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Therapeutic hypothermia: Time for a moratorium
Hipotermia terapéutica: tiempo para una moratoria
Servicio de Medicina Intensiva, Hospital Universitario Infanta Leonor, Madrid, Spain
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Palencia Herrejón, D. Díaz Díaz" "autores" => array:2 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Palencia Herrejón" "email" => array:1 [ 0 => "palenciah@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Díaz Díaz" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Medicina Intensiva, Hospital Universitario Infanta Leonor, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipotermia terapéutica: tiempo para una moratoria" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4268 "Ancho" => 3167 "Tamanyo" => 653323 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hypothermia induced in recovered cardiac arrest. Mortality and neurological recovery (random-effects meta-analysis model<span class="elsevierStyleSup">a</span>). (A) Effect of hypothermia on mortality. (B) Effect of hypothermia on neurological recovery. The confidence intervals, and the estimated prediction intervals are included<span class="elsevierStyleSup">a</span>. The random-effects meta-analysis model penalizes studies of large samples and low risk of bias such as Nielsen's compared to studies of small samples and high risk of bias.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Total or partial cooling of human beings has been used sporadically in a variety of diseases of the central nervous system for centuries. Intuitively it is believed that hypothermia may preserve neuronal viability and increase the chances of survival and functional recovery.</p><p id="par0010" class="elsevierStylePara elsevierViewall">However, it was not until the last decade that its use has been generalized in a particular situation–recovered cardiac arrests (RCA) after the publication, in the year 2002, of Holzer's study (HACA group) and Bernard et al.’s study<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,2</span></a> that found out that by inducing mild hypothermia (32–34<span class="elsevierStyleHsp" style=""></span>°C) mortality was lower and the chances of neurological recovery after an out-of-hospital RCA of presumed cardiac origin due to defibrillation rhythms were higher. The recommendation to use hypothermia came fast and it reached out to two groups that had not been evaluated in the clinical trials: non-defibrillation rhythms, and hospital cardiac arrests. As it has happened in other occasions, the desire to find effective therapies in a situation that leads to such higher mortality rates as RCAs is accompanied by an enthusiastic adherence and a not very critical evaluation of the apparently favourable results, so it is not surprising that such studies are usually referred to as “large sample” and “high quality” studies, when they are really small studies with important methodological limitations (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">After the support given by the scientific societies to therapeutical hypothermia (although with a less-than-expected adherence in the clinical practice) and the favourable sanction by the Cochrane collaboration in a questionable practice where it is the researchers of the clinical trials who make the assessments through systematic reviews and meta-analyses, some independent voices have talked about the low quality of evidence on which the recommendation of hypothermia is based and highlighted the need for conducting a more rigorous clinical trial. Nielsen et al.’s clinical trial,<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> published in 2013, is three times as big, in size, as all the other former trials and, in a transparent way, prospectively shows the study protocol, while applying a strict treatment to the control group, and clearly specifying what criteria should be followed in order to limit the therapeutic effort – something that was not done in the other trials yet despite the fact that it was a common practice after suffering a RCA, since it may clearly bias the results while favouring the group sought after by the researchers. Its results show that mild hypothermia (32–34<span class="elsevierStyleHsp" style=""></span>°C) does not improve mortality or neurological recovery compared to the control of temperature in the range of monothermia (36<span class="elsevierStyleHsp" style=""></span>°C), or perhaps it should be referred to as “minimal hypothermia”. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the main characteristics of the three main clinical trials on hypothermia in the management of RCA<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–3</span></a> focusing on its methodological quality, and showing why we should give more credit to Nielsen's study than to the other two studies that support the recommendations coming from the scientific societies.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Yet despite the publication of Nielsen's clinical trial and observational studies with results clearly negative on hypothermia in the management of intrahospital cardiac arrests,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> the scientific societies have underestimated the evidence against the effectiveness of hypothermia when the evidence in its favour is quantitative and qualitatively inferior. After taking the most recent studies into consideration, and in a decision difficult to understand, ILCOR has “tempered” its recommendations leaving the clinicians the option to choose and maintain, at least during 24<span class="elsevierStyleHsp" style=""></span>h, a target temperature between the wide range of 32 and 36<span class="elsevierStyleHsp" style=""></span>°C,<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> but without initiating the cooling process before hospital arrival, since this therapy that would be beneficial a few minutes later may be detrimental if administered earlier.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The theoretical mechanisms through which hypothermia may have neuroprotective effects in the clinical practice are highly varied. This means that it may be effective in different diseases of the central nervous system, and this is why hypothermia has been tested in a variety of severe neurological conditions among which the severe cranioencephalic traumatism,<a class="elsevierStyleCrossRefs" href="#bib0080"><span class="elsevierStyleSup">6,7</span></a> the acute bacterial meningitis,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> and the acute ischaemic stroke<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> are the main conditions due to their frequency and impact on healthcare. In all of them without exception, the hypothermia has given negative or detrimental results in recent significant clinical trials (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The absence of effectiveness of hypothermia in such different clinical circumstances seriously questions the biological plausibility of this therapy in neurocritical patients, and the excessive amount of adverse events and increased mortality in some patients<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">7–9</span></a> makes us think about implementing a moratorium in its use.</p><p id="par0040" class="elsevierStylePara elsevierViewall">It is always bad news when a therapy is ineffective or detrimental; at least, the lessons learned from the clinical trials should avoid making more mistakes, spending more money, or causing iatrogenia. <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the evidence from clinical trials conducted to assess the effects of induced hypothermia on mortality and neurological recovery in the management of recovered cardiac arrests; this effect was assessed by authors using one random-effects meta-analysis with the STATA v 13.1 statistics package. We may conclude that hypothermia has not proven its effectiveness in the management of cardiac arrests, or other diseases of the central nervous system (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>); today there is enough information to withdraw the recommendation to use hypothermia and if the scientific societies involved think that there is enough uncertainty (“equipoise”), they may promote the use of a new clinical trial to provide us with definitive information on what temperature should we used in the management of patients who suffer RCA. Meanwhile, the existing evidence claims that hypothermia should be avoided, and that the active control of temperature should occur in the range of normotherapy, or minimal hypothermia (36<span class="elsevierStyleHsp" style=""></span>°C)–not lower.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflict of interest</span><p id="par0045" class="elsevierStylePara elsevierViewall">The authors declare that while conducting this paper there were no conflicts of interests linked whatsoever.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-12-23" "fechaAceptado" => "2017-04-05" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Palencia Herrejón E, Díaz Díaz D. Hipotermia terapéutica: tiempo para una moratoria. Med Intensiva. 2017;41:425–428.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4268 "Ancho" => 3167 "Tamanyo" => 653323 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hypothermia induced in recovered cardiac arrest. Mortality and neurological recovery (random-effects meta-analysis model<span class="elsevierStyleSup">a</span>). (A) Effect of hypothermia on mortality. (B) Effect of hypothermia on neurological recovery. The confidence intervals, and the estimated prediction intervals are included<span class="elsevierStyleSup">a</span>. The random-effects meta-analysis model penalizes studies of large samples and low risk of bias such as Nielsen's compared to studies of small samples and high risk of bias.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Risk of bias</span>: A: high; B: low; D: unknown. <span class="elsevierStyleItalic">Scores</span>: A: 2; B: 0; D: 1 (higher scores are indicative of higher risk of bias).</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Source</span>: Hypothermia after.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a>, Bernard et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and Nielsen et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p>" "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Risk of bias</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Holzer \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Bernard \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Nielsen \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1. Randomization sequence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2. Blinded randomization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3. Blinded participants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4. Blinded assessors \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">5. Balanced groups \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6. Estimation of sample size \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">7. Intermediate analyses \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">8. Intention-to-treat analysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9. Losses to follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">10. Selective assessment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">11. Trial prospective registry \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">12. Publication of the protocol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">13. Funding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">14. Protocol of predefined limitation of therapeutic effort \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">15. Unplanned completion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Final grade \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Risk of bias score (0–30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1520375.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Other aspects</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Number of patients included \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">275 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">939 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Relative weight per sample size \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Low \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Low \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Optimal management of the control group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Contemporaneity of the study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Medium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Medium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">High \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1520377.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Risk of bias in Holzer (HACA), Bernard, and Nielsen's studies on therapeutic hypothermia after recovered cardiac arrests.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">RCA: recovered cardiac arrest; CET: cranioencephalic traumatism.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Trial \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Result \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cardiac arrest \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Nielsen et al., 2013<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">939 patients with RCA of cardiac origin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Negative \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cranioencephalic traumatism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NABIS-II, 2011<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">108 patients with nonpenetrating serious CET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prematurely interrupted due to futility \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cranioencephalic traumatism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Andrews et al., 2015<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">387 patients with serious CET and intracranial hypertension \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prematurely interrupted due to worse results in the hypothermia group \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Meningitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mourvillier et al., 2013<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">98 comatose patients with severe bacterial meningitis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Prematurely interrupted due to higher mortality in the hypothermia group \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ischaemic stroke \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Llanos Méndez and Prieto Uceda, 2014<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systematic review and meta-analysis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">More adverse events with hypothermia; tendency to higher mortality with hypothermia \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1520376.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The largest and most recent clinical trials on induced hypothermia in neurocritical patients.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "Hypothermia After Cardiac Arrest Study Group" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa012689" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2002" "volumen" => "346" "paginaInicial" => "549" "paginaFinal" => "556" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11856793" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0060" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 6 | 8 |
| 2024 October | 69 | 58 | 127 |
| 2024 September | 81 | 56 | 137 |
| 2024 August | 76 | 68 | 144 |
| 2024 July | 115 | 42 | 157 |
| 2024 June | 64 | 90 | 154 |
| 2024 May | 60 | 49 | 109 |
| 2024 April | 69 | 42 | 111 |
| 2024 March | 50 | 40 | 90 |
| 2024 February | 41 | 42 | 83 |
| 2024 January | 39 | 34 | 73 |
| 2023 December | 44 | 30 | 74 |
| 2023 November | 42 | 49 | 91 |
| 2023 October | 39 | 47 | 86 |
| 2023 September | 41 | 34 | 75 |
| 2023 August | 36 | 26 | 62 |
| 2023 July | 33 | 28 | 61 |
| 2023 June | 50 | 20 | 70 |
| 2023 May | 65 | 34 | 99 |
| 2023 April | 58 | 29 | 87 |
| 2023 March | 75 | 28 | 103 |
| 2023 February | 51 | 35 | 86 |
| 2023 January | 49 | 24 | 73 |
| 2022 December | 81 | 58 | 139 |
| 2022 November | 83 | 48 | 131 |
| 2022 October | 80 | 45 | 125 |
| 2022 September | 59 | 45 | 104 |
| 2022 August | 45 | 44 | 89 |
| 2022 July | 47 | 47 | 94 |
| 2022 June | 33 | 25 | 58 |
| 2022 May | 49 | 33 | 82 |
| 2022 April | 42 | 51 | 93 |
| 2022 March | 41 | 52 | 93 |
| 2022 February | 42 | 45 | 87 |
| 2022 January | 38 | 29 | 67 |
| 2021 December | 62 | 50 | 112 |
| 2021 November | 74 | 43 | 117 |
| 2021 October | 121 | 63 | 184 |
| 2021 September | 51 | 37 | 88 |
| 2021 August | 28 | 37 | 65 |
| 2021 July | 40 | 21 | 61 |
| 2021 June | 47 | 37 | 84 |
| 2021 May | 64 | 58 | 122 |
| 2021 April | 149 | 86 | 235 |
| 2021 March | 108 | 49 | 157 |
| 2021 February | 125 | 51 | 176 |
| 2021 January | 85 | 38 | 123 |
| 2020 December | 95 | 27 | 122 |
| 2020 November | 78 | 37 | 115 |
| 2020 October | 69 | 25 | 94 |
| 2020 September | 56 | 30 | 86 |
| 2020 August | 46 | 35 | 81 |
| 2020 July | 66 | 39 | 105 |
| 2020 June | 81 | 21 | 102 |
| 2020 May | 58 | 21 | 79 |
| 2020 April | 104 | 27 | 131 |
| 2020 March | 40 | 15 | 55 |
| 2020 February | 134 | 48 | 182 |
| 2020 January | 50 | 32 | 82 |
| 2019 December | 52 | 26 | 78 |
| 2019 November | 64 | 29 | 93 |
| 2019 October | 57 | 22 | 79 |
| 2019 September | 54 | 28 | 82 |
| 2019 August | 43 | 20 | 63 |
| 2019 July | 43 | 27 | 70 |
| 2019 June | 26 | 15 | 41 |
| 2019 May | 99 | 35 | 134 |
| 2019 April | 49 | 34 | 83 |
| 2019 March | 49 | 28 | 77 |
| 2019 February | 43 | 43 | 86 |
| 2019 January | 49 | 35 | 84 |
| 2018 December | 83 | 36 | 119 |
| 2018 November | 151 | 48 | 199 |
| 2018 October | 89 | 31 | 120 |
| 2018 September | 37 | 16 | 53 |
| 2018 August | 45 | 15 | 60 |
| 2018 July | 70 | 22 | 92 |
| 2018 June | 88 | 14 | 102 |
| 2018 May | 38 | 13 | 51 |
| 2018 April | 81 | 23 | 104 |
| 2018 March | 423 | 40 | 463 |
| 2018 February | 30 | 15 | 45 |
| 2018 January | 1 | 1 | 2 |
| 2017 November | 1 | 0 | 1 |
| 2017 October | 2 | 1 | 3 |
| 2017 September | 2 | 0 | 2 |
| 2017 July | 0 | 1 | 1 |
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