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Critically ill COVID-19 patients admitted to the intensive care unit (ICU) are at an increased risk of acquiring bacterial bloodstream infections (BSI). We aimed to describe patient characteristics, risk factors, and the microbiological spectrum in blood cultures and evaluate the impact of ICU-acquired BSI on outcomes in a Nordic setting. A prospective multicenter cohort study was conducted on adult invasively mechanically ventilated (IMV) COVID-19 patients. The primary aim was to identify the proportion of ICU-acquired BSI and its aetiology. Secondary outcomes were duration of IMV, length of stay (LOS), and mortality for individuals with and without BSI, respectively. Logistic regression was used to identify potential predictors of ICU-acquired BSI. Predictors were assessed by calculating an Area Under the Receiver Operating Characteristics (AUROC) curve. Of 354 included patients, 17% had an ICU-acquired BSI. Staphylococcus aureus was the most common pathogen. Patients with BSI had a longer duration of IMV (20 days versus 9 days, p < 0.001), longer ICU-LOS (24 days versus 11 days, p < 0.001), and hospital-LOS (38 days versus 24 days, p < 0.001). A BSI was associated with increased mortality; odds ratio (OR) 3.21, 95% CI: 1.61-6.38, p < 0.001. Adjusted analyses showed that higher BMI; OR 1.06, 95% CI: 1.01-1.11, p = 0.014, diabetes mellitus with organ complications; OR 2.66, 95% CI: 1.33-5.29, p = 0.005, and number of symptomatic days before ICU admission; OR 1.04, 95% CI: 1.01-1.07, p = 0.008, were associated with a BSI. The AUROC was 0.66 (95% CI: 0.58-0.74). ICU-acquired BSIs were found in 17% of critically ill COVID-19 patients and were associated with a longer duration of IMV and LOS as well as increased mortality. Staphylococcus aureus was the dominating pathogen. We found several factors associated with ICU-acquired BSIs at ICU admission. However, their ability to predict BSIs was poor.

Neutrophil gelatinase-associated lipocalin (NGAL) is a novel kidney injury and inflammation biomarker. We investigated whether NGAL could be used to predict continuous renal replacement therapy (CRRT) and mortality in critical coronavirus disease 2019 (COVID-19). This prospective multicenter cohort study included adult COVID-19 patients in six intensive care units (ICUs) in Sweden between May 11, 2020 and May 10, 2021. Blood was sampled at admission, days two and seven in the ICU. The samples were batch analyzed for NGAL, creatinine, and cystatin c after the end of the study period. Initiation of CRRT and 90-day survival were used as dependent variables in regression models. Of 498 included patients, 494 were analyzed regarding CRRT and 399 were analyzed regarding survival. Seventy patients received CRRT and 154 patients did not survive past 90 days. NGAL, in combination with creatinine and cystatin c, predicted the subsequent initiation of CRRT with an area under the curve (AUC) of 0.95. For mortality, NGAL, in combination with age and sex, had an AUC of 0.83. In conclusion, NGAL is a valuable biomarker for predicting subsequent initiation of CRRT and 90-day mortality in critical COVID-19. NGAL should be considered when developing future clinical scoring systems.

We aimed to describe and evaluate the National Early Warning Score (NEWS) in the 24 hours preceding an in-hospital cardiac arrest among general somatic ward patients. The 24 hours preceding the in-hospital cardiac arrest were divided into four timespans and analysed by a medical record review of 127:254 matched case-control patients. The median NEWS ranged from 3 (2–6) to 6 (3–9) points for cases vs 1 (0–3) to 1 (0–3) point for controls. The proportion of cases ranged from 23–45% at high risk vs 3–6% for controls. The NEWS high-risk category was associated with an increase of 3.17 (95% confidence interval (CI) 1.66–6.04) to 4.43 (95% CI 2.56–7.67) in odds of in-hospital cardiac arrest compared to the low-risk category. NEWS, with its intuitive and for healthcare staff easy to interpret risk classification, is suitable for discriminating deteriorating patients with major deviating vital signs scoring high risk on NEWS.

Background Endostatin is a promising biomarker for predicting acute kidney injury (AKI) and mortality in the intensive care unit (ICU). We investigated plasma endostatin levels at ICU admission as predictors of new-onset AKI within 48 h after ICU admission, renal replacement therapy (RRT) within 7 days after ICU admission, and 30-day mortality. Methods A retrospective multicentre study was performed with admissions to four ICUs. Blood samples were prospectively obtained at ICU admission and retrospectively analysed. The Kidney Disease: Improving Global Outcomes (KDIGO) criteria defined AKI. Endostatin at ICU admission was compared to and adjusted for creatinine, cystatin C, and the Simplified Acute Physiology Score 3 (SAPS-3). Regression models and mean areas under the receiver operating characteristic curves (AUCs) from repeated cross-validation were assessed. Results In total, 4732 admissions were included. Endostatin was associated with new-onset AKI (OR 1.7, 95% CI 1.5 - 1.9), new-onset stage 3 AKI (OR 1.4, 95% CI 1.2 - 1.6), and RRT (OR 1.2, 95% CI 1.05 - 1.4) independently of creatinine, cystatin C, and SAPS-3. Endostatin was superior to creatinine and cystatin C in predicting new-onset AKI (mean AUC 0.67 vs. 0.63, p  < 0.001). Adding endostatin to creatinine improved the prediction of new-onset AKI and new-onset stage 3 AKI, but not the need for RRT. Endostatin was not associated with 30-day mortality after adjusting for the SAPS-3 score. Conclusions Endostatin at ICU admission is an independent predictor of new-onset AKI and may improve early AKI risk assessment in the ICU. However, its predictive value for RRT and 30-day mortality appears limited. External validation and studies on its clinical utility are warranted.

Background Critical COVID-19 is associated with high mortality, and acute kidney injury (AKI) is common. Endostatin has emerged as a promising prognostic biomarker for predicting AKI and mortality in intensive care. This study aimed to investigate plasma endostatin at intensive care unit (ICU) admission as a biomarker for AKI, renal replacement therapy (RRT), and 90-day mortality in COVID-19. Methods A pre-planned retrospective analysis of a prospectively collected cohort of admissions with a primary SARS-CoV-2 infection to six ICUs in southern Sweden between May 2020 and May 2021 was undertaken. Endostatin at ICU admission was evaluated with multivariable logistic regression analyses adjusted for age, sex, C-reactive protein, and creatinine. Net reclassification index analyses were also performed. Results Four hundred eighty-four patients were included. Endostatin showed a non-linear association with AKI, RRT, and 90-day mortality. Endostatin levels of 100–200 ng/mL were associated with AKI on ICU day 1 (OR 5.1, 95% CI 1.5–18, p  = 0.0097), RRT during the ICU stay (OR 3.5, 95% CI 1.1–12, p  = 0.039), and 90-day mortality (OR 4.2, 95% CI 1.6–11, p  = 0.0037). Adding endostatin to creatinine improved prediction of AKI on ICU day 1, while adding it to a model containing age, sex, CRP, and creatinine improved prediction of both AKI on ICU day 1 and 90-day mortality, but not RRT. Conclusions Endostatin at ICU admission was independently associated with AKI, RRT, and 90-day mortality in ICU patients with COVID-19. In addition, endostatin improved the prediction of AKI and 90-day mortality, highlighting its potential as a biomarker for early risk stratification in intensive care.

BackgroundNeurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and total-tau protein (tau) are novel blood biomarkers of neurological injury, and may be used to predict outcomes in critical COVID-19.MethodsA prospective multicentre cohort study of 117 consecutive and critically ill COVID-19 patients in six intensive care units (ICUs) in southern Sweden between May and November 2020. Serial NfL, GFAP and tau were analysed in relation to mortality, the Glasgow Outcome Scale Extended (GOSE) and the physical (PCS) and mental (MCS) components of health-related quality of life at one year.ResultsNfL, GFAP and tau on ICU admission predicted one-year mortality with an area under the curve (AUC) of 0.82 (95% confidence interval [CI] 0.74-0.90), 0.72 (95% CI 0.62-0.82) and 0.66 (95% CI 0.54-0.77). NfL on admission was an independent predictor of one-year mortality (p = 0.039). Low NfL and GFAP values were associated with good PCS (≥45) at one year but not with good MCS (≥45) or GOSE (≥5).ConclusionsNfL on ICU admission was an independent predictor of mortality. High levels of NfL, GFAP and tau were associated with mortality but not with poor GOSE in survivors at one year. Low levels of NfL and GFAP were associated with improved physical health-related quality of life.

The National Early Warning Score – NEWS is a “track and trigger” scale designed to assess in-hospital patients’ vital signs and detect clinical deterioration. In this study the NEWS was translated into Swedish and its association with the need of intensive care was investigated. A total of 868 patient charts, recorded by the medical emergency team at a university hospital, containing the parameters needed to calculate the NEWS were audited. The NEWS was translated into Swedish and tested for inter-rater reliability with a perfect agreement (weighted κ=1.0) among the raters. The median score for patients admitted to the ICU were higher than for those who were not (10 vs. 8, p<0.0001). AUROC for discriminating admittance to the ICU was 0.68 (95% CI: 0.622–0.739, p<0.0001). A regression analysis showed that lower oxygen saturation and a lower level of consciousness were significantly associated with ICU admission (OR 1.27 [1.06–1.52], p=0.01 and OR 1.77 [1.12–2.82], p=0.02) and may predict admission to the ICU better than the other parameters. The Swedish translated NEWS seems to have excellent inter-rater reliability and can be used without risk of linguistic misinterpretation. High scores for the parameters oxygen saturation and level of consciousness in the NEWS may predict admission to the ICU.

The understanding of recovery after critical COVID-19 beyond the first year is limited. To describe changes in functional, physical, and mental health outcomes between 1 and 3 years among survivors of critical COVID-19 and to identify factors associated with incomplete recovery at 3 years. A prospective multicentre cohort study of survivors of critical COVID-19 with follow-up at 1 and 3 years. The primary outcome was functional outcome, assessed using the Glasgow Outcome Scale-Extended (GOSE), which ranges from 1 to 8, with scores of 6 or less indicating incomplete recovery. Secondary outcomes included return-to-work, physical and mental Health-Related Quality of Life (HRQoL), life satisfaction, fatigue, psychological symptoms (anxiety, depression, post-traumatic stress disorder), and respiratory symptoms. Multivariable logistic regression was used to identify factors associated with incomplete recovery (GOSE ≤ 6) at 3 years. Among 191 of 210 eligible participants, functional outcome declined from 1 to 3 years, and participants with incomplete recovery increased from 32% to 45%. Worse outcomes were observed in mental HRQoL, fatigue, depression, and post-traumatic stress, while return-to-work rates, physical HRQoL, life satisfaction, anxiety, and respiratory symptoms remained stable. Younger age [OR 0.70 (95% CI 0.54-0.91), p = 0.008] and higher Clinical Frailty Scale score [OR 1.54 (95% CI 1.04-2.28), p = 0.029] were independently associated with incomplete recovery at 3 years. Survivors of critical COVID-19 experienced a decline in functional outcome and worsening mental health between 1 and 3 years after ICU admission. Younger and frail survivors may require increased attention and support. ClinicalTrials.gov Identifier: NCT04974775, registered April 28, 2020.

Background Biomarkers can be of help to understand critical illness and to identify and stratify sepsis. Adrenomedullin is a vasoactive hormone, with reported prognostic and potentially therapeutic value in sepsis. The primary aim of this study was to investigate the association of circulating bioactive adrenomedullin (bio-ADM) levels at intensive care unit (ICU) admission with mortality in sepsis patients and in a general ICU population. Secondary aims included the association of bio-ADM with organ failure and the ability of bio-ADM to identify sepsis. Methods In this retrospective observational study, adult patients admitted to one of four ICUs during 2016 had admission bio-ADM levels analysed. Age-adjusted odds ratios (OR) with 95% CI for log-2 transformed bio-ADM, and Youden’s index derived cut-offs were calculated. The primary outcome was 30-day mortality, and secondary outcomes included the need for organ support and the ability to identify sepsis. Results Bio-ADM in 1867 consecutive patients were analysed; 632 patients fulfilled the sepsis-3 criteria of whom 267 had septic shock. The median bio-ADM in the entire ICU population was 40 pg/mL, 74 pg/mL in sepsis patients, 107 pg/mL in septic shock and 29 pg/mL in non-septic patients. The association of elevated bio-ADM and mortality in sepsis patients and the ICU population resulted in ORs of 1.23 (95% CI 1.07–1.41) and 1.22 (95% CI 1.12–1.32), respectively. The association with mortality remained after additional adjustment for lactate in sepsis patients. Elevated bio-ADM was associated with an increased need for dialysis with ORs of 2.28 (95% CI 2.01–2.59) and 1.97 (95% CI 1.64–2.36) for the ICU population and sepsis patients, respectively, and with increased need of vasopressors, OR 1.33 (95% CI 1.23–1.42) (95% CI 1.17–1.50) for both populations. Sepsis was identified with an OR of 1.78 (95% CI 1.64–1.94) for bio-ADM, after additional adjustment for severity of disease. A bio-ADM cut-off of 70 pg/mL differentiated between survivors and non-survivors in sepsis, but a Youden’s index derived threshold of 108 pg/mL performed better. Conclusions Admission bio-ADM is associated with 30-day mortality and organ failure in sepsis patients as well as in a general ICU population. Bio-ADM may be a morbidity-independent sepsis biomarker.

IntroductionCentral venous catheterisation is a common procedure in intensive care therapy and the use of central venous catheters is essential for treatment of many medical disorders. Although rare, central venous catheterisation is associated with mechanical complications that can be life-threatening if untreated. Real-time ultrasound guidance reduces the incidence of mechanical complications when compared with the anatomic landmark method. The purpose of this study is to determine the incidence of and potential risk factors associated with early mechanical complications of central venous catheterisation in an era where real-time ultrasound guidance has become clinical practice.Methods and analysisThis is a prospective, controlled, multicentre, observational study. All participating hospitals follow the same clinical guidelines for central venous catheterisation. Each central venous catheter insertion will be recorded in the common electronic chart system according to a recently revised template. An automated script-based search will identify all recorded central venous catheter insertion templates during the study period and relevant variables will be extracted. Outcome measures and independent variables are pre-defined in this study protocol. Multivariable and univariable logistic regression analysis will be used to determine associations and risk factors of mechanical complications.Ethics and disseminationThe Regional Ethical Review Board in Lund, Sweden has approved this study. The results will be submitted for publication in peer-reviewed medical journals and presented at national and international scientific meetings.Trial registration numberNCT03782324.