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Background: While SARS-CoV2 infection has been shown to be a significant risk-factor for several secondary bacterial, viral and Aspergillus infections, its impact on intensive care unit (ICU)-acquired candidemia (ICAC) remains poorly explored. Method: Using the REA-REZO network (French surveillance network of ICU-acquired infections), we included all adult patients hospitalized for a medical reason of admission in participating ICUs for at least 48 h from January 2020 to January 2023. To account for confounders, a non-parsimonious propensity score matching was performed. Rates of ICAC according to SARS-CoV2 status were compared in matched patients. Factors associated with ICAC in COVID-19 patients were also assessed using a Fine-Gray model. Results: A total of 55,268 patients hospitalized at least 48 h for a medical reason in 101 ICUs were included along the study period. Of those, 13,472 were tested positive for a SARS-CoV2 infection while 284 patients developed an ICAC. ICAC rate was higher in COVID-19 patients in both the overall population and the matched patients' cohort (0.8% (107/13,472) versus 0.4% (173/41,796); p < 0.001 and 0.8% (93/12,241) versus 0.5% (57/12,241); p = 0.004, respectively). ICAC incidence rate was also higher in those patients (incidence rate 0.51 per 1000 patients-days in COVID-19 patients versus 0.32 per 1000 patients-days; incidence rate ratio: 1.58 [95% CI:1.08–2.35]; p = 0.018). Finally, patients with ICAC had a higher ICU mortality rate (49.6% versus 20.2%; p < 0.001). Conclusion: In this large multicenter cohort of ICU patients, although remaining low, the rate of ICAC was higher among COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Physical inactivity and subsequent muscle atrophy are highly prevalent in neurocritical care and are recognized as key mechanisms underlying intensive care unit acquired weakness (ICUAW). The lack of quantifiable biomarkers for inactivity complicates the assessment of its relative importance compared to other conditions under the syndromic diagnosis of ICUAW. We hypothesize that active movement, as opposed to passive movement without active patient participation, can serve as a valid proxy for activity and may help predict muscle atrophy. To test this hypothesis, we utilized non-invasive, body-fixed accelerometers to compute measures of active movement and subsequently developed a machine learning model to predict muscle atrophy. Methods: This study was conducted as a single-center, prospective, observational cohort study as part of the MINCE registry (metabolism and nutrition in neurointensive care, DRKS-ID: DRKS00031472). Atrophy of rectus femoris muscle (RFM) relative to baseline (day 0) was evaluated at days 3, 7 and 10 after intensive care unit (ICU) admission and served as the dependent variable in a generalized linear mixed model with Least Absolute Shrinkage and Selection Operator regularization and nested-cross validation. Results: Out of 407 patients screened, 53 patients (age: 59.2 years (SD 15.9), 31 (58.5%) male) with a total of 91 available accelerometer datasets were enrolled. RFM thickness changed − 19.5% (SD 12.0) by day 10. Out of 12 demographic, clinical, nutritional and accelerometer-derived variables, baseline RFM muscle mass (beta − 5.1, 95% CI − 7.9 to − 3.8) and proportion of active movement (% activity) (beta 1.6, 95% CI 0.1 to 4.9) were selected as significant predictors of muscle atrophy. Including movement features into the prediction model substantially improved performance on an unseen test data set (including movement features: R2 = 79%; excluding movement features: R2 = 55%). Conclusion: Active movement, as measured with thigh-fixed accelerometers, is a key risk factor for muscle atrophy in neurocritical care patients. Quantifiable biomarkers reflecting the level of activity can support more precise phenotyping of ICUAW and may direct tailored interventions to support activity in the ICU. Studies addressing the external validity of these findings beyond the neurointensive care unit are warranted. Trial registration: DRKS00031472, retrospectively registered on 13.03.2023. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes virus-induced-senescence. There is an association between shorter telomere length (TL) in coronavirus disease 2019 (COVID-19) patients and hospitalization, severity, or even death. However, it remains unknown whether virus-induced-senescence is reversible. We aim to evaluate the dynamics of TL in COVID-19 patients 1 year after recovery from intensive care units (ICU). Longitudinal study enrolling 49 patients admitted to ICU due to COVID-19 (August 2020 to April 2021). Relative telomere length (RTL) quantification was carried out in whole blood by monochromatic multiplex real-time quantitative PCR (MMqPCR) assay at hospitalization (baseline) and 1 year after discharge (1-year visit). The association between RTL and ICU length of stay (LOS), invasive mechanical ventilation (IMV), prone position, and pulmonary fibrosis development at 1-year visit was evaluated. The median age was 60 years, 71.4% were males, median ICU-LOS was 12 days, 73.5% required IMV, and 38.8% required a prone position. Patients with longer ICU-LOS or who required IMV showed greater RTL shortening during follow-up. Patients who required pronation had a greater RTL shortening during follow-up. IMV patients who developed pulmonary fibrosis showed greater RTL reduction and shorter RTL at the 1-year visit. Patients with longer ICU-LOS and those who required IMV had a shorter RTL in peripheral blood, as observed 1 year after hospital discharge. Additionally, patients who required IMV and developed pulmonary fibrosis had greater telomere shortening, showing shorter telomeres at the 1-year visit. These patients may be more prone to develop cellular senescence and lung-related complications; therefore, closer monitoring may be needed. [ABSTRACT FROM AUTHOR]

Background: Vitamin K is essential for numerous physiological processes, including coagulation, bone metabolism, tissue calcification, and antioxidant activity. Deficiency, prevalent in critically ill ICU patients, impacts coagulation and increases the risk of bleeding and other complications. This review aims to elucidate the metabolism of vitamin K in the context of critical illness and identify a potential therapeutic approach. Methods: In December 2023, a scoping review was conducted using the PRISMA Extension for Scoping Reviews. Literature was searched in PubMed, Embase, and Cochrane databases without restrictions. Inclusion criteria were studies on adult ICU patients discussing vitamin K deficiency and/or supplementation. Results: A total of 1712 articles were screened, and 13 met the inclusion criteria. Vitamin K deficiency in ICU patients is linked to malnutrition, impaired absorption, antibiotic use, increased turnover, and genetic factors. Observational studies show higher PIVKA-II levels in ICU patients, indicating reduced vitamin K status. Risk factors include inadequate intake, disrupted absorption, and increased physiological demands. Supplementation studies suggest vitamin K can improve status but not normalize it completely. Vitamin K deficiency may correlate with prolonged ICU stays, mechanical ventilation, and increased mortality. Factors such as genetic polymorphisms and disrupted microbiomes also contribute to deficiency, underscoring the need for individualized nutritional strategies and further research on optimal supplementation dosages and administration routes. Conclusions: Addressing vitamin K deficiency in ICU patients is crucial for mitigating risks associated with critical illness, yet optimal management strategies require further investigation. Impact research: To the best of our knowledge, this review is the first to address the prevalence and progression of vitamin K deficiency in critically ill patients. It guides clinicians in diagnosing and managing vitamin K deficiency in intensive care and suggests practical strategies for supplementing vitamin K in critically ill patients. This review provides a comprehensive overview of the existing literature, and serves as a valuable resource for clinicians, researchers, and policymakers in critical care medicine. [ABSTRACT FROM AUTHOR]

Background: Gut colonization with multidrug-resistant organisms (MDRO) frequently precedes infection among patients in the intensive care unit (ICU), although the dynamics of colonization are not completely understood. We performed a systematic review and meta-analysis of ICU studies which described the cumulative incidence and rates of MDRO gut acquisition. Methods: We systematically searched PubMed, Embase, and Web of Science for studies published from 2010 to 2023 reporting on gut acquisition of MDRO in the ICU. MDRO were defined as multidrug resistant non-Pseudomonas Gram-negative bacteria (NP-GN), Pseudomonas spp., and vancomycin-resistant Enterococcus (VRE). We included observational studies which obtained perianal or rectal swabs at ICU admission (within 48 h) and at one or more subsequent timepoints. Our primary outcome was the incidence rate of gut acquisition of MDRO, defined as any MDRO newly detected after ICU admission (i.e., not present at baseline) for all patient-time at risk. The study was registered with PROSPERO, CRD42023481569. Results: Of 482 studies initially identified, 14 studies with 37,305 patients met criteria for inclusion. The pooled incidence of gut acquisition of MDRO during ICU hospitalization was 5% (range: 1–43%) with a pooled incidence rate of 12.2 (95% CI 8.1–18.6) per 1000 patient-days. Median time to acquisition ranged from 4 to 26 days after ICU admission. Results were similar for NP-GN and Pseudomonas spp., with insufficient data to assess VRE. Among six studies which provided sufficient data to perform curve fitting, there was a quasi-linear increase in gut MDRO colonization of 1.41% per day which was stable through 30 days of ICU hospitalization (R2 = 0.50, p < 0.01). Conclusions: Acquisition of gut MDRO was common in the ICU and increases with days spent in ICU through 30 days of follow-up. These data may guide future interventions seeking to prevent gut acquisition of MDRO in the ICU. [ABSTRACT FROM AUTHOR]

BackgroundCoronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far.MethodsIn this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria.ResultsWe included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2-9.7) in the MAFP group and 17.5% (95% CI 9.6-31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01-0.63; p = 0.017).ConclusionIn ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. Materials and methods The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. Results Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13–9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23–11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07–33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76–10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01–4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42–1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. Conclusion PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis.

Abstract Background Anticoagulants are widely used but can lead to iatrogenic events such as bleeding. Limited data exists regarding the characteristics and management of patients admitted to intensive care units (ICU) for severe anticoagulant-related extracranial bleeding. Methods A retrospective observational study was conducted in five French ICUs. From January 2007 to December 2018, all patients aged over 18 years admitted to ICU for extracranial bleeding while receiving therapeutic anticoagulation were included. Results 486 patients were included, mainly male (61%) with an average age of 73 ± 13 years. Most patients had comorbidities, including hypertension (68%), heart disease (49%) and diabetes (33%). Patients were treated by vitamin K antagonists (VKA, 54%), heparins (25%) and direct oral anticoagulants (DOAC, 7%). The incidence of patients admitted to ICU for anticoagulant-related bleeding increased from 3.2/1000 admissions in 2007 to 5.8/1000 in 2018. This increase was particularly high for DOAC class. Upon admission, patients exhibited severe organ failure, as evidenced by a high SOFA score (7 ± 4) and requirement for organ support therapies such as vasopressors (31.5%) and invasive mechanical ventilation (34%). Adherence to guidelines for the specific treatment of anticoagulant-related bleeding was generally low. ICU mortality was 27%. In multivariate analysis, five factors were independently associated with mortality: chronic hypertension, need for vasopressors, impaired consciousness, hyperlactatemia and prolonged aPTT > 1.2. Conclusion Anticoagulant-related extracranial bleeding requiring ICU admission is a serious complication responsible for organ failure and significant mortality. Its incidence is rising. The therapeutic management is suboptimal and could be improved by educational programs.

Background: Candidemia is a high-risk complication among intensive care unit (ICU) patients. While selective digestive decontamination (SDD) has been shown to be effective in preventing ICU-acquired bacterial secondary infection, its effects on ICU-acquired candidemia (ICAC) remain poorly explored. Therefore, we sought to assess the effects of SDD on ICAC. Method: Using the REA-REZO network, we included adult patients receiving mechanical ventilation for at least 48 h from January 2017 to January 2023. Non-parsimonious propensity score matching with a 1:1 ratio was performed to investigate the association between SDD and the rate of ICAC. Results: A total of 94 437 patients receiving at least 48 h of mechanical ventilation were included throughout the study period. Of those, 3 001 were treated with SDD and 651 patients developed ICAC. The propensity score matching included 2 931 patients in the SDD group and in the standard care group. In the matched cohort analysis as well as in the overall population, the rate of ICAC was lower in patients receiving SDD (0.8% versus 0.3%; p = 0.012 and 0.7% versus 0.3%; p = 0.006, respectively). Patients with ICAC had higher mortality rate (48.4% versus 29.8%; p < 0.001). Finally, mortality rates as well as ICU length of stay in the matched populations did not differ according to SDD (31.0% versus 31.1%; p = 0.910 and 9 days [5–18] versus 9 days [5–17]; p = 0.513, respectively). Conclusion: In this study with a low prevalence of ICAC, SDD was associated with a lower rate of ICAC that did not translate to higher survival. [ABSTRACT FROM AUTHOR]

Background: Sepsis survivors commonly experience functional impairment, which may limit return to work. We investigated return to work (RTW) of patients hospitalized with sepsis and the associations with patient and clinical characteristics. Methods: Working-age patients (18–60 years) admitted to a Norwegian hospital with sepsis between 2010 and 2021 were identified using the Norwegian Patient Registry and linked to sick-leave data from the Norwegian National Social Security System Registry. The main outcome was proportion of RTW in patients hospitalized with sepsis at 6 months, 1 year, and 2 years after discharge. Secondary outcomes were time trends in age-standardized proportions of RTW and probability of sustainable RTW (31 days of consecutive work). The time trends were calculated for each admission year, reported as percentage change with 95% confidence interval (CI). Time-to-event analysis, including crude and adjusted hazard risk (HRs), was used to explore the association between sustainable RTW, characteristics and subgroups of sepsis patients (intensive care unit (ICU) vs. non-ICU and COVID-19 vs. non-COVID-19). Results: Among 35.839 hospitalizations for sepsis among patients aged 18–60 years, 12.260 (34.2%) were working prior to hospitalization and included in this study. The mean age was 43.7 years. At 6 months, 1 year, and 2 years post-discharge, overall estimates showed that 58.6%, 67.5%, and 63.4%, respectively, were working. The time trends in age-standardized RTW for ICU and non-ICU sepsis patients remained stable over the study period, except the 2-year age-standardized RTW for non-ICU patients that declined by 1.51% (95% CI − 2.22 to − 0.79) per year, from 70.01% (95% CI 67.21 to 74.80) in 2010 to 57.04% (95% CI 53.81–60.28) in 2019. Characteristics associated with sustainable RTW were younger age, fewer comorbidities, and fewer acute organ dysfunctions. The probability of sustainable RTW was lower in ICU patients compared to non-ICU patients (HR 0.56; 95% CI 0.52–0.61) and higher in patients with COVID-19-related sepsis than in sepsis patients (HR 1.31; 95% CI 1.15–1.49). Conclusion: Absence of improvement in RTW proportions over time and the low probability of sustainable RTW in sepsis patients need attention, and further research to enhance outcomes for sepsis patients is required. [ABSTRACT FROM AUTHOR]

Abstract Background Sepsis is a heterogenous syndrome with limited therapeutic options. Identifying immunological endotypes through gene expression patterns in septic patients may lead to targeted interventions. We investigated whether patients admitted to a surgical intensive care unit (ICU) with sepsis and with high risk of mortality express similar endotypes to non-septic, but still critically ill patients using two multiplex transcriptomic metrics obtained both on admission to a surgical ICU and at set intervals. Methods We analyzed transcriptomic data from 522 patients in two single-site, prospective, observational cohorts admitted to surgical ICUs over a 5-year period ending in July 2020. Using an FDA-cleared analytical platform (nCounter FLEX®, NanoString, Inc.), we assessed a previously validated 29-messenger RNA transcriptomic classifier for likelihood of 30-day mortality (IMX-SEV-3) and a 33-messenger RNA transcriptomic endotype classifier. Clinical outcomes included all-cause mortality, development of chronic critical illness, and secondary infections. Univariate and multivariate analyses were performed to assess for true effect and confounding. Results Sepsis was associated with a significantly higher predicted and actual hospital mortality. At enrollment, the predominant endotype for both septic and non-septic patients was adaptive, though with significantly different distributions. Inflammopathic and coagulopathic septic patients, as well as inflammopathic non-septic patients, showed significantly higher frequencies of secondary infections compared to those with adaptive endotypes (p

Abstract Background The importance of assessing venous congestion in ICU patients is widely acknowledged, but its study is hampered by the lack of a practical evaluation tool. The Venous Excess Ultrasound Grading System (VExUS), based on a semi-quantitative combined ultrasound assessment, has been associated with acute kidney injury (AKI) in cardiac ICU patients. The objectives of this study were to assess the prevalence of congestion using VExUS in general ICU patients, and to evaluate the association between VExUS, AKI and death. Methods This prospective, observational study included adult patients within 24 h of ICU admission. VExUS and hemodynamic parameters were measured four times during the ICU stay: within 24 h of ICU admission, after day 1 (between 24 and 48 h), after day 2 (between 48 and 72 h), and last day of ICU stay. The prevalence of AKI during the first week in ICU and 28-day mortality were assessed. Results Among the 145 patients included, the percentage of patients with a VExUS score of 2 (moderate congestion) and 3 (severe congestion) was 16% and 6%, respectively. The prevalence did not change over the study period. There was no significant association between admission VExUS scores and AKI (p = 0.136) or 28-day mortality (p = 0.594). Admission VExUS ≥ 2 was not associated with AKI (OR 0.499, CI95% 0.21–1.17, p = 0.109) nor 28-day mortality (OR 0.75, CI95% 0.2–2.8, p = 0.669). The results were similar for VExUS scores measured at day 1 and day 2. Conclusions In general ICU cohort the prevalence of moderate to severe venous congestion was low. Early assessment of systemic venous congestion using VExUS scores was not associated with the development of AKI or with 28-day mortality.

Abstract The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients.

Background: Intensive Care survival continues to improve, and the number of ICU services is increasing globally. However, there is a growing awareness of the detrimental impact of the ICU environment on patients, families, and staff. Excessive noise and suboptimal lighting especially have been shown to adversely impact physical and mental recovery during and after an ICU admission. Current ICU designs have not kept up with advances in medical technology and models of care, and there is no current 'gold-standard' ICU design. Improvements in ICU designs are needed to optimise care delivery and patient outcomes. Methods: This manuscript describes a mixed-methods, multi-staged participatory design project aimed at redesigning and implementing two innovative ICU bedspaces. Guided by the action effect method and the consolidated framework for implementation research, the manuscript describes the processes taken to ensure the patient-centred problems were properly understood, the steps taken to develop and integrate solutions to identified problems, and the process of implementation planning and rebuilding in a live ICU. Results: Two innovative ICU bedspaces were rebuilt and implemented. They feature solutions to address all identified problems, including noise reduction, optimisation of lighting, access to nature via digital solutions, and patient connectivity and engagement, with solutions developed from various specialty fields, including IT improvements, technological innovations, and design and architectural solutions. Early evaluation demonstrates an improved lighting and acoustic environment. Conclusions: Optimising the ICU bedspace environment and improving the lighting and acoustic environment is possible. The impact on patient outcomes needs to be evaluated. [ABSTRACT FROM AUTHOR]

The goal of hemodynamic resuscitation is to optimize the microcirculation of organs to meet their oxygen and metabolic needs. Clinicians are currently blind to what is happening in the microcirculation of organs, which prevents them from achieving an additional degree of individualization of the hemodynamic resuscitation at tissue level. Indeed, clinicians never know whether optimization of the microcirculation and tissue oxygenation is actually achieved after macrovascular hemodynamic optimization. The challenge for the future is to have noninvasive, easy-to-use equipment that allows reliable assessment and immediate quantitative analysis of the microcirculation at the bedside. There are different methods for assessing the microcirculation at the bedside; all have strengths and challenges. The use of automated analysis and the future possibility of introducing artificial intelligence into analysis software could eliminate observer bias and provide guidance on microvascular-targeted treatment options. In addition, to gain caregiver confidence and support for the need to monitor the microcirculation, it is necessary to demonstrate that incorporating microcirculation analysis into the reasoning guiding hemodynamic resuscitation prevents organ dysfunction and improves the outcome of critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic, life-threatening disease commonly affecting immunocompromised patients. The distribution of predisposing diseases or conditions in critically ill patients admitted to intensive care unit (ICU) and subjected to diagnostic work-up for PJP has seldom been explored. Materials and methods: The primary objective of the study was to describe the characteristics of ICU patients subjected to diagnostic workup for PJP. The secondary objectives were: (i) to assess demographic and clinical variables associated with PJP; (ii) to assess the performance of Pneumocystis PCR on respiratory specimens and serum BDG for the diagnosis of PJP; (iii) to describe 30-day and 90-day mortality in the study population. Results: Overall, 600 patients were included in the study, of whom 115 had presumptive/proven PJP (19.2%). Only 8.8% of ICU patients subjected to diagnostic workup for PJP had HIV infection, whereas hematological malignancy, solid tumor, inflammatory diseases, and solid organ transplants were present in 23.2%, 16.2%, 15.5%, and 10.0% of tested patients, respectively. In multivariable analysis, AIDS (odds ratio [OR] 3.31; 95% confidence interval [CI] 1.13–9.64, p = 0.029), non-Hodgkin lymphoma (OR 3.71; 95% CI 1.23–11.18, p = 0.020), vasculitis (OR 5.95; 95% CI 1.07–33.22, p = 0.042), metastatic solid tumor (OR 4.31; 95% CI 1.76–10.53, p = 0.001), and bilateral ground glass on CT scan (OR 2.19; 95% CI 1.01–4.78, p = 0.048) were associated with PJP, whereas an inverse association was observed for increasing lymphocyte cell count (OR 0.64; 95% CI 0.42–1.00, p = 0.049). For the diagnosis of PJP, higher positive predictive value (PPV) was observed when both respiratory Pneumocystis PCR and serum BDG were positive compared to individual assay positivity (72% for the combination vs. 63% for PCR and 39% for BDG). Cumulative 30-day mortality and 90-day mortality in patients with presumptive/proven PJP were 52% and 67%, respectively. Conclusion: PJP in critically ill patients admitted to ICU is nowadays most encountered in non-HIV patients. Serum BDG when used in combination with respiratory Pneumocystis PCR could help improve the certainty of PJP diagnosis. [ABSTRACT FROM AUTHOR]

Background: Anticoagulants are widely used but can lead to iatrogenic events such as bleeding. Limited data exists regarding the characteristics and management of patients admitted to intensive care units (ICU) for severe anticoagulant-related extracranial bleeding. Methods: A retrospective observational study was conducted in five French ICUs. From January 2007 to December 2018, all patients aged over 18 years admitted to ICU for extracranial bleeding while receiving therapeutic anticoagulation were included. Results: 486 patients were included, mainly male (61%) with an average age of 73 ± 13 years. Most patients had comorbidities, including hypertension (68%), heart disease (49%) and diabetes (33%). Patients were treated by vitamin K antagonists (VKA, 54%), heparins (25%) and direct oral anticoagulants (DOAC, 7%). The incidence of patients admitted to ICU for anticoagulant-related bleeding increased from 3.2/1000 admissions in 2007 to 5.8/1000 in 2018. This increase was particularly high for DOAC class. Upon admission, patients exhibited severe organ failure, as evidenced by a high SOFA score (7 ± 4) and requirement for organ support therapies such as vasopressors (31.5%) and invasive mechanical ventilation (34%). Adherence to guidelines for the specific treatment of anticoagulant-related bleeding was generally low. ICU mortality was 27%. In multivariate analysis, five factors were independently associated with mortality: chronic hypertension, need for vasopressors, impaired consciousness, hyperlactatemia and prolonged aPTT > 1.2. Conclusion: Anticoagulant-related extracranial bleeding requiring ICU admission is a serious complication responsible for organ failure and significant mortality. Its incidence is rising. The therapeutic management is suboptimal and could be improved by educational programs. [ABSTRACT FROM AUTHOR]

Abstract Background Neisseria meningitidis is the leading responsible bacterium of Purpura Fulminans (PF) accounting for two thirds of PF. Skin biopsy is a simple and minimally invasive exam allowing to perform skin culture and polymerase chain reaction (PCR) to detect Neisseria meningitidis. We aimed to assess the sensitivity of skin biopsy in adult patients with meningococcal PF. Methods A 17-year multicenter retrospective cohort study including adult patients admitted to the ICU for a meningococcal PF in whom a skin biopsy with conventional and/or meningococcal PCR was performed. Results Among 306 patients admitted for PF, 195 had a meningococcal PF (64%) with a skin biopsy being performed in 68 (35%) of them. Skin biopsy was performed in median 1 day after the initiation of antibiotic therapy. Standard culture of skin biopsy was performed in 61/68 (90%) patients and grew Neisseria meningitidis in 28 (46%) of them. Neisseria meningitidis PCR on skin biopsy was performed in 51/68 (75%) patients and was positive in 50 (98%) of them. Among these 50 positive meningococcal PCR, five were performed 3 days or more after initiation of antibiotic therapy. Finally, skin biopsy was considered as contributive in 60/68 (88%) patients. Identification of the meningococcal serogroup was obtained with skin biopsy in 48/68 (71%) patients. Conclusions Skin biopsy with conventional culture and meningococcal PCR has a global sensitivity of 88% and should be systematically considered in case of suspected meningococcal PF even after the initiation of antimicrobial treatment.

Abstract Critical care is underprioritized. A global call to action is needed to increase equitable access to care and the quality of care provided to critically ill patients. Current challenges to effective critical care in resource-constrained settings are many. Estimates of the burden of critical illness are extrapolated from common etiologies, but the true burden remains ill-defined. Measuring the burden of critical illness is epidemiologically challenging but is thought to be increasing. Resources, infrastructure, and training are inadequate. Millions die unnecessarily due to critical illness. Solutions start with the implementation of first-step, patient care fundamentals known as Essential Emergency and Critical Care. Such essential care stands to decrease critical-illness mortality, augment pandemic preparedness, decrease postoperative mortality, and decrease the need for advanced level care. The entire healthcare workforce must be trained in these fundamentals. Additionally, physician and nurse specialists trained in critical care are needed and must be retained as leaders of critical care initiatives, researchers, and teachers. Context-specific research is mandatory to ensure care is appropriate for the patient populations served, not just duplicated from high-resourced settings. Governments must increase healthcare spending and invest in capacity to treat critically ill patients. Advocacy at all levels is needed to achieve universal health coverage for critically ill patients.

Abstract Background Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious complication in the ICU that results in increased mortality and risk of chronic kidney disease (CKD). Some studies suggest RRT modality may have an impact on long-term renal recovery after AKI. However, other predictive factors of severe long-term CKD in ICU patients with AKI requiring RRT are unknown. Methods We performed an ancillary study of the multicenter ELVIS trial in the population with AKI requiring RRT. Patients alive 3 months after RRT initiation were eligible. Serum creatinine levels available at 3, 6 and 12 months and 3 and 5 years were recorded. CKD stage was determined according to the glomerular filtration rate as estimated by the CKD-EPI formula. At each timepoint, two groups of patients were compared, a no/mild CKD group with normal or mildly to moderately decreased renal function (stages 1, 2 and 3 of the international classification) and a severe CKD group (stages 4 and 5). Our objective was to identify predictive factors of severe long-term CKD. Results Of the 287 eligible patients, 183 had follow-up at 3 months, 136 (74.3%) from the no/mild CKD group and 47 (25.7%) from the severe CKD group, and 122 patients at 5 years comprising 96 (78.7%) from the no/mild CKD group and 26 (21.3%) from the severe CKD group. Multivariate analysis showed that a long RRT period was associated with severe CKD up to 12 months (ORM12 = 1.03 95% CI [1.02–1.05] per day) and that a high SOFA score at the initiation of RRT was not associated with severe CKD up to 5 years (ORM60 = 0.85 95% CI [0.77–0.93] per point). Conclusion Severe long-term CKD was found in 21% of ICU survivors who underwent RRT for AKI. The duration of the RRT in AKI patients was identified as a new predictive factor for severe long-term CKD. This finding should be taken into consideration in future studies on the prognosis of ICU patients with AKI requiring RRT. Trial registration ELVIS trial was registered with ClinicalTrials.gov, number: NCT00875069 (June 16, 2014), and this ancillary study was registered with ClinicalTrials.gov, number: NCT03302624 (October 6, 2017).

Background: Sepsis is a heterogenous syndrome with limited therapeutic options. Identifying immunological endotypes through gene expression patterns in septic patients may lead to targeted interventions. We investigated whether patients admitted to a surgical intensive care unit (ICU) with sepsis and with high risk of mortality express similar endotypes to non-septic, but still critically ill patients using two multiplex transcriptomic metrics obtained both on admission to a surgical ICU and at set intervals. Methods: We analyzed transcriptomic data from 522 patients in two single-site, prospective, observational cohorts admitted to surgical ICUs over a 5-year period ending in July 2020. Using an FDA-cleared analytical platform (nCounter FLEX®, NanoString, Inc.), we assessed a previously validated 29-messenger RNA transcriptomic classifier for likelihood of 30-day mortality (IMX-SEV-3) and a 33-messenger RNA transcriptomic endotype classifier. Clinical outcomes included all-cause mortality, development of chronic critical illness, and secondary infections. Univariate and multivariate analyses were performed to assess for true effect and confounding. Results: Sepsis was associated with a significantly higher predicted and actual hospital mortality. At enrollment, the predominant endotype for both septic and non-septic patients was adaptive, though with significantly different distributions. Inflammopathic and coagulopathic septic patients, as well as inflammopathic non-septic patients, showed significantly higher frequencies of secondary infections compared to those with adaptive endotypes (p < 0.01). Endotypes changed during ICU hospitalization in 57.5% of patients. Patients who remained adaptive had overall better prognosis, while those who remained inflammopathic or coagulopathic had worse overall outcomes. For severity metrics, patients admitted with sepsis and a high predicted likelihood of mortality showed an inflammopathic (49.6%) endotype and had higher rates of cumulative adverse outcomes (67.4%). Patients at low mortality risk, whether septic or non-septic, almost uniformly presented with an adaptive endotype (100% and 93.4%, respectively). Conclusion: Critically ill surgical patients express different and evolving immunological endotypes depending upon both their sepsis status and severity of their clinical course. Future studies will elucidate whether endotyping critically ill, septic patients can identify individuals for targeted therapeutic interventions to improve patient management and outcomes. [ABSTRACT FROM AUTHOR]

Personalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent literature are presented. Low-dose enteral nutrition (EN) or parenteral nutrition (PN) can be started within 48 h of admission. While EN is preferred route of delivery, new data highlight PN can be given safely without increased risk; thus, when early EN is not feasible, provision of isocaloric PN is effective and results in similar outcomes. Indirect calorimetry (IC) measurement of energy expenditure (EE) is recommended by both European/American guidelines after stabilization post-ICU admission. Below-measured EE (~ 70%) targets should be used during early phase and increased to match EE later in stay. Low-dose protein delivery can be used early (~ D1-2) (< 0.8 g/kg/d) and progressed to ≥ 1.2 g/kg/d as patients stabilize, with consideration of avoiding higher protein in unstable patients and in acute kidney injury not on CRRT. Intermittent-feeding schedules hold promise for further research. Clinicians must be aware of delivered energy/protein and what percentage of targets delivered nutrition represents. Computerized nutrition monitoring systems/platforms have become widely available. In patients at risk of micronutrient/vitamin losses (i.e., CRRT), evaluation of micronutrient levels should be considered post-ICU days 5–7 with repletion of deficiencies where indicated. In future, we hope use of muscle monitors such as ultrasound, CT scan, and/or BIA will be utilized to assess nutrition risk and monitor response to nutrition. Use of specialized anabolic nutrients such as HMB, creatine, and leucine to improve strength/muscle mass is promising in other populations and deserves future study. In post-ICU setting, continued use of IC measurement and other muscle measures should be considered to guide nutrition. Research on using rehabilitation interventions such as cardiopulmonary exercise testing (CPET) to guide post-ICU exercise/rehabilitation prescription and using anabolic agents such as testosterone/oxandrolone to promote post-ICU recovery is needed. [ABSTRACT FROM AUTHOR]

Background: The importance of assessing venous congestion in ICU patients is widely acknowledged, but its study is hampered by the lack of a practical evaluation tool. The Venous Excess Ultrasound Grading System (VExUS), based on a semi-quantitative combined ultrasound assessment, has been associated with acute kidney injury (AKI) in cardiac ICU patients. The objectives of this study were to assess the prevalence of congestion using VExUS in general ICU patients, and to evaluate the association between VExUS, AKI and death. Methods: This prospective, observational study included adult patients within 24 h of ICU admission. VExUS and hemodynamic parameters were measured four times during the ICU stay: within 24 h of ICU admission, after day 1 (between 24 and 48 h), after day 2 (between 48 and 72 h), and last day of ICU stay. The prevalence of AKI during the first week in ICU and 28-day mortality were assessed. Results: Among the 145 patients included, the percentage of patients with a VExUS score of 2 (moderate congestion) and 3 (severe congestion) was 16% and 6%, respectively. The prevalence did not change over the study period. There was no significant association between admission VExUS scores and AKI (p = 0.136) or 28-day mortality (p = 0.594). Admission VExUS ≥ 2 was not associated with AKI (OR 0.499, CI95% 0.21–1.17, p = 0.109) nor 28-day mortality (OR 0.75, CI95% 0.2–2.8, p = 0.669). The results were similar for VExUS scores measured at day 1 and day 2. Conclusions: In general ICU cohort the prevalence of moderate to severe venous congestion was low. Early assessment of systemic venous congestion using VExUS scores was not associated with the development of AKI or with 28-day mortality. [ABSTRACT FROM AUTHOR]

Abstract Background Fluid overload and venous congestion are associated with morbi-mortality in the ICU (intensive care unit). Administration of diuretics to correct the fluid balance is common, although there is no strong relationship between the consequent fluid loss and clinical improvement. The aim of the study was to evaluate the ability of the portal pulsatility index, the renal venous impedance index, and the VEXUS score (venous ultrasound congestion score) to predict appropriate diuretic-induced fluid depletion. Methods The study had a prospective, observational, single-center observational design and was conducted in a university-affiliated medico-surgical ICU. Adult patients for whom the clinician decided to introduce loop diuretic treatment were included. Hemodynamic and ultrasound measurements (including the portal pulsatility index, renal venous impedance index and VEXUS score) were performed at inclusion and 2 hours after the initiation of the diuretics. The patients’ characteristics were noted at inclusion, 24 h later, and at ICU discharge. The appropriate diuretic-induced fluid depletion was defined by a congestive score lower than 3 after diuretic fluid depletion. The congestive score included clinical and biological parameters of congestion. Results Eighty-one patients were included, and 43 (53%) patients presented with clinically significant congestion score at inclusion. Thirty-four patients (42%) had an appropriate response to diuretic-induced fluid depletion. None of the left- and right-sided echocardiographic parameters differed between the two groups. The baseline portal pulsatility index was the best predictor of appropriate response to diuretic-induced fluid depletion (AUC = 0.80, CI95%:0.70–0.92, p = 0.001), followed by the renal venous impedance index (AUC = 0.72, CI95% 0.61–0.84, p = 0.001). The baseline VEXUS score (AUC of 0.66 CI95% 0.53–0.79, p = 0.012) was poorly predictive of appropriate response to diuretic-induced fluid depletion. Conclusion The portal pulsatility index and the renal venous impedance index were predictive of the appropriate response to diuretic-induced fluid depletion in ICU patients. The portal pulsatility index should be evaluated in future randomized studies.

Background: Neisseria meningitidis is the leading responsible bacterium of Purpura Fulminans (PF) accounting for two thirds of PF. Skin biopsy is a simple and minimally invasive exam allowing to perform skin culture and polymerase chain reaction (PCR) to detect Neisseria meningitidis. We aimed to assess the sensitivity of skin biopsy in adult patients with meningococcal PF. Methods: A 17-year multicenter retrospective cohort study including adult patients admitted to the ICU for a meningococcal PF in whom a skin biopsy with conventional and/or meningococcal PCR was performed. Results: Among 306 patients admitted for PF, 195 had a meningococcal PF (64%) with a skin biopsy being performed in 68 (35%) of them. Skin biopsy was performed in median 1 day after the initiation of antibiotic therapy. Standard culture of skin biopsy was performed in 61/68 (90%) patients and grew Neisseria meningitidis in 28 (46%) of them. Neisseria meningitidis PCR on skin biopsy was performed in 51/68 (75%) patients and was positive in 50 (98%) of them. Among these 50 positive meningococcal PCR, five were performed 3 days or more after initiation of antibiotic therapy. Finally, skin biopsy was considered as contributive in 60/68 (88%) patients. Identification of the meningococcal serogroup was obtained with skin biopsy in 48/68 (71%) patients. Conclusions: Skin biopsy with conventional culture and meningococcal PCR has a global sensitivity of 88% and should be systematically considered in case of suspected meningococcal PF even after the initiation of antimicrobial treatment. [ABSTRACT FROM AUTHOR]

Abstract Introduction Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in intensive care unit (ICU) patients with circulatory shock is limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock. Methods We analyzed a dataset from an international, multicenter, pragmatic randomized clinical trial (RCT) evaluating protein dose in ICU patients. Data were collected from ICU admission, and EEN was defined as initiating 48 h. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. The regression analysis model controlled for age, mNUTRIC score, APACHE II score, sepsis, and Site. Results We included 626 patients, from 52 ICUs in 14 countries. Median age was 60 years [18–93], 55% had septic shock, 99% received norepinephrine alone, 91% received EN alone, and 50.3% were randomized to a usual protein dose. Forty-two percent of EEN patients had persistent organ dysfunction syndrome plus death at day 28, compared to 53% in the DEN group (p = 0.04). EEN was associated with more ICU-free days (9.3 ± 9.2 vs. 5.7 ± 7.9, p = 0.0002), more days alive and free of vasopressors (7.1 ± 3.1 vs. 6.3 ± 3.2, p = 0.007), and shorter duration of MV among survivors (9.8 ± 10.9 vs. 13.8 ± 14.5, p = 0.0002). This trend was no longer observed in the adjusted analysis. There were no differences in ICU/60-day mortality or feeding intolerance rates between groups. Conclusion In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes, but no longer when adjusting for illness severity. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.

Abstract Introduction Rapid molecular tests could accelerate the control of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenemase-producing organisms (CPO) in intensive care units (ICUs). Objective and methods This interventional 12-month cohort study compared a loop-mediated isothermal amplification (LAMP) assay performed directly on rectal swabs with culturing methods (control period, 6 months), during routine ICU screening. Contact precautions (CP) were implemented for CPO or non-E. coli ESBL-producing Enterobacterales (nEcESBL-PE) carriers. Using survival analysis, we compared the time intervals from admission to discontinuation of unnecessary preemptive CP among patients at-risk and the time intervals from screening to implementation of CP among newly identified carriers. We also compared diagnostic performances, and nEcESBL-PE/CPO acquisition rates. This study is registered, ISRCTN 23588440. Results We included 1043 patients. During the intervention and control phases, 92/147 (62.6%) and 47/86 (54.7%) of patients at-risk screened at admission were candidates for early discontinuation of preemptive CP. The LAMP assay had a positive predictive value (PPV) of 44.0% and a negative predictive value (NPV) of 99.9% for CPO, and 55.6% PPV and 98.2% NPV for nEcESBL-PE. Due to result notification and interpretation challenges, the median time from admission to discontinuation of preemptive CP increased during the interventional period from 80.5 (95% CI 71.5–132.1) to 88.3 (95% CI 57.7–103.7) hours (p = 0.47). Due to the poor PPV, we had to stop using the LAMP assay to implement CP. No difference was observed regarding the incidence of nEcESBL-PE and CPO acquisition. Conclusion A rapid screening strategy with LAMP assays performed directly on rectal swabs had no benefit for infection control in a low-endemicity setting.

Abstract Background Acute respiratory distress syndrome (ARDS) has different phenotypes and distinct short-term outcomes. Patients with non-focal ARDS have a higher short-term mortality than focal ones. The aim of this study was to assess the impact of the morphological phenotypes of ARDS on long-term outcomes. Methods This was a secondary analysis of the LIVE study, a prospective, randomised control trial, assessing the usefulness of a personalised ventilator setting according to lung morphology in moderate-to-severe ARDS. ARDS was classified as focal (consolidations only in the infero-posterior part of the lungs) or non-focal. Outcomes were assessed using mortality and functional scores for quality of life at the 1-year follow-up. Results A total of 124 focal ARDS and 236 non-focal ARDS cases were included. The 1-year mortality was higher for non-focal ARDS than for focal ARDS (37% vs. 24%, p = 0.012). Non-focal ARDS (hazard ratio, 3.44; 95% confidence interval, 1.80–6.59; p

Critical care is underprioritized. A global call to action is needed to increase equitable access to care and the quality of care provided to critically ill patients. Current challenges to effective critical care in resource-constrained settings are many. Estimates of the burden of critical illness are extrapolated from common etiologies, but the true burden remains ill-defined. Measuring the burden of critical illness is epidemiologically challenging but is thought to be increasing. Resources, infrastructure, and training are inadequate. Millions die unnecessarily due to critical illness. Solutions start with the implementation of first-step, patient care fundamentals known as Essential Emergency and Critical Care. Such essential care stands to decrease critical-illness mortality, augment pandemic preparedness, decrease postoperative mortality, and decrease the need for advanced level care. The entire healthcare workforce must be trained in these fundamentals. Additionally, physician and nurse specialists trained in critical care are needed and must be retained as leaders of critical care initiatives, researchers, and teachers. Context-specific research is mandatory to ensure care is appropriate for the patient populations served, not just duplicated from high-resourced settings. Governments must increase healthcare spending and invest in capacity to treat critically ill patients. Advocacy at all levels is needed to achieve universal health coverage for critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious complication in the ICU that results in increased mortality and risk of chronic kidney disease (CKD). Some studies suggest RRT modality may have an impact on long-term renal recovery after AKI. However, other predictive factors of severe long-term CKD in ICU patients with AKI requiring RRT are unknown.Methods: We performed an ancillary study of the multicenter ELVIS trial in the population with AKI requiring RRT. Patients alive 3 months after RRT initiation were eligible. Serum creatinine levels available at 3, 6 and 12 months and 3 and 5 years were recorded. CKD stage was determined according to the glomerular filtration rate as estimated by the CKD-EPI formula. At each timepoint, two groups of patients were compared, a no/mild CKD group with normal or mildly to moderately decreased renal function (stages 1, 2 and 3 of the international classification) and a severe CKD group (stages 4 and 5). Our objective was to identify predictive factors of severe long-term CKD.Results: Of the 287 eligible patients, 183 had follow-up at 3 months, 136 (74.3%) from the no/mild CKD group and 47 (25.7%) from the severe CKD group, and 122 patients at 5 years comprising 96 (78.7%) from the no/mild CKD group and 26 (21.3%) from the severe CKD group. Multivariate analysis showed that a long RRT period was associated with severe CKD up to 12 months (ORM12 = 1.03 95% CI [1.02-1.05] per day) and that a high SOFA score at the initiation of RRT was not associated with severe CKD up to 5 years (ORM60 = 0.85 95% CI [0.77-0.93] per point).Conclusion: Severe long-term CKD was found in 21% of ICU survivors who underwent RRT for AKI. The duration of the RRT in AKI patients was identified as a new predictive factor for severe long-term CKD. This finding should be taken into consideration in future studies on the prognosis of ICU patients with AKI requiring RRT. Trial registration ELVIS trial was registered with ClinicalTrials.gov, number: NCT00875069 (June 16, 2014), and this ancillary study was registered with ClinicalTrials.gov, number: NCT03302624 (October 6, 2017). [ABSTRACT FROM AUTHOR]

Abstract Background Evidence about the impact of the pandemic of COVID-19 on the incidence rates of blood cultures contaminations and bloodstream infections in intensive care units (ICUs) remains scant. The objective of this study was to investigate the nationwide epidemiology of positive blood cultures drawn in ICUs during the first two pandemic waves of COVID-19 in Switzerland. Methods We analyzed data on positive blood cultures among ICU patients, prospectively collected through a nationwide surveillance system (ANRESIS), from March 30, 2020, to May 31, 2021, a 14-month timeframe that included a first wave of COVID-19, which affected the French and Italian-speaking regions, an interim period (summer 2020) and a second wave that affected the entire country. We used the number of ICU patient-days provided by the Swiss Federal Office of Public Health as denominator to calculate incidence rates of blood culture contaminations and bloodstream infections (ICU-BSI). Incidence rate ratios comparing the interim period with the second wave were determined by segmented Poisson regression models. Results A total of 1099 blood culture contaminations and 1616 ICU-BSIs were identified in 52 ICUs during the study. Overall, more episodes of blood culture contaminations and ICU-BSI were observed during the pandemic waves, compared to the interim period. The proportions of blood culture contaminations and ICU-BSI were positively associated with the ICU occupancy rate, which was higher during the COVID-19 waves. During the more representative second wave (versus interim period), we observed an increased incidence of blood culture contaminations (IRR 1.57, 95% CI 1.16–2.12) and ICU-BSI (IRR 1.20, 95% CI 1.03–1.39). Conclusions An increase in blood culture contaminations and ICU-BSIs was observed during the second COVID-19 pandemic wave, especially in months when the ICU burden of COVID-19 patients was high.

Introduction: Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes.Methods: We conducted a single-center retrospective cohort study among adult patients (> 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort.Results: We identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95-0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87-0.93, p < 0.0001), as well as a shorter ICU LOS (IRR 0.90, 95% CI 0.82-0.99, p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (- 1.6, 95% CI - 2.8 to - 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26-0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients.Conclusion: 4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients. [ABSTRACT FROM AUTHOR]

Background: Fluid overload and venous congestion are associated with morbi-mortality in the ICU (intensive care unit). Administration of diuretics to correct the fluid balance is common, although there is no strong relationship between the consequent fluid loss and clinical improvement. The aim of the study was to evaluate the ability of the portal pulsatility index, the renal venous impedance index, and the VEXUS score (venous ultrasound congestion score) to predict appropriate diuretic-induced fluid depletion.Methods: The study had a prospective, observational, single-center observational design and was conducted in a university-affiliated medico-surgical ICU. Adult patients for whom the clinician decided to introduce loop diuretic treatment were included. Hemodynamic and ultrasound measurements (including the portal pulsatility index, renal venous impedance index and VEXUS score) were performed at inclusion and 2 hours after the initiation of the diuretics. The patients' characteristics were noted at inclusion, 24 h later, and at ICU discharge. The appropriate diuretic-induced fluid depletion was defined by a congestive score lower than 3 after diuretic fluid depletion. The congestive score included clinical and biological parameters of congestion.Results: Eighty-one patients were included, and 43 (53%) patients presented with clinically significant congestion score at inclusion. Thirty-four patients (42%) had an appropriate response to diuretic-induced fluid depletion. None of the left- and right-sided echocardiographic parameters differed between the two groups. The baseline portal pulsatility index was the best predictor of appropriate response to diuretic-induced fluid depletion (AUC = 0.80, CI95%:0.70-0.92, p = 0.001), followed by the renal venous impedance index (AUC = 0.72, CI95% 0.61-0.84, p = 0.001). The baseline VEXUS score (AUC of 0.66 CI95% 0.53-0.79, p = 0.012) was poorly predictive of appropriate response to diuretic-induced fluid depletion.Conclusion: The portal pulsatility index and the renal venous impedance index were predictive of the appropriate response to diuretic-induced fluid depletion in ICU patients. The portal pulsatility index should be evaluated in future randomized studies. [ABSTRACT FROM AUTHOR]

Abstract Background Drowning is a global threat and one of the leading causes of injury around the world. The impact of drowning conditions including water salinity on patients’ prognosis remains poorly explored in Intensive Care Units (ICUs) patients. Methods We conducted a retrospective multicenter study on patients admitted to 14 ICUs in the west of France from January 2013 to January 2020. We first compared demographic and clinical characteristics at admission as well as clinical courses of these patients according to the salinity of drowning water. Then, we aimed to identify variables associated with 28-day survival using a Cox proportional hazard model. Results Of the 270 consecutive included patients, drowning occurred in seawater in 199 patients (73.7%) and in freshwater in 71 patients (26.3%). Day-28 mortality was observed in 55 patients (20.4%). Freshwater was independently associated with 28-day mortality (Adjusted Hazard Ratio (aHR) 1.84 [95% Confidence Interval (CI) 1.03–3.29], p = 0.04). A higher proportion of freshwater patients presented psychiatric comorbidities (47.9 vs. 19.1%; p

Abstract Background Coronavirus disease 19 (COVID-19)-associated pulmonary aspergillosis (CAPA) emerged as important fungal complications in patients with COVID-19-associated severe acute respiratory failure (ARF). Whether mould active antifungal prophylaxis (MAFP) can prevent CAPA remains elusive so far. Methods In this observational study, we included all consecutive patients admitted to intensive care units with COVID-19-associated ARF between September 1, 2020, and May 1, 2021. We compared patients with versus without antifungal prophylaxis with respect to CAPA incidence (primary outcome) and mortality (secondary outcome). Propensity score adjustment was performed to account for any imbalances in baseline characteristics. CAPA cases were classified according to European Confederation of Medical Mycology (ECMM)/International Society of Human and Animal Mycoses (ISHAM) consensus criteria. Results We included 132 patients, of whom 75 (57%) received antifungal prophylaxis (98% posaconazole). Ten CAPA cases were diagnosed, after a median of 6 days following ICU admission. Of those, 9 CAPA cases were recorded in the non-prophylaxis group and one in the prophylaxis group, respectively. However, no difference in 30-day ICU mortality could be observed. Thirty-day CAPA incidence estimates were 1.4% (95% CI 0.2–9.7) in the MAFP group and 17.5% (95% CI 9.6–31.4) in the group without MAFP (p = 0.002). The respective subdistributional hazard ratio (sHR) for CAPA incidence comparing the MAFP versus no MAFP group was of 0.08 (95% CI 0.01–0.63; p = 0.017). Conclusion In ICU patients with COVID-19 ARF, antifungal prophylaxis was associated with significantly reduced CAPA incidence, but this did not translate into improved survival. Randomized controlled trials are warranted to evaluate the efficacy and safety of MAFP with respect to CAPA incidence and clinical outcomes.

Abstract Background The intensity of ventilation, reflected by driving pressure (ΔP) and mechanical power (MP), has an association with outcome in invasively ventilated patients with or without acute respiratory distress syndrome (ARDS). It is uncertain if a similar association exists in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure. Methods We aimed to investigate the impact of intensity of ventilation on patient outcome. The PRoVENT-COVID study is a national multicenter observational study in COVID-19 patients receiving invasive ventilation. Ventilator parameters were collected a fixed time points on the first calendar day of invasive ventilation. Mean dynamic ΔP and MP were calculated for individual patients at time points without evidence of spontaneous breathing. A Cox proportional hazard model, and a double stratification analysis adjusted for confounders were used to estimate the independent associations of ΔP and MP with outcome. The primary endpoint was 28-day mortality. Results In 825 patients included in this analysis, 28-day mortality was 27.5%. ΔP was not independently associated with mortality (HR 1.02 [95% confidence interval 0.88–1.18]; P = 0.750). MP, however, was independently associated with 28-day mortality (HR 1.17 [95% CI 1.01–1.36]; P = 0.031), and increasing quartiles of MP, stratified on comparable levels of ΔP, had higher risks of 28-day mortality (HR 1.15 [95% CI 1.01–1.30]; P = 0.028). Conclusions In this cohort of critically ill invasively ventilated COVID-19 patients with acute respiratory failure, we show an independent association of MP, but not ΔP with 28-day mortality. MP could serve as one prognostic biomarker in addition to ΔP in these patients. Efforts aiming at limiting both ΔP and MP could translate in a better outcome. Trial registration Clinicaltrials.gov (study identifier NCT04346342).

Introduction: Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in intensive care unit (ICU) patients with circulatory shock is limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock. Methods: We analyzed a dataset from an international, multicenter, pragmatic randomized clinical trial (RCT) evaluating protein dose in ICU patients. Data were collected from ICU admission, and EEN was defined as initiating < 48 h from ICU admission and DEN > 48 h. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. The regression analysis model controlled for age, mNUTRIC score, APACHE II score, sepsis, and Site. Results: We included 626 patients, from 52 ICUs in 14 countries. Median age was 60 years [18–93], 55% had septic shock, 99% received norepinephrine alone, 91% received EN alone, and 50.3% were randomized to a usual protein dose. Forty-two percent of EEN patients had persistent organ dysfunction syndrome plus death at day 28, compared to 53% in the DEN group (p = 0.04). EEN was associated with more ICU-free days (9.3 ± 9.2 vs. 5.7 ± 7.9, p = 0.0002), more days alive and free of vasopressors (7.1 ± 3.1 vs. 6.3 ± 3.2, p = 0.007), and shorter duration of MV among survivors (9.8 ± 10.9 vs. 13.8 ± 14.5, p = 0.0002). This trend was no longer observed in the adjusted analysis. There were no differences in ICU/60-day mortality or feeding intolerance rates between groups. Conclusion: In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes, but no longer when adjusting for illness severity. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Rapid molecular tests could accelerate the control of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and carbapenemase-producing organisms (CPO) in intensive care units (ICUs).Objective and Methods: This interventional 12-month cohort study compared a loop-mediated isothermal amplification (LAMP) assay performed directly on rectal swabs with culturing methods (control period, 6 months), during routine ICU screening. Contact precautions (CP) were implemented for CPO or non-E. coli ESBL-producing Enterobacterales (nEcESBL-PE) carriers. Using survival analysis, we compared the time intervals from admission to discontinuation of unnecessary preemptive CP among patients at-risk and the time intervals from screening to implementation of CP among newly identified carriers. We also compared diagnostic performances, and nEcESBL-PE/CPO acquisition rates. This study is registered, ISRCTN 23588440.Results: We included 1043 patients. During the intervention and control phases, 92/147 (62.6%) and 47/86 (54.7%) of patients at-risk screened at admission were candidates for early discontinuation of preemptive CP. The LAMP assay had a positive predictive value (PPV) of 44.0% and a negative predictive value (NPV) of 99.9% for CPO, and 55.6% PPV and 98.2% NPV for nEcESBL-PE. Due to result notification and interpretation challenges, the median time from admission to discontinuation of preemptive CP increased during the interventional period from 80.5 (95% CI 71.5-132.1) to 88.3 (95% CI 57.7-103.7) hours (p = 0.47). Due to the poor PPV, we had to stop using the LAMP assay to implement CP. No difference was observed regarding the incidence of nEcESBL-PE and CPO acquisition.Conclusion: A rapid screening strategy with LAMP assays performed directly on rectal swabs had no benefit for infection control in a low-endemicity setting. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) has different phenotypes and distinct short-term outcomes. Patients with non-focal ARDS have a higher short-term mortality than focal ones. The aim of this study was to assess the impact of the morphological phenotypes of ARDS on long-term outcomes.Methods: This was a secondary analysis of the LIVE study, a prospective, randomised control trial, assessing the usefulness of a personalised ventilator setting according to lung morphology in moderate-to-severe ARDS. ARDS was classified as focal (consolidations only in the infero-posterior part of the lungs) or non-focal. Outcomes were assessed using mortality and functional scores for quality of life at the 1-year follow-up.Results: A total of 124 focal ARDS and 236 non-focal ARDS cases were included. The 1-year mortality was higher for non-focal ARDS than for focal ARDS (37% vs. 24%, p = 0.012). Non-focal ARDS (hazard ratio, 3.44; 95% confidence interval, 1.80-6.59; p < 0.001), age, McCabe score, haematological cancers, SAPS II, and renal replacement therapy were independently associated with 1-year mortality. This difference was driven by mortality during the first 90 days (28 vs. 16%, p = 0.010) but not between 90 days and 1 year (7 vs. 6%, p = 0.591), at which point only the McCabe score was independently associated with mortality. Morphological phenotypes had no impact on patient-reported outcomes.Conclusion: Lung morphologies reflect the acute phase of ARDS and its short-term impact but not long-term outcomes, which seem only influenced by comorbidities.Trial Registration: NCT02149589; May 29, 2014. [ABSTRACT FROM AUTHOR]

Abstract Background This systematic review and meta-analysis aimed to determine the effectiveness of systematic early mobilization in improving muscle strength and physical function in mechanically ventilated intensive care unit (ICU) patients. Methods We conducted a two-stage systematic literature search in MEDLINE, EMBASE and the Cochrane Library until January 2019 for randomized controlled trials (RCTs) examining the effects of early mobilization initiated within 7 days after ICU admission compared with late mobilization, standard early mobilization or no mobilization. Priority outcomes were Medical Research Council Sum Score (MRC-SS), incidence of ICU-acquired weakness (ICUAW), 6-min walk test (6MWT), proportion of patients reaching independence, time needed until walking, SF-36 Physical Function Domain Score (PFS) and SF-36 Physical Health Component Score (PCS). Meta-analysis was conducted where sufficient comparable evidence was available. We evaluated the certainty of evidence according to the GRADE approach. Results We identified 12 eligible RCTs contributing data from 1304 participants. Two RCTs were categorized as comparing systematic early with late mobilization, nine with standard early mobilization and one with no mobilization. We found evidence for a benefit of systematic early mobilization compared to late mobilization for SF-36 PFS (MD 12.3; 95% CI 3.9–20.8) and PCS (MD 3.4; 95% CI 0.01–6.8), as well as on the proportion of patients reaching independence and the time needed to walking, but not for incidence of ICUAW (RR 0.62; 95% CI 0.38–1.03) or MRC-SS. For systematic early compared to standard early mobilization, we found no statistically significant benefit on MRC-SS (MD 5.8; 95% CI − 1.4 to 13.0), incidence of ICUAW (RR 0.90; 95% CI 0.63–1.27), SF-36 PFS (MD 8.1; 95% CI − 15.3 to 31.4) or PCS (MD − 2.4; 95% CI − 6.1 to 1.3) or other priority outcomes except for change in 6MWT from baseline. Generally, effects appeared stronger for systematic early compared to late mobilization than to standard early mobilization. We judged the certainty of evidence for all outcomes as very low to low. Conclusion The evidence regarding a benefit of systematic early mobilization remained inconclusive. However, our findings indicate that the larger the difference in the timing between the intervention and the comparator, the more likely an RCT is to find a benefit for early mobilization. Study Registration: PROSPERO (CRD42019122555).

Abstract Background There is wide variability between intensivists in the decisions to forgo life-sustaining treatment (DFLST). Advance directives (ADs) allow patients to communicate their end-of-life wishes to physicians. We assessed whether ADs reduced variability in DFLSTs between intensivists. Methods We conducted a multicenter, prospective, simulation study. Eight patients expressed their wishes in ADs after being informed about DFLSTs by an intensivist-investigator. The participating intensivists answered ten questions about the DFLSTs of each patient in two scenarios, referring to patients’ characteristics without ADs (round 1) and then with (round 2). DFLST score ranged from 0 (no-DFLST) to 10 (DFLST for all questions). The main outcome was variability in DFLSTs between intensivists, expressed as relative standard deviation (RSD). Results A total of 19,680 decisions made by 123 intensivists from 27 ICUs were analyzed. The DFLST score was higher with ADs than without (6.02 95% CI [5.85; 6.19] vs 4.92 95% CI [4.75; 5.10], p

Abstract Background Data on SARS-CoV-2 load in lower respiratory tract (LRT) are scarce. Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients. Methods We conducted a binational study merging prospectively collected data from two COVID-19 reference centers in France and Switzerland. First, we described the viral shedding duration (i.e., time to negativity) in LRT samples. Second, we analyzed viral load in LRT samples. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms’ onset and date of sampling. Results From March to May 2020, 267 LRT samples were performed in 90 patients from both centers. The median time to negativity was 29 (IQR 23; 34) days. Prolonged viral shedding was not associated with age, gender, cardiac comorbidities, diabetes, immunosuppression, corticosteroids use, or antiviral therapy. The LRT viral load tended to be higher in non-survivors. This difference was statistically significant after adjusting for the time interval between onset of symptoms and date of sampling (OR 3.78, 95% CI 1.13–12.64, p = 0.03). Conclusions The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the viral load in the LRT was associated with the 6-week mortality.

Abstract Background Neurotropism of SARS-CoV-2 and its neurological manifestations have now been confirmed. We aimed at describing delirium and neurological symptoms of COVID-19 in ICU patients. Methods We conducted a bicentric cohort study in two French ICUs of Strasbourg University Hospital. All the 150 patients referred for acute respiratory distress syndrome due to SARS-CoV-2 between March 3 and May 5, 2020, were included at their admission. Ten patients (6.7%) were excluded because they remained under neuromuscular blockers during their entire ICU stay. Neurological examination, including CAM-ICU, and cerebrospinal fluid analysis, electroencephalography, and magnetic resonance imaging (MRI) were performed in some of the patients with delirium and/or abnormal neurological examination. The primary endpoint was to describe the incidence of delirium and/or abnormal neurological examination. The secondary endpoints were to describe the characteristics of delirium, to compare the duration of invasive mechanical ventilation and ICU length of stay in patients with and without delirium and/or abnormal neurological symptoms. Results The 140 patients were aged in median of 62 [IQR 52; 70] years old, with a median SAPSII of 49 [IQR 37; 64] points. Neurological examination was normal in 22 patients (15.7%). One hundred eighteen patients (84.3%) developed a delirium with a combination of acute attention, awareness, and cognition disturbances. Eighty-eight patients (69.3%) presented an unexpected state of agitation despite high infusion rates of sedative treatments and neuroleptics, and 89 (63.6%) patients had corticospinal tract signs. Brain MRI performed in 28 patients demonstrated enhancement of subarachnoid spaces in 17/28 patients (60.7%), intraparenchymal, predominantly white matter abnormalities in 8 patients, and perfusion abnormalities in 17/26 patients (65.4%). The 42 electroencephalograms mostly revealed unspecific abnormalities or diffuse, especially bifrontal, slow activity. Cerebrospinal fluid examination revealed inflammatory disturbances in 18/28 patients, including oligoclonal bands with mirror pattern and elevated IL-6. The CSF RT-PCR SARS-CoV-2 was positive in one patient. The delirium/neurological symptoms in COVID-19 patients were responsible for longer mechanical ventilation compared to the patients without delirium/neurological symptoms. Delirium/neurological symptoms could be secondary to systemic inflammatory reaction to SARS-CoV-2. Conclusions and relevance Delirium/neurological symptoms in COVID-19 patients are a major issue in ICUs, especially in the context of insufficient human and material resources. Trial registration NA.

Abstract Background High serum levels of certain aromatic microbial metabolites (AMM) are associated with severity and mortality in critically ill patients. Omics-based studies suggest gut dysbiosis and reduced microbiome diversity in critical conditions. However, the landscape of gut microbial metabolites is still to be outlined, not to mention the interplay correlation between the metabolome and gut microbiome in critically ill patients. The aim of this study was to analyze the association between serum and fecal levels of AMM and compare them with the composition of gut microbiota in critically ill patients in the acute and chronic stages. Methods In this prospective observational pilot study, we analyzed the temporal dynamics of the gut microbiome and the AMM spectrum across two distinct subgroups—acute critical ill (ACI) patients with nosocomial pneumonia and chronically critically ill (CCI) patients (9 subjects each group)—as well as performed comparison with 23 healthy volunteers. The AMM levels for each patient were measured using GC-MS in simultaneously taken serum and fecal samples (SFS). These parameters were compared with 16S rRNA fecal microbiome profiles. Results The observed proportions of bacterial taxa suggest a significant gut dysbiosis in the ACI and the CCI patients. Stronger imbalance in microbiome composition and dynamics observed in the ACI patients compared to the CCI ones resonates with a higher severity in the former group. The total levels of AMM in serum samples were higher for the ACI patients than for the CCI patients (3.7 (1.4–6.3) and 1.1 (1.0–1.6) μM, respectively; p = 0.0003). The qualitative composition of the SFS was also altered. We discovered significant associations between gut microbial taxa levels and metabolite concentrations in blood serum as well as in feces in each of the ACI and the CCI patients. Conclusions Aromatic microbial metabolite profiles in the gut and the serum are interlinked and reflect a disruption of the gut microbial community in critically ill patients.

Abstract Introduction Patient safety and critical care quality remain a challenging issue in the ICU. However, the effects of the national quality improvement (QI) program remain unknown in China. Methods A national ICU QI program was implemented in a controlled cohort of 586 hospitals from 2016 to 2018. The effects of the QI program on critical care quality were comprehensively investigated. Main results A total of 81,461,554 patients were enrolled in 586 hospitals, and 1,587,724 patients were admitted to the ICU over 3 years. In 2018, there was a significantly higher number of ICU beds (2016 vs. 2018: 10668 vs. 13,661, P = 0.0132) but a lower doctor-to-bed ratio (2016 vs. 2018: 0.64 (0.50, 0.83) vs. 0.60 (0.45, 0.75), P = 0.0016) and nurse-to-bed ratio (2016 vs. 2018: 2.00 (1.64, 2.50) vs. 2.00 (1.50, 2.40), P = 0.031) than in 2016. Continuous and significant improvements in the ventilator-associated pneumonia (VAP) incidence rate, microbiology detection rate before antibiotic use and deep vein thrombosis (DVT) prophylaxis rate were associated with the implementation of the QI program (VAP incidence rate (per 1000 ventilator-days), 2016 vs. 2017 vs. 2018: 11.06 (4.23, 22.70) vs. 10.20 (4.25, 23.94) vs. 8.05 (3.13, 17.37), P = 0.0002; microbiology detection rate before antibiotic use (%), 2016 vs. 2017 vs. 2018: 83.91 (49.75, 97.87) vs. 84.14 (60.46, 97.24) vs. 90.00 (69.62, 100), P