was read the article
array:23 [ "pii" => "S2173572721001521" "issn" => "21735727" "doi" => "10.1016/j.medine.2020.05.014" "estado" => "S300" "fechaPublicacion" => "2021-12-01" "aid" => "1527" "copyright" => "Elsevier España, S.L.U. and SEMICYUC" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Intensiva. 2021;45:532-40" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemSiguiente" => array:18 [ "pii" => "S217357272100151X" "issn" => "21735727" "doi" => "10.1016/j.medine.2020.05.013" "estado" => "S300" "fechaPublicacion" => "2021-12-01" "aid" => "1524" "copyright" => "Elsevier España, S.L.U. and SEMICYUC" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Intensiva. 2021;45:541-51" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Clinical risk factors for early mortality in patients with community-acquired septic shock. The importance of adequate source control" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "541" "paginaFinal" => "551" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Factores de riesgo clínico asociados a mortalidad precoz en pacientes con <span class="elsevierStyleItalic">shock</span> séptico de origen comunitario. La importancia de un control del foco adecuado" ] ] "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" => 1222 "Ancho" => 2084 "Tamanyo" => 106645 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Distribution of annual early and late deaths during the period of study (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.576).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Vallés, E. Diaz, J. Carles Oliva, M. Martínez, A. Navas, J. Mesquida, G. Gruartmoner, C. de Haro, J. Mestre, C. Guía, A. Rodriguez, A. Ochagavía" "autores" => array:12 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Vallés" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Diaz" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Carles Oliva" ] 3 => array:2 [ "nombre" => "M." "apellidos" => "Martínez" ] 4 => array:2 [ "nombre" => "A." "apellidos" => "Navas" ] 5 => array:2 [ "nombre" => "J." "apellidos" => "Mesquida" ] 6 => array:2 [ "nombre" => "G." "apellidos" => "Gruartmoner" ] 7 => array:2 [ "nombre" => "C." "apellidos" => "de Haro" ] 8 => array:2 [ "nombre" => "J." "apellidos" => "Mestre" ] 9 => array:2 [ "nombre" => "C." "apellidos" => "Guía" ] 10 => array:2 [ "nombre" => "A." "apellidos" => "Rodriguez" ] 11 => array:2 [ "nombre" => "A." "apellidos" => "Ochagavía" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217357272100151X?idApp=WMIE" "url" => "/21735727/0000004500000009/v2_202201010839/S217357272100151X/v2_202201010839/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S2173572721001569" "issn" => "21735727" "doi" => "10.1016/j.medine.2021.03.001" "estado" => "S300" "fechaPublicacion" => "2021-12-01" "aid" => "1658" "copyright" => "Elsevier España, S.L.U. and SEMICYUC" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Intensiva. 2021;45:516-31" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "OLA strategy for ARDS: Its effect on mortality depends on achieved recruitment (PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>) and mechanical power. Systematic review and meta-analysis with meta-regression" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "516" "paginaFinal" => "531" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estrategia OLA para el SDRA: su efecto en la mortalidad depende del reclutamiento alcanzado (PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>) y la potencia mecánica. Revisión sistemática y metaanálisis con metarregresión" ] ] "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" => 2263 "Ancho" => 2917 "Tamanyo" => 315681 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">PRISMA 2009 (11) Flow diagram of the study selection process. PEEP: positive end-expiratory pressure. VT: tidal volume. RMs: recruitment manoeuvres. Exp.: experimental.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "V. Modesto i Alapont, A. Medina Villanueva, P. del Villar Guerra, C. Camilo, S. Fernández-Ureña, F. Gordo-Vidal, R. Khemani" "autores" => array:7 [ 0 => array:2 [ "nombre" => "V." "apellidos" => "Modesto i Alapont" ] 1 => array:2 [ "nombre" => "A." "apellidos" => "Medina Villanueva" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "del Villar Guerra" ] 3 => array:2 [ "nombre" => "C." "apellidos" => "Camilo" ] 4 => array:2 [ "nombre" => "S." "apellidos" => "Fernández-Ureña" ] 5 => array:2 [ "nombre" => "F." "apellidos" => "Gordo-Vidal" ] 6 => array:2 [ "nombre" => "R." "apellidos" => "Khemani" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572721001569?idApp=WMIE" "url" => "/21735727/0000004500000009/v2_202201010839/S2173572721001569/v2_202201010839/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Hemodynamic resuscitation with fluids bolus and norepinephrine increases severity of lung damage in an experimental model of septic shock" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "532" "paginaFinal" => "540" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "P. Guijo Gonzalez, M.A. Gracia Romero, A. Gil Cano, M. Garcia Rojo, M. Cecconi, I.M. Monge Garcia" "autores" => array:6 [ 0 => array:4 [ "nombre" => "P." "apellidos" => "Guijo Gonzalez" "email" => array:1 [ 0 => "pedro_guijo@hotmail.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M.A." "apellidos" => "Gracia Romero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Gil Cano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "M." "apellidos" => "Garcia Rojo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "M." "apellidos" => "Cecconi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] 5 => array:3 [ "nombre" => "I.M." "apellidos" => "Monge Garcia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Intensive Care Medicine Department, Hospital del SAS Jerez, Jerez de la Frontera, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Research Group in Critical Disorders (GREPAC), Institut Hospital del Mar d’Investigacions Mèdiques (IMIM), Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Critical Care Department, Hospital del Mar, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Derpartment of Pathology, Hospital Universitario Puerta del Mar, Cadiz, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Department of Anaesthesia and Intensive Care, IRCCS Instituto Clínico Humanitas, Humanitas University, Milan, Italy" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "La resucitación hemodinámica con bolos de fluidos y noradrenalina incrementa la severidad del daño pulmonar en un modelo experimental de <span class="elsevierStyleItalic">shock</span> séptico" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1542 "Ancho" => 2508 "Tamanyo" => 415154 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Evolution over time of hemodynamic measurements of each group. Circles represent mean values and vertical lines are SD. SHAM: Sham-operated group, ETX-NR: Non-resuscitated septic group. ETX-R: Resuscitated septic group. Cardiac index (CI), mean arterial pressure (MAP), stroke volume (SV) and heart rate (HR). When ETX was administered there was an increase in the CI (secondary to an increase in HR), with a progressive reduction in MAP. The administration of fluids increased CI, SV and MAP; However MAP's baseline levels were not reached, so all animals required dose of norepinephrine. *<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005 ETX-R vs. basal. <elsevierMultimedia ident="202201010839440881"></elsevierMultimedia><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005 ETX-R vs. SHAM. #<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005 ETX-R vs. ETX-NR.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Severe sepsis and septic shock are the most frequent causes of admission in intensive care units, with a high mortality rate around 30%.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a> Recently reviewed definitions characterize sepsis as life-threatening organ dysfunction, while septic shock is a subset of sepsis in which particularly profound circulatory, cellular and metabolic abnormalities substantially increase mortality.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a> Hemodynamic resuscitation, by means of fluid bolus (30<span class="elsevierStyleHsp" style=""></span>mL·kg<span class="elsevierStyleSup">−1</span>) and subsequent norepinephrine (NE), has once again been considered by the Surviving Sepsis Campaign (SSC) as a cornerstone of the initial treatment of septic shock.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">3</span></a> The rationale for these recommendations is that, in the early phase of severe sepsis and septic shock, restoring intravascular volume and maintaining end-organ perfusion are the top priorities.<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">3,4</span></a> However, the optimal strategy of hemodynamic resuscitation in the early hours of severe sepsis and septic shock is still controversial. Given the evidence of harm associated with positive fluid balance accumulated in septic patients from hospital admission to Intensive Care Unit (ICU) discharge,<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">5–7</span></a> there is a growing concern about the undesirable effects of this strategy, such as acute respiratory distress syndrome (ARDS).<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">8–10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">ARDS is a devastating complication of sepsis that influences its clinical management and outcomes.<a class="elsevierStyleCrossRefs" href="#bib0255"><span class="elsevierStyleSup">11,12</span></a> On the one hand, studies have established a strong relationship between fluid administration and the appearance of ARDS.<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">13–18</span></a> On the other hand, the cardiovascular effects of NE on the development of lung injury have not been adequately investigated. NE, due to its ability to increase venous return and myocardial contraction in septic shock patients, increases pulmonary flow and perfusion,<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">19–22</span></a> which would likely increase the severity of lung injury.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Because up to 40% of sepsis patients develop ARDS,<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a> and given that sepsis is a systemic inflammation state with high capillary permeability, it is possible that the effects of hemodynamic resuscitation in the early phase of septic shock could lead to enhaced pulmonary edema and increased the risk for ARDS development. The purpose of this experimental study is to investigate the effects of bolus fluid administration and infusion of NE on the development of lung injury. We hypothesized that this strategy used in the early phase of septic shock leads to lung injury development.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Patients and methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This study was approved by the Ethics Committee of the University of Cadiz (license 07-9604) and the Junta de Andalucía. Animal care and use procedures conformed to national and European Union regulations and guidelines (Spanish Royal Decree 53/2013 and EU Directive 2010/63/EU).</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Anesthesia and instrumentation</span><p id="par0025" class="elsevierStylePara elsevierViewall">Eighteen New-Zealand rabbits (weight 2.51<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.13<span class="elsevierStyleHsp" style=""></span>kg) were anesthetized with an intramuscular dose of xylazine hydrochloride (10<span class="elsevierStyleHsp" style=""></span>mg·kg<span class="elsevierStyleSup">−1</span>) and ketamine (40<span class="elsevierStyleHsp" style=""></span>mg·kg<span class="elsevierStyleSup">−1</span>). The adequacy of anesthesia throughout the experiment was assessed by the absence of any significant blood pressure and/or heart rate change, either spontaneous or in response to a noxious stimulus (tail clamping). The rabbits were tracheotomized, intubated and mechanically ventilated (Servo 900c; Siemens-Elema, Solna, Sweden) in a volume-controlled mode, with a tidal volume of 8<span class="elsevierStyleHsp" style=""></span>mL·kg<span class="elsevierStyleSup">−1</span>, PEEP of 0 cmH<span class="elsevierStyleInf">2</span>O, inspiratory-to-expiratory ratio of 1:2, inspired oxygen fraction of 0.6, and a respiratory rate adjusted to maintain an end-tidal CO between 35–45<span class="elsevierStyleHsp" style=""></span>mmHg. The anesthesia was maintained with a continuous intravenous infusion of ketamine (15–20<span class="elsevierStyleHsp" style=""></span>mg·kg<span class="elsevierStyleSup">−1</span>·h<span class="elsevierStyleSup">−1</span>), midazolam (1–3<span class="elsevierStyleHsp" style=""></span>mg·kg<span class="elsevierStyleSup">−1</span>·h<span class="elsevierStyleSup">−1</span>) and muscular blockade with rocuronium bromide (1<span class="elsevierStyleHsp" style=""></span>mg·kg<span class="elsevierStyleSup">−1</span>·h<span class="elsevierStyleSup">−1</span>). Ringer's lactate solution (6<span class="elsevierStyleHsp" style=""></span>mL·kg<span class="elsevierStyleSup">−1</span>·h<span class="elsevierStyleSup">−1</span>) was administered as maintenance fluid therapy.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Hemodynamic monitoring</span><p id="par0030" class="elsevierStylePara elsevierViewall">A pediatric esophageal Doppler probe (KDP72; CardioQ Combi, Deltex Medical, Chichester, UK) was introduced into the esophagus until the optimal outline and maximal peak velocity of aortic blood waveform was obtained. Consecutive transesophageal Doppler measurements for 60<span class="elsevierStyleHsp" style=""></span>seconds at the beginning and after 1, 2, 3 and 4<span class="elsevierStyleHsp" style=""></span>h (end of experiment) were completed and averaged to calculate variables as the heart rate (HR), stroke volume (SV) and cardiac index (CI). Systolic, diastolic and mean arterial pressure, were continuously measured by an indwelling femoral artery catheter connected to a pressure transducer (TruWave®, Edwards Lifesciences LLC, Irvine, CA, USA).</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Respiratory monitoring</span><p id="par0035" class="elsevierStylePara elsevierViewall">Continuous non-invasive measurements of flow, pressure and volume in the animal's airway were obtained using a spirometry monitor (Datex-Ohmeda M-COV, Helsinki, Finland) with a neonatal flow sensor (Patient Spirometry Kit 8004382, GE Healthcare, Helsinki, Finland) connected directly to the animal's tracheal tube. Dynamic compliance of the respiratory system (C<span class="elsevierStyleInf"><span class="elsevierStyleItalic">dyn</span></span>) and the peak pressure (P<span class="elsevierStyleInf"><span class="elsevierStyleItalic">peak</span></span>) were measured and averaged during a period of 60<span class="elsevierStyleHsp" style=""></span>s at the beginning and after 2, 3 and 4<span class="elsevierStyleHsp" style=""></span>h (end of experiment).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Experimental protocol</span><p id="par0040" class="elsevierStylePara elsevierViewall">After 5<span class="elsevierStyleHsp" style=""></span>min of stabilization and baseline measurements of hemodynamic and lung mechanics, the animals were assigned using a computer-generated random sequence to three groups (6 animals each): a sham-operated group (SHAM), a non-resuscitated septic group (ETX-NR), and a septic group with hemodynamic resuscitation (ETX-R). In septic animals, a purified endotoxin-lipopolysaccharide (ETX) prepared from <span class="elsevierStyleItalic">Escherichia coli</span> 055:B5 (Sigma Chemical, St. Louis, MO) was intravenously infused over a period of 10<span class="elsevierStyleHsp" style=""></span>min (1<span class="elsevierStyleHsp" style=""></span>mg·kg<span class="elsevierStyleSup">−1</span>). The dose and rate of the ETX was selected based on previous publications.<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a> However, to determine the best way for ETX administration, we required 8 animals. SHAM animals received an equivalent volume of normal saline. Three hours after ETX infusion, animals in the ETX-R group received a fluid bolus (Ringer's lactate) of 20<span class="elsevierStyleHsp" style=""></span>mL·kg<span class="elsevierStyleSup">−1</span>, and if the mean arterial pressure (MAP) was lower than the baseline measurement, NE infusion was started at 0.25<span class="elsevierStyleHsp" style=""></span>mcg·kg<span class="elsevierStyleSup">−1</span>·min<span class="elsevierStyleSup">−1</span>. NE was increased 0.10<span class="elsevierStyleHsp" style=""></span>mcg·kg<span class="elsevierStyleSup">−1</span>·min<span class="elsevierStyleSup">−1</span> every 3<span class="elsevierStyleHsp" style=""></span>min until reaching a MAP similar to the baseline level. A schematic representation of the experimental protocol is shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. After completion of the study protocol, animals were euthanized by a lethal dose of chloride potassium.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Histological analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">At the end of the experiment, the left lung was excised and immersed in 10% formaldehyde for at least 24<span class="elsevierStyleHsp" style=""></span>h. Tissue samples were dehydrated with graded alcohol, embedded in paraffin, and cut in a series of 5<span class="elsevierStyleHsp" style=""></span>μm-thick slices that were stained with hematoxylin and eosin. After the histological preparations were obtained, they were scanned to obtain digital preparations (3DHistech, Budapest, Hungary). An expert pathologist then evaluated these tissue sections in a blinded fashion using the following scoring system to determine the degree of lung injury: 0, no damage; 1, mild damage (present in 1–3 areas of 1<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">2</span>); 2, moderate damage (present in more than 3 areas of 1<span class="elsevierStyleHsp" style=""></span>mm<span class="elsevierStyleSup">2</span> and less than 75% of the tissue section); 3, severe damage (present in more than 75% of the tissue section). These scores used the combined assessments of six parameters: accumulation of neutrophils in alveolar or interstitial space, reactive type II pneumocytes with atypical nuclei in the alveolus, alveolar congestion/collapse, alveolar wall thickening, alveolar hemorrhage and hyaline membrane formation, presenting a score from 0 to 18 ranging from normal histology to maximum damage.<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">25,26,27</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Statistical analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">Data are expressed as the mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation (<span class="elsevierStyleItalic">SD</span>), unless otherwise stated. Normality of data was checked by the Shapiro–Wilk test. We used a two-way analysis of variance (ANOVA) for repeated measures to determine the statistical significance of group differences in the respiratory and hemodynamic parameters at different time points. The Greenhouse–Geisser correction was used when violation of sphericity was detected by the Mauchly test. When statistical significance was indicated, it was further examined by a post hoc analysis (Bonferroni test). Baseline parameters and the differences within-subjects were evaluated using a repeated-measures ANOVA. The data obtained from the histopathological study were analyzed according to intensity and extension score using the non-parametric Kruskal Wallis test. The differences between each pair of 2 groups were assessed by Mann–Whitney <span class="elsevierStyleItalic">U</span> test. A <span class="elsevierStyleItalic">p</span> value <0.05 was considered statistically significant, unless otherwise indicated. Data were analyzed by using MedCalc Statistical Software version 16.8 (MedCalc Software bvba, Ostend, Belgium) and SPSS (SPSS 21, SPPS Inc, Chicago, IL).</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">In the 18 rabbits randomly allocated to three different groups, we found that each group had similar baseline characteristics for any of the hemodynamic and respiratory variables measured, except for the C<span class="elsevierStyleInf">dyn</span> (<a class="elsevierStyleCrossRef" href="#sec0090">Supplementary File, Table S1</a>).</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Hemodynamic changes</span><p id="par0060" class="elsevierStylePara elsevierViewall">Infusion of ETX resulted in a hyperdynamic hemodynamic profile with a progressive increase in CI (mostly secondary to a higher HR) and a reduction in blood pressure. In the ETX-R group, although the administration of fluids increased CI, stroke volume (SV) and MAP by 20%, 11% and 18% respectively, MAP's baseline levels were not reached, so NE was necessary in all cases (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Hemodynamic effects during different experimental stages are detailed in <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary File, Table S2</a>.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Respiratory changes</span><p id="par0065" class="elsevierStylePara elsevierViewall">As shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>, infusion of ETX caused a significance decrease and increase in the C<span class="elsevierStyleInf"><span class="elsevierStyleItalic">dyn</span></span> and P<span class="elsevierStyleInf"><span class="elsevierStyleItalic">peak</span></span> respectively. However, although resuscitation worsened C<span class="elsevierStyleInf"><span class="elsevierStyleItalic">dyn</span></span> by 20% and P<span class="elsevierStyleInf"><span class="elsevierStyleItalic">peak</span></span> by 16% in the ETX-R group compared to the ETX-NR group, differences were no statistically significant. Respiratory effects during the different experimental stages are summarized in <a class="elsevierStyleCrossRef" href="#sec0090">Supplementary File, Table S3</a>.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Histopathological findings</span><p id="par0070" class="elsevierStylePara elsevierViewall">As can be seen in <a class="elsevierStyleCrossRefs" href="#fig0020">Figs. 4 and 5</a>, the main difference between both ETX groups and the SHAM group was the greatest presence of reactive type II pneumocytes in both septic groups (SHAM: 0.38; ETX-NR: 0.96; ETX-R: 1.21; <span class="elsevierStyleItalic">p</span>: <0.001). In the ETX-R group, a greater accumulation of neutrophils in the alveolar or the interstitial space (SHAM: 0.79; ETX-NR: 0.83; ETX-R: 1.72; <span class="elsevierStyleItalic">p</span> 0.003), thickening of the alveolar wall (SHAM: 0.62; ETX-NR: 0.51; ETX-R: 1.79; <span class="elsevierStyleItalic">p</span> <0.001), alveolar hemorrhage (SHAM: 0.38; ETX-NR: 0.61; ETX-R: 0.83; <span class="elsevierStyleItalic">p</span> <0.001) and alveolar congestion/collapse with non-aerated areas (SHAM: 0.21; ETX-NR: 0.08; ETX-R: 1.20; <span class="elsevierStyleItalic">p</span> <0.001) were observed. No hyaline membranes were observed in any of the animals. Lung injury scores were larger in the ETX-R group than for the SHAM group and the ETX-NR group (6.75, 2.71 and 2.96 respectively; <span class="elsevierStyleItalic">p</span> <0.001).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">Hemodynamic resuscitation by means of fluids and NE is currently considered as the first-line resuscitation therapy by the international SSC.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">3</span></a> This guideline recommends an initial bolus of 30<span class="elsevierStyleHsp" style=""></span>mL·kg<span class="elsevierStyleSup">−1</span> of fluid followed by infusion of vasopressors if the blood pressure goal is not achieved. The most important finding of our experimental study was that bolus fluid administration and late NE in the early hours of endotoxic septic shock has a negative influence on lung injury development. When ETX was administered to induce septic shock, an increase in reactive type II pneumocytes was found, which suggests epithelial damage.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> However, when fluids and NE were administered to restore blood pressure, they resulted in greater histopathological findings with an increase in neutrophils infiltration, reactive type II pneumocytes, alveolar congestion/collapse and alveolar wall thickening, and a larger lung injury score.</p><p id="par0080" class="elsevierStylePara elsevierViewall">It can be assumed that increased pulmonary blood flow, due to administration of fluids (20<span class="elsevierStyleHsp" style=""></span>mL·kg<span class="elsevierStyleSup">−1</span>) and NE infusion, combined with a capillary permeability disorder, were the mechanisms responsible for the worsening of lung inflammatory damage initiated by endotoxemia. Although this is likely to be the price to pay for adequate hemodynamic optimization, our findings provide valuable information about the consequences and damaging effects of this strategy in septic shock.</p><p id="par0085" class="elsevierStylePara elsevierViewall">ARDS is a catastrophic form of lung injury characterized by diffuse alveolar damage with severe inflammation and high permeability protein-rich edema.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">12</span></a> Recent studies suggest that the development of lung damage appears as a consequence of several impacts, which act as if it were a chain reaction.<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> So, when an initial insult occurs, it primes an inflammatory response which damages and sensitizes the lungs without developing ARDS. However, if further impacts occur (second hits), even if they are less intense, an exaggerated inflammatory response arises, which can lead to gradual progression from initial lung injury to clinical ARDS. Our results suggest that this strategy of resuscitation might behave as a second hit influencing the progression of lung injury and favoring the development of ARDS.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Previous studies have shown how the amount of administered fluids increases the likelihood of developing ARDS among patients at risk.<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">13,30</span></a> Jia et al. retrospectively demonstrated that net fluid balance during the first 48<span class="elsevierStyleHsp" style=""></span>h of mechanically ventilated patients was associated with the development of ARDS.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a> In addition, Hughes et al. found that among patients admitted after major surgery, the amount of fluid infused during surgery was independently associated with ARDS.<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Despite multiple studies showing the overall association between the amount of fluids administered and the development of ARDS, the consequences of the aggressive amount of fluid during hemodynamic resuscitation in the early phase of septic shock has not been well analyzed. Unfortunately, most of the studies have been retrospective in nature with small sample sizes. Our experimental study addresses this question and found an association between fluid administration and late NE used in the early phase of endotoxic septic shock and the development of lung injury. Seethala et al. highlighted the role of the amount of fluid administered to septic patients during the first 6<span class="elsevierStyleHsp" style=""></span>h of care and the development of ARDS. However, this association was present in patients without shock.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> Similarly, Chang et al. retrospectively examined a cohort of 75 patients hospitalized with ARDS secondary to severe sepsis or septic shock and demonstrated that total volume of fluid infused during the first 6 or 24<span class="elsevierStyleHsp" style=""></span>h of care did not increase the risk of ARDS after 72<span class="elsevierStyleHsp" style=""></span>h of hospitalization.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">32</span></a> However, the novelty of our experimental study is that histopathological findings suggest that, although clinically it may not be manifested during the first days of hospitalization, the damaged lung can be silently initiated during resuscitation in the early phase of septic shock. Andrews et al. conducted a randomized controlled trial in Zambian patients with septic shock and found that the amount of fluid during the first 6<span class="elsevierStyleHsp" style=""></span>h of care (4 vs. 2.5<span class="elsevierStyleHsp" style=""></span>l; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) was associated with increased mortality (48% vs. 33%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.03), but also with an increase of respiratory complications, such as hypoxemia and tachypnea (35.8% vs. 22.3%; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.03).<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">33</span></a> A recent experimental study with an ovine septic shock model observed that fluid resuscitation led to increase in biomarker cardiac stress and endothelial glycocalyx shedding.<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">NE could also contribute in a detrimental way to the development of lung injury. It is known that when NE is administered after fluid replacement, it is able to boost cardiac output through an improve in cardiac preload and cardiac contractility in septic shock patients. It increases the flow and perfusion in the pulmonary vascular system, which worsens the severity of lung damage.<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">19–20</span></a> In addition NE, as it rises pulmonary vascular pressure, can also increase capillary hydrostatic pressure, which would extend transcapillary filtration, favoring pulmonary edema.<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">35,36</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">An important application of this study is that, although the administration of fluids and NE in the early hours of septic shock is adequate at a cardiovascular point of view, we should assess whether the increase in pulmonary blood flow produced by this strategy, could have harmful effects on the lungs. We believe that a restrictive resuscitation strategy with less fluid in patients with septic shock could restore hemodynamics as well as reduce lung damage. In this context, several studies have investigated the consequences of restrictive strategies in patients with septic shock.<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">37</span></a> For example, Permpikul et al. recently observed how with the early perfusion of NE, the amount of fluid administered in the first hours of admission was lower, without greater vasopressor requirement or a higher mortality rate.<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">38</span></a> Ranjit et al., in addition to the decreased fluid administration, also observed a lower need for ventilator support in pediatric patients.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a> However, the consequences of this strategy on ARDS have not yet been investigated. We suggest that this strategy would decrease the high incidence and severity of ARDS in septic patients.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Our study has several limitations. First, the short duration of our experiment does not allow us to evaluate the final evolution of lung damage. The follow-up of only four hours is limited to assess the consequences of the period of lung ischemia in the ETX-NR group. However, our aim was to determine the direct consequences of increased pulmonary blood flow during the first phase of hemodynamic resuscitation. Moreover, even in the early phase of this resuscitation, histopathological findings showed alterations suggestive of ARDS. Second, the evaluation the state of shock and guide resuscitation was not based on parameters of tissue hypoperfusion used in clinical practice, such as arterial pH, blood lactate, or P(v-a)CO. Furthermore, blood gases as a measure of lung function were not used, so lung damage was only determined by lung histology. Third, the amount of fluids administered in our study was less than recommended by the SSC. However, our intention was to evaluate if, even with the administration of less quantity of fluids than recommended, lung injury was already established. Also, the deleterious effects of aggressive fluid administration are well-known. Therefore, although the SSC recommends the administration of 30<span class="elsevierStyleHsp" style=""></span>mL·kg<span class="elsevierStyleSup">−1</span> in the first hours of resuscitation, nowadays we tend to limit the volume contribution to the optimization of VO2/DO2 dependency. It's likely that a dose of 30<span class="elsevierStyleHsp" style=""></span>mL·kg<span class="elsevierStyleSup">−1</span> would have been more appropriate from the hemodynamic point of view, however, the histopathological alterations would probably also have been greater. Fourth, the use of mechanical ventilation without PEEP could influence the development of lung injury behaving as an additional impact, although it was common in all groups. Experimental studies have shown that when lung injury is induced by mechanical ventilation without PEEP, there are other histopathological findings.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> Fifth, although our findings show that this strategy can be detrimental to lung injury, we did not analyze the effects of fluids nor NE alone. Nevertheless, Passmore et al. already analyzed this in an ovine model of septic shock, and did not find any histopathological lung differences between both treatments.<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">40</span></a> Finally, our experimental study was carried out in young rabbits, so our results should be interpreted with caution when extrapolated to human lung injury.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Conclusions</span><p id="par0115" class="elsevierStylePara elsevierViewall">Our experimental study shows that increasing pulmonary blood flow with fluids and NE until reaching a MAP endpoint in endotoxic septic shock has direct deleterious effects on lung damage. The relations between this strategy and the inflammatory lung injury were explained by histopathologic findings. These findings suggest that once lung damage has been initiated by endotexemia, the aggressive administration of fluids and NE act as second hits. More studies are required to assess whether the prevention of these second hits could result in a decrease in the incidence and severity of lung damage.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Contributions of the authors</span><p id="par0120" class="elsevierStylePara elsevierViewall">P.G.G.: designed the study, participated in the experiments, acquired and interpreted the data, performed the statistical analysis, and draft the manuscript. M.I.M.G. and M.G.R.: participated in the experiments, acquired and interpreted the data, performed the statistical analysis and helped to draft the manuscript. A.G.C.: designed the study, acquired and interpreted the data, performed the statistical analysis, and helped to draft the manuscript. M.G.R.: Pathology study. M.C.: contributed in the conception and design of the study. All the authors approved the final manuscript, and have also ensured that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Funding</span><p id="par0125" class="elsevierStylePara elsevierViewall">This work was supported by the St George's University of London, UK, and performed at the Servicio Central de Experimentación y Producción Animal (SEPA) of the University of Cadiz, Spain.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Conflict of interests</span><p id="par0130" class="elsevierStylePara elsevierViewall">M.I.M.G. is consultant to Edwards Lifescences and received honoraria and/or travel expenses from Deltex Medical. M.C. has received honoraria and/ot travel expenses from Edwards Lifescences, LiDCO, Cheetah, Bmeye, Masimo and Deltex Medical. P.G.G., M.G.R. and A.G.C. have no relevant financial relationships or conflicts of interest to disclose.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1639798" "titulo" => "Abstract" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Setting" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Patients" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Interventions" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Main variables of interest" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1462152" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1639799" "titulo" => "Resumen" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0045" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0050" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0055" "titulo" => "Ámbito" ] 3 => array:2 [ "identificador" => "abst0060" "titulo" => "Participantes" ] 4 => array:2 [ "identificador" => "abst0065" "titulo" => "Intervención" ] 5 => array:2 [ "identificador" => "abst0070" "titulo" => "Principales variables de interés" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1462153" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Anesthesia and instrumentation" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Hemodynamic monitoring" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Respiratory monitoring" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Experimental protocol" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Histological analysis" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Hemodynamic changes" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Respiratory changes" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Histopathological findings" ] ] ] 7 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0075" "titulo" => "Contributions of the authors" ] 10 => array:2 [ "identificador" => "sec0080" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interests" ] 12 => array:2 [ "identificador" => "xack578936" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2019-11-11" "fechaAceptado" => "2020-05-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1462152" "palabras" => array:5 [ 0 => "Septic shock" 1 => "Acute respiratory distress syndrome" 2 => "Endotoxemia" 3 => "Resuscitation" 4 => "Fluid" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1462153" "palabras" => array:5 [ 0 => "Shock séptico" 1 => "Síndrome de distrés respiratorio agudo" 2 => "Endotoxemia" 3 => "Resucitación" 4 => "Fluidos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hemodynamic resuscitation is considered a cornerstone of the initial treatment of septic shock. However, there is growing concern about its side effects. Our objective was to assess the relationship between fluid administration and norepinephrine infusion and the development of lung injury.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Design</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Randomized in vivo study in rabbits.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Setting</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">University animal research laboratory.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Patients</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Eighteen New Zealand rabbits. Control group (SHAM, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6), Sepsis group with or without hemodynamic resuscitation (ETX-R, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6; ETX-NR, <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6).</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Interventions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Sepsis was induced by intravenous lipopolysaccharide administration and animals were followed-up for 4<span class="elsevierStyleHsp" style=""></span>h. Hemodynamic resuscitation with Ringer lactate (20<span class="elsevierStyleHsp" style=""></span>mL·kg<span class="elsevierStyleSup">−1</span>) was administered and later norepinephrine was initiated 3<span class="elsevierStyleHsp" style=""></span>h after sepsis induction. At the end, the left lung was excised.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Main variables of interest</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">An indwelling arterial catheter and an esophageal Doppler were placed. Lung mechanics were monitored with side stream spirometry. Lung damage was analyzed by histopathological examination.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">The SHAM group did not show hemodynamic or respiratory changes. Lipopolysaccharide administration aimed an increase in cardiac output and arterial hypotension. In the ETX-NR group, animals remained hypotensive until the end of the experiment. Resuscitation with fluids and norepinephrine reversed arterial hypotension. Compared to the ETX-NR group, the remaining lung of the ETX-R group showed greater accumulation of neutrophils and reactive type-II pneumocytes, thicker alveolar wall, alveolar hemorrhage and non-aerated pulmonary areas. Lung injury score was larger in the ETX-R group.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">In our experimental study, following a strategy with bolus fluids and late norepinephrine used in the early phase of endotoxic septic shock has a negative influence on the development of lung injury.</p></span>" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Design" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Setting" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Patients" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Interventions" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Main variables of interest" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objetivo</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La resucitación hemodinámica es considerada piedra angular en el tratamiento inicial del <span class="elsevierStyleItalic">shock</span> séptico. Sin embargo, existe creciente preocupación sobre sus efectos indeseables. Nuestro objetivo fue evaluar la relación entre la administración de fluidos e infusión de noradrenalina y el desarrollo de lesión pulmonar.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Diseño</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Estudio aleatorizado en animales vivos.</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Ámbito</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Laboratorio universitario de investigación.</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Participantes</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Dieciocho conejos de raza New Zealand White. Grupo control (SHAM, n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6), grupo séptico con o sin resucitación hemodinámica (ETX-R, n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6; ETX-NR, n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6).</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Intervención</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">La sepsis fue inducida tras administración intravenosa de lipopolisacárido, y los animales fueron seguidos durante 4<span class="elsevierStyleHsp" style=""></span>h. La resucitación hemodinámica mediante suero Ringer lactato (20<span class="elsevierStyleHsp" style=""></span>ml·kg<span class="elsevierStyleSup">-1</span>) y posterior noradrenalina fue iniciada a las 3<span class="elsevierStyleHsp" style=""></span>h de ser inducida la sepsis. Al final del estudio, el pulmón izquierdo fue extraído.</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Principales variables de interés</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Fueron empleados catéter arterial y doppler esofágico. La mecánica pulmonar fue monitorizada con sensor de flujo. El daño pulmonar fue analizado mediante examen histopatológico.</p></span> <span id="abst0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">El grupo control no mostró cambios hemodinámicos ni respiratorios. La administración del lipopolisacárido produjo un incremento del gasto cardíaco e hipotensión arterial. En el grupo ETX-NR, los animales permanecieron hipotensos hasta el final del estudio. La resucitación con fluidos y noradrenalina revirtió la hipotensión arterial. Comparados con el grupo ETX-NR, en el grupo ETX-R el estudio histopatológico mostró mayor acumulación de neutrófilos, así como mayor presencia de neumocitos activados tipo II, engrosamiento de la pared alveolar, hemorragia alveolar y zonas pulmonares no aireadas. La escala final de daño pulmonar fue mayor en el grupo ETX-R.</p></span> <span id="abst0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">En nuestro estudio experimental, la estrategia basada en la administración de fluidos y posterior infusión de noradrenalina en la fase precoz del <span class="elsevierStyleItalic">shock</span> séptico tiene una influencia negativa sobre el desarrollo de la lesión pulmonar.</p></span>" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0045" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0050" "titulo" => "Diseño" ] 2 => array:2 [ "identificador" => "abst0055" "titulo" => "Ámbito" ] 3 => array:2 [ "identificador" => "abst0060" "titulo" => "Participantes" ] 4 => array:2 [ "identificador" => "abst0065" "titulo" => "Intervención" ] 5 => array:2 [ "identificador" => "abst0070" "titulo" => "Principales variables de interés" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0145" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0095" ] ] ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2085 "Ancho" => 2508 "Tamanyo" => 289575 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Schematic representation of the study protocol.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1542 "Ancho" => 2508 "Tamanyo" => 415154 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Evolution over time of hemodynamic measurements of each group. Circles represent mean values and vertical lines are SD. SHAM: Sham-operated group, ETX-NR: Non-resuscitated septic group. ETX-R: Resuscitated septic group. Cardiac index (CI), mean arterial pressure (MAP), stroke volume (SV) and heart rate (HR). When ETX was administered there was an increase in the CI (secondary to an increase in HR), with a progressive reduction in MAP. The administration of fluids increased CI, SV and MAP; However MAP's baseline levels were not reached, so all animals required dose of norepinephrine. *<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005 ETX-R vs. basal. <elsevierMultimedia ident="202201010839440881"></elsevierMultimedia><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005 ETX-R vs. SHAM. #<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005 ETX-R vs. ETX-NR.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 649 "Ancho" => 2091 "Tamanyo" => 132858 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Evolution over time of respiratory measurements of each group. SHAM: sham-operated group; ETX: non-resuscitated septic group; ETX-R: resuscitated septic group. Circles represent mean values and vertical lines are SD. Dynamic compliance of respiratory system (Cdyn) and the peak pressure (Ppeak) during endotoxemia and resuscitation monitoring period. Although hemodynamic resuscitation worsened the lung mechanics, it was not significant. *<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005 ETX-R vs. basal. <elsevierMultimedia ident="202201010839440882"></elsevierMultimedia><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005 ETX-R vs. SHAM. #<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.005 ETX-R vs. ETX-NR.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 940 "Ancho" => 1508 "Tamanyo" => 76495 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Graphical representation of histopathological variables (mean value of intensity and extension) analyzed in each group. Lung injury score 0–3. SHAM: sham-operated group; ETX: non-resuscitated septic group; ETX-R: resuscitated septic group. Hemodynamic resuscitation resulted in greater score of lung injury. *Indicate statistically significant difference from SHAM, ETX-NR and ETX-R by the non-parametric Kruskal Wallis test (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01).</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 1845 "Ancho" => 1674 "Tamanyo" => 676950 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Microscopic aspects of the lungs from SHAM group (A), and the ETX-R (B, C, D, E). (A) normal lung. (B) Neutrophils in interstitium and alveolar wall. (C) Reactive Type II pneumocytes with hyperchromatic nuclei and nuclear membrane irregularity. (D) Thickened alveolar walls with intramural neutrophils, macrophages and fibroblasts. (E) Area with pulmonary emphysema. (F) Gross pathology surface of lung in the SHAM (left) and ETX-R (right) animals. Last one shows more intense damage, especially hemorrhagic areas and lung edema. SHAM: sham-operated group; ETX: non-resuscitated septic group; ETX-R: resuscitated septic group (HE ×40).</p>" ] ] 5 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 130658 ] ] 6 => array:5 [ "identificador" => "202201010839440881" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 28 "Ancho" => 11 "Tamanyo" => 322 ] ] ] 7 => array:5 [ "identificador" => "202201010839440882" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 28 "Ancho" => 11 "Tamanyo" => 322 ] ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0205" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Assessment of global incidence and mortality o hospital-treated sepsis: current estimates and limitations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Fleischmann" 1 => "A. Scherag" 2 => "N.K. Adhikari" 3 => "C.S. Hartog" 4 => "T. Tsaganos" 5 => "P. Schlattmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201504-0781OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2016" "volumen" => "193" "paginaInicial" => "259" "paginaFinal" => "272" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26414292" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0210" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The third international consensus definitions for sepsis and septic shock (Sepsis-3)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Singer" 1 => "C.S. Deutschman" 2 => "C.W. Seymour" 3 => "M. Shankar-Hari" 4 => "D. Annane" 5 => "M. Bauer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2016.0287" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2016" "volumen" => "315" "paginaInicial" => "801" "paginaFinal" => "810" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26903338" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0215" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Surviving sepsis campaign: International guidelines for management of sepsis and septic shock" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Rhodes" 1 => "L.E. Evans" 2 => "W. Alhazzani" 3 => "M.M. Levy" 4 => "M. Antonelli" 5 => "R. Ferrer" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-017-4683-6" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2017" "volumen" => "43" "paginaInicial" => "304" "paginaFinal" => "377" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28101605" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0220" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of sepsis: early resuscitation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "E.P. Rivers" 1 => "V. Coba" 2 => "A. Visbal" 3 => "M. Whitmill" 4 => "D. Amponsah" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ccm.2008.06.005" "Revista" => array:6 [ "tituloSerie" => "Clin Chest Med" "fecha" => "2008" "volumen" => "29" "paginaInicial" => "689" "paginaFinal" => "704" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18954703" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0225" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fluid volume, fluid balance and patient outcome in severe sepsis and septic shock: a systematic review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B.M. Tigabu" 1 => "M. Davari" 2 => "A. Kebriaeezadeh" 3 => "M. Mojtahedzadeh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcrc.2018.08.018" "Revista" => array:6 [ "tituloSerie" => "J Crit Care" "fecha" => "2018" "volumen" => "48" "paginaInicial" => "153" "paginaFinal" => "159" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30199843" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0230" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P.E. Marik" 1 => "W.T. Linde-Zwirble" 2 => "E.A. Bittner" 3 => "J. Sahatjian" 4 => "D. Hansell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-016-4675-y" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2017" "volumen" => "43" "paginaInicial" => "625" "paginaFinal" => "632" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28130687" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0235" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "J.H. Boyd" 1 => "J. Forbes" 2 => "T.A. Nakada" 3 => "K.R. Walley" 4 => "J.A. Russell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e3181feeb15" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2011" "volumen" => "39" "paginaInicial" => "259" "paginaFinal" => "265" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20975548" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0240" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Severe sepsis and septic shock trials (ProCESS, ARISE, ProMISe): what is optimal resuscitation?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "T.M. Osborn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ccc.2016.12.004" "Revista" => array:6 [ "tituloSerie" => "Crit Care Clin" "fecha" => "2017" "volumen" => "33" "paginaInicial" => "323" "paginaFinal" => "344" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28284298" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0245" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemodynamic support in the early phase of septic shock: a review of challenges and unanswered questions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "O. Lesur" 1 => "E. Delile" 2 => "P. Asfar" 3 => "P. Radermacher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13613-018-0449-8" "Revista" => array:5 [ "tituloSerie" => "Ann Intensive Care" "fecha" => "2018" "volumen" => "8" "paginaInicial" => "102" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30374729" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0250" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute respiratory distress syndrome: prevention and early recognition" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C. De Haro" 1 => "I. Martin-Loeches" 2 => "E. Torrents" 3 => "A. Artigas" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Ann Intensive Care" "fecha" => "2013" "volumen" => "3" "paginaInicial" => "1" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0255" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The epidemiology of acute respiratory distress syndrome in patients presenting to the emergency department with severe sepsis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.E. Mikkelsen" 1 => "C.V. Shah" 2 => "N.J. Meyer" 3 => "D.F. Gaieski" 4 => "S. Lyon" 5 => "A.N. Miltiades" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Shock" "fecha" => "2013" "volumen" => "40" "paginaInicial" => "375" "paginaFinal" => "381" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0260" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute respiratory distress: from syndrome to disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P. Cardinal-Fernández" 1 => "E. Correger" 2 => "J. Villanueva" 3 => "F. Rios" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medin.2015.11.006" "Revista" => array:6 [ "tituloSerie" => "Med Intensiva" "fecha" => "2016" "volumen" => "40" "paginaInicial" => "169" "paginaFinal" => "175" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26754207" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0265" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adult respiratory distress syndrome risk factors for injured patients undergoing damage control laparotomy: AAST multicenter post hoc analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.D. Zielinski" 1 => "D. Jenkins" 2 => "B.A. Cotton" 3 => "K. Inaba" 4 => "G. Vercruysse" 5 => "R. Coimbra" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/TA.0000000000000421" "Revista" => array:6 [ "tituloSerie" => "J Trauma Acute Care Surg" "fecha" => "2014" "volumen" => "77" "paginaInicial" => "886" "paginaFinal" => "891" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25248057" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0270" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for ARDS in patients receiving mechanical ventilation for >48<span class="elsevierStyleHsp" style=""></span>h" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "X. Jia" 1 => "A. Malhotra" 2 => "M. Saeed" 3 => "R.G. Mark" 4 => "D. Talmor" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.07-1121" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2008" "volumen" => "133" "paginaInicial" => "853" "paginaFinal" => "861" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18263691" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0275" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens. A randomized assessor-blinded multicenter trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Brandstrup" 1 => "H. Tønnesen" 2 => "R. Beier-Holgersen" 3 => "E. Hjortsø" 4 => "H. Ørding" 5 => "K. Lindorff-Larsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.sla.0000094387.50865.23" "Revista" => array:6 [ "tituloSerie" => "Ann Surg" "fecha" => "2003" "volumen" => "238" "paginaInicial" => "641" "paginaFinal" => "648" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14578723" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0280" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "perioperative fluid management strategies in major surgery: a stratified meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "T. Corcoran" 1 => "J.E. Rhodes" 2 => "S. Clarke" 3 => "P.S. Myles" 4 => "K.M. Ho" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1213/ANE.0b013e318240d6eb" "Revista" => array:6 [ "tituloSerie" => "Anesth Analg" "fecha" => "2012" "volumen" => "114" "paginaInicial" => "640" "paginaFinal" => "651" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22253274" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0285" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The relationship between ARDS, pulmonary infiltration, fluid balance, and hemodynamics in critically ill surgical patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.H. Bishop" 1 => "J. Jorgens" 2 => "W.C. Shoemaker" 3 => "P.L. Appel" 4 => "A. Fleming" 5 => "D. Williams" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Am Surg" "fecha" => "1991" "volumen" => "57" "paginaInicial" => "785" "paginaFinal" => "792" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1746795" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0290" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intraoperative risk factors for acute respiratory distress syndrome in critically ill patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C.G. Hughes" 1 => "L. Weavind" 2 => "A. Banerjee" 3 => "N.D. Mercaldo" 4 => "J.S. Schildcrout" 5 => "P.P. Pandharipande" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Anesth Analg" "fecha" => "2010" "volumen" => "111" "paginaInicial" => "464" "paginaFinal" => "467" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0295" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O. Hamzaoui" 1 => "J.F. Georger" 2 => "X. Monnet" 3 => "H. Ksouri" 4 => "J. Maizel" 5 => "C. Richard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/cc9207" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2010" "volumen" => "14" "paginaInicial" => "R142" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20670424" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0300" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Norepinephrine exerts an inotropic effect during the early phase of human septic shock" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "O. Hamzaoui" 1 => "M. Jozwiak" 2 => "T. Gefriaud" 3 => "B. Sztrymf" 4 => "D. Prat" 5 => "F. Jacobs" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Br J Anaesth" "fecha" => "2018" "volumen" => "120" "paginaInicial" => "517" "paginaFinal" => "524" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0305" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of norepinephrine on right ventricular function in septic shock patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Martin" 1 => "G. Perrin" 2 => "P. Saux" 3 => "L. Papazian" 4 => "F. Gouin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Int Care Med" "fecha" => "1994" "volumen" => "20" "paginaInicial" => "444" "paginaFinal" => "447" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0310" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effects of norepinephrine on mean systemic pressure and venous return in human septic shock" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Persichini" 1 => "S. Silva" 2 => "J.L. Teboul" 3 => "M. Jozwiak" 4 => "D. Chemla" 5 => "C. Richard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e318260c6c3" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2012" "volumen" => "40" "paginaInicial" => "3146" "paginaFinal" => "3153" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22926333" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0315" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for the development of acute lung injury in patients with septic shock: an observational cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Iscimen" 1 => "R. Cartin-Ceba" 2 => "M. Yilmaz" 3 => "H. Khan" 4 => "R.D. Hubmayr" 5 => "B. Afessa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0b013e31816fc2c0" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2008" "volumen" => "36" "paginaInicial" => "1518" "paginaFinal" => "1522" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18434908" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0320" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cardiac contractility is not depressed in early canine endotoxic shock" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.R. Pinsky" 1 => "P. Rico" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.161.4.9904033" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2000" "volumen" => "161" "paginaInicial" => "1087" "paginaFinal" => "1093" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10764295" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0325" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An official American Thoracic Society workshop report: features and measurements of experimental acute lung injury in animals" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Matute-Bello" 1 => "G. Downey" 2 => "B.B. Moore" 3 => "S.D. Groshong" 4 => "M.A. Matthay" 5 => "A.S. Slutsky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/rcmb.2009-0210ST" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "2011" "volumen" => "44" "paginaInicial" => "725" "paginaFinal" => "738" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21531958" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0330" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ARDS: what experimental models have taught us" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P.R. Rocco" 1 => "Nieman GF:" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-016-4268-9" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2016" "volumen" => "42" "paginaInicial" => "806" "paginaFinal" => "810" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26928038" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0335" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on acute respiratory distress syndrome's pathology. Recent insights into in vivo alveolar regeneration" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. Ficial" 1 => "M. Chilosi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Shortness Breath" "fecha" => "2014" "volumen" => "3" "paginaInicial" => "102" "paginaFinal" => "107" ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0340" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "I.Y. Adamson" 1 => "D.H. Bowden" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Lab Invest" "fecha" => "1974" "volumen" => "30" "paginaInicial" => "35" "paginaFinal" => "42" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/4812806" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0345" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modeling the two-hit hypothesis for evaluating strategies to prevent organ injury after shock/resuscitation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "O.D. Rotstein" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "J Trauma" "fecha" => "2003" "volumen" => "54" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0350" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A positive fluid balance is an independent prognostic factor in patients with sepsis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Acheampong" 1 => "J.L. Vincent" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Crit Care" "fecha" => "2015" "volumen" => "19" "paginaInicial" => "251" ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0355" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early risk factors and the role of fluid administration in developing acute respiratory distress syndrome in septic patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.R. Seethala" 1 => "P.C. Hou" 2 => "I.P. Aisiku" 3 => "G. Frendl" 4 => "P.K. Park" 5 => "M.E. Mikkelsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13613-017-0233-1" "Revista" => array:5 [ "tituloSerie" => "Ann Intensive Care" "fecha" => "2017" "volumen" => "7" "paginaInicial" => "11" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28116595" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0360" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Volume of fluids administered during resuscitation for severe sepsis and septic shock and the development of the acute respiratory distress syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "D.W. Chang" 1 => "R. Huynh" 2 => "E. Sandoval" 3 => "N. Han" 4 => "C.J. Coil" 5 => "B.J. Spellberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcrc.2014.06.005" "Revista" => array:6 [ "tituloSerie" => "J Crit Care" "fecha" => "2014" "volumen" => "29" "paginaInicial" => "1011" "paginaFinal" => "1015" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25027612" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0365" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effect of an early resuscitation protocol on in-hospital mortality among adults with sepsis and hypotension: a randomized clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Andrews" 1 => "M.W. Semler" 2 => "L. Muchemwa" 3 => "L. Kelly" 4 => "S. Lakhi" 5 => "D.C. Heimburger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2017.10913" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2017" "volumen" => "318" "paginaInicial" => "1233" "paginaFinal" => "1240" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28973227" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0370" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Unintended consequences: fluid resuscitation worsens shock in an ovine model of endotoxemia" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Byrne" 1 => "N.G. Obonyo" 2 => "S.D. Diab" 3 => "K.R. Dunster" 4 => "M.R. Passmore" 5 => "A.C. Boon" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2018" "volumen" => "198" "paginaInicial" => "1043" "paginaFinal" => "1054" ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0375" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Consequences of vascular flow on lung injury induced by mechanical ventilation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.F. Broccard" 1 => "J.R. Hotchkiss" 2 => "N. Kuwayama" 3 => "D.A. Olson" 4 => "S. Jamal" 5 => "D.O. Wangensteen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.157.6.9612006" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1998" "volumen" => "157" "paginaInicial" => "1935" "paginaFinal" => "1942" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9620930" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0380" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Blood flow vs. venous pressure effects on filtration coefficient in oleic acid-injured lung" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Anglade" 1 => "M. Corboz" 2 => "A. Menaouar" 3 => "J.C. Parker" 4 => "S. Sanou" 5 => "S. Bayat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1152/jappl.1998.84.3.1011" "Revista" => array:6 [ "tituloSerie" => "J Appl Physiol" "fecha" => "1998" "volumen" => "84" "paginaInicial" => "1011" "paginaFinal" => "1023" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9480964" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0385" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early versus delayed administration of norepinephrine in patients with septic shock" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X. Bai" 1 => "W. Yu" 2 => "W. Ji" 3 => "Z. Lin" 4 => "S. Tan" 5 => "K. Duan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13054-014-0532-y" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2014" "volumen" => "18" "paginaInicial" => "532" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25277635" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0390" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early use of norepinephrine in septic shock resuscitation (CENSER): a randomized trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Permpikul" 1 => "S. Tongyoo" 2 => "T. Viarasilpa" 3 => "T. Trainarongsakul" 4 => "T. Chakorn" 5 => "S. Udompanturak" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201806-1034OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2019" "volumen" => "199" "paginaInicial" => "1097" "paginaFinal" => "1105" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30704260" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0395" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early norepinephrine decreases fluid and ventilatory requirements in pediatric vasodilatory septic shock" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Ranjit" 1 => "R. Natraj" 2 => "S.K. Kandath" 3 => "N. Kissoon" 4 => "B. Ramakrishnan" 5 => "P.E. Marik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4103/0972-5229.192036" "Revista" => array:6 [ "tituloSerie" => "Indian J Crit Care Med" "fecha" => "2016" "volumen" => "20" "paginaInicial" => "561" "paginaFinal" => "569" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27829710" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0400" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.R. Passmore" 1 => "L. Byrne" 2 => "N.G. Obonyo" 3 => "L.E. See Hoe" 4 => "A.C. Boon" 5 => "S.D. Diab" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12931-018-0935-4" "Revista" => array:5 [ "tituloSerie" => "Respir Res" "fecha" => "2018" "volumen" => "19" "paginaInicial" => "231" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30466423" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack578936" "titulo" => "Acknowledgments" "texto" => "<p id="par0135" class="elsevierStylePara elsevierViewall">We thank Dr. Carlos Costela Villodres, from the Servicio Central de Experimentación y Producción Animal (SEPA) of the University of Cádiz, for his valuable technical assistance. The work was performed at the Servicio Central de Experimentación y Producción Animal (SEPA) of the University of Cadiz, Spain.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/21735727/0000004500000009/v2_202201010839/S2173572721001521/v2_202201010839/en/main.assets" "Apartado" => array:4 [ "identificador" => "411" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735727/0000004500000009/v2_202201010839/S2173572721001521/v2_202201010839/en/main.pdf?idApp=WMIE&text.app=https://medintensiva.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173572721001521?idApp=WMIE" ]
Year/Month | Html | Total | |
---|---|---|---|
2024 November | 2 | 2 | 4 |
2024 October | 88 | 37 | 125 |
2024 September | 79 | 38 | 117 |
2024 August | 75 | 51 | 126 |
2024 July | 50 | 25 | 75 |
2024 June | 47 | 49 | 96 |
2024 May | 55 | 29 | 84 |
2024 April | 47 | 47 | 94 |
2024 March | 46 | 21 | 67 |
2024 February | 39 | 45 | 84 |
2024 January | 59 | 40 | 99 |
2023 December | 65 | 41 | 106 |
2023 November | 59 | 52 | 111 |
2023 October | 90 | 32 | 122 |
2023 September | 56 | 45 | 101 |
2023 August | 24 | 12 | 36 |
2023 July | 34 | 23 | 57 |
2023 June | 38 | 22 | 60 |
2023 May | 45 | 40 | 85 |
2023 April | 30 | 22 | 52 |
2023 March | 52 | 29 | 81 |
2023 February | 41 | 28 | 69 |
2023 January | 28 | 33 | 61 |
2022 December | 66 | 44 | 110 |
2022 November | 62 | 35 | 97 |
2022 October | 46 | 35 | 81 |
2022 September | 40 | 31 | 71 |
2022 August | 29 | 40 | 69 |
2022 July | 33 | 45 | 78 |
2022 June | 30 | 22 | 52 |
2022 May | 33 | 25 | 58 |
2022 April | 40 | 38 | 78 |
2022 March | 47 | 68 | 115 |