Furosemide versus placebo for fluid overload in intensive care patients-The randomised GODIF trial second version: Statistical analysis plan.

BACKGROUND: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. METHODS: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. CONCLUSION: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. TRIAL REGISTRATIONS: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.

Utility and limitations of patient-adjusted D-dimer cut-off levels for diagnosis of venous thromboembolism-A systematic review and meta-analysis.

PURPOSE: To systematically assess test performance of patient-adapted D-dimer cut-offs for the diagnosis of venous thromboembolism (VTE). METHODS: Systematic review and analysis of articles published in PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. Investigations assessing patient-adjusted D-dimer thresholds for the exclusion of VTE were included. A hierarchical summary receiver operating characteristic model was used to assess diagnostic accuracy. Risk of bias was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 score. RESULTS: A total of 68 studies involving 141,880 patients met the inclusion criteria. The standard cut-off revealed a sensitivity of 0.99 (95% confidence interval [CI] 0.98-0.99) and specificity of 0.23 (95% CI 0.16-0.31). Sensitivity was comparable to the standard cut-off for age-adjustment (0.97 [95% CI 0.96-0.98]) and YEARS algorithm (0.98 [95% CI 0.91-1.00]) but lower for pretest probability (PTP)-adjusted (0.95 [95% CI 0.89-0.98) and COVID-19-adapted thresholds (0.93 [95% CI 0.82-0.98]). Specificity was significantly higher across all adjustment strategies (age: 0.43 [95% CI 0.36-0.50]; PTP: 0.63 [95% CI 0.51-0.73]; YEARS algorithm: 0.65 [95% CI 0.39-0.84]; and COVID-19: 0.51 [95% CI 0.40-0.63]). The YEARS algorithm provided the best negative likelihood ratio (0.03 [95% CI 0.01-0.15]), followed by age-adjusted (both 0.07 [95% CI 0.05-0.09]), PTP (0.08 [95% CI 0.04-0.17), and COVID-19-adjusted thresholds (0.13 [95% CI 0.05-0.32]). CONCLUSIONS: This study indicates that adjustment of D-dimer thresholds to patient-specific factors is safe and embodies considerable potential for reduction of imaging. However, robustness, safety, and efficiency vary considerably among different adjustment strategies with a high degree of heterogeneity.

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure.

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

Red Blood Cell Transfusion in the Intensive Care Unit.

Importance: Red blood cell (RBC) transfusion is common among patients admitted to the intensive care unit (ICU). Despite multiple randomized clinical trials of hemoglobin (Hb) thresholds for transfusion, little is known about how these thresholds are incorporated into current practice. Objective: To evaluate and describe ICU RBC transfusion practices worldwide. Design, Setting, and Participants: International, prospective, cohort study that involved 3643 adult patients from 233 ICUs in 30 countries on 6 continents from March 2019 to October 2022 with data collection in prespecified weeks. Exposure: ICU stay. Main Outcomes and Measures: The primary outcome was the occurrence of RBC transfusion during ICU stay. Additional outcomes included the indication(s) for RBC transfusion (consisting of clinical reasons and physiological triggers), the stated Hb threshold and actual measured Hb values before and after an RBC transfusion, and the number of units transfused. Results: Among 3908 potentially eligible patients, 3643 were included across 233 ICUs (median of 11 patients per ICU [IQR, 5-20]) in 30 countries on 6 continents. Among the participants, the mean (SD) age was 61 (16) years, 62% were male (2267/3643), and the median Sequential Organ Failure Assessment score was 3.2 (IQR, 1.5-6.0). A total of 894 patients (25%) received 1 or more RBC transfusions during their ICU stay, with a median total of 2 units per patient (IQR, 1-4). The proportion of patients who received a transfusion ranged from 0% to 100% across centers, from 0% to 80% across countries, and from 19% to 45% across continents. Among the patients who received a transfusion, a total of 1727 RBC transfusions were administered, wherein the most common clinical indications were low Hb value (n = 1412 [81.8%]; mean [SD] lowest Hb before transfusion, 7.4 [1.2] g/dL), active bleeding (n = 479; 27.7%), and hemodynamic instability (n = 406 [23.5%]). Among the events with a stated physiological trigger, the most frequently stated triggers were hypotension (n = 728 [42.2%]), tachycardia (n = 474 [27.4%]), and increased lactate levels (n = 308 [17.8%]). The median lowest Hb level on days with an RBC transfusion ranged from 5.2 g/dL to 13.1 g/dL across centers, from 5.3 g/dL to 9.1 g/dL across countries, and from 7.2 g/dL to 8.7 g/dL across continents. Approximately 84% of ICUs administered transfusions to patients at a median Hb level greater than 7 g/dL. Conclusions and Relevance: RBC transfusion was common in patients admitted to ICUs worldwide between 2019 and 2022, with high variability across centers in transfusion practices.

Renal Function-Adjusted D-Dimer Levels in Critically Ill Patients With Suspected Thromboembolism.

OBJECTIVES: Diagnosing thromboembolic disease typically includes D-dimer testing and use of clinical scores in patients with low to intermediate pretest probability. However, renal dysfunction is often observed in patients with thromboembolic disease and was previously shown to be associated with increased D-dimer levels. We seek to validate previously suggested estimated glomerular filtration rate-adjusted D-dimer cutoff levels. Furthermore, we strive to explore whether the type of renal dysfunction affects estimated glomerular filtration rate-adjusted D-dimer test characteristics. DESIGN: Single-center retrospective data analysis from electronic healthcare records of all emergency department patients admitted for suspected thromboembolic disease. SETTING: Tertiary care academic hospital. SUBJECTS: Exclusion criteria were as follows: age less than 16 years old, patients with active bleeding, and/or incomplete records. INTERVENTIONS: Test characteristics of previously suggested that estimated glomerular filtration rate-adjusted D-dimer cutoff levels (> 333 µg/L [estimated glomerular filtration rate, > 60 mL/min/1.73 m], > 1,306 µg/L [30-60 mL/min/1.73 m], and > 1,663 µg/L [< 30 mL/min/1.73 m]) were validated and compared with the conventional D-dimer cutoff level of 500 µg/L. MAIN RESULTS: A total of 14,477 patients were included in the final analysis, with 467 patients (3.5%) diagnosed with thromboembolic disease. Renal dysfunction was observed in 1,364 (9.4%) of the total population. When adjusted D-dimer levels were applied, test characteristics remained stable: negative predictive value (> 99%), sensitivity (91.2% vs 93.4%), and specificity (42.7% vs 50.7%) when compared with the conventional D-dimer cutoff level to rule out thromboembolic disease (< 500 µg/L). Comparable characteristics were also observed when adjusted D-dimer cutoff levels were applied in patients with acute kidney injury (negative predictive value, 98.8%; sensitivity, 95.8%; specificity, 39.2%) and/or "acute on chronic" renal dysfunction (negative predictive value, 98.0%; sensitivity, 92.9%; specificity, 48.5%). CONCLUSIONS: D-Dimer cutoff levels adjusted for renal dysfunction appear feasible and safe assessing thromboembolic disease in critically ill patients. Furthermore, adjusted D-dimer cutoff levels seem reliable in patients with acute kidney injury and "acute on chronic" renal dysfunction. In patients with estimated glomerular filtration rate less than 60 mL/min/1.73 m, the false-positive rate can be reduced when estimated glomerular filtration rate-adjusted D-dimer cutoff levels are applied.

Mannitol for the Prevention of Peri-Operative Acute Kidney Injury: A Systematic Review.

OBJECTIVE/BACKGROUND: Post-operative acute kidney injury (AKI) is a frequent peri-operative complication that negatively affects morbidity and mortality. Mannitol is frequently used peri-operatively for renal protection, although evidence for its use is ambiguous. A systematic review was conducted to clarify whether there is evidence supporting peri-operative mannitol administration for the prevention of post-operative AKI. METHODS: A systematic literature search was performed in MEDLINE/Pubmed, Embase, the Cochrane Library, Clinical Trials registry, and the Cochrane Central Register of Controlled Trials (CENTRAL). Eligibility criteria were (i) population (studies involving adult patients undergoing surgery or a related intervention); (ii) intervention (intravenous mannitol administered in either the pre- or intra-operative period with comparison to controls); and (iii) predefined outcomes (post-operative AKI or respective renal end points/surrogates). RESULTS: In total, 1,538 articles published between January 1990 and October 2018 were identified. After checking for eligibility, 22 studies, including 17 prospective and/or randomised controlled trials and five retrospective studies, were included. The investigations involved various fields of surgery, such as aortic surgery, cardiac surgery with cardiopulmonary bypass, and urological procedures, including partial nephrectomy. Significant heterogeneity, limited sample size, and mostly short follow up periods were noted. CONCLUSION: Given the available evidence, the peri-operative use of mannitol to prevent AKI cannot be considered an evidence based intervention in cardiac surgery, partial nephrectomy, and/or other major surgery. Further research is required with a focus on patients at high risk of post-operative AKI.

Fluid management in patients undergoing cardiac surgery: effects of an acetate- versus lactate-buffered balanced infusion solution on hemodynamic stability (HEMACETAT).

BACKGROUND: Recent evidence suggests that acetate-buffered infusions result in better hemodynamic stabilization than 0.9% saline in patients undergoing major surgery. The choice of buffer in balanced crystalloid solutions may modify their hemodynamic effects. We therefore compared the inopressor requirements of Ringer's acetate and lactate for perioperative fluid management in patients undergoing cardiac surgery. METHODS: Using a randomized controlled double-blind design, we compared Ringer's acetate (RA) to Ringer's lactate (RL) with respect to the average rate of inopressor administered until postoperative hemodynamic stabilization was achieved. Secondary outcomes were the cumulative dose of inopressors, the duration of inopressor administration, the total fluid volume administered, and the changes in acid-base homeostasis. Patients undergoing elective valvular cardiac surgery were included. Patients with severe cardiac, renal, or liver disease were excluded from the study. RESULTS: Seventy-five patients were randomly allocated to the RA arm, 73 to the RL. The hemodynamic profiles were comparable between the groups. The groups did not differ with respect to the average rate of inopressors (RA 2.1 mcg/kg/h, IQR 0.5-8.1 vs. RL 1.7 mcg/kg/h, IQR 0.7-8.2, p = 0.989). Cumulative doses of inopressors and time on individual and combined inopressors did not differ between the groups. No differences were found in acid-base parameters and their evolution over time. CONCLUSION: In this study, hemodynamic profiles of patients receiving Ringer's lactate and Ringer's acetate were comparable, and the evolution of acid-base parameters was similar. These study findings should be evaluated in larger, multi-center studies. TRIAL REGISTRATION: Clinicaltrials.gov NCT02895659 . Registered 16 September 2016.

Fall-related emergency department admission: fall environment and settings and related injury patterns in 6357 patients with special emphasis on the elderly.

PRINCIPALS: Throughout the world, falls are a major public health problem and a socioeconomic burden. Nevertheless there is little knowledge about how the injury types may be related to the aetiology and setting of the fall, especially in the elderly. We have therefore analysed all patients presenting with a fall to our Emergency Department (ED) over the past five years. METHODS: Our retrospective data analysis comprised adult patients admitted to our Emergency Department between January 1, 2006, and December 31, 2010, in relation to a fall. RESULTS: Of a total of 6357 patients 78% (n = 4957) patients were younger than 75 years. The main setting for falls was patients home (n = 2239, 35.3%). In contrast to the younger patients, the older population was predominantly female (56.3% versus 38.6%; P < 0.0001). Older patients were more likely to fall at home and suffer from medical conditions (all P < 0.0001). Injuries to the head (P < 0.0001) and to the lower extremity (P < 0.019) occurred predominantly in the older population. Age was the sole predictor for recurrent falls (OR 1.2, P < 0.0001). CONCLUSION: Falls at home are the main class of falls for all age groups, particularly in the elderly. Fall prevention strategies must therefore target activities of daily living. Even though falls related to sports mostly take place in the younger cohort, a significant percentage of elderly patients present with falls related to sporting activity. Falls due to medical conditions were most likely to result in mild traumatic brain injury.

Influence of fluid accumulation on major adverse kidney events in critically ill patients - an observational cohort study.

BACKGROUND: Fluid accumulation (FA) is known to be associated with acute kidney injury (AKI) during intensive care unit (ICU) stay but data on mid-term renal outcome is scarce. The aim of this study was to investigate the association between FA at ICU day 3 and major adverse kidney events in the first 30 days after ICU admission (MAKE30). METHODS: Retrospective, single-center cohort study including adult ICU patients with sufficient data to compute FA and MAKE30. We defined FA as a positive cumulative fluid balance greater than 5% of bodyweight. The association between FA and MAKE30, including its sub-components, as well as the serum creatinine trajectories during ICU stay were examined. In addition, we performed a sensitivity analysis for the stage of AKI and the presence of chronic kidney disease (CKD). RESULTS: Out of 13,326 included patients, 1,100 (8.3%) met the FA definition. FA at ICU day 3 was significantly associated with MAKE30 (adjusted odds ratio [aOR] 1.96; 95% confidence interval [CI] 1.67-2.30; p < 0.001) and all sub-components: need for renal replacement therapy (aOR 3.83; 95%CI 3.02-4.84), persistent renal dysfunction (aOR 1.72; 95%CI 1.40-2.12), and 30-day mortality (aOR 1.70; 95%CI 1.38-2.09), p all < 0.001. The sensitivity analysis showed an association of FA with MAKE30 independent from a pre-existing CKD, but exclusively in patients with AKI stage 3. Furthermore, FA was independently associated with the creatinine trajectory over the whole observation period. CONCLUSIONS: Fluid accumulation is significantly associated with MAKE30 in critically ill patients. This association is independent from pre-existing CKD and strongest in patients with AKI stage 3.

Dog bite injuries: primary and secondary emergency department presentations--a retrospective cohort study.

UNLABELLED: Dog bites in humans are a complex problem, embracing both public health and animal welfare. The primary aim of this study is to examine primary and secondary presentations related to dog bite injuries in adults. METHODS: We retrospectively assessed all adult patients admitted with a dog bite injury to the Emergency Department of Bern University Hospital. RESULTS: A total of 431 patients were eligible for the study. Forty-nine (11.4%) of all patients were admitted with secondary presentations. Bites to the hands were most common (177, 41.1%). All patients (47, 100%) with secondary presentations were admitted because of signs of infection. The median time since the dog bite was 3.8 days (SD 3.9, range 1-21). Thirty-one patients had already been treated with antibiotic; coamoxicillin was the most common primary antibiotic therapy (27/47 patients, 57.4%). Patients with injuries to the hand were at increased risk of secondary presentations (OR 2.08, 95% CI 1.21-3.55, P < 0.006). CONCLUSION: Dog bite injuries to the hands are a major problem. They often lead to infectious complications. Immediate antibiotic therapy should carefully be evaluated for each patient.

Active fluid de-resuscitation in critically ill patients with septic shock: A systematic review and meta-analysis.

PURPOSE: To evaluate the impact of active fluid de-resuscitation on mortality in critically ill patients with septic shock. METHODS: A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. Trials investigating active fluid de-resuscitation and reporting data on mortality in patients with septic shock were eligible. The primary objective was the impact of active de-resuscitation in patients with septic shock on short-term mortality. Secondary outcomes were whether de-resuscitation lead to a fluid separation, and the impact of de-resuscitation on patient-centred outcomes. RESULTS: Thirteen trials (8,030 patients) were included in the systematic review, whereof 5 randomised-controlled trials (RCTs) were included in the meta-analysis. None of the RCTs showed a reduction in mortality with active de-resuscitation measures (relative risk (RR) 1.12 [95%-CI 0.84 - 1.48]). Fluid separation was achieved by two RCTs. Evidence from non-randomised trials suggests a mortality benefit with de-resuscitation strategies and indicates a trend towards a more negative fluid balance. Patient-centred outcomes were not influenced in the RCTs, and only one non-randomised trial revealed an impact on the duration of mechanical ventilation and renal replacement requirement (RRT). CONCLUSION: We found no evidence for superiority of active fluid de-resuscitation compared to usual care regarding mortality, fluid balance or patient-centred outcomes in patients with septic shock. Current evidence is limited by the lack of high-quality RCTs in patients with septic shock, the small sample sizes and the heterogeneity of the applied de-resuscitation techniques. In addition, validity of the majority of RCTs is compromised by their inability to achieve fluid separation.

Choice of creep or maintenance fluid type and their impact on total daily ICU sodium burden in critically ill patients: A systematic review and meta-analysis.

PURPOSE: Maintenance and hidden/creep fluids are a major source of fluid and sodium intake in intensive care unit (ICU) patients. Recent research indicates that low versus high sodium content maintenance fluids could decrease fluid and sodium burden. We conducted a systematic review (SR) with meta-analysis to summarize the impact of maintenance fluid choice on total daily sodium in ICU patients. MATERIALS AND METHODS: Systematic literature search in Pubmed, Embase, the Cochrane Library and the. CLINICAL TRIALS REGISTRY: Only controlled clinical trials were included. EXCLUSION CRITERIA: trials on resuscitation fluids, performed in the emergency department only and in pediatric patients. Primary objective was the reduction in mean total sodium intake with low versus high sodium content maintenance/creep fluids. RESULTS: Five studies (1105 patients) were included. Heterogeneity was high.Risk of bias was moderate. Mean daily sodium reduction was 117 mmol (95%Confidence Interval [CI] -174; -59; p < 0.001) with low versus high sodium content maintenance/creep fluids. Incidence of hyperchloremia was lower (OR 0.26; 95%CI 0.1; 0.64) with low sodium. There were no differences in the incidences of hyper-/hyponatremia and fluid balances. CONCLUSION: Using low sodium content maintenance/creep fluids substantially reduces daily sodium burden in adult ICU patients. Significant knowledge/research gaps exist regarding relevance and safety. TRIAL REGISTRATION: PROSPERO 2022 CRD42022300577 (February 2022).

Protocolised early de-resuscitation in septic shock (REDUCE): protocol for a randomised controlled multicentre feasibility trial.

BACKGROUND: Fluid overload is associated with excess mortality in septic shock. Current approaches to reduce fluid overload include restrictive administration of fluid or active removal of accumulated fluid. However, evidence on active fluid removal is scarce. The aim of this study is to assess the efficacy and feasibility of an early de-resuscitation protocol in patients with septic shock. METHODS: All patients admitted to the intensive care unit (ICU) with a septic shock are screened, and eligible patients will be randomised in a 1:1 ratio to intervention or standard of care. INTERVENTION: Fluid management will be performed according to the REDUCE protocol, where resuscitation fluid will be restricted to patients showing signs of poor tissue perfusion. After the lactate has peaked, the patient is deemed stable and assessed for active de-resuscitation (signs of fluid overload). The primary objective of this study is the proportion of patients with a negative cumulative fluid balance at day 3 after ICU. Secondary objectives are cumulative fluid balances throughout the ICU stay, number of patients with fluid overload, feasibility and safety outcomes and patient-centred outcomes. The primary outcome will be assessed by a logistic regression model adjusting for the stratification variables (trial site and chronic renal failure) in the intention-to-treat population. ETHICS AND DISSEMINATION: The study was approved by the respective ethical committees (No 2020-02197). The results of the REDUCE trial will be published in an international peer-reviewed medical journal regardless of the results. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04931485.

Dysphagia Post-Extubation Affects Long-Term Mortality in Mixed Adult ICU Patients-Data From a Large Prospective Observational Study With Systematic Dysphagia Screening.

Data on long-term effects of post-extubation dysphagia is lacking. We investigate mid- and long-term clinical outcomes in a large sample of ICU patients with systematic dysphagia screening. DESIGN: Outcome analysis with a follow-up of 6 years or death (whichever occurred earlier) of ICU patients from a prospective observational trial (Dysphagia in Mechanically Ventilated ICU Patients study) with systematic dysphagia screening. SETTING: ICU of a tertiary care academic center. PATIENTS: Nine-hundred thirty-three mixed medical-surgical ICU patients (median age, 66 yr; interquartile range [IQR], 54-74, Acute Physiology and Chronic Health Evaluation II score 19 [IQR, 14-24], 71% male). INTERVENTIONS: ICU patients were followed up for a mean follow-up period of 1,731 ± 772 days (4.7 ± 2.1 yr). Primary outcome measures were 180-day and 360-day all-cause mortality in ICU patients with versus without dysphagia. MEASUREMENTS AND MAIN RESULTS: Two-hundred seventy-three patients died (29.3%) during the observational interval (n = 76 lost to follow-up). In dysphagia screening positive versus negative ICU patients, mortality at 180 days was 16% versus 5.8% (excess mortality 10.2%), whereas mortality at 360 days was 25% versus 9.1% (excess mortality 15.9%). Adjustment for confounders in a Cox model revealed a significant association of dysphagia with all-cause mortality in a time-dependent manner. The risk of death in ICU patients with versus without post-extubation dysphagia declined from about 2.5 times higher to about equal risk for both groups over the first year (i.e. 1.03 yr) post-ICU admission (at 360 d: hazard ratio [HR], 1.03; 95% CI, 0.42-3.70). The mean mortality HR for the first year post-ICU admission was HR 2.09 (95% CI, 1.34-3.24; p = 0.0009). CONCLUSIONS: Long-term follow-up of a large cohort of medical-surgical adult ICU patients systematically screened for dysphagia showed that dysphagia is associated with increased hazards for death for up to 1 year after ICU admission. Our data underline effects of post-extubation dysphagia on long-term clinical outcomes in affected critically ill patients.

Fluid Overload Phenotypes in Critical Illness-A Machine Learning Approach.

BACKGROUND: The detrimental impact of fluid overload (FO) on intensive care unit (ICU) morbidity and mortality is well known. However, research to identify subgroups of patients particularly prone to fluid overload is scarce. The aim of this cohort study was to derive "FO phenotypes" in the critically ill by using machine learning techniques. METHODS: Retrospective single center study including adult intensive care patients with a length of stay of ≥3 days and sufficient data to compute FO. Data was analyzed by multivariable logistic regression, fast and frugal trees (FFT), classification decision trees (DT), and a random forest (RF) model. RESULTS: Out of 1772 included patients, 387 (21.8%) met the FO definition. The random forest model had the highest area under the curve (AUC) (0.84, 95% CI 0.79-0.86), followed by multivariable logistic regression (0.81, 95% CI 0.77-0.86), FFT (0.75, 95% CI 0.69-0.79) and DT (0.73, 95% CI 0.68-0.78) to predict FO. The most important predictors identified in all models were lactate and bicarbonate at admission and postsurgical ICU admission. Sepsis/septic shock was identified as a risk factor in the MV and RF analysis. CONCLUSION: The FO phenotypes consist of patients admitted after surgery or with sepsis/septic shock with high lactate and low bicarbonate.

Fluid overload and mortality in critically ill patients with severe heart failure and cardiogenic shock-An observational cohort study.

Objective: Patients with heart failure (HF) and cardiogenic shock are especially prone to the negative effects of fluid overload (FO); however, fluid resuscitation in respective patients is sometimes necessary resulting in FO. We aimed to study the association of FO at ICU discharge with 30-day mortality in patients admitted to the ICU due to severe heart failure and/or cardiogenic shock. Methods: Retrospective, single-center cohort study. Patients with admission diagnoses of severe HF and/or cardiogenic shock were eligible. The following exclusion criteria were applied: (I) patients younger than 16 years, (II) patients admitted to our intermediate care unit, and (III) patients with incomplete data to determine FO at ICU discharge. We used a cumulative weight-adjusted definition of fluid balance and defined more than 5% as FO. The data were analyzed by univariate and adjusted univariate logistic regression. Results: We included 2,158 patients in our analysis. 185 patients (8.6%) were fluid overloaded at ICU discharge. The mean FO in the FO group was 7.2% [interquartile range (IQR) 5.8-10%]. In patients with FO at ICU discharge, 30-day mortality was 22.7% compared to 11.7% in non-FO patients (p < 0.001). In adjusted univariate logistic regression, we did not observe any association of FO at discharge with 30-day mortality [odds ratio (OR) 1.48; 95% confidence interval (CI) 0.81-2.71, p = 0.2]. No association between FO and 30-day mortality was found in the subgroups with HF only or cardiogenic shock (all p > 0.05). Baseline lactate (adjusted OR 1.27; 95% CI 1.13-1.42; p < 0.001) and cardiac surgery at admission (adjusted OR 1.94; 95% CI 1.0-3.76; p = 0.05) were the main associated factors with FO at ICU discharge. Conclusion: In patients admitted to the ICU due to severe HF and/or cardiogenic shock, FO at ICU discharge seems not to be associated with 30-day mortality.

Characteristics and outcomes of medical emergency team calls in a Swiss tertiary centre - a retrospective observational study.

AIMS OF THE STUDY: To describe reasons for medical emergency team (MET) activation over time, to analyse outcomes, and to describe the circadian distribution of MET calls and Intensive Care Unit (ICU) admissions following MET activation. METHODS: Monocentric retrospective observational study of prospectively collected data on all MET calls between 1st of January 2012 until 31st of May 2019. We analysed data on baselines, referring wards, and disposition of all MET patients. In addition, we allocated all MET calls to the hourly intervals over the 24-hour cycle of the day in order to identify peak times of team activation. RESULTS: A total of 4068 calls in 3277 patients (37% female, n = 1210) were analysed. The mean age was 65.9 years (± 15.7). The MET dose (defined as MET calls/1000 hospital admissions) remained relatively stable over the years with a median of 8.0 calls/1000 hospitalisations (interquartile range [IQR] 7.0-10.0). A total of 2526 calls (62%) occurred out of hours (17:00 to 8:00). The hourly rate of MET activations was greatest during the evening shift (33.8% of calls in seven hours), followed by the day shift (35.8% calls in nine hours) and night shift (30.4% in eight hours). Over the years, staff concern was the main reason for a MET call (n = 1192, 34%), followed by low peripheral oxygen saturation (SpO2) not responding to oxygen therapy (n = 776, 22%). Abnormal respiratory rate was a trigger to call the MET in 44 cases (1.3%), and was not documented prior to 2017. Overall, in-hospital mortality was 22%. CONCLUSION: While most common reasons for MET calls over the years were staff concern and low SpO2, abnormal respiratory rate was the least frequent, but increased after the introduction of the quick sequential organ failure assessment (qSOFA) in 2016. Most MET calls occurred out of hours with peak hours during the evening shift, highlighting the importance of resource allocation during this shift when planning to introduce a MET system in a hospital. In-hospital mortality after a MET call was 22%.

COVID-19-associated acute respiratory distress syndrome (CARDS): Current knowledge on pathophysiology and ICU treatment - A narrative review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus-19 disease (COVID-19) and is a major health concern. Following two SARS-CoV-2 pandemic "waves," intensive care unit (ICU) specialists are treating a large number of COVID19-associated acute respiratory distress syndrome (ARDS) patients. From a pathophysiological perspective, prominent mechanisms of COVID19-associated ARDS (CARDS) include severe pulmonary infiltration/edema and inflammation leading to impaired alveolar homeostasis, alteration of pulmonary physiology resulting in pulmonary fibrosis, endothelial inflammation (endotheliitis), vascular thrombosis, and immune cell activation. Although the syndrome ARDS serves as an umbrella term, distinct, i.e., CARDS-specific pathomechanisms and comorbidities can be noted (e.g., virus-induced endotheliitis associated with thromboembolism) and some aspects of CARDS can be considered ARDS "atypical." Importantly, specific evidence-based medical interventions for CARDS (with the potential exception of corticosteroid use) are currently unavailable, limiting treatment efforts to mostly supportive ICU care. In this article, we will discuss the underlying pulmonary pathophysiology and the clinical management of CARDS. In addition, we will outline current and potential future treatment approaches.

(TIMP2) x (IGFBP7) as early renal biomarker for the prediction of acute kidney injury in aortic surgery (TIGER). A single center observational study.

OBJECTIVE: Postoperative acute kidney injury (po-AKI) is frequently observed after major vascular surgery and impacts on mortality rates. Early identification of po-AKI patients using the novel urinary biomarkers insulin-like growth factor-binding-protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) might help in early identification of individuals at risk of AKI and enable timely introduction of preventative or therapeutic interventions with the aim of reducing the incidence of po-AKI. We investigated whether biomarker-based monitoring would allow for early detection of po-AKI in patients undergoing abdominal aortic interventions. METHODS: In an investigator-initiated prospective single-center observational study in a tertiary care academic center, adult patients with emergency/ elective abdominal aortic repair were included. Patients were tested for concentrations of urinary (TIMP-2) x (IGFBP7) at baseline, after surgical interventions (PO), and in the mornings of the first postoperative day (POD1). The primary endpoint was a difference in urinary (TIMP-2) x (IGFBP7) levels at POD1 in patients with/ without po-AKI (all KDIGO stages, po-AKI until seven days after surgery). Secondary endpoints included sensitivity/ specificity analyses of previously proposed cut-off levels and clinical outcome measures (e.g. need for renal replacement therapy). RESULTS: 93 patients (n = 71 open surgery) were included. Po-AKI was observed in 33% (31/93) of patients. Urinary (TIMP-2) x (IGFBP7) levels at POD1 did not differ between patients with/ without AKI (median 0.39, interquartile range [IQR] 0.13-1.05 and median 0.23, IQR 0.14-0.53, p = .11, respectively) and PO (median 0.2, IQR 0.08-0.42, 0.18, IQR 0.09-0.46; p = .79). Higher median (TIMP-2) x (IGFBP7) levels were noted in KDIGO stage 3 pAKI patients at POD1 (3.75, IQR 1.97-6.92; p = .003). Previously proposed cutoff levels (0.3, 2) showed moderate sensitivity/ specificity (0.58/0.58 and 0.16/0.98, respectively). CONCLUSION: In a prospective monocentric observational study in patients after abdominal aortic repair, early assessment of urinary (TIMP-2) x (IGFBP7) did not appear to have adequate sensitivity/ specificity to identify patients that later developed postoperative AKI. CLINICALTRIALS.GOV: NCT03469765, registered March 19, 2018.

Correction: (TIMP2) x (IGFBP7) as early renal biomarker for the prediction of acute kidney injury in aortic surgery (TIGER). A single center observational study.

[This corrects the article DOI: 10.1371/journal.pone.0244658.].