Corrected QT interval during therapeutic hypothermia in hypoxic ischaemic encephalopathy

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d’Hebron, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "El intervalo QT corregido durante la hipotermia terapéutica en la encefalopatía hipóxico-isquémica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1275 "Ancho" => 1589 "Tamanyo" => 97271 ] ] "descripcion" => array:1 [ "en" => "There were no statistically significant differences in the QTc interval during therapeutic hypothermia based on the use or lack of use of inotropic support (P=.669)." ] ] ] "textoCompleto" => "IntroductionModerate and severe HIE (clinically significant HIE) is an important cause of neonatal mortality and future neurodevelopmental disability. In recent years, several clinical trials and meta-analyses have demonstrated that the reduction of body temperature by 3–4°C (moderate hypothermia) by total body or selective head cooling initiated early (before 6h from birth) and maintained for 72h is effective in reducing mortality and severe disability in children that survive a perinatal hypoxic-ischaemic insult.<a class="elsevierStyleCrossRefs" href="#bib0130">1–4</a>None of the studies published to date has described significant cardiovascular or haemodynamic complications resulting from moderate hypothermia, including the development of arrhythmias, whose incidence (with the exception of sinus bradycardia) has not been observed to increase during therapeutic hypothermia,<a class="elsevierStyleCrossRefs" href="#bib0140">3–6</a> even when there has been accidental overcooling.There is extensive documentation on the effects of hypothermia on the cardiovascular system of adults. From the earliest assessments of the effects of cooling performed in survivors of severe accidental hypothermia to animal model studies, there has been growing evidence on the association between cooling and sinus bradycardia, as well as other disturbances of the electrical activity of the heart.<a class="elsevierStyleCrossRefs" href="#bib0160">7–9</a> The joint guidelines of the International Liaison European Resuscitation Council and European Resuscitation Council<a class="elsevierStyleCrossRef" href="#bib0175">10</a> and the guideline of the American Heart Association<a class="elsevierStyleCrossRef" href="#bib0180">11</a> both describe the potential arrythmogenicity of hypothermia<a class="elsevierStyleCrossRefs" href="#bib0185">12–15</a> in adults treated with hypothermia after experiencing cardiac arrest due to ventricular arrhythmia.Hypothermia has the potential to increase the risk of arrhythmia, as it decreases the rate of depolarization in pacemaker cells while simultaneously increasing the duration of action potentials. This leads to a reduction in heart rate and other abnormalities, including the prolongation of PR and QTc intervals.<a class="elsevierStyleCrossRefs" href="#bib0205">16,17</a> A prolonged QTc interval in and of itself increases the risk of developing polymorphic ventricular tachycardias.<a class="elsevierStyleCrossRef" href="#bib0215">18</a> The evidence that is currently available is practically limited to studies conducted in adults, which have not found an increased incidence of potentially severe arrhythmias as long as the hypothermia was moderate (32–34.5°C) and electrolyte levels were monitored. There have been reports of ventricular arrhythmias in patients cooled to temperatures of less than 32°C<a class="elsevierStyleCrossRef" href="#bib0220">19</a> and hypokalaemia.<a class="elsevierStyleCrossRef" href="#bib0225">20</a>The aim of our study was to determine whether therapeutic hypothermia in newborns with significant EHI is associated with the incidence of arrhythmias and specifically with QTc prolongation.Materials and methodsWe conducted an observational prospective study in newborns with neonatal asphyxia treated with moderate hypothermia that were admitted to the neonatal intensive care unit (NICU) of the Hospital Universitario Vall d’Hebron (HUVH) between November 2012 and October 2013. The study included all newborns with perinatal asphyxia and significant HIE that met the criteria for treatment with therapeutic hypothermia and received this treatment at the NICU of the HUVH during the period under study. Moderate hypothermia in all included patients consisted of total body cooling by means of a servo-controlled temperature regulation system following the protocol of the hospital.We collected data for demographic and clinical variables of interest for the included patients (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). In all patients, 12-lead electrocardiograms (ECGs) were performed during therapeutic hypothermia (one ECG every 24h during the three days of treatment) and during rewarming until the patient reached a normal body temperature (one ECG performed for every one-degree increase in body temperature: 34.5, 35.5 and 36.5°C). A seventh ECG was performed at one week of life. The ECGs were evaluated following a standardised approach by two researchers. The duration of the QTc interval was calculated by applying Bazett's formula to five cycles from the lead II tracing in each of the ECGs, and other relevant features were also assessed, including the PR interval, QRS, repolarization, heart axis and heart rate. We analysed the presence of heart rhythm and conduction abnormalities in all ECGs.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>We used the following electrocardiographic definitions, which were based in the European Society of Cardiology guidelines for the interpretation of the neonatal ECG<a class="elsevierStyleCrossRef" href="#bib0230">21</a>:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-Sinus bradycardia: heart rate less than or equal to 93 beats per minute (bpm) the first day of life, less than or equal to 91bpm up to the third day of life, and less than or equal to 90bpm up to the seventh day of life, inclusive, with a regular heart rhythm;</li><li class="elsevierStyleListItem" id="lsti0010">-Normal QTc: value less than 450milliseconds (ms);</li><li class="elsevierStyleListItem" id="lsti0015">-Prolonged QTc: calculated value greater than 450ms;</li><li class="elsevierStyleListItem" id="lsti0020">-Prolonged PR: intervals lasting more than 140ms.</li></ul>The presence and severity of significant HIE were classified as moderate or severe using the semiquantitative scale developed by Garcia-Alix.<a class="elsevierStyleCrossRef" href="#bib0235">22</a> All patients underwent a cranial magnetic resonance imaging (MRI) scan between 5 and 7 days of life, with severity graded according to the criteria of van Rooij et al.<a class="elsevierStyleCrossRef" href="#bib0240">23</a>We collected data on variables perceived as potential confounding factors due to their association with QT prolongation in the literature, including serum levels of potassium, magnesium and calcium, and the use of drugs that prolong the QTc interval as well as vasoactive drugs (adrenaline, dopamine and dobutamine).The study protocol was reviewed and approved by the Clinical Research Ethics Committee of the HUVH, and we safeguarded the confidentiality of all the data obtained from the patients in the study.Statistical analysisWe conducted a descriptive analysis of demographic and clinical variables and of the results of diagnostic tests. We present categorical variables as percentages and frequencies. Continuous variables (gestational age and weight) are expressed as median and interquartile range.We compared values of the primary outcome variable, the corrected QTc measured in ms, in relation to subgroups by means of generalised linear models for an accurate analysis of repeated measurements in each participant. Statistical significance was defined as P<.05. We performed the analysis with the statistical software SPSS version 20.0 (IBM Corp, Armonk, USA).ResultsA total of 19 patients were included in the study, of whom 73.5% (n=14) had transferred from other facilities (with passive hypothermia initiated during transport). Forty-seven percent were male newborns, the median gestational age was 40+2 weeks (36+6–41+1 weeks), and the median weight 3020g (2400–3400g). Ten patients (53%) had moderate HIE based on the clinical assessment (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).Sentinel events were identified in 53% of patients (n=10), the most frequent of which were placental abruption (n=3) and obstructed labour (n=3). Other documented events were umbilical cord prolapse, uterine rupture, chorioamnionitis or foetal-maternal haemorrhage.Based on the cranial MRI scan performed between days 5 and 7 of life, eleven patients (58%) had a van Roij score equal to or greater than 4.All patients were monitored by amplitude-integrated electroencephalography (EEGa) during hypothermia, the rewarming period and the days that followed. Fifty-eight percent of patients (n=11) had clinical/electrical seizures, and all of them received anticonvulsant therapy. The baseline EEGa showed a burst suppression pattern in 32% of patients (n=6), a low voltage pattern in 21% (n=4) and an isoelectric pattern in 21% (n=4).The ECG tracings revealed a prolonged QTc interval in all patients during hypothermia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). In 84% of patients (n=16), this prolongation was detected in all the ECGs performed during hypothermia. In three patients, one of the recordings did not show a prolonged QTc. After rewarming, the QTc interval normalised in all patients.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The analysis of the ECG recordings taken during rewarming showed that at 34.5°C, 47% of the patients (n=9) still had a prolonged QTc interval, and at 35.5°C, 10% of patients (n=2) still had a prolonged QTc interval. None of the patients had a prolonged QTc interval at temperatures above 36°C.We did not find statistically significant differences in the QTc interval prolongation based on the degree of HIE (P=.192) or the use or lack of inotropic support (P=.669) (<a class="elsevierStyleCrossRefs" href="#fig0010">Figs. 2 and 3</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia>None of the patients developed potentially severe arrhythmias. The measured serum levels of potassium, magnesium and calcium were within normal ranges in all patients. There was no documented use of other drugs that could prolong the QT interval (with the exception of the use of vasoactive drugs described above).Sinus bradycardia was detected at some point during therapeutic hypothermia in 73.5% of patients (n=14) by continuous cardiorespiratory monitoring. Prolongation of the PR interval was detected in none.One of the patients with moderate HIE developed an isolated episode of paroxysmal supraventricular tachycardia during admission (at 10 days post birth) that required antiarrhythmic therapy, which was discontinued prior to discharge from the unit. We did not find an association between this episode of arrhythmia and the therapeutic hypothermia, nor observed a prolongation of the QTc interval at any point of his stay in the unit after it had normalised with rewarming.DiscussionThere is a dearth of published evidence on the association of the electrical activity of the heart and therapeutic hypothermia for significant HIE in the neonatal population. The efficacy and safety of this treatment have been demonstrated, and there is cumulative evidence on the development of sinus bradycardia as a frequent and reversible side effect of hypothermia. The association of hypothermia with low blood pressure secondary to the decreased heart rate and requiring inotropic support has also been described. Very few publications address other potential effects of hypothermia in neonates, and they consist of isolated cases that suggest that it may lead to abnormal prolongation of the QTc interval that resolves with rewarming.<a class="elsevierStyleCrossRefs" href="#bib0245">24,25</a>This is the first prospective study performed in newborns with significant HIE treated with moderate hypothermia with the purpose of analysing the association of the QTc interval with body temperature in this population.In all our patients, moderate hypothermia induced a prolonged QTc interval during treatment. Also, the QTc interval normalised in all patients once their body temperatures reached normal physiological ranges (equal to or higher than 36°C).In any case, the prolongation of the QTc interval in newborns with significant HIE subjected to hypothermia did not seem to increase the risk of developing potentially severe arrhythmias.It does not seem that potentially confounding factors, such as the use of inotropic support or the degree of the hypoxic-ischaemic insult (severity of encephalopathy), influence the behaviour of the QTc interval in relation to temperature.Sinus bradycardia is a frequent side effect of hypothermia in newborns, as has been documented in multiple studies and observations. Although studies conducted in adults found a nearly universal prolongation of the PR interval in association with hypothermia, PR intervals greater than 140ms have not been observed in studied patients (none exceeded 120ms).It could be useful to perform an ECG after rewarming to confirm the presence of a normal QTc interval to avoid missing potential congenital QT interval abnormalities, and this test could be carried out immediately after completing rewarming or at a later time. This ECG can be particularly relevant in survivors of postnatal collapse treated with off-protocol hypothermia, in whom assessment for a pathological arrhythmia as a potential cause of postnatal collapse could be contemplated. We consider that once ECG features are confirmed to be normal after rewarming, it is not necessary to follow up these patients in the cardiology department.There are some limitations to this study. Due to the lack of studies analysing QTc prolongation in newborns with significant HIE treated with hypothermia in the existing literature, we had to undertake this study as exploratory research with the purpose of increasing our knowledge of this association in newborns and obtaining the necessary data to design future confirmatory studies that would test specific hypotheses and carry out a formal sample size calculation. Since hypothermia must be induced as early as possible in these patients, we could not use each case as its own control, and it was not possible to obtain ECGs prior to cooling.ConclusionsModerate hypothermia for the treatment of newborns with asphyxia and significant HIE seems to induce a transient prolongation of the QTc interval that resolves with rewarming to normal body temperature (greater than 36°C). At the temperature used in therapeutic (moderate) hypothermia, there seems to be no risk of developing severe ventricular arrhythmias as long as factors such as serum electrolyte levels or the use of drugs that prolong the QTc interval are within normal ranges.We believe that these patients do not require a followup programme if their QTc interval have normalised after reaching a normal body temperature.Further and more powerful studies are needed to assess more accurately the association between body temperature and the QTc interval and other electrocardiographic parameters.Conflict of interestsThe authors have no conflict of interests to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres763812" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec765191" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres763813" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec765192" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conclusions" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflict of interests" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-11-03" "fechaAceptado" => "2016-01-11" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec765191" "palabras" => array:5 [ 0 => "Asphyxia" 1 => "Hypoxic ischaemic encephalopathy" 2 => "Arrhythmia" 3 => "Newborn" 4 => "Induced hypothermia" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec765192" "palabras" => array:5 [ 0 => "Asfixia" 1 => "Encefalopatía hipóxico-isquémica" 2 => "Arritmia" 3 => "Neonato" 4 => "Hipotermia inducida" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionTherapeutic hypothermia is the standard treatment for hypoxic ischaemic encephalopathy (HIE), despite not knowing all its effects and complications. Sinus bradycardia is one of the consequences of cooling that has been previously documented in the literature, but little is known about the cardiac electrical activity in these patients. ObjectiveTo determine the corrected QT (QTc) interval in newborns treated with therapeutic hypothermia for HIE. Materials and methodsA prospective observational study was conducted in all patients treated with hypothermia for HIE that were admitted to our Unit between November 2012 and October 2013. ECGs were performed during hypothermia (every 24h), during the re-warming period (at 34.5°C, 35.5°C, 36.5°C), and on the 7th day of life. ResultsA total of 19 patients were included. A prolonged QTc was observed in all patients during hypothermia, and 84% (n=16) had prolonged QTc in all the ECGs during treatment. In 3 patients, one of the ECGs did not have a prolonged QTc. After re-warming, the QTc interval returned to normal in all patients. No statistically significant differences were seen when the degree of HIE (P=.192) or the use of inotropic support (P=.669) were considered. ConclusionsTherapeutic hypothermia applied to asphyxiated newborns with HIE seems to induce a QTc prolongation that resolves when the patient regains physiological temperature." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa hipotermia es el tratamiento estándar en la encefalopatía hipóxico isquémica (EHI) a pesar de que todavía no se conocen todos sus efectos y complicaciones. La bradicardia sinusal está ampliamente descrita en la literatura como consecuencia de dicho enfriamiento pero se ha estudiado poco la actividad eléctrica cardiaca en este grupo de pacientes. ObjetivoDeterminar si existe un alargamiento del intervalo QT corregido (QTc) durante la hipotermia en neonatos con EHI moderada-grave y su evolución durante el tratamiento. Material y métodosSe reclutó a pacientes con EHI tratados con hipotermia entre noviembre del 2012 y octubre del 2013. Se realizaron electrocardiogramas (ECG) durante la hipotermia (uno cada 24 h durante el tratamiento) y durante el recalentamiento (a 34,5, 35,5 y 36,5°C). Se realizó un séptimo ECG a la semana de vida. ResultadosSe incluyó a un total de 19 pacientes. Se observó un alargamiento del QTc en todos los pacientes durante la hipotermia. En 84% de los pacientes (n=16), el alargamiento se apreció en todos los ECG durante la hipotermia. Tras el recalentamiento, todos los pacientes presentaron una normalización del mismo. No se encontraron diferencias estadísticamente significativas al evaluar la prolongación del QTc según el grado de EHI (p=0,192) y según el uso de soporte inotrópico o no (p=0,669). Ningún paciente presentó arritmias potencialmente graves. ConclusionesLa hipotermia moderada aplicada a los recién nacidos con EHI moderada-grave parece inducir una prolongación en el intervalo QTc temporal que se resuelve con el recalentamiento del paciente hasta temperatura fisiológica." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Material y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Vega L, Boix H, Albert D, Delgado I, Castillo F. El intervalo QT corregido durante la hipotermia terapéutica en la encefalopatía hipóxico-isquémica. An Pediatr (Barc). 2016;85:312–317." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1203 "Ancho" => 1663 "Tamanyo" => 94490 ] ] "descripcion" => array:1 [ "en" => "QTc interval in relation to temperature (hypothermia, rewarming and seventh day of life)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1306 "Ancho" => 1630 "Tamanyo" => 100672 ] ] "descripcion" => array:1 [ "en" => "There were no statistically significant differences in the QTc interval during therapeutic hypothermia based on the degree of HIE (P=.192)." ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1275 "Ancho" => 1589 "Tamanyo" => 97271 ] ] "descripcion" => array:1 [ "en" => "There were no statistically significant differences in the QTc interval during therapeutic hypothermia based on the use or lack of use of inotropic support (P=.669)." ] ] 3 => 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" => "Degree of HIE based on the semiquantitative scale of Garcia-Alix.F, female; GA, gestational age; M, male; MRI, magnetic resonance imaging (van Rooij score); VH, Hospital Vall D’ Hebron." "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient \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">Weight (g) \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">GA (weeks+days) \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">Sex \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">Sentinel event \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">Point of origin \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">Degree of HIE \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">MRI \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">Seizures \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">Inotropic support \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">Death \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3450 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40+6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">43+1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3020 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40+5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40+2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4490 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36+6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2030 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2085 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35+6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40+4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3300 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35+5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">VH \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35+5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3300 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35+5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3300 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41+1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Si \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40+5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3200 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41+3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38+4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \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">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Severe \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \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">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41+4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">External \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moderate \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1261748.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Demographic, clinical and outcome data of the patients." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib0130" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.D. Gluckman" 1 => "J.S. Wyatt" 2 => "D. Azzopardi" 3 => "R. Ballard" 4 => "A.D. Edwards" 5 => "D.M. Ferriero" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(05)17946-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2005" "volumen" => "365" "paginaInicial" => "663" "paginaFinal" => "670" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15721471" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0135" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Shankaran" 1 => "A.R. Laptook" 2 => "R.A. Ehrenkranz" 3 => "J.E. Tyson" 4 => "S.A. McDonald" 5 => "E.F. 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Corrected QT interval during therapeutic hypothermia in hypoxic ischaemic encephalopathy

El intervalo QT corregido durante la hipotermia terapéutica en la encefalopatía hipóxico-isquémica

Laia Vegaa, Héctor Boixa,

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hboix@vhebron.net

Corresponding author.

, Dimpna Albertb, Ignacio Delgadoc, Félix Castilloa

a Servicio de Neonatología, Hospital Universitario Vall d’Hebron, Barcelona, Spain

b Servicio de Cardiología Pediátrica, Hospital Universitario Vall d’Hebron, Barcelona, Spain

c Servicio de Radiología Pediátrica, Hospital Universitario Vall d’Hebron, Barcelona, Spain

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including the development of arrhythmias&#44; whose incidence &#40;with the exception of sinus bradycardia&#41; has not been observed to increase during therapeutic hypothermia&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">3&#8211;6</span></a> even when there has been accidental overcooling&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">There is extensive documentation on the effects of hypothermia on the cardiovascular system of adults&#46; From the earliest assessments of the effects of cooling performed in survivors of severe accidental hypothermia to animal model studies&#44; there has been growing evidence on the association between cooling and sinus bradycardia&#44; as well as other disturbances of the electrical activity of the heart&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">7&#8211;9</span></a> The joint guidelines of the International Liaison European Resuscitation Council and European Resuscitation Council<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">10</span></a> and the guideline of the American Heart Association<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a> both describe the potential arrythmogenicity of hypothermia<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">12&#8211;15</span></a> in adults treated with hypothermia after experiencing cardiac arrest due to ventricular arrhythmia&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Hypothermia has the potential to increase the risk of arrhythmia&#44; as it decreases the rate of depolarization in pacemaker cells while simultaneously increasing the duration of action potentials&#46; This leads to a reduction in heart rate and other abnormalities&#44; including the prolongation of PR and QTc intervals&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">16&#44;17</span></a> A prolonged QTc interval in and of itself increases the risk of developing polymorphic ventricular tachycardias&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a> The evidence that is currently available is practically limited to studies conducted in adults&#44; which have not found an increased incidence of potentially severe arrhythmias as long as the hypothermia was moderate &#40;32&#8211;34&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#41; and electrolyte levels were monitored&#46; There have been reports of ventricular arrhythmias in patients cooled to temperatures of less than 32<span class="elsevierStyleHsp" style=""></span>&#176;C<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">19</span></a> and hypokalaemia&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of our study was to determine whether therapeutic hypothermia in newborns with significant EHI is associated with the incidence of arrhythmias and specifically with QTc prolongation&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Materials and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">We conducted an observational prospective study in newborns with neonatal asphyxia treated with moderate hypothermia that were admitted to the neonatal intensive care unit &#40;NICU&#41; of the Hospital Universitario Vall d&#8217;Hebron &#40;HUVH&#41; between November 2012 and October 2013&#46; The study included all newborns with perinatal asphyxia and significant HIE that met the criteria for treatment with therapeutic hypothermia and received this treatment at the NICU of the HUVH during the period under study&#46; Moderate hypothermia in all included patients consisted of total body cooling by means of a servo-controlled temperature regulation system following the protocol of the hospital&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We collected data for demographic and clinical variables of interest for the included patients &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; In all patients&#44; 12-lead electrocardiograms &#40;ECGs&#41; were performed during therapeutic hypothermia &#40;one ECG every 24<span class="elsevierStyleHsp" style=""></span>h during the three days of treatment&#41; and during rewarming until the patient reached a normal body temperature &#40;one ECG performed for every one-degree increase in body temperature&#58; 34&#46;5&#44; 35&#46;5 and 36&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#46; A seventh ECG was performed at one week of life&#46; The ECGs were evaluated following a standardised approach by two researchers&#46; The duration of the QTc interval was calculated by applying Bazett&#39;s formula to five cycles from the lead II tracing in each of the ECGs&#44; and other relevant features were also assessed&#44; including the PR interval&#44; QRS&#44; repolarization&#44; heart axis and heart rate&#46; We analysed the presence of heart rhythm and conduction abnormalities in all ECGs&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">We used the following electrocardiographic definitions&#44; which were based in the European Society of Cardiology guidelines for the interpretation of the neonatal ECG<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">21</span></a>&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0045" class="elsevierStylePara elsevierViewall">Sinus bradycardia&#58; heart rate less than or equal to 93 beats per minute &#40;bpm&#41; the first day of life&#44; less than or equal to 91<span class="elsevierStyleHsp" style=""></span>bpm up to the third day of life&#44; and less than or equal to 90<span class="elsevierStyleHsp" style=""></span>bpm up to the seventh day of life&#44; inclusive&#44; with a regular heart rhythm&#59;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0050" class="elsevierStylePara elsevierViewall">Normal QTc&#58; value less than 450<span class="elsevierStyleHsp" style=""></span>milliseconds &#40;ms&#41;&#59;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Prolonged QTc&#58; calculated value greater than 450<span class="elsevierStyleHsp" style=""></span>ms&#59;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Prolonged PR&#58; intervals lasting more than 140<span class="elsevierStyleHsp" style=""></span>ms&#46;</p></li></ul></p><p id="par0065" class="elsevierStylePara elsevierViewall">The presence and severity of significant HIE were classified as moderate or severe using the semiquantitative scale developed by Garcia-Alix&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">22</span></a> All patients underwent a cranial magnetic resonance imaging &#40;MRI&#41; scan between 5 and 7 days of life&#44; with severity graded according to the criteria of van Rooij et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">We collected data on variables perceived as potential confounding factors due to their association with QT prolongation in the literature&#44; including serum levels of potassium&#44; magnesium and calcium&#44; and the use of drugs that prolong the QTc interval as well as vasoactive drugs &#40;adrenaline&#44; dopamine and dobutamine&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The study protocol was reviewed and approved by the Clinical Research Ethics Committee of the HUVH&#44; and we safeguarded the confidentiality of all the data obtained from the patients in the study&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0080" class="elsevierStylePara elsevierViewall">We conducted a descriptive analysis of demographic and clinical variables and of the results of diagnostic tests&#46; We present categorical variables as percentages and frequencies&#46; Continuous variables &#40;gestational age and weight&#41; are expressed as median and interquartile range&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">We compared values of the primary outcome variable&#44; the corrected QTc measured in ms&#44; in relation to subgroups by means of generalised linear models for an accurate analysis of repeated measurements in each participant&#46; Statistical significance was defined as <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46; We performed the analysis with the statistical software SPSS version 20&#46;0 &#40;IBM Corp&#44; Armonk&#44; USA&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0090" class="elsevierStylePara elsevierViewall">A total of 19 patients were included in the study&#44; of whom 73&#46;5&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; had transferred from other facilities &#40;with passive hypothermia initiated during transport&#41;&#46; Forty-seven percent were male newborns&#44; the median gestational age was 40<span class="elsevierStyleSup">&#43;2</span> weeks &#40;36<span class="elsevierStyleSup">&#43;6</span>&#8211;41<span class="elsevierStyleSup">&#43;1</span> weeks&#41;&#44; and the median weight 3020<span class="elsevierStyleHsp" style=""></span>g &#40;2400&#8211;3400<span class="elsevierStyleHsp" style=""></span>g&#41;&#46; Ten patients &#40;53&#37;&#41; had moderate HIE based on the clinical assessment &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Sentinel events were identified in 53&#37; of patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>10&#41;&#44; the most frequent of which were placental abruption &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41; and obstructed labour &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#46; Other documented events were umbilical cord prolapse&#44; uterine rupture&#44; chorioamnionitis or foetal-maternal haemorrhage&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Based on the cranial MRI scan performed between days 5 and 7 of life&#44; eleven patients &#40;58&#37;&#41; had a van Roij score equal to or greater than 4&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">All patients were monitored by amplitude-integrated electroencephalography &#40;EEGa&#41; during hypothermia&#44; the rewarming period and the days that followed&#46; Fifty-eight percent of patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11&#41; had clinical&#47;electrical seizures&#44; and all of them received anticonvulsant therapy&#46; The baseline EEGa showed a burst suppression pattern in 32&#37; of patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&#44; a low voltage pattern in 21&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41; and an isoelectric pattern in 21&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The ECG tracings revealed a prolonged QTc interval in all patients during hypothermia &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; In 84&#37; of patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&#44; this prolongation was detected in all the ECGs performed during hypothermia&#46; In three patients&#44; one of the recordings did not show a prolonged QTc&#46; After rewarming&#44; the QTc interval normalised in all patients&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">The analysis of the ECG recordings taken during rewarming showed that at 34&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 47&#37; of the patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#41; still had a prolonged QTc interval&#44; and at 35&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; 10&#37; of patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#41; still had a prolonged QTc interval&#46; None of the patients had a prolonged QTc interval at temperatures above 36<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">We did not find statistically significant differences in the QTc interval prolongation based on the degree of HIE &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;192&#41; or the use or lack of inotropic support &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;669&#41; &#40;<a class="elsevierStyleCrossRefs" href="#fig0010">Figs&#46; 2 and 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0125" class="elsevierStylePara elsevierViewall">None of the patients developed potentially severe arrhythmias&#46; The measured serum levels of potassium&#44; magnesium and calcium were within normal ranges in all patients&#46; There was no documented use of other drugs that could prolong the QT interval &#40;with the exception of the use of vasoactive drugs described above&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Sinus bradycardia was detected at some point during therapeutic hypothermia in 73&#46;5&#37; of patients &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41; by continuous cardiorespiratory monitoring&#46; Prolongation of the PR interval was detected in none&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">One of the patients with moderate HIE developed an isolated episode of paroxysmal supraventricular tachycardia during admission &#40;at 10 days post birth&#41; that required antiarrhythmic therapy&#44; which was discontinued prior to discharge from the unit&#46; We did not find an association between this episode of arrhythmia and the therapeutic hypothermia&#44; nor observed a prolongation of the QTc interval at any point of his stay in the unit after it had normalised with rewarming&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">There is a dearth of published evidence on the association of the electrical activity of the heart and therapeutic hypothermia for significant HIE in the neonatal population&#46; The efficacy and safety of this treatment have been demonstrated&#44; and there is cumulative evidence on the development of sinus bradycardia as a frequent and reversible side effect of hypothermia&#46; The association of hypothermia with low blood pressure secondary to the decreased heart rate and requiring inotropic support has also been described&#46; Very few publications address other potential effects of hypothermia in neonates&#44; and they consist of isolated cases that suggest that it may lead to abnormal prolongation of the QTc interval that resolves with rewarming&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">24&#44;25</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">This is the first prospective study performed in newborns with significant HIE treated with moderate hypothermia with the purpose of analysing the association of the QTc interval with body temperature in this population&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In all our patients&#44; moderate hypothermia induced a prolonged QTc interval during treatment&#46; Also&#44; the QTc interval normalised in all patients once their body temperatures reached normal physiological ranges &#40;equal to or higher than 36<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">In any case&#44; the prolongation of the QTc interval in newborns with significant HIE subjected to hypothermia did not seem to increase the risk of developing potentially severe arrhythmias&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">It does not seem that potentially confounding factors&#44; such as the use of inotropic support or the degree of the hypoxic-ischaemic insult &#40;severity of encephalopathy&#41;&#44; influence the behaviour of the QTc interval in relation to temperature&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Sinus bradycardia is a frequent side effect of hypothermia in newborns&#44; as has been documented in multiple studies and observations&#46; Although studies conducted in adults found a nearly universal prolongation of the PR interval in association with hypothermia&#44; PR intervals greater than 140<span class="elsevierStyleHsp" style=""></span>ms have not been observed in studied patients &#40;none exceeded 120<span class="elsevierStyleHsp" style=""></span>ms&#41;&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">It could be useful to perform an ECG after rewarming to confirm the presence of a normal QTc interval to avoid missing potential congenital QT interval abnormalities&#44; and this test could be carried out immediately after completing rewarming or at a later time&#46; This ECG can be particularly relevant in survivors of postnatal collapse treated with off-protocol hypothermia&#44; in whom assessment for a pathological arrhythmia as a potential cause of postnatal collapse could be contemplated&#46; We consider that once ECG features are confirmed to be normal after rewarming&#44; it is not necessary to follow up these patients in the cardiology department&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">There are some limitations to this study&#46; Due to the lack of studies analysing QTc prolongation in newborns with significant HIE treated with hypothermia in the existing literature&#44; we had to undertake this study as exploratory research with the purpose of increasing our knowledge of this association in newborns and obtaining the necessary data to design future confirmatory studies that would test specific hypotheses and carry out a formal sample size calculation&#46; Since hypothermia must be induced as early as possible in these patients&#44; we could not use each case as its own control&#44; and it was not possible to obtain ECGs prior to cooling&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conclusions</span><p id="par0180" class="elsevierStylePara elsevierViewall">Moderate hypothermia for the treatment of newborns with asphyxia and significant HIE seems to induce a transient prolongation of the QTc interval that resolves with rewarming to normal body temperature &#40;greater than 36<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#46; At the temperature used in therapeutic &#40;moderate&#41; hypothermia&#44; there seems to be no risk of developing severe ventricular arrhythmias as long as factors such as serum electrolyte levels or the use of drugs that prolong the QTc interval are within normal ranges&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">We believe that these patients do not require a followup programme if their QTc interval have normalised after reaching a normal body temperature&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">Further and more powerful studies are needed to assess more accurately the association between body temperature and the QTc interval and other electrocardiographic parameters&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflict of interests</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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            0 => "Asphyxia"
            1 => "Hypoxic ischaemic encephalopathy"
            2 => "Arrhythmia"
            3 => "Newborn"
            4 => "Induced hypothermia"
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            0 => "Asfixia"
            1 => "Encefalopat&#237;a hip&#243;xico-isqu&#233;mica"
            2 => "Arritmia"
            3 => "Neonato"
            4 => "Hipotermia inducida"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Therapeutic hypothermia is the standard treatment for hypoxic ischaemic encephalopathy &#40;HIE&#41;&#44; despite not knowing all its effects and complications&#46; Sinus bradycardia is one of the consequences of cooling that has been previously documented in the literature&#44; but little is known about the cardiac electrical activity in these patients&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine the corrected QT &#40;QTc&#41; interval in newborns treated with therapeutic hypothermia for HIE&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A prospective observational study was conducted in all patients treated with hypothermia for HIE that were admitted to our Unit between November 2012 and October 2013&#46; ECGs were performed during hypothermia &#40;every 24<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; during the re-warming period &#40;at 34&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44;&#160;35&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#44;&#160;36&#46;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#44; and on the 7th day of life&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 19 patients were included&#46; A prolonged QTc was observed in all patients during hypothermia&#44; and 84&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41; had prolonged QTc in all the ECGs during treatment&#46; In 3 patients&#44; one of the ECGs did not have a prolonged QTc&#46; After re-warming&#44; the QTc interval returned to normal in all patients&#46; No statistically significant differences were seen when the degree of HIE &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;192&#41; or the use of inotropic support &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;669&#41; were considered&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Therapeutic hypothermia applied to asphyxiated newborns with HIE seems to induce a QTc prolongation that resolves when the patient regains physiological temperature&#46;</p></span>"
        "secciones" => array:5 [
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            "titulo" => "Introduction"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La hipotermia es el tratamiento est&#225;ndar en la encefalopat&#237;a hip&#243;xico isqu&#233;mica &#40;EHI&#41; a pesar de que todav&#237;a no se conocen todos sus efectos y complicaciones&#46; La bradicardia sinusal est&#225; ampliamente descrita en la literatura como consecuencia de dicho enfriamiento pero se ha estudiado poco la actividad el&#233;ctrica cardiaca en este grupo de pacientes&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Determinar si existe un alargamiento del intervalo QT corregido &#40;QTc&#41; durante la hipotermia en neonatos con EHI moderada-grave y su evoluci&#243;n durante el tratamiento&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Material y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se reclut&#243; a pacientes con EHI tratados con hipotermia entre noviembre del 2012 y octubre del 2013&#46; Se realizaron electrocardiogramas &#40;ECG&#41; durante la hipotermia &#40;uno cada 24 h durante el tratamiento&#41; y durante el recalentamiento &#40;a 34&#44;5&#44; 35&#44;5 y 36&#44;5<span class="elsevierStyleHsp" style=""></span>&#176;C&#41;&#46; Se realiz&#243; un s&#233;ptimo ECG a la semana de vida&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Se incluy&#243; a un total de 19 pacientes&#46; Se observ&#243; un alargamiento del QTc en todos los pacientes durante la hipotermia&#46; En 84&#37; de los pacientes &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>16&#41;&#44; el alargamiento se apreci&#243; en todos los ECG durante la hipotermia&#46; Tras el recalentamiento&#44; todos los pacientes presentaron una normalizaci&#243;n del mismo&#46; No se encontraron diferencias estad&#237;sticamente significativas al evaluar la prolongaci&#243;n del QTc seg&#250;n el grado de EHI &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;192&#41; y seg&#250;n el uso de soporte inotr&#243;pico o no &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;669&#41;&#46; Ning&#250;n paciente present&#243; arritmias potencialmente graves&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La hipotermia moderada aplicada a los reci&#233;n nacidos con EHI moderada-grave parece inducir una prolongaci&#243;n en el intervalo QTc temporal que se resuelve con el recalentamiento del paciente hasta temperatura fisiol&#243;gica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Vega L&#44; Boix H&#44; Albert D&#44; Delgado I&#44; Castillo F&#46; El intervalo QT corregido durante la hipotermia terap&#233;utica en la encefalopat&#237;a hip&#243;xico-isqu&#233;mica&#46; An Pediatr &#40;Barc&#41;&#46; 2016&#59;85&#58;312&#8211;317&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">There were no statistically significant differences in the QTc interval during therapeutic hypothermia based on the degree of HIE &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;192&#41;&#46;</p>"
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      2 => array:7 [
        "identificador" => "fig0015"
        "etiqueta" => "Fig&#46; 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
            "Alto" => 1275
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            "Tamanyo" => 97271
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">There were no statistically significant differences in the QTc interval during therapeutic hypothermia based on the use or lack of use of inotropic support &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;669&#41;&#46;</p>"
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      3 => 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" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Degree of HIE based on the semiquantitative scale of Garcia-Alix&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">F&#44; female&#59; GA&#44; gestational age&#59; M&#44; male&#59; MRI&#44; magnetic resonance imaging &#40;van Rooij score&#41;&#59; VH&#44; Hospital Vall D&#8217; Hebron&#46;</p>"
          "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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patient&nbsp;\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">Weight &#40;g&#41;&nbsp;\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">GA &#40;weeks<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>days&#41;&nbsp;\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">Sex&nbsp;\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">Sentinel event&nbsp;\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">Point of origin&nbsp;\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">Degree of HIE&nbsp;\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">MRI&nbsp;\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">Seizures&nbsp;\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">Inotropic support&nbsp;\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">Death&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3450&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40<span class="elsevierStyleSup">&#43;6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">VH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\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">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">43<span class="elsevierStyleSup">&#43;1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">VH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3020&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\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">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40<span class="elsevierStyleSup">&#43;5</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40<span class="elsevierStyleSup">&#43;2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">VH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4490&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36<span class="elsevierStyleSup">&#43;6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\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">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2030&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">VH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2085&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35<span class="elsevierStyleSup">&#43;6</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\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">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40<span class="elsevierStyleSup">&#43;4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35<span class="elsevierStyleSup">&#43;5</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">VH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\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">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35<span class="elsevierStyleSup">&#43;5</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35<span class="elsevierStyleSup">&#43;5</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41<span class="elsevierStyleSup">&#43;1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Si&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\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">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40<span class="elsevierStyleSup">&#43;5</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\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">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3200&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41<span class="elsevierStyleSup">&#43;3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3600&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38<span class="elsevierStyleSup">&#43;4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\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">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">External&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Severe&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\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">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">41<span class="elsevierStyleSup">&#43;4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">F&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Demographic&#44; clinical and outcome data of the patients&#46;</p>"
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Selective head cooling with mild systemic hypothermia after neonatal encephalopathy&#58; multicentre randomised trial"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46;D&#46; Gluckman"
                            1 => "J&#46;S&#46; Wyatt"
                            2 => "D&#46; Azzopardi"
                            3 => "R&#46; Ballard"
                            4 => "A&#46;D&#46; Edwards"
                            5 => "D&#46;M&#46; Ferriero"
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                        ]
                      ]
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                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(05)17946-X"
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                        "paginaInicial" => "663"
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              "referencia" => array:1 [
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                      "titulo" => "Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Shankaran"
                            1 => "A&#46;R&#46; Laptook"
                            2 => "R&#46;A&#46; Ehrenkranz"
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                      "doi" => "10.1056/NEJMcps050929"
                      "Revista" => array:6 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16221780"
                            "web" => "Medline"
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                    0 => array:2 [
                      "titulo" => "Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy&#58; synthesis and meta-analysis of trial data"
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                          "etal" => true
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                            2 => "A&#46;J&#46; Gunn"
                            3 => "H&#46; Halliday"
                            4 => "E&#46; Juszczak"
                            5 => "M&#46; Levene"
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                        ]
                      ]
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                  "host" => array:1 [
                    0 => array:1 [
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              "referencia" => array:1 [
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                      "titulo" => "Cooling for newborns with hypoxic ischaemic encephalopathy"
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                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Jacobs"
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                            2 => "W&#46; Tarnow-Mordi"
                            3 => "T&#46; Inder"
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                          ]
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                      ]
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2004"
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              "referencia" => array:1 [
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                    0 => array:2 [
                      "titulo" => "Moderate hypothermia in neonatal encephalopathy&#58; efficacy outcomes"
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                          "etal" => true
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                            0 => "D&#46;J&#46; Eicher"
                            1 => "C&#46;L&#46; Wagner"
                            2 => "L&#46;P&#46; Katikaneni"
                            3 => "T&#46;C&#46; Hulsey"
                            4 => "W&#46;T&#46; Bass"
                            5 => "D&#46;A&#46; Kaufman"
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                        ]
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                  ]
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                      ]
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                      "titulo" => "Hypothermia&#58; a systematic review and meta-analysis of clinical trials"
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                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;S&#46; Shah"
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                    0 => array:2 [
                      "doi" => "10.1016/j.siny.2010.02.003"
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                        "tituloSerie" => "Semin Fetal Neonatal Med"
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                        "volumen" => "15"
                        "paginaInicial" => "238"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20211588"
                            "web" => "Medline"
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                          "etal" => false
                          "autores" => array:1 [
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                        "tituloSerie" => "Br Heart J"
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                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46; Thompson"
                            1 => "J&#46; Rick"
                            2 => "F&#46; Chmelik"
                            3 => "W&#46; Nelson"
                          ]
                        ]
                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
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                        "volumen" => "10"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/833527"
                            "web" => "Medline"
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Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2016.10.001

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2022 November	61	42	103
2022 October	85	52	137
2022 September	46	35	81
2022 August	51	47	98
2022 July	40	34	74
2022 June	48	41	89
2022 May	53	33	86
2022 April	90	26	116
2022 March	100	34	134
2022 February	102	35	137
2022 January	107	38	145
2021 December	61	47	108
2021 November	72	50	122
2021 October	63	88	151
2021 September	36	42	78
2021 August	38	42	80
2021 July	26	39	65
2021 June	51	34	85
2021 May	51	47	98
2021 April	124	44	168
2021 March	88	35	123
2021 February	43	20	63
2021 January	51	29	80
2020 December	45	18	63
2020 November	50	17	67
2020 October	45	15	60
2020 September	43	25	68
2020 August	46	13	59
2020 July	42	14	56
2020 June	55	21	76
2020 May	67	21	88
2020 April	36	29	65
2020 March	42	21	63
2020 February	40	13	53
2020 January	31	15	46
2019 December	64	23	87
2019 November	26	12	38
2019 October	41	12	53
2019 September	36	6	42
2019 August	70	20	90
2019 July	44	39	83
2019 June	45	26	71
2019 May	68	20	88
2019 April	56	26	82
2019 March	47	14	61
2019 February	44	20	64
2019 January	40	17	57
2018 December	60	31	91
2018 November	89	32	121
2018 October	147	29	176
2018 September	37	10	47
2018 August	7	0	7
2018 July	2	0	2
2018 June	4	0	4
2018 May	11	0	11
2018 April	15	0	15
2018 March	18	0	18
2018 February	12	0	12
2018 January	22	0	22
2017 December	17	0	17
2017 November	17	0	17
2017 October	20	0	20
2017 September	8	0	8
2017 August	17	0	17
2017 July	18	1	19
2017 June	27	6	33
2017 May	32	17	49
2017 April	17	3	20
2017 March	10	5	15
2017 February	13	10	23
2017 January	17	9	26
2016 December	31	30	61
2016 November	0	14	14

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