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Background: In our metabolomics studies we have noticed that repeated NMR acquisition on the same sample can result in altered metabolite signal intensities. Aims: To investigate the reproducibility of repeated NMR acquisition on selected metabolites in serum and plasma from two large human metabolomics studies. Methods: Two peak regions for each metabolite were integrated and changes occurring after reacquisition were correlated. Results: Integral changes were generally small, but serum citrate signals decreased significantly in some samples. Conclusions: Several metabolite integrals were not reproducible in some of the repeated spectra. Following established protocols, randomising analysis order and biomarker validation are important. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Acute kidney injury (AKI) is a serious complication of cardiac surgery. Statins may prevent post-surgical AKI, yet methodological concerns about existing studies raise questions about the magnitude of a protective effect. We sought to determine the effect of initiating a statin prior to elective cardiac surgery on post-surgical AKI in a regional Danish surgical cohort. METHODS: We identified adults who underwent cardiac surgery during 2006-11 using the Western Denmark Heart Registry. Presurgical medication use, pre- and post-surgical serum creatinine (sCr) measures, and other patient characteristics were obtained from Danish population-based registries. Post-surgical AKI was assessed using sCr measures within 5 days of surgery. The adjusted risk ratio (RR) of AKI and 95% confidence interval (CI) were estimated for patients who initiated a statin within 100 days prior to surgery compared with patients without prior statin use; long-term statin users were excluded to reduce healthy-user bias. Subanalyses were stratified by surgery type: coronary artery bypass grafting (CABG) and non-CABG surgeries. RESULTS: We identified 1929 CABG and 1775 non-CABG patients. AKI occurred in 25% of CABG and 28% of non-CABG surgeries, and in 29% of the non-users and 21% of the statin initiators. Half of CABG patients and 9% of non-CABG patients initiated a statin prior to surgery. The adjusted RRs for the effect of statin initiation on AKI were as follows: all surgeries combined, RR = 0.86 (95% CI: 0.74, 0.98); CABG, RR = 0.88 (0.74, 1.05); non-CABG RR = 0.87 (0.68, 1.11). CONCLUSIONS: Presurgical statin initiation is associated with a reduction in AKI risk after cardiac surgery. [ABSTRACT FROM AUTHOR]

Background: New‐onset atrial fibrillation or flutter (NOAF) is a common arrhythmia in adult intensive care unit (ICU) patients. Intravenous amiodarone is one of the most used anti‐arrhythmic drugs, despite its risk of inducing acute amiodarone‐induced pulmonary toxicity (APT). We aimed to outline the body of evidence on acute APT in ICU patients with NOAF. Methods: We performed a systematic search using the population, intervention, comparison, and outcome (PICO) approach. We included studies of adults admitted to the ICU, who developed NOAF during their ICU stay, were treated with amiodarone, and reported on acute APT, irrespective of research design. The CASE guidelines were applied to evaluate the quality of the included studies, and study results are reported in accordance with the preferred reporting items for systematic reviews and meta‐analyses. Results: No randomised controlled trials or observational studies were identified. Nine case reports and one retrospective case series of fatal outcomes in ICU patients treated with amiodarone for NOAF constituted the evidence base. The quality of the included studies was high with a mean of 10 (range 8–12) of the 13 CASE guideline criteria fulfilled. The studies included a total of 16 critically ill adults who was diagnosed with acute APT after a mean of 9 days (range 2–20 days) following initiation of amiodarone with a mean total dose of amiodarone of 4553 mg (range 1100–13,500 mg) predominantly administrated intravenously. Three out of nine patients in the case reports died in the ICU during the amiodarone treatment. No long‐term follow‐up was conducted for the survivors. Conclusion: Acute APT in adult ICU patients treated with amiodarone for NOAF is poorly described and is based on a total of 16 reported cases. Additional studies assessing the safety of amiodarone in critically ill adults with NOAF in the ICU is warranted. [ABSTRACT FROM AUTHOR]

Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX). Post-hoc analyses from the ICU-ROX trial suggested that lower oxygen targets may be preferable for patients with hypoxic ischaemic encephalopathy [[12]] while higher oxygen targets might be preferable for patients with other brain pathologies and sepsis [[13]]. Published simultaneously with the ICU-ROX trial, a French multicentre RCT LOCO2 ( I N i = 205) comparing conservative and liberal oxygen regimens in patients with acute respiratory distress syndrome (ARDS) raised the possibility that conservative oxygen therapy might increase the risk of mesenteric ischaemia [[9]]. Although published RCTs comparing oxygen therapies in critically ill patients specified different oxygen therapy regimens in their methods, the exposures to oxygen which actually occurred in their respective higher and lower target groups were broadly similar. [Extracted from the article]

Purpose: Optimal oxygenation targets for patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are not clearly defined due to substantial variability in design of previous trials. This study aimed to perform a pre-specified individual patient data meta-analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) and the Handling Oxygenation Targets in coronavirus disease 2019 (COVID-19) (HOT-COVID) trials to compare targeting a partial pressure of arterial oxygen (PaO2) of 8–12 kPa in adult ICU patients, assessing both benefits and harms. Methods: We assessed 90-day all-cause mortality and days alive without life support in 90 days using a generalised mixed model. Heterogeneity of treatment effects (HTE) was evaluated in 14 subgroups, and results graded using the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN). Results: At 90 days, mortality was 40.4% (724/1792) in the 8 kPa group and 40.9% (733/1793) in the 12 kPa group (risk ratio, 0.99; 95% confidence interval [CI] 0.92–1.07; P = 0.80). No difference was observed in number of days alive without life support. Subgroup analyses indicated more days alive without life support in COVID-19 patients targeting 8 kPa (P = 0.04) (moderate credibility), and lower mortality (P = 0.03) and more days alive without life support (P = 0.02) in cancer-patients targeting 12 kPa (low credibility). Conclusion: This study reported no overall differences comparing a PaO2 target of 8–12 kPa on mortality or days alive without life support in 90 days. Subgroup analyses suggested HTE in patients with COVID-19 (moderate credibility) and cancer (low credibility). [ABSTRACT FROM AUTHOR]

The article responds to a letter regarding a meta-analysis of the HOT-ICU and HOT-COVID trials, focusing on subgroup analyses, particularly for cancer patients. The authors used ICEMAN to assess credibility and found significant interactions for patients with COVID-19 and cancer. Despite a low credibility rating, the study suggests that cancer patients may require different oxygenation targets in the ICU, although further research is needed to confirm this hypothesis. The authors acknowledge the complexity of the relationship between cancer and oxygenation but maintain their initial hypothesis based on the study's findings. [Extracted from the article]

Background: In the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial, a lower (8 kPa) vs a higher (12 kPa) PaO2 target did not affect mortality amongst critically ill adult patients. We used Bayesian statistics to evaluate any heterogeneity in the effect of oxygenation targets on mortality between different patient groups within the HOT-ICU trial.Methods: We analysed 90-day all-cause mortality using adjusted Bayesian logistic regression models, and assessed heterogeneous treatment effects according to four selected baseline variables using both hierarchical models of subgroups and models with interactions on the continuous scales. Results are presented as mortality probability (%) and relative risk (RR) with 95% credibility intervals (CrI).Results: All 2888 patients in the intention-to-treat cohort of the HOT-ICU trial were included. The adjusted 90-day mortality rates were 43.0% (CrI: 38.3-47.8%) and 42.3% (CrI: 37.7-47.1%) in the lower and higher oxygenation groups, respectively (RR 1.02 [CrI: 0.93-1.11]), with 36.5% probability of an RR <1.00. Analyses of heterogeneous treatment effects suggested a dose-response relationship between baseline norepinephrine dose and increased mortality with the lower oxygenation target, with 95% probability of increased mortality associated with the lower oxygenation target as norepinephrine doses increased.Conclusions: A lower oxygenation target was unlikely to affect overall mortality amongst critically ill adult patients with acute hypoxaemic respiratory failure. However, our results suggest an increasing mortality risk for patients with a lower oxygen target as the baseline norepinephrine dose increases. These findings warrant additional investigation.Clinical Trial Registration: NCT03174002. [ABSTRACT FROM AUTHOR]

Background: Liberal oxygen supplementation is often used in acute illness but has, in some studies, been associated with harm.Research Question: The goal of this study was to assess the benefits and harms of higher vs lower oxygenation strategies in acutely ill adults.Study Design and Methods: This study was an updated systematic review with meta-analysis and Trial Sequential Analysis (TSA) of randomized clinical trials. A clear differentiation (separation) was made between a higher (liberal) oxygenation and a lower (conservative) oxygenation strategy and their effects on all-cause mortality, serious adverse events, quality of life, lung injury, sepsis, and cardiovascular events at time points closest to 90 days in acutely ill adults.Results: The study included 50 randomized clinical trials of 21,014 participants; 36 trials with a total of 20,166 participants contributed data to the analyses. Meta-analysis and TSAs showed no difference between higher and lower oxygenation strategies in trials at overall low risk of bias except for blinding: mortality relative risk (RR), 0.98 (95% CI, 0.89-1.09; TSA-adjusted CI, 0.86-1.12; low certainty evidence); serious adverse events RR, 0.99 (95% CI, 0.89-1.12; TSA-adjusted CI, 0.83-1.19; low certainty evidence). The corresponding summary estimates including trials with overall low and high risk of bias showed similar results. No difference was found between higher and lower oxygenation strategies in meta-analyses and TSAs regarding quality of life, lung injury, sepsis, and cardiovascular events (very low certainty evidence).Interpretation: No evidence was found of beneficial or harmful effects of higher vs lower oxygenation strategies in acutely ill adults (low to very low certainty evidence).Clinical Trial Registration: PROSPERO; No.: CRD42017058011; URL: https://www.crd.york.ac.uk/prospero/. [ABSTRACT FROM AUTHOR]

Background: Supplemental oxygen therapy is commonly required for respiratory failure requiring mechanical ventilation in the ICU. However, hyperoxaemia may be injurious and may increase mortality. We evaluated the relationship amongst the degree of hyperoxaemia and changes in fraction of inspired oxygen (Fio2) in response to hyperoxaemia, as well as associations with mortality in mechanically ventilated ICU patients.Methods: We retrospectively identified all invasively mechanically ventilated patients admitted to five ICUs, and retrieved all oxygen tension (Pao2) and Fio2 data. We assessed the time between arterial blood gas (ABG) samples, proportions of patients with hyperoxaemia, and changes in Fio2 when hyperoxaemia was present. The primary outcome was the association between Pao2 (assessed by mechanically ventilated exposure-time-divided area under the curve [AUC]) and mortality (in-ICU and post-ICU discharge) using a multistate illness-death model with transition intensities estimated by Cox proportional hazards models.Results: We assessed 177 769 ABG analyses obtained from 4998 patients between January 2012 and June 2016. The median time between ABGs was 3 h (inter-quartile range: 2-4 h); the median Pao2 was 11.3 kPa (9.8-13.6 kPa), and Fio2 was 0.40 (0.35-0.50). Hyperoxaemia (Pao2 >13.7 kPa) was present in 23.9% of the ABGs, and hyperoxaemia seemed to be disregarded when Fio2 was <0.40, as >50% of these Fio2 values were not subsequently reduced. AUC Pao2 >16.0 kPa was associated with increased ICU mortality (adjusted hazard ratio: 1.75; 95% confidence interval: 1.28-2.40).Conclusions: In mechanically ventilated ICU patients, hyperoxaemia was common. Although oxygen supplementation was often reduced when hyperoxaemia was observed, several patients remained hyperoxaemic. Hyperoxaemia was associated with increased ICU mortality in these patients. [ABSTRACT FROM AUTHOR]

Background: Pre-intensive care unit (ICU) induction of targeted temperature management (TTM) with cold intravenous (i.v.) fluids does not appear to improve outcomes after in out-of-hospital cardiac arrest (OHCA). We hypothesized that this may be due to ineffective cooling and side effects.Methods: A post hoc analysis of a sub-group of patients (n = 352) in the TTH48 trial (NCT01689077) who received or did not receive pre-ICU cooling using cold i.v. fluids. Data collection included patient characteristics, cardiac arrest factors, cooling methods, side effects and continuous core temperature measurements. The primary endpoint was the time to target temperature (TTT, <34 °C), and the secondary endpoints included the incidence of circulatory side effects, abnormal electrolyte levels and hypoxia within the first 24 h of ICU care. A difference of 1 h in the TTT was determined as clinically significant a priori.Results: Of 352 patients included in the present analysis, 110 received pre-ICU cold fluids. The median time to the return of spontaneous circulation (ROSC) and TTT in the pre-ICU cold fluids group was longer than that of the group that did not receive pre-ICU cold fluids (318 vs. 281 min, p < 0.01). In a linear regression model including the treatment centre, body mass index (BMI), chronic heart failure, diabetes mellitus and time to ROSC, the use of pre-ICU cold i.v. fluids was not associated with a shorter time to the target temperature (standardized beta coefficient: 0.06, 95% CI for B -49 and 16, p  =  0.32). According to the receipt or not of pre-ICU cold i.v. fluids, there was no difference in the proportion of patients with hypoxia on ICU admission (1.8% vs. 3.3%, p =  0.43) or the proportion of patients with electrolyte abnormalities (hyponatremia: 1.8% vs. 2.9% p = 0.54; hypokalaemia: 1.8% vs. 4.5%, p =  0.20). Furthermore, there was no difference in hospital mortality between the groups.Conclusions: The initiation of TTM with cold i.v. fluids before ICU arrival did not decrease the TTT. We detected no significant between-group difference in mortality or the incidence of side effects according to the administration or not of pre-ICU cold i.v fluids. [ABSTRACT FROM AUTHOR]

The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC) with no clear effect on long-term outcomes. The objective of the current manuscript was to evaluate the hemodynamic effects of intra-cardiac arrest vasopressin and methylprednisolone during the first 24 hours after ROSC. The VAM-IHCA trial randomized patients with in-hospital cardiac arrest to a combination of vasopressin and methylprednisolone or placebo during the cardiac arrest. This study is a post hoc analysis focused on the hemodynamic effects of the intervention after ROSC. Post-ROSC data on the administration of glucocorticoids, mean arterial blood pressure, heart rate, blood gases, vasopressor and inotropic therapy, and sedation were collected. Total vasopressor dose between the two groups was calculated based on noradrenaline-equivalent doses for adrenaline, phenylephrine, terlipressin, and vasopressin. The present study included all 186 patients who achieved ROSC in the VAM IHCA-trial of which 100 patients received vasopressin and methylprednisolone and 86 received placebo. The number of patients receiving glucocorticoids during the first 24 hours was 22/86 (26%) in the placebo group and 14/100 (14%) in the methylprednisolone group with no difference in the cumulative hydrocortisone-equivalent dose. There was no significant difference between the groups in the mean cumulative noradrenaline-equivalent dose (vasopressin and methylprednisolone: 603 ug/kg [95CI% 227; 979] vs. placebo: 651 ug/kg [95CI% 296; 1007], mean difference −48 ug/kg [95CI% −140; 42.9], p = 0.30), mean arterial blood pressure, or lactate levels. There was no difference between groups in arterial blood gas values and vital signs. Treatment with vasopressin and methylprednisolone during cardiac arrest caused no difference in mean arterial blood pressure, vasopressor use, or arterial blood gases within the first 24 hours after ROSC when compared to placebo. [ABSTRACT FROM AUTHOR]

Aim: To describe the use of invasive mechanical ventilation core strategies, adjuvant treatments and the occurrence of barotrauma and prolonged ventilation in ICU patients with COVID-19 in Denmark, retrospectively., Methods: All ICUs admitting COVID-19 patients in Denmark from 10 March 2020 to 2 April 2021 were invited to participate. All patients with COVID-19 who received invasive mechanical ventilation were included and data was retrospectively collected from electronic patient records., Results: A total of 774 patients were invasively ventilated during the first two waves and included; 70% were males and the median age was 69 years. 340 (51.5%) of patients never exceeded tidal volumes of 8 mL/kg. For all patients, tidal volumes under 8 mL/kg were applied in 77.6% (IQR 54.5%-96.2%) of the time on ventilator in the ICU; plateau pressure was below 30 cm H 2 O in 125 (80.6%) patients; prone positioning was used in 44.7% of patients. In ICU, 169 of 774 (21.8%) patients experienced barotrauma and 220 (28.4%) prolonged ventilation. At 90 days, 306 (39.5%) had died., Conclusions: Lung protective ventilation and prone positioning were used in many of the Danish ICU patients with COVID-19, but barotrauma, prolonged ventilation and death occurred frequently., (© 2025 Acta Anaesthesiologica Scandinavica Foundation.)

Background: Oxygen supplementation is ubiquitous in intensive care unit (ICU) patients with chronic obstructive pulmonary disease (COPD) and acute hypoxaemia, but the optimal oxygenation target has not been established., Methods: This was a pre-planned subgroup analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) trial, which allocated patients with acute hypoxaemia to a lower oxygenation target (partial pressure of arterial oxygen [ P ao 2 ] of 8 kPa) vs a higher target ( P ao 2 of 12 kPa) during ICU admission, for up to 90 days; the allocation was stratified for presence or absence of COPD. Here, we report key outcomes for patients with COPD., Results: The HOT-ICU trial enrolled 2928 patients of whom 563 had COPD; 277 were allocated to the lower and 286 to the higher oxygenation group. After allocation, the median P ao 2 was 9.1 kPa (inter-quartile range 8.7-9.9) in the lower group vs 12.1 kPa (11.2-12.9) in the higher group. Data for arterial carbon dioxide ( P aco 2 ) were available for 497 patients (88%) with no between-group difference in time-weighted average; median P aco 2 6.0 kPa (5.2-7.2) in the lower group vs 6.2 kPa (5.4-7.3) in the higher group. At 90 days, 122/277 patients (44%) in the lower oxygenation group had died vs 132/285 patients (46%) in the higher (relative risk 0.98; 95% confidence interval 0.82-1.17; P =0.67). No statistically significant differences were found in any secondary outcome., Conclusions: In ICU patients with COPD and acute hypoxaemia, a lower vs a higher oxygenation target did not reduce mortality. There were no between-group differences in P aco 2 or in secondary outcomes., Clinical Trial Registration: NCT03174002, EudraCT number 2017-000632-34., (© 2024 The Authors.)

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial., Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU)., Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023., Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU., Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days., Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital., Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg., Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.

Importance: Midline catheters (MCs) are widely used, but safety and efficacy compared with peripherally inserted central catheters (PICCs) has not been adequately evaluated., Objective: To compare the safety and efficacy of MCs with PICCs among adult patients with an anticipated intravenous therapy lasting from 5 to 28 days., Design, Setting, and Participants: This parallel, 2-group, open-label, randomized clinical trial (RCT) was conducted in Denmark from October 2018 to February 2022 at a single academic tertiary care center. Adult inpatients and outpatients were consecutively randomized., Intervention: Patients were randomized in a 1:1 ratio to either the MC group or the PICC control group., Main Outcomes and Measures: The primary outcome was catheter-related bloodstream infection (CRBSI), analyzed using the Fisher exact test. Secondary outcomes were symptomatic catheter-related thrombosis and catheter failure, including mechanical cause, phlebitis, infiltration, pain in relation to drug or fluid administration, and leaking from the puncture site. Incidence rate ratios (IRRs) were calculated to assess between-group failure rates over device dwell time using Poisson regression. An intention-to-treat analysis was performed., Results: A total of 304 patients (mean [SD] age, 64.6 [13.5] years; 130 [42.8%] female) were included in the analysis, and 152 patients were allocated to each catheter group. The incidence of CRBSI was low, with 0 in the MC group and 1 in the PICC control group (P > .99). The MC group had a higher catheter-related complication rate (20 [13.2%] vs 11 [7.2%]), and an IRR of 2.37 (95% CI, 1.12-5.02; P = .02) for complications compared with the PICC control group. In a post hoc analysis stratified by catheter dwell time, no significant difference in complication rate (IRR, 1.16; 95% CI, 0.50-2.68; P = .73) was found between the 2 groups for catheters used less than 16 days., Conclusions and Relevance: In this RCT with patients who received medium- to long-term intravenous therapy, the incidence of CRBSI was low, with no difference between MCs and PICCs. The use of MCs resulted in a higher incidence of catheter-related complications compared with use of PICCs. This finding should be balanced in the decision of type of catheter used at the individual patient level., Trial Registration: ClinicalTrials.gov Identifier: NCT04140916.

Background: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers., Methods: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice., Results: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF., Conclusions: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF., (© 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Platform trials focus on the perpetual testing of many interventions in a disease or a setting. These trials have lasting organizational, administrative, data, analytic, and operational frameworks making them highly efficient. The use of adaptation often increases the probabilities of allocating participants to better interventions and obtaining conclusive results. The COVID-19 pandemic showed the potential of platform trials as a fast and valid way to improved treatments. This review gives an overview of key concepts and elements using the Intensive Care Platform Trial (INCEPT) as an example., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Background: Patients admitted to an intensive care unit (ICU) with active haematological malignancy and hypoxaemic respiratory failure have a high mortality. Oxygen supplementation is essential, but limited information exists on the optimum oxygenation targets in these patients., Methods: This subgroup analysis was specified before completion of the Handling Oxygenation Targets in the ICU (HOT-ICU) trial. The trial investigated the effects of a lower (8 kPa) vs a higher (12 kPa) arterial oxygenation target and was stratified for active haematological malignancy, chronic obstructive pulmonary disease, and site. We here report the primary outcome (90-day mortality) and selected secondary outcomes in the subgroup of patients with active haematological malignancy., Results: The HOT-ICU trial included 168 patients with active haematological malignancy; 82 were randomly allocated to an arterial oxygenation target of 8 kPa, and 86 to 12 kPa. At 90 days, 53/81 patients (65%) in the lower-oxygenation group and 47/86 patients (55%) in the higher-oxygenation group had died: adjusted relative risk 1.22 (95% confidence interval 0.95-1.56); at 1 year, the numbers were 58/81 (72%) vs 56/86 (65%): adjusted relative risk 1.11 (95% confidence interval 0.90-1.36). No statistically significant differences were found for any secondary outcomes., Conclusion: In ICU patients with active haematological malignancies and hypoxaemic respiratory failure, we found a high mortality at 90 days and 1 year. Our results did not preclude clinically relevant benefits or harms of a lower oxygenation target in patients with active haematological malignancy. A randomised trial may, therefore, be worthwhile for these patients., Clinical Trial Registration: NCT03174002., (© 2022 The Authors.)

Objective: Cardiopulmonary comorbidity is common in vascular surgery. General anaesthesia (GA) may impair perfusion and induce respiratory depression. Regional anaesthesia (RA), including neuraxial or peripheral nerve blocks, may therefore be associated with a better outcome., Methods: This was a nationwide retrospective cohort study. All open inguinal and infra-inguinal arterial surgical reconstructions from 2005 to 2017 were included. Data were extracted from national registries. Multivariable linear and logistic regression models and propensity score matching were used. The propensity score was derived by developing a model that predicted the probability that a given patient would receive GA based on age, comorbidity, anticoagulant medication, procedure type, and the urgency of surgery. Matching was performed in four groups based on American Society of Anesthesiologists' score I - II, score III - V, and gender. Outcome parameters included surgical and general complications (bleeding, thrombosis/embolus, cardiac, pulmonary, renal, cerebral, and >3 days intensive care therapy), length of stay, and 30 day mortality, hypothesising a better outcome after RA., Results: There were 10 509 procedures in the GA group and 6 850 in the RA group. After propensity score matching, 6 267 procedures were included in each group. Surgical and general complications were significantly more common after GA in both matched (3.8 vs. 2.5%, p < .001 and 6.5 vs. 4.2%, p < .001) and unmatched analyses (3.8 vs. 2.5%, p < .001 and 6.5 vs. 4.2%, p < .001). The 30 day mortality rate was significantly higher after GA, in matched and un matched analyses (3.1 vs. 2.4%, p = .019 and 4.1 vs. 2.4%, p < .001). There was no difference in length of stay., Conclusion: RA may be associated with a better outcome, compared with GA, after open inguinal and infra-inguinal peripheral vascular surgery. In the clinical context when RA is not feasible, GA can still be considered safe., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Objective: To describe the clinical trial "Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest" (VAM-IHCA)., Methods: The VAM-IHCA trial is an investigator-initiated, multicenter, randomized, placebo-controlled, parallel group, double-blind, superiority trial of vasopressin and methylprednisolone during adult in-hospital cardiac arrest. The study drugs consist of 40 mg methylprednisolone and 20 IU of vasopressin given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU).The primary outcome is return of spontaneous circulation and key secondary outcomes include survival and survival with a favorable neurological outcome at 30 days. 492 patients will be enrolled. The trial was registered at the EU Clinical Trials Register (EudraCT Number: 2017-004773-13) on Jan. 25, 2018 and ClinicalTrials.gov (Identifier: NCT03640949) on Aug. 21, 2018., Results: The trial started in October 2018 and the last patient is anticipated to be included in January 2021. The primary results will be reported after 3-months follow-up and are, therefore, anticipated in mid-2021., Conclusion: The current article describes the design of the VAM-IHCA trial. The results from this trial will help clarify whether the combination of vasopressin and methylprednisolone when administered during in-hospital cardiac arrest improves outcomes., (© 2021 Published by Elsevier B.V.)

Background: In patients with septic shock, mortality is high, and survivors experience long-term physical, mental and social impairments. The ongoing Conservative vs Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial assesses the benefits and harms of a restrictive vs standard-care intravenous (IV) fluid therapy. The hypothesis is that IV fluid restriction improves patient-important long-term outcomes., Aim: To assess the predefined patient-important long-term outcomes in patients randomised into the CLASSIC trial., Methods: In this pre-planned follow-up study of the CLASSIC trial, we will assess all-cause mortality, health-related quality of life (HRQoL) and cognitive function 1 year after randomisation in the two intervention groups. The 1-year mortality will be collected from electronic patient records or central national registries in most participating countries. We will contact survivors and assess EuroQol 5-Dimension, -5-Level (EQ-5D-5L) and EuroQol-Visual Analogue Scale and Montreal Cognitive Assessment 5-minute protocol score. We will analyse mortality by logistic regression and use general linear models to assess HRQoL and cognitive function., Discussion: With this pre-planned follow-up study of the CLASSIC trial, we will provide patient-important data on long-term survival, HRQoL and cognitive function of restrictive vs standard-care IV fluid therapy in patients with septic shock., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

This article reviews fellowship training in adult cardiac, thoracic, and vascular anesthesia and critical care from the perspective of European program initiators and educational leaders in these subspecialties together with current training fellows. Currently, the European Association of Cardiothoracic Anaesthesiology (EACTA) network has 20 certified fellowship positions each year in 10 hosting centers within 7 European countries, with 2 positions outside Europe (São Paulo, Brazil). Since 2009, 42 fellows have completed the fellowship training. The aim of this article is to provide an overview of the rationale, requirements, and contributions of the fellows, in the context of the developmental progression of the EACTA fellowship in adult cardiac, thoracic, and vascular anesthesia and critical care from inception to present. A summary of the program structure, accreditation of host centers, requirements to join the program, teaching and assessment tools, certification, and training requirements in transesophageal electrocardiography is outlined. In addition, a description of the current state of EACTA fellowships across Europe, and a perspective for future steps and challenges to the educational program, is provided., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Prophylaxis for gastrointestinal stress ulceration is frequently given to patients in the intensive care unit (ICU), but its risks and benefits are unclear., Methods: In this European, multicenter, parallel-group, blinded trial, we randomly assigned adults who had been admitted to the ICU for an acute condition (i.e., an unplanned admission) and who were at risk for gastrointestinal bleeding to receive 40 mg of intravenous pantoprazole (a proton-pump inhibitor) or placebo daily during the ICU stay. The primary outcome was death by 90 days after randomization., Results: A total of 3298 patients were enrolled; 1645 were randomly assigned to the pantoprazole group and 1653 to the placebo group. Data on the primary outcome were available for 3282 patients (99.5%). At 90 days, 510 patients (31.1%) in the pantoprazole group and 499 (30.4%) in the placebo group had died (relative risk, 1.02; 95% confidence interval [CI], 0.91 to 1.13; P=0.76). During the ICU stay, at least one clinically important event (a composite of clinically important gastrointestinal bleeding, pneumonia, Clostridium difficile infection, or myocardial ischemia) had occurred in 21.9% of patients assigned to pantoprazole and 22.6% of those assigned to placebo (relative risk, 0.96; 95% CI, 0.83 to 1.11). In the pantoprazole group, 2.5% of patients had clinically important gastrointestinal bleeding, as compared with 4.2% in the placebo group. The number of patients with infections or serious adverse reactions and the percentage of days alive without life support within 90 days were similar in the two groups., Conclusions: Among adult patients in the ICU who were at risk for gastrointestinal bleeding, mortality at 90 days and the number of clinically important events were similar in those assigned to pantoprazole and those assigned to placebo. (Funded by Innovation Fund Denmark and others; SUP-ICU ClinicalTrials.gov number, NCT02467621 .).