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Contains fulltext : 293877.pdf (Publisher’s version ) (Open Access) OBJECTIVES: Early Warning Scores (EWSs) have a great potential to assist clinical decision-making in the emergency department (ED). However, many EWS contain methodological weaknesses in development and validation and have poor predictive performance in older patients. The aim of this study was to develop and externally validate an International Early Warning Score (IEWS) based on a recalibrated National Early warning Score (NEWS) model including age and sex and evaluate its performance independently at arrival to the ED in three age categories (18-65, 66-80, > 80 yr). DESIGN: International multicenter cohort study. SETTING: Data was used from three Dutch EDs. External validation was performed in two EDs in Denmark. PATIENTS: All consecutive ED patients greater than or equal to 18 years in the Netherlands Emergency department Evaluation Database (NEED) with at least two registered vital signs were included, resulting in 95,553 patients. For external validation, 14,809 patients were included from a Danish Multicenter Cohort (DMC). MEASUREMENTS AND MAIN RESULTS: Model performance to predict in-hospital mortality was evaluated by discrimination, calibration curves and summary statistics, reclassification, and clinical usefulness by decision curve analysis. In-hospital mortality rate was 2.4% ( n = 2,314) in the NEED and 2.5% ( n = 365) in the DMC. Overall, the IEWS performed significantly better than NEWS with an area under the receiving operating characteristic of 0.89 (95% CIs, 0.89-0.90) versus 0.82 (0.82-0.83) in the NEED and 0.87 (0.85-0.88) versus 0.82 (0.80-0.84) at external validation. Calibration for NEWS predictions underestimated risk in older patients and overestimated risk in the youngest, while calibration improved for IEWS with a substantial reclassification of patients from low to high risk and a standardized net benefit of 5-15% in the relevant risk range for all age categories. CONCLUSIONS: The IEWS substantially improves in-hospital mortality prediction for all ED patients greater than or equal to18 years.

Study objective: To investigate how age affects the predictive performance of the National Early Warning Score (NEWS) at arrival to the emergency department (ED) regarding inhospital mortality and intensive care admission.Methods: International multicenter retrospective cohorts from 2 Danish and 3 Dutch ED. Development cohort: 14,809 Danish patients aged >= 18 years with at least systolic blood pressure or pulse measured from the Danish Multicenter Cohort. External validation cohort: 50,448 Dutch patients aged >18 years with all vital signs measured from the Netherlands Emergency Department Evaluation Database (NEED). Multivariable logistic regression was used for model building. Performance was evaluated overall and within age categories: 18 to 64 years, 65 to 80 years, and more than 80 years.Results: In the Danish Multicenter Cohort, a total of 2.5% died inhospital, and 2.8% were admitted to the ICU, compared with 2.8% and 1.6%, respectively, in the NEED. Age did not add information for the prediction of intensive care admission but was the strongest predictor for inhospital mortality. For NEWS alone, severe underestimation of risk was observed for persons above 80 while overall Area Under Receiver Operating Characteristic (AUROC) was 0.82 (confidence interval [CI] 0.80 to 0.84) in the Danish Multicenter Cohort versus 0.75 (CI 0.75 to 0.77) in the NEED. When combining NEWS with age, underestimation of risks was eliminated for persons above 80, and overall AUROC increased significantly to 0.86 (CI 0.85 to 0.88) in the Danish Multicenter Cohort versus 0.82 (CI 0.81 to 0.83) in the NEED.Conclusion: Combining NEWS with age improved the prediction performance regarding inhospital mortality, mostly for persons aged above 80, and can potentially improve decision policies at arrival to EDs.

Appropriate interpretation of blood tests is important for risk stratification and guidelines used in the Emergency Department (ED) (such as SIRS or CURB-65). The impact of abnormal blood test values on mortality may change with increasing age due to (patho)-physiologic changes. The aim of this study was therefore to assess the effect of age on the case-mix adjusted association between biomarkers of renal function and homeostasis, inflammation and circulation and in-hospital mortality. This observational multi-center cohort study has used the Netherlands Emergency department Evaluation Database (NEED), including all consecutive ED patients ≥ 18 years of three hospitals. A generalized additive logistic regression model was used to visualize the association between in-hospital mortality, age and five blood tests (creatinine, sodium, leukocytes, C-reactive Protein, and hemoglobin). Multivariable logistic regression analyses were used to assess the association between the number of abnormal blood test values and mortality per age category (18–50; 51–65; 66–80; > 80 years). Of the 94,974 included patients, 2550 (2.7%) patients died in-hospital. Mortality increased gradually for C-reactive Protein (CRP), and had a U-shaped association for creatinine, sodium, leukocytes, and hemoglobin. Age significantly affected the associations of all studied blood tests except in leukocytes. In addition, with increasing age categories, case-mix adjusted mortality increased with the number of abnormal blood tests. In summary, the association between blood tests and (adjusted) mortality depends on age. Mortality increases gradually or in a U-shaped manner with increasing blood test values. Age-adjusted numerical scores may improve risk stratification. Our results have implications for interpretation of blood tests and their use in risk stratification tools and acute care guidelines.Trial registration number Netherlands Trial Register (NTR) NL8422, 03/2020.

BackgroundAppropriate interpretation of vital signs is essential for risk stratification in the emergency department (ED) but may change with advancing age. In several guidelines, risk scores such as the Systemic Inflammatory Response Syndrome(SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) scores, commonly used in emergency medicine practice (as well as critical care) specify a single cut-off or threshold for each of the commonly measured vital signs. Although a single cut-off may be convenient, it is unknown whether a single cut-off for vital signs truly exists and if the association between vital signs and in-hospital mortality differs per age-category.AimsTo assess the association between initial vital signs and case-mix adjusted in-hospital mortality in different age categories.MethodsObservational multicentre cohort study using the Netherlands Emergency Department Evaluation Database (NEED) in which consecutive ED patients ≥18 years were included between 1 January 2017 and 12 January 2020. The association between vital signs and case-mix adjusted mortality were assessed in three age categories (18-65; 66-80; >80 years) using multivariable logistic regression. Vital signs were each divided into five to six categories, for example, systolic blood pressure (SBP) categories (≤80, 81–100, 101–120, 121–140, >140 mm Hg).ResultsWe included 101 416 patients of whom 2374 (2.3%) died. Adjusted ORs for mortality increased gradually with decreasing SBP and decreasing peripheral oxygen saturation (SpO2). Diastolic blood pressure (DBP), mean arterial pressure (MAP) and heart rate (HR) had quasi-U-shaped associations with mortality. Mortality did not increase for temperatures anywhere in the range between 35.5°C and 42.0°C, with a single cut-off around 35.5°C below which mortality increased. Single cut-offs were also found for MAP 22/min. For all vital signs, older patients had larger increases in absolute mortality compared with younger patients.ConclusionFor SBP, DBP, SpO2and HR, no single cut-off existed. The impact of changing vital sign categories on prognosis was larger in older patients. Our results have implications for the interpretation of vital signs in existing risk stratification tools and acute care guidelines.

Purpose: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. Materials & methods: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. Results: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when con -sidering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. Conclusions: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients. ? 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

Background: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands.Methods: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios.Results: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO(2)) of 85-90% as acceptable for 15 minutes, and a PaO2 7-To kPa (53-75 mmHg) and SaO(2) 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO(2)) if SaO(2) was 90-95% or PaO2 was 12 kPa (90 mmHg).Conclusion: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO(2) targets in the lower physiological range and would adjust ventilation settings accordingly.

Objective: To describe the effect of implementation of a Rapid Response System (RRS) on the composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death. Design: Pragmatic prospective Dutch multi-center before-after trial, Cost and Outcomes analysis of Medical Emergency Teams (COMET) trial. Setting: Twelve hospitals participated, each including two surgical and two non-surgical wards between April 2009 and November 2011. The Modified Early Warning Score (MEWS) and Situation-Background-Assessment-Recommendation (SBAR) instruments were implemented over seven months. The Rapid Response Team (RRT) was then implemented during the following 17 months. The effects of implementing the RRT were measured in the last 5 months of this period. Patients: All patients 18 years and older admitted to the study wards were included. Measurements and main results: In total 166,569 patients were included in the study representing 1,031,172 hospital admission days. No differences were observed in patient demographics between periods. The composite endpoint of cardiopulmonary arrest, unplanned ICU admission, or death per 1000 admissions was significantly reduced in the RRT versus the before phase, adjusted odds ratio (OR) 0.847 (95% CI 0.725-0.989, p=0.036). Cardiopulmonary arrests and in hospital mortality were also significantly reduced, OR 0.607 (95 CI 0.393-0.937, p=0.018) and OR 0.802 (95% CI 0.644-1.0, p=0.05) respectively. Unplanned ICU admissions showed a declining trend, OR 0.878 (95% CI 0.755-1.021, p=0.092) whereas severity of illness at the moment of ICU admission was not different between periods. Conclusions: In this study, introduction of nationwide implementation of RRSs was associated with a decrease in the composite endpoint of cardiopulmonary arrests, unplanned ICU admissions and mortality in patients on general hospital wards. These findings support the implementation of RRSs in hospitals to reduce severe adverse events.

Importance It remains uncertain whether invasive ventilation should use low tidal volumes in critically ill patients without acute respiratory distress syndrome (ARDS). Objective To determine whether a low tidal volume ventilation strategy is more effective than an intermediate tidal volume strategy. Design, Setting, and Participants A randomized clinical trial, conducted from September 1, 2014, through August 20, 2017, including patients without ARDS expected to not be extubated within 24 hours after start of ventilation from 6 intensive care units in the Netherlands. Interventions Invasive ventilation using low tidal volumes (n = 477) or intermediate tidal volumes (n = 484). Main Outcomes and Measures The primary outcome was the number of ventilator-free days and alive at day 28. Secondary outcomes included length of ICU and hospital stay; ICU, hospital, and 28- and 90-day mortality; and development of ARDS, pneumonia, severe atelectasis, or pneumothorax. Results In total, 961 patients (65% male), with a median age of 68 years (interquartile range [IQR], 59-76), were enrolled. At day 28, 475 patients in the low tidal volume group had a median of 21 ventilator-free days (IQR, 0-26), and 480 patients in the intermediate tidal volume group had a median of 21 ventilator-free days (IQR, 0-26) (mean difference, –0.27 [95% CI, –1.74 to 1.19]; P = .71). There was no significant difference in ICU (median, 6 vs 6 days; 0.39 [–1.09 to 1.89]; P = .58) and hospital (median, 14 vs 15 days; –0.60 [–3.52 to 2.31]; P = .68) length of stay or 28-day (34.9% vs 32.1%; hazard ratio [HR], 1.12 [0.90 to 1.40]; P = .30) and 90-day (39.1% vs 37.8%; HR, 1.07 [0.87 to 1.31]; P = .54) mortality. There was no significant difference in the percentage of patients developing the following adverse events: ARDS (3.8% vs 5.0%; risk ratio [RR], 0.86 [0.59 to 1.24]; P = .38), pneumonia (4.2% vs 3.7%; RR, 1.07 [0.78 to 1.47]; P = .67), severe atelectasis (11.4% vs 11.2%; RR, 1.00 [0.81 to 1.23]; P = .94), and pneumothorax (1.8% vs 1.3%; RR, 1.16 [0.73 to 1.84]; P = .55). Conclusions and Relevance In patients in the ICU without ARDS who were expected not to be extubated within 24 hours of randomization, a low tidal volume strategy did not result in a greater number of ventilator-free days than an intermediate tidal volume strategy. Trial Registration ClinicalTrials.gov Identifier:NCT02153294

Background The purpose of this study was to assess the effect of replacing all-cause mortality by death without limitation of medical treatments (LOMT) as the endpoint in a study of rapid response teams (RRTs) in hospitalized patients. We also described the time course of LOMT orders in patients dying on a general ward and the influence of RRTs on such orders. Methods This study is a secondary analysis of the COMET trial, a pragmatic prospective Dutch multicenter before-after study. We repeated the original analysis of the influence of RRTs on death before hospital discharge by replacing all-cause mortality by death without an LOMT order. In a subgroup of all patients dying before hospital discharge, we documented patient demographics, admission characteristics and LOMT orders of each patient. Patients age 18 years or above were included. Results In total, 166,569 patients were included in the study. The unadjusted ORs were 0.865 (95 % CI 0.77-0.98) in the original analysis using all-cause mortality and 0.557 (95 % CI 0.40-0.78) when choosing death without LOMT as the endpoint. In total, 3408 patients died before discharge. At time of death, 2910 (85 %) had an LOMT order. Median time from last change in LOMT status and death was 2 days (IQR 1–5) in the before-phase and median time after introduction of the RRT was 1 day (IQR 1–4) (p value not significant). Conclusions The improvement in survival of hospitalized patients after introduction of a rapid response team in the COMET study was more pronounced when choosing death without limitation of medical treatment, rather than all deaths as the endpoint. Most patients who died during hospitalization had limitation of medical treatments ordered, often shortly before death. Rapid response teams did not influence the institution of limitation of medical treatments.

SummaryBackground Coagulopathy has a high prevalence in critically ill patients. An increased International Normalized Ratio (INR) is a common trigger to transfuse fresh frozen plasma (FFP), even in the absence of bleeding. Therefore, FFP is frequently administered to these patients. However, the efficacy of FFP in correcting hemostatic disorders in non-bleeding recipients has been questioned. Objectives To assess whether INR prolongation parallels changes in the results of other tests investigating hemostasis, and to evaluate the coagulant effects of a fixed dose of FFP in non-bleeding critically ill patients with a coagulopathy. Methods Markers of coagulation, individual factor levels and levels of natural anticoagulants were measured. Also, thrombin generation and thromboelastometry (ROTEM) assays were performed before and after FFP transfusion (12 mL kg−1) to 38 non-bleeding critically ill patients with an increased INR (1.5–3.0). Results At baseline, levels of factor II, FV, FVII, protein C, protein S and antithrombin were reduced, and thrombin generation was impaired. ROTEM variables were within reference ranges, except for a prolonged INTEM clot formation time. FFP transfusion increased the levels of coagulation factors (FII, 34% [interquartile range (IQR) 26–46] before vs. 44% [IQR 38–52] after; FV, 48% [IQR 28–76] before vs. 58% [IQR 44–90] after; and FVII, 25% [IQR 16–38] before vs. 37% [IQR 28–55] after), and the levels of anticoagulant proteins. Thrombin generation was unaffected by FFP transfusion (endogenous thrombin potential, 72% [IQR 51–88] before vs. 71% [IQR 42–89] after), whereas ROTEM EXTEM clotting time and maximum clot firmness slightly improved in response to FFP. Conclusion In non-bleeding critically ill patients with a coagulopathy, FFP transfusion failed to induce a more procoagulant state.

Contains fulltext : 52407.pdf ( ) (Open Access) INTRODUCTION: The aim of the study was to assess the influence of annual volume and factors related to intensive care unit (ICU) organization on in-hospital mortality among patients admitted to the ICU with severe sepsis. METHODS: A retrospective cohort study was conducted using the database of the Dutch National Intensive Care Evaluation (NICE) registry. Analyses were based on consecutive patients admitted between 1 January 2003 and 30 June 2005 who fulfilled criteria for severe sepsis within the first 24 hours of admission. A 13-item questionnaire was sent to all 32 ICUs across The Netherlands that participated in the NICE registry within this period in order to obtain information on ICU organization and staffing. The association between in-hospital mortality and factors related to ICU organization was investigated using logistic regression analysis, combined with generalized estimation equations to account for potential correlations of outcomes within ICUs. Correction for patient-related factors took place by including Simplified Acute Physiology Score II, age, sex and number of dysfunctioning organ systems in the analyses. RESULTS: Analyses based on 4,605 patients from 28 ICUs (questionnaire response rate 90.6%) revealed that a higher annual volume of severe sepsis patients is associated with a lower in-hospital mortality (P = 0.029). The presence of a medium care unit (MCU) as a step-down facility with intermediate care is associated with a higher in-hospital mortality (P = 0.013). For other items regarding ICU organization, no independent significant relationships with in-hospital mortality were found. CONCLUSION: A larger annual volume of patients with severe sepsis admitted to Dutch ICUs is associated with lower in-hospital mortality in this patient group. The presence of a MCU as a step-down facility is associated with greater in-hospital mortality. No other significant associations between in-hospital mortality and factors related to ICU organization were found.

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