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Basic Research
Blood Loss and Transcapillary Refill in Uncontrolled Treated Hemorrhage in Dogs
Elias Aissar SallumI,
Corresponding author
easallum.fnr@terra.com.br

Tel: 55 11 3289.3343
, Sueli SinozakiII, Ana Maria CalilIII, Raul CoimbraVI, Maurício Rocha E SilvaII, Luis Francisco Poli de FigueiredoV, Dario BiroliniI
I Departamento de Cirurgia, Divisão de Cirurgia Geral do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brazil
II Departamento de Cirurgia, Divisão de Cirurgia Experimental do Instituto do Coração (INCOR) - São Paulo/SP, Brazil
III Escola de Enfermagem da Universidade de São Paulo - São Paulo/SP, Brazil
IV Departamento de Cirurgia, Divisão de Trauma da Universidade de San Diego Califórnia/USA
V Departamento de Cirurgia, Divisão de Técnica Cirúrgica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - São Paulo/SP, Brasil
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Volume resuscitation has been the mainstay of treatment for hypotensive trauma victims&#46;<a class="elsevierStyleCrossRef" href="#bib1">1</a> However&#44; controversy remains because there are concerns that this approach&#44; before the control of bleeding&#44; may result in increased blood loss due to increased blood pressure&#44; which would dislodge blood clots&#44; and the dilution of clotting factors&#46;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib5">5</a></p><p id="para20" class="elsevierStylePara elsevierViewall">Hypotensive resuscitation and no fluid regimens are some strategies for avoidance of the potential side effects of volume infusion in uncontrolled hemorrhage&#46;<a class="elsevierStyleCrossRefs" href="#bib2">2&#44;3&#44;5&#44;6</a> On the other hand&#44; studies using small volumes of hypertonic saline or hypertonic saline plus dextran &#40;HSD&#41; have shown hemodynamic benefits and no significant increase in blood loss in several models of uncontrolled hemorrhage&#46;<a class="elsevierStyleCrossRef" href="#bib7">7</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib15">15</a> None of the clinical studies evaluating hypertonic saline or hypertonic saline plus dextran &#40;HSD&#41; as the first fluid volumes infused into hypotensive patients suggested increased bleeding&#46; On the contrary&#44; these studies systematically suggest that hemodynamic benefits are achieved with less fluid and blood products in comparison to what is required for standard isotonic resuscitation&#46;<a class="elsevierStyleCrossRef" href="#bib15">15</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib24">24</a></p><p id="para30" class="elsevierStylePara elsevierViewall">In the present study&#44; we promoted a retroperitoneal hemorrhage with class III shock by ATLS with a simulation of blunt abdominal injury<a class="elsevierStyleCrossRefs" href="#bib1">1&#44;25</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib27">27</a> by bilateral posterior iliac artery puncture to evaluate fluid shifts and blood loss after HSD or isotonic saline infusion&#44; in comparison to no fluid replacement&#46; Our hypothesis is that small volumes of HSD promote volume expansion and hemodynamic benefits&#44; in spite of modest increases in blood loss&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">MATERIALS AND METHODS</span><p id="para40" class="elsevierStylePara elsevierViewall">This project was previously approved by the Ethics Committee of the Heart Institute and conforms to National Institutes of Health guidelines for the use of experimental animals&#46;</p><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">Surgical preparation</span><p id="para50" class="elsevierStylePara elsevierViewall">Experiments were performed on 21 male mongrel dogs weighing 16&#46;8 &#177; 2&#46;2 kg &#40;STD DEV&#41; that had been splenectomized under sterile conditions three days before the experiment&#44; under 2&#37; halothane anesthesia to avoid the effect of splenic contraction and release of red cells to the circulation during shock&#46;</p><p id="para60" class="elsevierStylePara elsevierViewall">Dogs were fed standard dog chow and water ad libitum in the divisional kennel&#46; Food was removed 12 h prior to the experiment&#44; and water was discontinued 1 h before intravenous anesthesia with 1&#46;5 mg&#47;kg of morphine and 25 mg&#47;kg of pentobarbital sodium&#46; Animals were endotracheally intubated and mechanically ventilated &#40;FiO<span class="elsevierStyleInf">2</span>&#61;50&#37;&#44; TV&#61;10 cc&#47;kg&#44; respiratory rate&#61;12 rpm&#41; during the whole experiment&#46; An arterial blood sample was drawn before the experiments and used to adjust the ventilator settings&#46;</p><p id="para70" class="elsevierStylePara elsevierViewall">The following interventions were performed through cutdown incisions&#58; 1&#41; bilateral femoral artery dissection for the introduction of Veress needles positioned under radioscopy with their tips at the level of the 6<span class="elsevierStyleSup">th</span> - 7<span class="elsevierStyleSup">th</span> vertebral body to create a retroperitoneal hematoma &#40;see description of the experimental model below&#41;&#59; 2&#41; A 5F triple lumen Swan-Ganz catheter &#40;Baxter Health Care Corporation&#41; was introduced through the right internal jugular&#46; The tip of the catheter was positioned into the pulmonary artery under fluoroscopic guidance and pressure wave analysis&#46; The catheter was connected to a pressure monitor &#40;MP 100 WSW&#44; Biopac System&#44; USA&#41;&#44; and all pressure measurements were stored in a computer system &#40;Acknowledge III&#41; for analysis as well as for the collection of mixed venous blood&#59; 3&#41; Large bore &#40;P240&#41; polyethylene cannulae were inserted into the right common carotid artery and connected to a strain gauge transducer coupled to a model 1290-CP recorder to control mean arterial pressure&#59; 4&#41; A short catheter number 14 was inserted into the left external jugular vein for Tc<span class="elsevierStyleSup">99m</span> infusion and volume replacement&#59; 5&#41; A 4F Foley catheter was used for urinary output monitoring&#46;</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Hemorrhage Model</span><p id="para80" class="elsevierStylePara elsevierViewall">The hemorrhage model of a retroperitoneal hematoma utilized in the present study was initially described by Cruz Jr&#46;<a class="elsevierStyleCrossRef" href="#bib28">28</a> Briefly&#44; after dissection of both femoral arteries in the groin&#44; a Veress needle was introduced into each artery&#44; advanced towards the common iliac artery under fluoroscopic visualization and pushed against the posterior-lateral wall of the vessel to create an injury&#46;</p><p id="para90" class="elsevierStylePara elsevierViewall">At the end of the experiment&#44; animals were sacrificed by an intravenous injection of pentobarbital &#40;50 mg&#47;kg&#41;&#44; followed by 20 ml of 19&#46;1&#37; KCl&#46; An autopsy was performed to document the severity and extent of the retroperitoneal hematoma and the size and location of the iliac artery injury&#46; The iliac arteries were dissected free&#44; and each perforation created by the Veress needle was measured&#46;</p><p id="para100" class="elsevierStylePara elsevierViewall">Exclusion criteria included&#58; a&#41; animals with initial hemoglobin levels &#60; 10 g&#47;dL&#44; b&#41; arterial injuries &#8804; 5 mm&#44; c&#41; extension of the hematoma greater than the area of image acquisition of the gamma camera&#44; d&#41; peritoneal perforation with subsequent bleeding into the peritoneal cavity&#44; and e&#41; mean arterial pressure &#40;MAP&#41; 50&#37; higher than initial MAP five minutes after arterial injury&#46;</p><p id="para110" class="elsevierStylePara elsevierViewall">The study was divided into two phases&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">Phase I&#58; Development of a method for the quantification of blood loss&#46; Experiment A &#8211; Physical Simulation</span><p id="para120" class="elsevierStylePara elsevierViewall">Physical simulation was performed to verify the reliability of quantifying a known&#44; pre-determined volume of fluid using sequential gamma camera image acquisitions&#46; Initially&#44; a plastic syringe filled with 10 mL of water&#44; containing <span class="elsevierStyleSup">99m</span> Technetium &#40;<span class="elsevierStyleSup">99m</span>Tc&#44; Instituto de Pesquisas Energ&#233;ticas e Nucleares&#47;CNEN&#44; Universidade de S&#227;o Paulo&#44; Brazil&#41; with a known amount of radioactivity &#40;2 mCi&#41; was placed under the gamma camera and radioactivity was measured&#46; A plastic bag was then filled with successive 50 mL aliquots of water containing <span class="elsevierStyleSup">99m</span>Tc &#40;2 mCi&#41; up to a total volume of 1300 mL&#46; Radioactivity in the syringe was compared with that in the plastic bag to establish a correction factor accounting for the geometry of the bag containing larger amounts of radiolabeled fluid&#46; Measurements were performed in triplicate&#46;</p><p id="para130" class="elsevierStylePara elsevierViewall">The following equation describes the correction factor used by ROCHA &#40;1976&#41;<a class="elsevierStyleCrossRef" href="#bib29">29</a> for the measurement of radioactivity in the plastic bag containing <span class="elsevierStyleSup">99m</span>Tc dissolved in water&#58;<elsevierMultimedia ident="formula10"></elsevierMultimedia>where RC is the radioactivity in the bag &#40;&#8220;real&#8221; count&#41;&#59; MC is the measured radioactivity&#59; 0&#46;15 is the attenuation factor for water&#59; D is the thickness of the bag&#59; and CF is the required correction factor&#46; An operative value for CF was determined from averaged RC values within the expected range of blood loss in the retroperitoneal hematoma&#46;</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">Experiment B &#8211; Artificially Created Retroperitoneal Hematoma</span><p id="para140" class="elsevierStylePara elsevierViewall">This set of experiments was performed to establish the correction factor due to photon attenuation caused by the presence of the abdominal wall and intra-abdominal contents in the quantification of an artificially created retroperitoneal hematoma of a known&#44; pre-determined volume <a class="elsevierStyleCrossRef" href="#bib29">29</a>&#46;</p><p id="para150" class="elsevierStylePara elsevierViewall">Five male mongrel dogs weighing 16&#46;8&#177;2&#46;6 kg were used&#46; Blood &#40;250 mL&#41; was withdrawn and radiolabeled with <span class="elsevierStyleSup">99m</span> Tc &#40;<span class="elsevierStyleSup">99m</span> Tc &#8211; TCK-11&#44; CIS Bio International&#44; France&#44; <span class="elsevierStyleSup">99m</span> Tc activity of 2 mCi&#44; Instituto de Pesquisa de Energia Nuclear&#44; Universidade de S&#227;o Paulo&#44; Brazil&#41;&#46; A syringe containing 10 mL of labeled blood was kept aside&#44; and an image was acquired at the end of each experiment for radioactivity measurements&#46;</p><p id="para160" class="elsevierStylePara elsevierViewall">Following a midline laparotomy&#44; two polyethylene catheters &#40;PE240&#41; were positioned in the area where a retroperitoneal hematoma secondary to bilateral iliac artery injury would be located&#46; The abdominal wall was then closed&#44; and the catheters were subsequently used to inject aliquots of 50 mL of blood mixed with <span class="elsevierStyleSup">99m</span>Tc-labeled red blood cells into the retroperitoneal space&#46;</p><p id="para170" class="elsevierStylePara elsevierViewall">Radioactivity measurements were performed successively&#44; at five-minute intervals following blood injection&#46; The volume of the retroperitoneal hematoma was calculated as described in Experiment A&#44; accounting for the dorsoventral thickness of the abdominal wall of the animal&#46; In this set of experiments&#44; the injected volume was limited to a maximum of 200 mL because the sutures securing the catheters in place were not reliably tight for volumes greater than 200 mL&#46;</p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle120">Experiment C &#8211; In Vivo Retroperitoneal Hematoma</span><p id="para180" class="elsevierStylePara elsevierViewall">This set of experiments was performed to determine the volume of blood present in a retroperitoneal hematoma &#40;VRPH&#41; in vivo&#46; In one group of animals&#44; a gamma camera and <span class="elsevierStyleSup">99m</span>Tc-radiolabeled red blood cells were used to determine the blood volume present in the retroperitoneal hematoma &#91;GC group &#40;n&#61;7&#41;&#93;&#46; In another group&#44; the dilution technique with <span class="elsevierStyleSup">99m</span>Tc- and Chromium &#40;<span class="elsevierStyleSup">51</span>Cr&#44; Instituto de Pesquisas Energ&#233;ticas e Nucleares&#47;CNEN&#44; Universidade de S&#227;o Paulo&#44; Brazil&#44; 200 &#956;Ci&#41;-radiolabeled red blood cells was used to quantify the initial and final circulating blood volumes &#40;CBV&#41;&#44; respectively &#91;DT group &#40;n&#61;5&#41;&#93;&#46;</p></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle130">Quantification of Bleeding Volume</span><p id="para190" class="elsevierStylePara elsevierViewall">A portable gamma camera &#40;Elscint&#44; model Apex 209M&#44; Israel&#41; with a parallel collimator was positioned 5cm above the abdomen&#44; centered over the putative area of the retroperitoneal hematoma&#46; Images were acquired over 5 min at 15-min intervals throughout the experiment&#46; At the end of each experiment&#44; the cumulative radioactivity for each measurement was analyzed&#46; Because of the short half-life of <span class="elsevierStyleSup">99m</span>Tc &#40;six hours&#41;&#44; all counts were corrected for activity decay in the standard fashion&#46;</p></span><span id="cesec90" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle140">Measurement of initial circulating red blood cell volume and total blood volume</span><p id="para200" class="elsevierStylePara elsevierViewall">Initial circulating red blood cell volume &#40;CRCV&#41; was determined by means of isotope dilution of the radioactive tracer technetium &#40;<span class="elsevierStyleSup">99m</span>Tc&#41;&#44; as applied by Kowalsky and Perry&#44; 1987&#46;<a class="elsevierStyleCrossRef" href="#bib30">30</a> Previously-labeled red blood cells &#40;3 mL&#41; containing a known total load of tracer &#40;L&#41; were injected into the systemic circulation and allowed to mix uniformly over a period of 15 min&#46; A syringe containing 10 mL of labeled blood was kept aside&#44; and a radioactivity measurement of the sample was obtained at the end of each experiment to establish the baseline count of radioactive tracer per mL&#46; A separate blood sample was collected for determination of the initial hematocrit &#40;Htc&#41; and for determining tracer concentration &#40;C&#41; using a scintillation counter &#40;Phillips Medical System Division&#44; model XL 1100 and XL 1151&#44; Eindhoven&#44; Netherlands&#41;&#46; CRCV was calculated according to the following equation&#58;<elsevierMultimedia ident="formula20"></elsevierMultimedia></p><p id="para210" class="elsevierStylePara elsevierViewall">The circulating blood volume &#40;CBV&#41; was calculated as demonstrated below&#58;<elsevierMultimedia ident="formula30"></elsevierMultimedia></p><p id="para220" class="elsevierStylePara elsevierViewall">Plasma volume &#40;PV&#41; was determined by subtracting CRCV from CBV&#46;</p></span><span id="cesec100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle150">Phase II&#46; Resuscitated uncontrolled hemorrhage Experiment D &#8211; in vivo retroperitoneal hematoma followed by fluid resuscitation</span><p id="para230" class="elsevierStylePara elsevierViewall">The experiments were initiated 15 minutes after the injection of <span class="elsevierStyleSup">99m</span>Tc-labeled red cells&#44; when the first radioactivity measurement was obtained using the gamma camera &#40;baseline measurement value&#44; <a class="elsevierStyleCrossRef" href="#f3-cln_65p67">Figure 3</a>&#41;&#46; The arterial lesions were subsequently created &#40;T0&#41;&#46;</p><elsevierMultimedia ident="f3-cln_65p67"></elsevierMultimedia><p id="para240" class="elsevierStylePara elsevierViewall">The experiment lasted a total of 75 minutes&#44; during which six radioactivity measurements&#44; 15 minutes apart&#44; were obtained &#40;T0&#44; T15&#44; T30&#44; T45&#44; T60&#44; T75&#41;&#46; Coinciding with the time of each radioactivity measurement&#44; mean arterial pressure &#40;MAP&#41; and cardiac index &#40;CI&#41; were determined&#44; and arterial blood samples were obtained for Htc measurements&#46;</p><p id="cpt10" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="f9-cln_65p67"></elsevierMultimedia></p><span id="cesec110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle160">Study groups</span><p id="para250" class="elsevierStylePara elsevierViewall">Five minutes before T30&#44; the animals were randomly assigned to one of three groups&#44; according to the fluid resuscitation regimen&#58; NT&#44; untreated controls &#40;n&#61;7&#41; in which the animals underwent bilateral iliac artery injury and were observed for 75 min without any fluid resuscitation&#59; LR &#40;n&#61;7&#41; in which the animals received 32 mL&#47;kg of lactated Ringer&#8217;s&#59; or HSD &#40;n&#61;7&#41;&#44; in which animals received 4 mL&#47;kg of 7&#46;5&#37; NaCl&#44; 6&#37; Dextran 70 in five minutes&#44; and followed up to 75 min&#46;</p></span><span id="cesec120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle170">Volume of Red Cells in the Hematoma &#40;VRCH&#41;</span><p id="para260" class="elsevierStylePara elsevierViewall">The VRCH was calculated considering the initial circulating red blood cell volume &#40;CRCV&#41; determined by the dilution technique and the VRPH&#44; as described in Experiment C&#46; Before fluid resuscitation &#40;T30&#41;&#44; the VRCH was calculated as follows <a class="elsevierStyleCrossRef" href="#bib30">30</a>&#58;<elsevierMultimedia ident="formula40"></elsevierMultimedia></p><p id="para270" class="elsevierStylePara elsevierViewall">For all time points after fluid resuscitation&#44; the VRCH was calculated according to the following equation<a class="elsevierStyleCrossRef" href="#bib30">30</a>&#58;<elsevierMultimedia ident="formula50"></elsevierMultimedia></p><p id="para280" class="elsevierStylePara elsevierViewall">where <span class="elsevierStyleItalic">Tx</span> is the time point of the actual measurement&#46;</p></span><span id="cesec130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle180">Volume of Retroperitoneal Hematoma &#40;VRPH&#41;</span><p id="para290" class="elsevierStylePara elsevierViewall">Before fluid resuscitation &#40;T30&#41;&#44; the VRPH &#40;mL&#47;kg&#41; was calculated according to the following equation <a class="elsevierStyleCrossRef" href="#bib30">30</a>&#58;<elsevierMultimedia ident="formula60"></elsevierMultimedia></p><p id="para300" class="elsevierStylePara elsevierViewall">After fluid resuscitation&#44; the VRPH was calculated as follows <a class="elsevierStyleCrossRef" href="#bib30">30</a>&#58;<elsevierMultimedia ident="formula70"></elsevierMultimedia></p></span><span id="cesec140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle190">Circulating Red Cell Volume &#40;CRCV&#41;</span><p id="para310" class="elsevierStylePara elsevierViewall">The CRCV &#40;mL&#47;kg&#41; was determined by the difference between the initial circulating red cell volume &#40;CRCV&#41; and the VRPH&#46;</p></span><span id="cesec150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle200">Circulating Blood Volume &#40;CBV&#41;</span><p id="para320" class="elsevierStylePara elsevierViewall">The CBV &#40;mL&#47;kg&#41; at a specific time point &#40;Tx&#41; was calculated by dividing the CRVC &#40;Tx&#41; by the Htc &#40;Tx&#41;&#46;</p></span><span id="cesec160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle210">Expected Circulating Blood Volume &#40;ECBV&#41;</span><p id="para330" class="elsevierStylePara elsevierViewall">The ECBV &#40;mL&#47;kg&#41; at Tx was calculated as the difference between the initial CBV and the VRPH at Tx until T30&#46; After volume resuscitation &#40;T45 and beyond&#41;&#44; ECBV for the LR group was calculated as follows&#58;<elsevierMultimedia ident="formula80"></elsevierMultimedia></p><p id="para340" class="elsevierStylePara elsevierViewall">where VI is the volume of the resuscitation fluid used&#44; i&#46;e&#46;&#44; 32 mL&#47;kg for LR- and 4 mL&#47;kg for HSD-resuscitated animals&#46;</p></span><span id="cesec170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle220">Transcapillary Refill &#40;TR&#41;</span><p id="para350" class="elsevierStylePara elsevierViewall">TR &#40;mL&#47;kg&#41; was calculated as follows&#58;<elsevierMultimedia ident="formula90"></elsevierMultimedia></p><p id="para360" class="elsevierStylePara elsevierViewall">Volume of Retroperitoneal Bleeding Before Fluid Resuscitation &#40;VRB shock&#41;</p><p id="para370" class="elsevierStylePara elsevierViewall">The VRB shock &#40;&#37; of CRCV&#41; caused by the arterial injuries was calculated from T0 to T30 as follows&#58;<elsevierMultimedia ident="formula100"></elsevierMultimedia></p><p id="para380" class="elsevierStylePara elsevierViewall">Volume of Retroperitoneal Bleeding After Fluid Resuscitation &#40;VRBresus&#41;</p><p id="para390" class="elsevierStylePara elsevierViewall">The VRB<span class="elsevierStyleItalic">resus</span> occurring after fluid resuscitation &#40;from T30 to T75&#41; was calculated as follows&#58;<elsevierMultimedia ident="formula110"></elsevierMultimedia></p></span></span><span id="cesec180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle230">Statistical analysis</span><p id="para400" class="elsevierStylePara elsevierViewall">Data are presented as the mean &#177; standard error of the mean&#46; For comparisons of continuous variables&#44; either the Student&#8217;s t-test or two-way analysis of variance &#40;ANOVA&#41; with Turkey&#8217;s B correction for multiple comparisons was used&#46; A p value &#60; 0&#46;05 was considered statistically significant&#46;</p></span></span><span id="cesec190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle240">RESULTS</span><span id="cesec200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle250">Phase I&#58; Development of a method for the quantification of blood loss&#46; Experiment A &#8211; Physical Simulation and Experiment B &#8211; Artificially-Created Retroperitoneal Hematoma</span><p id="para410" class="elsevierStylePara elsevierViewall">A final CF value of 0&#46;015 was determined after averaging RC values obtained from multiple measurements &#40;see methods&#41;&#46; A comparison between a known volume in the plastic bag and the calculated volume based on radioactivity measurements by the gamma camera &#40;Experiment A&#41; was made&#46; For a volume of 50 mL&#44; the observed averaged error was 17&#37;&#44; and the error was greater than 8&#37; for volumes larger than 800 mL&#46; A significant correlation was observed between the expected and the measured volumes of fluid in the bag&#44; within a range of 100 &#8211; 800 mL&#44; with a calculated error of less than 3&#37; &#40;<a class="elsevierStyleCrossRef" href="#f1-cln_65p67">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="f1-cln_65p67"></elsevierMultimedia><p id="para420" class="elsevierStylePara elsevierViewall">The range of variation for calculated values obtained from sequential radioactivity measurements in this phase was between 4&#37; and 6&#37; from the mean&#46; Because results of measurements obtained during Experiment A were reliably linear within the 100 mL to 900 mL range&#44; and because blood volumes in the retroperitoneum following induction of a hematoma ranged from 400 mL to 600 mL&#44; the CF value obtained in Experiment B&#44; which accounted for the thickness of the animal&#8217;s abdominal wall&#44; was extrapolated and used in Experiment C&#46;</p></span><span id="cesec210" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle260">Experiment C &#8211; In Vivo Retroperitoneal Hematoma</span><p id="para430" class="elsevierStylePara elsevierViewall">Cardiac index &#40;panel A&#41;&#44; mean arterial pressure &#40;panel B&#41;&#44; and hematocrit &#40;panel C&#41; were measured before &#40;time &#61; 0 min&#41; and after &#40;time &#61; 15 min and 30 min&#41; the creation of bilateral iliac artery injuries &#40;<a class="elsevierStyleCrossRef" href="#f2-cln_65p67">Figure 2</a>&#41;&#46; No differences were observed in these parameters between the GC and DT groups&#46; Retroperitoneal hematoma formation led to a significant decrease in cardiac index and mean arterial pressure at 15 min and 30 min &#40;p&#60;0&#46;001&#41;&#46;</p><elsevierMultimedia ident="f2-cln_65p67"></elsevierMultimedia><p id="para440" class="elsevierStylePara elsevierViewall">Examples of gamma camera images acquired from one animal during Experiment C&#44; taken before and 5&#44; 10&#44; 15&#44; 30&#44; and 75 minutes after the arterial injuries were created&#44; are shown in <a class="elsevierStyleCrossRef" href="#f3-cln_65p67">Figure 3</a>&#46; Background images and radiation obtained from a syringe containing blood and a radiotracer &#40;see methods&#41; are shown for comparison&#46; Every third image acquired by the gamma camera was used for quantification of the retroperitoneal bleeding volume&#46;</p><p id="para450" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#f4-cln_65p67">Figure 4</a> represents the volume of the retroperitoneal hematoma &#40;VRPH&#41; and volume of red cells in the hematoma &#40;VRCH&#41; over time measured at 5-min intervals&#46; Bleeding was more pronounced within the first five minutes after the arterial injury was created&#44; and it ended spontaneously by 15 minutes after the bilateral iliac artery injuries were created&#46;</p><elsevierMultimedia ident="f4-cln_65p67"></elsevierMultimedia><p id="para460" class="elsevierStylePara elsevierViewall">Comparisons between the volume of the retroperitoneal hematoma &#40;VRPH&#41;&#44; volume of red cells in the hematoma &#40;VRCH&#41;&#44; and plasma volume of animals in the gamma camera &#40;GC group&#41; or the dilution technique &#40;DT Group&#41; are shown in <a class="elsevierStyleCrossRef" href="#f5-cln_65p67">Figure 5</a>&#46; No significant differences were found when comparing these two methods&#46;</p><elsevierMultimedia ident="f5-cln_65p67"></elsevierMultimedia><p id="para470" class="elsevierStylePara elsevierViewall">In a comparison between the circulating blood volume &#40;CBV&#41; measured in the GC and DT groups&#44; a significant decrease in the circulating blood volume in both groups was observed&#44; which paralleled the formation of the hematoma &#40;<a class="elsevierStyleCrossRef" href="#f6-cln_65p67">Figure 6</a>&#41;&#46;</p><elsevierMultimedia ident="f6-cln_65p67"></elsevierMultimedia><p id="para480" class="elsevierStylePara elsevierViewall">More importantly&#44; the gamma camera technique was as accurate as the classic dilution technique in determining the total red blood cell volume in the hematoma &#40;31&#46;2 &#177; 1&#46;4&#37; for the GC group vs&#46; 32&#46;8 &#177; 3&#46;9&#37; for the DT group&#44; p &#62; 0&#46;7&#41;&#46;</p></span><span id="cesec220" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle270">Phase II-Resuscitated uncontrolled hemorrhage Experiment D &#8211; In vivo retroperitoneal hematoma and fluid resuscitation</span><p id="para490" class="elsevierStylePara elsevierViewall">A total of 25 animals were used in Experiment D&#46; Four animals were excluded&#44; one due to anemia before the beginning of the experiment and three because of bleeding from the retroperitoneum into the peritoneal cavity&#46;</p><p id="para500" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#f7-cln_65p67">Figure 7</a> presents the results of MAP&#44; CI&#44; and Htc measurements throughout the experiment&#46; The mean arterial pressure &#40;MAP&#41; decreased significantly during the first fifteen min after the injury&#44; and it increased equally in all groups &#40;panel A&#41;&#46; A reduction in cardiac index &#40;CI&#41; was observed 15 min after injury in all groups&#46; After fluid resuscitation&#44; a significant increase in CI was observed in LR- and HSD-treated animals &#40;T45&#41; when compared with the NT group &#40;&#42; p&#60;0&#46;05 NT vs&#46; LR and HSD&#41; &#40;panel B&#41;&#46; The mean pulmonary artery pressure and pulmonary capillary wedge pressure were similar to the cardiac index&#46; The hematocrit &#40;Htc&#41; was significantly reduced during the first fifteen minutes after the injury&#46; After fluid resuscitation occurred&#44; there was an initial decrease in the Htc in treated groups &#40;from T30 to T45&#41;&#44; which was similar in all groups from T45 to T75 &#40;panel C&#41;&#46; The hemoglobin level was similar to the hematocrit&#46;</p><elsevierMultimedia ident="f7-cln_65p67"></elsevierMultimedia><p id="para510" class="elsevierStylePara elsevierViewall">CBV&#44; CRCV&#44; VRPH&#44; VRCH&#44; and TR results are shown in <a class="elsevierStyleCrossRef" href="#f8-cln_65p67">Figure 8</a>&#46;</p><elsevierMultimedia ident="f8-cln_65p67"></elsevierMultimedia><p id="para520" class="elsevierStylePara elsevierViewall">CBV was equally reduced during the initial 15 minutes after injury in all groups&#46; Fluid resuscitation with subsequent rebleeding led to a decrease in CBV in both treatment groups&#44; although changes were more pronounced in LR-treated animals &#40;p&#60;0&#46;05 NT vs&#46; LR&#41; &#40;panel A&#41;&#46;</p><p id="para530" class="elsevierStylePara elsevierViewall">The circulating red cell volume &#40;CRCV&#41; decreased slightly during hemorrhage&#46; Fluid resuscitation with subsequent rebleeding led to a decrease in CBV in both treatment groups&#44; although changes were more pronounced in LR-treated animals &#40;p&#60;0&#46;05 NT vs&#46; LR&#59; p&#60;0&#46;05 LR vs&#46; HSD&#41; &#40;panel B&#41;&#46;</p><p id="para540" class="elsevierStylePara elsevierViewall">Blood volume in the retroperitoneal hematoma &#40;VRPH&#41; at 15-minute intervals is shown&#46; Bleeding was more pronounced in the initial 15 minutes after the bilateral iliac artery injuries were created&#46; Significantly higher VRPH was observed in LR-treated animals when compared to the HSD group&#44; indicating more pronounced rebleeding &#40;p&#60;0&#46;05 NT vs&#46; LR and HSD&#59; p&#60;0&#46;05 LR vs&#46; HSD&#41; &#40;panel C&#41;&#46;</p><p id="para550" class="elsevierStylePara elsevierViewall">The volume of red cells in the retroperitoneal hematoma &#40;VRCH&#41; at 15-minute intervals is shown&#46; Bleeding was more pronounced in the initial 15 minutes after the bilateral iliac artery injuries were created&#46; Fluid resuscitation with subsequent rebleeding led to an increase in VRCH in both treated groups&#46; No differences between LR- and HSD-treated animals were observed &#40;p&#60;0&#46;05 NT vs&#46; LR and HSD&#41; &#40;panel D&#41;&#46;</p><p id="para560" class="elsevierStylePara elsevierViewall">Transcapillary refill increased in all groups during hemorrhage&#46; Fluid resuscitation determined plateaus in the NT group&#46; It increased in HSD-treated animals and decreased significantly in the LR group &#40;p&#60;0&#46;05 NT and HSD vs&#46; LR&#41; &#40;panel E&#41;&#46; In addition&#44; LR-treated animals had negative TR values&#44; indicating transcapillary leaks&#44; while HSD-treated animals had significantly increased transcapillary refill&#46;</p></span></span><span id="cesec230" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle280">DISCUSSION</span><p id="para570" class="elsevierStylePara elsevierViewall">The ideal fluid resuscitation used in the treatment of hemorrhagic shock remains a subject of significant debate&#46; Issues regarding infusion volume&#44; sodium load&#44; rebleeding&#44; pulmonary complications&#44; and ultimately mortality have not yet been solved&#46; Recently&#44; hypertonic resuscitation regained attention due to its immunomodulatory potential&#46;</p><p id="para580" class="elsevierStylePara elsevierViewall">Evidence points to the fact that hypertonic saline resuscitation decreases the amount of fluid required to restore tissue perfusion when compared to LR&#46; More importantly&#44; however&#44; is the fact that hypertonic saline solutions draw fluid from the interstitium into the intravascular space&#46; This effect is in contrast to isotonic or hypotonic saline solutions&#44; which lead to leaks into the interstitial space of at least two-thirds of the total infusion volume&#44; leading to significant decreases in the intravascular volume and formation of tissue edema&#44; further compromising tissue perfusion&#46; In addition&#44; improvements in microcirculatory blood flow&#44; decreased neutrophil adhesiveness&#44; and reduced susceptibility to sepsis after hemorrhagic shock have been documented after hypertonic saline resuscitation&#46;<a class="elsevierStyleCrossRefs" href="#bib9">9&#44;12&#44;14</a>&#8211;<a class="elsevierStyleCrossRefs" href="#bib15">15&#44;31</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib36">36</a></p><p id="para590" class="elsevierStylePara elsevierViewall">Several animal models have been used to simulate naturally occurring uncontrolled hemorrhage leading to shock by creating mesenteric injury&#44;<a class="elsevierStyleCrossRef" href="#bib37">37</a> major vascular injury&#44;<a class="elsevierStyleCrossRef" href="#bib38">38</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib39">39</a> solid organ injury&#44;<a class="elsevierStyleCrossRefs" href="#bib11">11&#44;40</a> external hemorrhage&#44;<a class="elsevierStyleCrossRefs" href="#bib2">2&#44;4</a> and retroperitoneal hematomas&#46;<a class="elsevierStyleCrossRef" href="#bib28">28</a> Several studies quantified blood loss by weighing surgical sponges&#44; some used the clearance technique with Evans&#8217; blue or green indocyanine&#44; and others employed the dilution technique with radiolabeled albumin or red blood cells radiolabeled with <span class="elsevierStyleSup">99m</span>Tc&#44;<a class="elsevierStyleCrossRefs" href="#bib41">41&#44;42</a> or <span class="elsevierStyleSup">51</span>Cr&#46; <a class="elsevierStyleCrossRef" href="#bib43">43</a></p><p id="para600" class="elsevierStylePara elsevierViewall">The gamma camera was developed in 1964&#46; With the development of short half-life radioisotopes and low energy photon emission&#44; this apparatus is now widely employed in diagnostic procedures&#46; It has been used in the evaluation of ventricular function<a class="elsevierStyleCrossRef" href="#bib44">44</a> and in the detection of bleeding sites secondary to upper or lower gastrointestinal pathology&#46;<a class="elsevierStyleCrossRef" href="#bib45">45</a> This study is the first to report use of a gamma camera to reliably quantify major blood loss in an experimental setting&#46;</p><p id="para610" class="elsevierStylePara elsevierViewall">We selected the present animal model because it reflects the clinical scenario seen in pelvic fractures or vascular injuries contained by the retroperitoneum&#44; allowing us to adequately quantify bleeding volumes before and after fluid resuscitation&#46; Average blood loss in the present study was 31&#37;&#44; which corresponds to a class 3 hemorrhage according to the American College of Surgeons Committee on Trauma&#46;<a class="elsevierStyleCrossRef" href="#bib1">1</a></p><p id="para620" class="elsevierStylePara elsevierViewall">We compared gamma camera measurements with the dilutional technique and found the gamma camera to be potentially useful for the follow-up of experimental uncontrolled hemorrhage models&#46; When compared to previously described methods&#44; this technique has many potential advantages&#46; It allows for the detection of an area of hemorrhage&#44; quantification of bleeding&#44; and determination of the moment at which bleeding ceases&#46; It is non-invasive and can result in values closer to reality when compared to previously described methods&#46; It is&#44; however&#44; strictly limited to experimental conditions since it requires labeling of blood before hemorrhage begins&#46; Another shortcoming is that the spleen must be removed to avoid distribution of red cells between two dynamically different compartments&#46;</p><p id="para630" class="elsevierStylePara elsevierViewall">Other important points should be emphasized&#46; The circulating blood volume within the acquisition area of the gamma camera must not vary&#44; although this restriction is of small significance within the abdominal cavity&#46; The use of a second radioisotope is not feasible because it may interfere with image acquisition&#46; Therefore&#44; validation had to be performed in a separate group of experiments&#46;</p><p id="para640" class="elsevierStylePara elsevierViewall">Bleeding into a confined space&#44; as occurs in the retroperitoneum&#44; is very difficult to quantify&#46; Direct measurements of blood loss are usually performed by draining blood from the abdominal cavity and weighing sponges&#59; however&#44; errors as large as 60&#37; have been described with these and other less accurate methods&#46;<a class="elsevierStyleCrossRefs" href="#bib40">40&#44;46</a> These methods were not applicable to our model because retroperitoneal hematomas are usually formed by clotted blood&#46; Computed tomography scanning has been frequently used in the diagnosis of hemoperitoneum&#59; however&#44; the quantification of retroperitoneal bleeding volume by this method is inaccurate&#44; and its use is contraindicated in patients who are in shock&#46; The use of labeled plasma albumin to evaluate the circulating plasma volume can be misleading because of normal protein leakage into the extravascular compartment&#44; resulting in calculated values higher than the actual values&#46;<a class="elsevierStyleCrossRef" href="#bib47">47</a> Other devices developed to measure bleeding volume have proven to be costly and difficult to use&#46;<a class="elsevierStyleCrossRef" href="#bib45">45</a> Even with the use of <span class="elsevierStyleSup">99m</span>Tc or <span class="elsevierStyleSup">51</span>Cr-labeled red blood cells in the dilution technique&#44; it is difficult to determine the moment at which bleeding stops or resumes&#46;<a class="elsevierStyleCrossRefs" href="#bib41">41&#44;43</a> In addition&#44; radiolabeled red cells must be injected at each time point of interest to determine the circulating blood volume after hemorrhage starts&#46; A homogeneous distribution of the labeled red cells in the circulation is always required&#44; which requires 15 minutes to occur&#46; Therefore&#44; it is not possible to determine the circulating volumes at shorter time intervals&#46; The present method covers all of these shortcomings&#46; Employing the two techniques &#40;dilution and gamma camera&#41; to quantify the initial circulating blood volume and the volume of blood present in the retroperitoneal space allows for attainment of important parameters&#46; The circulating blood volume&#44; red cell and plasma volumes after injury&#44; as well as the transcapillary refill can be measured over short time intervals&#46;</p><p id="para650" class="elsevierStylePara elsevierViewall">The use of a portable gamma camera in the present study introduced a new application to an old method&#46;<a class="elsevierStyleCrossRef" href="#bib48">48</a> This method of monitoring bleeding volumes has a number of positive aspects to be considered in future research&#58; 1&#41; it is possible to quantify blood loss at relatively short time intervals&#44; 2&#41; the natural interruption of bleeding is clearly demonstrated&#44; and 3&#41; the gamma camera is as reliable as the dilution technique in measuring several parameters&#44; as demonstrated in the present study&#46; However&#44; there are a number of restrictions to this method&#46; For each experiment&#44; a value for the correction factor must be determined&#46; Furthermore&#44; the method is strictly for experimental use&#44; and the spleen must be removed if large animals are to be used&#44; to avoid sequestration of volume in the splenic parenchyma and the effects of splenic contraction with subsequent changes in the circulating blood volume&#46;</p><p id="para660" class="elsevierStylePara elsevierViewall">Several studies have reported increased rebleeding with aggressive fluid resuscitation&#46; Strategies for controlling blood loss and therefore the use of blood components have also been reported&#46;<a class="elsevierStyleCrossRef" href="#bib49">49</a> The volume of rebleeding has been related to the sodium load of the solution&#44; amount of fluid resuscitation&#44; and the resultant hemodilution&#46; One research study&#44;<a class="elsevierStyleCrossRef" href="#bib4">4</a> using an animal model of uncontrolled hemorrhage&#44; reported higher rebleeding volumes in animals treated with hypertonic saline with or without dextran&#44; compared to non-treated animals or with animals treated with conventional isotonic resuscitation regimens&#46;<a class="elsevierStyleCrossRef" href="#bib4">4</a> However&#44; the total sodium load was different between groups&#46; Several studies suggested that a state of &#8220;controlled hypotension&#8221; is probably the best strategy before definitive control of the bleeding site is achieved&#46;<a class="elsevierStyleCrossRef" href="#bib2">2</a>&#8211;<a class="elsevierStyleCrossRef" href="#bib6">6</a></p><p id="para670" class="elsevierStylePara elsevierViewall">Hemodynamic parameters such as the MAP&#44; CI&#44; and Htc have been used to monitor the hemodynamic response to fluid resuscitation and to detect new or recurrent bleeding episodes&#46; MAP decreased during bleeding and increased in all groups after T30&#46; The increase in MAP in the NT group can be explained by the action of compensatory mechanisms&#44; such as vasoconstriction and tachycardia&#44; in an attempt to maintain adequate perfusion to the heart and brain&#46; MAP increased in the HSD and LR groups to levels slightly higher than those in the NT group up to T45&#44; most likely due to fluid infusion&#46; However&#44; MAP decreased again in the resuscitated groups&#44; most likely because of rebleeding&#46; The same observations were made with CI measurements&#46; Hemodilution and rebleeding contributed to decreases in Htc after fluid resuscitation in both resuscitation groups&#46; Changes observed in the hemodynamic parameters and in Htc levels were paralleled by those seen in VRPH&#44; VRCH&#44; CBV&#44; CRCV&#44; and TR&#46; LR-treated animals had higher rebleeding volumes as indicated by increased VRPH compared to the HSD group&#46;</p><p id="para680" class="elsevierStylePara elsevierViewall">TR following hypertonic saline resuscitation has been demonstrated in animal models of controlled hemorrhage&#46;<a class="elsevierStyleCrossRef" href="#bib9">9</a>&#8211;<a class="elsevierStyleCrossRefs" href="#bib10">10&#44;12&#44;50</a> In the present study&#44; hemorrhage led to transcapillary refill during the initial fifteen minutes after hemorrhage started in all groups&#46; No transcapillary refill was observed during the shock period &#40;T15 to T30&#41;&#46; After fluid resuscitation and despite the occurrence of rebleeding in both resuscitated groups&#44; a clear loss of intravascular volume to the interstitial space &#40;transcapillary leak&#41; was observed in LR-resuscitated animals&#46; In contrast&#44; TR was clearly observed in HSD-treated animals&#46;</p></span><span id="cesec240" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle290">CONCLUSION</span><p id="para690" class="elsevierStylePara elsevierViewall">This model produces an effective bilateral retroperitoneal hematoma &#40;red cell loss of nearly 31&#37;&#41;&#46; Fluid resuscitation with either HSD or LR increased MAP&#44; but it also led to rebleeding&#46; Higher rebleeding volumes were observed in LR-treated animals&#44; despite similar sodium loads given to HSD-treated animals&#46; Transcapillary refill was only present in HSD-treated animals&#46; LR-treated animals developed capillary leaks&#46; The combination of increased recruitment of fluid to the intravascular space associated with decreased rebreeding volumes makes HSD&#44; in the present model of uncontrolled hemorrhage&#44; superior to LR resuscitation&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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        0 => array:2 [
          "identificador" => "xpalclavsec1582918"
          "titulo" => "KEYWORDS&#58;"
        ]
        1 => array:2 [
          "identificador" => "cesec10"
          "titulo" => "INTRODUCTION"
        ]
        2 => array:3 [
          "identificador" => "cesec20"
          "titulo" => "MATERIALS AND METHODS"
          "secciones" => array:9 [
            0 => array:2 [
              "identificador" => "cesec30"
              "titulo" => "Surgical preparation"
            ]
            1 => array:2 [
              "identificador" => "cesec40"
              "titulo" => "Hemorrhage Model"
            ]
            2 => array:2 [
              "identificador" => "cesec50"
              "titulo" => "Phase I&#58; Development of a method for the quantification of blood loss&#46; Experiment A &#8211; Physical Simulation"
            ]
            3 => array:2 [
              "identificador" => "cesec60"
              "titulo" => "Experiment B &#8211; Artificially Created Retroperitoneal Hematoma"
            ]
            4 => array:2 [
              "identificador" => "cesec70"
              "titulo" => "Experiment C &#8211; In Vivo Retroperitoneal Hematoma"
            ]
            5 => array:2 [
              "identificador" => "cesec80"
              "titulo" => "Quantification of Bleeding Volume"
            ]
            6 => array:2 [
              "identificador" => "cesec90"
              "titulo" => "Measurement of initial circulating red blood cell volume and total blood volume"
            ]
            7 => array:3 [
              "identificador" => "cesec100"
              "titulo" => "Phase II&#46; Resuscitated uncontrolled hemorrhage Experiment D &#8211; in vivo retroperitoneal hematoma followed by fluid resuscitation"
              "secciones" => array:7 [
                0 => array:2 [
                  "identificador" => "cesec110"
                  "titulo" => "Study groups"
                ]
                1 => array:2 [
                  "identificador" => "cesec120"
                  "titulo" => "Volume of Red Cells in the Hematoma &#40;VRCH&#41;"
                ]
                2 => array:2 [
                  "identificador" => "cesec130"
                  "titulo" => "Volume of Retroperitoneal Hematoma &#40;VRPH&#41;"
                ]
                3 => array:2 [
                  "identificador" => "cesec140"
                  "titulo" => "Circulating Red Cell Volume &#40;CRCV&#41;"
                ]
                4 => array:2 [
                  "identificador" => "cesec150"
                  "titulo" => "Circulating Blood Volume &#40;CBV&#41;"
                ]
                5 => array:2 [
                  "identificador" => "cesec160"
                  "titulo" => "Expected Circulating Blood Volume &#40;ECBV&#41;"
                ]
                6 => array:2 [
                  "identificador" => "cesec170"
                  "titulo" => "Transcapillary Refill &#40;TR&#41;"
                ]
              ]
            ]
            8 => array:2 [
              "identificador" => "cesec180"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        3 => array:3 [
          "identificador" => "cesec190"
          "titulo" => "RESULTS"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "cesec200"
              "titulo" => "Phase I&#58; Development of a method for the quantification of blood loss&#46; Experiment A &#8211; Physical Simulation and Experiment B &#8211; Artificially-Created Retroperitoneal Hematoma"
            ]
            1 => array:2 [
              "identificador" => "cesec210"
              "titulo" => "Experiment C &#8211; In Vivo Retroperitoneal Hematoma"
            ]
            2 => array:2 [
              "identificador" => "cesec220"
              "titulo" => "Phase II-Resuscitated uncontrolled hemorrhage Experiment D &#8211; In vivo retroperitoneal hematoma and fluid resuscitation"
            ]
          ]
        ]
        4 => array:2 [
          "identificador" => "cesec230"
          "titulo" => "DISCUSSION"
        ]
        5 => array:2 [
          "identificador" => "cesec240"
          "titulo" => "CONCLUSION"
        ]
        6 => array:1 [
          "titulo" => "REFERENCES"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2009-09-13"
    "fechaAceptado" => "2009-10-20"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "KEYWORDS&#58;"
          "identificador" => "xpalclavsec1582918"
          "palabras" => array:5 [
            0 => "Retroperitoneal hematoma"
            1 => "Uncontrolled hemorrhage"
            2 => "Shock"
            3 => "Hypertonic saline solution"
            4 => "Small volume resuscitation"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:2 [
        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJETIVE&#58;</span><p id="spara100" class="elsevierStyleSimplePara elsevierViewall">This study evaluated retroperitoneal hematomas produced by bilateral injury of iliac arteries &#40;uncontrolled hemorrhage&#41;&#44; blood volume loss&#44; transcapillary refill&#44; the effects of volume replacement on retroperitoneal bleeding and the hemodynamic changes with and without treatment&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">METHODS&#58;</span><p id="spara110" class="elsevierStyleSimplePara elsevierViewall">Initial blood volume was determined with Tc<span class="elsevierStyleSup">99m</span>-labelled red cells&#44; and bleeding was evaluated by means of a portable scintillation camera positioned over the abdomen&#46; Previously splenectomized mongrel dogs &#40;16&#46;8 &#177; 2&#46;2 kg&#41; were submitted to hemorrhage for 30 minutes and randomized into three groups&#58; I - no treatment &#40;n&#61;7&#41;&#59; II - treatment with 32 mL&#47;kg of Lactated Ringer&#8217;s for three to five minutes &#40;n&#61;7&#41;&#59; and III <span class="elsevierStyleBold">-</span> treatment with 4 mL&#47;kg of 7&#46;5&#37; NaCl plus 6&#46;0&#37; dextran 70 for three to five minutes &#40;n&#61;7&#41;&#46; They were studied for an additional 45 minutes&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">RESULTS&#58;</span><p id="spara120" class="elsevierStyleSimplePara elsevierViewall">Volume replacement produced transitory recovery in hemodynamic variables&#44; including mean pulmonary artery pressure&#44; pulmonary capillary wedge pressure and cardiac index&#44; with significant increase in dogs treated with 32 mL&#47;kg of Lactated Ringer&#8217;s and 7&#46;5&#37; NaCl plus 6&#46;0&#37; dextran 70 &#40;p&#60;0&#46;001&#44; against no treatment&#41;&#44; along with a decrease &#40;p&#60;0&#46;001&#41; in the systemic vascular resistance index&#46; Groups II and III had significant initial decreases in hematocrit and hemoglobin&#46; The treated dogs &#40;groups II and III&#41; presented rebleeding&#44; which was greater during treatment with 32 mL&#47;kg of Lactated Ringer&#8217;s &#40;group II&#41;&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">CONCLUSIONS&#58;</span><p id="spara130" class="elsevierStyleSimplePara elsevierViewall">Despite the rebleeding observed in treated groups&#44; the utilization of hypertonic saline solution with dextran proved to be effective in the initial reanimation&#44; producing evident transcapillary refill&#44; while the Lactated Ringer&#8217;s solution produced capillary extravasation and was ineffective in the initial volume replacement in this model of uncontrolled hemorrhage&#46;</p></span>"
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            "identificador" => "ceabs10"
            "titulo" => "OBJETIVE&#58;"
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            "titulo" => "METHODS&#58;"
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          2 => array:2 [
            "identificador" => "ceabs30"
            "titulo" => "RESULTS&#58;"
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          3 => array:2 [
            "identificador" => "ceabs40"
            "titulo" => "CONCLUSIONS&#58;"
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      0 => array:7 [
        "identificador" => "f1-cln_65p67"
        "etiqueta" => "Figure 1"
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          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Comparison between a known volume in the plastic bag and the calculated volume based on radioactivity measurements made by use of the gamma camera &#40;Experiment A&#41;&#46; For a volume of 50 mL&#44; the observed averaged error was 17&#37;&#44; and the error was greater than 8&#37; for volumes larger than 800 mL&#46; For volumes between 100 mL and 900 mL&#44; there was a significant correlation between the calculated volume and the known volume in the bag</p>"
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      1 => array:7 [
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        "etiqueta" => "Figure 2"
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        "figura" => array:1 [
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          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Cardiac index &#40;Panel A&#41;&#44; Mean Arterial Pressure &#40;Panel B&#41;&#44; and Hematocrit &#40;Panel C&#41; were measured before &#40;time &#61; 0 min&#41; and after &#40;time &#61; 15 min and 30 min&#41; the creation of bilateral iliac artery injuries&#46; No differences were observed in these parameters between the GC and DT groups&#46; Retroperitoneal hematoma formation led to a significant decrease in cardiac index and mean arterial pressure at 15 min and 30 min &#40;p&#60;0&#46;001&#41;</p>"
        ]
      ]
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        "etiqueta" => "Figure 3"
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          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Examples of gamma camera images acquired from one animal during Experiment C taken before and 5&#44; 10&#44; 15&#44; 30&#44; and 75 minutes after the arterial injuries are presented&#46; Background images and radiation obtained from a syringe containing blood and radiotracer &#40;see methods&#41; are shown for comparison</p>"
        ]
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        "etiqueta" => "Figure 4"
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          "en" => "<p id="spara40" class="elsevierStyleSimplePara elsevierViewall">Volume of the retroperitoneal hematoma &#40;VRPH&#41; and volume of red cells in the hematoma &#40;VRCH&#41; at five-minute intervals in Experiment C &#40;no fluid resuscitation&#41;&#46; Bleeding was more pronounced during the initial 15 minutes after the bilateral iliac artery injuries were created</p>"
        ]
      ]
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        "etiqueta" => "Figure 5"
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          "en" => "<p id="spara50" class="elsevierStyleSimplePara elsevierViewall">Comparison between the volume of the retroperitoneal hematoma &#40;VRPH&#41;&#44; volume of red cells in the hematoma &#40;VRCH&#41;&#44; and plasma volume of animals in the GC and DT groups&#46; No differences were found between these two methods</p>"
        ]
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        "etiqueta" => "Figure 6"
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        "descripcion" => array:1 [
          "en" => "<p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Comparison between the circulating blood volume &#40;CBV&#41; measured in the GC and DT groups&#46; Both methods of measurement were equally accurate in determining total circulating blood volume and its components</p>"
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        "etiqueta" => "Figure 7"
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          "en" => "<p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Panel A &#8211; Mean arterial pressure &#40;MAP&#41; decreased significantly during the initial fifteen minutes after the injury&#44; and it increased equally in all groups&#46; Panel B &#8211; Reduction in cardiac index &#40;CI&#41; was observed 15 minutes after injury in all groups&#46; After fluid resuscitation&#44; a significant increase in CI was observed in LR- and HSD-treated animals &#40;T45&#41; when compared with the NT group&#46; Panel C &#8211; Hematocrit &#40;Htc&#41; was similar in all groups during the experiment&#46; &#42; p&#60;0&#46;05 CT vs&#46; LR and HSD&#44; &#8224; p&#60;0&#46;05 CT vs&#46; LR</p>"
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        "etiqueta" => "Figure 8"
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          "en" => "<p id="spara80" class="elsevierStyleSimplePara elsevierViewall">Panel A &#8211;Circulating blood volume &#40;CBV&#41; was reduced equally during the initial 15 minutes in all groups&#46; Fluid resuscitation with subsequent rebleeding led to a decrease in CBV in both treatment groups&#44; although changes were more pronounced in LR-treated animals&#46; Panel B &#8211; Circulating red cell volume &#40;CRCV&#41; decreased slightly during hemorrhage&#46; No statistically significant differences were observed when comparing LR and HSD treatments&#44; although LR animals had lower values&#46; Panel C &#8211; Blood volume in the retroperitoneal hematoma &#40;VRPH&#41; at 15-minute intervals is shown&#46; Bleeding was more pronounced in the initial 15 minutes after bilateral iliac artery injuries were created&#46; Significantly higher VRPH was observed in LR-treated animals when compared to the HSD group&#44; indicating more pronounced rebleeding&#46; Panel D &#8211; Volume of red cells in the retroperitoneal hematoma &#40;VRCH&#41; at 15-minute intervals is shown&#46; No differences between LR- and HSD-treated animals were observed&#46; Panel E &#8211; Transcapillary refill increased in all groups during hemorrhage&#44; reached a plateau in the NT group&#44; significantly increased in HSD-treated animals and decreased significantly in the LR group</p>"
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        "etiqueta" => "Scheme 1"
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          "en" => "<p id="spara90" class="elsevierStyleSimplePara elsevierViewall">SCHEME OF EXPERIMENTAL MOMENTS</p>"
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