Editorial
Crash 3. A new international effort in the management of traumatic hemorrhagic brain damage
Crash 3. Un nuevo esfuerzo internacional para el manejo de la lesión cerebral hemorrágica traumática
M.A. Muñoz-Sánchez, J.J. Egea-Guerrero
, F. Murillo-Cabezas, on behalf of the Spanish CRASH-3 Collaborators
Corresponding author
UGC Cuidados Críticos y Urgencias, Hospital Universitario Virgen del Rocío, Sevilla, Spain
Read
1181
Timeswas read the article
615
Total PDF
566
Total HTML
Share statistics
array:22 [ "pii" => "S2173572712001415" "issn" => "21735727" "doi" => "10.1016/j.medine.2012.04.007" "estado" => "S300" "fechaPublicacion" => "2012-11-01" "aid" => "465" "copyright" => "Elsevier España, S.L. and SEMICYUC" "copyrightAnyo" => "2012" "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Med Intensiva. 2012;36:527-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2668 "formatos" => array:3 [ "EPUB" => 156 "HTML" => 1687 "PDF" => 825 ] ] "itemSiguiente" => array:18 [ "pii" => "S2173572712001336" "issn" => "21735727" "doi" => "10.1016/j.medine.2012.03.005" "estado" => "S300" "fechaPublicacion" => "2012-11-01" "aid" => "440" "copyright" => "Elsevier España, S.L. and SEMICYUC" "documento" => "article" "crossmark" => 0 "subdocumento" => "sco" "cita" => "Med Intensiva. 2012;36:529-30" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2415 "formatos" => array:3 [ "EPUB" => 166 "HTML" => 1521 "PDF" => 728 ] ] "en" => array:10 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Can we predict the duration of the decannulation process?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "529" "paginaFinal" => "530" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "¿Podemos predecir la duración del proceso de decanulación?" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.M. Añón" "autores" => array:1 [ 0 => array:2 [ "nombre" => "J.M." "apellidos" => "Añón" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572712001336?idApp=WMIE" "url" => "/21735727/0000003600000008/v1_201212101010/S2173572712001336/v1_201212101010/en/main.assets" ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>" "titulo" => "Crash 3. A new international effort in the management of traumatic hemorrhagic brain damage" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "527" "paginaFinal" => "528" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M.A. Muñoz-Sánchez, J.J. Egea-Guerrero, F. Murillo-Cabezas" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M.A." "apellidos" => "Muñoz-Sánchez" ] 1 => array:4 [ "nombre" => "J.J." "apellidos" => "Egea-Guerrero" "email" => array:2 [ 0 => "juanjoegea@hotmail.com" 1 => "juanj.egea.sspa@juntadeandalucia.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Murillo-Cabezas" ] 3 => array:1 [ "colaborador" => "on behalf of the Spanish CRASH-3 Collaborators" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "UGC Cuidados Críticos y Urgencias, Hospital Universitario Virgen del Rocío, Sevilla, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Crash 3. Un nuevo esfuerzo internacional para el manejo de la lesión cerebral hemorrágica traumática" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Despite the advances in recent decades in the monitorization, diagnosis and treatment of severe traumatic brain injury (STBI), and which have reduced mortality in the developed countries, 50% of all patients admitted to hospital due to STBI continue to suffer significant life-long sequelae.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The probability of death or of sequelae is largely dependent upon the amount of brain tissue destroyed, and this in turn is conditioned by the extent of the primary damage resulting from the magnitude of the biomechanical impact and by the different causes of secondary brain lesions which inexorably worsen the outcome.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Hemorrhagic lesions, in the form of intraaxial hematomas or extraaxial hematomas, are found in 50% of all STBIs and have a strong impact upon the outcome. In general, extraaxial lesions, specifically subdural hematomas and epidural hematomas, are identified from the first computed tomography (CT) scan after the traumatism, tend to be unilateral, and are mostly amenable to surgical drainage. In contrast, intraaxial lesions, in the form of intraparenchymal hematomas or hemorrhagic contusions, can be multiple, tend to increase in size or manifest as new lesions appearing in neighboring or distant areas in the first hours or days, and are difficult to deal with from the surgical perspective.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> It has been documented that in up to 50% of all cases, the hemorrhagic lesions increase in the hours following admission to hospital.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Servadei et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> reported that among the 16% of STBIs without mass-type lesions showing worsening on the successive CT scans, 74% exhibited a new hemorrhagic lesion that was not present in the CT study upon admission. However, the most significant aspect of the increase or appearance of hemorrhagic lesions is the neurological deterioration they cause, and their negative impact upon the functional and life prognosis of the patient.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The most widely accepted mechanism for explaining the expansion of hemorrhagic lesions is continued blood loss secondary to vessel disruption at the time of trauma. Recently, a new mechanism has been proposed<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> which could explain hemorrhagic progression of the initial injury, or the appearance of new lesions, due to late alteration of the cerebral microvasculature secondary to a molecular process triggered by the primary impact. The concomitant presence of coagulopathy−either latent or clearly demonstrable–would be responsible for the continuous bleeding, thus justifying the search for strategies to normalize coagulation.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> To date it has not been possible to firmly demonstrate the relationship between coagulation alterations and the late increase or appearance of brain hemorrhage in STBI. Nevertheless, Allard et al.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> observed progression of bleeding in 80% of the patients with some coagulation disorder versus in 36% without coagulation disorders.</p><p id="par0020" class="elsevierStylePara elsevierViewall">With the purpose of normalizing coagulation and interrupting the progression of bleeding in STBI, Zaaroor et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> used recombinant factor VII in 12 patients, with relative success in reducing the development of hemorrhagic damage. The limited number of patients involved precluded the drawing of conclusions, however. Posteriorly, in a clinical trial with this same drug in which its efficacy in application to traumatic brain hematoma was investigated, no decrease could be demonstrated in either mortality or in the hematoma progression rate on contrasting the treatment group versus the placebo series, at any of the doses tested.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> On the other hand, in a series of patients with severe bleeding (trauma and perisurgical patients), recombinant factor VII produced thrombotic complications in over 6% of the cases−fundamentally in arterial territories.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> An added consideration here is the high cost of the drug, which presently makes it inaccessible in many countries.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In contrast, tranexamic acid, an inexpensive and widely used antifibrinolytic agent, significantly lowered mortality among trauma patients with hemorrhagic shock,<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> with no additional increase in thrombotic complications. In a traumatic brain injury subgroup comprising individuals at risk or with significant extracranial bleeding and belonging to this same clinical trial, a cohort nested case-control study was made with the primary aim of determining whether tranexamic acid reduces the progression of intracranial bleeding.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The investigation comprised 133 traumatic brain injury cases in the treatment arm and 137 subjects in the placebo arm. Forty-eight hours after trauma in the treated group, after adjusting for age, level of consciousness and initial bleeding volume, the authors found the mean total volume increment of the intracranial hematoma to be 3.8<span class="elsevierStyleHsp" style=""></span>ml less than that in the placebo group, and mortality furthermore was seen to be lower in the treated series (11% versus 18%). Likewise, the treatment group presented a lesser rate of new focal ischemic lesions attributable to the hemostatic drug (5% versus 9%).</p><p id="par0030" class="elsevierStylePara elsevierViewall">These promising results have led to the proposal of a new randomized, placebo-controlled, multicenter, international clinical trial involving patients with traumatic brain injuries, a Glasgow score of <12 points, and intracranial hemorrhagic lesions. The primary objective is to determine whether the early administration of tranexamic acid improves the diagnosis of these individuals. This trial, known as Crash 3 (information available at <a href="http://crash3.lshtm.ac.uk/">http://crash3.lshtm.ac.uk</a>), is currently in the screening phase for new research sites. To date, 8 Spanish hospitals, including our own, have entered the project. We consider that this clinical trial offers an opportunity to contribute to medical knowledge in a field where the therapeutic repertoire is severely limited. Moreover, the study will allow the inclusion of those Spanish Units treating moderate and severe traumatic brain injury cases that wish to participate in a consolidated and reputed international research network, the CRASH Trial Collaborators−the results of which are accepted for publication by the leading medical journals.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,15</span></a></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle">Conflict of interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</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 "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara">Please cite this article as: Muñoz-Sánchez MA, et al. Crash 3. Un nuevo esfuerzo internacional para el manejo de la lesión cerebral hemorrágica traumática. Med Intensiva. 2012;36:527–8.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of long-term disability following traumatic brain injury hospitalization. United States, 2003" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.W. Selassie" 1 => "E. Zaloshnja" 2 => "J.A. Langlois" 3 => "T. Miller" 4 => "P. Jones" 5 => "C. Steiner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.HTR.0000314531.30401.39" "Revista" => array:7 [ "tituloSerie" => "J Head Trauma Rehabil" "fecha" => "2008" "volumen" => "23" "paginaInicial" => "123" "paginaFinal" => "131" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18362766" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0161642010003118" "estado" => "S300" "issn" => "01616420" ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The prognostic value of the temporal course of S100 beta protein in post-acute severe brain injury: a prospective and observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Murillo-Cabezas" 1 => "M.A. Muñoz-Sánchez" 2 => "M.D. Rincón-Ferrari" 3 => "J.F. Martín-Rodríguez" 4 => "R. Amaya-Villar" 5 => "S. García-Gómez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3109/02699051003652823" "Revista" => array:6 [ "tituloSerie" => "Brain Inj" "fecha" => "2010" "volumen" => "24" "paginaInicial" => "609" "paginaFinal" => "619" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20235763" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural history of brain contusion: an analysis of radiological and clinical progression" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H. Alahmadi" 1 => "S. Vachhrajani" 2 => "M.D. Cusimano" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3171/2009.5.JNS081369" "Revista" => array:7 [ "tituloSerie" => "J Neurosurg" "fecha" => "2010" "volumen" => "112" "paginaInicial" => "1139" "paginaFinal" => "1145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19575576" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0161642009005685" "estado" => "S300" "issn" => "01616420" ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Progression of traumatic intracerebral hemorrhage: a prospective observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R.K. Narayan" 1 => "A.I. Maas" 2 => "F. Servadei" 3 => "B.E. Skolnick" 4 => "M.N. Tillinger" 5 => "L.F. Marshall" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/neu.2007.0385" "Revista" => array:6 [ "tituloSerie" => "J Neurotrauma" "fecha" => "2008" "volumen" => "25" "paginaInicial" => "629" "paginaFinal" => "639" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18491950" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The value of the “worst” computed tomographic scan in clinical studies of moderate and severe head injury. European Brain Injury Consortium" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Servadei" 1 => "G.D. Murray" 2 => "K. Penny" 3 => "G.M. Teasdale" 4 => "M. Dearden" 5 => "F. Iannotti" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Neurosurgery" "fecha" => "2000" "volumen" => "46" "paginaInicial" => "70" "paginaFinal" => "75" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10626937" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0161642010001867" "estado" => "S300" "issn" => "01616420" ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intracranial bleeding in patients with traumatic brain injury: a prognostic study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P. Perel" 1 => "I. Roberts" 2 => "O. Bouamra" 3 => "M. Woodford" 4 => "J. Mooney" 5 => "F. Lecky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-227X-9-15" "Revista" => array:5 [ "tituloSerie" => "BMC Emerg Med" "fecha" => "2009" "volumen" => "9" "paginaInicial" => "15" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19650902" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemorrhagic progression of a contusion after traumatic brain injury: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "D. Kurland" 1 => "C. Hong" 2 => "B. Aarabi" 3 => "V. Gerzanich" 4 => "J.M. Simard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/neu.2011.2122" "Revista" => array:6 [ "tituloSerie" => "J Neurotrauma" "fecha" => "2012" "volumen" => "29" "paginaInicial" => "19" "paginaFinal" => "31" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21988198" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prognostic value of admission laboratory parameters in traumatic brain injury: results from the IMPACT study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.G. Van Beek" 1 => "A.N. Mushkudiani" 2 => "E.W. Steyerberg" 3 => "I. Butcher" 4 => "G.S. McHugh" 5 => "J. Lu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/neu.2006.0034" "Revista" => array:7 [ "tituloSerie" => "J Neurotrauma" "fecha" => "2007" "volumen" => "24" "paginaInicial" => "315" "paginaFinal" => "328" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17375996" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0161642008006064" "estado" => "S300" "issn" => "01616420" ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Abnormal coagulation tests are associated with progression of traumatic intracranial hemorrhage" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.B. Allard" 1 => "S. Scarpelini" 2 => "S.G. Rhind" 3 => "A.J. Baker" 4 => "P.N. Shek" 5 => "H. Tien" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/TA.0b013e3181ad5d37" "Revista" => array:6 [ "tituloSerie" => "J Trauma" "fecha" => "2009" "volumen" => "67" "paginaInicial" => "959" "paginaFinal" => "967" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19901655" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Administration off label of recombinant factor-VIIa (rFVIIa) to patients with blunt or penetrating brain injury without coagulopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M. Zaaroor" 1 => "J.F. Soustiel" 2 => "B. Brenner" 3 => "Y. Bar-Lavie" 4 => "U. Martinovitz" 5 => "L. Levi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Acta Neurochirg (Wien)" "fecha" => "2008" "volumen" => "150" "paginaInicial" => "663" "paginaFinal" => "668" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "R.K. Narayan" 1 => "A.I. Maas" 2 => "L.F. Marshall" 3 => "F. Servadei" 4 => "B.E. Skolnick" 5 => "M.N. Tillinger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1227/01.neu.0000316281.07124.ea" "Revista" => array:6 [ "tituloSerie" => "Neurosurgery" "fecha" => "2008" "volumen" => "62" "paginaInicial" => "776" "paginaFinal" => "786" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18596428" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alternativas terapéuticas en la hemorragia masiva" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E. Fernández-Hinojosa" 1 => "F. Murillo-Cabezas" 2 => "A. Puppo Moreno" 3 => "S.R. Leal Noval" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medin.2011.11.010" "Revista" => array:6 [ "tituloSerie" => "Med Intensiva" "fecha" => "2012" "volumen" => "36" "paginaInicial" => "496" "paginaFinal" => "503" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22321860" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "CRASH-2 Trial Collaborators" 1 => "H. Shakur" 2 => "I. Roberts" 3 => "R. Bautista" 4 => "J. Caballero" 5 => "T. Coats" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(10)60835-5" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2010" "volumen" => "376" "paginaInicial" => "23" "paginaFinal" => "32" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20554319" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "El ácido tranexámico disminuye la mortalidad del <span class="elsevierStyleItalic">shock</span> hemorrágico traumático" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Muñoz-Sánchez" 1 => "F. Murillo-Cabezas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medin.2011.01.012" "Revista" => array:6 [ "tituloSerie" => "Med Intensiva" "fecha" => "2011" "volumen" => "35" "paginaInicial" => "286" "paginaFinal" => "287" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21377233" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Crash-2 Trial Collaborators" 1 => "Intracranial Bleeding Study" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "BMJ" "fecha" => "2011" "volumen" => "343" "paginaInicial" => "d3795" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21724564" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735727/0000003600000008/v1_201212101010/S2173572712001415/v1_201212101010/en/main.assets" "Apartado" => array:4 [ "identificador" => "401" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Editorials" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735727/0000003600000008/v1_201212101010/S2173572712001415/v1_201212101010/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572712001415?idApp=WMIE" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 13 | 17 |
| 2024 October | 41 | 57 | 98 |
| 2024 September | 52 | 43 | 95 |
| 2024 August | 69 | 53 | 122 |
| 2024 July | 33 | 26 | 59 |
| 2024 June | 33 | 39 | 72 |
| 2024 May | 31 | 31 | 62 |
| 2024 April | 30 | 44 | 74 |
| 2024 March | 29 | 32 | 61 |
| 2024 February | 28 | 36 | 64 |
| 2024 January | 26 | 37 | 63 |
| 2023 December | 31 | 43 | 74 |
| 2023 November | 23 | 21 | 44 |
| 2023 October | 21 | 27 | 48 |
| 2023 September | 24 | 34 | 58 |
| 2023 August | 22 | 15 | 37 |
| 2023 July | 27 | 30 | 57 |
| 2023 June | 23 | 16 | 39 |
| 2023 May | 19 | 18 | 37 |
Show all
