Prevalence and characteristics of medical emergency teams in Switzerland: a nationwide survey of intensive care units.

BACKGROUND: Medical Emergency Teams (METs) have been implemented in many hospitals worldwide and are considered an integral part of the hospital patient safety system. However, data on prevalence, staffing and activation criteria of METs are scarce. Such data are important as they may help to identify areas of quality improvement and barriers to implementation of rapid response systems (RRS). This survey aimed to analyze current characteristics, prevalence, and organization of METs in Switzerland. METHODS: We conducted a cross-sectional nationwide online survey, inviting physicians' and nurses' representatives from all registered adult intensive care units (ICU) in Switzerland. RESULTS: Of the 74 hospitals invited to participate in the survey, 57 responded (response rate 77%). We obtained 82 individual responses (from 50 physicians and 32 nurses). Twenty-five hospitals (44%) have a MET in place. In most Swiss hospitals, METs are composed of ICU consultants (64%) and ICU nurses (40%) and are activated by phone, with a usual response time of less than 10 minutes. The most common triggers are single abnormal vital signs (80%), while multiple-parameter warning scores are less commonly used (28%). While more than half of the nurses have regular trainings for their MET members (57%), most MET physicians (63%) do not. Systematic data collection of MET calls occurs in only 43% of institutions. Finally, the most common reasons for not having a MET are staff shortage (44%) and lack of funding (19%). CONCLUSIONS: Less than 50% of Swiss hospitals with an adult ICU have a MET in place. METs in Switzerland typically include an ICU doctor and an ICU nurse and are available 24/7. Major barriers to MET introduction are staff shortage and lack of funding.

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.

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.

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.

Early Rehabilitation Interventions and Physical Therapy in Adults Who Were Critically Ill With COVID-19 Pneumonia: A Retrospective Observational Study.

OBJECTIVE: The primary objective of this observational study was to analyze the time to the first edge-of-bed (EOB) mobilization in adults who were critically ill with severe versus non-severe COVID-19 pneumonia. Secondary objectives included the description of early rehabilitation interventions and physical therapy delivery. METHODS: All adults with laboratory-confirmed COVID-19 requiring intensive care unit admission for ≥72 hours were included and divided according to their lowest PaO2/FiO2 ratio into severe (≤100 mmHg) or non-severe (>100 mmHg) COVID-19 pneumonia. Early rehabilitation interventions consisted of in-bed activities, EOB or out-of-bed mobilizations, standing, and walking. The Kaplan-Meier estimate and logistic regression were used to investigate the primary outcome time-to-EOB and factors associated with delayed mobilization. RESULTS: Among the 168 patients included in the study (mean age = 63 y [SD = 12 y]; Sequential Organ Failure Assessment = 11 [interquartile range = 9-14]), 77 (46%) were classified as non-severe, and 91 (54%) were classified as severe COVID-19 pneumonia. Median time-to-EOB was 3.9 days (95% CI = 2.3-5.5) with significant differences between subgroups (non-severe = 2.5 days [95% CI = 1.8-3.5]; severe = 7.2 days [95% CI = 5.7-8.8]). Extracorporeal membrane oxygenation use and high Sequential Organ Failure Assessment scores (adjusted effect = 13.7 days [95% CI = 10.1-17.4] and 0.3 days [95% CI = 0.1-0.6]) were significantly associated with delayed EOB mobilization. Physical therapy started within a median of 1.0 days (95% CI = 0.9-1.2) without subgroup differences. CONCLUSION: This study shows that early rehabilitation and physical therapy within the recommended 72 hours during the COVID-19 pandemic could be maintained regardless of disease severity. In this cohort, the median time-to-EOB was fewer than 4 days, with disease severity and advanced organ support significantly delaying the time-to-EOB. IMPACT: Early rehabilitation in the intensive care unit could be sustained in adults who are critically ill with COVID-19 pneumonia and can be implemented with existing protocols. Screening based on the PaO2/FiO2 ratio might reveal patients at risk and increased need for physical therapy.

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.

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%.

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.

CAR T-cell therapy and critical care : A survival guide for medical emergency teams.

Chimeric antigen receptor (CAR) T­cells are genetically engineered to give T­cells the ability to attack specific cancer cells, and to improve outcome of patients with refractory/relapsed aggressive B­cell malignancies. To date, several CAR T­cell products are approved and additional products with similar indication or extended to other malignancies are currently being evaluated. Side effects of CAR T­cell treatment are potentially severe or even life-threatening immune-related toxicities, specifically cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Consequently, medical emergency teams (MET) are increasingly involved in the assessment and management of CAR T­cell recipients. This article describes the principles of CAR T­cell therapy and summarizes the main complications and subsequent therapeutic interventions aiming to provide a survival guide for METs with a proposed management algorithm.

Fluid Overload and Mortality in Adult Critical Care Patients-A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Fluid administration in combination with the increase in vasopermeability induced by critical illness often results in significant fluid overload in critically ill patients. Recent research indicates that mortality is increased in patients who have received large volumes of fluids. We have systematically reviewed and synthesized the evidence on fluid overload and mortality in critically ill patients and have performed a meta-analysis of available data from observational studies. DATA SOURCES: A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. STUDY SELECTION AND DATA EXTRACTION: All studies were eligible that investigated the impact of fluid overload (defined by weight gain > 5%) or positive cumulative fluid balance on mortality in adult critical care patients. We excluded animal studies and trials in pediatric populations (age < 16 years old), pregnant women, noncritically ill patients, very specific subpopulations of critically ill patients, and on early goal-directed therapy. Randomized controlled trials were only evaluated in the section on systematic review. Assessment followed the Cochrane/meta-analysis of observational trials in epidemiology guidelines for systematic reviews. DATA SYNTHESIS: A total of 31 observational and three randomized controlled trials including 31,076 ICU patients met the inclusion criteria. Only observational studies were included in the meta-analysis. Fluid overload and cumulative fluid balance were both associated with pooled mortality: after 3 days of ICU stay, adjusted relative risk for fluid overload was 8.83 (95% CI, 4.03-19.33), and for cumulative fluid balance 2.15 (95% CI, 1.51-3.07), at any time point, adjusted relative risk for fluid overload was 2.79 (95% CI, 1.55-5.00) and 1.39 (95% CI, 1.15-1.69) for cumulative fluid balance. Fluid overload was associated with mortality in patients with both acute kidney injury (adjusted relative risk, 2.38; 95% CI, 1.75-2.98) and surgery (adjusted relative risk, 6.17; 95% CI, 4.81-7.97). Cumulative fluid balance was linked to mortality in patients with sepsis (adjusted relative risk, 1.66; 95% CI, 1.39-1.98), acute kidney injury (adjusted relative risk, 2.63; 95% CI, 1.30-5.30), and respiratory failure (adjusted relative risk, 1.19; 95% CI, 1.03-1.43). The risk of mortality increased by a factor of 1.19 (95% CI, 1.11-1.28) per liter increase in positive fluid balance. CONCLUSIONS: This systematic review and meta-analysis of observational studies reporting adjusted risk estimates suggests that fluid overload and positive cumulative fluid balance are associated with increased mortality in a general population and defined subgroups of critically ill patients.

The effect of dexmedetomidine on vasopressor requirements in patients with septic shock: a subgroup analysis of the Sedation Practice in Intensive Care Evaluation [SPICE III] Trial.

BACKGROUND: Septic shock is associated with decreased vasopressor responsiveness. Experimental data suggest that central alpha2-agonists like dexmedetomidine (DEX) increase vasopressor responsiveness and reduce catecholamine requirements in septic shock. However, DEX may also cause hypotension and bradycardia. Thus, it remains unclear whether DEX is hemodynamically safe or helpful in this setting. METHODS: In this post hoc subgroup analysis of the Sedation Practice in Intensive Care Evaluation (SPICE III) trial, an international randomized trial comparing early sedation with dexmedetomidine to usual care in critically patients receiving mechanical ventilation, we studied patients with septic shock admitted to two tertiary ICUs in Australia and Switzerland. The primary outcome was vasopressor requirements in the first 48 h after randomization, expressed as noradrenaline equivalent dose (NEq [µg/kg/min] = noradrenaline + adrenaline + vasopressin/0.4). RESULTS: Between November 2013 and February 2018, 417 patients were recruited into the SPICE III trial at both sites. Eighty-three patients with septic shock were included in this subgroup analysis. Of these, 44 (53%) received DEX and 39 (47%) usual care. Vasopressor requirements in the first 48 h were similar between the two groups. Median NEq dose was 0.03 [0.01, 0.07] µg/kg/min in the DEX group and 0.04 [0.01, 0.16] µg/kg/min in the usual care group (p = 0.17). However, patients in the DEX group had a lower NEq/MAP ratio, indicating lower vasopressor requirements to maintain the target MAP. Moreover, on adjusted multivariable analysis, higher dexmedetomidine dose was associated with a lower NEq/MAP ratio. CONCLUSIONS: In critically ill patients with septic shock, patients in the DEX group received similar vasopressor doses in the first 48 h compared to the usual care group. On multivariable adjusted analysis, dexmedetomidine appeared to be associated with lower vasopressor requirements to maintain the target MAP. TRIAL REGISTRATION: The SPICE III trial was registered at ClinicalTrials.gov ( NCT01728558 ).

Hypertonic saline for fluid resuscitation in ICU patients post-cardiac surgery (HERACLES): a double-blind randomized controlled clinical trial.

PURPOSE: Recent evidence questions a liberal approach to fluid resuscitation in intensive care unit (ICU) patients. Here, we assess whether use of hypertonic saline applied as single infusion at ICU admission after cardiac surgery can reduce cumulative perioperative fluid volume. METHODS: Prospective randomized double-blind single-center clinical trial investigates effects of a single infusion of hypertonic saline (HS) versus normal saline (comparator). Primary endpoint was the cumulative amount of fluid administered in patients in the hypertonic saline versus the 0.9% saline groups (during ICU stay). Upon ICU admission, patients received a single infusion of 5 ml/kg body weight of 7.3% NaCl (or 0.9% NaCl) over 60 min. Patients undergoing cardiac surgery for elective valvular and/or coronary heart disease were included. Patients with advanced organ dysfunction, infection, and/or patients on chronic steroid medication were excluded. RESULTS: A total of 101 patients were randomized to receive the study intervention (HS n = 53, NS n = 48). Cumulative fluid intake on the ICU (primary endpoint) did not differ between the HS and the NS groups [median 3193 ml (IQR 2052-4333 ml) vs. 3345 ml (IQR 2332-5043 ml)]. Postoperative urinary output until ICU discharge was increased in HS-treated patients [median 2250 ml (IQR 1640-2690 ml) vs. 1545 ml (IQR 1087-1976 ml)], and ICU fluid balance was lower in the HS group when compared to the NS group [296 ml (IQR - 441 to 1412 ml) vs. 1137 ml (IQR 322-2660 ml)]. CONCLUSION: In a monocentric prospective double-blind randomized clinical trial, we observed that hypertonic saline did not reduce the total fluid volume administered on the ICU in critically ill cardiac surgery patients. Hypertonic saline infusion was associated with timely increase in urinary output. Variations in electrolyte and acid-base homeostasis were transient, but substantial in all patients.

Cytokine Removal in Critically Ill Patients Requiring Surgical Therapy for Infective Endocarditis (RECReATE): An Investigator-initiated Prospective Randomized Controlled Clinical Trial Comparing Two Established Clinical Protocols.

INTRODUCTION: Infective endocarditis (IE) and other severe infections induce significant changes in the immune response in a considerable number of affected patients. Numerous IE patients develop a persistent functional immunological phenotype that can best be characterized by a profound anti-inflammation and/ or functional "anergy." This is pronounced in patients with unresolved infectious foci and was previously referred to as "injury-associated immunosuppression" (IAI). IAI can be assessed by measurement of the monocytic human leukocyte antigen-DR (mHLA-DR) expression, a global functional marker of immune competence. Persistence of IAI is associated with prolonged intensive care unit length of stay, increased secondary infection rates, and death. Immunomodulation to reverse IAI was shown beneficial in early immunostimulatory (randomized controlled) clinical trials. METHODS: Prospective 1:1 randomized controlled clinical study to compare the course of mHLA-DR in patients scheduled for cardiac surgery for IE. Patients will receive either best standard of care plus cytokine adsorption during surgery while on cardiopulmonary bypass (protocol A) versus best standard of care alone, that is, surgery without cytokine adsorption (protocol B). A total of 54 patients will be recruited and randomized. The primary endpoint is a change in quantitative expression of mHLA-DR (antibodies per cell on CD14+ monocytes/ macrophages, assessed using a quantitative standardized assay) from baseline (preoperation [pre-OP], visit 1) to day 1 post-OP (visit 4). DISCUSSION: This randomized controlled clinical trial (RECReATE) will compare 2 clinical treatment protocols and will investigate whether cytokine adsorption restores monocytic immune competence (reflected by increased mHLA-DR expression) in patients with IE undergoing cardiac surgery. TRIAL REGISTRATION: This protocol was registered in ClinicalTrials.gov, under number NCT03892174, first listed on March 27, 2019.

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.

Hypertonic saline for fluid resuscitation after cardiac surgery (HERACLES): study protocol for a preliminary randomised controlled clinical trial.

BACKGROUND: Intraoperative and postoperative management of cardiac surgery patients is complex, involving the application of differential vasopressors and volume therapy. It has been shown that a positive fluid balance has a major impact on postoperative outcome. Today, the advantages and disadvantages of buffered crystalloid solutes are a topic of controversy, with no consensus being reached so far. The use of hypertonic saline (HS) has shown promising results with respect to lower total fluid balance and postoperative weight gain in critically ill patients in preliminary studies. However, collection of more data on HS in critically ill patients seems warranted. This preliminary study aims to investigate whether fluid resuscitation using HS in patients following cardiac surgery results in less total fluid volume being administered. METHODS: In a prospective double-blind randomised controlled clinical trial, we aim to recruit 96 patients undergoing elective cardiac surgery for ischaemic and/or valvular heart disease. After postoperative admission to the intensive care unit (ICU), patients will be randomly assigned to receive 5 ml/kg ideal body weight HS (7.3% NaCl) or normal saline (NS, 0.9% NaCl) infused within 60 min. Blood and urine samples will be collected preoperatively and postoperatively up to day 6 to assess changes in renal, cardiac, inflammatory, acid-base, and electrolyte parameters. Additionally, we will perform renal ultrasonography studies to assess renal blood flow before, during, and after infusion, and we will measure total body water using preoperative and postoperative body composition analysis (bioimpedance). Patients will be followed up for 90 days. DISCUSSION: The key objective of this study is to assess the cumulative amount of fluid administered in the intervention (HS) group versus control (NS) group during the ICU stay. In this preliminary, prospective, randomised controlled clinical trial we will test the hypothesis that use of HS results in less total fluids infused and less postoperative weight gain when compared to the standard of intensive care in cardiac surgery patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03280745 . Registered on 12 September 2017.

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.