Preventive analgesia in hip or knee arthroplasty: A systematic review | Revista Española de Cirugía Ortopédica y Traumatología (English Edition)

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Díaz-Heredia, E. Loza, I. Cebreiro, M.Á. Ruiz Iban" "autores" => array:4 [ 0 => array:4 [ "nombre" => "J." "apellidos" => "Díaz-Heredia" "email" => array:1 [ 0 => "jorgedh@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "E." "apellidos" => "Loza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "I." "apellidos" => "Cebreiro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "M.Á." "apellidos" => "Ruiz Iban" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Traumatología y Cirugía Ortopédica, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Salud Musculoesquelética, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Analgesia preventiva en artroplastia de cadera o rodilla: una revisión sistemática" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1611 "Ancho" => 2169 "Tamanyo" => 123277 ] ] "descripcion" => array:1 [ "en" => "Flow diagram of the articles included." ] ] ] "textoCompleto" => "IntroductionPreventive analgesia is defined as a set of pharmacological and non-pharmacological strategies that are implemented before creating a surgical wound with the goal of preventing or minimizing the pain caused by damaging surgical stimuli.<a class="elsevierStyleCrossRefs" href="#bib0260">1,2</a> The main objectives are to reduce acute pain due to tissue damage, prevent pathological modulation associated to pain on the central nervous system and inhibit the persistence of postoperative pain and the development of chronic pain. Preventive analgesia can also reduce the intake of analgesic drugs in the postoperative period.Several experimental studies<a class="elsevierStyleCrossRefs" href="#bib0270">3,4</a> have confirmed that, at least in animals, the administration of analgesic drugs before tissue aggression is more effective to control pain than their administration subsequent to the damage.However, these results have not been reproduced in a conclusive manner in everyday clinical practice. Several systematic reviews including the analysis of over 80 controlled clinical trials have shown that the starting time of analgesia did not affect the control of postoperative pain, regardless of the type of preventive analgesia employed.<a class="elsevierStyleCrossRef" href="#bib0280">5</a> This conclusion is not completely categorical, since most of the existing studies are based on short-term interventions on postoperative pain, so their influence on the development of central hypersensitivity to pain<a class="elsevierStyleCrossRefs" href="#bib0285">6–8</a> cannot be reliably assessed. Moreover, there may be differences depending on the type of surgery.The objective of the present work is to systematically review the literature to analyze the effectiveness and safety of preventive perioperative treatment using pharmacological measures in patients with an indication of hip or knee arthroplasty in relation to postoperative pain.Materials and methodsA systematic literature review was conducted following the Cochrane Collaboration guide.<a class="elsevierStyleCrossRef" href="#bib0300">9</a>Study selection criteriaThe studies selected included adult patients with an indication of knee and/or hip arthroplasty who suffered moderate to intense preoperative pain (≥4 in the analog visual scale). These studies should assess the use (effectiveness and safety) of a specific pharmacological treatment (preventive) soon before the intervention (not necessarily the previous 24–48h). The treatments included oral formulations (opioids, non-steroidal anti-inflammatory drugs [NSAIDs], analgesics, corticoids, anticonvulsants and antidepressants), topical (including capsaicin, topical lidocaine, topical NSAIDs and topical massage with vaseline), transdermal patches, etc. The studies should have compared the effect against active drugs, placebo or other procedures (exercise, etc.). The main indicator of the result (effectiveness) was postoperative pain, whilst secondary indicators of the result (effectiveness) included savings on opioids, days of hospital admission, quality of life, function, satisfaction, etc. Other variables analyzed included: digestive hemorrhage, constipation and cost.Lastly, we only included studies with the following designs: metaanalyses, systematic reviews, clinical trials and observational studies.We excluded studies conducted on animals, basic science, articles on prosthetic revisions and prostheses due to fractures, studies in which all the patients suffered a chronic inflammatory disease (rheumatoid arthritis, lupus, etc.), non-pharmacological measures, joint infiltrations (of every kind, including infiltrations of hyaluronic acid), symptomatic slow acting drugs for osteoarthritis (SYSADOAS), and articles in which the preventive treatment was based exclusively on anesthetic block.Search strategyIn order to conduct this review, we screened through the following bibliographic databases: Medline (from the beginning until May 2013), Embase (from the beginning until May 2013), and Cochrane Library (from the beginning until May 2013). Given the volume of citations retrieved we did not search national and international congresses. Subsequently, we conducted a secondary manual search of the bibliography of the articles which were eventually included in the systematic review.<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the search strategies on Medline, as well as the number of citations retrieved. This search used the terms Mesh and terms in free text. As limitations, we only searched for articles which worked with human subjects and which were published in English or Spanish.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Selection of studiesThree reviewers independently analyzed the articles retrieved with the search strategy in the different bibliographic databases to select those which fulfilled the criteria defined and analyzed the articles included in detail. Discrepancies were resolved by one of the reviewers, expert in methodology. The results of the searches were initially depurated by title and abstract or by the entire article in cases without an abstract, in sessions with a maximum duration of 20min. After this process, the articles selected were analyzed in detail (read in their entirety). <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the flow diagram of the article selection process.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Lastly, we conducted a manual search of the references included in the articles selected for a detailed analysis. All references were retrieved through the Internet and entered into the EndNote software program to facilitate their management.Data collection and quality assessment of the studiesThe three reviewers gathered data from the included studies using specific templates which were previously designed for this review. The Oxford quality scale<a class="elsevierStyleCrossRef" href="#bib0305">10</a> was used to assess the methodological quality of the studies included.Analysis and presentation of dataWe created evidence tables to describe the main features of the studies included. Some of the results were expressed as number and percentage (%), mean and standard deviation, median and interquartile range (p25–p75), others as odds ratio, relative risk or hazard ratio and 95% confidence intervals. We only assessed the possibility of conducting a metaanalysis in case of homogeneity.ResultsWe initially included 60 articles to be read in detail (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Out of these, we finally included 36 (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The articles excluded and the reasons for their exclusion are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>, and their references in Annex 1. The main conclusions, along with their level of evidence and recommendation grade are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>The epidemiological data of the study populations are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The patients were adults with a mean age over 50 years, with a slightly higher proportion of females, who presented moderate to severe pain ≥4 in the analog visual scale. Postoperative pain was mainly assessed through an analog visual scale. In general, the quality of the studies was moderate, with some isolated studies of higher quality but with a small “n”.There was considerable variability in terms of the drugs used, which included paracetamol, non-selective NSAIDs, Cox-2 (Coxib) selective NSAIDs, opioids, corticoids, antidepressants, anticonvulsants and others, such as magnesium sulfate, ketamine, nimodipine and clonidine.The preventive analgesia strategy was also highly variable. We included one study which defined “preventive” administration as that administered in the 2 weeks prior to the surgery,<a class="elsevierStyleCrossRef" href="#bib0310">11</a> but most of the studies referred to analgesia administered 24–48h prior to the intervention or at the time of inducing anesthesia. In many studies, the strategy not only consisted preoperative administration, but also included analgesic treatment during the surgery and/or in the following hours.Overall, we observed that, in most studies, preventive analgesia decreased postoperative pain and the intake of opioids during the first hours after surgery. Below are the results obtained, grouped by analgesia strategy.Preventive treatment with NSAIDsIn general, the administration of NSAIDs as a preventive strategy was effective and seemed to decrease both pain and consumption of opioids in the immediate postoperative period. Coxib presented the advantage of not causing alterations in platelet aggregation, which did not alter the rate of hemorrhagic complications.The use of ibuprofen<a class="elsevierStyleCrossRef" href="#bib0310">11</a> 2 weeks prior to the surgery was not found to influence pain control in the postoperative period. A single dose of diclofenac and ketorolac<a class="elsevierStyleCrossRefs" href="#bib0315">12,13</a> before inducing anesthesia decreased the consumption of morphine and its secondary effects compared to placebo in the first 24h after the intervention. On the other hand, dexketoprofen<a class="elsevierStyleCrossRef" href="#bib0325">14</a> administered 24h prior to the surgery and up to 48h after the intervention improved pain at 15h and decreased the consumption of opioids.A total of five studies used celecoxib preventively,<a class="elsevierStyleCrossRefs" href="#bib0330">15–19</a> administered between 1h and 2 weeks before surgery. The result was a decrease in pain and consumption of opioids in the immediate postoperative period (the first 72h). Long-term results were not as consistent. One study<a class="elsevierStyleCrossRef" href="#bib0340">17</a> which used celecoxib 1h before and for 3 weeks after the surgery observed an improvement of postoperative pain compared to placebo up to 28 days later. The use of tenoxicam<a class="elsevierStyleCrossRef" href="#bib0355">20</a> 1h before the intervention did not influence pain improvement and consumption of opioids in the short term. After 9 postoperative days, despite no differences in pain compared to placebo being observed, the consumption of opioids was lower among the treated group.The effect of etoricoxib 1 and 2h prior to the surgery was also assessed,<a class="elsevierStyleCrossRef" href="#bib0360">21</a> and a decrease in the levels of interleukin-6 and prostaglandin E-2 in the blood compared to the control group was observed, as well as a lower level of pain, which was maintained until the third or fourth day. The consumption of opioids was higher among the control group during the first postoperative 12h. The use of rofecoxib<a class="elsevierStyleCrossRefs" href="#bib0365">22–24</a> 1h before the intervention decreased the length of hospital admission and improved postoperative pain and analgesic intake after 2 days. These results were not maintained after discharge.It was observed that lornoxicam<a class="elsevierStyleCrossRef" href="#bib0380">25</a> at high doses 15min before the surgery and at low doses in the postoperative period decreased the consumption of opioids, but this was not associated to a clear decrease of postoperative pain. Parecoxib<a class="elsevierStyleCrossRefs" href="#bib0335">16,26</a> during induction of anesthesia and 12h after it improved postoperative pain and decreased the intake of morphine. The analgesic effects were still evident after 24h when two injections separated by 12h were administered.Preventive analgesia strategies with NSAIDs were safe, except for an increase of perioperative bleeding, which was observed with ibuprofen<a class="elsevierStyleCrossRef" href="#bib0310">11</a> and ketorolac.<a class="elsevierStyleCrossRef" href="#bib0320">13</a> This effect was not observed with parecoxib<a class="elsevierStyleCrossRefs" href="#bib0335">16,26</a> and celecoxib.<a class="elsevierStyleCrossRefs" href="#bib0330">15,17–19</a>Preventive treatment with opioidsIn general, preventive administration of opioids is safe and decreases the consumption of opioids in the immediate postoperative period. Several studies also reported an improvement in immediate postoperative analgesia. There are no data regarding their long-term effects.Several studies have used morphine<a class="elsevierStyleCrossRefs" href="#bib0360">21,27–32</a> in oral, intravenous and intramuscular formulations applied from 1h before the surgery up to the moment of anesthetic induction and have observed a decrease in the levels of pain and consumption of opioids during the first postoperative hours, except in the case of a low quality study,<a class="elsevierStyleCrossRef" href="#bib0390">27</a> in which the pain increased among patients treated with oral morphine 1h prior to the surgery.The use of oxycodone<a class="elsevierStyleCrossRefs" href="#bib0345">18,19</a> was assessed in two low-quality studies and obtained contradictory results both for pain control and opioid intake in the postoperative period. The use of methadone<a class="elsevierStyleCrossRef" href="#bib0420">33</a> just after the induction and before the intervention decreased the postoperative requirement for analgesia.Preventive treatment with corticoidsIn general, preventive use of corticoids seems to decrease both pain and opioid consumption in the postoperative period at 48h, but not after 6 months or 1 year.The use of dexamethasone<a class="elsevierStyleCrossRefs" href="#bib0425">34–36</a> and methylprednisolone<a class="elsevierStyleCrossRefs" href="#bib0440">37,38</a> were also assessed. One low-quality study<a class="elsevierStyleCrossRef" href="#bib0435">36</a> used dexamethasone during anesthetic induction and the results, assessed at 6 months and 1 year, showed no improvement in pain and opioid consumption. Another study, in which dexamethasone was used minutes before surgery,<a class="elsevierStyleCrossRef" href="#bib0425">34</a> reported an improvement of dynamic pain during rehabilitation and a decrease in opioid consumption during the postoperative period, albeit with no effect on pain at rest. One study<a class="elsevierStyleCrossRef" href="#bib0430">35</a> associated dexamethasone with gabapentin and ketamine in a multimodal analgesia protocol and observed an improvement in the levels of postoperative pain, but no decrease in opioid intake. Two studies<a class="elsevierStyleCrossRefs" href="#bib0385">26,27</a> reported that the use of methylprednisolone prior to surgery improved postoperative pain at 48h and decreased opioid intake.Preventive treatment with anticonvulsantsIn general, preventive administration of pregabalin seemed to decrease neuropathic pain and opioid consumption in the immediate and long-term postoperative period. However, there is not enough evidence of its effect on postoperative nociceptive pain. Its secondary effects could represent a limitation. There is not enough conclusive evidence about gabapentin.One study<a class="elsevierStyleCrossRef" href="#bib0450">39</a> assessed neuropathic pain following knee arthroplasty after administering pregabalin 24h before the surgery and 2 weeks after the intervention and reported a decrease in neuropathic pain up to 6 months after the surgery, as well as reduced intrahospital consumption of opioids, shorter hospital stay and increased range of movement during the first 30 days of rehabilitation (compared to placebo). However, the secondary effects, particularly somnolence and obnubilation, were more pronounced with pregabalin.Gabapentin has been used on its own and as part of multimodal analgesia protocols. Isolated gabapentin administered 2h prior to the surgery was used in two studies.<a class="elsevierStyleCrossRefs" href="#bib0455">40,41</a> The first of them<a class="elsevierStyleCrossRef" href="#bib0455">40</a> concluded that it did not decrease the level of pain and opioid consumption compared to placebo in the immediate postoperative period and after 6 months, whereas the second study<a class="elsevierStyleCrossRef" href="#bib0460">41</a> did observe a reduced consumption of opioids among patients treated with gabapentin. However, the latter was a low-quality study, with a short follow-up period. Gabapentin<a class="elsevierStyleCrossRef" href="#bib0430">35</a> used as part of a multimodal analgesia protocol including dexamethasone, ketamine and NSAIDs improved postoperative pain with no differences regarding opioid intake compared to the use of isolated NSAIDs.Preventive treatment with other drugsThe use of ketamine and magnesium sulfate during induction of anesthesia seemed to have a beneficial effect on pain control and opioid intake during the immediate postoperative period. There is insufficient evidence about nimodipine, duloxetine and clonidine as a preventive strategy for postoperative analgesia and opioid consumption.Ketamine administered during anesthetic induction could have a preventive effect. One study<a class="elsevierStyleCrossRef" href="#bib0465">42</a> administered it on its own and reported that, although no variations in the level of pain were observed during the first 48h after the intervention, there was a decrease in opioid intake and knee flexion was recovered faster. Another study<a class="elsevierStyleCrossRef" href="#bib0410">31</a> associated ketamine and morphine and reported an improvement in postoperative analgesia.The use of magnesium sulfate<a class="elsevierStyleCrossRef" href="#bib0470">43</a> in anesthetic induction reduced postoperative pain and opioid consumption during the first 48h after the intervention. Nimodipine<a class="elsevierStyleCrossRef" href="#bib0475">44</a> administered 1h prior to the surgery and for 48h in the postoperative period did not reduce the level of pain and increased the use of morphine 12h after the surgery. On the other hand, the use of duloxetine<a class="elsevierStyleCrossRef" href="#bib0480">45</a> 2h before the surgery and on the morning after did not change postoperative pain, but decreased the use of opioids during hospital admission. Clonidine<a class="elsevierStyleCrossRef" href="#bib0485">46</a> administered 1.5h before the surgery, and 12 and 24h after the initial dose, did not improve postoperative pain, but reduced the use of morphine.Preventive treatment with various interventionsIt seems that the use of combinations of several analgesics as a preventive strategy has a beneficial effect and reduces postoperative pain and analgesic requirements.One study<a class="elsevierStyleCrossRef" href="#bib0490">47</a> using a preoperative protocol with rofecoxib, tramadol, paracetamol and dexamethasone and a postoperative combination of rofecoxib, tramadol, paracetamol, hydrocodone and opioids reported a significant reduction in the level of pain compared to placebo.It has not been proven that adding anesthetic blocks (femoral nerve) to oxycodone and celecoxib (2–12h before the surgery) improved postoperative analgesia up to 12 weeks.<a class="elsevierStyleCrossRef" href="#bib0345">18</a> The preventive use of oxycodone and celecoxib or valdecoxib from the time of surgery and in the postoperative period decreased the consumption of opioids, nausea, vomiting and the length of hospital admission.<a class="elsevierStyleCrossRef" href="#bib0350">19</a>Furthermore, the preoperative use of gabapentin, ketamine and dexamethasone, combined with paracetamol and ketorolac improved postoperative pain compared to the use of paracetamol and ketorolac alone. There were no differences regarding morphine consumption.<a class="elsevierStyleCrossRef" href="#bib0430">35</a> The use of ketamine with morphine and epidural anesthesia with lidocaine prior to the intervention provided better postoperative analgesia compared to general anesthesia.<a class="elsevierStyleCrossRef" href="#bib0410">31</a>DiscussionPreventive analgesia refers to treatments started on the days before the intervention or during anesthetic induction with the objective of reducing pain and drug intake in the postoperative period. This strategy is particularly relevant among patients undergoing hip and knee arthroplasty, as these are aggressive procedures with extensive tissue damage which are usually performed on patients with previously established chronic pain.<a class="elsevierStyleCrossRef" href="#bib0495">48</a>There are no clinical guidelines which determine the most adequate medication and pattern. In a similar review to the present one which included various types of interventions, Buvanendran<a class="elsevierStyleCrossRef" href="#bib0500">49</a> highlighted that NSAIDs had consistently proven their capacity to reduce postoperative pain levels and opioid consumption. On the other hand, the study also recommended the preoperative use of gabapentin and local anesthetic during surgery as part of multimodal analgesia protocols. NSAIDs proved their effectiveness in a metaanalysis conducted by Ong<a class="elsevierStyleCrossRef" href="#bib0505">50</a> which evaluated studies including all types of surgeries.This systematic literature review analyzed the effectiveness and safety of drug treatments proposed in different studies, as well as the patterns described for patients undergoing knee or hip arthroplasty.There are no homogeneous, high-quality studies providing sufficient evidence to recommend a specific preventive strategy or administration protocol. However, it seems that the administration of one or several analgesics at some point during the preoperative process reduces the consumption of analgesics and pain during the postoperative period.<a class="elsevierStyleCrossRefs" href="#bib0345">18,19</a>Both traditional<a class="elsevierStyleCrossRefs" href="#bib0310">11–14</a> and Cox-2<a class="elsevierStyleCrossRefs" href="#bib0330">15–17,20–23,25,26</a> NSAIDs, as well as opioids<a class="elsevierStyleCrossRefs" href="#bib0390">27–33</a> and corticoids<a class="elsevierStyleCrossRefs" href="#bib0425">34,37,38</a> have been shown to be effective. The use of neuroleptics<a class="elsevierStyleCrossRefs" href="#bib0450">39,41</a> could have some beneficial effect on the management of postoperative neuropathic pain, with no evidence of its effect on nociceptive pain.<a class="elsevierStyleCrossRefs" href="#bib0430">35,40</a> The use of ketamine<a class="elsevierStyleCrossRef" href="#bib0465">42</a> and magnesium sulfate<a class="elsevierStyleCrossRef" href="#bib0470">43</a> during anesthetic induction seems to have a beneficial effect. There is insufficient evidence to determine the effects of nimodipine,<a class="elsevierStyleCrossRef" href="#bib0475">44</a> duloxetine<a class="elsevierStyleCrossRef" href="#bib0480">45</a> and clonidine<a class="elsevierStyleCrossRef" href="#bib0485">46</a> as part of a preventive strategy. It appears that using combinations of several analgesics as part of a preventive strategy decreases pain and the need for postoperative analgesics.<a class="elsevierStyleCrossRefs" href="#bib0350">19,35,47</a>As a limitation of our review, we could highlight that the considerable variability of drugs and preventive strategies described in the literature have notably hindered a generalization of results. We also observed the presence of various different types of bias which affected the validity of numerous studies, therefore conditioning the reproducibility of results. However, the epidemiological characteristics of the population included in the studies selected were similar to those of patients in whom knee or hip arthroplasty is indicated in our country.<a class="elsevierStyleCrossRef" href="#bib0510">51</a> Another limitation of the present study is that it only conducts a systematic review, without delving into a metaanalysis enabling the results of the different studies to be synthesized and thus allowing a better assessment of the strength of the treatments. However, the wide variability in drugs and doses used in the studies made this approach unfeasible.In conclusion, there is insufficient evidence to recommend a specific preventive strategy or administration protocol. However, we believe that administration of Cox-2 and/or opioids during the weeks prior to the intervention, associated to the use of drugs such as corticoids, ketamine and magnesium sulfate during anesthetic induction could be safe and effective strategies for the management of postoperative pain in patients undergoing hip or knee arthroplasty.FundingThe present article obtained funding from MSD. MSD did not participate in the definition of the topic, development of the review, conclusions and drafting of the work.Conflict of interestDr. Díaz Heredia declares a conflict of interest directly related to the present original: “I have received payment from MSD as consultant to elaborate the present work”, as well as not directly related to the present original: “I have received payment for teaching activities from the following companies: Biomet, Grunenthal, MSD, Pfizer, Smith and Nephew; I have received financing for research projects from the following companies: Biomet, Grunenthal and MSD”.Dr. Loza Santamaría declares a conflict of interest directly related to the present original: “I have received payment from MSD as methodologist to conduct the present study”, as well as not directly related to the present original: “I have received financing for research projects from the following companies: Pfizer, Roche, Abbvie, Novartis and MSD”.Dr. Cebreiro declares a conflict of interest directly related to the present original: “I have received payment from MSD as consultant to elaborate the present study”.Dr. Ruiz Iban declares a conflict of interest directly related to the present original: “I have received payment from MSD as consultant to elaborate the present study”, as well as not directly related to the present original: “I have received payment as a consultant from the following companies: Biomet, Bristol-Myers Squibb, Grunenthal, MSD; I have received payment for teaching activities from the following companies: Astelas, Biomet, Bristol-Myers Squibb, Grunenthal, MSD, Pfizer, Smith and Nephew and Zambon; I have received financing for research projects from the following companies: Biomet, Grunenthal and MSD”.Level of evidenceLevel of evidence II.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this study.Confidentiality of dataThe authors declare that no patient data appear in this article.Right to privacy and informed consentThe authors declare that no patient data appear in this article." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres436195" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec459517" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres436194" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec459516" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study selection criteria" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Search strategy" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Selection of studies" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Data collection and quality assessment of the studies" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Analysis and presentation of data" ] ] ] 6 => array:3 [ "identificador" => "sec0040" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Preventive treatment with NSAIDs" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Preventive treatment with opioids" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Preventive treatment with corticoids" ] 3 => array:2 [ "identificador" => "sec0060" "titulo" => "Preventive treatment with anticonvulsants" ] 4 => array:2 [ "identificador" => "sec0065" "titulo" => "Preventive treatment with other drugs" ] 5 => array:2 [ "identificador" => "sec0070" "titulo" => "Preventive treatment with various interventions" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Level of evidence" ] 11 => array:3 [ "identificador" => "sec0095" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0100" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0105" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0110" "titulo" => "Right to privacy and informed consent" ] ] ] 12 => array:2 [ "identificador" => "xack130893" "titulo" => "Acknowledgements" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-03-20" "fechaAceptado" => "2014-09-16" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec459517" "palabras" => array:4 [ 0 => "Knee arthroplasty" 1 => "Hip arthroplasty" 2 => "Preventive analgesia" 3 => "Systematic review" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec459516" "palabras" => array:4 [ 0 => "Artroplastia de rodilla" 1 => "Artroplastia de cadera" 2 => "Analgesia preventiva" 3 => "Revisión sistemática" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo analyze the efficacy and safety of preventive analgesia in patients undergoing hip or knee arthroplasty due to osteoarthritis. MethodsA systematic literature review was performed, using a defined a sensitive strategy on Medline, Embase and Cochrane Library up to May 2013. The inclusion criteria were: patients undergoing knee and/or hip arthroplasty, adults with moderate or severe pain (≥4 on a Visual Analog Scale). The intervention, the use (efficacy and safety) of pharmacological treatment (preventive) close to surgery was recorded. Oral, topical and skin patch drugs were included. Systematic reviews, meta-analysis, controlled trials and observational studies were selected. ResultsA total of 36 articles, of moderate quality, were selected. The patients included were representative of those undergoing knee and/or hip arthroplasty in Spain. They had a mean age >50 years, higher number of women, and reporting moderate to severe pain (≥4 on a Visual Analog Scale). Post-surgical pain was mainly evaluated with a Visual Analog Scale. A wide variation was found as regards the drugs used in the preventive protocols, including acetaminophen, classic NSAID, Cox-2, opioids, corticosteroids, antidepressants, analgesics for neuropathic pain, as well as others, such as magnesium, ketamine, nimodipine or clonidine. In general, all of them decreased post-surgical pain without severe adverse events. ConclusionsThe use or one or more pre-surgical analgesics decreases the use of post-surgical drugs, at least for short term pain." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoAnalizar la eficacia y la seguridad de la analgesia preventiva en pacientes que son sometidos a artroplastia de cadera o rodilla por artrosis. MétodosSe realizó una revisión sistemática: se definió una estrategia de búsqueda bibliográfica sensible en Medline, Embase y Cochrane Library hasta mayo de 2013; se definió la población con los siguientes criterios: pacientes con indicación de artroplastia de cadera y/o rodilla, adultos, dolor moderado a intenso (≥4 en la Escala Visual Analógica), la intervención, el uso (eficacia y seguridad) del tratamiento farmacológico (preventivo) próximo a la cirugía. Se incluyeron formulaciones orales, tópicas y parches. Se incluyeron revisiones sistemáticas, metaanálisis, ensayos clínicos y estudios observacionales. ResultadosSe incluyeron 36 artículos de calidad moderada. Incluían pacientes representativos de aquellos a los que se les indica una artroplastia de cadera o rodilla en nuestro país, adultos, con una edad media superior a 50 años, ligera mayor proporción de mujeres y que presentan dolor de moderado a grave (≥4 en la Escala Visual Analógica). El dolor posquirúrgico se evaluó sobre todo con la Escala Visual Analógica. Existe mucha variabilidad en cuanto a los fármacos utilizados incluyendo paracetamol, AINE clásicos, AINE selectivos de la Cox-2, opioides, corticoides, antidepresivos, analgésicos para el tratamiento del dolor neuropático y otros como sulfato magnésico, ketamina, nimodipino o clonidina. Todos en general parecen mejorar el dolor posquirúrgico sin presentar acontecimientos adversos graves. ConclusionesEl uso de uno o varios analgésicos en el preoperatorio disminuye el consumo de analgésicos y el dolor en el posoperatorio, al menos el dolor agudo." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "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: Díaz-Heredia J, Loza E, Cebreiro I, Ruiz Iban MÁ. Analgesia preventiva en artroplastia de cadera o rodilla: una revisión sistemática. Rev Esp Cir Ortop Traumatol. 2015;59:73–90." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1611 "Ancho" => 2169 "Tamanyo" => 123277 ] ] "descripcion" => array:1 [ "en" => "Flow diagram of the articles included." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"># \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" 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valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">((((((((((((((((«Review»[Publication Type] OR Review, Systematic OR Review, Multicase OR Review Literature OR Review, Academic OR Review of Reported Cases OR Review)) OR (((«Clinical Trial»[Publication Type]) OR «Validation Studies»[Publication Type]) OR «Evaluation Studies»[Publication Type])) OR («Clinical Trial, Phase I»[Publication Type] OR Clinical Trial, Phase 1)) OR («Clinical Trial, Phase II»[Publication Type] OR Clinical Trial, Phase 2 OR Clinical Trial, Phase II)) OR («Clinical Trial, Phase III»[Publication Type] OR Clinical Trial, Phase 3 OR Clinical Trial, Phase III)) OR («Clinical Trial, Phase IV»[Publication Type] OR Clinical Trial, Phase 4 OR Clinical Trial, Phase IV)) OR («Controlled Clinical Trial»[Publication Type])) OR («Multicenter Study»[Publication Type] OR Multicenter Studies OR Multicenter Study)) OR («Randomized Controlled Trial»[Publication Type] OR Randomized Controlled Trial)) OR («Cohort Studies»[Mesh] OR Cohort Study OR Studies, Cohort OR Study, Cohort OR Concurrent Studies OR Studies, Concurrent OR Concurrent Study OR Study, Concurrent OR Historical Cohort Studies OR Studies, Historical Cohort OR Cohort Studies, Historical OR Cohort Study, Historical OR Historical Cohort Study OR Study, Historical Cohort OR Analysis, Cohort OR Analyses, Cohort OR Cohort Analyses OR Cohort Analysis OR Closed Cohort Studies OR Cohort Studies, Closed OR Closed Cohort Study OR Cohort Study, Closed OR Study, Closed Cohort OR Studies, Closed Cohort OR Incidence Studies OR Incidence Study OR Studies, Incidence OR Study, Incidence OR Cohort Studies)) OR («Cohort Studies»[Mesh] OR cohort study OR studies, cohort OR study, cohort OR concurrent studies OR studies, concurrent OR concurrent study OR study, concurrent OR historical cohort studies OR studies, historical cohort OR cohort studies, historical OR cohort study, historical OR historical cohort study OR study, historical cohort OR analysis, cohort OR analysis, cohort OR cohort analyses OR cohort analysis OR closed cohort studies OR cohort studies, closed OR closed cohort study OR cohort study, closed OR study, closed cohort OR studies, closed cohort OR incidence studies OR incidence study OR studies, incidence OR study, incidence OR cohort studies)) OR («Longitudinal Studies»[Mesh] OR Longitudinal Study OR Studies, Longitudinal OR Study, Longitudinal OR Longitudinal Survey OR Longitudinal Surveys OR Survey, Longitudinal OR Surveys, Longitudinal OR Longitudinal Studies)) OR («Follow-Up Studies»[Mesh] OR Follow Up Studies OR Follow-Up Study OR Studies, Follow-Up OR Study, Follow-Up OR Followup Studies OR Followup Study OR Studies, Followup OR Study, Followup OR Follow-Up Studies)) OR («Prospective Studies»[Mesh] OR Prospective Study OR Studies, Prospective OR Study, Prospective OR Prospective Studies)) OR («meta-analysis»[Publication Type] OR «meta-analysis as topic»[MeSH Terms] OR «meta-analysis»[All Fields])) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4,426,305 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">#1 AND #2 AND #3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4729 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Risk factors[MH] OR causalities OR multifactorial causality OR causalities, multifactorial OR causality, multifactorial OR multifactorial causalities OR multiple causation OR causation, multiple OR causations, multiple OR multiple causations OR reinforcing factors OR factors, reinforcing OR factors, reinforcing OR reinforcing factor OR causation OR causations OR enabling factors OR enabling factor OR factors, enabling OR factors, enabling OR predisposing factors OR factors, predisposing OR factors, predisposing OR predisposing factor OR determinant OR predictor OR predict* OR prognostic \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1,542,865 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Search «pain, postoperative»[MeSH Terms] OR («pain»[All Fields] AND «postoperative»[All Fields]) OR «postoperative pain»[All Fields] OR («postoperative»[All Fields] AND «pain»[All Fields]) OR («pain, postoperative»[MeSH Terms] OR («pain»[All Fields] AND «postoperative»[All Fields]) OR «postoperative pain»[All Fields] OR («postoperative»[All Fields] AND «pains»[All Fields]) OR «postoperative pains»[All Fields]) OR «pain»[MeSH Terms] OR «pain»[All Fields] \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">536,118 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Osteoarthritides OR Osteoarthrosis OR Osteoarthroses OR Arthritis, Degenerative OR Arthritides, Degenerative OR Coxarthrosis OR Arthroplasties, Replacement, Hip OR Arthroplasties, Replacement, Hip OR Hip Prosthesis Implantation OR Hip Replacement, Total OR Hip Replacements, Total OR Arthroplasties, Replacement, Knee OR Knee Replacement, Total OR Knee Replacements, Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">315,207 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab680826.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Search strategy in Medline." ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "h: hours; iv: intravenous; kg: kilogram; mg: milligram; min: minute; ml: milliliter; RCT: randomized clinical trial; THA: total hip arthroplasty; TKA: total knee arthroplasty." "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"># \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">Study \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">Population \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">Intervention \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">Measurement of outcome \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">Comments \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Adam 2005,<a class="elsevierStyleCrossRef" href="#bib0465">42</a> RCT, 3 month follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=40 TKA• Mean age 68 years• 70% females• Criteria ASA I–III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Ketamine- >0.05ml/kg, iv in bolus following anesthetic induction- 3μgkg−1min−1 iv (continuous infusion) intraoperator- 1.5μgkg−1min−1 iv (continuous infusion) during 48h after surgery• Saline solution (same volume) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• Knee flexion• Days of hospital admission• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Alexander 2002,<a class="elsevierStyleCrossRef" href="#bib0315">12</a> RCT double blind placebo control, 24h follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=99 TKA or THA• Mean age 64 years• 63% females• Moderate basal pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Diclofenac 75mg iv and ketorolac 60mg iv (before anesthetic induction) in a single dose• Placebo iv \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Beaupre 2012,<a class="elsevierStyleCrossRef" href="#bib0345">18</a> observational prospective, 12 weeks follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=39 TKA• Mean age 65 years• 50% females• Moderate basal pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Oxycodone 10mg oral and celecoxib 100–200mg oral (2–12h before surgery)• Anesthetic block (femoral nerve) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain up to 12 weeks• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 2b• Very small sample size \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bergeron 2009,<a class="elsevierStyleCrossRef" href="#bib0435">36</a> RCT double blind, 6 weeks follow-up, evaluation 1 year later \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=50 TKA• do not provide more information \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Dexamethasone 40mg iv in anesthetic induction• Saline solution \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain at 6 weeks and 1 year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1cmultiple biases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bugter 2003<a class="elsevierStyleCrossRef" href="#bib0310">11</a>, RCT double blind placebo control, 16 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=36 THA• Mean age 61 years• 70% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Ibuprofen 600mg/8h oral 2 weeks before surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain at 24h• Postoperative opioid intake at 24h• Perioperative bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1c• multiple biases• Very small sample size \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Buvanendran 2003,<a class="elsevierStyleCrossRef" href="#bib0365">22</a> RCT double blind placebo control, 8 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=70 TKA• Mean age 61 years• 67% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Rofecoxib 50mg oral preoperative 24h before and 2 weeks after surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative intake of opioids and other related drugs during hospital admission• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Buvanendran 2010,<a class="elsevierStyleCrossRef" href="#bib0450">39</a> RCT double blind placebo control, 6 months follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=240 TKA• Mean age 21 years• 68% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Pregabalin 300mg oral 24h before and 2 weeks after surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain until 6 months• Postoperative opioid intake• Days of hospital admission• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Casey 2006,<a class="elsevierStyleCrossRef" href="#bib0475">44</a> RCT double blind placebo control, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=40 TKA• Mean age 71 years• 58% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Nimodipine 90mg oral 1h prior to surgery and for 48h more• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative opioid intake \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 2b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clarke 2009_1,<a class="elsevierStyleCrossRef" href="#bib0455">40</a> RCT placebo control, 6 months follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=126 TKA• Mean age 62 years• 35% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Gabapentin 100–600mg 2h before and 2h after surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain until 6 months• Postoperative opioid intake until 6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clarke 2009_2,<a class="elsevierStyleCrossRef" href="#bib0460">41</a> RCT placebo control, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=40 TKA• Mean age 61 years• 61% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Gabapentin 100–600mg 2h before and 2h after surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain at 2 days• Postoperative opioid intake at 2 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 2b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Duellman 2009,<a class="elsevierStyleCrossRef" href="#bib0350">19</a> observational retrospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=127 TKA or THA• Mean age 62 years• 48% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Oxycodone and celecoxib or valdecoxib (from surgery, different doses and patterns) and during postoperative period \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative opioid intake• Days of hospital admission• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 2b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Eggers 1999,<a class="elsevierStyleCrossRef" href="#bib0355">20</a> RCT placebo control, 9 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=101 TKA• Mean age 67 years• <50% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Tenoxicam 40mg oral 1h before surgery +20mg iv at 24h+20mg oral 8 days• Tenoxicam 40mg iv 1h after surgery + 20mg iv at 24h + 20mg oral 8 days• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain at 48h and 3–9 days• Postoperative opioid intake at 48h and at 3–9 days• Postoperative consumption of analgesics at 48h, 3–9 days• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Feng 2008,<a class="elsevierStyleCrossRef" href="#bib0370">23</a> RCT placebo control, 3 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=34 TKA• Mean age 66 years• 69% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Rofecoxib 25mg 1h before surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain at 48–72h• Postoperative opioid intake at 48–72h• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 2b• Very small sample size \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fletcher 1995,<a class="elsevierStyleCrossRef" href="#bib0320">13</a> RCT double blind placebo control, 5 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=60 THA• Mean age 64 years• 60% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Ketorolac 60mg some hours before surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• Perioperative bleeding \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hendolin 1996,<a class="elsevierStyleCrossRef" href="#bib0390">27</a> RCT, follow-up 24h \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=41 TKA• Mean age 70 years• 90% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Morphine 0.14mg/kg intramuscular 1h before surgery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Pain postoperative• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 2b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ho 2010,<a class="elsevierStyleCrossRef" href="#bib0480">45</a> observational prospective, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=50 TKA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Duloxetine 60mg 2h before surgery and following day• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Huang 2008,<a class="elsevierStyleCrossRef" href="#bib0330">15</a> RCT, 7 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=80 TKA• Mean age 70 years• Moderate basal pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Celecoxib 400mg 1h prior to surgery+200mg/12h 5 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain at 48–72h• Postoperative opioid intake at 48–72h• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 2a \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Inan 2007,<a class="elsevierStyleCrossRef" href="#bib0380">25</a> RCT double blind placebo control, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=46 TKA• Elderly• >80% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Lornoxicam high dose 15min before surgery and a low postoperative dose• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Iohom 2002,<a class="elsevierStyleCrossRef" href="#bib0325">14</a> RCT placebo control, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=30 THA• Mean age 62 years• ASA I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Dexketoprofen 25mg 24h prior to surgery and up to 48h after surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain at 15h• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b• Very small sample size \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Ittichaikulthol 2010,<a class="elsevierStyleCrossRef" href="#bib0335">16</a> RCT placebo control, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=120 THA and TKA• Age 18–75 years• ASA I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Parecoxib 40mg 1h before surgery• Celecoxib 400mg preoperative• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hwang 2009,<a class="elsevierStyleCrossRef" href="#bib0470">43</a> observational prospective, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=40 ARC• Mean age <50 years• 45% females• Criteria ASA I-II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Magnesium sulfate- 50mg/kg infusion iv 15min before surgery- 15mg/kg infusion iv during surgery• Saline solution (same volume) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain a 48h• Postoperative opioid intake 48h• Global satisfaction• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Kardash 2008,<a class="elsevierStyleCrossRef" href="#bib0425">34</a> RCT double blind placebo control, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=50 THA, unilateral or total• Mean age 68 years• 50% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Dexamethasone 40mg iv, 10min before surgery• Ibuprofen 400mg/6h oral (during 48h)• Paracetamol 650mg/6h oral (during 48h)• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• CRP levels• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lunn 2011,<a class="elsevierStyleCrossRef" href="#bib0445">38</a> RCT double blind placebo control, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=48 TKA• Mean age 66 years• 50% females• ASA I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Methylprednisolone 125mg (2ml) iv, single dose before surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain at 48h• Opioid savings at 48h• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Lunn 2013,<a class="elsevierStyleCrossRef" href="#bib0440">37</a> double blind placebo control, 2 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=48 THA• Mean age 66 years• 56% females• ASA I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Methylprednisolone 125mg (2ml) iv, single dose before surgery• Placebo \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain at 48h• Opioid savings at 48h• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mallory 2002,<a class="elsevierStyleCrossRef" href="#bib0375">24</a> observational prospective, 24 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=317 TKA or THA• Mean age 64 years• 50% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Rofecoxib or celecoxib 2 weeks before surgery and for 10 days after \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Days of hospital admission• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 2a \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Martinez 2007,<a class="elsevierStyleCrossRef" href="#bib0385">26</a> RCT placebo control, 5 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=78 THA• Mean age 63 years• 50% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Pre group:- Parecoxib 40mg iv in induction and 12h after induction- Placebo 40mg iv. During surgical wound closure• Post group:- Parecoxib 40mg iv. During wound closure and 12h after induction- Placebo 40mg iv. During induction• Control group:- Placebo 40mg iv. During induction, wound closure and 12h after induction \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• Perioperative bleeding• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mc Swiney 1997<a class="elsevierStyleCrossRef" href="#bib0400">29</a>, RCT double blind, 24h follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=50 TKA• No explicit data provided on basal characteristics. Authors indicate that there were no differences between groups \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Experimental group:- Morphine 0.125mg/kg (60ml saline solution) iv• Control group:- Morphine 0.125mg/kg intramuscular in opposite leg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Meurnier 2007,<a class="elsevierStyleCrossRef" href="#bib0340">17</a> RCT placebo control, 1 year follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=44 TKA• Mean age 68 years• 55% females• ASA I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Celecoxib 200mg oral 1h before surgery and during 3 weeks after (2 times per day)• Placebo 200mg oral 1h before surgery and during 3 weeks after (2 times per day)• Anesthetic technique: subarachnoid spinal with 17.5 isobaric bupivacaine at 20mg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain until 28 days• Perioperative bleeding• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Park 1996,<a class="elsevierStyleCrossRef" href="#bib0485">46</a> RCT double blind placebo control, 36h follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Population (n=39) TKA• Mean age 67 years• 60% females• ASA I–III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Clonidine 5μgkg−1 oral 1.5h before surgery, 12h and 24h after initial dose• Placebo same dose oral \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Porter 1983,<a class="elsevierStyleCrossRef" href="#bib0420">33</a> RCT double blind \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=26 THA or TKA• Mean age 63 years• 50% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Group I: methadone 10mg iv just after induction of anesthesia• Group P: methadone 10mg, iv. After intervention (3h after induction)• Group I: neuromuscular block pancuronium 0.1mg/kg• Group P: bupivacaine 0.5% extradural \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b• Very small sample size \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rasmussen 2010,<a class="elsevierStyleCrossRef" href="#bib0430">35</a> RCT double blind placebo control, 24h follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=42 THA• Mean age 71 years• 57% females• ASA I–III• Moderate basal pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Experimental group:- Gabapentin 1200mg 1h before anesthesia- Dexamethasone 8mg iv before anesthetic induction- Ketamine 0.15mg/kg preoperative- Paracetamol 1g q hour before anesthesia- Ketorolac 15mg at the end of surgery• Control group:- Placebo 1200mg 1h before anesthesia- Placebo 8mg iv before anesthetic induction- Paracetamol 1g 1h before anesthesia- Ketorolac 15mg at the end of surgery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reiter 2003,<a class="elsevierStyleCrossRef" href="#bib0415">32</a> RCT double blind placebo control, 24h follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=98 TKA or THA• Mean age 62 years• 60% females• ASA I–III \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Morphine 20mg oral 1h before surgery• Placebo 20mg oral 1h before surgery• Anesthesia with phentanyl 3μg/kg iv, thiopental 3–5mg/kg iv and vecuronium 0.1mg/kg iv. Maintained with isoflurane and nitrous oxide at 60% in O2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Pain postoperative• Postoperative opioid intake• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Renner 2011,<a class="elsevierStyleCrossRef" href="#bib0360">21</a> RCT double blind, 24h follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=11 THA• Mean age 68 years• 83% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Etoricoxib 120mg oral 2h before surgery; 120mg oral 1 day after surgery• Placebo oral 2h before surgery, oral 1 day after surgery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Inhibition of prostaglandin production• Suppression of IL-6 increase• Postoperative pain• Postoperative opioid intake• Overall satisfaction• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b• Very small sample size \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Skinner 2004,<a class="elsevierStyleCrossRef" href="#bib0490">47</a> observational prospective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=102 TKA or THA• Mean age 63 years• 65% females \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Experimental group:- Preoperative (immediately before surgery): rofecoxib 50mg oral; tramadol 50mg oral; paracetamol 650mg oral; dexamethasone 2mg oral- Postoperative (hospital): rofecoxib 50mg/day oral; tramadol 50mg/6h oral; paracetamol 650mg/6h oral; hydrocodone 5mg/paracetamol 500mg oral, 1–2 tablets/4h and iv opioids on demand- Postoperative (following discharge): rofecoxib 50mg/day oral; tramadol 50mg/6h oral; hydrocodone 5mg/paracetamol 500mg oral 1–2 comp/4h- Postoperative (following heparin, 14 days): rofecoxib 50mg/day oral; tramadol 50mg/6h oral; aspirin 350mg/day- Bupivacaine 0.25% intraarticular 2ml/h during 48h (for TKA patients)• Control group: conventional therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Quality 2b \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Slowey 1985,<a class="elsevierStyleCrossRef" href="#bib0405">30</a> RCT, 24h follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=30 THA• Mean age 65 years• 60% females• ASA I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Intramuscular group: morphine 15mg intramuscular 1h before surgery; placebo oral 1h before surgery (3 tablets)• Oral group-60: placebo intramuscular 1h before surgery; morphine 30mg LC oral 1h before surgery (2 tablets); placebo oral 1h before surgery (1 tablet)• Oral group-90: placebo intramuscular 1h before surgery; morphine 30mg LC oral 1h before surgery (3 tablets) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b• Very small sample size \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Wong 1997,<a class="elsevierStyleCrossRef" href="#bib0410">31</a> observational prospective 3 days follow-up \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• n=45 TKA• Mean age 61 years• 50% females• ASA I–II \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Group G:- 30min before surgery and upon incision: saline solution 15ml iv- 30 and 60min postoperative: saline solution 10ml• Group EA:- 30min before surgery and upon incision: lidocaine 2% 15ml iv- 30 and 60min postoperative: lidocaine 2% 10ml; morphine 1.5mg, ketamine 20mg• Group EB:-30min before surgery and upon incision: lidocaine 2% 15ml iv, morphine 1.5mg, ketamine 20mg-30 and 60min postoperative: lidocaine 2% 10ml• Anesthetic technique: general anesthesia (group G), epidural lidocaine (groups EA, EB) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Postoperative pain• Postoperative opioid intake• Overall satisfaction• Adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Quality 1b \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab680824.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Evidence table." ] ] 3 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"># \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">Study \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">Reasons for exclusion \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Barreveld 2013 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Systematic review including studies of hip and knee arthroplasties, as well as other types of surgery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Becchi 2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Main objective was analgesia with continuous psoas compartment block (no preventive analgesia with drug treatment) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Berger 2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No comparison group \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Brooks 2003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Case report describing an epidural catheter \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bullingham 1984 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Description of a treatment with sublingual buprenorphine initially administered perioperatively. The preemptive effect was not evaluated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Buvanendran 2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Study evaluating plasma concentrations of pregabalin in blood and in LCR. Pain was not evaluated \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clarke 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Review of articles on the use of gabapentin and pregabalin in different pathologies not exclusively TKA and THA \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">De Oliveira 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Metaanalysis on the preoperative use of ketorolac. Mixing articles from various specialties \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Du Manoir 2003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Use of nefopam in postoperative treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fransen 2004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Inclusion of revision surgeries \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Fu 2010 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Inclusion of intraarticular infiltrations \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Kilickan 2000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Evolution of epidural analgesia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Moretti 2012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Evaluation of a postoperative treatment \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hebl 2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Three patients in the intervention group and four patients in the control group presented a diagnosis of rheumatoid arthritis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Koinig 1988 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Arthroscopy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Notarnicola 2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Only anesthetic block \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Perrin 2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Series of cases, pilot study with a very small sample size \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reuben 2002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The author retracted \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reuben 2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The author retracted \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Reuben 2008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">The author retracted \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Rosenberg 2006 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Summary of several studies, insufficient data to complete data collection form \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Schroer 2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Preventive treatment was the same for all patients, placebo was administered in the postoperative period \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Southworth 2009 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Inclusion of other types of surgeries \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Straube 2005 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Inclusion of other types of surgeries \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab680827.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Studies excluded after full reading and reasons for exclusion." ] ] 4 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "LE: level of evidence; RG: recommendation grade." "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">Conclusion \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">LE; RG \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">- Preventive analgesia with NSAIDs seems to decrease both pain and opioid consumption in the postoperative period- Results were more consistent and longer-lasting with Cox-2 than with traditional NSAIDs- With traditional NSAIDs there were no significant adverse events except for perioperative bleeding, which did not appear with Cox-2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1b; A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">- Preventive analgesia with opioids reduced the consumption of analgesics in the postoperative period. An improvement of analgesia was also observed in the immediate postoperative period, albeit not in the long term-Safe strategies, with no significant adverse events \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1b; A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">- Preventive analgesia with corticoids seems to reduce both pain and opioid consumption in the postoperative period at 48h, but not after 6 months or 1 year \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2a; B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">- Preventive analgesia with pregabalin seemed to reduce neuropathic pain in the short and long term- There is insufficient evidence to determine the effect on postoperative nociceptive pain and consumption of opioids- Preventive analgesia with gabapentin did not influence postoperative pain \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2b; B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">- The use of ketamine and magnesium sulfate during analgesic induction seemed to have a beneficial effect on pain control and opioid consumption in the immediate postoperative period \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1b; A \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">- There is insufficient evidence to determine the effect of preventive analgesia with nimodipine, duloxetine and clonidine \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2b; B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">- Preventive analgesia with combinations of various analgesics reduced pain and the need for analgesics after surgery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2b; B \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">- There is insufficient evidence to recommend a specific strategy for preventive analgesia or administration protocol. However, it seems that administration of one or more analgesics at some point during the preoperative process reduces postoperative pain and consumption of analgesics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2b; B \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab680825.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Level of evidence and recommendation grade were established according to the Oxford quality scale." ] ] ] "descripcion" => array:1 [ "en" => "Main conclusions along with level of evidence and recommendation grade<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:51 [ 0 => array:3 [ "identificador" => "bib0260" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pre-emptive analgesia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.B. Dahl" 1 => "S. Moiniche" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/bmb/ldh030" "Revista" => array:6 [ "tituloSerie" => "Br Med Bull" "fecha" => "2004" "volumen" => "71" "paginaInicial" => "13" "paginaFinal" => "27" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15596866" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0265" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "S. Moiniche" 1 => "H. Kehlet" 2 => "J.B. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/19888856/0000005900000002/v2_201502210342/S1988885615000097/v2_201502210342/en/main.assets" "Apartado" => array:4 [ "identificador" => "7579" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/19888856/0000005900000002/v2_201502210342/S1988885615000097/v2_201502210342/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1988885615000097?idApp=UINPBA00004N"]

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Preventive analgesia in hip or knee arthroplasty: A systematic review

Analgesia preventiva en artroplastia de cadera o rodilla: una revisión sistemática

J. Díaz-Herediaa,

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jorgedh@gmail.com

Corresponding author.

, E. Lozab, I. Cebreiroa, M.Á. Ruiz Ibana

a Servicio de Traumatología y Cirugía Ortopédica, Hospital Universitario Ramón y Cajal, Madrid, Spain

b Instituto de Salud Musculoesquelética, Madrid, Spain

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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">Preventive analgesia is defined as a set of pharmacological and non-pharmacological strategies that are implemented before creating a surgical wound with the goal of preventing or minimizing the pain caused by damaging surgical stimuli&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">1&#44;2</span></a> The main objectives are to reduce acute pain due to tissue damage&#44; prevent pathological modulation associated to pain on the central nervous system and inhibit the persistence of postoperative pain and the development of chronic pain&#46; Preventive analgesia can also reduce the intake of analgesic drugs in the postoperative period&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Several experimental studies<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">3&#44;4</span></a> have confirmed that&#44; at least in animals&#44; the administration of analgesic drugs before tissue aggression is more effective to control pain than their administration subsequent to the damage&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">However&#44; these results have not been reproduced in a conclusive manner in everyday clinical practice&#46; Several systematic reviews including the analysis of over 80 controlled clinical trials have shown that the starting time of analgesia did not affect the control of postoperative pain&#44; regardless of the type of preventive analgesia employed&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">5</span></a> This conclusion is not completely categorical&#44; since most of the existing studies are based on short-term interventions on postoperative pain&#44; so their influence on the development of central hypersensitivity to pain<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">6&#8211;8</span></a> cannot be reliably assessed&#46; Moreover&#44; there may be differences depending on the type of surgery&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The objective of the present work is to systematically review the literature to analyze the effectiveness and safety of preventive perioperative treatment using pharmacological measures in patients with an indication of hip or knee arthroplasty in relation to postoperative pain&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">A systematic literature review was conducted following the Cochrane Collaboration guide&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">9</span></a></p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study selection criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">The studies selected included adult patients with an indication of knee and&#47;or hip arthroplasty who suffered moderate to intense preoperative pain &#40;&#8805;4 in the analog visual scale&#41;&#46; These studies should assess the use &#40;effectiveness and safety&#41; of a specific pharmacological treatment &#40;preventive&#41; soon before the intervention &#40;not necessarily the previous 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; The treatments included oral formulations &#40;opioids&#44; non-steroidal anti-inflammatory drugs &#91;NSAIDs&#93;&#44; analgesics&#44; corticoids&#44; anticonvulsants and antidepressants&#41;&#44; topical &#40;including capsaicin&#44; topical lidocaine&#44; topical NSAIDs and topical massage with vaseline&#41;&#44; transdermal patches&#44; etc&#46; The studies should have compared the effect against active drugs&#44; placebo or other procedures &#40;exercise&#44; etc&#46;&#41;&#46; The main indicator of the result &#40;effectiveness&#41; was postoperative pain&#44; whilst secondary indicators of the result &#40;effectiveness&#41; included savings on opioids&#44; days of hospital admission&#44; quality of life&#44; function&#44; satisfaction&#44; etc&#46; Other variables analyzed included&#58; digestive hemorrhage&#44; constipation and cost&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Lastly&#44; we only included studies with the following designs&#58; metaanalyses&#44; systematic reviews&#44; clinical trials and observational studies&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">We excluded studies conducted on animals&#44; basic science&#44; articles on prosthetic revisions and prostheses due to fractures&#44; studies in which all the patients suffered a chronic inflammatory disease &#40;rheumatoid arthritis&#44; lupus&#44; etc&#46;&#41;&#44; non-pharmacological measures&#44; joint infiltrations &#40;of every kind&#44; including infiltrations of hyaluronic acid&#41;&#44; symptomatic slow acting drugs for osteoarthritis &#40;SYSADOAS&#41;&#44; and articles in which the preventive treatment was based exclusively on anesthetic block&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Search strategy</span><p id="par0045" class="elsevierStylePara elsevierViewall">In order to conduct this review&#44; we screened through the following bibliographic databases&#58; Medline &#40;from the beginning until May 2013&#41;&#44; Embase &#40;from the beginning until May 2013&#41;&#44; and Cochrane Library &#40;from the beginning until May 2013&#41;&#46; Given the volume of citations retrieved we did not search national and international congresses&#46; Subsequently&#44; we conducted a secondary manual search of the bibliography of the articles which were eventually included in the systematic review&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the search strategies on Medline&#44; as well as the number of citations retrieved&#46; This search used the terms <span class="elsevierStyleItalic">Mesh</span> and terms in free text&#46; As limitations&#44; we only searched for articles which worked with human subjects and which were published in English or Spanish&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Selection of studies</span><p id="par0055" class="elsevierStylePara elsevierViewall">Three reviewers independently analyzed the articles retrieved with the search strategy in the different bibliographic databases to select those which fulfilled the criteria defined and analyzed the articles included in detail&#46; Discrepancies were resolved by one of the reviewers&#44; expert in methodology&#46; The results of the searches were initially depurated by title and abstract or by the entire article in cases without an abstract&#44; in sessions with a maximum duration of 20<span class="elsevierStyleHsp" style=""></span>min&#46; After this process&#44; the articles selected were analyzed in detail &#40;read in their entirety&#41;&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the flow diagram of the article selection process&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Lastly&#44; we conducted a manual search of the references included in the articles selected for a detailed analysis&#46; All references were retrieved through the Internet and entered into the EndNote software program to facilitate their management&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Data collection and quality assessment of the studies</span><p id="par0065" class="elsevierStylePara elsevierViewall">The three reviewers gathered data from the included studies using specific templates which were previously designed for this review&#46; The Oxford quality scale<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">10</span></a> was used to assess the methodological quality of the studies included&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Analysis and presentation of data</span><p id="par0070" class="elsevierStylePara elsevierViewall">We created evidence tables to describe the main features of the studies included&#46; Some of the results were expressed as number and percentage &#40;&#37;&#41;&#44; mean and standard deviation&#44; median and interquartile range &#40;p25&#8211;p75&#41;&#44; others as odds ratio&#44; relative risk or hazard ratio and 95&#37; confidence intervals&#46; We only assessed the possibility of conducting a metaanalysis in case of homogeneity&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall">We initially included 60 articles to be read in detail &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Out of these&#44; we finally included 36 &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The articles excluded and the reasons for their exclusion are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#44; and their references in Annex 1&#46; The main conclusions&#44; along with their level of evidence and recommendation grade are shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The epidemiological data of the study populations are shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; The patients were adults with a mean age over 50 years&#44; with a slightly higher proportion of females&#44; who presented moderate to severe pain &#8805;4 in the analog visual scale&#46; Postoperative pain was mainly assessed through an analog visual scale&#46; In general&#44; the quality of the studies was moderate&#44; with some isolated studies of higher quality but with a small &#8220;<span class="elsevierStyleItalic">n</span>&#8221;&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">There was considerable variability in terms of the drugs used&#44; which included paracetamol&#44; non-selective NSAIDs&#44; Cox-2 &#40;Coxib&#41; selective NSAIDs&#44; opioids&#44; corticoids&#44; antidepressants&#44; anticonvulsants and others&#44; such as magnesium sulfate&#44; ketamine&#44; nimodipine and clonidine&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The preventive analgesia strategy was also highly variable&#46; We included one study which defined &#8220;preventive&#8221; administration as that administered in the 2 weeks prior to the surgery&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">11</span></a> but most of the studies referred to analgesia administered 24&#8211;48<span class="elsevierStyleHsp" style=""></span>h prior to the intervention or at the time of inducing anesthesia&#46; In many studies&#44; the strategy not only consisted preoperative administration&#44; but also included analgesic treatment during the surgery and&#47;or in the following hours&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Overall&#44; we observed that&#44; in most studies&#44; preventive analgesia decreased postoperative pain and the intake of opioids during the first hours after surgery&#46; Below are the results obtained&#44; grouped by analgesia strategy&#46;</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Preventive treatment with NSAIDs</span><p id="par0100" class="elsevierStylePara elsevierViewall">In general&#44; the administration of NSAIDs as a preventive strategy was effective and seemed to decrease both pain and consumption of opioids in the immediate postoperative period&#46; Coxib presented the advantage of not causing alterations in platelet aggregation&#44; which did not alter the rate of hemorrhagic complications&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The use of ibuprofen<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">11</span></a> 2 weeks prior to the surgery was not found to influence pain control in the postoperative period&#46; A single dose of diclofenac and ketorolac<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">12&#44;13</span></a> before inducing anesthesia decreased the consumption of morphine and its secondary effects compared to placebo in the first 24<span class="elsevierStyleHsp" style=""></span>h after the intervention&#46; On the other hand&#44; dexketoprofen<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">14</span></a> administered 24<span class="elsevierStyleHsp" style=""></span>h prior to the surgery and up to 48<span class="elsevierStyleHsp" style=""></span>h after the intervention improved pain at 15<span class="elsevierStyleHsp" style=""></span>h and decreased the consumption of opioids&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">A total of five studies used celecoxib preventively&#44;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">15&#8211;19</span></a> administered between 1<span class="elsevierStyleHsp" style=""></span>h and 2 weeks before surgery&#46; The result was a decrease in pain and consumption of opioids in the immediate postoperative period &#40;the first 72<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; Long-term results were not as consistent&#46; One study<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">17</span></a> which used celecoxib 1<span class="elsevierStyleHsp" style=""></span>h before and for 3 weeks after the surgery observed an improvement of postoperative pain compared to placebo up to 28 days later&#46; The use of tenoxicam<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">20</span></a> 1<span class="elsevierStyleHsp" style=""></span>h before the intervention did not influence pain improvement and consumption of opioids in the short term&#46; After 9 postoperative days&#44; despite no differences in pain compared to placebo being observed&#44; the consumption of opioids was lower among the treated group&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The effect of etoricoxib 1 and 2<span class="elsevierStyleHsp" style=""></span>h prior to the surgery was also assessed&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">21</span></a> and a decrease in the levels of interleukin-6 and prostaglandin E-2 in the blood compared to the control group was observed&#44; as well as a lower level of pain&#44; which was maintained until the third or fourth day&#46; The consumption of opioids was higher among the control group during the first postoperative 12<span class="elsevierStyleHsp" style=""></span>h&#46; The use of rofecoxib<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">22&#8211;24</span></a> 1<span class="elsevierStyleHsp" style=""></span>h before the intervention decreased the length of hospital admission and improved postoperative pain and analgesic intake after 2 days&#46; These results were not maintained after discharge&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">It was observed that lornoxicam<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">25</span></a> at high doses 15<span class="elsevierStyleHsp" style=""></span>min before the surgery and at low doses in the postoperative period decreased the consumption of opioids&#44; but this was not associated to a clear decrease of postoperative pain&#46; Parecoxib<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">16&#44;26</span></a> during induction of anesthesia and 12<span class="elsevierStyleHsp" style=""></span>h after it improved postoperative pain and decreased the intake of morphine&#46; The analgesic effects were still evident after 24<span class="elsevierStyleHsp" style=""></span>h when two injections separated by 12<span class="elsevierStyleHsp" style=""></span>h were administered&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Preventive analgesia strategies with NSAIDs were safe&#44; except for an increase of perioperative bleeding&#44; which was observed with ibuprofen<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">11</span></a> and ketorolac&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">13</span></a> This effect was not observed with parecoxib<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">16&#44;26</span></a> and celecoxib&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">15&#44;17&#8211;19</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Preventive treatment with opioids</span><p id="par0130" class="elsevierStylePara elsevierViewall">In general&#44; preventive administration of opioids is safe and decreases the consumption of opioids in the immediate postoperative period&#46; Several studies also reported an improvement in immediate postoperative analgesia&#46; There are no data regarding their long-term effects&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Several studies have used morphine<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">21&#44;27&#8211;32</span></a> in oral&#44; intravenous and intramuscular formulations applied from 1<span class="elsevierStyleHsp" style=""></span>h before the surgery up to the moment of anesthetic induction and have observed a decrease in the levels of pain and consumption of opioids during the first postoperative hours&#44; except in the case of a low quality study&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">27</span></a> in which the pain increased among patients treated with oral morphine 1<span class="elsevierStyleHsp" style=""></span>h prior to the surgery&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">The use of oxycodone<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">18&#44;19</span></a> was assessed in two low-quality studies and obtained contradictory results both for pain control and opioid intake in the postoperative period&#46; The use of methadone<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">33</span></a> just after the induction and before the intervention decreased the postoperative requirement for analgesia&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Preventive treatment with corticoids</span><p id="par0145" class="elsevierStylePara elsevierViewall">In general&#44; preventive use of corticoids seems to decrease both pain and opioid consumption in the postoperative period at 48<span class="elsevierStyleHsp" style=""></span>h&#44; but not after 6 months or 1 year&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">The use of dexamethasone<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">34&#8211;36</span></a> and methylprednisolone<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">37&#44;38</span></a> were also assessed&#46; One low-quality study<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">36</span></a> used dexamethasone during anesthetic induction and the results&#44; assessed at 6 months and 1 year&#44; showed no improvement in pain and opioid consumption&#46; Another study&#44; in which dexamethasone was used minutes before surgery&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">34</span></a> reported an improvement of dynamic pain during rehabilitation and a decrease in opioid consumption during the postoperative period&#44; albeit with no effect on pain at rest&#46; One study<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">35</span></a> associated dexamethasone with gabapentin and ketamine in a multimodal analgesia protocol and observed an improvement in the levels of postoperative pain&#44; but no decrease in opioid intake&#46; Two studies<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">26&#44;27</span></a> reported that the use of methylprednisolone prior to surgery improved postoperative pain at 48<span class="elsevierStyleHsp" style=""></span>h and decreased opioid intake&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Preventive treatment with anticonvulsants</span><p id="par0155" class="elsevierStylePara elsevierViewall">In general&#44; preventive administration of pregabalin seemed to decrease neuropathic pain and opioid consumption in the immediate and long-term postoperative period&#46; However&#44; there is not enough evidence of its effect on postoperative nociceptive pain&#46; Its secondary effects could represent a limitation&#46; There is not enough conclusive evidence about gabapentin&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">One study<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">39</span></a> assessed neuropathic pain following knee arthroplasty after administering pregabalin 24<span class="elsevierStyleHsp" style=""></span>h before the surgery and 2 weeks after the intervention and reported a decrease in neuropathic pain up to 6 months after the surgery&#44; as well as reduced intrahospital consumption of opioids&#44; shorter hospital stay and increased range of movement during the first 30 days of rehabilitation &#40;compared to placebo&#41;&#46; However&#44; the secondary effects&#44; particularly somnolence and obnubilation&#44; were more pronounced with pregabalin&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Gabapentin has been used on its own and as part of multimodal analgesia protocols&#46; Isolated gabapentin administered 2<span class="elsevierStyleHsp" style=""></span>h prior to the surgery was used in two studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">40&#44;41</span></a> The first of them<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">40</span></a> concluded that it did not decrease the level of pain and opioid consumption compared to placebo in the immediate postoperative period and after 6 months&#44; whereas the second study<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">41</span></a> did observe a reduced consumption of opioids among patients treated with gabapentin&#46; However&#44; the latter was a low-quality study&#44; with a short follow-up period&#46; Gabapentin<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">35</span></a> used as part of a multimodal analgesia protocol including dexamethasone&#44; ketamine and NSAIDs improved postoperative pain with no differences regarding opioid intake compared to the use of isolated NSAIDs&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Preventive treatment with other drugs</span><p id="par0170" class="elsevierStylePara elsevierViewall">The use of ketamine and magnesium sulfate during induction of anesthesia seemed to have a beneficial effect on pain control and opioid intake during the immediate postoperative period&#46; There is insufficient evidence about nimodipine&#44; duloxetine and clonidine as a preventive strategy for postoperative analgesia and opioid consumption&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Ketamine administered during anesthetic induction could have a preventive effect&#46; One study<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">42</span></a> administered it on its own and reported that&#44; although no variations in the level of pain were observed during the first 48<span class="elsevierStyleHsp" style=""></span>h after the intervention&#44; there was a decrease in opioid intake and knee flexion was recovered faster&#46; Another study<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">31</span></a> associated ketamine and morphine and reported an improvement in postoperative analgesia&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The use of magnesium sulfate<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">43</span></a> in anesthetic induction reduced postoperative pain and opioid consumption during the first 48<span class="elsevierStyleHsp" style=""></span>h after the intervention&#46; Nimodipine<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">44</span></a> administered 1<span class="elsevierStyleHsp" style=""></span>h prior to the surgery and for 48<span class="elsevierStyleHsp" style=""></span>h in the postoperative period did not reduce the level of pain and increased the use of morphine 12<span class="elsevierStyleHsp" style=""></span>h after the surgery&#46; On the other hand&#44; the use of duloxetine<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">45</span></a> 2<span class="elsevierStyleHsp" style=""></span>h before the surgery and on the morning after did not change postoperative pain&#44; but decreased the use of opioids during hospital admission&#46; Clonidine<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">46</span></a> administered 1&#46;5<span class="elsevierStyleHsp" style=""></span>h before the surgery&#44; and 12 and 24<span class="elsevierStyleHsp" style=""></span>h after the initial dose&#44; did not improve postoperative pain&#44; but reduced the use of morphine&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Preventive treatment with various interventions</span><p id="par0185" class="elsevierStylePara elsevierViewall">It seems that the use of combinations of several analgesics as a preventive strategy has a beneficial effect and reduces postoperative pain and analgesic requirements&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">One study<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">47</span></a> using a preoperative protocol with rofecoxib&#44; tramadol&#44; paracetamol and dexamethasone and a postoperative combination of rofecoxib&#44; tramadol&#44; paracetamol&#44; hydrocodone and opioids reported a significant reduction in the level of pain compared to placebo&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">It has not been proven that adding anesthetic blocks &#40;femoral nerve&#41; to oxycodone and celecoxib &#40;2&#8211;12<span class="elsevierStyleHsp" style=""></span>h before the surgery&#41; improved postoperative analgesia up to 12 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">18</span></a> The preventive use of oxycodone and celecoxib or valdecoxib from the time of surgery and in the postoperative period decreased the consumption of opioids&#44; nausea&#44; vomiting and the length of hospital admission&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">19</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Furthermore&#44; the preoperative use of gabapentin&#44; ketamine and dexamethasone&#44; combined with paracetamol and ketorolac improved postoperative pain compared to the use of paracetamol and ketorolac alone&#46; There were no differences regarding morphine consumption&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">35</span></a> The use of ketamine with morphine and epidural anesthesia with lidocaine prior to the intervention provided better postoperative analgesia compared to general anesthesia&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">31</span></a></p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Discussion</span><p id="par0205" class="elsevierStylePara elsevierViewall">Preventive analgesia refers to treatments started on the days before the intervention or during anesthetic induction with the objective of reducing pain and drug intake in the postoperative period&#46; This strategy is particularly relevant among patients undergoing hip and knee arthroplasty&#44; as these are aggressive procedures with extensive tissue damage which are usually performed on patients with previously established chronic pain&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">48</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">There are no clinical guidelines which determine the most adequate medication and pattern&#46; In a similar review to the present one which included various types of interventions&#44; Buvanendran<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">49</span></a> highlighted that NSAIDs had consistently proven their capacity to reduce postoperative pain levels and opioid consumption&#46; On the other hand&#44; the study also recommended the preoperative use of gabapentin and local anesthetic during surgery as part of multimodal analgesia protocols&#46; NSAIDs proved their effectiveness in a metaanalysis conducted by Ong<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">50</span></a> which evaluated studies including all types of surgeries&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">This systematic literature review analyzed the effectiveness and safety of drug treatments proposed in different studies&#44; as well as the patterns described for patients undergoing knee or hip arthroplasty&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">There are no homogeneous&#44; high-quality studies providing sufficient evidence to recommend a specific preventive strategy or administration protocol&#46; However&#44; it seems that the administration of one or several analgesics at some point during the preoperative process reduces the consumption of analgesics and pain during the postoperative period&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">18&#44;19</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Both traditional<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">11&#8211;14</span></a> and Cox-2<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">15&#8211;17&#44;20&#8211;23&#44;25&#44;26</span></a> NSAIDs&#44; as well as opioids<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">27&#8211;33</span></a> and corticoids<a class="elsevierStyleCrossRefs" href="#bib0425"><span class="elsevierStyleSup">34&#44;37&#44;38</span></a> have been shown to be effective&#46; The use of neuroleptics<a class="elsevierStyleCrossRefs" href="#bib0450"><span class="elsevierStyleSup">39&#44;41</span></a> could have some beneficial effect on the management of postoperative neuropathic pain&#44; with no evidence of its effect on nociceptive pain&#46;<a class="elsevierStyleCrossRefs" href="#bib0430"><span class="elsevierStyleSup">35&#44;40</span></a> The use of ketamine<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">42</span></a> and magnesium sulfate<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">43</span></a> during anesthetic induction seems to have a beneficial effect&#46; There is insufficient evidence to determine the effects of nimodipine&#44;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">44</span></a> duloxetine<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">45</span></a> and clonidine<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">46</span></a> as part of a preventive strategy&#46; It appears that using combinations of several analgesics as part of a preventive strategy decreases pain and the need for postoperative analgesics&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">19&#44;35&#44;47</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">As a limitation of our review&#44; we could highlight that the considerable variability of drugs and preventive strategies described in the literature have notably hindered a generalization of results&#46; We also observed the presence of various different types of bias which affected the validity of numerous studies&#44; therefore conditioning the reproducibility of results&#46; However&#44; the epidemiological characteristics of the population included in the studies selected were similar to those of patients in whom knee or hip arthroplasty is indicated in our country&#46;<a class="elsevierStyleCrossRef" href="#bib0510"><span class="elsevierStyleSup">51</span></a> Another limitation of the present study is that it only conducts a systematic review&#44; without delving into a metaanalysis enabling the results of the different studies to be synthesized and thus allowing a better assessment of the strength of the treatments&#46; However&#44; the wide variability in drugs and doses used in the studies made this approach unfeasible&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">In conclusion&#44; there is insufficient evidence to recommend a specific preventive strategy or administration protocol&#46; However&#44; we believe that administration of Cox-2 and&#47;or opioids during the weeks prior to the intervention&#44; associated to the use of drugs such as corticoids&#44; ketamine and magnesium sulfate during anesthetic induction could be safe and effective strategies for the management of postoperative pain in patients undergoing hip or knee arthroplasty&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Funding</span><p id="par0240" class="elsevierStylePara elsevierViewall">The present article obtained funding from MSD&#46; MSD did not participate in the definition of the topic&#44; development of the review&#44; conclusions and drafting of the work&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interest</span><p id="par0245" class="elsevierStylePara elsevierViewall">Dr&#46; D&#237;az Heredia declares a conflict of interest directly related to the present original&#58; &#8220;I have received payment from MSD as consultant to elaborate the present work&#8221;&#44; as well as <span class="elsevierStyleItalic">not</span> directly related to the present original&#58; &#8220;I have received payment for teaching activities from the following companies&#58; Biomet&#44; Grunenthal&#44; MSD&#44; Pfizer&#44; Smith and Nephew&#59; I have received financing for research projects from the following companies&#58; Biomet&#44; Grunenthal and MSD&#8221;&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Dr&#46; Loza Santamar&#237;a declares a conflict of interest directly related to the present original&#58; &#8220;I have received payment from MSD as methodologist to conduct the present study&#8221;&#44; as well as <span class="elsevierStyleItalic">not</span> directly related to the present original&#58; &#8220;I have received financing for research projects from the following companies&#58; Pfizer&#44; Roche&#44; Abbvie&#44; Novartis and MSD&#8221;&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Dr&#46; Cebreiro declares a conflict of interest directly related to the present original&#58; &#8220;I have received payment from MSD as consultant to elaborate the present study&#8221;&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Dr&#46; Ruiz Iban declares a conflict of interest directly related to the present original&#58; &#8220;I have received payment from MSD as consultant to elaborate the present study&#8221;&#44; as well as <span class="elsevierStyleItalic">not</span> directly related to the present original&#58; &#8220;I have received payment as a consultant from the following companies&#58; Biomet&#44; Bristol-Myers Squibb&#44; Grunenthal&#44; MSD&#59; I have received payment for teaching activities from the following companies&#58; Astelas&#44; Biomet&#44; Bristol-Myers Squibb&#44; Grunenthal&#44; MSD&#44; Pfizer&#44; Smith and Nephew and Zambon&#59; I have received financing for research projects from the following companies&#58; Biomet&#44; Grunenthal and MSD&#8221;&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Level of evidence</span><p id="par0265" class="elsevierStylePara elsevierViewall">Level of evidence <span class="elsevierStyleSmallCaps">II</span>&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Ethical disclosures</span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Protection of human and animal subjects</span><p id="par0280" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Confidentiality of data</span><p id="par0285" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Right to privacy and informed consent</span><p id="par0290" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span></span>"
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            4 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "Analysis and presentation of data"
            ]
          ]
        ]
        6 => array:3 [
          "identificador" => "sec0040"
          "titulo" => "Results"
          "secciones" => array:6 [
            0 => array:2 [
              "identificador" => "sec0045"
              "titulo" => "Preventive treatment with NSAIDs"
            ]
            1 => array:2 [
              "identificador" => "sec0050"
              "titulo" => "Preventive treatment with opioids"
            ]
            2 => array:2 [
              "identificador" => "sec0055"
              "titulo" => "Preventive treatment with corticoids"
            ]
            3 => array:2 [
              "identificador" => "sec0060"
              "titulo" => "Preventive treatment with anticonvulsants"
            ]
            4 => array:2 [
              "identificador" => "sec0065"
              "titulo" => "Preventive treatment with other drugs"
            ]
            5 => array:2 [
              "identificador" => "sec0070"
              "titulo" => "Preventive treatment with various interventions"
            ]
          ]
        ]
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          "identificador" => "sec0075"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0080"
          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Conflict of interest"
        ]
        10 => array:2 [
          "identificador" => "sec0090"
          "titulo" => "Level of evidence"
        ]
        11 => array:3 [
          "identificador" => "sec0095"
          "titulo" => "Ethical disclosures"
          "secciones" => array:3 [
            0 => array:2 [
              "identificador" => "sec0100"
              "titulo" => "Protection of human and animal subjects"
            ]
            1 => array:2 [
              "identificador" => "sec0105"
              "titulo" => "Confidentiality of data"
            ]
            2 => array:2 [
              "identificador" => "sec0110"
              "titulo" => "Right to privacy and informed consent"
            ]
          ]
        ]
        12 => array:2 [
          "identificador" => "xack130893"
          "titulo" => "Acknowledgements"
        ]
        13 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2014-03-20"
    "fechaAceptado" => "2014-09-16"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec459517"
          "palabras" => array:4 [
            0 => "Knee arthroplasty"
            1 => "Hip arthroplasty"
            2 => "Preventive analgesia"
            3 => "Systematic review"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec459516"
          "palabras" => array:4 [
            0 => "Artroplastia de rodilla"
            1 => "Artroplastia de cadera"
            2 => "Analgesia preventiva"
            3 => "Revisi&#243;n sistem&#225;tica"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To analyze the efficacy and safety of preventive analgesia in patients undergoing hip or knee arthroplasty due to osteoarthritis&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A systematic literature review was performed&#44; using a defined a sensitive strategy on Medline&#44; Embase and Cochrane Library up to May 2013&#46; The inclusion criteria were&#58; patients undergoing knee and&#47;or hip arthroplasty&#44; adults with moderate or severe pain &#40;&#8805;4 on a Visual Analog Scale&#41;&#46; The intervention&#44; the use &#40;efficacy and safety&#41; of pharmacological treatment &#40;preventive&#41; close to surgery was recorded&#46; Oral&#44; topical and skin patch drugs were included&#46; Systematic reviews&#44; meta-analysis&#44; controlled trials and observational studies were selected&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 36 articles&#44; of moderate quality&#44; were selected&#46; The patients included were representative of those undergoing knee and&#47;or hip arthroplasty in Spain&#46; They had a mean age &#62;50 years&#44; higher number of women&#44; and reporting moderate to severe pain &#40;&#8805;4 on a Visual Analog Scale&#41;&#46; Post-surgical pain was mainly evaluated with a Visual Analog Scale&#46; A wide variation was found as regards the drugs used in the preventive protocols&#44; including acetaminophen&#44; classic NSAID&#44; Cox-2&#44; opioids&#44; corticosteroids&#44; antidepressants&#44; analgesics for neuropathic pain&#44; as well as others&#44; such as magnesium&#44; ketamine&#44; nimodipine or clonidine&#46; In general&#44; all of them decreased post-surgical pain without severe adverse events&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The use or one or more pre-surgical analgesics decreases the use of post-surgical drugs&#44; at least for short term pain&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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        ]
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Analizar la eficacia y la seguridad de la analgesia preventiva en pacientes que son sometidos a artroplastia de cadera o rodilla por artrosis&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; una revisi&#243;n sistem&#225;tica&#58; se defini&#243; una estrategia de b&#250;squeda bibliogr&#225;fica sensible en Medline&#44; Embase y Cochrane Library hasta mayo de 2013&#59; se defini&#243; la poblaci&#243;n con los siguientes criterios&#58; pacientes con indicaci&#243;n de artroplastia de cadera y&#47;o rodilla&#44; adultos&#44; dolor moderado a intenso &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>4 en la Escala Visual Anal&#243;gica&#41;&#44; la intervenci&#243;n&#44; el uso &#40;eficacia y seguridad&#41; del tratamiento farmacol&#243;gico &#40;preventivo&#41; pr&#243;ximo a la cirug&#237;a&#46; Se incluyeron formulaciones orales&#44; t&#243;picas y parches&#46; Se incluyeron revisiones sistem&#225;ticas&#44; metaan&#225;lisis&#44; ensayos cl&#237;nicos y estudios observacionales&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 36 art&#237;culos de calidad moderada&#46; Inclu&#237;an pacientes representativos de aquellos a los que se les indica una artroplastia de cadera o rodilla en nuestro pa&#237;s&#44; adultos&#44; con una edad media superior a 50 a&#241;os&#44; ligera mayor proporci&#243;n de mujeres y que presentan dolor de moderado a grave &#40;&#8805;<span class="elsevierStyleHsp" style=""></span>4 en la Escala Visual Anal&#243;gica&#41;&#46; El dolor posquir&#250;rgico se evalu&#243; sobre todo con la Escala Visual Anal&#243;gica&#46; Existe mucha variabilidad en cuanto a los f&#225;rmacos utilizados incluyendo paracetamol&#44; AINE cl&#225;sicos&#44; AINE selectivos de la Cox-2&#44; opioides&#44; corticoides&#44; antidepresivos&#44; analg&#233;sicos para el tratamiento del dolor neurop&#225;tico y otros como sulfato magn&#233;sico&#44; ketamina&#44; nimodipino o clonidina&#46; Todos en general parecen mejorar el dolor posquir&#250;rgico sin presentar acontecimientos adversos graves&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El uso de uno o varios analg&#233;sicos en el preoperatorio disminuye el consumo de analg&#233;sicos y el dolor en el posoperatorio&#44; al menos el dolor agudo&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "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="npar0010">Please cite this article as&#58; D&#237;az-Heredia J&#44; Loza E&#44; Cebreiro I&#44; Ruiz Iban M&#193;&#46; Analgesia preventiva en artroplastia de cadera o rodilla&#58; una revisi&#243;n sistem&#225;tica&#46; Rev Esp Cir Ortop Traumatol&#46; 2015&#59;59&#58;73&#8211;90&#46;</p>"
      ]
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flow diagram of the articles included&#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">&#35;&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">Search terms&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">Citations&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" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#35;6 Filters&#58; Humans&#59; English&#59; Spanish&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#35;4 AND &#35;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#40;&#171;Review&#187;&#91;Publication Type&#93; OR Review&#44; Systematic OR Review&#44; Multicase OR Review Literature OR Review&#44; Academic OR Review of Reported Cases OR Review&#41;&#41; OR &#40;&#40;&#40;&#171;Clinical Trial&#187;&#91;Publication Type&#93;&#41; OR &#171;Validation Studies&#187;&#91;Publication Type&#93;&#41; OR &#171;Evaluation Studies&#187;&#91;Publication Type&#93;&#41;&#41; OR &#40;&#171;Clinical Trial&#44; Phase I&#187;&#91;Publication Type&#93; OR Clinical Trial&#44; Phase 1&#41;&#41; OR &#40;&#171;Clinical Trial&#44; Phase II&#187;&#91;Publication Type&#93; OR Clinical Trial&#44; Phase 2 OR Clinical Trial&#44; Phase <span class="elsevierStyleSmallCaps">II</span>&#41;&#41; OR &#40;&#171;Clinical Trial&#44; Phase III&#187;&#91;Publication Type&#93; OR Clinical Trial&#44; Phase 3 OR Clinical Trial&#44; Phase <span class="elsevierStyleSmallCaps">III</span>&#41;&#41; OR &#40;&#171;Clinical Trial&#44; Phase IV&#187;&#91;Publication Type&#93; OR Clinical Trial&#44; Phase 4 OR Clinical Trial&#44; Phase <span class="elsevierStyleSmallCaps">IV</span>&#41;&#41; OR &#40;&#171;Controlled Clinical Trial&#187;&#91;Publication Type&#93;&#41;&#41; OR &#40;&#171;Multicenter Study&#187;&#91;Publication Type&#93; OR Multicenter Studies OR Multicenter Study&#41;&#41; OR &#40;&#171;Randomized Controlled Trial&#187;&#91;Publication Type&#93; OR Randomized Controlled Trial&#41;&#41; OR &#40;&#171;Cohort Studies&#187;&#91;Mesh&#93; OR Cohort Study OR Studies&#44; Cohort OR Study&#44; Cohort OR Concurrent Studies OR Studies&#44; Concurrent OR Concurrent Study OR Study&#44; Concurrent OR Historical Cohort Studies OR Studies&#44; Historical Cohort OR Cohort Studies&#44; Historical OR Cohort Study&#44; Historical OR Historical Cohort Study OR Study&#44; Historical Cohort OR Analysis&#44; Cohort OR Analyses&#44; Cohort OR Cohort Analyses OR Cohort Analysis OR Closed Cohort Studies OR Cohort Studies&#44; Closed OR Closed Cohort Study OR Cohort Study&#44; Closed OR Study&#44; Closed Cohort OR Studies&#44; Closed Cohort OR Incidence Studies OR Incidence Study OR Studies&#44; Incidence OR Study&#44; Incidence OR Cohort Studies&#41;&#41; OR &#40;&#171;Cohort Studies&#187;&#91;Mesh&#93; OR cohort study OR studies&#44; cohort OR study&#44; cohort OR concurrent studies OR studies&#44; concurrent OR concurrent study OR study&#44; concurrent OR historical cohort studies OR studies&#44; historical cohort OR cohort studies&#44; historical OR cohort study&#44; historical OR historical cohort study OR study&#44; historical cohort OR analysis&#44; cohort OR analysis&#44; cohort OR cohort analyses OR cohort analysis OR closed cohort studies OR cohort studies&#44; closed OR closed cohort study OR cohort study&#44; closed OR study&#44; closed cohort OR studies&#44; closed cohort OR incidence studies OR incidence study OR studies&#44; incidence OR study&#44; incidence OR cohort studies&#41;&#41; OR &#40;&#171;Longitudinal Studies&#187;&#91;Mesh&#93; OR Longitudinal Study OR Studies&#44; Longitudinal OR Study&#44; Longitudinal OR Longitudinal Survey OR Longitudinal Surveys OR Survey&#44; Longitudinal OR Surveys&#44; Longitudinal OR Longitudinal Studies&#41;&#41; OR &#40;&#171;Follow-Up Studies&#187;&#91;Mesh&#93; OR Follow Up Studies OR Follow-Up Study OR Studies&#44; Follow-Up OR Study&#44; Follow-Up OR Followup Studies OR Followup Study OR Studies&#44; Followup OR Study&#44; Followup OR Follow-Up Studies&#41;&#41; OR &#40;&#171;Prospective Studies&#187;&#91;Mesh&#93; OR Prospective Study OR Studies&#44; Prospective OR Study&#44; Prospective OR Prospective Studies&#41;&#41; OR &#40;&#171;meta-analysis&#187;&#91;Publication Type&#93; OR &#171;meta-analysis as topic&#187;&#91;MeSH Terms&#93; OR &#171;meta-analysis&#187;&#91;All Fields&#93;&#41;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#44;426&#44;305&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#35;1 AND &#35;2 AND &#35;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4729&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Risk factors&#91;MH&#93; OR causalities OR multifactorial causality OR causalities&#44; multifactorial OR causality&#44; multifactorial OR multifactorial causalities OR multiple causation OR causation&#44; multiple OR causations&#44; multiple OR multiple causations OR reinforcing factors OR factors&#44; reinforcing OR factors&#44; reinforcing OR reinforcing factor OR causation OR causations OR enabling factors OR enabling factor OR factors&#44; enabling OR factors&#44; enabling OR predisposing factors OR factors&#44; predisposing OR factors&#44; predisposing OR predisposing factor OR determinant OR predictor OR predict&#42; OR prognostic&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Osteoarthritides OR Osteoarthrosis OR Osteoarthroses OR Arthritis&#44; Degenerative OR Arthritides&#44; Degenerative OR Coxarthrosis OR Arthroplasties&#44; Replacement&#44; Hip OR Arthroplasties&#44; Replacement&#44; Hip OR Hip Prosthesis Implantation OR Hip Replacement&#44; Total OR Hip Replacements&#44; Total OR Arthroplasties&#44; Replacement&#44; Knee OR Knee Replacement&#44; Total OR Knee Replacements&#44; Total&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">h&#58; hours&#59; iv&#58; intravenous&#59; kg&#58; kilogram&#59; mg&#58; milligram&#59; min&#58; minute&#59; ml&#58; milliliter&#59; RCT&#58; randomized clinical trial&#59; THA&#58; total hip arthroplasty&#59; TKA&#58; total knee arthroplasty&#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">&#35;&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">Study&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">Population&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">Intervention&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">Measurement of outcome&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">Comments&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" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Adam 2005&#44;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">42</span></a> RCT&#44; 3 month follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40 TKA&#8226; Mean age 68 years&#8226; 70&#37; females&#8226; Criteria ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Ketamine- &#62;0&#46;05<span class="elsevierStyleHsp" style=""></span>ml&#47;kg&#44; iv in bolus following anesthetic induction- 3<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span> iv &#40;continuous infusion&#41; intraoperator- 1&#46;5<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span><span class="elsevierStyleHsp" style=""></span>min<span class="elsevierStyleSup">&#8722;1</span> iv &#40;continuous infusion&#41; during 48<span class="elsevierStyleHsp" style=""></span>h after surgery&#8226; Saline solution &#40;same volume&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Knee flexion&#8226; Days of hospital admission&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Alexander 2002&#44;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">12</span></a> RCT double blind placebo control&#44; 24<span class="elsevierStyleHsp" style=""></span>h follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>99 TKA or THA&#8226; Mean age 64 years&#8226; 63&#37; females&#8226; Moderate basal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Diclofenac 75<span class="elsevierStyleHsp" style=""></span>mg iv and ketorolac 60<span class="elsevierStyleHsp" style=""></span>mg iv &#40;before anesthetic induction&#41; in a single dose&#8226; Placebo iv&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Beaupre 2012&#44;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">18</span></a> observational prospective&#44; 12 weeks follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39 TKA&#8226; Mean age 65 years&#8226; 50&#37; females&#8226; Moderate basal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Oxycodone 10<span class="elsevierStyleHsp" style=""></span>mg oral and celecoxib 100&#8211;200<span class="elsevierStyleHsp" style=""></span>mg oral &#40;2&#8211;12<span class="elsevierStyleHsp" style=""></span>h before surgery&#41;&#8226; Anesthetic block &#40;femoral nerve&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain up to 12 weeks&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 2b&#8226; Very small sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bergeron 2009&#44;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">36</span></a> RCT double blind&#44; 6 weeks follow-up&#44; evaluation 1 year later&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50 TKA&#8226; do not provide more information&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Dexamethasone 40<span class="elsevierStyleHsp" style=""></span>mg iv in anesthetic induction&#8226; Saline solution&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain at 6 weeks and 1 year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1cmultiple biases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bugter 2003<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">11</span></a>&#44; RCT double blind placebo control&#44; 16 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; n&#61;36 THA&#8226; Mean age 61 years&#8226; 70&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Ibuprofen 600<span class="elsevierStyleHsp" style=""></span>mg&#47;8<span class="elsevierStyleHsp" style=""></span>h oral 2 weeks before surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain at 24<span class="elsevierStyleHsp" style=""></span>h&#8226; Postoperative opioid intake at 24<span class="elsevierStyleHsp" style=""></span>h&#8226; Perioperative bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1c&#8226; multiple biases&#8226; Very small sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Buvanendran 2003&#44;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">22</span></a> RCT double blind placebo control&#44; 8 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70 TKA&#8226; Mean age 61 years&#8226; 67&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Rofecoxib 50<span class="elsevierStyleHsp" style=""></span>mg oral preoperative 24<span class="elsevierStyleHsp" style=""></span>h before and 2 weeks after surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative intake of opioids and other related drugs during hospital admission&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Buvanendran 2010&#44;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">39</span></a> RCT double blind placebo control&#44; 6 months follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>240 TKA&#8226; Mean age 21 years&#8226; 68&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Pregabalin 300<span class="elsevierStyleHsp" style=""></span>mg oral 24<span class="elsevierStyleHsp" style=""></span>h before and 2 weeks after surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain until 6 months&#8226; Postoperative opioid intake&#8226; Days of hospital admission&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Casey 2006&#44;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">44</span></a> RCT double blind placebo control&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40 TKA&#8226; Mean age 71 years&#8226; 58&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Nimodipine 90<span class="elsevierStyleHsp" style=""></span>mg oral 1<span class="elsevierStyleHsp" style=""></span>h prior to surgery and for 48<span class="elsevierStyleHsp" style=""></span>h more&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative opioid intake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clarke 2009&#95;1&#44;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">40</span></a> RCT placebo control&#44; 6 months follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>126 TKA&#8226; Mean age 62 years&#8226; 35&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Gabapentin 100&#8211;600<span class="elsevierStyleHsp" style=""></span>mg 2<span class="elsevierStyleHsp" style=""></span>h before and 2<span class="elsevierStyleHsp" style=""></span>h after surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain until 6 months&#8226; Postoperative opioid intake until 6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clarke 2009&#95;2&#44;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">41</span></a> RCT placebo control&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40 TKA&#8226; Mean age 61 years&#8226; 61&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Gabapentin 100&#8211;600<span class="elsevierStyleHsp" style=""></span>mg 2<span class="elsevierStyleHsp" style=""></span>h before and 2<span class="elsevierStyleHsp" style=""></span>h after surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain at 2 days&#8226; Postoperative opioid intake at 2 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Duellman 2009&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">19</span></a> observational retrospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>127 TKA or THA&#8226; Mean age 62 years&#8226; 48&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Oxycodone and celecoxib or valdecoxib &#40;from surgery&#44; different doses and patterns&#41; and during postoperative period&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative opioid intake&#8226; Days of hospital admission&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Eggers 1999&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">20</span></a> RCT placebo control&#44; 9 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>101 TKA&#8226; Mean age 67 years&#8226; &#60;50&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Tenoxicam 40<span class="elsevierStyleHsp" style=""></span>mg oral 1<span class="elsevierStyleHsp" style=""></span>h before surgery &#43;20<span class="elsevierStyleHsp" style=""></span>mg iv at 24<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>mg oral 8 days&#8226; Tenoxicam 40<span class="elsevierStyleHsp" style=""></span>mg iv 1<span class="elsevierStyleHsp" style=""></span>h after surgery &#43; 20<span class="elsevierStyleHsp" style=""></span>mg iv at 24<span class="elsevierStyleHsp" style=""></span>h &#43; 20<span class="elsevierStyleHsp" style=""></span>mg oral 8 days&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain at 48<span class="elsevierStyleHsp" style=""></span>h and 3&#8211;9 days&#8226; Postoperative opioid intake at 48<span class="elsevierStyleHsp" style=""></span>h and at 3&#8211;9 days&#8226; Postoperative consumption of analgesics at 48<span class="elsevierStyleHsp" style=""></span>h&#44; 3&#8211;9 days&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Feng 2008&#44;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">23</span></a> RCT placebo control&#44; 3 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34 TKA&#8226; Mean age 66 years&#8226; 69&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Rofecoxib 25<span class="elsevierStyleHsp" style=""></span>mg 1<span class="elsevierStyleHsp" style=""></span>h before surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain at 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h&#8226; Postoperative opioid intake at 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 2b&#8226; Very small sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fletcher 1995&#44;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">13</span></a> RCT double blind placebo control&#44; 5 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>60 THA&#8226; Mean age 64 years&#8226; 60&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Ketorolac 60<span class="elsevierStyleHsp" style=""></span>mg some hours before surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Perioperative bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hendolin 1996&#44;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">27</span></a> RCT&#44; follow-up 24<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>41 TKA&#8226; Mean age 70 years&#8226; 90&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Morphine 0&#46;14<span class="elsevierStyleHsp" style=""></span>mg&#47;kg intramuscular 1<span class="elsevierStyleHsp" style=""></span>h before surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Pain postoperative&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ho 2010&#44;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">45</span></a> observational prospective&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50 TKA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Duloxetine 60<span class="elsevierStyleHsp" style=""></span>mg 2<span class="elsevierStyleHsp" style=""></span>h before surgery and following day&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Huang 2008&#44;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">15</span></a> RCT&#44; 7 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>80 TKA&#8226; Mean age 70 years&#8226; Moderate basal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Celecoxib 400<span class="elsevierStyleHsp" style=""></span>mg 1<span class="elsevierStyleHsp" style=""></span>h prior to surgery<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>200<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h 5 days&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain at 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h&#8226; Postoperative opioid intake at 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 2a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Inan 2007&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">25</span></a> RCT double blind placebo control&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>46 TKA&#8226; Elderly&#8226; &#62;80&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Lornoxicam high dose 15<span class="elsevierStyleHsp" style=""></span>min before surgery and a low postoperative dose&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Iohom 2002&#44;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">14</span></a> RCT placebo control&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30 THA&#8226; Mean age 62 years&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Dexketoprofen 25<span class="elsevierStyleHsp" style=""></span>mg 24<span class="elsevierStyleHsp" style=""></span>h prior to surgery and up to 48<span class="elsevierStyleHsp" style=""></span>h after surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain at 15<span class="elsevierStyleHsp" style=""></span>h&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&#8226; Very small sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Ittichaikulthol 2010&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">16</span></a> RCT placebo control&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>120 THA and TKA&#8226; Age 18&#8211;75 years&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Parecoxib 40<span class="elsevierStyleHsp" style=""></span>mg 1<span class="elsevierStyleHsp" style=""></span>h before surgery&#8226; Celecoxib 400<span class="elsevierStyleHsp" style=""></span>mg preoperative&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hwang 2009&#44;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">43</span></a> observational prospective&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40 ARC&#8226; Mean age &#60;50 years&#8226; 45&#37; females&#8226; Criteria ASA <span class="elsevierStyleSmallCaps">I</span>-<span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Magnesium sulfate- 50<span class="elsevierStyleHsp" style=""></span>mg&#47;kg infusion iv 15<span class="elsevierStyleHsp" style=""></span>min before surgery- 15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg infusion iv during surgery&#8226; Saline solution &#40;same volume&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain a 48<span class="elsevierStyleHsp" style=""></span>h&#8226; Postoperative opioid intake 48<span class="elsevierStyleHsp" style=""></span>h&#8226; Global satisfaction&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Kardash 2008&#44;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">34</span></a> RCT double blind placebo control&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50 THA&#44; unilateral or total&#8226; Mean age 68 years&#8226; 50&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Dexamethasone 40<span class="elsevierStyleHsp" style=""></span>mg iv&#44; 10<span class="elsevierStyleHsp" style=""></span>min before surgery&#8226; Ibuprofen 400<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h oral &#40;during 48<span class="elsevierStyleHsp" style=""></span>h&#41;&#8226; Paracetamol 650<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h oral &#40;during 48<span class="elsevierStyleHsp" style=""></span>h&#41;&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; CRP levels&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lunn 2011&#44;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">38</span></a> RCT double blind placebo control&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>48 TKA&#8226; Mean age 66 years&#8226; 50&#37; females&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Methylprednisolone 125<span class="elsevierStyleHsp" style=""></span>mg &#40;2<span class="elsevierStyleHsp" style=""></span>ml&#41; iv&#44; single dose before surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain at 48<span class="elsevierStyleHsp" style=""></span>h&#8226; Opioid savings at 48<span class="elsevierStyleHsp" style=""></span>h&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Lunn 2013&#44;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">37</span></a> double blind placebo control&#44; 2 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>48 THA&#8226; Mean age 66 years&#8226; 56&#37; females&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Methylprednisolone 125<span class="elsevierStyleHsp" style=""></span>mg &#40;2<span class="elsevierStyleHsp" style=""></span>ml&#41; iv&#44; single dose before surgery&#8226; Placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain at 48<span class="elsevierStyleHsp" style=""></span>h&#8226; Opioid savings at 48<span class="elsevierStyleHsp" style=""></span>h&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mallory 2002&#44;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">24</span></a> observational prospective&#44; 24 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>317 TKA or THA&#8226; Mean age 64 years&#8226; 50&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Rofecoxib or celecoxib 2 weeks before surgery and for 10 days after&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Days of hospital admission&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 2a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Martinez 2007&#44;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">26</span></a> RCT placebo control&#44; 5 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>78 THA&#8226; Mean age 63 years&#8226; 50&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Pre group&#58;- Parecoxib 40<span class="elsevierStyleHsp" style=""></span>mg iv in induction and 12<span class="elsevierStyleHsp" style=""></span>h after induction- Placebo 40<span class="elsevierStyleHsp" style=""></span>mg iv&#46; During surgical wound closure&#8226; Post group&#58;- Parecoxib 40<span class="elsevierStyleHsp" style=""></span>mg iv&#46; During wound closure and 12<span class="elsevierStyleHsp" style=""></span>h after induction- Placebo 40<span class="elsevierStyleHsp" style=""></span>mg iv&#46; During induction&#8226; Control group&#58;- Placebo 40<span class="elsevierStyleHsp" style=""></span>mg iv&#46; During induction&#44; wound closure and 12<span class="elsevierStyleHsp" style=""></span>h after induction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Perioperative bleeding&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Mc Swiney 1997<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">29</span></a>&#44; RCT double blind&#44; 24<span class="elsevierStyleHsp" style=""></span>h follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50 TKA&#8226; No explicit data provided on basal characteristics&#46; Authors indicate that there were no differences between groups&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Experimental group&#58;- Morphine 0&#46;125<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#40;60<span class="elsevierStyleHsp" style=""></span>ml saline solution&#41; iv&#8226; Control group&#58;- Morphine 0&#46;125<span class="elsevierStyleHsp" style=""></span>mg&#47;kg intramuscular in opposite leg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Meurnier 2007&#44;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">17</span></a> RCT placebo control&#44; 1 year follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44 TKA&#8226; Mean age 68 years&#8226; 55&#37; females&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Celecoxib 200<span class="elsevierStyleHsp" style=""></span>mg oral 1<span class="elsevierStyleHsp" style=""></span>h before surgery and during 3 weeks after &#40;2 times per day&#41;&#8226; Placebo 200<span class="elsevierStyleHsp" style=""></span>mg oral 1<span class="elsevierStyleHsp" style=""></span>h before surgery and during 3 weeks after &#40;2 times per day&#41;&#8226; Anesthetic technique&#58; subarachnoid spinal with 17&#46;5 isobaric bupivacaine at 20<span class="elsevierStyleHsp" style=""></span>mg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain until 28 days&#8226; Perioperative bleeding&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Park 1996&#44;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">46</span></a> RCT double blind placebo control&#44; 36<span class="elsevierStyleHsp" style=""></span>h follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Population &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#41; TKA&#8226; Mean age 67 years&#8226; 60&#37; females&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Clonidine 5<span class="elsevierStyleHsp" style=""></span>&#956;g<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleSup">&#8722;1</span> oral 1&#46;5<span class="elsevierStyleHsp" style=""></span>h before surgery&#44; 12<span class="elsevierStyleHsp" style=""></span>h and 24<span class="elsevierStyleHsp" style=""></span>h after initial dose&#8226; Placebo same dose oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Porter 1983&#44;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">33</span></a> RCT double blind&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>26 THA or TKA&#8226; Mean age 63 years&#8226; 50&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Group <span class="elsevierStyleSmallCaps">I</span>&#58; methadone 10<span class="elsevierStyleHsp" style=""></span>mg iv just after induction of anesthesia&#8226; Group P&#58; methadone 10<span class="elsevierStyleHsp" style=""></span>mg&#44; iv&#46; After intervention &#40;3<span class="elsevierStyleHsp" style=""></span>h after induction&#41;&#8226; Group <span class="elsevierStyleSmallCaps">I</span>&#58; neuromuscular block pancuronium 0&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#8226; Group P&#58; bupivacaine 0&#46;5&#37; extradural&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&#8226; Very small sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rasmussen 2010&#44;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">35</span></a> RCT double blind placebo control&#44; 24<span class="elsevierStyleHsp" style=""></span>h follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42 THA&#8226; Mean age 71 years&#8226; 57&#37; females&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">III</span>&#8226; Moderate basal pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Experimental group&#58;- Gabapentin 1200<span class="elsevierStyleHsp" style=""></span>mg 1<span class="elsevierStyleHsp" style=""></span>h before anesthesia- Dexamethasone 8<span class="elsevierStyleHsp" style=""></span>mg iv before anesthetic induction- Ketamine 0&#46;15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg preoperative- Paracetamol 1<span class="elsevierStyleHsp" style=""></span>g q hour before anesthesia- Ketorolac 15<span class="elsevierStyleHsp" style=""></span>mg at the end of surgery&#8226; Control group&#58;- Placebo 1200<span class="elsevierStyleHsp" style=""></span>mg 1<span class="elsevierStyleHsp" style=""></span>h before anesthesia- Placebo 8<span class="elsevierStyleHsp" style=""></span>mg iv before anesthetic induction- Paracetamol 1<span class="elsevierStyleHsp" style=""></span>g 1<span class="elsevierStyleHsp" style=""></span>h before anesthesia- Ketorolac 15<span class="elsevierStyleHsp" style=""></span>mg at the end of surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">32&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reiter 2003&#44;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">32</span></a> RCT double blind placebo control&#44; 24<span class="elsevierStyleHsp" style=""></span>h follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>98 TKA or THA&#8226; Mean age 62 years&#8226; 60&#37; females&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Morphine 20<span class="elsevierStyleHsp" style=""></span>mg oral 1<span class="elsevierStyleHsp" style=""></span>h before surgery&#8226; Placebo 20<span class="elsevierStyleHsp" style=""></span>mg oral 1<span class="elsevierStyleHsp" style=""></span>h before surgery&#8226; Anesthesia with phentanyl 3<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;kg iv&#44; thiopental 3&#8211;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg iv and vecuronium 0&#46;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg iv&#46; Maintained with isoflurane and nitrous oxide at 60&#37; in O<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Pain postoperative&#8226; Postoperative opioid intake&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Renner 2011&#44;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">21</span></a> RCT double blind&#44; 24<span class="elsevierStyleHsp" style=""></span>h follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>11 THA&#8226; Mean age 68 years&#8226; 83&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Etoricoxib 120<span class="elsevierStyleHsp" style=""></span>mg oral 2<span class="elsevierStyleHsp" style=""></span>h before surgery&#59; 120<span class="elsevierStyleHsp" style=""></span>mg oral 1 day after surgery&#8226; Placebo oral 2<span class="elsevierStyleHsp" style=""></span>h before surgery&#44; oral 1 day after surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Inhibition of prostaglandin production&#8226; Suppression of IL-6 increase&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Overall satisfaction&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&#8226; Very small sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Skinner 2004&#44;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">47</span></a> observational prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>102 TKA or THA&#8226; Mean age 63 years&#8226; 65&#37; females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Experimental group&#58;- Preoperative &#40;immediately before surgery&#41;&#58; rofecoxib 50<span class="elsevierStyleHsp" style=""></span>mg oral&#59; tramadol 50<span class="elsevierStyleHsp" style=""></span>mg oral&#59; paracetamol 650<span class="elsevierStyleHsp" style=""></span>mg oral&#59; dexamethasone 2<span class="elsevierStyleHsp" style=""></span>mg oral- Postoperative &#40;hospital&#41;&#58; rofecoxib 50<span class="elsevierStyleHsp" style=""></span>mg&#47;day oral&#59; tramadol 50<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h oral&#59; paracetamol 650<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h oral&#59; hydrocodone 5<span class="elsevierStyleHsp" style=""></span>mg&#47;paracetamol 500<span class="elsevierStyleHsp" style=""></span>mg oral&#44; 1&#8211;2 tablets&#47;4<span class="elsevierStyleHsp" style=""></span>h and iv opioids on demand- Postoperative &#40;following discharge&#41;&#58; rofecoxib 50<span class="elsevierStyleHsp" style=""></span>mg&#47;day oral&#59; tramadol 50<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h oral&#59; hydrocodone 5<span class="elsevierStyleHsp" style=""></span>mg&#47;paracetamol 500<span class="elsevierStyleHsp" style=""></span>mg oral 1&#8211;2 comp&#47;4<span class="elsevierStyleHsp" style=""></span>h- Postoperative &#40;following heparin&#44; 14 days&#41;&#58; rofecoxib 50<span class="elsevierStyleHsp" style=""></span>mg&#47;day oral&#59; tramadol 50<span class="elsevierStyleHsp" style=""></span>mg&#47;6<span class="elsevierStyleHsp" style=""></span>h oral&#59; aspirin 350<span class="elsevierStyleHsp" style=""></span>mg&#47;day- Bupivacaine 0&#46;25&#37; intraarticular 2<span class="elsevierStyleHsp" style=""></span>ml&#47;h during 48<span class="elsevierStyleHsp" style=""></span>h &#40;for TKA patients&#41;&#8226; Control group&#58; conventional therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Quality 2b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Slowey 1985&#44;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">30</span></a> RCT&#44; 24<span class="elsevierStyleHsp" style=""></span>h follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30 THA&#8226; Mean age 65 years&#8226; 60&#37; females&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Intramuscular group&#58; morphine 15<span class="elsevierStyleHsp" style=""></span>mg intramuscular 1<span class="elsevierStyleHsp" style=""></span>h before surgery&#59; placebo oral 1<span class="elsevierStyleHsp" style=""></span>h before surgery &#40;3 tablets&#41;&#8226; Oral group-60&#58; placebo intramuscular 1<span class="elsevierStyleHsp" style=""></span>h before surgery&#59; morphine 30<span class="elsevierStyleHsp" style=""></span>mg LC oral 1<span class="elsevierStyleHsp" style=""></span>h before surgery &#40;2 tablets&#41;&#59; placebo oral 1<span class="elsevierStyleHsp" style=""></span>h before surgery &#40;1 tablet&#41;&#8226; Oral group-90&#58; placebo intramuscular 1<span class="elsevierStyleHsp" style=""></span>h before surgery&#59; morphine 30<span class="elsevierStyleHsp" style=""></span>mg LC oral 1<span class="elsevierStyleHsp" style=""></span>h before surgery &#40;3 tablets&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&#8226; Very small sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Wong 1997&#44;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">31</span></a> observational prospective 3 days follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45 TKA&#8226; Mean age 61 years&#8226; 50&#37; females&#8226; ASA <span class="elsevierStyleSmallCaps">I</span>&#8211;<span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Group G&#58;- 30<span class="elsevierStyleHsp" style=""></span>min before surgery and upon incision&#58; saline solution 15<span class="elsevierStyleHsp" style=""></span>ml iv- 30 and 60<span class="elsevierStyleHsp" style=""></span>min postoperative&#58; saline solution 10<span class="elsevierStyleHsp" style=""></span>ml&#8226; Group EA&#58;- 30<span class="elsevierStyleHsp" style=""></span>min before surgery and upon incision&#58; lidocaine 2&#37; 15<span class="elsevierStyleHsp" style=""></span>ml iv- 30 and 60<span class="elsevierStyleHsp" style=""></span>min postoperative&#58; lidocaine 2&#37; 10<span class="elsevierStyleHsp" style=""></span>ml&#59; morphine 1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#44; ketamine 20<span class="elsevierStyleHsp" style=""></span>mg&#8226; Group EB&#58;-30<span class="elsevierStyleHsp" style=""></span>min before surgery and upon incision&#58; lidocaine 2&#37; 15<span class="elsevierStyleHsp" style=""></span>ml iv&#44; morphine 1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#44; ketamine 20<span class="elsevierStyleHsp" style=""></span>mg-30 and 60<span class="elsevierStyleHsp" style=""></span>min postoperative&#58; lidocaine 2&#37; 10<span class="elsevierStyleHsp" style=""></span>ml&#8226; Anesthetic technique&#58; general anesthesia &#40;group G&#41;&#44; epidural lidocaine &#40;groups EA&#44; EB&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Postoperative pain&#8226; Postoperative opioid intake&#8226; Overall satisfaction&#8226; Adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Quality 1b&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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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">&#35;&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">Study&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">Reasons for exclusion&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" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Barreveld 2013&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Systematic review including studies of hip and knee arthroplasties&#44; as well as other types of surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Becchi 2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Main objective was analgesia with continuous psoas compartment block &#40;no preventive analgesia with drug treatment&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Berger 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No comparison group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Brooks 2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Case report describing an epidural catheter&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bullingham 1984&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Description of a treatment with sublingual buprenorphine initially administered perioperatively&#46; The preemptive effect was not evaluated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Buvanendran 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Study evaluating plasma concentrations of pregabalin in blood and in LCR&#46; Pain was not evaluated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Clarke 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Review of articles on the use of gabapentin and pregabalin in different pathologies not exclusively TKA and THA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">De Oliveira 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Metaanalysis on the preoperative use of ketorolac&#46; Mixing articles from various specialties&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Du Manoir 2003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Use of nefopam in postoperative treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fransen 2004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Inclusion of revision surgeries&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Fu 2010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Inclusion of intraarticular infiltrations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Kilickan 2000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Evolution of epidural analgesia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Moretti 2012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Evaluation of a postoperative treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Hebl 2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Three patients in the intervention group and four patients in the control group presented a diagnosis of rheumatoid arthritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Koinig 1988&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Arthroscopy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Notarnicola 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Only anesthetic block&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Perrin 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Series of cases&#44; pilot study with a very small sample size&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reuben 2002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The author retracted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reuben 2007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The author retracted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Reuben 2008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">The author retracted&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Rosenberg 2006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Summary of several studies&#44; insufficient data to complete data collection form&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Schroer 2011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Preventive treatment was the same for all patients&#44; placebo was administered in the postoperative period&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Southworth 2009&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Inclusion of other types of surgeries&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Straube 2005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Inclusion of other types of surgeries&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Studies excluded after full reading and reasons for exclusion&#46;</p>"
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        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">LE&#58; level of evidence&#59; RG&#58; recommendation grade&#46;</p>"
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                0 => """
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                  \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">Conclusion&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">LE&#59; RG&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" title="table-entry  " align="left" valign="top">- Preventive analgesia with NSAIDs seems to decrease both pain and opioid consumption in the postoperative period- Results were more consistent and longer-lasting with Cox-2 than with traditional NSAIDs- With traditional NSAIDs there were no significant adverse events except for perioperative bleeding&#44; which did not appear with Cox-2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1b&#59; A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">- Preventive analgesia with opioids reduced the consumption of analgesics in the postoperative period&#46; An improvement of analgesia was also observed in the immediate postoperative period&#44; albeit not in the long term-Safe strategies&#44; with no significant adverse events&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1b&#59; A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">- Preventive analgesia with corticoids seems to reduce both pain and opioid consumption in the postoperative period at 48<span class="elsevierStyleHsp" style=""></span>h&#44; but not after 6 months or 1 year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2a&#59; B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">- Preventive analgesia with pregabalin seemed to reduce neuropathic pain in the short and long term- There is insufficient evidence to determine the effect on postoperative nociceptive pain and consumption of opioids- Preventive analgesia with gabapentin did not influence postoperative pain&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&#59; B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">- The use of ketamine and magnesium sulfate during analgesic induction seemed to have a beneficial effect on pain control and opioid consumption in the immediate postoperative period&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1b&#59; A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">- There is insufficient evidence to determine the effect of preventive analgesia with nimodipine&#44; duloxetine and clonidine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&#59; B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">- Preventive analgesia with combinations of various analgesics reduced pain and the need for analgesics after surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&#59; B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">- There is insufficient evidence to recommend a specific strategy for preventive analgesia or administration protocol&#46; However&#44; it seems that administration of one or more analgesics at some point during the preoperative process reduces postoperative pain and consumption of analgesics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2b&#59; B&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Main conclusions along with level of evidence and recommendation grade<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></p>"
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    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
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          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:51 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                        ]
                      ]
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                  ]
                  "host" => array:1 [
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                      "Revista" => array:6 [
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            1 => array:3 [
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              "etiqueta" => "2"
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                  "contribucion" => array:1 [
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                      "autores" => array:1 [
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                            0 => "S&#46; Moiniche"
                            1 => "H&#46; Kehlet"
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                      "Revista" => array:6 [
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            2 => array:3 [
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17019235"
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            3 => array:3 [
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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                      "titulo" => "A qualitative systematic review of the role of <span class="elsevierStyleItalic">N</span>-methyl-<span class="elsevierStyleSmallCaps">d</span>-aspartate receptor antagonists in preventive analgesia"
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                          "etal" => false
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                      "titulo" => "Impact of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery&#58; a systematic review of randomized controlled trials"
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                            0 => "G&#46;C&#46; McCarthy"
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                      "Revista" => array:6 [
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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        "texto" => "<p id="par0270" class="elsevierStylePara elsevierViewall">The authors wish to thank Cristina Benitez and Eduardo Junco for their contribution to the development of the systematic review&#46;</p> <p id="par0275" class="elsevierStylePara elsevierViewall">The authors also wish to thank Merck Sharp and Dohme for their funding to conduct the present systematic review&#46;</p>"
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Article information

ISSN: 19888856
Original language: English

DOI:10.1016/j.recote.2015.01.006

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	2	0	2
2024 October	11	3	14
2024 September	13	5	18
2024 August	16	12	28
2024 July	19	5	24
2024 June	23	3	26
2024 May	16	5	21
2024 April	27	4	31
2024 March	51	7	58
2024 February	41	6	47
2024 January	21	6	27
2023 December	34	11	45
2023 November	22	4	26
2023 October	31	7	38
2023 September	24	2	26
2023 August	21	3	24
2023 July	13	4	17
2023 June	36	1	37
2023 May	58	1	59
2023 April	48	1	49
2023 March	61	2	63
2023 February	37	26	63
2023 January	32	16	48
2022 December	22	12	34
2022 November	26	15	41
2022 October	18	13	31
2022 September	27	12	39
2022 August	21	9	30
2022 July	20	11	31
2022 June	15	12	27
2022 May	17	23	40
2022 April	13	10	23
2022 March	10	12	22
2022 February	13	5	18
2022 January	25	6	31
2021 December	34	12	46
2021 November	33	12	45
2021 October	22	11	33
2021 September	36	17	53
2021 August	28	8	36
2021 July	18	9	27
2021 June	15	9	24
2021 May	13	6	19
2021 April	20	13	33
2021 March	11	10	21
2021 February	10	10	20
2021 January	13	12	25
2018 June	0	2	2
2018 May	0	5	5
2018 April	0	9	9
2018 March	0	1	1
2018 February	8	1	9
2018 January	5	0	5
2017 December	14	1	15
2017 November	8	1	9
2017 October	12	8	20
2017 September	14	3	17
2017 August	10	2	12
2017 July	11	8	19
2017 June	18	4	22
2017 May	9	0	9
2017 April	8	2	10
2017 March	10	9	19
2016 December	0	1	1
2016 November	0	1	1
2016 October	0	1	1
2016 September	0	2	2
2016 July	0	1	1
2016 June	0	2	2
2016 May	0	5	5
2016 April	0	4	4
2016 March	0	8	8
2016 February	0	9	9
2016 January	0	8	8
2015 December	0	8	8
2015 November	0	7	7
2015 October	0	10	10
2015 September	0	4	4
2015 August	1	0	1
2015 July	0	4	4
2015 June	0	1	1
2015 May	0	2	2
2015 April	1	1	2
2015 March	1	5	6

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