Efficacy and safety of topical tranexamic acid in knee arthroplasty

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In addition, knee surgery is usually performed with tourniquet; this measure facilitates the intervention; however, it results in tissue damage that favours fibrinolysis.<a class="elsevierStyleCrossRef" href="#bib0220">7</a>TXA is an antifibrinolytic, which acts by competitively blocking plasminogen and reducing the degradation of fibrin by plasmin.<a class="elsevierStyleCrossRef" href="#bib0225">8</a>The administration of TXA perioperatively is one of the key measures for the prevention of surgery-associated anaemia.For decades it has been used intravenously in major orthopaedic surgery, reducing bleeding and transfusion needs.<a class="elsevierStyleCrossRefs" href="#bib0230">9,10</a>However, the bioavailability of TXA in the surgical site is low, that is, only a low percentage of the total administered reaches the site of action.<a class="elsevierStyleCrossRef" href="#bib0240">11</a> There is a risk of developing embolic complications associated with the use of intravenous TXA.<a class="elsevierStyleCrossRefs" href="#bib0245">12–16</a> Consequently, the application of systemic TXA is considered a relative contraindication for all patients with a history of embolic disease or hypercoagulable states. Unfortunately, this group is elevated among patients who are candidates for joint replacement surgery.Its topical application has been proposed in order to safely standardize the use of TXA in knee surgery. In this way, the systemic effect is cancelled, avoiding possible associated complications. This allows its application in all patients regardless of their previous comorbidity, since there is no contraindication for its application in this way.This modification in the route of administration facilitates the systematic application of a measure that has been shown to reduce postoperative anaemia in an effective manner, as well as reducing the surgical risk and facilitating early recovery, which results in shorter hospital stays and lower costs.<a class="elsevierStyleCrossRefs" href="#bib0270">17–21</a>The objective of the present study is to prospectively evaluate postoperative anaemia, the transfusion rate and the complications associated with the topical use of TXA in total knee arthroplasty. Secondly, the results of its topical application will be compared with the intravenous one.Material and methodsA prospective observational study was designed from November 2015 to February 2016, with a minimum follow-up of one year.A total of 90 patients were included in the study, and they underwent primary knee arthroplasty at the Alcorcón Foundation University Hospital. They were randomly classified into group A (n=30), in which the application of TXA was topical; group B (n=30), in which the administration was intravenous; and group C (n=30), in which TXA was not administered.The exclusion criteria were having had previous coagulopathies and receiving chronic anticoagulant treatment.The administration of TXA is carried out in accordance with the protocol approved by the centre's Hemotherapy Committee. The application consists of the administration of 1g of TXA before the release of preventive ischaemia. In group A, it was applied directly in deep layers, placing the drainage in the subcutaneous tissue and keeping it closed one hour after having finished the surgical wound closure. In group B it was administered intravenously, and drainage was implemented in the same way as in group A.All the patients were operated on once spinal anaesthesia was applied and with preventive ischaemia at 300mmHg. Normothermia and hypotension were controlled during surgery. The approach in all cases was medial parapatellar, using a prosthesis cemented with posterior stabilized polyethylene without patellar replacement. The prosthetic model was NexGen® Flex (Zimmer). The surgical wound closure was made by layers, placing a suction drain in subcutaneous cellular tissue. Afterwards, a compressive bandage was applied on the entire limb. Drainage was removed when the output was less than 100cc in 24h. Twelve hours after surgery, the first dose of weight-adjusted prophylactic low molecular weight heparin was administered. Walking began 24h after surgery, following a radiography and postoperative blood tests. Antithrombotic prophylaxis was maintained 30 days after the intervention.During admission, all patients underwent the early mobilization protocol, which continued on an outpatient basis after hospital discharge.Traumatology follow-up was performed at months 1, 3 and 6 and 1 year after the intervention.Data collection was performed directly from the electronic medical record. Tabulation was carried out in Excel format for subsequent analysis with SPSS®.Quantitative variables were analyzed with measures of central tendency and qualitative variables with percentages. The means were compared with the t-Student test for variables with normal distribution and with the nonparametric Mann–Whitney U test when they did not have this distribution. Frequencies were compared with the Chi-square test or the Fisher exact test.Relevant demographic data were collected, such as age, sex, comorbidities, anaesthetic risk (ASA), coagulopathies and pharmacological treatment that could alter coagulation (anti-platelet agents and non-steroidal anti-inflammatory drugs). We also analyzed preoperative haemoglobin, postoperative haemoglobin at 24h, differential haemoglobin (difference between preoperative and postoperative), drainage output (total, at 24 and 48h) and days of drainage. In addition, complications during admission and subsequent follow-up were recorded, among which were deep vein thrombosis, thromboembolism, infection of the surgical wound and persistent wound staining.Finally, we identified those cases that needed blood transfusion in the postoperative period. The criteria for transfusion were postoperative anaemia with haemoglobin levels below 8g/dl with clinical and/or hemodynamic impact.ResultsIn the demographic data analysis (age, sex, baseline comorbidities, ASA anaesthetic risk) no statistically significant differences were found between the 3 groups, so it can be considered a homogeneous population. The mean age was 72.79 years (SD 7.11). Regarding the anaesthetic risk, the distribution was 2% for ASA 1, 88% for ASA 2 and 10% for ASA 3 (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Antiplatelet medication and other drugs that can interfere with coagulation, such as non-steroidal anti-inflammatory drugs, were studied, but no differences were found between the 3 groups.No differences were observed in the preoperative haemoglobin: group A 14.12 (SD 1.5) g/dl, group B 13.91 (SD 1.14) g/dl and group C 13.6 (SD 1.46) g/dl. There were also no differences in the duration of the intervention: group A 108min, group B 110min and group C 111min.However, differences were found in the differential haemoglobin between groups, with mean anaemia being lower in the group in which TXA was applied topically (1.95)g/dl) compared to the group in which it was administered intravenously (2.25g/dl) and the group in which it was not administered (2.96g/dl) (p<0.01). The application of TXA decreased postoperative anaemia, with this being even lower with topical administration.Transfusion of packed red cells were only necessary in 3 patients in the postoperative period, finding no differences between the 3 groups (p>0.05).Regarding the drainage output, significant differences were found, with the total output and output in the first 24h being lower in the topical application group. The total output was 195ml in group A, 466ml in group B and 718ml in group C (p<0.01). On the first postoperative day, the drainage output was lower in group A (137ml) compared to group B (344ml) and group C (603ml). In addition, the number of days that drainage was maintained was greater in group C (2 days), in which TXA was not administered, compared to the groups in which it was used: group A (1.1 days) and group B (1.6 days) (p<0.01). The decrease in the drainage output with the administration of TXA was more significant in the topical application, which facilitates the rapid removal of it with the consequent early onset of mobility (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>There were no differences between the groups in terms of the complications studied. In addition, no thromboembolic complications were detected in any of the 3 groups.DiscussionThe application of TXA in primary knee arthroplasty reduces postoperative anaemia.<a class="elsevierStyleCrossRefs" href="#bib0230">9,22–24</a> However, studies have recently been published that have shown a similar result in postoperative drainage in its topical application.<a class="elsevierStyleCrossRefs" href="#bib0310">25–27</a> Wong et al. demonstrated the decrease in drainage output using a topical dose of 1.5 and 3g compared to placebo, without finding differences between both doses.<a class="elsevierStyleCrossRef" href="#bib0310">25</a> Gómez-Barrena et al. have verified that the application of 3g of topical TXA is not inferior to intravenous administration in postoperative output at 24 and 48h.<a class="elsevierStyleCrossRef" href="#bib0315">26</a>The results of the present study coincide with those of both authors in that both topical and intravenous application decrease drainage output in knee arthroplasty, with this reduction being greater in topical application. This is due to the fact that, at equal doses, a greater concentration is achieved in the surgical field.TXA reduces postoperative haemorrhage, achieving higher post-surgical haemoglobin levels.<a class="elsevierStyleCrossRefs" href="#bib0310">25,27–30</a> Wong et al. showed 16% higher levels of postoperative haemoglobin compared to placebo.<a class="elsevierStyleCrossRef" href="#bib0310">25</a>These results coincide with those obtained, in which anaemia was lower with the intravenous application of TXA (2.25g/dl) compared to the control group (group C 2.96g/dl), and still lower in the topical application group (group A 1.95g/dl).A decrease in bleeding leads to less inflammation in the operated limb<a class="elsevierStyleCrossRef" href="#bib0340">31</a> and an earlier recovery.<a class="elsevierStyleCrossRefs" href="#bib0275">18,19</a> In the present study it was possible to quantify that the removal of drainage occurred a day earlier in the groups in which TXA was applied compared to the control group, a fact that has not yet been reported in the literature. This fact facilitates early mobility and recovery, reducing the costs of hospitalization and comorbidity associated with this intervention.<a class="elsevierStyleCrossRefs" href="#bib0270">17,20</a>In order to minimize the risks associated with the use of TXA, the present study was designed with the administration of a low 1g dose, both in topical and intravenous application. It has been proven that the beneficial effects are the same with respect to high doses of 2–3g used in other studies.<a class="elsevierStyleCrossRefs" href="#bib0310">25–29</a>In addition, in order to improve the topical distribution of TXA without an excessive amount of product, a 10ml physiological saline preparation was made for the dilution of 1g of TXA. Most authors use preparations of more than 100ml,<a class="elsevierStyleCrossRefs" href="#bib0310">25–29</a> although it is true that data on the theoretical benefit of low-volume applications has already been published.<a class="elsevierStyleCrossRef" href="#bib0345">32</a>Finally, no differences were found regarding complications between the 3 groups, which reinforces the safe use of TXA in knee arthroplasty.<a class="elsevierStyleCrossRefs" href="#bib0230">9,22–37</a> Our research group advocates the topical use of TXA as a further step in the intervention so as to achieve its application in all patients.In our experience, there were no differences in transfusion rates, probably because these are very low, and the sample is limited. Rodríguez-Merchán et al. have published a series of knee arthroplasties in which the transfusion rate was lower in the group treated with topical TXA (7%) compared to the control group (30%).<a class="elsevierStyleCrossRef" href="#bib0345">32</a>The application of TXA is an effective and safe measure in the prevention of postoperative haemorrhage in knee arthroplasty, regardless of the route of administration. Topical application of a low 1g dose has demonstrated a decreased drainage output and postoperative haemoglobin, with the consequent early drainage removal. In most cases this entails early recovery and a reduction in the costs associated with the intervention.Conflict of interestsThere is no conflict of interest in the conduct of this study." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres1124471" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1059026" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1124470" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1059025" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Material and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-09-08" "fechaAceptado" => "2018-01-11" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1059026" "palabras" => array:4 [ 0 => "Tranexamic acid" 1 => "Total knee arthroplasty" 2 => "Intraarticular administration" 3 => "Topical" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1059025" "palabras" => array:4 [ 0 => "Ácido tranexámico" 1 => "Artroplastia de rodilla" 2 => "Aplicación intraarticular" 3 => "Tópico" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Introduction and objectiveTranexamic acid (TXA) is commonly used to control postoperative blood loss in total knee arthroplasty. In order to avoid adverse effects associated with intravenous administration, topical use has been proposed as an alternative. Our aim was to evaluate the efficacy and safety of topical TXA in total knee arthroplasty. Material and methodsA total of 90 patients scheduled for unilateral total knee arthroplasty were included in a prospective randomized study. All surgeries were performed under spinal anaesthesia, tourniquet and the same postoperative protocol. Patients were allocated to one of the 3 groups according to the application of TXA: group A (n=30) 1g of topical TXA; group B (n=30) 1g of TXA intravenous and in group C or the control group (n=30) no drug was administrated. Parameters related to blood loss and drain outputs were compared between the 3 groups. ResultsThe results revealed that post-operative decrease in haemoglobin level was significantly lower in group A (1.95g/dL) than group B (2.25g/dL) and group C (2.96g/dL), p<0.01. Total postoperative blood loss was lower in group A (195mL) than group B (466mL) and group C (718mL), p<0.01. There was no significant difference in complications and allogenic blood transfusion rate between the 3 groups. ConclusionsAccording to the results, topical application of 1g TXA significantly reduced blood loss in patients undergoing total knee arthroplasty more than intravenous or no administration of TXA." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "Introducción y objetivoLa administración de ácido tranexámico (ATX) es efectiva reduciendo la pérdida de sangre en la artroplastia de rodilla. Con el fin de evitar los efectos adversos de la administración intravenosa, se ha propuesto el uso tópico del mismo. Nuestro objetivo es evaluar la eficacia y seguridad de ATX tópico para reducir la hemorragia postoperatoria en la artroplastia de rodilla. Material y métodosUn total de 90 pacientes intervenidos de artroplastia total de rodilla unilateral fueron incluidos en un estudio prospectivo y aleatorizado. Todas las intervenciones fueron llevadas a cabo bajo anestesia espinal, con isquemia preventiva y bajo el mismo régimen postoperatorio. Los pacientes fueron divididos en 3 grupos en función de la administración del ATX: grupo A (n=30) 1g de ATX tópico; grupo B (n=30) 1g de ATX intravenoso, y grupo C o control (n=30), al que no se administró ningún fármaco. Se analizaron los parámetros de pérdida de sangre y débito de drenajes en los 3 grupos. ResultadosLos resultados mostraron que el descenso del nivel de hemoglobina fue menor en el grupo A (1,95dl) respecto el grupo B (2,25g/dl) y el grupo C (2,96g/dl), p<0,01. Respecto a la hemorragia postoperatoria, también fue inferior en el grupo A (195ml) respecto el grupo B (466ml) y el grupo C (718ml), p<0,01. No hubo diferencias en las complicaciones y la tasa de transfusiones de sangre entre los 3 grupos. ConclusionesLa aplicación tópica de 1g de ATX reduce significativamente la pérdida de sangre en pacientes intervenidos de artroplastia total de rodilla, en mayor magnitud que la aplicación intravenosa y la no administración." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: López-Hualda Á, Dauder-Gallego C, Ferreño-Márquez D, Martínez-Martín J. Eficacia y seguridad del ácido tranexámico tópico en la artroplastia de rodilla. Med Clin (Barc). 2018;151:431–434." ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "ASA: American Society of Anaesthesiologists; IV: intravenousThe values are expressed as a percentage or average±standard deviation." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group A (topical) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group B (IV) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group C (control) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72.9±7.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">73.1±7.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72.4±6.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.331 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.232 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ASA II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.584 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preoperative haemoglobin (g/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.1±1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.9±1.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.6±1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.182 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Duration of the intervention (min) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">108.1±21.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">110.3±20.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">111.6±20.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.485 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1915972.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "t-Student or Mann–Whitney test for continuous variables and Fisher's exact test for categorical variables." ] ] ] "descripcion" => array:1 [ "en" => "Preoperative characteristics of the groups." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "IV: intravenousThe values are expressed as average±standard deviation." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group A (topical) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group B (IV) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group C (control) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Postoperative haemoglobin (g/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.2±1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.6±1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.01±1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.144 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Differential haemoglobin (g/dl) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.9±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2±0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.9±1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.033 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Drainage 24h (cc) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">137±154 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">344±168 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">603±375 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total drainage (cc) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">195±141 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">466±211 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">718±414 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Days of drainage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.1±0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.6±0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.1±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1915973.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "t-Student or Mann–Whitney test for continuous variables and Fisher's exact test for categorical variables." ] ] ] "descripcion" => array:1 [ "en" => "Postoperative variables." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:37 [ 0 => array:3 [ "identificador" => "bib0190" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The epidemiology of revision total knee and hip arthroplasty in England and Wales: a comparative analysis with projections for the United States. A study using the National Joint Registry dataset" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Patel" 1 => "G. Pavlou" 2 => "R.E. Mújica-Mota" 3 => "A.D. Toms" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1302/0301-620X.97B8.35170" "Revista" => array:6 [ "tituloSerie" => "Bone Joint J" "fecha" => "2015" "volumen" => "97-B" "paginaInicial" => "1076" "paginaFinal" => "1081" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26224824" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0195" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Factors that influence blood loss and need for transfusion following total knee arthroplasty" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Boutsiadis" 1 => "R.J. Reynolds" 2 => "M. Saffarini" 3 => "J.C. 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Original article

Efficacy and safety of topical tranexamic acid in knee arthroplasty

Eficacia y seguridad del ácido tranexámico tópico en la artroplastia de rodilla

Álvaro López-Hualda

Corresponding author

alhualda@hotmail.com

Corresponding author.

, Cristina Dauder-Gallego, David Ferreño-Márquez, Javier Martínez-Martín

Cirugía Ortopédica y Traumatología, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain

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    "titulo" => "Efficacy and safety of topical tranexamic acid in knee arthroplasty"
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        "autoresLista" => "&#193;lvaro L&#243;pez-Hualda, Cristina Dauder-Gallego, David Ferre&#241;o-M&#225;rquez, Javier Mart&#237;nez-Mart&#237;n"
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            "nombre" => "&#193;lvaro"
            "apellidos" => "L&#243;pez-Hualda"
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          1 => array:2 [
            "nombre" => "Cristina"
            "apellidos" => "Dauder-Gallego"
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            "nombre" => "David"
            "apellidos" => "Ferre&#241;o-M&#225;rquez"
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            "apellidos" => "Mart&#237;nez-Mart&#237;n"
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            "entidad" => "Cirug&#237;a Ortop&#233;dica y Traumatolog&#237;a&#44; Hospital Universitario Fundaci&#243;n Alcorc&#243;n&#44; Alcorc&#243;n&#44; Madrid&#44; Spain"
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    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Eficacia y seguridad del &#225;cido tranex&#225;mico t&#243;pico en la artroplastia de rodilla"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Knee replacement is one of the most frequent procedures in orthopaedic surgery&#59; it is estimated that it will reach 3&#46;48 million a year in 2030&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">1</span></a> One of the main problems associated with this intervention is perioperative haemorrhage&#44; estimated at 800&#8211;1800<span class="elsevierStyleHsp" style=""></span>ml&#44; which sometimes requires blood transfusions&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">2&#44;3</span></a> Transfusions of blood products are associated with multiple risks&#44; such as infection of the surgical site&#44; immunological reactions&#44; longer rehabilitation times and hospital stays&#44; that is&#44; all this translates into a significant increase in costs and comorbidity associated with surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">4&#8211;6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In order to prevent postoperative anaemia&#44; a series of measures have been proposed&#44; such as careful surgical technique&#44; exhaustive haemostasis&#44; preoperative haemoglobin optimization and the application of TXA&#46; In addition&#44; knee surgery is usually performed with tourniquet&#59; this measure facilitates the intervention&#59; however&#44; it results in tissue damage that favours fibrinolysis&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">7</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">TXA is an antifibrinolytic&#44; which acts by competitively blocking plasminogen and reducing the degradation of fibrin by plasmin&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The administration of TXA perioperatively is one of the key measures for the prevention of surgery-associated anaemia&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">For decades it has been used intravenously in major orthopaedic surgery&#44; reducing bleeding and transfusion needs&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">However&#44; the bioavailability of TXA in the surgical site is low&#44; that is&#44; only a low percentage of the total administered reaches the site of action&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">11</span></a> There is a risk of developing embolic complications associated with the use of intravenous TXA&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">12&#8211;16</span></a> Consequently&#44; the application of systemic TXA is considered a relative contraindication for all patients with a history of embolic disease or hypercoagulable states&#46; Unfortunately&#44; this group is elevated among patients who are candidates for joint replacement surgery&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Its topical application has been proposed in order to safely standardize the use of TXA in knee surgery&#46; In this way&#44; the systemic effect is cancelled&#44; avoiding possible associated complications&#46; This allows its application in all patients regardless of their previous comorbidity&#44; since there is no contraindication for its application in this way&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">This modification in the route of administration facilitates the systematic application of a measure that has been shown to reduce postoperative anaemia in an effective manner&#44; as well as reducing the surgical risk and facilitating early recovery&#44; which results in shorter hospital stays and lower costs&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">17&#8211;21</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The objective of the present study is to prospectively evaluate postoperative anaemia&#44; the transfusion rate and the complications associated with the topical use of TXA in total knee arthroplasty&#46; Secondly&#44; the results of its topical application will be compared with the intravenous one&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0050" class="elsevierStylePara elsevierViewall">A prospective observational study was designed from November 2015 to February 2016&#44; with a minimum follow-up of one year&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">A total of 90 patients were included in the study&#44; and they underwent primary knee arthroplasty at the Alcorc&#243;n Foundation University Hospital&#46; They were randomly classified into group A &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&#44; in which the application of TXA was topical&#59; group B &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&#44; in which the administration was intravenous&#59; and group C &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&#44; in which TXA was not administered&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The exclusion criteria were having had previous coagulopathies and receiving chronic anticoagulant treatment&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The administration of TXA is carried out in accordance with the protocol approved by the centre&#39;s Hemotherapy Committee&#46; The application consists of the administration of 1<span class="elsevierStyleHsp" style=""></span>g of TXA before the release of preventive ischaemia&#46; In group A&#44; it was applied directly in deep layers&#44; placing the drainage in the subcutaneous tissue and keeping it closed one hour after having finished the surgical wound closure&#46; In group B it was administered intravenously&#44; and drainage was implemented in the same way as in group A&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">All the patients were operated on once spinal anaesthesia was applied and with preventive ischaemia at 300<span class="elsevierStyleHsp" style=""></span>mmHg&#46; Normothermia and hypotension were controlled during surgery&#46; The approach in all cases was medial parapatellar&#44; using a prosthesis cemented with posterior stabilized polyethylene without patellar replacement&#46; The prosthetic model was NexGen<span class="elsevierStyleSup">&#174;</span> Flex &#40;Zimmer&#41;&#46; The surgical wound closure was made by layers&#44; placing a suction drain in subcutaneous cellular tissue&#46; Afterwards&#44; a compressive bandage was applied on the entire limb&#46; Drainage was removed when the output was less than 100<span class="elsevierStyleHsp" style=""></span>cc in 24<span class="elsevierStyleHsp" style=""></span>h&#46; Twelve hours after surgery&#44; the first dose of weight-adjusted prophylactic low molecular weight heparin was administered&#46; Walking began 24<span class="elsevierStyleHsp" style=""></span>h after surgery&#44; following a radiography and postoperative blood tests&#46; Antithrombotic prophylaxis was maintained 30 days after the intervention&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">During admission&#44; all patients underwent the early mobilization protocol&#44; which continued on an outpatient basis after hospital discharge&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Traumatology follow-up was performed at months 1&#44; 3 and 6 and 1 year after the intervention&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Data collection was performed directly from the electronic medical record&#46; Tabulation was carried out in Excel format for subsequent analysis with SPSS<span class="elsevierStyleSup">&#174;</span>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Quantitative variables were analyzed with measures of central tendency and qualitative variables with percentages&#46; The means were compared with the <span class="elsevierStyleItalic">t</span>-Student test for variables with normal distribution and with the nonparametric Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test when they did not have this distribution&#46; Frequencies were compared with the Chi-square test or the Fisher exact test&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Relevant demographic data were collected&#44; such as age&#44; sex&#44; comorbidities&#44; anaesthetic risk &#40;ASA&#41;&#44; coagulopathies and pharmacological treatment that could alter coagulation &#40;anti-platelet agents and non-steroidal anti-inflammatory drugs&#41;&#46; We also analyzed preoperative haemoglobin&#44; postoperative haemoglobin at 24<span class="elsevierStyleHsp" style=""></span>h&#44; differential haemoglobin &#40;difference between preoperative and postoperative&#41;&#44; drainage output &#40;total&#44; at 24 and 48<span class="elsevierStyleHsp" style=""></span>h&#41; and days of drainage&#46; In addition&#44; complications during admission and subsequent follow-up were recorded&#44; among which were deep vein thrombosis&#44; thromboembolism&#44; infection of the surgical wound and persistent wound staining&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Finally&#44; we identified those cases that needed blood transfusion in the postoperative period&#46; The criteria for transfusion were postoperative anaemia with haemoglobin levels below 8<span class="elsevierStyleHsp" style=""></span>g&#47;dl with clinical and&#47;or hemodynamic impact&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0105" class="elsevierStylePara elsevierViewall">In the demographic data analysis &#40;age&#44; sex&#44; baseline comorbidities&#44; ASA anaesthetic risk&#41; no statistically significant differences were found between the 3 groups&#44; so it can be considered a homogeneous population&#46; The mean age was 72&#46;79 years &#40;SD 7&#46;11&#41;&#46; Regarding the anaesthetic risk&#44; the distribution was 2&#37; for ASA 1&#44; 88&#37; for ASA 2 and 10&#37; for ASA 3 &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">Antiplatelet medication and other drugs that can interfere with coagulation&#44; such as non-steroidal anti-inflammatory drugs&#44; were studied&#44; but no differences were found between the 3 groups&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">No differences were observed in the preoperative haemoglobin&#58; group A 14&#46;12 &#40;SD 1&#46;5&#41; g&#47;dl&#44; group B 13&#46;91 &#40;SD 1&#46;14&#41; g&#47;dl and group C 13&#46;6 &#40;SD 1&#46;46&#41; g&#47;dl&#46; There were also no differences in the duration of the intervention&#58; group A 108<span class="elsevierStyleHsp" style=""></span>min&#44; group B 110<span class="elsevierStyleHsp" style=""></span>min and group C 111<span class="elsevierStyleHsp" style=""></span>min&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">However&#44; differences were found in the differential haemoglobin between groups&#44; with mean anaemia being lower in the group in which TXA was applied topically &#40;1&#46;95&#41;<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; compared to the group in which it was administered intravenously &#40;2&#46;25<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; and the group in which it was not administered &#40;2&#46;96<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; The application of TXA decreased postoperative anaemia&#44; with this being even lower with topical administration&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Transfusion of packed red cells were only necessary in 3 patients in the postoperative period&#44; finding no differences between the 3 groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Regarding the drainage output&#44; significant differences were found&#44; with the total output and output in the first 24<span class="elsevierStyleHsp" style=""></span>h being lower in the topical application group&#46; The total output was 195<span class="elsevierStyleHsp" style=""></span>ml in group A&#44; 466<span class="elsevierStyleHsp" style=""></span>ml in group B and 718<span class="elsevierStyleHsp" style=""></span>ml in group C &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; On the first postoperative day&#44; the drainage output was lower in group A &#40;137<span class="elsevierStyleHsp" style=""></span>ml&#41; compared to group B &#40;344<span class="elsevierStyleHsp" style=""></span>ml&#41; and group C &#40;603<span class="elsevierStyleHsp" style=""></span>ml&#41;&#46; In addition&#44; the number of days that drainage was maintained was greater in group C &#40;2 days&#41;&#44; in which TXA was not administered&#44; compared to the groups in which it was used&#58; group A &#40;1&#46;1 days&#41; and group B &#40;1&#46;6 days&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46; The decrease in the drainage output with the administration of TXA was more significant in the topical application&#44; which facilitates the rapid removal of it with the consequent early onset of mobility &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0135" class="elsevierStylePara elsevierViewall">There were no differences between the groups in terms of the complications studied&#46; In addition&#44; no thromboembolic complications were detected in any of the 3 groups&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0140" class="elsevierStylePara elsevierViewall">The application of TXA in primary knee arthroplasty reduces postoperative anaemia&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">9&#44;22&#8211;24</span></a> However&#44; studies have recently been published that have shown a similar result in postoperative drainage in its topical application&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">25&#8211;27</span></a> Wong et al&#46; demonstrated the decrease in drainage output using a topical dose of 1&#46;5 and 3<span class="elsevierStyleHsp" style=""></span>g compared to placebo&#44; without finding differences between both doses&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">25</span></a> G&#243;mez-Barrena et al&#46; have verified that the application of 3<span class="elsevierStyleHsp" style=""></span>g of topical TXA is not inferior to intravenous administration in postoperative output at 24 and 48<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">26</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The results of the present study coincide with those of both authors in that both topical and intravenous application decrease drainage output in knee arthroplasty&#44; with this reduction being greater in topical application&#46; This is due to the fact that&#44; at equal doses&#44; a greater concentration is achieved in the surgical field&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">TXA reduces postoperative haemorrhage&#44; achieving higher post-surgical haemoglobin levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">25&#44;27&#8211;30</span></a> Wong et al&#46; showed 16&#37; higher levels of postoperative haemoglobin compared to placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">25</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">These results coincide with those obtained&#44; in which anaemia was lower with the intravenous application of TXA &#40;2&#46;25<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; compared to the control group &#40;group C 2&#46;96<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#44; and still lower in the topical application group &#40;group A 1&#46;95<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">A decrease in bleeding leads to less inflammation in the operated limb<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">31</span></a> and an earlier recovery&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">18&#44;19</span></a> In the present study it was possible to quantify that the removal of drainage occurred a day earlier in the groups in which TXA was applied compared to the control group&#44; a fact that has not yet been reported in the literature&#46; This fact facilitates early mobility and recovery&#44; reducing the costs of hospitalization and comorbidity associated with this intervention&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">17&#44;20</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">In order to minimize the risks associated with the use of TXA&#44; the present study was designed with the administration of a low 1<span class="elsevierStyleHsp" style=""></span>g dose&#44; both in topical and intravenous application&#46; It has been proven that the beneficial effects are the same with respect to high doses of 2&#8211;3<span class="elsevierStyleHsp" style=""></span>g used in other studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">25&#8211;29</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">In addition&#44; in order to improve the topical distribution of TXA without an excessive amount of product&#44; a 10<span class="elsevierStyleHsp" style=""></span>ml physiological saline preparation was made for the dilution of 1<span class="elsevierStyleHsp" style=""></span>g of TXA&#46; Most authors use preparations of more than 100<span class="elsevierStyleHsp" style=""></span>ml&#44;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">25&#8211;29</span></a> although it is true that data on the theoretical benefit of low-volume applications has already been published&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">32</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Finally&#44; no differences were found regarding complications between the 3 groups&#44; which reinforces the safe use of TXA in knee arthroplasty&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">9&#44;22&#8211;37</span></a> Our research group advocates the topical use of TXA as a further step in the intervention so as to achieve its application in all patients&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">In our experience&#44; there were no differences in transfusion rates&#44; probably because these are very low&#44; and the sample is limited&#46; Rodr&#237;guez-Merch&#225;n et al&#46; have published a series of knee arthroplasties in which the transfusion rate was lower in the group treated with topical TXA &#40;7&#37;&#41; compared to the control group &#40;30&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">32</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">The application of TXA is an effective and safe measure in the prevention of postoperative haemorrhage in knee arthroplasty&#44; regardless of the route of administration&#46; Topical application of a low 1<span class="elsevierStyleHsp" style=""></span>g dose has demonstrated a decreased drainage output and postoperative haemoglobin&#44; with the consequent early drainage removal&#46; In most cases this entails early recovery and a reduction in the costs associated with the intervention&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0190" class="elsevierStylePara elsevierViewall">There is no conflict of interest in the conduct of this study&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Tranexamic acid &#40;TXA&#41; is commonly used to control postoperative blood loss in total knee arthroplasty&#46; In order to avoid adverse effects associated with intravenous administration&#44; topical use has been proposed as an alternative&#46; Our aim was to evaluate the efficacy and safety of topical TXA in total knee arthroplasty&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A total of 90 patients scheduled for unilateral total knee arthroplasty were included in a prospective randomized study&#46; All surgeries were performed under spinal anaesthesia&#44; tourniquet and the same postoperative protocol&#46; Patients were allocated to one of the 3 groups according to the application of TXA&#58; group A &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41; 1<span class="elsevierStyleHsp" style=""></span>g of topical TXA&#59; group B &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41; 1<span class="elsevierStyleHsp" style=""></span>g of TXA intravenous and in group C or the control group &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41; no drug was administrated&#46; Parameters related to blood loss and drain outputs were compared between the 3 groups&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The results revealed that post-operative decrease in haemoglobin level was significantly lower in group A &#40;1&#46;95<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#41; than group B &#40;2&#46;25<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#41; and group C &#40;2&#46;96<span class="elsevierStyleHsp" style=""></span>g&#47;dL&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#46; Total postoperative blood loss was lower in group A &#40;195<span class="elsevierStyleHsp" style=""></span>mL&#41; than group B &#40;466<span class="elsevierStyleHsp" style=""></span>mL&#41; and group C &#40;718<span class="elsevierStyleHsp" style=""></span>mL&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#46; There was no significant difference in complications and allogenic blood transfusion rate between the 3 groups&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">According to the results&#44; topical application of 1<span class="elsevierStyleHsp" style=""></span>g TXA significantly reduced blood loss in patients undergoing total knee arthroplasty more than intravenous or no administration of TXA&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La administraci&#243;n de &#225;cido tranex&#225;mico &#40;ATX&#41; es efectiva reduciendo la p&#233;rdida de sangre en la artroplastia de rodilla&#46; Con el fin de evitar los efectos adversos de la administraci&#243;n intravenosa&#44; se ha propuesto el uso t&#243;pico del mismo&#46; Nuestro objetivo es evaluar la eficacia y seguridad de ATX t&#243;pico para reducir la hemorragia postoperatoria en la artroplastia de rodilla&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Un total de 90 pacientes intervenidos de artroplastia total de rodilla unilateral fueron incluidos en un estudio prospectivo y aleatorizado&#46; Todas las intervenciones fueron llevadas a cabo bajo anestesia espinal&#44; con isquemia preventiva y bajo el mismo r&#233;gimen postoperatorio&#46; Los pacientes fueron divididos en 3 grupos en funci&#243;n de la administraci&#243;n del ATX&#58; grupo A &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41; 1<span class="elsevierStyleHsp" style=""></span>g de ATX t&#243;pico&#59; grupo B &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41; 1<span class="elsevierStyleHsp" style=""></span>g de ATX intravenoso&#44; y grupo C o control &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#41;&#44; al que no se administr&#243; ning&#250;n f&#225;rmaco&#46; Se analizaron los par&#225;metros de p&#233;rdida de sangre y d&#233;bito de drenajes en los 3 grupos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los resultados mostraron que el descenso del nivel de hemoglobina fue menor en el grupo A &#40;1&#44;95<span class="elsevierStyleHsp" style=""></span>dl&#41; respecto el grupo B &#40;2&#44;25<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41; y el grupo C &#40;2&#44;96<span class="elsevierStyleHsp" style=""></span>g&#47;dl&#41;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#46; Respecto a la hemorragia postoperatoria&#44; tambi&#233;n fue inferior en el grupo A &#40;195<span class="elsevierStyleHsp" style=""></span>ml&#41; respecto el grupo B &#40;466<span class="elsevierStyleHsp" style=""></span>ml&#41; y el grupo C &#40;718<span class="elsevierStyleHsp" style=""></span>ml&#41;&#44; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#46; No hubo diferencias en las complicaciones y la tasa de transfusiones de sangre entre los 3 grupos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La aplicaci&#243;n t&#243;pica de 1<span class="elsevierStyleHsp" style=""></span>g de ATX reduce significativamente la p&#233;rdida de sangre en pacientes intervenidos de artroplastia total de rodilla&#44; en mayor magnitud que la aplicaci&#243;n intravenosa y la no administraci&#243;n&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n y objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; L&#243;pez-Hualda &#193;&#44; Dauder-Gallego C&#44; Ferre&#241;o-M&#225;rquez D&#44; Mart&#237;nez-Mart&#237;n J&#46; Eficacia y seguridad del &#225;cido tranex&#225;mico t&#243;pico en la artroplastia de rodilla&#46; Med Clin &#40;Barc&#41;&#46; 2018&#59;151&#58;431&#8211;434&#46;</p>"
      ]
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">ASA&#58; American Society of Anaesthesiologists&#59; IV&#58; intravenous</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">The values are expressed as a percentage or average<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group A &#40;topical&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group B &#40;IV&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group C &#40;control&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">73&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;331&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;232&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ASA II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;584&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preoperative haemoglobin &#40;g&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;182&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Duration of the intervention &#40;min&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">108&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">110&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;485&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">t</span>-Student or Mann&#8211;Whitney test for continuous variables and Fisher&#39;s exact test for categorical variables&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Preoperative characteristics of the groups&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">IV&#58; intravenous</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">The values are expressed as average<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group A &#40;topical&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group B &#40;IV&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group C &#40;control&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Postoperative haemoglobin &#40;g&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;01<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;144&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Differential haemoglobin &#40;g&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;033&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Drainage 24<span class="elsevierStyleHsp" style=""></span>h &#40;cc&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">137<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>154&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">344<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>168&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">603<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>375&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total drainage &#40;cc&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">195<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">466<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>211&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">718<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>414&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Days of drainage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
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