Efficacy and safety of dexmedetomidine in maintaining hemodynamic stability in pediatric cardiac surgery: a systematic review and meta-analysis

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pediatric cardiac surgery: a systematic review and meta-analysis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "15" "paginaFinal" => "25" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Qing Wang, Chuikai Chen, Li Wang" "autores" => array:3 [ 0 => array:3 [ "nombre" => "Qing" "apellidos" => "Wang" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "1" "identificador" => "fn1" ] ] ] 1 => array:3 [ "nombre" => "Chuikai" "apellidos" => "Chen" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "1" "identificador" => "fn1" ] ] ] 2 => array:4 [ "nombre" => "Li" "apellidos" => "Wang" "email" => array:1 [ 0 => "dy135783@126.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0002" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0001" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Hainan Women and Children's Medical Center, Department of Anesthesiology, Haikou, China" "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "The First Hospital of Hebei Medical University, Department of Anesthesiology, Shijiazhuang, China" "etiqueta" => "b" "identificador" => "aff0002" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0006" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 3313 "Ancho" => 2500 "Tamanyo" => 375665 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0006" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Forest plot of comparison between before and after infusion of DEX and Comparison between Dexmedetomidine and Control (Placebo): A, heart rate; B, junctional ectopic tachycardia." ] ] ] "textoCompleto" => "IntroductionDexmedetomidine (DEX) has a high alpha-2/ alpha-1 receptor activity ratio and a selective binding ratio of 1620 alpha-2: alpha-1 receptors. DEX which has sedative, anti-anxiety and analgesic effects, and does not lead to respiratory inhibition is a highly selective and specific alpha-2 adrenergic receptor agonist.<a class="elsevierStyleCrossRefs" href="#bib0001">1–5</a> It is reported that DEX which is the main sedative in the intensive care unit and the only sedative in the diagnosis of invasive surgery and magnetic resonance imaging in the intensive care unit,<a class="elsevierStyleCrossRefs" href="#bib0006">6–10</a> is part of a balanced anesthetic for the prevention and treatment of sudden mental disorders. The use of DEX in adults has the opposite effect on blood pressure. The increase of systemic vascular resistance leads to an increase in blood pressure through the activation of peripheral alpha-2b adrenergic receptors, and the sympathetic nerve reduces blood pressure through the activation of alpha-2a adrenergic receptors in the central nervous system.<a class="elsevierStyleCrossRef" href="#bib0011">11</a>,<a class="elsevierStyleCrossRef" href="#bib0012">12</a> At the clinical dose, the effect of the central sympathetic nerve is superior to that of peripheral vasoconstriction, resulting in an overall decrease in blood pressure. In children, hemodynamic effects such as heart rate (HR) and arterial pressure decrease caused by slow injection of DEX for more than 10 min have been well described.<a class="elsevierStyleCrossRef" href="#bib0013">13</a> However, rapid administration of DEX may lead to transient hypertension. In adults, biphasic hemodynamic responses can be observed within 2 min after injection of DEX. In the beginning, blood pressure increases and reflex bradycardia occurs, and then blood pressure and heart rate stabilize below the baseline.<a class="elsevierStyleCrossRef" href="#bib0014">14</a> Therefore, the safe dose of DEX needs to be further described in detail.At present, the use of DEX in pediatric intensive care units is increasing due to its good sedation, analgesia and anti-anxiety effects, especially the prophylactic and postoperative medication should be used to maintain the hemodynamic stability of cardiac surgery in children. Hence, the present study's systematic review focused on investigating the effectiveness and adverse events of DEX in maintaining hemodynamic stability in pediatric cardiac surgery, hoping to provide comprehensive and strong evidence that DEX should be used to maintain hemodynamic stability in pediatric cardiac surgery.MethodsThis systematic review followed methods depicted in Cochrane Handbook for Systematic Reviews of Interventions version 6.0.<a class="elsevierStyleCrossRef" href="#bib0015">15</a> The authors performed the report according to PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols).<a class="elsevierStyleCrossRef" href="#bib0016">16</a>Search strategyFive electronic databases such as PubMed, Cochrane, Web of Science, WANFANG DATA, and China National Knowledge Infrastructure were selected to systematically search the articles related to the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery up to February 18, 2021. The search formula was (Dexmedetomidine) or (Dexmedetomidine [MeSH Terms]) and (pediatric cardiac surgery) or (pediatric cardiac surgery [MeSH Terms]) and (Hemodynamic) or (Hemodynamic [MeSH Terms]). In addition, the references included in the systematic search were also searched carefully, in order not to omit any related articles, and to make a comprehensive report on the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery.Inclusion and exclusion criteriaAccording to the inclusion criteria, two researchers assessed the title and abstract of the articles initially searched to determine whether the articles were included in this study. When the tworesearchers disagreed, they consulted a third researcher for a decision. Articles that met the following inclusion criteria according to participants, interventions, comparisons, outcomes, and study design (PICOS) protocol, would be adopted. First, the people studied in the articles were infants and young children. Second, each study included at least one pair of comparisons of hemodynamic parameters before and after cardiac surgery with DEX. Moreover, one group of subjects received DEX treatment, and the other group received control treatment (other treatments without DEX). Third, in the study hemodynamic parameters were measured, including heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), diastolic blood pressure (DBP), systolic blood pressure (SBP), and so on. Fourth, only the randomized controlled trials (RCT) were included, to ensure the quality of the combined results. In addition, studies that could not provide effective analytical data were subsequently excluded.Data extraction and quality assessmentThe two researchers independently extracted the following data provided by the study and entered the data into the extraction table: the study title, the name of the author, the publication time of the study, the sample size, the demographic characteristics of the subjects, the treatment method and dose of DEX, the hemodynamic indicators, the time of measurement, and the specific characteristics of adverse events. Hemodynamic stability was defined as the blood pressure and heart rate change observed no statistically significant. In addition, bradycardia and tachycardia were respectively defined as a 30% decrease and increase from baseline when comparing the lowest and highest HR during dexmedetomidine infusion with the baseline HR. A hypertensive or hypotensive episode was defined as a 30% change from baseline and or if the SBP was below or above the 5th to 95th percentile for age. After data extraction was completed, a third researcher would double-check the consistency of the data extracted by the previous two researchers.RCT meeting the inclusion criteria was evaluated and then incorporated into the final system review and meta-analysis. Each of the two researchers evaluated the included study according to the RCT quality assessment section of the Cochrane handbook for systematic reviews of interventions 6. 0.<a class="elsevierStyleCrossRef" href="#bib0015">15</a> For each included study, the two researchers assessed several kinds of bias, such as blind bias, selection bias, incomplete outcome data bias, selective reporting bias, and other biases. When they had different opinions, a third researcher would make the final decision on the risk of bias based on the opinions of the previous two researchers. According to the regulations of the Cochrane manual, the authors determined whether the final quality of the study was low-risk, medium-risk, or high-risk based on the conclusions of the overall quality assessment.Statistical analysisResults were merged across studies by using Stata version 15.1 (Stata Corp MP., College Station, TX, USA).<a class="elsevierStyleCrossRef" href="#bib0017">17</a>,<a class="elsevierStyleCrossRef" href="#bib0018">18</a> Given the differences in the demographic characteristics of the subjects, the differences in the use of prophylactic drugs before and after cardiac surgery in children, the differences in dosage and mode of medication, and the inconsistency of measurement time points, a random effect model was applied to combine the results in this study. Considering the high heterogeneity among various studies, it was impractical to calculate the exact amount of effect, but the effect of drug use and the source of high heterogeneity could be discussed, which is of guiding significance for the safe use of drugs in the future and avoiding adverse events in DEX. The authors calculated the standardized mean deviation (SMD) of hemodynamic parameters before and after the administration of DEX in pediatric cardiac surgery and the odds ratio (OR) of the number of adverse events between the DEX group and the control group to evaluate the hemodynamic stability. Besides, the method of calculating and studying the merging standard deviation referred to the Cochrane handbook.<a class="elsevierStyleCrossRef" href="#bib0015">15</a> Q test and I2 statistics were used to estimate the heterogeneity of the study. If the I2 value was 0%, 40%, and 60%, respectively, it was considered to have low, medium, and high heterogeneity, respectively.<a class="elsevierStyleCrossRef" href="#bib0015">15</a> Indicators for evaluating hemodynamic stability will be shown in a forest plot. Egger's test was adopted to weigh the publication bias of the results, and Duval and Tweedie's trim and fill test to assess the sensitivity of the results.<a class="elsevierStyleCrossRef" href="#bib0019">19</a>,<a class="elsevierStyleCrossRef" href="#bib0020">20</a> Unless the p value was less than 0.001, the exact p value would be provided. Except that p < 0.10 in Egger's test was considered to be statistically significant, other p < 0.05 could be considered to be statistically significant.ResultsLiterature search, study characteristics and quality assessment107 articles were retrieved by database system retrieval and 24 by manual retrieval. After 16 repeated articles were removed, 85 articles that did not meet the inclusion criteria were excluded by screening the titles and abstracts of the articles. (not related to dexmedetomidine n = 8; review or in vitro/ animal studies or letter or editorial or conference paper n = 24; Non-pediatric cardiac surgery n = 40; not related to hemodynamics n = 13). Subsequently, 6 of 30 articles screened in the full text were excluded due to a lack of available data. Finally, a total of 9 studies were included in qualitative analysis and 15 in quantitative analysis (<a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>). The whole screening process included 1042 pediatric patients who underwent cardiac surgery treated with DEX for meta-analysis and 1332 pediatric patients who underwent cardiac surgery without DEX treatment. The basic features of 15 studies included in the meta-analysis are shown in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1.</a><a class="elsevierStyleCrossRefs" href="#bib0021">21–35</a><elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="tbl0001"></elsevierMultimedia>Based on the quality assessment part of the Cochrane handbook, a systematic evaluation was conducted to assess the bias risk of all included articles, such as selection bias, selective report bias, incomplete report bias, and publication bias. According to the Cochrane handbook, the quality of the literature was defined as low, moderate and high risk. All the included studies strictly followed the principle of random distribution, and before the beginning of the study, the subjects with chronic diseases who might cause adverse harm in the course of the study and those who were more likely to have complications in the course of the study were excluded. Therefore, the lack of data that could damage the effectiveness of the test was not possible. Both items were rated as low risk and the rest included in the overall evaluation of RCT were considered low risk of bias, which indicated that the quality of the meta-analysis was favorable and the result of the meta-analysis was reliable (<a class="elsevierStyleCrossRef" href="#fig0002">Figs. 2</a> and <a class="elsevierStyleCrossRef" href="#fig0003">3</a>).<elsevierMultimedia ident="fig0002"></elsevierMultimedia><elsevierMultimedia ident="fig0003"></elsevierMultimedia>HemodynamicsComparison between before and after infusion of DEXSBP. 9 groups on the changes of SBP before and after DEX treatment in pediatric cardiac surgery, it was found that the SBP of patients treated with DEX during or after cardiac surgery decreased compared with the baseline SBP, but the difference was not statistically significant (SMD = -0.35, 95% CI: -0.72, 0.01; <a class="elsevierStyleCrossRef" href="#fig0004">Fig. 4</a>A).<a class="elsevierStyleCrossRef" href="#bib0022">22</a>,<a class="elsevierStyleCrossRef" href="#bib0024">24</a>,<a class="elsevierStyleCrossRefs" href="#bib0026">26–28</a> Sensitivity analysis was used to study the sources of heterogeneity. Then, it was found that heterogeneity may be related to one group of research Mukhtar et al. and research Jooste et al., respectively.<a class="elsevierStyleCrossRef" href="#bib0027">27</a>,<a class="elsevierStyleCrossRef" href="#bib0028">28</a><elsevierMultimedia ident="fig0004"></elsevierMultimedia>MAP. 8 groups reported MAP data before and after DEX treatment during or after pediatric cardiac surgery. The combined results of 8 groups showed that MAP also observed a downward trend, and the difference was not statistically significant (SMD =-0.83, 95% CI: -1.87,0.21; <a class="elsevierStyleCrossRef" href="#fig0004">Fig. 4</a>B)(21, 23, 25, 29, 30). Through sensitivity analysis, it was found that the main source of heterogeneity may be related to a group in the study of Lam et al. and research in the study of Hammer et al.<a class="elsevierStyleCrossRef" href="#bib0023">23</a>,<a class="elsevierStyleCrossRef" href="#bib0030">30</a>DBP and CVP. Similar to SBP and MAP, DBP and CVP also showed a downward trend, and the difference was not statistically significant (DBP: SMD = -0.79, 95%CI: -1.66, 0.08; CVP: SMD = -0.67 95%CI: -2.49, 1.15; <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 5</a>A and B).<a class="elsevierStyleCrossRefs" href="#bib0023">23–29</a> Through sensitivity analysis, it was found that the heterogeneity of DBP came from the study of Mukhtar et al.<a class="elsevierStyleCrossRef" href="#bib0027">27</a> Frustratingly, the hemodynamic index of CVP had strong heterogeneity and no obvious trend. Therefore, the guiding significance of this index remains to be further discussed.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>HR. 15 groups reported HR data before and after DEX treatment during or after pediatric cardiac surgery. The combined results of 15 groups found that HR showed a significant downward trend, and the difference was statistically significant (SMD = -1.71, 95%CI: -2.29, -1.13; <a class="elsevierStyleCrossRef" href="#fig0006">Fig. 6</a>A).<a class="elsevierStyleCrossRefs" href="#bib0021">21–28</a> Obviously, the decrease of HR in a group in Lam et al., and the study of Chen et al. and a group in Jooste et al. were significantly stronger than those in the other groups.<a class="elsevierStyleCrossRef" href="#bib0023">23</a>,<a class="elsevierStyleCrossRef" href="#bib0025">25</a>,<a class="elsevierStyleCrossRef" href="#bib0028">28</a><elsevierMultimedia ident="fig0006"></elsevierMultimedia>Comparison between dexmedetomidine and control (Placebo)Junctional Ectopic Tachycardia (JET). Five studies revealed that the probability of JET during and after cardiac surgery treated with DEX was significantly lower than those of placebo groups (OR = 0.32, 95%CI: 0.20, 0.50; <a class="elsevierStyleCrossRef" href="#fig0006">Fig. 6</a>B).<a class="elsevierStyleCrossRefs" href="#bib0031">31-35</a> The five studies showed low heterogeneity, indicating that DEX can reduce the heart rate during and after pediatric cardiac surgery and effectively reduce the incidence of JET.Publication bias assessment and sensitivity analysisEgger's test was used to analyze publication bias. It suggested that there was a publication bias in indices SBP and JET, but no publication bias was observed in other indexes. Duval and Tweedie's Trim and Fill Test of indexes MAP and DBP found that the effect quantity was not stable, and their guiding significance needs to be further discussed (<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>).<elsevierMultimedia ident="tbl0002"></elsevierMultimedia>DiscussionIn quantitative analysis, the high heterogeneity of meta-analysis results did not have a serious impact on the interpretation of the stability of hemodynamic indexes, which truly reflected the situation that may be faced in the clinical application of DEX. It was obvious that in the forest map, the mean and standard deviation of each group in the research were not merged, but regarded as one of the merged objects in the form of study, which was the main source of high heterogeneity in this study. The reason why the data were processed in that manner was that nowadays, DEX is used in patients, whether prophylactic medication before operation or recovery medication after an operation, to bring stable hemodynamic effects to patients, and it is nothing new to effectively reduce the heart rate and blood pressure of patients.<a class="elsevierStyleCrossRef" href="#bib0013">13</a> Hence, it was only necessary to reconfirm the effect. Meanwhile, those studies that could not provide effective and analyzable data for meta-analysis studies also showed the same hemodynamic effects. The specific hemodynamic indicators were listed in supplemental Table 1.<a class="elsevierStyleCrossRefs" href="#bib0036">36–44</a> Based on the evidence of quantitative analysis and qualitative description, it was confirmed that DEX was able to reduce heart rate, blood pressure, stabilize hemodynamics and reduce the frequency of JET in preoperative preventive medication and postoperative recovery of pediatric cardiac surgery.It was assumed that the publication bias of the indicator SBP observed by Egger's test mainly came from the fact that the group was used as a unit of analysis, and research Chrysostomou et al.<a class="elsevierStyleCrossRef" href="#bib0022">22</a> and research Chrysostomou et al.<a class="elsevierStyleCrossRef" href="#bib0024">24</a> of the groups accounted for 62.87% of the total analysis of the index SBP. The software could not identify this process, and the effects in the two studies were very similar, so it was concluded that the index had a nonnegligible publication bias. Based on the analysis of the publication bias detected by the index JET, it was undeniable that there lacked small-sized sample study in the JET index. Nevertheless, it was obvious that all five studies showed that the frequency of JET in the DEX group was less than those in the placebo group, which has clinical significance. As for the sensitivity analysis of Duval and Tweedie's trim and fill, it was assumed the indexes MAP and DBP showed a downward trend after DEX treatment, and the effect of maintaining hemodynamic stability during and after cardiac surgery was confirmed. With part of the study cut-off, the difference changed from no statistical significance to statistically significant for clinical guidance, which was only related to the statistical analysis method.The adverse events caused by preoperative prophylaxis and postoperative recovery of DEX in pediatric cardiac surgery were presumed to be related to individual differences. All the adverse events reported in the study and after the administration of DEX in pediatric cardiac surgery were sorted out in <a class="elsevierStyleCrossRef" href="#tbl0003">Table 3.</a><a class="elsevierStyleCrossRef" href="#bib0021">21</a>,<a class="elsevierStyleCrossRef" href="#bib0022">22</a>,<a class="elsevierStyleCrossRef" href="#bib0039">39</a>,<a class="elsevierStyleCrossRef" href="#bib0040">40</a>,<a class="elsevierStyleCrossRefs" href="#bib0045">45–47</a> First, age had no significant effect on the pharmacokinetics of DEX, and the equilibrium half-life of different age groups was similar. But the decrease of tolerance to DEX may be caused by renal hypoplasia in some infants, which was not discussed in detail.<a class="elsevierStyleCrossRef" href="#bib0023">23</a>,<a class="elsevierStyleCrossRef" href="#bib0037">37</a> This study focused on the dose and mode of treatment of DEX. The main purpose of using the group as the unit of the meta-analysis was to observe the stability of hemodynamic indexes and whether it was related to the frequency of adverse events with different doses of DEX and different treatment methods in the same study. Observed from the forest map, it was found that different DEX treatments in the same study produced different hemodynamic effects, but there was no good consistency in the same incremental dose treatment between different studies (<a class="elsevierStyleCrossRefs" href="#fig0004">Figs. 4–6</a>, <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>). Second, as the original data of the study could not be obtained, the authors cannot analyze the correlation between the dose and effect index of different DEX treatments statistically. Third, what could be confirmed was that there were only a few cases of adverse events such as bradycardia, hypotension, and transient hypertension among the doses collected for preoperative prophylaxis and postoperative recovery of DEX for pediatric cardiac surgery (<a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>). However, the incidence of bradycardia due to DEX treatment in children with trisomy 21 syndrome was significantly higher than that in normal children.<a class="elsevierStyleCrossRef" href="#bib0047">47</a> Fourth, in addition to the commonly used method of slow injection of DEX in the application of DEX in children's cardiac surgery, rapid injection of DEX within 5 s to deal with emergencies was discussed. The hemodynamic indexes would temporarily increase within one minute after injection, but the hemodynamic indices would soon decrease to a stable level at 5 min.<a class="elsevierStyleCrossRef" href="#bib0028">28</a>,<a class="elsevierStyleCrossRef" href="#bib0037">37</a> All in all, it was likely that the adverse events in the process of preoperative prophylaxis and postoperative recovery of DEX in pediatric cardiac surgery were related to individual differences.<elsevierMultimedia ident="tbl0003"></elsevierMultimedia>JET can lead to significant hemodynamic instability in the postoperative period after cardiac surgery. As a preventive and therapeutic drug, shown in the results, dexmedetomidine can effectively reduce the frequency of JET. JET is a tachyarrhythmia related to surgery for congenital heart disease which could cause serious hemodynamic instability in the postoperative period. JET is a narrow QRS complex tachycardia with atrioventricular dissociation and a slower atrial rate as compared to ventricular rate. Atrioventricular asynchrony causes loss of atrial contraction contribution to cardiac output, resulting in hemodynamic instability. At present, the exact mechanism of JET is unknown and may be related to proximal conduction tissue injury associated with indirect stretch injury or suture surgery. The incidence of JET has been reported to range from 8% to 24%, depending on the patient's choice and surgical procedure.<a class="elsevierStyleCrossRef" href="#bib0048">48</a>,<a class="elsevierStyleCrossRef" href="#bib0049">49</a> While dexmedetomidine exerts sedative, analgesic and antianxiety effects through the pharmacological effects of α-2 adrenergic receptor agonist, the results of meta-analysis also showed that the use of dexmedetomidine in pediatric cardiac surgery can reduce heart rate and reduce the occurrence of JET.The authors investigated the indirect results of cardiac output in 9 articles included in the meta-analysis and 15 articles included in the qualitative analysis. The reduction in heart rate and blood pressure caused by the efficacy of dexmedetomidine for maintaining hemodynamic stability in pediatric cardiac surgery does not support the reduction in cardiac output. The above studies included at least one of the following indicators that did not support decreased cardiac output: absence of acidosis, unchanged inotropic requirement, central venous pressure, and left ventricular function. Therefore, the authors do not believe that the decrease in blood pressure is due to low cardiac output syndrome, but is the result of sedation, analgesia, and possibly the result of activation alpha-2 adrenergic receptors in the central nervous system.This study inevitably had some limitations: except for trisomy 21 syndrome, all the patients included in this review were patients without chronic diseases of kidney, liver or other organs, which had limitations in guiding the clinical application of DEX to prevent adverse events.In conclusion, the application of DEX for preoperative prophylaxis and postoperative recovery in pediatric cardiac surgery patients is effective in maintaining hemodynamic stability with reduced blood pressure with no statistical significance. Furthermore, the clinical dose of DEX is not significantly related to the occurrence of pediatric adverse events which may be related to individual differences.Ethics approval and consent to participateEthical approval was not needed because this is a meta-analysis.Data for referenceThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.FundingThis paper is supported by the Hainan Natural Science Foundation Youth Project (Grant No:819QN394)." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1653736" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Sources" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Summary of the findings" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1470018" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0002" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0003" "titulo" => "Search strategy" ] 1 => array:2 [ "identificador" => "sec0004" "titulo" => "Inclusion and exclusion criteria" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Data extraction and quality assessment" ] 3 => array:2 [ "identificador" => "sec0006" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "sec0007" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0008" "titulo" => "Literature search, study characteristics and quality assessment" ] 1 => array:3 [ "identificador" => "sec0009" "titulo" => "Hemodynamics" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Comparison between before and after infusion of DEX" ] 1 => array:2 [ "identificador" => "sec0011" "titulo" => "Comparison between dexmedetomidine and control (Placebo)" ] 2 => array:2 [ "identificador" => "sec0012" "titulo" => "Publication bias assessment and sensitivity analysis" ] ] ] ] ] 5 => array:2 [ "identificador" => "sec0013" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0014" "titulo" => "Ethics approval and consent to participate" ] 7 => array:2 [ "identificador" => "sec0014g" "titulo" => "Data for reference" ] 8 => array:2 [ "identificador" => "sec0014r" "titulo" => "Funding" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-03-23" "fechaAceptado" => "2021-05-24" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1470018" "palabras" => array:4 [ 0 => "Dexmedetomidine" 1 => "Infant patients" 2 => "Hemodynamics" 3 => "Cardiac surgery" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectivesDexmedetomidine (DEX) is a highly selective alpha-2 adrenergic receptor agonist, which is the main sedative in the intensive care unit. This study aims to investigate the effectiveness and adverse events of DEX in maintaining hemodynamic stability in pediatric cardiac surgery. SourcesDatabases such as PubMed, Cochrane, Web of Science, WANFANG STATA and China National Knowledge Infrastructure were searched for articles about the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery up to 18th Feb. 2021. Only randomized controlled trials were included and random-effects model meta-analysis was applied to calculate the standardized mean deviation (SMD), odds ratio (OR) and 95% confidence interval (CI). Summary of the findingsFifteen articles were included for this meta-analysis, and 9 articles for qualitative analysis. The results showed that preoperative prophylaxis and postoperative recovery of DEX in pediatric patients undergoing cardiac surgery were effective in maintaining systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and reducing heart rate (HR) (SBP: SMD = -0.35,95% CI: -0.72, 0.01; MAP: SMD = -0.83, 95% CI: -1.87,0.21; DBP: SMD = -0.79,95% CI: -1.66,0.08; HR: SMD = -1.71,95% CI: -2.29, -1.13). In addition, the frequency of Junctional Ectopic Tachycardia in the DEX treatment group was lower than that in the placebo group. ConclusionsThe application of DEX for preoperative prophylaxis and postoperative recovery in pediatric cardiac surgery patients are effective in maintaining hemodynamic stability, and the clinical dose of DEX is not significantly related to the occurrence of pediatric adverse events which may be related to individual differences." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Sources" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Summary of the findings" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusions" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "Qing Wang and Chuikai Chen contribute equally." "identificador" => "fn1" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<elsevierMultimedia ident="ecom0001"></elsevierMultimedia>" "etiqueta" => "Appendix" "titulo" => "Supplementary materials" "identificador" => "sec0016" ] ] ] ] "multimedia" => array:10 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3250 "Ancho" => 2500 "Tamanyo" => 375647 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Study selection flowchart, systematic review and meta-analysis of the role of dexmedetomidine in efficacy and safety of dexmedetomidine in maintaining hemodynamic stability in pediatric cardiac surgery." ] ] 1 => array:8 [ "identificador" => "fig0002" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1056 "Ancho" => 2500 "Tamanyo" => 197488 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Risk of bias graph: Review authors' judgments about each risk of bias item presented as percentages across all included studies." ] ] 2 => array:8 [ "identificador" => "fig0003" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 3095 "Ancho" => 1472 "Tamanyo" => 427219 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Risk of bias summary: Review authors' judgments about each risk of bias item for each included study." ] ] 3 => array:8 [ "identificador" => "fig0004" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 3311 "Ancho" => 2500 "Tamanyo" => 389772 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0004" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Forest plot of comparison between before and after infusion of DEX: A, systolic blood pressure; B, mean arterial blood pressure." ] ] 4 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 3311 "Ancho" => 2500 "Tamanyo" => 348675 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Forest plot of comparison between before and after infusion of DEX: A, diastolic blood pressure; B, central venous pressure." ] ] 5 => array:8 [ "identificador" => "fig0006" "etiqueta" => "Figure 6" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr6.jpeg" "Alto" => 3313 "Ancho" => 2500 "Tamanyo" => 375665 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0006" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Forest plot of comparison between before and after infusion of DEX and Comparison between Dexmedetomidine and Control (Placebo): A, heart rate; B, junctional ectopic tachycardia." ] ] 6 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0007" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Dex, dexmedetomidine; mo, month.Age show in mean ± SD or median (interquartile range)." "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"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Author, Year \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">No. of cases \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Age (mo) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Dex dose/ Administration \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0005"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Su et al. 2013<a class="elsevierStyleCrossRef" href="#bib0021">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0006"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0007"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">8.3 ± 3.5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.35μg/kg, 0.7μg/kg, 1μg/kg loading dose with infusion rate of 0.25 μg/kg/h, 0.50 μg/kg/h, 0.75μg/kg/h respectively \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0009"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Chrysostomou et al. 2009<a class="elsevierStyleCrossRef" href="#bib0022">22</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">3.9 ± 3.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.10–1.25 μg/kg/h infusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Lam et al. 2012<a class="elsevierStyleCrossRef" href="#bib0023">23</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">3.5 ± 2.6 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.10–1.50 μg/kg/h infusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0017"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Chrysostomou et al. 2006<a class="elsevierStyleCrossRef" href="#bib0024">24</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">96.0 ± 12.2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.20, 0.40, 0.60 µg/kg/h infusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Chen et al. 2013<a class="elsevierStyleCrossRef" href="#bib0025">25</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">36.0 ± 24.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.50 μg/kg loading dose with constant speed infusion in 10 min; 0.50 μg/kg/h infusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Lazol et al. 2010<a class="elsevierStyleCrossRef" href="#bib0026">26</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">10.0 ± 92.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">from 0.50 μg/kg to 1.00 μg/kg, infused at a rate of 0.10 μg/kg /min \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Mukhtar et al. 2006<a class="elsevierStyleCrossRef" href="#bib0027">27</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">28.0 ± 13.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.50 μg/kg loading dose with constant speed infusion in 10 min \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0033"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Jooste et al. 2010<a class="elsevierStyleCrossRef" href="#bib0028">28</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">74.0 ± 26.5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.50 μg/kg loading dose in five seconds \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Chen et al. 2014<a class="elsevierStyleCrossRef" href="#bib0029">29</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">11.7 ± 3.9 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">from 0.20 to 0.30 μg/kg/h with a 0.30 μg/kg loading dose \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Hammer et al. 2008<a class="elsevierStyleCrossRef" href="#bib0030">30</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">156.0 ± 6.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.00 μg/kg/h for 10 min, followed by 0.70 μg/kg/h for 10 min. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Chrysostomou et al. 2011<a class="elsevierStyleCrossRef" href="#bib0031">31</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">4.8 (0.16-198) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.1–1.5 μg/kg/h infusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0049"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Kadam et al. 2015<a class="elsevierStyleCrossRef" href="#bib0032">32</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">38.1 ± 62.4 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.75 μg/kg/h infusion after a loading dose of 1 mcg/kg over 15 min \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Rajput et al. 2014<a class="elsevierStyleCrossRef" href="#bib0033">33</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">110 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">33.2 ± 18.8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.5 μg/kg over 10 min followed by a continuous infusion of 0.5 μg/ kg/h. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0057"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Shuplock et al. 2015<a class="elsevierStyleCrossRef" href="#bib0034">34</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">468 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">26.1 (5.8–59.8) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.5–0.84 μg/kg/h infusion \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Amrousy et al. 2017<a class="elsevierStyleCrossRef" href="#bib0035">35</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">17.3 ± 4.1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.5 μg/kg over 20 min followed by a continuous infusion of 0.5 μg/ kg/h. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2810636.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics of included studies for meta-analysis." ] ] 7 => array:8 [ "identificador" => "tbl0002" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0008" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Evaluation of publication bias for the meta-analyses containing at least six studies.SBP, Systolic Blood Pressure; MAP, Mean Arterial Pressure; DBP, Diastolic Blood Pressure; CVP, Central Venous Pressure; HR, Heart rate; JET, Junctional Ectopic Tachycardia." "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"><a name="en0065"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col">Index \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0066"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Egger's regression</th><a name="en0067"></a><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Duval and Tweedie's trim and fill</th></tr><tr title="table-row"><a name="en0068"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0069"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Intercept \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0070"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">p \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0071"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Original OR \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0072"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Studies trimmed \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0073"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Adjusted OR \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0074"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_colgroup " colspan="6" align="left" valign="top">Comparison between before and after infusion of dexmedetomidine</td></tr><tr title="table-row"><a name="en0075"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">SBP \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-2.991 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.050 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-0.35 (-0.72, 0.01) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-0.35 (-0.72, 0.01) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0081"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MAP \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">16.573 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.487 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-0.83 (-1.87, 0.21) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-1.24 (-2.21, -0.27) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0087"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">DBP \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-0.283 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.976 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-0.79 (-1.66, 0.08) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-1.00 (-1.81, -0.18) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0093"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">CVP \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-4.932 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.537 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-0.67 (-2.49, 1.15) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-1.05 (-2.82, 0.72) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0099"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">HR \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-3.539 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.120 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-1.71 (-2.29, -1.13) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-1.71 (-2.29, -1.13) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0105"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">JET \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0106"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">-1.842 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.083 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.32 (0.20, 0.50) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="top">0.32 (0.20, 0.50) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2810635.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Evaluation of publication bias and sensitivity analysis." ] ] 8 => array:8 [ "identificador" => "tbl0003" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0009" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "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"><a name="en0111"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Author, Year \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0112"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">No. of cases \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0113"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Procedure \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0114"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Dexmedetomidine Dosing Regimen \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0115"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Adverse events \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0116"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Su et al. 2013<a class="elsevierStyleCrossRef" href="#bib0021">21</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">bidirectional Glenn and atrial septectomy \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.7μg/kg loading dose with infusion rate of 0.50 μg/kg/h \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">One patient developed Bradycardia was classified as a dose-limiting toxicity. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0121"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Shepard et al. 2011<a class="elsevierStyleCrossRef" href="#bib0045">45</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0123"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Postoperative day three of replacement mitral-valve surgery, 21 hours after the initiation of DEX \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.60 μg/kg/h \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">One patient unsuccessful atrial capture \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0126"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Tokuhira et al. 2009<a class="elsevierStyleCrossRef" href="#bib0039">39</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0127"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0128"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Pediatric ICU admission \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.3–0.4μg/kg/h \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0130"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Two patients unsuccessful atrial capture \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0131"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Hosokawa et al. 2010<a class="elsevierStyleCrossRef" href="#bib0040">40</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Pediatric ICU admission \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0134"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.60 μg/kg/h \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0135"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Twelve patients were considered to be bradycardia and hypotension \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0136"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Chrysostomou et al. 2009<a class="elsevierStyleCrossRef" href="#bib0022">22</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0138"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Pediatric ICU admission \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.1–1.25 μg/kg/h \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0140"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">58 hypotensive events (3%) and 44 bradycardic events (3%). \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0141"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Tewari et al. 2021<a class="elsevierStyleCrossRef" href="#bib0046">46</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Pediatric ICU admission \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0144"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">0.25–0.75μg/kg/h \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Two patients were considered to be Tachycardia, the other two were for hypertension and one for hypotension. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0146"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Ueno et al. 2016<a class="elsevierStyleCrossRef" href="#bib0047">47</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">124 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0148"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Pediatric ICU admission \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">1.00 μg/kg/h \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0150"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">There were five of 30 patients with trisomy 21 and 2 of 94 controls complicated by bradycardia, and the incidence of bradycardia occurred at a significantly higher rate in patients with trisomy 21 than in controls. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2810634.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Adverse events reported in the study and after the administration of DEX in pediatric cardiac 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Qing Wanga,1, Chuikai Chena,1, Li Wangb,

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dy135783@126.com

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a Hainan Women and Children's Medical Center, Department of Anesthesiology, Haikou, China

b The First Hospital of Hebei Medical University, Department of Anesthesiology, Shijiazhuang, China

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            "entidad" => "The First Hospital of Hebei Medical University<span class="elsevierStyleBold">&#44;</span> Department of Anesthesiology<span class="elsevierStyleBold">&#44;</span> Shijiazhuang<span class="elsevierStyleBold">&#44;</span> China"
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          "en" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Forest plot of comparison between before and after infusion of DEX and Comparison between Dexmedetomidine and Control &#40;Placebo&#41;&#58; A&#44; heart rate&#59; B&#44; junctional ectopic tachycardia&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Introduction</span><p id="para0007" class="elsevierStylePara elsevierViewall">Dexmedetomidine &#40;DEX&#41; has a high alpha-2&#47; alpha-1 receptor activity ratio and a selective binding ratio of 1620 alpha-2&#58; alpha-1 receptors&#46; DEX which has sedative&#44; anti-anxiety and analgesic effects&#44; and does not lead to respiratory inhibition is a highly selective and specific alpha-2 adrenergic receptor agonist&#46;<a class="elsevierStyleCrossRefs" href="#bib0001"><span class="elsevierStyleSup">1&#8211;5</span></a> It is reported that DEX which is the main sedative in the intensive care unit and the only sedative in the diagnosis of invasive surgery and magnetic resonance imaging in the intensive care unit&#44;<a class="elsevierStyleCrossRefs" href="#bib0006"><span class="elsevierStyleSup">6&#8211;10</span></a> is part of a balanced anesthetic for the prevention and treatment of sudden mental disorders&#46; The use of DEX in adults has the opposite effect on blood pressure&#46; The increase of systemic vascular resistance leads to an increase in blood pressure through the activation of peripheral alpha-2b adrenergic receptors&#44; and the sympathetic nerve reduces blood pressure through the activation of alpha-2a adrenergic receptors in the central nervous system&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> At the clinical dose&#44; the effect of the central sympathetic nerve is superior to that of peripheral vasoconstriction&#44; resulting in an overall decrease in blood pressure&#46; In children&#44; hemodynamic effects such as heart rate &#40;HR&#41; and arterial pressure decrease caused by slow injection of DEX for more than 10&#160;min have been well described&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> However&#44; rapid administration of DEX may lead to transient hypertension&#46; In adults&#44; biphasic hemodynamic responses can be observed within 2&#160;min after injection of DEX&#46; In the beginning&#44; blood pressure increases and reflex bradycardia occurs&#44; and then blood pressure and heart rate stabilize below the baseline&#46;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> Therefore&#44; the safe dose of DEX needs to be further described in detail&#46;</p><p id="para0008" class="elsevierStylePara elsevierViewall">At present&#44; the use of DEX in pediatric intensive care units is increasing due to its good sedation&#44; analgesia and anti-anxiety effects&#44; especially the prophylactic and postoperative medication should be used to maintain the hemodynamic stability of cardiac surgery in children&#46; Hence&#44; the present study&#39;s systematic review focused on investigating the effectiveness and adverse events of DEX in maintaining hemodynamic stability in pediatric cardiac surgery&#44; hoping to provide comprehensive and strong evidence that DEX should be used to maintain hemodynamic stability in pediatric cardiac surgery&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Methods</span><p id="para0009" class="elsevierStylePara elsevierViewall">This systematic review followed methods depicted in Cochrane Handbook for Systematic Reviews of Interventions version 6&#46;0&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> The authors performed the report according to PRISMA-P &#40;Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a></p><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Search strategy</span><p id="para0010" class="elsevierStylePara elsevierViewall">Five electronic databases such as PubMed&#44; Cochrane&#44; Web of Science&#44; WANFANG DATA&#44; and China National Knowledge Infrastructure were selected to systematically search the articles related to the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery up to February 18&#44; 2021&#46; The search formula was &#40;Dexmedetomidine&#41; or &#40;Dexmedetomidine &#91;MeSH Terms&#93;&#41; and &#40;pediatric cardiac surgery&#41; or &#40;pediatric cardiac surgery &#91;MeSH Terms&#93;&#41; and &#40;Hemodynamic&#41; or &#40;Hemodynamic &#91;MeSH Terms&#93;&#41;&#46; In addition&#44; the references included in the systematic search were also searched carefully&#44; in order not to omit any related articles&#44; and to make a comprehensive report on the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Inclusion and exclusion criteria</span><p id="para0011" class="elsevierStylePara elsevierViewall">According to the inclusion criteria&#44; two researchers assessed the title and abstract of the articles initially searched to determine whether the articles were included in this study&#46; When the tworesearchers disagreed&#44; they consulted a third researcher for a decision&#46; Articles that met the following inclusion criteria according to participants&#44; interventions&#44; comparisons&#44; outcomes&#44; and study design &#40;PICOS&#41; protocol&#44; would be adopted&#46; First&#44; the people studied in the articles were infants and young children&#46; Second&#44; each study included at least one pair of comparisons of hemodynamic parameters before and after cardiac surgery with DEX&#46; Moreover&#44; one group of subjects received DEX treatment&#44; and the other group received control treatment &#40;other treatments without DEX&#41;&#46; Third&#44; in the study hemodynamic parameters were measured&#44; including heart rate &#40;HR&#41;&#44; mean arterial pressure &#40;MAP&#41;&#44; central venous pressure &#40;CVP&#41;&#44; diastolic blood pressure &#40;DBP&#41;&#44; systolic blood pressure &#40;SBP&#41;&#44; and so on&#46; Fourth&#44; only the randomized controlled trials &#40;RCT&#41; were included&#44; to ensure the quality of the combined results&#46; In addition&#44; studies that could not provide effective analytical data were subsequently excluded&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Data extraction and quality assessment</span><p id="para0012" class="elsevierStylePara elsevierViewall">The two researchers independently extracted the following data provided by the study and entered the data into the extraction table&#58; the study title&#44; the name of the author&#44; the publication time of the study&#44; the sample size&#44; the demographic characteristics of the subjects&#44; the treatment method and dose of DEX&#44; the hemodynamic indicators&#44; the time of measurement&#44; and the specific characteristics of adverse events&#46; Hemodynamic stability was defined as the blood pressure and heart rate change observed no statistically significant&#46; In addition&#44; bradycardia and tachycardia were respectively defined as a 30&#37; decrease and increase from baseline when comparing the lowest and highest HR during dexmedetomidine infusion with the baseline HR&#46; A hypertensive or hypotensive episode was defined as a 30&#37; change from baseline and or if the SBP was below or above the 5<span class="elsevierStyleSup">th</span> to 95<span class="elsevierStyleSup">th</span> percentile for age&#46; After data extraction was completed&#44; a third researcher would double-check the consistency of the data extracted by the previous two researchers&#46;</p><p id="para0013" class="elsevierStylePara elsevierViewall">RCT meeting the inclusion criteria was evaluated and then incorporated into the final system review and meta-analysis&#46; Each of the two researchers evaluated the included study according to the RCT quality assessment section of the Cochrane handbook for systematic reviews of interventions 6&#46; 0&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> For each included study&#44; the two researchers assessed several kinds of bias&#44; such as blind bias&#44; selection bias&#44; incomplete outcome data bias&#44; selective reporting bias&#44; and other biases&#46; When they had different opinions&#44; a third researcher would make the final decision on the risk of bias based on the opinions of the previous two researchers&#46; According to the regulations of the Cochrane manual&#44; the authors determined whether the final quality of the study was low-risk&#44; medium-risk&#44; or high-risk based on the conclusions of the overall quality assessment&#46;</p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Statistical analysis</span><p id="para0014" class="elsevierStylePara elsevierViewall">Results were merged across studies by using Stata version 15&#46;1 &#40;Stata Corp MP&#46;&#44; College Station&#44; TX&#44; USA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a> Given the differences in the demographic characteristics of the subjects&#44; the differences in the use of prophylactic drugs before and after cardiac surgery in children&#44; the differences in dosage and mode of medication&#44; and the inconsistency of measurement time points&#44; a random effect model was applied to combine the results in this study&#46; Considering the high heterogeneity among various studies&#44; it was impractical to calculate the exact amount of effect&#44; but the effect of drug use and the source of high heterogeneity could be discussed&#44; which is of guiding significance for the safe use of drugs in the future and avoiding adverse events in DEX&#46; The authors calculated the standardized mean deviation &#40;SMD&#41; of hemodynamic parameters before and after the administration of DEX in pediatric cardiac surgery and the odds ratio &#40;OR&#41; of the number of adverse events between the DEX group and the control group to evaluate the hemodynamic stability&#46; Besides&#44; the method of calculating and studying the merging standard deviation referred to the Cochrane handbook&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> Q test and <span class="elsevierStyleItalic">I<span class="elsevierStyleSup">2</span></span> statistics were used to estimate the heterogeneity of the study&#46; If the <span class="elsevierStyleItalic">I<span class="elsevierStyleSup">2</span></span> value was 0&#37;&#44; 40&#37;&#44; and 60&#37;&#44; respectively&#44; it was considered to have low&#44; medium&#44; and high heterogeneity&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> Indicators for evaluating hemodynamic stability will be shown in a forest plot&#46; Egger&#39;s test was adopted to weigh the publication bias of the results&#44; and Duval and Tweedie&#39;s trim and fill test to assess the sensitivity of the results&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a> Unless the p value was less than 0&#46;001&#44; the exact p value would be provided&#46; Except that <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;10 in Egger&#39;s test was considered to be statistically significant&#44; other <span class="elsevierStyleItalic">p</span>&#160;&#60;&#160;0&#46;05 could be considered to be statistically significant&#46;</p></span></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Results</span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Literature search&#44; study characteristics and quality assessment</span><p id="para0015" class="elsevierStylePara elsevierViewall">107 articles were retrieved by database system retrieval and 24 by manual retrieval&#46; After 16 repeated articles were removed&#44; 85 articles that did not meet the inclusion criteria were excluded by screening the titles and abstracts of the articles&#46; &#40;not related to dexmedetomidine <span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;8&#59; review or in vitro&#47; animal studies or letter or editorial or conference paper <span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;24&#59; Non-pediatric cardiac surgery <span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;40&#59; not related to hemodynamics <span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;13&#41;&#46; Subsequently&#44; 6 of 30 articles screened in the full text were excluded due to a lack of available data&#46; Finally&#44; a total of 9 studies were included in qualitative analysis and 15 in quantitative analysis &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#41;&#46; The whole screening process included 1042 pediatric patients who underwent cardiac surgery treated with DEX for meta-analysis and 1332 pediatric patients who underwent cardiac surgery without DEX treatment&#46; The basic features of 15 studies included in the meta-analysis are shown in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1&#46;</a><a class="elsevierStyleCrossRefs" href="#bib0021"><span class="elsevierStyleSup">21&#8211;35</span></a></p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0016" class="elsevierStylePara elsevierViewall">Based on the quality assessment part of the Cochrane handbook&#44; a systematic evaluation was conducted to assess the bias risk of all included articles&#44; such as selection bias&#44; selective report bias&#44; incomplete report bias&#44; and publication bias&#46; According to the Cochrane handbook&#44; the quality of the literature was defined as low&#44; moderate and high risk&#46; All the included studies strictly followed the principle of random distribution&#44; and before the beginning of the study&#44; the subjects with chronic diseases who might cause adverse harm in the course of the study and those who were more likely to have complications in the course of the study were excluded&#46; Therefore&#44; the lack of data that could damage the effectiveness of the test was not possible&#46; Both items were rated as low risk and the rest included in the overall evaluation of RCT were considered low risk of bias&#44; which indicated that the quality of the meta-analysis was favorable and the result of the meta-analysis was reliable &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Figs&#46;&#160;2</a> and <a class="elsevierStyleCrossRef" href="#fig0003">3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia><elsevierMultimedia ident="fig0003"></elsevierMultimedia></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">Hemodynamics</span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">Comparison between before and after infusion of DEX</span><p id="para0017" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">SBP&#46;</span> 9 groups on the changes of SBP before and after DEX treatment in pediatric cardiac surgery&#44; it was found that the SBP of patients treated with DEX during or after cardiac surgery decreased compared with the baseline SBP&#44; but the difference was not statistically significant &#40;SMD&#160;&#61;&#160;-0&#46;35&#44; 95&#37; CI&#58; -0&#46;72&#44; 0&#46;01&#59; <a class="elsevierStyleCrossRef" href="#fig0004">Fig&#46; 4</a>A&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0026"><span class="elsevierStyleSup">26&#8211;28</span></a> Sensitivity analysis was used to study the sources of heterogeneity&#46; Then&#44; it was found that heterogeneity may be related to one group of research Mukhtar et&#160;al&#46; and research Jooste et&#160;al&#46;&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a></p><elsevierMultimedia ident="fig0004"></elsevierMultimedia><p id="para0018" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">MAP&#46;</span> 8 groups reported MAP data before and after DEX treatment during or after pediatric cardiac surgery&#46; The combined results of 8 groups showed that MAP also observed a downward trend&#44; and the difference was not statistically significant &#40;SMD &#61;-0&#46;83&#44; 95&#37; CI&#58; -1&#46;87&#44;0&#46;21&#59; <a class="elsevierStyleCrossRef" href="#fig0004">Fig&#46; 4</a>B&#41;&#40;21&#44; 23&#44; 25&#44; 29&#44; 30&#41;&#46; Through sensitivity analysis&#44; it was found that the main source of heterogeneity may be related to a group in the study of Lam et&#160;al&#46; and research in the study of Hammer et&#160;al&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">30</span></a></p><p id="para0019" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">DBP and CVP</span>&#46; Similar to SBP and MAP&#44; DBP and CVP also showed a downward trend&#44; and the difference was not statistically significant &#40;DBP&#58; SMD&#160;&#61;&#160;-0&#46;79&#44; 95&#37;CI&#58; -1&#46;66&#44; 0&#46;08&#59; CVP&#58; SMD&#160;&#61;&#160;-0&#46;67 95&#37;CI&#58; -2&#46;49&#44; 1&#46;15&#59; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 5</a>A and B&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0023"><span class="elsevierStyleSup">23&#8211;29</span></a> Through sensitivity analysis&#44; it was found that the heterogeneity of DBP came from the study of Mukhtar et&#160;al&#46;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a> Frustratingly&#44; the hemodynamic index of CVP had strong heterogeneity and no obvious trend&#46; Therefore&#44; the guiding significance of this index remains to be further discussed&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="para0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">HR&#46;</span> 15 groups reported HR data before and after DEX treatment during or after pediatric cardiac surgery&#46; The combined results of 15 groups found that HR showed a significant downward trend&#44; and the difference was statistically significant &#40;SMD&#160;&#61;&#160;-1&#46;71&#44; 95&#37;CI&#58; -2&#46;29&#44; -1&#46;13&#59; <a class="elsevierStyleCrossRef" href="#fig0006">Fig&#46; 6</a>A&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0021"><span class="elsevierStyleSup">21&#8211;28</span></a> Obviously&#44; the decrease of HR in a group in Lam et&#160;al&#46;&#44; and the study of Chen et&#160;al&#46; and a group in Jooste et&#160;al&#46; were significantly stronger than those in the other groups&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a></p><elsevierMultimedia ident="fig0006"></elsevierMultimedia></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">Comparison between dexmedetomidine and control &#40;Placebo&#41;</span><p id="para0021" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleBold">Junctional Ectopic Tachycardia &#40;JET&#41;&#46;</span> Five studies revealed that the probability of JET during and after cardiac surgery treated with DEX was significantly lower than those of placebo groups &#40;OR&#160;&#61;&#160;0&#46;32&#44; 95&#37;CI&#58; 0&#46;20&#44; 0&#46;50&#59; <a class="elsevierStyleCrossRef" href="#fig0006">Fig&#46; 6</a>B&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0031"><span class="elsevierStyleSup">31-35</span></a> The five studies showed low heterogeneity&#44; indicating that DEX can reduce the heart rate during and after pediatric cardiac surgery and effectively reduce the incidence of JET&#46;</p></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019">Publication bias assessment and sensitivity analysis</span><p id="para0022" class="elsevierStylePara elsevierViewall">Egger&#39;s test was used to analyze publication bias&#46; It suggested that there was a publication bias in indices SBP and JET&#44; but no publication bias was observed in other indexes&#46; Duval and Tweedie&#39;s Trim and Fill Test of indexes MAP and DBP found that the effect quantity was not stable&#44; and their guiding significance needs to be further discussed &#40;<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia></span></span></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020">Discussion</span><p id="para0023" class="elsevierStylePara elsevierViewall">In quantitative analysis&#44; the high heterogeneity of meta-analysis results did not have a serious impact on the interpretation of the stability of hemodynamic indexes&#44; which truly reflected the situation that may be faced in the clinical application of DEX&#46; It was obvious that in the forest map&#44; the mean and standard deviation of each group in the research were not merged&#44; but regarded as one of the merged objects in the form of study&#44; which was the main source of high heterogeneity in this study&#46; The reason why the data were processed in that manner was that nowadays&#44; DEX is used in patients&#44; whether prophylactic medication before operation or recovery medication after an operation&#44; to bring stable hemodynamic effects to patients&#44; and it is nothing new to effectively reduce the heart rate and blood pressure of patients&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> Hence&#44; it was only necessary to reconfirm the effect&#46; Meanwhile&#44; those studies that could not provide effective and analyzable data for meta-analysis studies also showed the same hemodynamic effects&#46; The specific hemodynamic indicators were listed in supplemental Table 1&#46;<a class="elsevierStyleCrossRefs" href="#bib0036"><span class="elsevierStyleSup">36&#8211;44</span></a> Based on the evidence of quantitative analysis and qualitative description&#44; it was confirmed that DEX was able to reduce heart rate&#44; blood pressure&#44; stabilize hemodynamics and reduce the frequency of JET in preoperative preventive medication and postoperative recovery of pediatric cardiac surgery&#46;</p><p id="para0024" class="elsevierStylePara elsevierViewall">It was assumed that the publication bias of the indicator SBP observed by Egger&#39;s test mainly came from the fact that the group was used as a unit of analysis&#44; and research Chrysostomou et&#160;al&#46;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> and research Chrysostomou et&#160;al&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> of the groups accounted for 62&#46;87&#37; of the total analysis of the index SBP&#46; The software could not identify this process&#44; and the effects in the two studies were very similar&#44; so it was concluded that the index had a nonnegligible publication bias&#46; Based on the analysis of the publication bias detected by the index JET&#44; it was undeniable that there lacked small-sized sample study in the JET index&#46; Nevertheless&#44; it was obvious that all five studies showed that the frequency of JET in the DEX group was less than those in the placebo group&#44; which has clinical significance&#46; As for the sensitivity analysis of Duval and Tweedie&#39;s trim and fill&#44; it was assumed the indexes MAP and DBP showed a downward trend after DEX treatment&#44; and the effect of maintaining hemodynamic stability during and after cardiac surgery was confirmed&#46; With part of the study cut-off&#44; the difference changed from no statistical significance to statistically significant for clinical guidance&#44; which was only related to the statistical analysis method&#46;</p><p id="para0025" class="elsevierStylePara elsevierViewall">The adverse events caused by preoperative prophylaxis and postoperative recovery of DEX in pediatric cardiac surgery were presumed to be related to individual differences&#46; All the adverse events reported in the study and after the administration of DEX in pediatric cardiac surgery were sorted out in <a class="elsevierStyleCrossRef" href="#tbl0003">Table 3&#46;</a><a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0039"><span class="elsevierStyleSup">39</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">40</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">45&#8211;47</span></a> First&#44; age had no significant effect on the pharmacokinetics of DEX&#44; and the equilibrium half-life of different age groups was similar&#46; But the decrease of tolerance to DEX may be caused by renal hypoplasia in some infants&#44; which was not discussed in detail&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0037"><span class="elsevierStyleSup">37</span></a> This study focused on the dose and mode of treatment of DEX&#46; The main purpose of using the group as the unit of the meta-analysis was to observe the stability of hemodynamic indexes and whether it was related to the frequency of adverse events with different doses of DEX and different treatment methods in the same study&#46; Observed from the forest map&#44; it was found that different DEX treatments in the same study produced different hemodynamic effects&#44; but there was no good consistency in the same incremental dose treatment between different studies &#40;<a class="elsevierStyleCrossRefs" href="#fig0004">Figs&#46; 4&#8211;6</a>&#44; <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#41;&#46; Second&#44; as the original data of the study could not be obtained&#44; the authors cannot analyze the correlation between the dose and effect index of different DEX treatments statistically&#46; Third&#44; what could be confirmed was that there were only a few cases of adverse events such as bradycardia&#44; hypotension&#44; and transient hypertension among the doses collected for preoperative prophylaxis and postoperative recovery of DEX for pediatric cardiac surgery &#40;<a class="elsevierStyleCrossRef" href="#tbl0003">Table 3</a>&#41;&#46; However&#44; the incidence of bradycardia due to DEX treatment in children with trisomy 21 syndrome was significantly higher than that in normal children&#46;<a class="elsevierStyleCrossRef" href="#bib0047"><span class="elsevierStyleSup">47</span></a> Fourth&#44; in addition to the commonly used method of slow injection of DEX in the application of DEX in children&#39;s cardiac surgery&#44; rapid injection of DEX within 5&#160;s to deal with emergencies was discussed&#46; The hemodynamic indexes would temporarily increase within one minute after injection&#44; but the hemodynamic indices would soon decrease to a stable level at 5&#160;min&#46;<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0037"><span class="elsevierStyleSup">37</span></a> All in all&#44; it was likely that the adverse events in the process of preoperative prophylaxis and postoperative recovery of DEX in pediatric cardiac surgery were related to individual differences&#46;</p><elsevierMultimedia ident="tbl0003"></elsevierMultimedia><p id="para0026" class="elsevierStylePara elsevierViewall">JET can lead to significant hemodynamic instability in the postoperative period after cardiac surgery&#46; As a preventive and therapeutic drug&#44; shown in the results&#44; dexmedetomidine can effectively reduce the frequency of JET&#46; JET is a tachyarrhythmia related to surgery for congenital heart disease which could cause serious hemodynamic instability in the postoperative period&#46; JET is a narrow QRS complex tachycardia with atrioventricular dissociation and a slower atrial rate as compared to ventricular rate&#46; Atrioventricular asynchrony causes loss of atrial contraction contribution to cardiac output&#44; resulting in hemodynamic instability&#46; At present&#44; the exact mechanism of JET is unknown and may be related to proximal conduction tissue injury associated with indirect stretch injury or suture surgery&#46; The incidence of JET has been reported to range from 8&#37; to 24&#37;&#44; depending on the patient&#39;s choice and surgical procedure&#46;<a class="elsevierStyleCrossRef" href="#bib0048"><span class="elsevierStyleSup">48</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0049"><span class="elsevierStyleSup">49</span></a> While dexmedetomidine exerts sedative&#44; analgesic and antianxiety effects through the pharmacological effects of &#945;-2 adrenergic receptor agonist&#44; the results of meta-analysis also showed that the use of dexmedetomidine in pediatric cardiac surgery can reduce heart rate and reduce the occurrence of JET&#46;</p><p id="para0027" class="elsevierStylePara elsevierViewall">The authors investigated the indirect results of cardiac output in 9 articles included in the meta-analysis and 15 articles included in the qualitative analysis&#46; The reduction in heart rate and blood pressure caused by the efficacy of dexmedetomidine for maintaining hemodynamic stability in pediatric cardiac surgery does not support the reduction in cardiac output&#46; The above studies included at least one of the following indicators that did not support decreased cardiac output&#58; absence of acidosis&#44; unchanged inotropic requirement&#44; central venous pressure&#44; and left ventricular function&#46; Therefore&#44; the authors do not believe that the decrease in blood pressure is due to low cardiac output syndrome&#44; but is the result of sedation&#44; analgesia&#44; and possibly the result of activation alpha-2 adrenergic receptors in the central nervous system&#46;</p><p id="para0028" class="elsevierStylePara elsevierViewall">This study inevitably had some limitations&#58; except for trisomy 21 syndrome&#44; all the patients included in this review were patients without chronic diseases of kidney&#44; liver or other organs&#44; which had limitations in guiding the clinical application of DEX to prevent adverse events&#46;</p><p id="para0029" class="elsevierStylePara elsevierViewall">In conclusion&#44; the application of DEX for preoperative prophylaxis and postoperative recovery in pediatric cardiac surgery patients is effective in maintaining hemodynamic stability with reduced blood pressure with no statistical significance&#46; Furthermore&#44; the clinical dose of DEX is not significantly related to the occurrence of pediatric adverse events which may be related to individual differences&#46;</p></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0021">Ethics approval and consent to participate</span><p id="para0030" class="elsevierStylePara elsevierViewall">Ethical approval was not needed because this is a meta-analysis&#46;</p></span><span id="sec0014g" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Data for reference</span><p id="para9001" class="elsevierStylePara elsevierViewall">The datasets used and&#47;or analyzed during the current study are available from the corresponding author on reasonable request&#46;</p></span><span id="sec0014r" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0023">Funding</span><p id="para0033" class="elsevierStylePara elsevierViewall">This paper is supported by the <span class="elsevierStyleGrantSponsor" id="gs0001">Hainan Natural Science Foundation Youth Project</span> &#40;Grant No&#58;<span class="elsevierStyleGrantNumber" refid="gs0001">819QN394</span>&#41;&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Methods"
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                  "titulo" => "Comparison between before and after infusion of DEX"
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                  "titulo" => "Comparison between dexmedetomidine and control &#40;Placebo&#41;"
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                  "titulo" => "Publication bias assessment and sensitivity analysis"
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          "titulo" => "References"
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    "fechaRecibido" => "2021-03-23"
    "fechaAceptado" => "2021-05-24"
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          "clase" => "keyword"
          "titulo" => "Keywords"
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          "palabras" => array:4 [
            0 => "Dexmedetomidine"
            1 => "Infant patients"
            2 => "Hemodynamics"
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    "resumen" => array:1 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Objectives</span><p id="spara014" class="elsevierStyleSimplePara elsevierViewall">Dexmedetomidine &#40;DEX&#41; is a highly selective alpha-2 adrenergic receptor agonist&#44; which is the main sedative in the intensive care unit&#46; This study aims to investigate the effectiveness and adverse events of DEX in maintaining hemodynamic stability in pediatric cardiac surgery&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Sources</span><p id="spara015" class="elsevierStyleSimplePara elsevierViewall">Databases such as PubMed&#44; Cochrane&#44; Web of Science&#44; WANFANG STATA and China National Knowledge Infrastructure were searched for articles about the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery up to 18th Feb&#46; 2021&#46; Only randomized controlled trials were included and random-effects model meta-analysis was applied to calculate the standardized mean deviation &#40;SMD&#41;&#44; odds ratio &#40;OR&#41; and 95&#37; confidence interval &#40;CI&#41;&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Summary of the findings</span><p id="spara016" class="elsevierStyleSimplePara elsevierViewall">Fifteen articles were included for this meta-analysis&#44; and 9 articles for qualitative analysis&#46; The results showed that preoperative prophylaxis and postoperative recovery of DEX in pediatric patients undergoing cardiac surgery were effective in maintaining systolic blood pressure &#40;SBP&#41;&#44; mean arterial pressure &#40;MAP&#41;&#44; diastolic blood pressure &#40;DBP&#41; and reducing heart rate &#40;HR&#41; &#40;SBP&#58; SMD&#160;&#61;&#160;-0&#46;35&#44;95&#37; CI&#58; -0&#46;72&#44; 0&#46;01&#59; MAP&#58; SMD&#160;&#61;&#160;-0&#46;83&#44; 95&#37; CI&#58; -1&#46;87&#44;0&#46;21&#59; DBP&#58; SMD&#160;&#61;&#160;-0&#46;79&#44;95&#37; CI&#58; -1&#46;66&#44;0&#46;08&#59; HR&#58; SMD&#160;&#61;&#160;-1&#46;71&#44;95&#37; CI&#58; -2&#46;29&#44; -1&#46;13&#41;&#46; In addition&#44; the frequency of Junctional Ectopic Tachycardia in the DEX treatment group was lower than that in the placebo group&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusions</span><p id="spara017" class="elsevierStyleSimplePara elsevierViewall">The application of DEX for preoperative prophylaxis and postoperative recovery in pediatric cardiac surgery patients are effective in maintaining hemodynamic stability&#44; and the clinical dose of DEX is not significantly related to the occurrence of pediatric adverse events which may be related to individual differences&#46;</p></span>"
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          "leyenda" => "<p id="spara008" class="elsevierStyleSimplePara elsevierViewall">Dex&#44; dexmedetomidine&#59; mo&#44; month&#46;</p><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">Age show in mean &#177; SD or median &#40;interquartile range&#41;&#46;</p>"
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Author&#44; Year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">No&#46; of cases&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Age &#40;mo&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Dex dose&#47; Administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0005"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">Su et&#160;al&#46; 2013<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0007"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">8&#46;3&#160;&#177;&#160;3&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;35&#956;g&#47;kg&#44; 0&#46;7&#956;g&#47;kg&#44; 1&#956;g&#47;kg loading dose with infusion rate of 0&#46;25 &#956;g&#47;kg&#47;h&#44; 0&#46;50 &#956;g&#47;kg&#47;h&#44; 0&#46;75&#956;g&#47;kg&#47;h respectively&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0009"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">Chrysostomou et&#160;al&#46; 2009<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="top">3&#46;9&#160;&#177;&#160;3&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;10&#8211;1&#46;25 &#956;g&#47;kg&#47;h infusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Lam et&#160;al&#46; 2012<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">3&#46;5&#160;&#177;&#160;2&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;10&#8211;1&#46;50 &#956;g&#47;kg&#47;h infusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Chrysostomou et&#160;al&#46; 2006<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">96&#46;0&#160;&#177;&#160;12&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;20&#44; 0&#46;40&#44; 0&#46;60 &#181;g&#47;kg&#47;h infusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Chen et&#160;al&#46; 2013<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">36&#46;0&#160;&#177;&#160;24&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;50 &#956;g&#47;kg loading dose with constant speed infusion in 10 min&#59; 0&#46;50 &#956;g&#47;kg&#47;h infusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Lazol et&#160;al&#46; 2010<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">10&#46;0&#160;&#177;&#160;92&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">from 0&#46;50 &#956;g&#47;kg to 1&#46;00 &#956;g&#47;kg&#44; infused at a rate of 0&#46;10 &#956;g&#47;kg &#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Mukhtar et&#160;al&#46; 2006<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">28&#46;0&#160;&#177;&#160;13&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;50 &#956;g&#47;kg loading dose with constant speed infusion in 10 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Jooste et&#160;al&#46; 2010<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">74&#46;0&#160;&#177;&#160;26&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;50 &#956;g&#47;kg loading dose in five seconds&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Chen et&#160;al&#46; 2014<a class="elsevierStyleCrossRef" href="#bib0029"><span class="elsevierStyleSup">29</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">11&#46;7&#160;&#177;&#160;3&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">from 0&#46;20 to 0&#46;30 &#956;g&#47;kg&#47;h with a 0&#46;30 &#956;g&#47;kg loading dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Hammer et&#160;al&#46; 2008<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">30</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">156&#46;0&#160;&#177;&#160;6&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;00 &#956;g&#47;kg&#47;h for 10 min&#44; followed by 0&#46;70 &#956;g&#47;kg&#47;h for 10 min&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Chrysostomou et&#160;al&#46; 2011<a class="elsevierStyleCrossRef" href="#bib0031"><span class="elsevierStyleSup">31</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">4&#46;8 &#40;0&#46;16-198&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;1&#8211;1&#46;5 &#956;g&#47;kg&#47;h infusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Kadam et&#160;al&#46; 2015<a class="elsevierStyleCrossRef" href="#bib0032"><span class="elsevierStyleSup">32</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">38&#46;1&#160;&#177;&#160;62&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;75 &#956;g&#47;kg&#47;h infusion after a loading dose of 1 mcg&#47;kg over 15 min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Rajput et&#160;al&#46; 2014<a class="elsevierStyleCrossRef" href="#bib0033"><span class="elsevierStyleSup">33</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">110&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">33&#46;2&#160;&#177;&#160;18&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;5 &#956;g&#47;kg over 10&#160;min followed by a continuous infusion of 0&#46;5 &#956;g&#47; kg&#47;h&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Shuplock et&#160;al&#46; 2015<a class="elsevierStyleCrossRef" href="#bib0034"><span class="elsevierStyleSup">34</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">468&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">26&#46;1 &#40;5&#46;8&#8211;59&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;5&#8211;0&#46;84 &#956;g&#47;kg&#47;h infusion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Amrousy et&#160;al&#46; 2017<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">35</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">17&#46;3&#160;&#177;&#160;4&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;5 &#956;g&#47;kg over 20&#160;min followed by a continuous infusion of 0&#46;5 &#956;g&#47; kg&#47;h&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spara011" class="elsevierStyleSimplePara elsevierViewall">Evaluation of publication bias for the meta-analyses containing at least six studies&#46;</p><p id="spara012" class="elsevierStyleSimplePara elsevierViewall">SBP&#44; Systolic Blood Pressure&#59; MAP&#44; Mean Arterial Pressure&#59; DBP&#44; Diastolic Blood Pressure&#59; CVP&#44; Central Venous Pressure&#59; HR&#44; Heart rate&#59; JET&#44; Junctional Ectopic Tachycardia&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0065"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">Index&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0066"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Egger&#39;s regression</th><a name="en0067"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Duval and Tweedie&#39;s trim and fill</th></tr><tr title="table-row"><a name="en0068"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0069"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Intercept&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0070"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0071"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Original OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0072"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Studies trimmed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0073"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Adjusted OR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0074"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="6" align="left" valign="top">Comparison between before and after infusion of dexmedetomidine</td></tr><tr title="table-row"><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">SBP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-2&#46;991&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">0&#46;050&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-0&#46;35 &#40;-0&#46;72&#44; 0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-0&#46;35 &#40;-0&#46;72&#44; 0&#46;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MAP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">16&#46;573&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">0&#46;487&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-0&#46;83 &#40;-1&#46;87&#44; 0&#46;21&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-1&#46;24 &#40;-2&#46;21&#44; -0&#46;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">DBP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-0&#46;283&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="top">0&#46;976&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-0&#46;79 &#40;-1&#46;66&#44; 0&#46;08&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="top">-1&#46;00 &#40;-1&#46;81&#44; -0&#46;18&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">CVP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-4&#46;932&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">0&#46;537&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-0&#46;67 &#40;-2&#46;49&#44; 1&#46;15&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0099"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">HR&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="top">-3&#46;539&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="top">0&#46;120&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">JET&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">-1&#46;842&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="top">0&#46;083&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">0&#46;32 &#40;0&#46;20&#44; 0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="top">0&#46;32 &#40;0&#46;20&#44; 0&#46;50&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Su et&#160;al&#46; 2013<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">36&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">bidirectional Glenn and atrial septectomy&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">0&#46;7&#956;g&#47;kg loading dose with infusion rate of 0&#46;50 &#956;g&#47;kg&#47;h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0120"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">One patient developed Bradycardia was classified as a dose-limiting toxicity&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Shepard et&#160;al&#46; 2011<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">45</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Postoperative day three of replacement mitral-valve surgery&#44; 21 hours after the initiation of DEX&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;60 &#956;g&#47;kg&#47;h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">One patient unsuccessful atrial capture&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Tokuhira et&#160;al&#46; 2009<a class="elsevierStyleCrossRef" href="#bib0039"><span class="elsevierStyleSup">39</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">9&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Pediatric ICU admission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Two patients unsuccessful atrial capture&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Hosokawa et&#160;al&#46; 2010<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">40</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">56&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Pediatric ICU admission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Twelve patients were considered to be bradycardia and hypotension&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Chrysostomou et&#160;al&#46; 2009<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Pediatric ICU admission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">0&#46;1&#8211;1&#46;25 &#956;g&#47;kg&#47;h&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">58 hypotensive events &#40;3&#37;&#41; and 44 bradycardic events &#40;3&#37;&#41;&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Tewari et&#160;al&#46; 2021<a class="elsevierStyleCrossRef" href="#bib0046"><span class="elsevierStyleSup">46</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0142"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Pediatric ICU admission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">0&#46;25&#8211;0&#46;75&#956;g&#47;kg&#47;h&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Two patients were considered to be Tachycardia&#44; the other two were for hypertension and one for hypotension&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Ueno et&#160;al&#46; 2016<a class="elsevierStyleCrossRef" href="#bib0047"><span class="elsevierStyleSup">47</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="top">124&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">Pediatric ICU admission&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">1&#46;00 &#956;g&#47;kg&#47;h&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">There were five of 30 patients with trisomy 21 and 2 of 94 controls complicated by bradycardia&#44; and the incidence of bradycardia occurred at a significantly higher rate in patients with trisomy 21 than in controls&#46;&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 00217557
Original language: English

DOI:10.1016/j.jped.2021.05.008

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Year/Month	Html	Pdf	Total

2024 November	5	3	8
2024 October	26	23	49
2024 September	46	38	84
2024 August	66	52	118
2024 July	60	97	157
2024 June	58	29	87
2024 May	67	11	78
2024 April	53	36	89
2024 March	65	25	90
2024 February	60	39	99
2024 January	74	24	98
2023 December	31	30	61
2023 November	57	30	87
2023 October	113	39	152
2023 September	54	44	98
2023 August	42	18	60
2023 July	28	11	39
2023 June	45	26	71
2023 May	52	27	79
2023 April	42	21	63
2023 March	71	30	101
2023 February	64	32	96
2023 January	64	42	106
2022 December	107	48	155
2022 November	47	33	80
2022 October	67	55	122
2022 September	84	59	143
2022 August	100	50	150
2022 July	103	39	142
2022 June	61	32	93
2022 May	74	37	111
2022 April	87	50	137
2022 March	109	89	198
2022 February	107	42	149
2022 January	117	54	171
2021 December	11	9	20
2021 November	9	15	24
2021 October	10	18	28
2021 September	15	9	24
2021 August	9	10	19
2021 July	7	7	14

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