in adult ICU patients and describe the current platelet transfusion practice.

Background Intensive care unit (ICU) patients receive numerous interventions, but knowledge about potential interactions between these interventions is limited. Co-enrolment in randomized clinical trials represents a unique opportunity to investigate any such interactions. We aim to assess interactions in four randomized clinical trials with overlap in inclusion periods and patient populations. Methods This protocol and statistical analysis plan describes a secondary explorative analysis of interactions in four international ICU trials on pantoprazole, oxygenations targets, haloperidol and intravenous fluids, respectively. The primary outcome will be 90-day all-cause mortality. The secondary outcome will be days alive and out of hospital in 90 days after randomization. All patients included in the intention-to-treat populations of the four trials will be included. Four co-primary analyses will be conducted, one with each of the included trials as reference using a logistic regression model adjusted for the reference trial's stratification variables and for the co-interventions with interactions terms. The primary analytical measure of interest will be the analyses' tests of interaction. A p-value below .05 will be considered statically significant. The stratification variable- and co-intervention-adjusted effect estimates will be reported with 95% confidence intervals without adjustments for multiplicity. Conclusion This exploratory analysis will investigate the presence of any interactions between pantoprazole, oxygenation targets, haloperidol and amount of intravenous fluids in four international ICU trials using co-enrolment. Assessment of possible interactions represents valuable information to guide the design, statistical powering and conduct of future trials.

Background Clinical equipoise exists regarding intravenous (IV) fluid volumes in sepsis. The Conservative vs. Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial investigates the effect of restricted vs. standard IV fluid therapy in 1554 adult intensive care unit patients with septic shock. Methods This protocol describes secondary Bayesian analyses of the primary outcome (90-day all-cause mortality) and three secondary outcomes at day 90. We will analyse all binary outcomes with adjusted Bayesian logistic regressions and present results as conditional relative risks and risk differences with 95% credibility intervals (CrIs). The secondary count outcome will be analysed using adjusted Bayesian linear regression with results summarised as conditional mean differences and ratios of means with 95% Crls. We will use weakly informative priors for the primary analyses, and sceptical and evidence-based priors in the sensitivity analyses. Exact probabilities will be presented for any benefit/harm, clinically important benefit/harm and no clinically important difference. We will assess whether heterogeneity of treatment effects on mortality is present using Bayesian hierarchical models in subgroups and on the continuous scale using models with interactions according to five baseline variables assessing the overall severity of illness and the degree of circulatory and renal impairment. Discussion The outlined analyses will supplement the primary analysis of the CLASSIC trial by describing probabilities of beneficial and harmful effects and evaluating heterogeneity of treatment effects in a framework that may be easier to interpret for researchers and clinicians.

Purpose Systematic review and network meta-analysis to investigate the efficacy of noninvasive respiratory strategies, including noninvasive positive pressure ventilation (NIPPV) and high-flow nasal cannula (HFNC), in reducing extubation failure among critically ill adults. Methods We searched databases from inception through October 2021 for randomized controlled trials (RCTs) evaluating noninvasive respiratory support therapies (NIPPV, HFNC, conventional oxygen therapy, or a combination of these) following extubation in critically ill adults. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was reintubation. We used GRADE to rate the certainty of our findings. Results We included 36 RCTs (6806 patients). Compared to conventional oxygen therapy, NIPPV (OR 0.65 [95% CI 0.52-0.82]) and HFNC (OR 0.63 [95% CI 0.45-0.87]) reduced reintubation (both moderate certainty). Sensitivity analyses showed that the magnitude of the effect was highest in patients with increased baseline risk of reintubation. As compared to HFNC, no difference in incidence of reintubation was seen with NIPPV (OR 1.04 [95% CI 0.78-1.38], low certainty). Compared to conventional oxygen therapy, neither NIPPV (OR 0.8 [95% CI 0.61-1.04], moderate certainty) or HFNC (OR 0.9 [95% CI 0.66-1.24], low certainty) reduced short-term mortality. Consistent findings were demonstrated across multiple subgroups, including high- and low-risk patients. These results were replicated when evaluating noninvasive strategies for prevention (prophylaxis), but not in rescue (application only after evidence of deterioration) situations. Conclusions Our findings suggest that both NIPPV and HFNC reduced reintubation in critically ill adults, compared to conventional oxygen therapy. NIPPV did not reduce incidence of reintubation when compared to HFNC. These findings support the preventative application of noninvasive respiratory support strategies to mitigate

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., Funding Agencies|Novo Nordisk FoundationNovo Nordisk FoundationNovocure Limited; Research Council of Rigshospitalet [0062998, E-22703-06]

Purpose We compared dexamethasone 12 versus 6 mg daily for up to 10 days in patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia in the international, randomised, blinded COVID STEROID 2 trial. In the primary, conventional analyses, the predefined statistical significance thresholds were not reached. We conducted a pre-planned Bayesian analysis to facilitate probabilistic interpretation. Methods We analysed outcome data within 90 days in the intention-to-treat population (data available in 967 to 982 patients) using Bayesian models with various sensitivity analyses. Results are presented as median posterior probabilities with 95% credible intervals (CrIs) and probabilities of different effect sizes with 12 mg dexamethasone. Results The adjusted mean difference on days alive without life support at day 28 (primary outcome) was 1.3 days (95% CrI -0.3 to 2.9; 94.2% probability of benefit). Adjusted relative risks and probabilities of benefit on serious adverse reactions was 0.85 (0.63 to 1.16; 84.1%) and on mortality 0.87 (0.73 to 1.03; 94.8%) at day 28 and 0.88 (0.75 to 1.02; 95.1%) at day 90. Probabilities of benefit on days alive without life support and days alive out of hospital at day 90 were 85 and 95.7%, respectively. Results were largely consistent across sensitivity analyses, with relatively low probabilities of clinically important harm with 12 mg on all outcomes in all analyses. Conclusion We found high probabilities of benefit and low probabilities of clinically important harm with dexamethasone 12 mg versus 6 mg daily in patients with COVID-19 and severe hypoxaemia on all outcomes up to 90 days., Funding Agencies|Novo Nordisk FoundationNovo Nordisk FoundationNovocure Limited [0062998]; Rigshospitalets Research Council [E-22703-06]

Background The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the clinical practice guideline Surviving Sepsis Campaign International Guidelines for the Management of Septic Shock and Sepsis-Associated Organ Dysfunction in Children. The guideline can serve as a useful decision aid for clinicians managing children with suspected and confirmed septic shock and sepsis-associated organ dysfunction., Funding Agencies|SSAI

Introduction New-onset atrial fibrillation (NOAF) is frequently observed in critically ill patients and may be associated with prolonged hospital stay and increased mortality. Considerable variation exists in the reported frequencies of NOAF due to the lack of a standardised definition and detection method. Importantly, there are limited data on NOAF in the intensive care unit (ICU). Thus, we aim to provide contemporary epidemiological data on NOAF in the ICU.Methods and Analysis We have designed an international inception cohort study including at least 1,000 consecutive adult patients acutely admitted to the ICU without prior history of persistent or permanent AF. We will present data on the incidence, risk factors, used management strategies and outcomes of NOAF. We will register data daily during stay in the ICU for a maximum of 90 days after admission. The incidence of NOAF and management strategies used will be presented descriptively, and we will use Cox regression analyses including competing risk analyses to assess risk factors for NOAF and any association with 90-day mortality.Conclusion The outlined international AFIB-ICU inception cohort study will provide contemporary data on the incidence, risk factors, used management strategies and outcomes of NOAF in adult ICU patients.Ethics and dissemination This observational study poses no risk to the included patients. All participating sites will obtain relevant approvals according to national laws before patient enrollment. Funding sources will have no influence on data handling, analyses or writing of the manuscript. The study report(s) will be submitted to an international peer-reviewed journal.

Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. Methods The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. Discussion The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society., Funding Agencies|Rigshospitalets Research Council [E-22703-06]; Novo Nordisk FondenNovo Nordisk Foundation [0062998]

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., Funding Agencies|Novo Nordisk FoundationNovo Nordisk Foundation [0062998]; Rigshospitalets Research Council [E-22703-06]

Introduction Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists. Methods The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving >= 10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals. Discussion The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

Background The Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial is an ongoing randomised clinical trial exploring the benefits and harms of targeting a lower (8 kPa) versus a higher (12 kPa) arterial oxygenation target in adult patients acutely admitted to the intensive care unit (ICU) with hypoxaemic respiratory failure. Methods This protocol describes a secondary analysis of the primary trial outcome, 90-day all-cause mortality. We will analyse the primary outcome using Bayesian methods, which allows quantification of probabilities of all effect sizes. We will explore the presence of heterogeneity of treatment effects (HTE) using Bayesian hierarchical models in subgroups based on baseline parameters: (a) severity of illness (Sequential Organ Failure Assessment (SOFA) score), (b) severity of hypoxaemic respiratory failure (partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO(2)) ratio), (c) vasopressor requirement (highest noradrenaline dose in the 24 hours prior to randomisation), and (d) plasma lactate concentration (latest prior to randomisation). Additionally, we will perform separate assessments of the treatment effect interaction with each of the baseline parameters above on the continuous scale and present these using conditional effects plots. Conclusions This secondary analysis will aid the interpretation of the HOT-ICU trial by evaluating probabilities of all effect sizes. In addition, we will evaluate whether HTE is present, thus, further evaluating benefits and harms of a lower versus a higher oxygenation target in adult ICU patients with acute hypoxaemic respiratory failure.