was read the article
array:23 [ "pii" => "S2173572714000381" "issn" => "21735727" "doi" => "10.1016/j.medine.2013.04.004" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "594" "copyright" => "Elsevier España, S.L. and SEMICYUC" "copyrightAnyo" => "2012" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Med Intensiva. 2014;38:278-82" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2117 "formatos" => array:3 [ "EPUB" => 171 "HTML" => 1223 "PDF" => 723 ] ] "itemSiguiente" => array:18 [ "pii" => "S2173572714000393" "issn" => "21735727" "doi" => "10.1016/j.medine.2013.06.003" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "605" "copyright" => "Elsevier España, S.L. and SEMICYUC" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Med Intensiva. 2014;38:288-96" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2120 "formatos" => array:3 [ "EPUB" => 153 "HTML" => 1270 "PDF" => 697 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "External validation of the Simplified Acute Physiology Score (SAPS) 3 in Spain" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "288" "paginaFinal" => "296" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Validación externa de la puntuación de fisiología aguda simplificada (SAPS) 3 en España" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2580 "Ancho" => 1558 "Tamanyo" => 109036 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">ROC curve. Discrimination for Simplified Acute Physiology Score 3 model tested using the area under the Receiver Operating Characteristics curve (ROC area).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. López-Caler, M. García-Delgado, J. Carpio-Sanz, J. Álvarez-Rodríguez, E. Aguilar-Alonso, E. Castillo-Lorente, J.E. Barrueco-Francioni, R. Rivera-Fernández" "autores" => array:8 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "López-Caler" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "García-Delgado" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Carpio-Sanz" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Álvarez-Rodríguez" ] 4 => array:2 [ "nombre" => "E." "apellidos" => "Aguilar-Alonso" ] 5 => array:2 [ "nombre" => "E." "apellidos" => "Castillo-Lorente" ] 6 => array:2 [ "nombre" => "J.E." "apellidos" => "Barrueco-Francioni" ] 7 => array:2 [ "nombre" => "R." "apellidos" => "Rivera-Fernández" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572714000393?idApp=WMIE" "url" => "/21735727/0000003800000005/v1_201406130020/S2173572714000393/v1_201406130020/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173572714000332" "issn" => "21735727" "doi" => "10.1016/j.medine.2013.04.003" "estado" => "S300" "fechaPublicacion" => "2014-06-01" "aid" => "596" "copyright" => "Elsevier España, S.L. and SEMICYUC" "documento" => "article" "crossmark" => 0 "subdocumento" => "fla" "cita" => "Med Intensiva. 2014;38:271-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 3804 "formatos" => array:3 [ "EPUB" => 172 "HTML" => 2758 "PDF" => 874 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Acute renal failure according to the RIFLE and AKIN criteria: A multicenter study" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "271" "paginaFinal" => "277" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Insuficiencia renal aguda según RIFLE y AKIN: estudio multicéntrico" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "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" => 971 "Ancho" => 1547 "Tamanyo" => 70390 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Acute renal failure according to the AKIN and RIFLE classifications, and both classifications jointly.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G. Salgado, M. Landa, D. Masevicius, S. Gianassi, J.E. San-Román, L. Silva, M. Gimenez, O. Tejerina, P. Díaz-Cisneros, F. Ciccioli, J.L. do Pico" "autores" => array:11 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Salgado" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Landa" ] 2 => array:2 [ "nombre" => "D." "apellidos" => "Masevicius" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Gianassi" ] 4 => array:2 [ "nombre" => "J.E." "apellidos" => "San-Román" ] 5 => array:2 [ "nombre" => "L." "apellidos" => "Silva" ] 6 => array:2 [ "nombre" => "M." "apellidos" => "Gimenez" ] 7 => array:2 [ "nombre" => "O." "apellidos" => "Tejerina" ] 8 => array:2 [ "nombre" => "P." "apellidos" => "Díaz-Cisneros" ] 9 => array:2 [ "nombre" => "F." "apellidos" => "Ciccioli" ] 10 => array:2 [ "nombre" => "J.L." "apellidos" => "do Pico" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210569113001083" "doi" => "10.1016/j.medin.2013.04.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210569113001083?idApp=WMIE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572714000332?idApp=WMIE" "url" => "/21735727/0000003800000005/v1_201406130020/S2173572714000332/v1_201406130020/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Protein C zymogen in adults with severe sepsis or septic shock" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "278" "paginaFinal" => "282" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M. Crivellari, S. Silvetti, C. Gerli, G. Landoni, A. Franco, T. Bove, F. Pappalardo, A. Zangrillo" "autores" => array:8 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Crivellari" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Silvetti" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Gerli" ] 3 => array:4 [ "nombre" => "G." "apellidos" => "Landoni" "email" => array:1 [ 0 => "landoni.giovanni@hsr.it" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Franco" ] 5 => array:2 [ "nombre" => "T." "apellidos" => "Bove" ] 6 => array:2 [ "nombre" => "F." "apellidos" => "Pappalardo" ] 7 => array:2 [ "nombre" => "A." "apellidos" => "Zangrillo" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Anesthesia and Intensive Care, San Raffaele Scientific Institute, Milano, Italy" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Zimógeno de proteína C en adultos con sepsis grave o choque séptico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 873 "Ancho" => 1442 "Tamanyo" => 78669 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Trend of protein C zymogen during the 72<span class="elsevierStyleHsp" style=""></span>h of administration.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Severe sepsis and septic shock are life-threatening medical emergencies and are among the most significant challenges in critical care. Mortality rates approach 30–50%, and can be as high as 90% when multiple organ dysfunctions ensue.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Improvement in survival rates was achieved through early broad-spectrum antibiotic administration, organ supportive therapy, and, until recently, through Recombinant Human Activated Protein C (rhAPC) in selected patients at low risk of bleeding. A recent randomized study showed that rhAPC did not significantly reduce mortality at 28 or 90 days, as compared with placebo, in patients with septic shock.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Protein C (PC) is the vitamin K-dependent zymogen of a serine protease with antithrombotic, anti-inflammatory, and profibrinolytic properties.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Due to its action on the coagulation pathway, rhAPC, the active form of drug, exposes treated patients to a serious hemorrhagic risk<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–8</span></a> and its administration was subject to careful evaluation of the risk-to-benefit ratio. Attempts were made to use protein C zymogen, its “inactive” precursor, endowed with anti-inflammatory activity but devoid of anticoagulant properties. Among its advantages, PC is activated “on demand” in sites of major thrombin formation, and this is expected to limit or eliminate unwanted bleeding.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Few case series have been published on adult septic patients receiving protein C zymogen. We hereby describe the largest case series of adult patients with severe sepsis or septic shock receiving PC in a single center.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients and methods, setting and study population</span><p id="par0020" class="elsevierStylePara elsevierViewall">After ethical committee approval and with patients’ written consent, we collected data from 23 adult patients with severe sepsis or septic shock admitted to two intensive care units (ICU) of San Raffaele Scientific Institute over a 2-year period. Eleven of these 23 patients were already reported in other publications.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9,10</span></a> Inclusion criteria were represented by age >18 years, diagnosis of severe sepsis (acute organ dysfunction secondary to documented or suspected infection) or septic shock (severe sepsis plus hypotension not reversed with fluid resuscitation) and two or more organ failures due to sepsis of recent onset (less than 48<span class="elsevierStyleHsp" style=""></span>h); contraindication to receive rhAPC (recent major surgery in most patients); being admitted in the ICU. Exclusion criteria were represented by known allergy to the study product and inclusion in other studies.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In addition to current standard-of-care therapies for severe sepsis and septic shock, patients received PC concentrates (Ceprotin<span class="elsevierStyleSup">®</span>, Baxter, Wien) administered as a starting bolus (50<span class="elsevierStyleHsp" style=""></span>IU/kg) plus a 3<span class="elsevierStyleHsp" style=""></span>IU/kg/h continuous infusion over 72<span class="elsevierStyleHsp" style=""></span>h.</p><p id="par0030" class="elsevierStylePara elsevierViewall">We measured plasma PC activity, prothrombin time (PT), activated partial thromboplastin time (aPTT), Platelets (PLTs), C-reactive protein (CRP), white cell count (WBC), D-dimer and fibrinogen (FG) values at baseline, at 6 and 12<span class="elsevierStyleHsp" style=""></span>h after PC concentrate administration, then every 12<span class="elsevierStyleHsp" style=""></span>h for 60<span class="elsevierStyleHsp" style=""></span>h. The sequential organ assessment failure (SOFA) score, the Acute Physiology and Chronic Health Evaluation (APACHE II) score, and the simplified acute physiology score (SAPS II) were recorded at baseline (when patient received PC zymogen), daily for 7 days.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Laboratory methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">Serial venous samples (4.5<span class="elsevierStyleHsp" style=""></span>ml) were collected in siliconized Vacutainer tubes (Becton-Dickinson, Plymouth, UK) containing (0.5<span class="elsevierStyleHsp" style=""></span>ml) tri-sodium citrate (0.129<span class="elsevierStyleHsp" style=""></span>M) and in tubes containing 0.5<span class="elsevierStyleHsp" style=""></span>ml of a mixture of tri-sodium citrate and benzamidine–HCl (200<span class="elsevierStyleHsp" style=""></span>mM) at the following times: before the bolus dose, 6<span class="elsevierStyleHsp" style=""></span>h after bolus and every 12<span class="elsevierStyleHsp" style=""></span>h thereafter up to 72<span class="elsevierStyleHsp" style=""></span>h. Within 1<span class="elsevierStyleHsp" style=""></span>h from collection, platelet poor plasma was obtained by centrifugation for 10<span class="elsevierStyleHsp" style=""></span>min at 2000<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">g</span> at room temperature. PT (Hemoliance Recombiplastin, Instrumentation Laboratory, Lexington, MA), aPTT (STA aPTT Kaolin, Diagnostica Stago, Asnier sur Seine, France), FG (clotting assay, STA Fibrinogen, Stago), and D-dimer (STA Liatest D-D, Stago) determinations were performed on fresh citrated plasma samples with an automated coagulometer (STA, Stago). Plasma aliquots were snap-frozen with methanol and dry ice and stored at −70<span class="elsevierStyleHsp" style=""></span>°C for additional measurements in citrated plasma of PC anticoagulant activity (STA Protein C, Stago), and antithrombin (amidolytic activity, STA Antithrombin, Stago). Blood samples collected in tri-sodium citrate and benzamidine–HCl were also centrifuged as described above with plasma aliquots snap-frozen and stored at −70<span class="elsevierStyleHsp" style=""></span>°C. Within one month, prothrombin fragment 1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2 (F1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2, Enzygnost F1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2, Dade-Behring, Marburg) and thrombin-antithrombin III complex (TAT Enzygnost TAT micro, Dade-Behring, Marburg) were measured with commercially available ELISA kits.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistics</span><p id="par0040" class="elsevierStylePara elsevierViewall">Collected data were analyzed through repeated measure ANOVA, chi-square (<span class="elsevierStyleItalic">χ</span><span class="elsevierStyleSup">2</span>), and Friedman's test using SPSS<span class="elsevierStyleSup">®</span> 13 statistical package (Chicago, Illinois). The <span class="elsevierStyleItalic">Z</span>-test for two proportions was employed to compare expected versus observed mortality. A <span class="elsevierStyleItalic">p</span>-value <0.05 was considered statistically significant.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">We enrolled 23 consecutive patients with severe sepsis or septic shock. Twenty-one (91%) of them were surgical patients (18 cardiac surgery and one each for thoracic, vascular, urologic and abdominal surgery) and 1 patient presented to the emergency department with septic shock. Mean patient age was 63<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12 years (range 25–77) and 4 (17%) were female.</p><p id="par0050" class="elsevierStylePara elsevierViewall">All patients showed signs of sepsis-induced multiorgan dysfunction syndrome: 22 patients had respiratory failure, 16 had acute renal failure requiring renal replacement therapy and 16 had pharmacological sedation. The average APACHE II was 25<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5, mean SAPS II was 58<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14, and mean SOFA score was 14<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2. The timing from surgery (or ICU admission) to the first cultural sample was 5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.7 days while the timing from surgery (or ICU admission) to PC administration was 7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.1 days. Seventeen patients had single or multiple cultural examination (in 4 patients the germs were identified in multiple sites and in 6 patients more than one germ was identified). Blood culture (8 patients), bronchoalveolar lavage (10 patients) and urine culture (2 patients) were positive for the following germs: <span class="elsevierStyleItalic">Staphylococcus</span> spp. (7 patients), <span class="elsevierStyleItalic">Escherichia coli</span> (6 patients), <span class="elsevierStyleItalic">Acinetobacter</span> spp. (2 patients), <span class="elsevierStyleItalic">Proteus</span>, <span class="elsevierStyleItalic">Serratia marcescens</span>, <span class="elsevierStyleItalic">Streptococcus</span> spp., <span class="elsevierStyleItalic">Enterobacter cloacae</span>, <span class="elsevierStyleItalic">Klebsiella pneumonia</span>, <span class="elsevierStyleItalic">Citrobacter</span> and <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Baseline plasma PC activity was 33<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>18% [normal values 65–140%], and increased to 66<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>22% at 6<span class="elsevierStyleHsp" style=""></span>h after PC bolus (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). Afterwards, it remained constantly within normal range values during PC concentrate continuous infusion and was 90<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>25% at 72<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 to baseline) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Changes in laboratory variables after protein C concentrate administration showed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. A significantly increasing of ATIII values from 49<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15 to 81<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19 was observed at 60<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04), FG and fibrin D-dimer showed a trend toward reduction and PLT count tended to increase from 130 (×10<span class="elsevierStyleSup">9</span>/l)<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>121 (×10<span class="elsevierStyleSup">9</span>/l) to 120 (×10<span class="elsevierStyleSup">9</span>/l)<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>140 (×10<span class="elsevierStyleSup">9</span>/l) during the 60<span class="elsevierStyleHsp" style=""></span>h period.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">On the inflammatory viewpoint PCR values significantly decreased from 204<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>130.1 to 59<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>63.0 during 60<span class="elsevierStyleHsp" style=""></span>h (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01).</p><p id="par0070" class="elsevierStylePara elsevierViewall">We observed a rapid reduction of the SOFA (from 14<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2 to 7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>), the SAPS II (from 58<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14 to 37<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), and the APACHE II (from 25<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5 to 14<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) scores at 7 days.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Septic shock mortality rates in the literature approach 60% and the expected mortality in our sample population was 53<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17%. The <span class="elsevierStyleItalic">Z</span>-test for two proportions evidenced a significant reduction between the expected mortality (53%) and the observed mortality 30% (<span class="elsevierStyleItalic">Z</span> value<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.99, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.046). In fact, 7 patients of our sample died (30%), all of them by refractory shock. A post hoc analysis showed that the best results in terms of crude mortality were observed in the subgroup of 11 patients with a cardiac index ≥2.5<span class="elsevierStyleHsp" style=""></span>L/min/m<span class="elsevierStyleSup">2</span>. In that group, only 1 patient (9%) died (<span class="elsevierStyleItalic">Z</span> value<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3.5, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001).</p><p id="par0080" class="elsevierStylePara elsevierViewall">We observed two cases of hemorrhagic cystitis, respectively three days and two weeks after PC concentrate interruption. One case of bilateral jugular vein thrombosis was recorded as well. These phenomena could not be attributed to the drug administration. No bleeding complication was reported.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">To the best of our knowledge this is the largest case series ever reported on the use of PC zymogen. In this study we showed a favorable effects on coagulation, multiorgan function and survival in patients that received PC zymogen.</p><p id="par0090" class="elsevierStylePara elsevierViewall">PC levels increased from 33<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>18% to 66<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>22% [normal values 65–140%], at 6<span class="elsevierStyleHsp" style=""></span>h after PC bolus (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), and kept on increasing during the 72<span class="elsevierStyleHsp" style=""></span>h of administration (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 to baseline). Interestingly, all our patients had low baseline levels of PC. This finding is important because a low PC value is a strong predictor of unfavorable outcome<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11–14</span></a> and septic patients are associated with increased morbidity and mortality. Despite this baseline data we achieved a survival rate of 70%. Given the expected poor outcome on the basis of the score risks and our patients’ PC activity, the 70% survival rate may indicate that perhaps a beneficial drug effect on survival is present.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In our patients PC levels increased at 6<span class="elsevierStyleHsp" style=""></span>h after PC bolus and remained constant thereafter, furthermore ATIII levels significantly increased after drug administration.</p><p id="par0100" class="elsevierStylePara elsevierViewall">We also reported clinical benefit as documented by the significant reduction in the indices of organ dysfunction (the SOFA). Finally patient mortality was 30% versus the expected 53% and this difference was even more evident if only septic patients with cardiac index ≥2.5<span class="elsevierStyleHsp" style=""></span>L/min/m<span class="elsevierStyleSup">2</span> were considered (mortality was 9%).</p><p id="par0105" class="elsevierStylePara elsevierViewall">Consistently with the findings of the largest adult case series (20 patients) published so far<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> we achieved normalization of coagulation parameters as a increasing of ATIII, as indicated by prompt raise of plasma PC activity within normal values, and a decreasing of PCR levels; an improvement of indices of organ dysfunction and a beneficial effect on patient survival. Similar findings were noted in our previously published case series that included 9 of these 23 patients.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> A recent systematic review on all the published case reports and case series of adult septic patients receiving PC suggested that mortality rates are low when receiving this drug.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">One interesting finding of our case series is that the beneficial effects on survival were more important in the patients with high cardiac output. The results of our study are important especially in view of the paucity of drugs, techniques or strategies that might reduce perioperative mortality in critically ill patients.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Limitations</span><p id="par0115" class="elsevierStylePara elsevierViewall">Although this is the largest case series of adult patients receiving PC ever published in literature, the small sample size and the non randomized study design do not allow us to draw definitive conclusions on the beneficial effect of PC administration in severe sepsis or septic shock. Furthermore, we measured only PCR and not other inflammatory markers such as procalcitonin or interleukine-6. On top of this, we acknowledge that the diagnosis of sepsis after major surgery might be challenging and that SIRS without infection is to be taken into consideration. Lastly, in half of our patients sepsis was diagnosed in patients with ongoing LCOS, a condition that is frequent after cardiac surgery and that can further confound the clinical picture of these patients.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusions</span><p id="par0120" class="elsevierStylePara elsevierViewall">The favorable effects on coagulation, multiorgan function and survival suggest potential beneficial effects of PC concentrate on restoring homeostasis, at least as coagulation is concerned, and should raise interest in confirming our and others’ promising results through a randomized clinical trial or at least case match studies.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres345756" "titulo" => array:5 [ 0 => "Abstract" 1 => "Introduction" 2 => "Design, setting and participants" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec327356" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres345755" "titulo" => array:5 [ 0 => "Resumen" 1 => "Introducción" 2 => "Diseño, ámbito y participantes" 3 => "Resultados" 4 => "Conclusión" ] ] 3 => array:2 [ "identificador" => "xpalclavsec327357" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods, setting and study population" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Laboratory methods" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Statistics" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Results" ] 7 => array:3 [ "identificador" => "sec0030" "titulo" => "Discussion" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Limitations" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Conclusions" ] ] ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflict of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-11-20" "fechaAceptado" => "2013-04-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec327356" "palabras" => array:5 [ 0 => "Protein C zymogen" 1 => "Bleeding" 2 => "Sepsis" 3 => "Intensive care" 4 => "Critical care" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec327357" "palabras" => array:5 [ 0 => "Zimógeno de proteína C" 1 => "Hemorragia" 2 => "Sepsis" 3 => "Cuidados intensivos" 4 => "Cuidados críticos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Activated protein C is associated with a risk of bleeding and its effects on survival in septic shock patients are questionable. Protein C zymogen has no risk of bleeding and improves the outcome of patients with septic shock. We hereby describe the largest published case series of adult patients receiving protein C zymogen.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Design, setting and participants</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective study on 23 adult patients with severe sepsis or septic shock, two or more organ failures and at high risk for bleeding, treated with protein C zymogen (50<span class="elsevierStyleHsp" style=""></span>IU/kg bolus followed by continuous infusion of 3<span class="elsevierStyleHsp" style=""></span>IU/kg/h for 72<span class="elsevierStyleHsp" style=""></span>h).</p> <span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The <span class="elsevierStyleItalic">Z</span>-test evidenced a significant reduction between the expected mortality (53%) and the observed mortality 30% (<span class="elsevierStyleItalic">Z</span> value<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.99, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.046) in our sample population. Protein C levels increased from 34<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>18% to 66<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>22% at 6<span class="elsevierStyleHsp" style=""></span>h after PC bolus (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), and kept on increasing during 72<span class="elsevierStyleHsp" style=""></span>h of administration (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 to baseline). Sequential Organ Failure Assessment (SOFA), score of organ dysfunction, decreased from baseline to 7 days after administration of protein C from 14<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2 to 7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). No adverse event drug related was noted.</p> <span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Protein C zymogen administration is safe and its use in septic patients should be investigated through a randomized controlled trial.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0040">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La proteína C activada se asocia a un elevado riesgo de hemorragia, y sus efectos sobre la supervivencia en los pacientes con choque séptico son cuestionables. El zimógeno de proteína C no presenta ningún riesgo de hemorragia, y mejora los resultados en los pacientes con choque séptico. Describimos la serie de casos más amplia publicada de pacientes adultos tratados con zimógeno de proteína C.</p> <span class="elsevierStyleSectionTitle" id="sect0045">Diseño, ámbito y participantes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se ha llevado a cabo un estudio prospectivo en el que han participado 23 adultos con sepsis grave o choque séptico, 2 o más fallos orgánicos, y un elevado riesgo de hemorragia, tratados con zimógeno de proteína C (dosis en bolo de 50<span class="elsevierStyleHsp" style=""></span>UI/kg seguida de una infusión continua de 3<span class="elsevierStyleHsp" style=""></span>UI/kg/h durante 72<span class="elsevierStyleHsp" style=""></span>h).</p> <span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La prueba Z puso de manifiesto una disminución significativa entre la mortalidad prevista (53%), y la mortalidad observada 30% (valor Z<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1,99; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,046) en nuestra serie. Las concentraciones de proteína C incrementaron de 34<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>18% a 66<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>22% a las 6<span class="elsevierStyleHsp" style=""></span>h de la dosis en bolo (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001), y siguieron incrementando durante las 72<span class="elsevierStyleHsp" style=""></span>h siguientes a la administración (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001 respecto a la situación basal). La puntuación en la evaluación secuencial del fallo orgánico (SOFA) disminuyó entre la situación basal, y 7 días después de la administración de proteína C de 14<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2 a 7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4 (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,001). No se registraron reacciones farmacológicas adversas.</p> <span class="elsevierStyleSectionTitle" id="sect0055">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El zimógeno de proteína Z debería investigarse su utilización en los pacientes con sepsis mediante un estudio aleatorizado y controlado.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 873 "Ancho" => 1442 "Tamanyo" => 78669 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Trend of protein C zymogen during the 72<span class="elsevierStyleHsp" style=""></span>h of administration.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 707 "Ancho" => 1539 "Tamanyo" => 77708 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Variation of Sequential Organ Failure Assessment (SOFA), score during and after protein C zymogen administration.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Before bolus \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">After 6<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">12<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">24<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">36<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">48<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">60<span class="elsevierStyleHsp" style=""></span>h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span> value \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">aPTT (ratio) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">41<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>20.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">36<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>10.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.33 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">ATIII \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>26.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>21.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>23.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">81<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>18.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">D-dimer (mg/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.46 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FG (mg/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">550<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>163.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">526<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>204.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">626<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>209.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">672<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>116.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">717<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>120.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">674<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>137.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">654<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>134.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">INR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PCR (ng/ml) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">204<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>130.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">171<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>85.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">157<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>68.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">132<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>90.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">112<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>59.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>64.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>63.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Platelet count (×10<span class="elsevierStyleSup">9</span>/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">130<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>121 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">110<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>120 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">130<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>123 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">140<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>124 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">130<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>137 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">120<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.86 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">WBC counts (×10<span class="elsevierStyleSup">9</span>/l) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>11.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>17.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>21.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.97 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab515352.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Changes in laboratory variables throughout protein C concentrate administration.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:16 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The epidemiology of sepsis in the United States from 1979 through 2000" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G.S. Martin" 1 => "D.M. Mannino" 2 => "S. Eaton" 3 => "M. Moss" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa022139" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2003" "volumen" => "348" "paginaInicial" => "1546" "paginaFinal" => "1554" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12700374" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology of severe sepsis in the United States: analysis of incidence, outcome and associated costs of care" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.C. Angus" 1 => "W.T. Linde-Zwirble" 2 => "J. Lidicker" 3 => "G. Clermont" 4 => "J. Carcillo" 5 => "M.R. Pinsky" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2001" "volumen" => "29" "paginaInicial" => "1303" "paginaFinal" => "1310" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11445675" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drotrecogin alfa (activated) in adults with septic shock" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "For the PROWESS-SHOCK Study Group" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1202290" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "2055" "paginaFinal" => "2064" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22616830" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The protein C anticoagulant pathway" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "C.T. Esmon" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arterioscler Thromb" "fecha" => "1992" "volumen" => "12" "paginaInicial" => "135" "paginaFinal" => "145" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1311945" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy and safety of recombinant human activated protein C for severe sepsis" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "For the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group" "etal" => false ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJM200103083441001" "Revista" => array:6 [ "tituloSerie" => "New Eng J Med" "fecha" => "2001" "volumen" => "344" "paginaInicial" => "699" "paginaFinal" => "709" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11236773" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drotrecogin alfa (activated) for adults with severe sepsis and low risk of death" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Abraham" 1 => "P.F. Laterre" 2 => "R. Garg" 3 => "H. Levy" 4 => "D. Talwar" 5 => "B.L. Trzaskoma" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa050935" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2005" "volumen" => "353" "paginaInicial" => "1332" "paginaFinal" => "1341" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16192478" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Drotrecogin alfa (activated) treatment in severe sepsis from the global-label trial ENHANCE: further evidence for survival and safety and implication for early treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.L. Vincent" 1 => "G.R. Bernard" 2 => "R. Beale" 3 => "C. Doig" 4 => "C. Putensen" 5 => "J.F. Dhainaut" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2005" "volumen" => "33" "paginaInicial" => "2266" "paginaFinal" => "2277" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16215381" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation the use of drotrecogin alfa activated in adult severe sepsis: a Canadian multicenter observational study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Kanji" 1 => "M.M. Perreault" 2 => "C. Chant" 3 => "D. Williamson" 4 => "L. Burry" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-007-0555-9" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2007" "volumen" => "33" "paginaInicial" => "517" "paginaFinal" => "523" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17325837" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human protein C zymogen concentrate in patients with severe sepsis and multiple organ failure after adult cardiac surgery" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Crivellari" 1 => "P. Della Valle" 2 => "G. Landoni" 3 => "F. Pappalardo" 4 => "C. Gerli" 5 => "E. Bignami" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-009-1584-3" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2009" "volumen" => "35" "paginaInicial" => "1959" "paginaFinal" => "1963" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19649614" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human in protein C concentrates in adult septic patient" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Landoni" 1 => "M. Crivellari" 2 => "G. Monti" 3 => "C. Gerli" 4 => "P. Silvani" 5 => "A. Zangrillo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Signa Vitae" "fecha" => "2008" "volumen" => "3" "paginaInicial" => "13" "paginaFinal" => "17" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coagulation activation and tissue necrosis in meningococcal septic shock: severely reduced protein C levels predict a high mortality" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Fijnvandraat" 1 => "B. Derkx" 2 => "M. Peters" 3 => "R. Bijlmer" 4 => "A. Sturk" 5 => "M.H. Prins" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Thromb Haemost" "fecha" => "1995" "volumen" => "73" "paginaInicial" => "15" "paginaFinal" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7740486" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protein C/activated protein C pathway: overview of clinical trial results in severe sepsis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.F. Dhainaut" 1 => "S.B. Yan" 2 => "Y.E. Claessens" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Crit Care Med" "fecha" => "2004" "volumen" => "32" "numero" => "Suppl." "paginaInicial" => "S194" "paginaFinal" => "S201" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15118517" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protein C levels as prognostic indicator of outcome in sepsis and related diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.J. Fisher Jr." 1 => "S.B. Yan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Crit Care Med" "fecha" => "2000" "volumen" => "28" "numero" => "Suppl." "paginaInicial" => "S49" "paginaFinal" => "S56" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11007198" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Severe protein C deficiency predicts early death in severe sepsis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W.L. Macias" 1 => "D.R. Nelson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Crit Care Med" "fecha" => "2004" "volumen" => "32" "numero" => "Suppl." "paginaInicial" => "S223" "paginaFinal" => "S228" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15118522" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Protein C concentrate to restore physiological values in adult septic patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "F. Baratto" 1 => "F. Michielan" 2 => "M. Meroni" 3 => "A. Dal Palù" 4 => "A. Boscolo" 5 => "C. Ori" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-008-1140-6" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2008" "volumen" => "34" "paginaInicial" => "1707" "paginaFinal" => "1712" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18458873" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mortality reduction in cardiac anesthesia and intensive care: results of the first International Consensus Conference" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "G. Landoni" 1 => "J.G. Augoustides" 2 => "F. Guarracino" 3 => "F. Santini" 4 => "M. Ponschab" 5 => "D. Pasero" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "HSR Proc Intensive Care Cardiovasc Anesth" "fecha" => "2011" "volumen" => "3" "paginaInicial" => "9" "paginaFinal" => "19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23439940" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735727/0000003800000005/v1_201406130020/S2173572714000381/v1_201406130020/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/21735727/0000003800000005/v1_201406130020/S2173572714000381/v1_201406130020/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572714000381?idApp=WMIE" ]
Year/Month | Html | Total | |
---|---|---|---|
2024 November | 13 | 14 | 27 |
2024 October | 73 | 43 | 116 |
2024 September | 72 | 36 | 108 |
2024 August | 58 | 36 | 94 |
2024 July | 47 | 20 | 67 |
2024 June | 33 | 44 | 77 |
2024 May | 61 | 34 | 95 |
2024 April | 44 | 31 | 75 |
2024 March | 41 | 24 | 65 |
2024 February | 32 | 32 | 64 |
2024 January | 35 | 30 | 65 |
2023 December | 33 | 38 | 71 |
2023 November | 32 | 33 | 65 |
2023 October | 26 | 22 | 48 |
2023 September | 29 | 26 | 55 |
2023 August | 29 | 11 | 40 |
2023 July | 44 | 21 | 65 |
2023 June | 44 | 15 | 59 |
2023 May | 45 | 30 | 75 |
2023 April | 53 | 18 | 71 |
2023 March | 52 | 31 | 83 |
2023 February | 50 | 29 | 79 |
2023 January | 21 | 19 | 40 |
2022 December | 37 | 26 | 63 |
2022 November | 30 | 26 | 56 |
2022 October | 52 | 35 | 87 |
2022 September | 42 | 31 | 73 |
2022 August | 44 | 32 | 76 |
2022 July | 32 | 32 | 64 |
2022 June | 35 | 23 | 58 |
2022 May | 42 | 44 | 86 |
2022 April | 32 | 32 | 64 |
2022 March | 51 | 46 | 97 |
2022 February | 26 | 22 | 48 |
2022 January | 43 | 30 | 73 |
2021 December | 32 | 45 | 77 |
2021 November | 26 | 37 | 63 |
2021 October | 54 | 63 | 117 |
2021 September | 25 | 31 | 56 |
2021 August | 21 | 31 | 52 |
2021 July | 26 | 28 | 54 |
2021 June | 25 | 17 | 42 |
2021 May | 48 | 43 | 91 |
2021 April | 75 | 54 | 129 |
2021 March | 66 | 37 | 103 |
2021 February | 49 | 25 | 74 |
2021 January | 50 | 24 | 74 |
2020 December | 30 | 30 | 60 |
2020 November | 21 | 20 | 41 |
2020 October | 29 | 24 | 53 |
2020 September | 28 | 14 | 42 |
2020 August | 22 | 13 | 35 |
2020 July | 16 | 20 | 36 |
2020 June | 40 | 11 | 51 |
2020 May | 26 | 11 | 37 |
2020 April | 34 | 25 | 59 |
2020 March | 16 | 8 | 24 |
2020 February | 60 | 55 | 115 |
2020 January | 30 | 26 | 56 |
2019 December | 35 | 27 | 62 |
2019 November | 23 | 24 | 47 |
2019 October | 38 | 16 | 54 |
2019 September | 28 | 19 | 47 |
2019 August | 27 | 23 | 50 |
2019 July | 32 | 22 | 54 |
2019 June | 15 | 9 | 24 |
2019 May | 54 | 26 | 80 |
2019 April | 38 | 12 | 50 |
2019 March | 37 | 21 | 58 |
2019 February | 32 | 39 | 71 |
2019 January | 37 | 52 | 89 |
2018 December | 79 | 32 | 111 |
2018 November | 65 | 52 | 117 |
2018 October | 58 | 32 | 90 |
2018 September | 14 | 5 | 19 |
2018 August | 13 | 6 | 19 |
2018 July | 19 | 8 | 27 |
2018 June | 17 | 8 | 25 |
2018 May | 11 | 5 | 16 |
2018 April | 19 | 8 | 27 |
2018 March | 15 | 3 | 18 |
2018 February | 14 | 5 | 19 |
2018 January | 24 | 11 | 35 |
2017 December | 17 | 9 | 26 |
2017 November | 23 | 9 | 32 |
2017 October | 12 | 7 | 19 |
2017 September | 18 | 10 | 28 |
2017 August | 8 | 10 | 18 |
2017 July | 11 | 16 | 27 |
2017 June | 20 | 14 | 34 |
2017 May | 18 | 14 | 32 |
2017 April | 25 | 14 | 39 |
2017 March | 10 | 4 | 14 |
2017 February | 19 | 15 | 34 |
2017 January | 10 | 4 | 14 |
2016 December | 27 | 9 | 36 |
2016 November | 38 | 9 | 47 |
2016 October | 42 | 15 | 57 |
2016 September | 54 | 11 | 65 |
2016 August | 31 | 8 | 39 |
2016 July | 17 | 8 | 25 |
2015 December | 2 | 0 | 2 |