High levels of atrial natriuretic peptide and copeptin and mortality risk

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"identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:8 [ 0 => array:3 [ "entidad" => "Unidad de Cuidados Intensivos Pediátricos, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universidad de Oviedo, Oviedo, Asturias, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Red SAMID II, Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Centro de Salud de Tomiño, Servicio Gallego de Salud, Tomiño, Pontevedra, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Universidad Autónoma de Chile, Santiago, Chile" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "Servicio de Cuidados Intensivos Pediátricos, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "Universidad Complutense, Madrid, Spain" "etiqueta" => "h" "identificador" => "aff0040" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Asociación de valores elevados de péptido natriurético auricular y copeptina con riesgo de mortalidad" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1533 "Ancho" => 1545 "Tamanyo" => 113177 ] ] "descripcion" => array:1 [ "en" => "Comparison of serum levels of MR-proANP, copeptin and PCT in groups A (higher scores in the risk of mortality scales) and B (lower score in the risk of mortality scales). P<.001 for all three markers." ] ] ] "textoCompleto" => "IntroductionDetermining the prognosis of a critically ill child within 12h from admission in the paediatric intensive care unit (PICU) continues to be a clinical challenge. At present, the tools used most frequently to assess risk of mortality are scales based on clinical signs and routine laboratory tests. The abnormalities found in different sections of these scales give rise to a score that correlates to mortality in patients. The scales used most frequently are the Paediatric Risk of Mortality III (PRISM III) and the Paediatric Index of Mortality 2 (PIM 2).<a class="elsevierStyleCrossRefs" href="#bib0200">1–5</a>In recent years, it has been demonstrated that there are biomarkers whose plasma levels increase in relation to disease severity. Procalcitonin (PCT) emerged as a marker of sepsis<a class="elsevierStyleCrossRef" href="#bib0225">6</a> and later on was found to be helpful in determining disease severity and predicting patient outcomes.<a class="elsevierStyleCrossRef" href="#bib0230">7</a> Procalcitonin could help identify children at a higher risk of mortality.<a class="elsevierStyleCrossRef" href="#bib0235">8</a> There is also evidence that atrial natriuretic peptide (ANP) and copeptin are associated with severity in septic patients and mortality in critically ill adults.<a class="elsevierStyleCrossRefs" href="#bib0240">9–16</a> The secretion of ANP is primarily determined by increases in atrial wall tension,<a class="elsevierStyleCrossRef" href="#bib0280">17</a> and it modulates the permeability of the endothelium, acting on the regulation of blood volume and arterial pressure.<a class="elsevierStyleCrossRef" href="#bib0285">18</a> Arginine vasopressin (AVP) is secreted in response to osmotic or haemodynamic stimuli. Copeptin is the C-terminal portion of provasopressin.<a class="elsevierStyleCrossRefs" href="#bib0290">19–21</a> It has been regarded as an individual marker of the stress response<a class="elsevierStyleCrossRef" href="#bib0305">22</a> that is elevated during systemic infections.<a class="elsevierStyleCrossRef" href="#bib0310">23</a> Its levels have been associated with mortality risk in adult patients.<a class="elsevierStyleCrossRefs" href="#bib0260">13,24,25</a>Laboratory tests for measuring the levels of midregional pro-ANP (MR-proANP) and copeptin have recently become available. These peptides are synthesised from ANP and AVP, respectively, but they offer the advantage of having a longer half-life (ANP, 5–10min vs MR-proANP, 100–120min; AVP, 5–10min vs copeptin, ex vivo, several days), which makes them more suitable for everyday clinical practice.<a class="elsevierStyleCrossRefs" href="#bib0245">10,17,26</a>We thought it would be interesting to learn whether the association described in adults is also found in children, as thus far no data have been published on the association of these markers with an increased risk of mortality in paediatric patients. Thus, the aim of our study was to determine the levels of MR-proANP, copeptin and PCT in the first 12h following admission to the PICU to test the hypothesis that elevated levels of these markers could be associated with an increased risk of mortality. A secondary objective was to evaluate the hypothesis that elevated levels of these markers would correlate to a greater number of organ system failures.Patients and methodsWe conducted an observational study in two university hospital PICUs. The study was evaluated and approved by the Research Ethics Committee of the Hospital Universitario Central de Asturias. We obtained the informed consent of all parents and participants aged more than 12 years. The sample consisted of 254 patients aged less than 19 years. Newborns were excluded. Inclusion in the study required collection of a blood sample on the basis of clinical manifestations in the first 12h from admission, and signing of the informed consent form. We collected data for the following variables: age, weight, reason for admission to the PICU, diagnosis and previous history of disease. Respiratory rate, heart rate, blood pressure, oxygen saturation, urine output and the administration of vasopressor agents were recorded every hour. Radiologic and microbiological diagnostic tests were performed as deemed necessary by the physician in charge. Blood samples for culture were collected when infection was suspected based on the clinical manifestations or the patient had a body temperature greater than 38°C. The PIM 2 score was calculated at admission and the PRISM III within 12h from admission, as is customary in clinical practice. Both scales (PIM 2 and PRISM III) had been previously validated in both PICUs.<a class="elsevierStyleCrossRef" href="#bib0200">1</a> Samples for routine metabolic tests, including PCT levels, were collected within 12h from admission to the PICU. Samples of venous blood were collected in tubes containing ethylenediaminetetraacetic acid (EDTA). Plasma aliquots were frozen at −80°C for future measurement of MR-proANP and copeptin.Groups by risk of mortalityPatients were divided into two groups based on their mortality risk scores. The group with a high risk of mortality (group A) included patients with PIM 2 and PRISM III scores above the 75th percentile (n=33); the group with a low risk of mortality (group B) included patients with a PIM 2 and/or PRISM III at or below the 75th percentile (n=221).Groups by number of organ system failuresPatients were divided into two groups based on the number of organ system failures (cardiovascular, respiratory, neurologic, haematologic, renal and hepatic) following consensus criteria.<a class="elsevierStyleCrossRef" href="#bib0330">27</a> Group 1 included patients with more than one organ system failure (n=71), while group 2 included patients with fewer than two organ system failures (n=183).Biochemical analysis of the midregion of the proatrial natriuretic peptide and copeptinLevels of MR-proANP, copeptin and PCT were measured in plasma with EDTA using a sandwich immunoassay technique (TRACE technology; Brahms GmbH, Hennigsdorf, Germany). The detection limits were 4.3pmol/L for MR-proANP, 4.8pmol/L for copeptin and 0.02ng/mL for PCT.Statistical analysisWe summarised the clinical characteristics of patients and biomarker values as frequencies, percentages, medians and ranges. For the comparisons of two groups of patients (A vs B and 1 vs 2), we used the Mann–Whitney U test for continuous variables and the chi-square test for categorical variables. We also calculated the diagnostic yield (receiving operating characteristics [ROC]) curves and their respective areas under the curve (AUCs) for a confidence interval (CI) of 95%. Subsequently, we compared them with the aim of determining the marker with the highest yield for the prediction of mortality risk and of organ system failure. In order to compensate for the loss of data in paired comparisons, we used a bootstrap algorithm<a class="elsevierStyleCrossRef" href="#bib0335">28</a> to compare the AUCs. We used the Youden index to establish the cut-off point with the highest sensitivity and specificity for differentiating between the different groups (A vs B, and 1 vs 2). P values of less than 0.05 were considered statistically significant.ResultsSample characteristicsWe included 254 patients in the study (150 male). <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises their demographic, clinical and laboratory testing characteristics. More than half of the sample was aged less than 4 years. The most frequent reasons for admission were postoperative care, heart surgery, respiratory disease and infectious disease. A total of five patients (2%) died during their stay in the PICU. These five patients were in the group with a high predicted risk of mortality (group A). Patients in group A were younger than patients in group B.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Plasma levels of MR-proANP, copeptin and PCT were significantly higher in the group of patients with a higher risk of mortality (group A) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). MR-proANP, copeptin and PCT values were significantly higher in patients with more than one organ system failure (group 1) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Usefulness of midregion proatrial natriuretic peptide, copeptin and procalcitonin for predicting mortality risk in paediatric intensive care unitsTo assess the usefulness of MR-proANP, copeptin and PCT in predicting death and assessing risk of mortality in the PICU, we analysed the ROC curve for each of these biomarkers (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). We did not find statistically significant differences between the AUCs of the three biomarkers. Levels of MR-proANP greater than 106pmol/L had a sensitivity of 72% and a specificity of 70%, while levels of copeptin greater than 64pmol/L had a sensitivity of 70% and a specificity of 74%. The optimal cut-off point for PCT to predict risk of mortality was 2ng/mL, with a sensitivity and specificity of 80%.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>Usefulness of midregion proatrial natriuretic peptide, copeptin and procalcitonin for predicting the number of organ system failures<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a> shows the ROC curves for each biomarker. We found significant differences in the AUCs between MR-proANP and copeptin (P<.01). Differences in the AUCs were not significant in the comparisons between MR-proANP and PCT (P=.48) and between PCT and copeptin (P=.21). Levels of de MR-proANP greater than 101pmol/L had a sensitivity and specificity of 77%, while levels of copeptin greater than 64pmol/L had a sensitivity of 62% and a specificity of 80%. A PCT threshold of 4.1ng/mL had a sensitivity of 69% and a specificity of 88%.<elsevierMultimedia ident="fig0020"></elsevierMultimedia>DiscussionImproving the assessment of the prognosis of patients admitted to the PICU is a field of research relevant to clinical practice. Some biomarkers could help stratify critically ill children based on their risk of mortality.<a class="elsevierStyleCrossRefs" href="#bib0200">1,8</a> In our study of a heterogeneous sample of critically ill children, elevated levels of MR-proANP, copeptin and PCT were associated with higher scores in mortality risk scales and a greater number of organ system failures.The low mortality in our sample, which was similar to the rates currently reported for PICUs in developed countries, forced us to use mortality risk scores obtained using scales previously validated in our PICUs<a class="elsevierStyleCrossRef" href="#bib0200">1</a> as the reference for the prediction of patient prognosis. This will hinder the comparison of our results with those obtained in the adult population, although it is worth noting that all patients that died belonged to the group with high mortality risk scores. The low mortality also led us to use a second severity marker, organ failure, as a reference. More than 90% of patients in the high-mortality risk group had experienced at least two organ system failures.To date, few data are available on the potential of MR-proANP as a predictor of mortality risk, especially in the paediatric population. It has been investigated as a marker of severity in adult septic patients with promising results.<a class="elsevierStyleCrossRef" href="#bib0240">9</a> Elevated levels of MR-proANP at admission in critically ill patients have been associated with higher mortality.<a class="elsevierStyleCrossRefs" href="#bib0240">9–11</a> In our study, we found an AUC of 0.76 for the identification of critically ill children with different predicted mortality risks. Different AUCs have been found in various studies in relation to the risk of mortality: 0.72 in the studies by Lipinska et al.<a class="elsevierStyleCrossRef" href="#bib0245">10</a> and Nowak et al.<a class="elsevierStyleCrossRef" href="#bib0255">12</a> 0.88 in the study by Morgenthaler et al.<a class="elsevierStyleCrossRef" href="#bib0240">9</a> and 0.89 in the study by Wang et al.<a class="elsevierStyleCrossRef" href="#bib0340">29</a> Our cut-off point of 106pmol/L was lower than the cut-off points estimated in these adult series. This could be due to these studies having been performed with patients with different characteristics than the patients in our study, and with different methods. We studied a cohort of children and sought to differentiate the predicted mortality risk at the level of the 75th percentile, whereas the studies that we reviewed<a class="elsevierStyleCrossRefs" href="#bib0240">9,11,12,29,30</a> analysed adult populations and sought to differentiate between survivors and nonsurvivors. The study of Lipinska et al.<a class="elsevierStyleCrossRef" href="#bib0245">10</a> only included patients with sepsis. Another study carried out in adults by Berendes et al.<a class="elsevierStyleCrossRef" href="#bib0350">31</a> did not find an association between different levels of MR-proANP and the risk of mortality.As for copeptin, studies on adults have found areas under ROC curves ranging from 0.70 (Seligman et al.<a class="elsevierStyleCrossRef" href="#bib0355">32</a>) to 0.87 (Du et al.<a class="elsevierStyleCrossRef" href="#bib0265">14</a>), with intermediate values of 0.75 reported by Morgenthaler et al.<a class="elsevierStyleCrossRef" href="#bib0260">13</a> and of 0.83 by Lin et al.<a class="elsevierStyleCrossRef" href="#bib0360">33</a> Our AUC of 0.73 is within this range. We determined a cut-off point of 64pmol/L, similar to those of 64.8 and 62.7pmol/L by Seligman et al.<a class="elsevierStyleCrossRef" href="#bib0355">32</a> and Du et al.<a class="elsevierStyleCrossRef" href="#bib0265">14</a> respectively. Lin et al.<a class="elsevierStyleCrossRef" href="#bib0360">33</a> estimated a cut-off point of 52.7pmol/L, slightly below those reported in other studies. The AUC for high PCT values is also acceptable for predicting mortality risk, and it is known that PCT levels are directly correlated to severity of disease.<a class="elsevierStyleCrossRefs" href="#bib0230">7,34–36</a>As expected, the yield of MR-proANP, copeptin and PCT in identifying patients with more than one organ system failure was consistent with previous descriptions of the prediction of mortality risk in the literature. The values of the AUCs for the differentiation between groups 1 and 2 were acceptable for copeptin and good for PCT and MR-proANP (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>). For PCT, this cut-off value (4.1ng/mL) was higher than the cut-off value for the prediction of mortality risk (2.0ng/mL), while the cut-off points for MR-proANP and copeptin were similar for both predictions. Several studies have found an association between PCT elevation in the first 24h of admission<a class="elsevierStyleCrossRef" href="#bib0380">37</a> or following surgery<a class="elsevierStyleCrossRef" href="#bib0385">38</a> and the number of organ system failures. Lipinska et al.<a class="elsevierStyleCrossRef" href="#bib0245">10</a> and Boeck et al.<a class="elsevierStyleCrossRef" href="#bib0250">11</a> demonstrated the correlation between the levels of MR-proANP and the Sequential Organ Failure Assessment score. We did not find any studies that analysed the use of copeptin as a marker of multiple organ failure. In short, the information provided by these markers could improve the identification of patients with higher scores in mortality risk scales and more than one organ system failure.The PRISM III and PIM 2 scales have been validated for the stratification of mortality risk, but are used more frequently in health administration and research than in clinical decision-making.<a class="elsevierStyleCrossRefs" href="#bib0200">1,3,5</a> Therefore, it would be helpful to have a biomarker that can be measured rapidly and provide similar information. Our group previously observed in the same cohort of patients<a class="elsevierStyleCrossRef" href="#bib0235">8</a> that the midregion of proadrenomedullin (MR-proADM) could also be used to predict the risk of mortality (AUC, 0.866; 95% CI: 0.810–0.921) and the number of organ system failures (AUC, 0.922; 95% CI: 0.887–0.957). When we compared the AUCs, we found statistically significant differences between MR-proADM and MR-proANP (P<.05), and between MR-proADM and copeptin (P<.01). Thus, in our cohort MR-proADM had a higher predictive power than MR-proANP and copeptin. Several recent studies have also shown that MR-proADM levels could be good markers of severity in critically ill patients, both in children<a class="elsevierStyleCrossRefs" href="#bib0235">8,39</a> and adults.<a class="elsevierStyleCrossRef" href="#bib0260">13</a> To confirm our results, future studies should assess whether RM-proADM is a better prognostic predictor than the other three markers.There are several limitations to our study. First of all, we could not use mortality as the reference for differentiating patient prognoses because mortality was low in our sample. As an alternative, we used mortality risk scales and the number of organ system failures, while remaining aware of their limitations. Secondly, we conducted an observational study that did not allow us to draw conclusions regarding therapeutic interventions. Thirdly, our results may not be representative of other PICUs in Spain or other countries, as the sample consisted of patients from only two PICUs. The predictive power could be different for a different population. Last of all, biomarkers were analysed within 12h from admission to the PICU. Repeated measurement of biomarker levels in the early days of admission could increase their accuracy.ConclusionElevated levels of MR-proANP, copeptin and PCT are associated with higher mortality risk scores. There are no significant differences between these three markers. We found that MR-proANP had a stronger correlation with the number of organ system failures than copeptin.FundingThis study was partially funded by a grant from the Fundación Ernesto Sánchez Villares. The kits for the determination of MR-proANP and copeptin were provided by Brahms GmbH (Hennigsdorf, Germany).Conflicts of interestCorsino Rey has received funds from Brahms and Thermofisher to give presentations in conferences on subjects related to biomarkers and sepsis. The rest of the authors have no conflicts of interest to declare. The Fundación Ernesto Sánchez Villares and the Brahms and Thermofisher corporations did not participate in any way in the development of the article, including the study design, data collection and analysis, writing, and decision to submit for publication." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres763791" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec765174" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres763792" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec765173" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Groups by risk of mortality" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Groups by number of organ system failures" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Biochemical analysis of the midregion of the proatrial natriuretic peptide and copeptin" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Sample characteristics" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Usefulness of midregion proatrial natriuretic peptide, copeptin and procalcitonin for predicting mortality risk in paediatric intensive care units" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Usefulness of midregion proatrial natriuretic peptide, copeptin and procalcitonin for predicting the number of organ system failures" ] ] ] 7 => array:2 [ "identificador" => "sec0055" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0060" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0065" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-12-23" "fechaAceptado" => "2016-02-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec765174" "palabras" => array:7 [ 0 => "Mortality risk" 1 => "Organ failure" 2 => "Prognosis" 3 => "Atrial natriuretic peptide" 4 => "Copeptin" 5 => "Procalcitonin" 6 => "Critically ill children" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec765173" "palabras" => array:7 [ 0 => "Riesgo de mortalidad" 1 => "Fallo de órganos" 2 => "Pronóstico" 3 => "Péptido natriurético auricular" 4 => "Copeptina" 5 => "Procalcitonina" 6 => "Niños críticamente enfermos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo determine whether high levels of mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, and procalcitonin (PCT) plasma concentrations are associated with increased mortality risk. MethodsProspective observational study including 254 critically ill children. MR-proANP, copeptin and PCT were compared between children with high (Group A; n=33) and low (Group B; n=221) mortality risk, and between patients with failure of more than 1 organ (Group 1; n=71) and less than 2 (Group 2; n=183). ResultsMedian (range) of MR-proANP, copeptin, and PCT levels in group A vs B were, respectively: 209.4 (30.5–1415.8) vs. 75.0 (14.6–867.2)pmol/L (P<.001); 104.4 (7.4–460.9) vs. 26.6 (0.00–613.1)pmol/L (P<.001), and 7.8 (0.3–552.0) vs. 0.3 (0.02–107.0)ng/mL (P<.001). The area under the curve (AUC) for the differentiation of group A and B was 0.764 (95% CI: 0.674–0.854) for MR-proANP; 0.735 (0.642–0.827) for copeptin, and 0.842 (0.744–0.941) for PCT, with no statistical differences. The AUCs for the differentiation of group 1 and 2 were: 0.837 (0.784–0.891) for MR-proANP, 0.735 (0.666–0.804) for copeptin, and 0.804 (0.715–0.892) for PCT, with statistical differences between MR-proANP and copeptin, P=.01. ConclusionsHigh levels of MR-proANP, copeptin and PCT were associated with increased mortality risk scores. MR-proANP showed a higher association than copeptin with number of organs in failure." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoDeterminar si los niveles plasmáticos de región media del péptido natriurético proauricular (RM-proPNA), copeptina y procalcitonina (PCT) se asocian con aumento del riesgo de mortalidad. MétodosEstudio prospectivo observacional que incluyó a 254 niños críticamente enfermos. Se compararon los niveles de RM-proPNA, copeptina y PCT entre niños con alto (grupo A; n=33) y bajo (grupo B; n=221) riesgo de mortalidad y entre pacientes con un número de órganos en fallo mayor de 1 (grupo 1; n=71) y menor de 2 (grupo 2; n=183). ResultadosLas medianas (rangos) de RM-proPNA, copeptina y PCT en grupo A vs. grupo B fueron, respectivamente: 209,4 (30,5-1.415,8) vs. 75,0 (14,6-867,2) pmol/l (p<0,001); 104,4 (7,4-460,9) vs. 26,6 (0,00-613,1) pmol/l (p<0,001) y 7,8 (0,3-552,0) vs. 0,3 (0,02-107,0) ng/ml (p<0,001). El área bajo la curva (AUC) para diferenciar grupo A y B fue (intervalo de confianza del 95%): 0,764 (0,674-0,854) para RM-proPNA; 0,735 (0,642-0,827) para copeptina y 0,842 (0,744-0,941) para PCT, sin diferencias significativas. Las AUC para diferenciar los grupos 1 y 2 fueron: 0,837 (0,784-0,891) para RM-proPNA, 0,735 (0,666-0,804) para copeptina y 0,804 (0,715-0,892) para PCT, con diferencias significativas entre RM-proPNA y copeptina, p=0,01. ConclusionesLos niveles elevados de RM-proPNA, copeptina y PCT se asocian con aumento de las puntuaciones de riesgo de mortalidad. RM-proPNA mostró mayor asociación que la copeptina con el número de órganos en fallo." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Rey C, García-Cendón C, Martínez-Camblor P, López-Herce J, Concha-Torre A, Medina A, et al. Asociación de valores elevados de péptido natriurético auricular y copeptina con riesgo de mortalidad. An Pediatr (Barc). 2016;85:284–290." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1533 "Ancho" => 1545 "Tamanyo" => 113177 ] ] "descripcion" => array:1 [ "en" => "Comparison of serum levels of MR-proANP, copeptin and PCT in groups A (higher scores in the risk of mortality scales) and B (lower score in the risk of mortality scales). P<.001 for all three markers." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1533 "Ancho" => 1545 "Tamanyo" => 113459 ] ] "descripcion" => array:1 [ "en" => "Comparison of serum levels of MR-proANP, copeptin and PCT in groups 1 (number of organ system failures>1) and 2 (number of organ system failures<2). P<.001 for all three markers." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1596 "Ancho" => 1461 "Tamanyo" => 90283 ] ] "descripcion" => array:1 [ "en" => "ROC curves for MR-proANP, copeptin and PCT for mortality risk score prediction. The areas under the ROC curve were: 0.842 (95% CI: 0.744–0.941) for PCT, 0.764 (95% CI: 0.674–0.854) for MR-proANP and 0.735 (95% CI: 0.642–0.827) for copeptin. The differences between markers were not statistically significant (MR-proANP vs PCT, P=.23; MR-proANP vs copeptin, P=.64; PCT vs copeptin, P=.14)." ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 1563 "Ancho" => 1468 "Tamanyo" => 94225 ] ] "descripcion" => array:1 [ "en" => "ROC curves for MR-proANP, copeptin and PCT for the prediction of the number of organ system failures. The areas under the ROC curve were: 0.804 (95% CI: 0.715–0.892) for PCT, 0.837 (95% CI: 0.784–0.891) for MR-proANP and 0.735 (95% CI: 0.666–0.804) for copeptin. The difference between MR-proANP and copeptin was significant (P=.01). There were no significant differences between MR-proANP and PCT (P=.48) and between PCT and copeptin (P=.21)." ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "PRISM III and PIM 2 are expressed as mean±standard deviation, diagnosis at admission as absolute frequency and percentage, and the rest of the variables as median (range).Group A: group with highest mortality risk scores; Group B: group with lower mortality risk scores." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total sample (n=254) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group A (n=33) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group B (n=221) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Demographic and clinical characteristics</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age at admission (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 (0–224) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 (0–205) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 (0–224) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.012 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight (kg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.0 (2.7–87.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.0 (3.0–74.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.0 (2.7–87.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.005 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male sex (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.853 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Diagnosis at admission</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Postoperative care (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 (23.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (1.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 (98.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Heart surgery (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47 (18.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21 (44.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 (55.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.560 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Respiratory (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45 (17.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (2.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 (97.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Infectious (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 (15.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 (87.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Trauma (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (6.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (11.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (88.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neurologic (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (3.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 (0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Metabolic-renal (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (3.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (11.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 (88.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.039 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Other (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 (16.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 (7.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 (92.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PRISM III (score) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.1±5.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.3±6.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.4±3.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PIM 2 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.8±7.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.2±18.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.4±2.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1261710.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic and clinical characteristics." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:39 [ 0 => array:3 [ "identificador" => "bib0200" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prognostic indexes of mortality in pediatric intensive care units" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000008500000006/v1_201611291247/S234128791630120X/v1_201611291247/en/main.assets" "Apartado" => array:4 [ "identificador" => "26005" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000008500000006/v1_201611291247/S234128791630120X/v1_201611291247/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S234128791630120X?idApp=UINPBA00005H"]

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Original Article

High levels of atrial natriuretic peptide and copeptin and mortality risk

Asociación de valores elevados de péptido natriurético auricular y copeptina con riesgo de mortalidad

Corsino Reya,b,c,

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crey@uniovi.es
corsino.rey@sespa.princast.es

Corresponding author.

, Clara García-Cendónd, Pablo Martínez-Camblore,f, Jesús López-Hercec,g,h, Andrés Concha-Torrea, Alberto Medinaa, Ana Vivanco-Allendea, Juan Mayordomo-Colungaa

a Unidad de Cuidados Intensivos Pediátricos, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain

b Universidad de Oviedo, Oviedo, Asturias, Spain

c Red SAMID II, Instituto de Salud Carlos III, Madrid, Spain

d Centro de Salud de Tomiño, Servicio Gallego de Salud, Tomiño, Pontevedra, Spain

e Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain

f Universidad Autónoma de Chile, Santiago, Chile

g Servicio de Cuidados Intensivos Pediátricos, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain

h Universidad Complutense, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Determining the prognosis of a critically ill child within 12<span class="elsevierStyleHsp" style=""></span>h from admission in the paediatric intensive care unit &#40;PICU&#41; continues to be a clinical challenge&#46; At present&#44; the tools used most frequently to assess risk of mortality are scales based on clinical signs and routine laboratory tests&#46; The abnormalities found in different sections of these scales give rise to a score that correlates to mortality in patients&#46; The scales used most frequently are the Paediatric Risk of Mortality III &#40;PRISM III&#41; and the Paediatric Index of Mortality 2 &#40;PIM 2&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">1&#8211;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In recent years&#44; it has been demonstrated that there are biomarkers whose plasma levels increase in relation to disease severity&#46; Procalcitonin &#40;PCT&#41; emerged as a marker of sepsis<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">6</span></a> and later on was found to be helpful in determining disease severity and predicting patient outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">7</span></a> Procalcitonin could help identify children at a higher risk of mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a> There is also evidence that atrial natriuretic peptide &#40;ANP&#41; and copeptin are associated with severity in septic patients and mortality in critically ill adults&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">9&#8211;16</span></a> The secretion of ANP is primarily determined by increases in atrial wall tension&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">17</span></a> and it modulates the permeability of the endothelium&#44; acting on the regulation of blood volume and arterial pressure&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">18</span></a> Arginine vasopressin &#40;AVP&#41; is secreted in response to osmotic or haemodynamic stimuli&#46; Copeptin is the C-terminal portion of provasopressin&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">19&#8211;21</span></a> It has been regarded as an individual marker of the stress response<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">22</span></a> that is elevated during systemic infections&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">23</span></a> Its levels have been associated with mortality risk in adult patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">13&#44;24&#44;25</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Laboratory tests for measuring the levels of midregional pro-ANP &#40;MR-proANP&#41; and copeptin have recently become available&#46; These peptides are synthesised from ANP and AVP&#44; respectively&#44; but they offer the advantage of having a longer half-life &#40;ANP&#44; 5&#8211;10<span class="elsevierStyleHsp" style=""></span>min vs MR-proANP&#44; 100&#8211;120<span class="elsevierStyleHsp" style=""></span>min&#59; AVP&#44; 5&#8211;10<span class="elsevierStyleHsp" style=""></span>min vs copeptin&#44; ex vivo&#44; several days&#41;&#44; which makes them more suitable for everyday clinical practice&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">10&#44;17&#44;26</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We thought it would be interesting to learn whether the association described in adults is also found in children&#44; as thus far no data have been published on the association of these markers with an increased risk of mortality in paediatric patients&#46; Thus&#44; the aim of our study was to determine the levels of MR-proANP&#44; copeptin and PCT in the first 12<span class="elsevierStyleHsp" style=""></span>h following admission to the PICU to test the hypothesis that elevated levels of these markers could be associated with an increased risk of mortality&#46; A secondary objective was to evaluate the hypothesis that elevated levels of these markers would correlate to a greater number of organ system failures&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted an observational study in two university hospital PICUs&#46; The study was evaluated and approved by the Research Ethics Committee of the Hospital Universitario Central de Asturias&#46; We obtained the informed consent of all parents and participants aged more than 12 years&#46; The sample consisted of 254 patients aged less than 19 years&#46; Newborns were excluded&#46; Inclusion in the study required collection of a blood sample on the basis of clinical manifestations in the first 12<span class="elsevierStyleHsp" style=""></span>h from admission&#44; and signing of the informed consent form&#46; We collected data for the following variables&#58; age&#44; weight&#44; reason for admission to the PICU&#44; diagnosis and previous history of disease&#46; Respiratory rate&#44; heart rate&#44; blood pressure&#44; oxygen saturation&#44; urine output and the administration of vasopressor agents were recorded every hour&#46; Radiologic and microbiological diagnostic tests were performed as deemed necessary by the physician in charge&#46; Blood samples for culture were collected when infection was suspected based on the clinical manifestations or the patient had a body temperature greater than 38<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; The PIM 2 score was calculated at admission and the PRISM III within 12<span class="elsevierStyleHsp" style=""></span>h from admission&#44; as is customary in clinical practice&#46; Both scales &#40;PIM 2 and PRISM III&#41; had been previously validated in both PICUs&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">1</span></a> Samples for routine metabolic tests&#44; including PCT levels&#44; were collected within 12<span class="elsevierStyleHsp" style=""></span>h from admission to the PICU&#46; Samples of venous blood were collected in tubes containing ethylenediaminetetraacetic acid &#40;EDTA&#41;&#46; Plasma aliquots were frozen at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C for future measurement of MR-proANP and copeptin&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Groups by risk of mortality</span><p id="par0030" class="elsevierStylePara elsevierViewall">Patients were divided into two groups based on their mortality risk scores&#46; The group with a high risk of mortality &#40;group A&#41; included patients with PIM 2 and PRISM III scores above the 75th percentile &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#41;&#59; the group with a low risk of mortality &#40;group B&#41; included patients with a PIM 2 and&#47;or PRISM III at or below the 75th percentile &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>221&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Groups by number of organ system failures</span><p id="par0035" class="elsevierStylePara elsevierViewall">Patients were divided into two groups based on the number of organ system failures &#40;cardiovascular&#44; respiratory&#44; neurologic&#44; haematologic&#44; renal and hepatic&#41; following consensus criteria&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">27</span></a> Group 1 included patients with more than one organ system failure &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>71&#41;&#44; while group 2 included patients with fewer than two organ system failures &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>183&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Biochemical analysis of the midregion of the proatrial natriuretic peptide and copeptin</span><p id="par0040" class="elsevierStylePara elsevierViewall">Levels of MR-proANP&#44; copeptin and PCT were measured in plasma with EDTA using a sandwich immunoassay technique &#40;TRACE technology&#59; Brahms GmbH&#44; Hennigsdorf&#44; Germany&#41;&#46; The detection limits were 4&#46;3<span class="elsevierStyleHsp" style=""></span>pmol&#47;L for MR-proANP&#44; 4&#46;8<span class="elsevierStyleHsp" style=""></span>pmol&#47;L for copeptin and 0&#46;02<span class="elsevierStyleHsp" style=""></span>ng&#47;mL for PCT&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">We summarised the clinical characteristics of patients and biomarker values as frequencies&#44; percentages&#44; medians and ranges&#46; For the comparisons of two groups of patients &#40;A vs B and 1 vs 2&#41;&#44; we used the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test for continuous variables and the chi-square test for categorical variables&#46; We also calculated the diagnostic yield &#40;receiving operating characteristics &#91;ROC&#93;&#41; curves and their respective areas under the curve &#40;AUCs&#41; for a confidence interval &#40;CI&#41; of 95&#37;&#46; Subsequently&#44; we compared them with the aim of determining the marker with the highest yield for the prediction of mortality risk and of organ system failure&#46; In order to compensate for the loss of data in paired comparisons&#44; we used a bootstrap algorithm<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">28</span></a> to compare the AUCs&#46; We used the Youden index to establish the cut-off point with the highest sensitivity and specificity for differentiating between the different groups &#40;A vs B&#44; and 1 vs 2&#41;&#46; <span class="elsevierStyleItalic">P</span> values of less than 0&#46;05 were considered statistically significant&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Sample characteristics</span><p id="par0050" class="elsevierStylePara elsevierViewall">We included 254 patients in the study &#40;150 male&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises their demographic&#44; clinical and laboratory testing characteristics&#46; More than half of the sample was aged less than 4 years&#46; The most frequent reasons for admission were postoperative care&#44; heart surgery&#44; respiratory disease and infectious disease&#46; A total of five patients &#40;2&#37;&#41; died during their stay in the PICU&#46; These five patients were in the group with a high predicted risk of mortality &#40;group A&#41;&#46; Patients in group A were younger than patients in group B&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Plasma levels of MR-proANP&#44; copeptin and PCT were significantly higher in the group of patients with a higher risk of mortality &#40;group A&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; MR-proANP&#44; copeptin and PCT values were significantly higher in patients with more than one organ system failure &#40;group 1&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Usefulness of midregion proatrial natriuretic peptide&#44; copeptin and procalcitonin for predicting mortality risk in paediatric intensive care units</span><p id="par0060" class="elsevierStylePara elsevierViewall">To assess the usefulness of MR-proANP&#44; copeptin and PCT in predicting death and assessing risk of mortality in the PICU&#44; we analysed the ROC curve for each of these biomarkers &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; We did not find statistically significant differences between the AUCs of the three biomarkers&#46; Levels of MR-proANP greater than 106<span class="elsevierStyleHsp" style=""></span>pmol&#47;L had a sensitivity of 72&#37; and a specificity of 70&#37;&#44; while levels of copeptin greater than 64<span class="elsevierStyleHsp" style=""></span>pmol&#47;L had a sensitivity of 70&#37; and a specificity of 74&#37;&#46; The optimal cut-off point for PCT to predict risk of mortality was 2<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; with a sensitivity and specificity of 80&#37;&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Usefulness of midregion proatrial natriuretic peptide&#44; copeptin and procalcitonin for predicting the number of organ system failures</span><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a> shows the ROC curves for each biomarker&#46; We found significant differences in the AUCs between MR-proANP and copeptin &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#46; Differences in the AUCs were not significant in the comparisons between MR-proANP and PCT &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;48&#41; and between PCT and copeptin &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;21&#41;&#46; Levels of de MR-proANP greater than 101<span class="elsevierStyleHsp" style=""></span>pmol&#47;L had a sensitivity and specificity of 77&#37;&#44; while levels of copeptin greater than 64<span class="elsevierStyleHsp" style=""></span>pmol&#47;L had a sensitivity of 62&#37; and a specificity of 80&#37;&#46; A PCT threshold of 4&#46;1<span class="elsevierStyleHsp" style=""></span>ng&#47;mL had a sensitivity of 69&#37; and a specificity of 88&#37;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">Improving the assessment of the prognosis of patients admitted to the PICU is a field of research relevant to clinical practice&#46; Some biomarkers could help stratify critically ill children based on their risk of mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">1&#44;8</span></a> In our study of a heterogeneous sample of critically ill children&#44; elevated levels of MR-proANP&#44; copeptin and PCT were associated with higher scores in mortality risk scales and a greater number of organ system failures&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The low mortality in our sample&#44; which was similar to the rates currently reported for PICUs in developed countries&#44; forced us to use mortality risk scores obtained using scales previously validated in our PICUs<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">1</span></a> as the reference for the prediction of patient prognosis&#46; This will hinder the comparison of our results with those obtained in the adult population&#44; although it is worth noting that all patients that died belonged to the group with high mortality risk scores&#46; The low mortality also led us to use a second severity marker&#44; organ failure&#44; as a reference&#46; More than 90&#37; of patients in the high-mortality risk group had experienced at least two organ system failures&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">To date&#44; few data are available on the potential of MR-proANP as a predictor of mortality risk&#44; especially in the paediatric population&#46; It has been investigated as a marker of severity in adult septic patients with promising results&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">9</span></a> Elevated levels of MR-proANP at admission in critically ill patients have been associated with higher mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">9&#8211;11</span></a> In our study&#44; we found an AUC of 0&#46;76 for the identification of critically ill children with different predicted mortality risks&#46; Different AUCs have been found in various studies in relation to the risk of mortality&#58; 0&#46;72 in the studies by Lipinska et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a> and Nowak et al&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">12</span></a> 0&#46;88 in the study by Morgenthaler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">9</span></a> and 0&#46;89 in the study by Wang et al&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">29</span></a> Our cut-off point of 106<span class="elsevierStyleHsp" style=""></span>pmol&#47;L was lower than the cut-off points estimated in these adult series&#46; This could be due to these studies having been performed with patients with different characteristics than the patients in our study&#44; and with different methods&#46; We studied a cohort of children and sought to differentiate the predicted mortality risk at the level of the 75th percentile&#44; whereas the studies that we reviewed<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">9&#44;11&#44;12&#44;29&#44;30</span></a> analysed adult populations and sought to differentiate between survivors and nonsurvivors&#46; The study of Lipinska et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a> only included patients with sepsis&#46; Another study carried out in adults by Berendes et al&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">31</span></a> did not find an association between different levels of MR-proANP and the risk of mortality&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">As for copeptin&#44; studies on adults have found areas under ROC curves ranging from 0&#46;70 &#40;Seligman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a>&#41; to 0&#46;87 &#40;Du et al&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a>&#41;&#44; with intermediate values of 0&#46;75 reported by Morgenthaler et al&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a> and of 0&#46;83 by Lin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">33</span></a> Our AUC of 0&#46;73 is within this range&#46; We determined a cut-off point of 64<span class="elsevierStyleHsp" style=""></span>pmol&#47;L&#44; similar to those of 64&#46;8 and 62&#46;7<span class="elsevierStyleHsp" style=""></span>pmol&#47;L by Seligman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">32</span></a> and Du et al&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">14</span></a> respectively&#46; Lin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">33</span></a> estimated a cut-off point of 52&#46;7<span class="elsevierStyleHsp" style=""></span>pmol&#47;L&#44; slightly below those reported in other studies&#46; The AUC for high PCT values is also acceptable for predicting mortality risk&#44; and it is known that PCT levels are directly correlated to severity of disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">7&#44;34&#8211;36</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">As expected&#44; the yield of MR-proANP&#44; copeptin and PCT in identifying patients with more than one organ system failure was consistent with previous descriptions of the prediction of mortality risk in the literature&#46; The values of the AUCs for the differentiation between groups 1 and 2 were acceptable for copeptin and good for PCT and MR-proANP &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#46; For PCT&#44; this cut-off value &#40;4&#46;1<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; was higher than the cut-off value for the prediction of mortality risk &#40;2&#46;0<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41;&#44; while the cut-off points for MR-proANP and copeptin were similar for both predictions&#46; Several studies have found an association between PCT elevation in the first 24<span class="elsevierStyleHsp" style=""></span>h of admission<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">37</span></a> or following surgery<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">38</span></a> and the number of organ system failures&#46; Lipinska et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">10</span></a> and Boeck et al&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">11</span></a> demonstrated the correlation between the levels of MR-proANP and the Sequential Organ Failure Assessment score&#46; We did not find any studies that analysed the use of copeptin as a marker of multiple organ failure&#46; In short&#44; the information provided by these markers could improve the identification of patients with higher scores in mortality risk scales and more than one organ system failure&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The PRISM III and PIM 2 scales have been validated for the stratification of mortality risk&#44; but are used more frequently in health administration and research than in clinical decision-making&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">1&#44;3&#44;5</span></a> Therefore&#44; it would be helpful to have a biomarker that can be measured rapidly and provide similar information&#46; Our group previously observed in the same cohort of patients<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">8</span></a> that the midregion of proadrenomedullin &#40;MR-proADM&#41; could also be used to predict the risk of mortality &#40;AUC&#44; 0&#46;866&#59; 95&#37; CI&#58; 0&#46;810&#8211;0&#46;921&#41; and the number of organ system failures &#40;AUC&#44; 0&#46;922&#59; 95&#37; CI&#58; 0&#46;887&#8211;0&#46;957&#41;&#46; When we compared the AUCs&#44; we found statistically significant differences between MR-proADM and MR-proANP &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#41;&#44; and between MR-proADM and copeptin &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#46; Thus&#44; in our cohort MR-proADM had a higher predictive power than MR-proANP and copeptin&#46; Several recent studies have also shown that MR-proADM levels could be good markers of severity in critically ill patients&#44; both in children<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">8&#44;39</span></a> and adults&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">13</span></a> To confirm our results&#44; future studies should assess whether RM-proADM is a better prognostic predictor than the other three markers&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">There are several limitations to our study&#46; First of all&#44; we could not use mortality as the reference for differentiating patient prognoses because mortality was low in our sample&#46; As an alternative&#44; we used mortality risk scales and the number of organ system failures&#44; while remaining aware of their limitations&#46; Secondly&#44; we conducted an observational study that did not allow us to draw conclusions regarding therapeutic interventions&#46; Thirdly&#44; our results may not be representative of other PICUs in Spain or other countries&#44; as the sample consisted of patients from only two PICUs&#46; The predictive power could be different for a different population&#46; Last of all&#44; biomarkers were analysed within 12<span class="elsevierStyleHsp" style=""></span>h from admission to the PICU&#46; Repeated measurement of biomarker levels in the early days of admission could increase their accuracy&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusion</span><p id="par0105" class="elsevierStylePara elsevierViewall">Elevated levels of MR-proANP&#44; copeptin and PCT are associated with higher mortality risk scores&#46; There are no significant differences between these three markers&#46; We found that MR-proANP had a stronger correlation with the number of organ system failures than copeptin&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding</span><p id="par0110" class="elsevierStylePara elsevierViewall">This study was partially funded by a grant from the <span class="elsevierStyleGrantSponsor" id="gs1">Fundaci&#243;n Ernesto S&#225;nchez Villares</span>&#46; The kits for the determination of MR-proANP and copeptin were provided by Brahms GmbH &#40;Hennigsdorf&#44; Germany&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">Corsino Rey has received funds from <span class="elsevierStyleGrantSponsor" id="gs2">Brahms and Thermofisher</span> to give presentations in conferences on subjects related to biomarkers and sepsis&#46; The rest of the authors have no conflicts of interest to declare&#46; The Fundaci&#243;n Ernesto S&#225;nchez Villares and the Brahms and Thermofisher corporations did not participate in any way in the development of the article&#44; including the study design&#44; data collection and analysis&#44; writing&#44; and decision to submit for publication&#46;</p></span></span>"
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          "identificador" => "sec0010"
          "titulo" => "Patients and methods"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Groups by risk of mortality"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Groups by number of organ system failures"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Biochemical analysis of the midregion of the proatrial natriuretic peptide and copeptin"
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            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Statistical analysis"
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          "titulo" => "Results"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0040"
              "titulo" => "Sample characteristics"
            ]
            1 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Usefulness of midregion proatrial natriuretic peptide&#44; copeptin and procalcitonin for predicting mortality risk in paediatric intensive care units"
            ]
            2 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Usefulness of midregion proatrial natriuretic peptide&#44; copeptin and procalcitonin for predicting the number of organ system failures"
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          ]
        ]
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          "identificador" => "sec0055"
          "titulo" => "Discussion"
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          "titulo" => "Conclusion"
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        9 => array:2 [
          "identificador" => "sec0065"
          "titulo" => "Funding"
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        10 => array:2 [
          "identificador" => "sec0070"
          "titulo" => "Conflicts of interest"
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        11 => array:1 [
          "titulo" => "References"
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      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2015-12-23"
    "fechaAceptado" => "2016-02-03"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec765174"
          "palabras" => array:7 [
            0 => "Mortality risk"
            1 => "Organ failure"
            2 => "Prognosis"
            3 => "Atrial natriuretic peptide"
            4 => "Copeptin"
            5 => "Procalcitonin"
            6 => "Critically ill children"
          ]
        ]
      ]
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec765173"
          "palabras" => array:7 [
            0 => "Riesgo de mortalidad"
            1 => "Fallo de &#243;rganos"
            2 => "Pron&#243;stico"
            3 => "P&#233;ptido natriur&#233;tico auricular"
            4 => "Copeptina"
            5 => "Procalcitonina"
            6 => "Ni&#241;os cr&#237;ticamente enfermos"
          ]
        ]
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To determine whether high levels of mid-regional pro-atrial natriuretic peptide &#40;MR-proANP&#41;&#44; copeptin&#44; and procalcitonin &#40;PCT&#41; plasma concentrations are associated with increased mortality risk&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective observational study including 254 critically ill children&#46; MR-proANP&#44; copeptin and PCT were compared between children with high &#40;Group A&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#41; and low &#40;Group B&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>221&#41; mortality risk&#44; and between patients with failure of more than 1 organ &#40;Group 1&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>71&#41; and less than 2 &#40;Group 2&#59; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>183&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Median &#40;range&#41; of MR-proANP&#44; copeptin&#44; and PCT levels in group A vs B were&#44; respectively&#58; 209&#46;4 &#40;30&#46;5&#8211;1415&#46;8&#41; vs&#46; 75&#46;0 &#40;14&#46;6&#8211;867&#46;2&#41;<span class="elsevierStyleHsp" style=""></span>pmol&#47;L &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#59; 104&#46;4 &#40;7&#46;4&#8211;460&#46;9&#41; vs&#46; 26&#46;6 &#40;0&#46;00&#8211;613&#46;1&#41;<span class="elsevierStyleHsp" style=""></span>pmol&#47;L <span class="elsevierStyleItalic">&#40;P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; and 7&#46;8 &#40;0&#46;3&#8211;552&#46;0&#41; vs&#46; 0&#46;3 &#40;0&#46;02&#8211;107&#46;0&#41;<span class="elsevierStyleHsp" style=""></span>ng&#47;mL <span class="elsevierStyleItalic">&#40;P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; The area under the curve &#40;AUC&#41; for the differentiation of group A and B was 0&#46;764 &#40;95&#37; CI&#58; 0&#46;674&#8211;0&#46;854&#41; for MR-proANP&#59; 0&#46;735 &#40;0&#46;642&#8211;0&#46;827&#41; for copeptin&#44; and 0&#46;842 &#40;0&#46;744&#8211;0&#46;941&#41; for PCT&#44; with no statistical differences&#46; The AUCs for the differentiation of group 1 and 2 were&#58; 0&#46;837 &#40;0&#46;784&#8211;0&#46;891&#41; for MR-proANP&#44; 0&#46;735 &#40;0&#46;666&#8211;0&#46;804&#41; for copeptin&#44; and 0&#46;804 &#40;0&#46;715&#8211;0&#46;892&#41; for PCT&#44; with statistical differences between MR-proANP and copeptin&#44; <span class="elsevierStyleItalic">P</span>&#61;&#46;01&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">High levels of MR-proANP&#44; copeptin and PCT were associated with increased mortality risk scores&#46; MR-proANP showed a higher association than copeptin with number of organs in failure&#46;</p></span>"
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          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Determinar si los niveles plasm&#225;ticos de regi&#243;n media del p&#233;ptido natriur&#233;tico proauricular &#40;RM-proPNA&#41;&#44; copeptina y procalcitonina &#40;PCT&#41; se asocian con aumento del riesgo de mortalidad&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo observacional que incluy&#243; a 254 ni&#241;os cr&#237;ticamente enfermos&#46; Se compararon los niveles de RM-proPNA&#44; copeptina y PCT entre ni&#241;os con alto &#40;grupo A&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#41; y bajo &#40;grupo B&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>221&#41; riesgo de mortalidad y entre pacientes con un n&#250;mero de &#243;rganos en fallo mayor de 1 &#40;grupo 1&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>71&#41; y menor de 2 &#40;grupo 2&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>183&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Las medianas &#40;rangos&#41; de RM-proPNA&#44; copeptina y PCT en grupo A vs&#46; grupo B fueron&#44; respectivamente&#58; 209&#44;4 &#40;30&#44;5-1&#46;415&#44;8&#41; vs&#46; 75&#44;0 &#40;14&#44;6-867&#44;2&#41; pmol&#47;l &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#59; 104&#44;4 &#40;7&#44;4-460&#44;9&#41; vs&#46; 26&#44;6 &#40;0&#44;00-613&#44;1&#41; pmol&#47;l &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y 7&#44;8 &#40;0&#44;3-552&#44;0&#41; vs&#46; 0&#44;3 &#40;0&#44;02-107&#44;0&#41; ng&#47;ml &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; El &#225;rea bajo la curva &#40;AUC&#41; para diferenciar grupo A y B fue &#40;intervalo de confianza del 95&#37;&#41;&#58; 0&#44;764 &#40;0&#44;674-0&#44;854&#41; para RM-proPNA&#59; 0&#44;735 &#40;0&#44;642-0&#44;827&#41; para copeptina y 0&#44;842 &#40;0&#44;744-0&#44;941&#41; para PCT&#44; sin diferencias significativas&#46; Las AUC para diferenciar los grupos 1 y 2 fueron&#58; 0&#44;837 &#40;0&#44;784-0&#44;891&#41; para RM-proPNA&#44; 0&#44;735 &#40;0&#44;666-0&#44;804&#41; para copeptina y 0&#44;804 &#40;0&#44;715-0&#44;892&#41; para PCT&#44; con diferencias significativas entre RM-proPNA y copeptina&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los niveles elevados de RM-proPNA&#44; copeptina y PCT se asocian con aumento de las puntuaciones de riesgo de mortalidad&#46; RM-proPNA mostr&#243; mayor asociaci&#243;n que la copeptina con el n&#250;mero de &#243;rganos en fallo&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Rey C&#44; Garc&#237;a-Cend&#243;n C&#44; Mart&#237;nez-Camblor P&#44; L&#243;pez-Herce J&#44; Concha-Torre A&#44; Medina A&#44; et al&#46; Asociaci&#243;n de valores elevados de p&#233;ptido natriur&#233;tico auricular y copeptina con riesgo de mortalidad&#46; An Pediatr &#40;Barc&#41;&#46; 2016&#59;85&#58;284&#8211;290&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Comparison of serum levels of MR-proANP&#44; copeptin and PCT in groups A &#40;higher scores in the risk of mortality scales&#41; and B &#40;lower score in the risk of mortality scales&#41;&#46; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001 for all three markers&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Comparison of serum levels of MR-proANP&#44; copeptin and PCT in groups 1 &#40;number of organ system failures<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>1&#41; and 2 &#40;number of organ system failures<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#41;&#46; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001 for all three markers&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">ROC curves for MR-proANP&#44; copeptin and PCT for mortality risk score prediction&#46; The areas under the ROC curve were&#58; 0&#46;842 &#40;95&#37; CI&#58; 0&#46;744&#8211;0&#46;941&#41; for PCT&#44; 0&#46;764 &#40;95&#37; CI&#58; 0&#46;674&#8211;0&#46;854&#41; for MR-proANP and 0&#46;735 &#40;95&#37; CI&#58; 0&#46;642&#8211;0&#46;827&#41; for copeptin&#46; The differences between markers were not statistically significant &#40;MR-proANP vs PCT&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;23&#59; MR-proANP vs copeptin&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;64&#59; PCT vs copeptin&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;14&#41;&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ROC curves for MR-proANP&#44; copeptin and PCT for the prediction of the number of organ system failures&#46; The areas under the ROC curve were&#58; 0&#46;804 &#40;95&#37; CI&#58; 0&#46;715&#8211;0&#46;892&#41; for PCT&#44; 0&#46;837 &#40;95&#37; CI&#58; 0&#46;784&#8211;0&#46;891&#41; for MR-proANP and 0&#46;735 &#40;95&#37; CI&#58; 0&#46;666&#8211;0&#46;804&#41; for copeptin&#46; The difference between MR-proANP and copeptin was significant &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41;&#46; There were no significant differences between MR-proANP and PCT &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;48&#41; and between PCT and copeptin &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;21&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">PRISM III and PIM 2 are expressed as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#44; diagnosis at admission as absolute frequency and percentage&#44; and the rest of the variables as median &#40;range&#41;&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Group A&#58; group with highest mortality risk scores&#59; Group B&#58; group with lower mortality risk scores&#46;</p>"
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Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2016.10.003

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Year/Month	Html	Pdf	Total

2024 November	7	9	16
2024 October	37	39	76
2024 September	37	38	75
2024 August	48	62	110
2024 July	40	37	77
2024 June	46	31	77
2024 May	48	24	72
2024 April	46	27	73
2024 March	46	25	71
2024 February	46	32	78
2024 January	31	29	60
2023 December	51	23	74
2023 November	47	24	71
2023 October	36	32	68
2023 September	23	20	43
2023 August	36	16	52
2023 July	31	26	57
2023 June	40	31	71
2023 May	40	23	63
2023 April	24	15	39
2023 March	55	26	81
2023 February	33	17	50
2023 January	21	18	39
2022 December	55	22	77
2022 November	62	39	101
2022 October	56	36	92
2022 September	26	29	55
2022 August	35	49	84
2022 July	31	37	68
2022 June	25	33	58
2022 May	42	32	74
2022 April	26	22	48
2022 March	39	51	90
2022 February	28	24	52
2022 January	32	33	65
2021 December	23	39	62
2021 November	40	41	81
2021 October	64	90	154
2021 September	31	28	59
2021 August	27	42	69
2021 July	19	25	44
2021 June	25	39	64
2021 May	35	51	86
2021 April	94	84	178
2021 March	54	33	87
2021 February	28	24	52
2021 January	31	21	52
2020 December	33	27	60
2020 November	23	14	37
2020 October	22	16	38
2020 September	31	15	46
2020 August	11	14	25
2020 July	45	22	67
2020 June	27	17	44
2020 May	19	17	36
2020 April	23	10	33
2020 March	29	14	43
2020 February	24	19	43
2020 January	10	8	18
2019 December	58	25	83
2019 November	8	5	13
2019 October	28	18	46
2019 September	22	9	31
2019 August	57	23	80
2019 July	33	16	49
2019 June	31	19	50
2019 May	32	24	56
2019 April	68	33	101
2019 March	40	13	53
2019 February	39	12	51
2019 January	37	21	58
2018 December	57	25	82
2018 November	55	37	92
2018 October	68	18	86
2018 September	20	20	40
2018 July	2	0	2
2018 June	6	0	6
2018 May	3	0	3
2018 April	25	0	25
2018 March	25	0	25
2018 February	12	0	12
2018 January	11	0	11
2017 December	21	0	21
2017 November	27	0	27
2017 October	27	0	27
2017 September	24	0	24
2017 August	18	0	18
2017 July	13	0	13
2017 June	15	5	20
2017 May	18	6	24
2017 April	9	6	15
2017 March	9	5	14
2017 February	12	6	18
2017 January	13	3	16
2016 December	40	19	59
2016 November	0	18	18

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