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      Nucleated red blood cells as predictors of mortality in patients with acute respiratory distress syndrome (ARDS): an observational study


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          Nucleated red blood cells (NRBCs) in critically ill patients are associated with increased mortality and poor outcome. The aim of the present study was to evaluate the predictive value of NRBCs in patients with acute respiratory distress syndrome (ARDS).


          This observational study was conducted at an ARDS referral center and included patients from 2007 to 2014. Daily NRBC counts were assessed and the predictive validity of NRBCs on mortality was statistically evaluated. A cutoff for prediction of mortality based on NRBCs was evaluated using ROC analysis and specified according to Youden’s method. Multivariate nonparametric analysis for longitudinal data was applied to prove for differences between groups over the whole time course. Independent predictors of mortality were identified with multiple logistic and Cox’ regression analyses. Kaplan–Meier estimations visualized the survival; the corresponding curves were tested for differences with the log-rank test.


          A total of 404 critically ill ARDS patients were analyzed. NRBCs were found in 75.5% of the patients, which was associated with longer length of ICU stay [22 (11; 39) vs. 14 (7; 26) days; p < 0.05] and higher mortality rates (50.8 vs. 27.3%; p < 0.001). Logistic regression analysis with mortality as response showed NRBC positivity per se to be an independent risk factor for mortality in ARDS with a doubled risk for ICU death (OR 2.03; 95% CI 1.16–3.55; p < 0.05). Also, NRBC value at ICU admission was found to be an independent risk factor for mortality (OR 3.25; 95% CI 1.09–9.73, p = 0.035). A cutoff level of 220 NRBC/µl was associated with a more than tripled risk of ICU death (OR 3.2; 95% CI 1.93–5.35; p < 0.0001). ARDS patients below this threshold level had a significant survival advantage (median survival 85 days vs. 29 days; log rank p < 0.001). Presence of a severe ARDS was identified as independent risk factor for the occurrence of NRBCs > 220/µl (OR 1.81; 95% CI 1.1–2.97; p < 0.05).


          NRBCs may predict mortality in ARDS with high prognostic power. The presence of NRBCs in the blood might be regarded as a marker of disease severity indicating a higher risk of ICU death.

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          Estimation of the Youden Index and its associated cutoff point.

          The Youden Index is a frequently used summary measure of the ROC (Receiver Operating Characteristic) curve. It both, measures the effectiveness of a diagnostic marker and enables the selection of an optimal threshold value (cutoff point) for the marker. In this paper we compare several estimation procedures for the Youden Index and its associated cutoff point. These are based on (1) normal assumptions; (2) transformations to normality; (3) the empirical distribution function; (4) kernel smoothing. These are compared in terms of bias and root mean square error in a large variety of scenarios by means of an extensive simulation study. We find that the empirical method which is the most commonly used has the overall worst performance. In the estimation of the Youden Index the kernel is generally the best unless the data can be well transformed to achieve normality whereas in estimation of the optimal threshold value results are more variable.
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            Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study.

            To re-examine the epidemiology of acute lung injury (ALI) in European intensive care units (ICUs). A 2-month inception cohort study in 78 ICUs of 10 European countries. All patients admitted for more than 4 h were screened for ALI and followed up to 2 months. Acute lung injury occurred in 463 (7.1%) of 6,522 admissions and 16.1% of all mechanically ventilated patients; 65.4% cases occurred on ICU admission. Among 136 patients initially presenting with "mild ALI" (200< PaO2/FiO2 < or =300), 74 (55%) evolved to acute respiratory distress syndrome (ARDS) within 3 days. Sixty-two patients (13.4%) remained with mild ALI and 401 had ARDS. The crude ICU and hospital mortalities were 22.6% and 32.7% (p<0.001), and 49.4% and 57.9% (p=0.0005), respectively, for mild ALI and ARDS. ARDS patients initially received a mean tidal volume of 8.3+/-1.9 ml/kg and a mean PEEP of 7.7+/-3.6 cmH2O; air leaks occurred in 15.9%. After multivariate analysis, mortality was associated with age (odds ratio (OR) =1.2 per 10 years; 95% confidence interval (CI): 1.05-1.36), immuno-incompetence (OR: 2.88; Cl: 1.57-5.28), the severity scores SAPS II (OR: 1.16 per 10% expected mortality; Cl: 1.02-1.31) and logistic organ dysfunction (OR: 1.25 per point; Cl: 1.13-1.37), a pH less than 7.30 (OR: 1.88; Cl: 1.11-3.18) and early air leak (OR: 3.16; Cl: 1.59-6.28). Acute lung injury was frequent in our sample of European ICUs (7.1%); one third of patients presented with mild ALI, but more than half rapidly evolved to ARDS. While the mortality of ARDS remains high, that of mild ALI is twice as low, confirming the grading of severity between the two forms of the syndrome.
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              Fifty Years of Research in ARDS.Gas Exchange in Acute Respiratory Distress Syndrome

              Acute respiratory distress syndrome (ARDS) is characterized by severe impairment of gas exchange. Hypoxemia is mainly due to intrapulmonary shunt, whereas increased alveolar dead space explains the alteration of CO2 clearance. Assessment of the severity of gas exchange impairment is a requisite for the characterization of the syndrome and the evaluation of its severity. Confounding factors linked to hemodynamic status can greatly influence the relationship between the severity of lung injury and the degree of hypoxemia and/or the effects of ventilator settings on gas exchange. Apart from situations of rescue treatment, targeting optimal gas exchange in ARDS has become less of a priority compared with prevention of injury. A complex question for clinicians is to understand when improvement in oxygenation and alveolar ventilation is related to a lower degree or risk of injury for the lungs. In this regard, a full understanding of gas exchange mechanism in ARDS is imperative for individualized symptomatic support of patients with ARDS.

                Author and article information

                +49-30-450551002 , mario.menk@charite.de
                Ann Intensive Care
                Ann Intensive Care
                Annals of Intensive Care
                Springer International Publishing (Cham )
                27 March 2018
                27 March 2018
                : 8
                [1 ]Department of Anaesthesiology and Operative Intensive Care Medicine (CCM/CVK), Charité – University Medicine Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
                [2 ]ISNI 0000 0001 1093 4868, GRID grid.433743.4, Central Institute of Laboratory Medicine, , DRK Klinikum Berlin Westend, ; Spandauer Damm 130, 14050 Berlin, Germany
                [3 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, Charité - University Medicine Berlin, ; Charitéplatz 1, 10117 Berlin, Germany
                [4 ]Sostana GmbH, Wildensteiner Straße 27, 10318 Berlin, Germany
                © The Author(s) 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

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