Perioperative medicine role in painful knee prosthesis prevention | Revista Española de Anestesiología y Reanimación (English Edition)

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Martínez-Pastor, C. Dürsteler, C. Hernández, X. Sala-Blanch" "autores" => array:5 [ 0 => array:4 [ "nombre" => "T." "apellidos" => "Cuñat" "email" => array:1 [ 0 => "cunat@clinic.cat" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J.C." "apellidos" => "Martínez-Pastor" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Dürsteler" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "C." "apellidos" => "Hernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "X." "apellidos" => "Sala-Blanch" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Anestesiología, Reanimación y Tratamiento del dolor, Hospital Clínic de Barcelona, Barcelona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Traumatología y Cirugía Ortopédica, Hospital Clinic de Barcelona, Barcelona, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anestesiología y Reanimación, Hospital Sant Joan de Déu de Barcelona, Esplugues de Llobregat, Barcelona, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Papel de la medicina perioperatoria en la prevención de la prótesis de rodilla dolorosa" ] ] "textoCompleto" => "IntroductionTotal knee arthroplasty (TKA) is one of the most frequent inpatient orthopaedic surgeries in Spain (approximately 47,000 in 2017)<a class="elsevierStyleCrossRef" href="#bib0005">1</a>. It is a cost-effective procedure that greatly improves the quality of life of patients suffering from advanced knee osteoarthritis. In 20% of cases, however, chronic pain persists after surgery, even without direct involvement of the prosthesis (infection, loosening of parts, alignment problems)<a class="elsevierStyleCrossRef" href="#bib0010">2</a>.Ideally, therefore, patients who would not benefit from knee replacement should be identified before undergoing surgery, either to avoid the cost of the procedure, or to optimize their status and correct their predisposing factors. This will ultimately reduce the incidence of chronic postoperative pain.The indication for TKA is usually based on certain variables, such as quality of life, expected outcome, comorbidities, psychological resources and pain coping strategies, functional demands, technical factors, and risk of infection; however, the risk factors for postoperative pain have yet to be fully established<a class="elsevierStyleCrossRef" href="#bib0015">3</a>.The aim of this review is to provide an overview of the current state of the knowledge on the causes of painful knee prosthesis, specifically factors that can be identified and improved perioperatively.We conducted a non-systematic review of studies published in Pubmed and ScienceDirect, searching for clinical and epidemiological articles, systematic reviews, descriptive reviews, consensus documents, expert meetings, and meta-analyses published in English up to 15 May 2020 The following search terms were used: «total knee arthroplasty», «chronic postsurgical knee pain», «risk factors». The search was not limited by date, due to the paucity of interdisciplinary studies analysing perioperative anaesthesia in these patients.Definitions and developmentAcute postoperative pain is inextricably associated with tissue damage and postoperative inflammation. Pain should completely disappear after this preliminary repair stage, but this is not always the case, giving rise to persistent postoperative pain (PPP) or chronic postoperative pain. This has been arbitrarily defined as pain that lasts more than 3 months after the intervention and that affects the patient's quality of life. To reach a diagnosis of PPP, organic causes of persistent pain such as prosthetic dysfunction or infection must first be ruled out. The clinical picture is dominated by pain both at rest and on movement that is localised in the area of the surgery and may radiate into adjacent areas<a class="elsevierStyleCrossRef" href="#bib0020">4</a>.Nerve injury during surgery may give rise to neuropathic pain (NP). The International Association for the Study of Pain (IASP) defines NP as pain caused by injury or disease of the somatosensory nervous system<a class="elsevierStyleCrossRef" href="#bib0025">5</a>. Although nerve injury is a common occurrence, it is not always associated with the development of NP. However, NP can develop 6 months after surgery in up to 12.7% of all patients who undergo TKA, and requires multidisciplinary diagnosis and treatment (non-pharmacological, pharmacological and/or interventional)<a class="elsevierStyleCrossRefs" href="#bib0030">6,7</a>.There is a growing body of evidence on the factors—preoperative, intraoperative and postoperative—associated with the development of PPP. These risk factors can be categorised as genetic, demographic, clinical, surgical, analgesic, inflammatory and psychological (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>)<a class="elsevierStyleCrossRef" href="#bib0040">8</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Postoperative factorsGenetic factorsGenomics is a constantly evolving field in pain medicine, although its role in the development of PPP has yet to be fully explained. Despite improvements in our understanding of the biological signalling pathways responsible for the transition from acute to chronic pain after TKA, the specific genetic fingerprints involved and their relative weight remain unclear<a class="elsevierStyleCrossRef" href="#bib0045">9</a>.Associations have been found between allelic variations of the catechol-0-methyltransferase gene and the presence of PPP, and the KCNJ6 genes, which code for the GIRK protein (G-protein-activated inwardly-rectifying potassium channels) and OPRM1 have been correlated with a higher requirement for opioids in the postoperative period of TKA<a class="elsevierStyleCrossRefs" href="#bib0050">10,11</a>.The presence of central sensitization diseases, such as fibromyalgia, are a clear risk factor for the appearance of PPP, and although these diseases are known to be largely determined by environmental factors, polymorphisms of the 5-HT2A receptor, the serotonin transporter gene, dopamine D4 receptor gene, and catechol-0-methyltransferase have also been associated with their development. Other genes whose polymorphisms have been linked to the appearance of central sensitization are GARB3, TAAR1, GBP1, RGS4, CNR1, GRIA4<a class="elsevierStyleCrossRefs" href="#bib0060">12,13</a>.Genes encoding TRPV4 (Transient receptor potential cation channel, subfamily V, member 4) and IL1RN (Interleukin 1 Receptor Antagonist) have been associated with cartilage loss and poor outcomes in osteoarthritis, and are known to contribute to pain<a class="elsevierStyleCrossRef" href="#bib0070">14</a>. The cytokines interleukin (IL)-1 and IL-6 and the protein tumour necrosis factor α (TNF-α) are associated with joint pain. For example, elevated preoperative synovial levels of TNF-α have been associated with the appearance of subacute or subchronic pain 6 weeks after TKA. IL-8 and other cytokines have also been positively correlated with osteolysis after TKA, which can cause mechanical pain when the implant fixation fails<a class="elsevierStyleCrossRefs" href="#bib0075">15,16</a>.Scientists studying RNA expression have discovered that the biological pathways of genes encoding the proteins involved in angiogenesis, apoptosis, cell adhesion, cytoskeleton, ossification, proteolysis, cell differentiation, extracellular matrix production, chemokines, cytokines and enzymes are more highly expressed in patients with osteoarthritis. Epigenetic factors are also likely to contribute to the development of PPP, and advances in genome, transcriptome, and proteome analysis may allow investigators to develop individual perioperative strategies to prevent this complication<a class="elsevierStyleCrossRef" href="#bib0085">17</a>.Demographic factorsFemale gender has been associated with the risk of developing PPP after primary knee arthroplasty. This finding, however, is debatable, since the risk decreases significantly in both clinical and statistical terms when the intensity of preoperative pain and pain catastrophising are factored in to multivariate analytical models<a class="elsevierStyleCrossRef" href="#bib0090">18</a>.Younger age (less than 65 years) at TKA surgery is also a risk factor for PPP, greater consumption of opioids, and a worse quality of life 6 months after surgery vs. before surgery<a class="elsevierStyleCrossRefs" href="#bib0015">3,19,20</a>.A higher body mass index has not been associated with an increased risk of developing PPP, although it has been associated with the development of knee osteoarthritis<a class="elsevierStyleCrossRef" href="#bib0105">21</a>. Hamdi et al., found that bariatric surgery improved knee function at 3 months, but not knee pain. The authors speculate that this may be due to an increase in high-impact exercise after surgery, resulting in a loss of lean mass and increased pain<a class="elsevierStyleCrossRef" href="#bib0110">22</a>.Socioeconomic factors may also play an important role in increasing the risk of developing PPP. Some studies have shown that people living in communities with high levels of poverty are more likely to report greater pain and functional decline 2 years after TKA<a class="elsevierStyleCrossRef" href="#bib0115">23</a>. The stress associated with pain and functional limitations also affects the individual’s psychological health and their tendency to catastrophise pain<a class="elsevierStyleCrossRef" href="#bib0120">24</a>.Clinical factorsSeveral studies have shown that the presence and severity of pre-TKA medical comorbidities contribute to PPP. One of the tools used to measure the potential impact of comorbidities on PPP is the Charlson Deyo Comorbidity Index. Ischaemic heart disease and congestive heart failure (both included in the Charlson Deyo Index), together with anxiety and depression, are predictors of PPP. However, their exact weight in the risk stratification of post-surgical pain remains unclear<a class="elsevierStyleCrossRefs" href="#bib0125">25,26</a>.Evidence has shown that severe pre-surgical pain is one of the main risk factors for the appearance of persistent pain after prosthetic knee and hip surgery<a class="elsevierStyleCrossRef" href="#bib0015">3</a>. Pain in patients with osteoarthritis of the knee has been assessed using various different scales, specifically: the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale; the Knee injury and Osteoarthritis Outcome Score; the pain domain of the Oxford Knee Score; patient-rated pain using the Visual Analogue Scale (VAS), or the Numeric Rating Scale (NRS); and qualitative parameters defined during clinical interviews. Despite this, the extent to which these preoperative tests can predict PPP and influence clinical decision-making, and their capacity to estimate which patients will actually suffer from PPP, has yet to be defined<a class="elsevierStyleCrossRef" href="#bib0135">27</a>.Chronic pain is known to cause peripheral and central sensitization. Central sensitization features have been identified in almost all disease that involve chronic pain, and it is considered the main underlying cause of pain in diseases such as fibromyalgia. In neurophysiological terms, central sensitization is characterized by a reduction in the threshold of nociceptive afferent receptors in the presence of a painful stimulus, increased discharge in response to the stimulus, and even spontaneous discharge. Clinically, it is related to generalized hyperalgesia and allodynia. Evidence has now shown that this process is caused by neuroinflammation in the peripheral and central nervous system. Neuroinflammation is characterized by increased vascular permeability, leukocyte infiltration, and activation of glial cells, such as astrocytes, in the spinal cord, leading to the release of pro-inflammatory cytokines and chemokines that can act as neuromodulators to induce sensitization in excitatory synapses (facilitation) and inhibitory synapses (dis-inhibition). These mediators can also affect synapses in different spinal segments distant from the initial lesion site<a class="elsevierStyleCrossRef" href="#bib0140">28</a>.In this respect, quantitative sensory testing has shown that pre-surgical mechanical allodynia and thermal hyperalgesia are associated with the development of PPP in patients undergoing TKA<a class="elsevierStyleCrossRefs" href="#bib0145">29,30</a>. This has been confirmed by functional magnetic resonance imaging studies that show grey matter changes in pain processing regions of the brain, indicating neurochemical imbalances and resting state connectivity alterations in pronociceptive and antinociceptive regions of the brain<a class="elsevierStyleCrossRef" href="#bib0155">31</a>.The distribution of pain can also affect the appearance of PPP. Generalised preoperative pain, other types of chronic pain, contralateral knee pain, and concomitant low back pain have been associated with an increased risk of PPP<a class="elsevierStyleCrossRefs" href="#bib0160">32–34</a>.Opioid treatment can induce tolerance (the need to progressively up-titrate the opioid to maintain the same analgesic effect) and hyperalgesia (increased pain in response to a painful stimulus). Preoperative administration of opioids has been associated with a greater demand for opioid analgesics in the immediate postoperative period and at 12 months, and can prolong the time needed to reduce daily consumption to preoperative baseline levels. Hyperalgesia, which has also been defined as a risk factor for PPP<a class="elsevierStyleCrossRefs" href="#bib0095">19,35</a>, could increase the risk of postoperative complications, and has been associated with worse postoperative functional outcomes<a class="elsevierStyleCrossRef" href="#bib0180">36</a>.Severely impaired physical function, diagnosed by the function subscale of the WOMAC index, and severe pain on movement before surgery may predispose the patient to PPP. Although this could suggest that an early surgical intervention could protect against the subsequent development of PPP, no physical function or symptom cut-off points have been defined, and the indication for surgery should be based on a global assessment<a class="elsevierStyleCrossRefs" href="#bib0185">37,38</a>.Psychological factorsThe presence of psychological factors such as anxiety, depression and maladaptive responses, such as catastrophizing, have been identified as independent predictors of PPP<a class="elsevierStyleCrossRef" href="#bib0090">18</a>.One of aims of fast-track surgery programmes, and more recently prehabilitation, is to optimise the patient’s psychological status during the perioperative period, particularly prior to surgery, focussing specifically on their expectations and attitude towards the intervention. This is achieved by educational and informative sessions that empower and motivate patients, helping them understand the surgery and realise that they are part of the process and must work towards their recovery and the resolution of their problem<a class="elsevierStyleCrossRef" href="#bib0195">39</a>. However, there is still no evidence to show the benefit of “bundles” of psychological interventions and their effect on PPP after TKA<a class="elsevierStyleCrossRef" href="#bib0200">40</a>.Kinesiophobia is defined as an excessive, irrational and debilitating fear of movement and physical activity, and is often the result of a feeling of vulnerability arising from a painful injury. A randomised trial recently showed that the use of cognitive-behavioural therapy in patients suffering from kinesiophobia after TKA improved pain and patient-perceived knee function 6 months after surgery and reduced pain catastrophizing<a class="elsevierStyleCrossRef" href="#bib0205">41</a>.Intraoperative factorsSurgical factorsSurgical factors such as aseptic loosening, polyethylene wear, instability, and prosthetic stiffness are treatable causes of PPP, which can also be prevented by implementing procedures to ensure optimal alignment and uniform tension across the range of motion of the prosthesis. Implant alignment can be improved by using computer-assisted navigation<a class="elsevierStyleCrossRef" href="#bib0085">17</a>.Intra-articular PPP may also originate in the patellofemoral joint, and can be due to incorrect positioning, patella maltracking, avascular necrosis of the patella, fracture, or patella clunk<a class="elsevierStyleCrossRef" href="#bib0210">42</a>.Maltracking is one of the most common causes of patellofemoral-related postoperative pain after TKA. Patella clunk, meanwhile, is less common, and is described as a painful, palpable, sometimes even audibly click that occurs when the knee is hyperextended (over 30−45°)<a class="elsevierStyleCrossRef" href="#bib0210">42</a>.Avascular necrosis of the patella is a far rarer source of anterior knee pain after TKA. The vascular supply to the patella arises from the peripatellar anastomotic ring, with contributions from the superior and inferomedial and inferolateral genicular arteries<a class="elsevierStyleCrossRef" href="#bib0210">42</a>.Correct sizing and rotation of the tibial component are important for implant longevity and to avoid postoperative complications such as patellar maltracking, tissue impingement, subsidence, and loosening. An undersized tibial component may lack sufficient cortical support, causing it to subside and loosen. On the other hand, an oversized tibial component or a mismatch between the implant and the proximal surface of the tibia creates overloading of the tibial baseplate. This occurs after TKA surgery in around 13% of patients, and can cause soft tissue impingement and postoperative pain<a class="elsevierStyleCrossRef" href="#bib0215">43</a>.Popliteal pain after TKA is usually referred pain that originates in patellofemoral joint. In some rare cases it is caused by impingement or snapping of the tendon on the residual lateral osteophyte or on components of the prominent lateral condyles of the femur. When suspected, ultrasound-guided infiltration of local anaesthetic can be performed for diagnostic and therapeutic purposes. If conservative treatment fails to relieve pain, surgical release can be performed using an open or arthroscopic technique<a class="elsevierStyleCrossRef" href="#bib0220">44</a>.Nerve injuries after TKA occur in 0.3%–1.3% of patients. Peroneal nerve injury is the most common complication, although sciatic and femoral neuropathy have also been described<a class="elsevierStyleCrossRef" href="#bib0225">45</a>. Risk factors for peroneal nerve injury include: pre-surgical valgus deformities and flexion contracture of the knee, previous neuropathy, the presence of haematoma and tourniquet time lasting over 120 min. The clinical picture ranges from motor paralysis of the peroneal nerve to a complex regional syndrome that usually resolves spontaneously within a few days or, in some cases, weeks<a class="elsevierStyleCrossRef" href="#bib0230">46</a>.Another relatively frequent injury than can occur during TKA performed with a standard midline skin incision is transection of the infrapatellar branch of the saphenous nerve or some of its terminal branches. This usually results in numbness in the area around the nerve distal to the point of nerve dissection. Occasionally, it can cause neuropathic pain, which can occur with knee flexion or when climbing stairs, or even painful neuroma<a class="elsevierStyleCrossRef" href="#bib0235">47</a>.Prior surgery is, in general, a risk factor for postoperative pain, and both arthroscopy and ligament reconstruction have been linked to earlier TKA. However, no studies have so far investigated the association between prior arthroscopy and chronic post-TKA pain. Revision surgery after TKA is associated with a higher risk of chronic postoperative pain, lower quality of life, physical function, and satisfaction compared with primary TKA. Pain, often more severe than the initial pain, will persist in approximately 50% of patients with osteoarthritis who undergo revision surgery for TKA-related pain<a class="elsevierStyleCrossRef" href="#bib0240">48</a>.Anaesthesia factorsThe decision of whether to administer general or neuraxial anaesthesia depends on several factors, including anticoagulant treatment, cardiopulmonary reserve, patient preference, and the protocols in place in each institution. There is no consensus on the superiority of one technique over the other, but recent evidence has shown that neuraxial anaesthesia is associated with lower morbidity and mortality and a shorter hospital stay. However, these benefits can vary, depending on the anaesthetic technique (nerve blocks and airway management) and drugs (halogenated, total intravenous anaesthesia) used. For example, some authors have reported that total intravenous general anaesthesia using target-controlled infusion (TCI) of propofol and remifentanil results in less nausea and vomiting, shorter time to ambulation, and shorter hospital stay<a class="elsevierStyleCrossRef" href="#bib0245">49</a>.There is no evidence to date to show that any particular intraoperative anaesthesia technique, beyond correct analgesic management, prevents the development of post-TKA PPP. Therefore, the choice of technique should be individualised to each patient.Special mention should be made of intraoperative intrathecal administration of morphine. Although we are aware of its potential role in postoperative analgesia, and the use of low-dose morphine to reduce the risk of side effects (pruritus, nausea and vomiting or respiratory depression), there is no evidence of its superiority to other locoregional techniques in TKA<a class="elsevierStyleCrossRefs" href="#bib0250">50–52</a>.This, coupled with the potential risk of adverse effects, is why clinical guidelines on anaesthetic management in TKA do not recommend morphine as a first line strategy, and further research is required to determine its potential impact on fast-track programmes in TKA and its role in the prevention of PPP<a class="elsevierStyleCrossRef" href="#bib0265">53</a>.Postoperative factorsManagement of acute postoperative painAcute pain in the first 72 h of TKA is associated with the development of PPP. Buvanendran et al., using the WOMAC index, found acute postoperative pain to be a predictor of chronic pain 6 months after TKA. According to the authors, their findings show that more suitable analgesic strategies and postoperative interventions to treat anxiety and catastrophizing are needed in order to limit the role of unmodifiable factors associated with PPP, such as genetics<a class="elsevierStyleCrossRef" href="#bib0270">54</a>.Enhanced recovery after surgery (ERAS) programmesThe aim of fast-track surgery and ERAS programmes is to restore physical function and reduce postoperative pain as quickly as possible. This call for a multidisciplinary approach that has so far succeeded in reducing postoperative complications and surgery-related morbidity and mortality. ERAS programmes involve various perioperative actions: preoperative education and preparation (treatment of anaemia, diabetes mellitus, malnutrition and smoking), minimally invasive surgery, multimodal anaesthesia and analgesia, and early rehabilitation<a class="elsevierStyleCrossRef" href="#bib0275">55</a>.In ERAS programmes, managing patient expectations, identifying patients with psychiatric comorbidities, catastrophism, or chronic pain (with or without associated opioid treatment) are the key to improving patient satisfaction and preventing the occurrence of PPP. However, there is currently no evidence of the impact that ERAS programmes might have on the appearance of PPP<a class="elsevierStyleCrossRef" href="#bib0275">55</a>.PhysiotherapyPhysiotherapy in the first 24 postoperative hours has been shown to reduce hospital stay, pain after surgery and opioid consumption, and is therefore a core component of ERAS programmes<a class="elsevierStyleCrossRefs" href="#bib0275">55,56</a>.There is no consensus on the duration, frequency or intensity of physiotherapy after TKA. Some studies have shown that protocols involving specific activities (for example, walking or climbing stairs) improve range of motion, proprioception and muscle function and therefore reduce the risk of PPP after TKA. However, there is a need for more research on this and also on the benefit of home rehabilitation under the guidance of physiotherapist vs hospital-based physiotherapy<a class="elsevierStyleCrossRef" href="#bib0285">57</a>.The physiotherapy and preoperative physical exercise regimens included in prehabilitation programmes can reduce morbidity and mortality in certain surgical populations, and also improve preoperative function. There is limited evidence from studies in patients scheduled for TKA, and those published so far have not shown clinically relevant benefits in function, quality of life, or pain after surgery. This is because patients with more advanced osteoarthritis and several comorbidities would benefit the most from physical exercise, but experience difficulty in performing the exercises. Therefore, more research is required to determine the potential impact of prehabilitation on patients scheduled for TKA and on the subsequent development of PPP<a class="elsevierStyleCrossRef" href="#bib0275">55</a>.Analgesic techniquesMultimodal analgesic protocols are based on the inhibition of pain signals from peripheral nociceptors to the central nervous system using oral and intravenous analgesics, analgesic adjuvants, regional anaesthesia techniques, surgical wound infiltration, and non-pharmacological techniques.Locoregional anaesthesia, which combines local periarticular infiltration (local analgesia infiltration) or distal peripheral nerve blocks with adductor canal blockade (with or without a catheter), is one of the core elements of these protocols. These distal approaches include iPACK (Interspace between the popliteal artery and capsule of the posterior knee block), selective tibial nerve blocks, and geniculate nerve blocks<a class="elsevierStyleCrossRefs" href="#bib0290">58,59</a>. Although there is no solid evidence to show their superiority in terms of analgesia, they have been shown to cause less muscle paralysis and to be as effective as femoral and sciatic nerve blocks in TKA<a class="elsevierStyleCrossRef" href="#bib0300">60</a>.Multimodal perioperative analgesia in TKA can involve the administration of various drugs, such as dexmedetomidine, dexamethasone, paracetamol, non-steroidal anti-inflammatory drugs, ketamine and gabapentinoids to achieve different analgesic targets. However, there is scant evidence to show the usefulness of these drugs in the prevention of PPP<a class="elsevierStyleCrossRef" href="#bib0305">61</a>.Dexmedetomidine is an alpha-2 adrenergic agonist. When used as an anaesthesia adjuvant it prolongs the duration of analgesia while reducing both opioid requirements and the incidence of postoperative delirium. However, although intraoperative dexmedetomidine may be effective in preventing post-surgical chronic pain due to its anti-inflammatory and antinociceptive effect, there is currently no evidence of its benefit in TKA<a class="elsevierStyleCrossRefs" href="#bib0310">62,63</a>.Dexamethasone is a long-acting corticosteroid widely used perioperatively as a component of multimodal analgesia regimens (at intermediate doses) and as an antiemetic (at low doses). In TKA, it has been shown to reduce postoperative pain, opioid consumption, and hospital stay without increasing the incidence of postoperative complications<a class="elsevierStyleCrossRefs" href="#bib0275">55,64</a>. However, despite its potential role in neuroinflammation, it cannot be recommended to treat post-surgical chronic pain on the basis of the evidence currently available<a class="elsevierStyleCrossRef" href="#bib0325">65</a>.Paracetamol and nonsteroidal anti-inflammatory drugs, which when administered in combination have a synergistic effect, are essential in the postoperative multimodal treatment of TKA<a class="elsevierStyleCrossRef" href="#bib0330">66</a>. Selective cyclooxygenase 2 inhibitors have emerged as an alternative, as they are associated with fewer gastrointestinal side effects and have a minimal effect on the coagulation cascade. Studies have also shown that they do not increase osseointegration deficits or bleeding<a class="elsevierStyleCrossRef" href="#bib0335">67</a>. Although they could theoretically reduce secondary hyperalgesia and central sensitization, there is no evidence that their administration in the postoperative period can reduce the risk of postoperative chronic pain<a class="elsevierStyleCrossRef" href="#bib0340">68</a>.Ketamine, at subanaesthetic doses, has a powerful analgesic effect that reduces acute pain and opioid consumption in the postoperative period of TKA. It could also help prevent post-surgical chronic pain, although this needs to be confirmed in studies focussed on obtain clinically relevant outcomes stratified by pre-surgical pain and central sensitization. In the case of chronic post-TKA pain, there is limited evidence showing a decrease in neuropathic pain at 12 months after surgery in patients who received continuous perfusion of ketamine during surgery and in the first 48 postoperative months. However, further studies that stratify its benefit by pain and pre-surgical central sensitization are needed<a class="elsevierStyleCrossRefs" href="#bib0275">55,69</a>.Buvanendran et al. observed that perioperative administration of pregabalin in patients undergoing TKA can reduce the incidence of neuropathic pain at 3 and 6 months after surgery<a class="elsevierStyleCrossRef" href="#bib0030">6</a>. However, caution should be exercised when gabapentinoids are co-administered with opioids, since this has recently been observed to increase the incidence of postoperative respiratory complications after primary knee and hip arthroplasties. This finding, coupled with uncertainties surrounding their beneficial effect on acute postoperative pain, has ruled out gabapentinoids as a first-line analgesic in the fast-track management of TKA<a class="elsevierStyleCrossRefs" href="#bib0265">53,70–72</a>.Similarly, duloxetine could reduce the effects of central sensitization associated with TKA-induced tissue damage, but current evidence shows that, despite its opioid-sparing effect, it provides no analgesic benefit after surgery<a class="elsevierStyleCrossRef" href="#bib0365">73</a>. However, it could reduce pain and improve the quality of recovery after 2 postoperative weeks when administered in patients with criteria for central sensitization measured on the Central Sensitization Inventory scale<a class="elsevierStyleCrossRef" href="#bib0370">74</a>.Transcutaneous electrical nerve stimulation (TENS) has an analgesic effect in the immediate postoperative period of TKA that reduces the need for rescue opioids and could improve long-term pain control<a class="elsevierStyleCrossRefs" href="#bib0375">75,76</a>.Acupuncture and cryotherapy could also be effective in controlling pain in the immediate postoperative period and reduce the need for opioids. Although the use of continuous passive motion (CPM) devices could reduce postoperative opioid consumption, they do not seem to confer benefits in terms of function, pain and quality of life after TKA<a class="elsevierStyleCrossRef" href="#bib0380">76</a>.Inflammatory factorsOsteoarthritis is often associated with inflammatory joint changes, such as synovitis, and inflammation is considered a risk factor for the progression of osteoarthritis. Peripheral injury is known to lead to local inflammation and increased levels of IL-1β, IL-6, IL-8, and TNF-α, which in turn increases peripheral sensitization to pain. Studies have also shown that an increase in preoperative levels of TNF-α, matrix metalloproteinase-13 (MMP-13) and IL-6 in synovial fluid are associated with a higher incidence of chronic pain<a class="elsevierStyleCrossRef" href="#bib0385">77</a>.Periprosthetic joint infections, though rare (0–2%.4%), are associated with severe pain, impaired function, poor quality of life, and even death in severe cases. Some infections respond well to revision surgery, which may involve debridement or prosthetic replacement. This can achieve good functional outcomes, similar to those achieved in prosthetic replacement due to aseptic failure. However, chronic infections that require multiple surgeries are generally associated with a higher risk of chronic postoperative pain, less quality of life, and greater sensitivity to pain<a class="elsevierStyleCrossRef" href="#bib0385">77</a>.Smoking, body mass index greater than 30 kg/m2, diabetes, depression, frailty, and the use of corticosteroids are associated with a high risk of periprosthetic infection. Identifying and correcting these factors at an early stage could reduce the risk of periprosthetic infection, and with it, chronic postoperative pain<a class="elsevierStyleCrossRef" href="#bib0390">78</a>.ConclusionsTKA is the most common indication for hospital admission in Spain. Estimates suggest that by 2030 the number of procedures will quadruple, mainly due to an increase in the number of risk factors for developing knee osteoarthritis. More than 20% of patients undergoing TKA will experience persistent pain that will affect their quality of life.Preoperative screening to identify patients at risk for developing painful prostheses may help clinicians evaluate whether they will really benefit from the procedure, or whether conservative treatment would be more advisable. Another approach would be to prevent and reverse factors associated with PPP. in this regard, the future might lie in the creation of multimodal perioperative programmes (prehabilitation) that allow clinicians to closely monitor this risk group during surgery in order to prevent the appearance of PPP.Conflict of interestsNone." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1769532" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1554940" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1769533" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1554939" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Definitions and development" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Postoperative factors" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Genetic factors" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Demographic factors" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Clinical factors" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Psychological factors" ] ] ] 7 => array:3 [ "identificador" => "sec0040" "titulo" => "Intraoperative factors" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Surgical factors" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Anaesthesia factors" ] ] ] 8 => array:3 [ "identificador" => "sec0055" "titulo" => "Postoperative factors" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Management of acute postoperative pain" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Enhanced recovery after surgery (ERAS) programmes" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Physiotherapy" ] 3 => array:2 [ "identificador" => "sec0075" "titulo" => "Analgesic techniques" ] ] ] 9 => array:2 [ "identificador" => "sec0080" "titulo" => "Inflammatory factors" ] 10 => array:2 [ "identificador" => "sec0085" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0090" "titulo" => "Conflict of interests" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-05-20" "fechaAceptado" => "2021-03-25" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1554940" "palabras" => array:5 [ 0 => "Total knee arthroplasty" 1 => "Persistent postsurgical pain" 2 => "Chronic pain" 3 => "Risk factors" 4 => "Perioperative medicine" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1554939" "palabras" => array:5 [ 0 => "Artroplastia total de rodilla" 1 => "Dolor postquirúrgico persistente" 2 => "Dolor crónico" 3 => "Factores de riesgo" 4 => "Medicina perioperatoria" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Total knee arthroplasty is one of the most frequently performed orthopaedic surgeries. However, up to 20% of patients develop persistent postoperative pain. Persistent postoperative pain may be an extension of acute postoperative pain, but can also occur after more than 3 months without symptoms. Risk factors associated with persistent postoperative pain after arthroplasty have now been characterised within the patient’s perioperative context (preoperative, intraoperative and postoperative), and can be grouped under genetic, demographic, clinical, surgical, analgesic, inflammatory and psychological factors. Identification and prevention of persistent postoperative pain through a multimodal and biopsychosocial approach is essential in the context of perioperative medicine, and has been shown to prevent or ameliorate postoperative pain." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "La artroplastia total de rodilla (ATR) es una de las cirugías realizadas con más frecuencia en ortopedia. No obstante, hasta un 20% de los pacientes mostrarán persistencia del dolor después del procedimiento. El dolor postquirúrgico persistente (DPP) puede ser una continuación del dolor agudo tras la cirugía o aparecer después de un período asintomático durante más de 3 meses.En la actualidad, se han caracterizado los factores de riesgo que se asocian a DPP tras la ATR. Forman parte del contexto perioperatorio del paciente (preoperatorio, intraoperatorio y postoperatorio) y se pueden agrupar en diferentes dimensiones: genéticas, demográficas, clínicas, quirúrgicas, analgésicas, inflamatorias y psicológicas.Su identificación y prevención, mediante un abordaje multimodal y biopsicosocial, es esencial en el contexto de la medicina perioperatoria y ha demostrado que puede prevenir o mejorar el dolor tras la cirugía." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Cuñat T, Martínez-Pastor JC, Dürsteler C, Hernández C, Sala-Blanch X. Papel de la medicina perioperatoria en la prevención de la prótesis de rodilla dolorosa. Rev Esp Anestesiol Reanim. 2022;69:411–420." ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "The following is Supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0100" ] ] ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Identification and stratification of patients at risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Demographic factors: female gender, young age (under 65 years), scant socioeconomic support \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Clinical factors: presence and severity of preoperative comorbidities, anxiety and depression, preoperative chronic pain and impact on physical function, central sensitization, opioid consumption \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Psychological factors: anxiety and depression, catastrophizing and kinesiophobia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="1" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Management of perioperative anaesthetic and surgical factors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hospitalisation based on ERAS programmes \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Appropriate management of acute postoperative pain \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Early physiotherapy and rehabilitation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Use of locoregional anaesthesia techniques that promote early rehabilitation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Perioperative use of multimodal pharmacological analgesic measures (dexamethasone, non-steroidal anti-inflammatory drugs, dexmedetomidine, ketamine, gabapentin and duloxetine) and non-pharmacological measures (TENS) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Perioperative measures to prevent PPP." ] ] 1 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.docx" "ficheroTamanyo" => 31335 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:78 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Ministerio de Sanidad, Consumo y Bienestar Social - Estadísticas / Estudios - Sistema de Información Sanitaria del SNS n.d. 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Perioperative medicine role in painful knee prosthesis prevention

Papel de la medicina perioperatoria en la prevención de la prótesis de rodilla dolorosa

T. Cuñata,

Corresponding author

cunat@clinic.cat

Corresponding author.

, J.C. Martínez-Pastorb, C. Dürstelera, C. Hernándezc, X. Sala-Blancha

a Servicio de Anestesiología, Reanimación y Tratamiento del dolor, Hospital Clínic de Barcelona, Barcelona, Spain

b Servicio de Traumatología y Cirugía Ortopédica, Hospital Clinic de Barcelona, Barcelona, Spain

c Servicio de Anestesiología y Reanimación, Hospital Sant Joan de Déu de Barcelona, Esplugues de Llobregat, Barcelona, Spain

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specifically factors that can be identified and improved perioperatively&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted a non-systematic review of studies published in Pubmed and ScienceDirect&#44; searching for clinical and epidemiological articles&#44; systematic reviews&#44; descriptive reviews&#44; consensus documents&#44; expert meetings&#44; and meta-analyses published in English up to 15 May 2020 The following search terms were used&#58; &#171;total knee arthroplasty&#187;&#44; &#171;chronic postsurgical knee pain&#187;&#44; &#171;risk factors&#187;&#46; The search was not limited by date&#44; due to the paucity of interdisciplinary studies analysing perioperative anaesthesia in these patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Definitions and development</span><p id="par0030" class="elsevierStylePara elsevierViewall">Acute postoperative pain is inextricably associated with tissue damage and postoperative inflammation&#46; Pain should completely disappear after this preliminary repair stage&#44; but this is not always the case&#44; giving rise to persistent postoperative pain &#40;PPP&#41; or chronic postoperative pain&#46; This has been arbitrarily defined as pain that lasts more than 3 months after the intervention and that affects the patient&#39;s quality of life&#46; To reach a diagnosis of PPP&#44; organic causes of persistent pain such as prosthetic dysfunction or infection must first be ruled out&#46; The clinical picture is dominated by pain both at rest and on movement that is localised in the area of the surgery and may radiate into adjacent areas<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Nerve injury during surgery may give rise to neuropathic pain &#40;NP&#41;&#46; The International Association for the Study of Pain &#40;IASP&#41; defines NP as pain caused by injury or disease of the somatosensory nervous system<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&#46; Although nerve injury is a common occurrence&#44; it is not always associated with the development of NP&#46; However&#44; NP can develop 6 months after surgery in up to 12&#46;7&#37; of all patients who undergo TKA&#44; and requires multidisciplinary diagnosis and treatment &#40;non-pharmacological&#44; pharmacological and&#47;or interventional&#41;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;7</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">There is a growing body of evidence on the factors&#8212;preoperative&#44; intraoperative and postoperative&#8212;associated with the development of PPP&#46; These risk factors can be categorised as genetic&#44; demographic&#44; clinical&#44; surgical&#44; analgesic&#44; inflammatory and psychological &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Postoperative factors</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Genetic factors</span><p id="par0045" class="elsevierStylePara elsevierViewall">Genomics is a constantly evolving field in pain medicine&#44; although its role in the development of PPP has yet to be fully explained&#46; Despite improvements in our understanding of the biological signalling pathways responsible for the transition from acute to chronic pain after TKA&#44; the specific genetic fingerprints involved and their relative weight remain unclear<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a>&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Associations have been found between allelic variations of the catechol-0-methyltransferase gene and the presence of PPP&#44; and the KCNJ6 genes&#44; which code for the GIRK protein &#40;G-protein-activated inwardly-rectifying potassium channels&#41; and OPRM1 have been correlated with a higher requirement for opioids in the postoperative period of TKA<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The presence of central sensitization diseases&#44; such as fibromyalgia&#44; are a clear risk factor for the appearance of PPP&#44; and although these diseases are known to be largely determined by environmental factors&#44; polymorphisms of the 5-HT2A receptor&#44; the serotonin transporter gene&#44; dopamine D4 receptor gene&#44; and catechol-0-methyltransferase have also been associated with their development&#46; Other genes whose polymorphisms have been linked to the appearance of central sensitization are GARB3&#44; TAAR1&#44; GBP1&#44; RGS4&#44; CNR1&#44; GRIA4<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Genes encoding TRPV4 &#40;Transient receptor potential cation channel&#44; subfamily V&#44; member 4&#41; and IL1RN &#40;Interleukin 1 Receptor Antagonist&#41; have been associated with cartilage loss and poor outcomes in osteoarthritis&#44; and are known to contribute to pain<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a>&#46; The cytokines interleukin &#40;IL&#41;-1 and IL-6 and the protein tumour necrosis factor &#945; &#40;TNF-&#945;&#41; are associated with joint pain&#46; For example&#44; elevated preoperative synovial levels of TNF-&#945; have been associated with the appearance of subacute or subchronic pain 6 weeks after TKA&#46; IL-8 and other cytokines have also been positively correlated with osteolysis after TKA&#44; which can cause mechanical pain when the implant fixation fails<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Scientists studying RNA expression have discovered that the biological pathways of genes encoding the proteins involved in angiogenesis&#44; apoptosis&#44; cell adhesion&#44; cytoskeleton&#44; ossification&#44; proteolysis&#44; cell differentiation&#44; extracellular matrix production&#44; chemokines&#44; cytokines and enzymes are more highly expressed in patients with osteoarthritis&#46; Epigenetic factors are also likely to contribute to the development of PPP&#44; and advances in genome&#44; transcriptome&#44; and proteome analysis may allow investigators to develop individual perioperative strategies to prevent this complication<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Demographic factors</span><p id="par0070" class="elsevierStylePara elsevierViewall">Female gender has been associated with the risk of developing PPP after primary knee arthroplasty&#46; This finding&#44; however&#44; is debatable&#44; since the risk decreases significantly in both clinical and statistical terms when the intensity of preoperative pain and pain catastrophising are factored in to multivariate analytical models<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Younger age &#40;less than 65 years&#41; at TKA surgery is also a risk factor for PPP&#44; greater consumption of opioids&#44; and a worse quality of life 6 months after surgery vs&#46; before surgery<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;19&#44;20</span></a>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A higher body mass index has not been associated with an increased risk of developing PPP&#44; although it has been associated with the development of knee osteoarthritis<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&#46; Hamdi et al&#46;&#44; found that bariatric surgery improved knee function at 3 months&#44; but not knee pain&#46; The authors speculate that this may be due to an increase in high-impact exercise after surgery&#44; resulting in a loss of lean mass and increased pain<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Socioeconomic factors may also play an important role in increasing the risk of developing PPP&#46; Some studies have shown that people living in communities with high levels of poverty are more likely to report greater pain and functional decline 2 years after TKA<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a>&#46; The stress associated with pain and functional limitations also affects the individual&#8217;s psychological health and their tendency to catastrophise pain<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Clinical factors</span><p id="par0090" class="elsevierStylePara elsevierViewall">Several studies have shown that the presence and severity of pre-TKA medical comorbidities contribute to PPP&#46; One of the tools used to measure the potential impact of comorbidities on PPP is the Charlson Deyo Comorbidity Index&#46; Ischaemic heart disease and congestive heart failure &#40;both included in the Charlson Deyo Index&#41;&#44; together with anxiety and depression&#44; are predictors of PPP&#46; However&#44; their exact weight in the risk stratification of post-surgical pain remains unclear<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;26</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Evidence has shown that severe pre-surgical pain is one of the main risk factors for the appearance of persistent pain after prosthetic knee and hip surgery<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#46; Pain in patients with osteoarthritis of the knee has been assessed using various different scales&#44; specifically&#58; the Western Ontario and McMaster Universities Osteoarthritis Index &#40;WOMAC&#41; pain subscale&#59; the Knee injury and Osteoarthritis Outcome Score&#59; the pain domain of the Oxford Knee Score&#59; patient-rated pain using the Visual Analogue Scale &#40;VAS&#41;&#44; or the Numeric Rating Scale &#40;NRS&#41;&#59; and qualitative parameters defined during clinical interviews&#46; Despite this&#44; the extent to which these preoperative tests can predict PPP and influence clinical decision-making&#44; and their capacity to estimate which patients will actually suffer from PPP&#44; has yet to be defined<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Chronic pain is known to cause peripheral and central sensitization&#46; Central sensitization features have been identified in almost all disease that involve chronic pain&#44; and it is considered the main underlying cause of pain in diseases such as fibromyalgia&#46; In neurophysiological terms&#44; central sensitization is characterized by a reduction in the threshold of nociceptive afferent receptors in the presence of a painful stimulus&#44; increased discharge in response to the stimulus&#44; and even spontaneous discharge&#46; Clinically&#44; it is related to generalized hyperalgesia and allodynia&#46; Evidence has now shown that this process is caused by neuroinflammation in the peripheral and central nervous system&#46; Neuroinflammation is characterized by increased vascular permeability&#44; leukocyte infiltration&#44; and activation of glial cells&#44; such as astrocytes&#44; in the spinal cord&#44; leading to the release of pro-inflammatory cytokines and chemokines that can act as neuromodulators to induce sensitization in excitatory synapses &#40;facilitation&#41; and inhibitory synapses &#40;dis-inhibition&#41;&#46; These mediators can also affect synapses in different spinal segments distant from the initial lesion site<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">In this respect&#44; quantitative sensory testing has shown that pre-surgical mechanical allodynia and thermal hyperalgesia are associated with the development of PPP in patients undergoing TKA<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29&#44;30</span></a>&#46; This has been confirmed by functional magnetic resonance imaging studies that show grey matter changes in pain processing regions of the brain&#44; indicating neurochemical imbalances and resting state connectivity alterations in pronociceptive and antinociceptive regions of the brain<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The distribution of pain can also affect the appearance of PPP&#46; Generalised preoperative pain&#44; other types of chronic pain&#44; contralateral knee pain&#44; and concomitant low back pain have been associated with an increased risk of PPP<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32&#8211;34</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Opioid treatment can induce tolerance &#40;the need to progressively up-titrate the opioid to maintain the same analgesic effect&#41; and hyperalgesia &#40;increased pain in response to a painful stimulus&#41;&#46; Preoperative administration of opioids has been associated with a greater demand for opioid analgesics in the immediate postoperative period and at 12 months&#44; and can prolong the time needed to reduce daily consumption to preoperative baseline levels&#46; Hyperalgesia&#44; which has also been defined as a risk factor for PPP<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19&#44;35</span></a>&#44; could increase the risk of postoperative complications&#44; and has been associated with worse postoperative functional outcomes<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a>&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Severely impaired physical function&#44; diagnosed by the function subscale of the WOMAC index&#44; and severe pain on movement before surgery may predispose the patient to PPP&#46; Although this could suggest that an early surgical intervention could protect against the subsequent development of PPP&#44; no physical function or symptom cut-off points have been defined&#44; and the indication for surgery should be based on a global assessment<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37&#44;38</span></a>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Psychological factors</span><p id="par0125" class="elsevierStylePara elsevierViewall">The presence of psychological factors such as anxiety&#44; depression and maladaptive responses&#44; such as catastrophizing&#44; have been identified as independent predictors of PPP<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">One of aims of fast-track surgery programmes&#44; and more recently prehabilitation&#44; is to optimise the patient&#8217;s psychological status during the perioperative period&#44; particularly prior to surgery&#44; focussing specifically on their expectations and attitude towards the intervention&#46; This is achieved by educational and informative sessions that empower and motivate patients&#44; helping them understand the surgery and realise that they are part of the process and must work towards their recovery and the resolution of their problem<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a>&#46; However&#44; there is still no evidence to show the benefit of &#8220;bundles&#8221; of psychological interventions and their effect on PPP after TKA<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Kinesiophobia is defined as an excessive&#44; irrational and debilitating fear of movement and physical activity&#44; and is often the result of a feeling of vulnerability arising from a painful injury&#46; A randomised trial recently showed that the use of cognitive-behavioural therapy in patients suffering from kinesiophobia after TKA improved pain and patient-perceived knee function 6 months after surgery and reduced pain catastrophizing<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a>&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Intraoperative factors</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Surgical factors</span><p id="par0140" class="elsevierStylePara elsevierViewall">Surgical factors such as aseptic loosening&#44; polyethylene wear&#44; instability&#44; and prosthetic stiffness are treatable causes of PPP&#44; which can also be prevented by implementing procedures to ensure optimal alignment and uniform tension across the range of motion of the prosthesis&#46; Implant alignment can be improved by using computer-assisted navigation<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Intra-articular PPP may also originate in the patellofemoral joint&#44; and can be due to incorrect positioning&#44; patella maltracking&#44; avascular necrosis of the patella&#44; fracture&#44; or patella clunk<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Maltracking is one of the most common causes of patellofemoral-related postoperative pain after TKA&#46; Patella clunk&#44; meanwhile&#44; is less common&#44; and is described as a painful&#44; palpable&#44; sometimes even audibly click that occurs when the knee is hyperextended &#40;over 30&#8722;45&#176;&#41;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Avascular necrosis of the patella is a far rarer source of anterior knee pain after TKA&#46; The vascular supply to the patella arises from the peripatellar anastomotic ring&#44; with contributions from the superior and inferomedial and inferolateral genicular arteries<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a>&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Correct sizing and rotation of the tibial component are important for implant longevity and to avoid postoperative complications such as patellar maltracking&#44; tissue impingement&#44; subsidence&#44; and loosening&#46; An undersized tibial component may lack sufficient cortical support&#44; causing it to subside and loosen&#46; On the other hand&#44; an oversized tibial component or a mismatch between the implant and the proximal surface of the tibia creates overloading of the tibial baseplate&#46; This occurs after TKA surgery in around 13&#37; of patients&#44; and can cause soft tissue impingement and postoperative pain<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Popliteal pain after TKA is usually referred pain that originates in patellofemoral joint&#46; In some rare cases it is caused by impingement or snapping of the tendon on the residual lateral osteophyte or on components of the prominent lateral condyles of the femur&#46; When suspected&#44; ultrasound-guided infiltration of local anaesthetic can be performed for diagnostic and therapeutic purposes&#46; If conservative treatment fails to relieve pain&#44; surgical release can be performed using an open or arthroscopic technique<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Nerve injuries after TKA occur in 0&#46;3&#37;&#8211;1&#46;3&#37; of patients&#46; Peroneal nerve injury is the most common complication&#44; although sciatic and femoral neuropathy have also been described<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a>&#46; Risk factors for peroneal nerve injury include&#58; pre-surgical valgus deformities and flexion contracture of the knee&#44; previous neuropathy&#44; the presence of haematoma and tourniquet time lasting over 120&#8239;min&#46; The clinical picture ranges from motor paralysis of the peroneal nerve to a complex regional syndrome that usually resolves spontaneously within a few days or&#44; in some cases&#44; weeks<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a>&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Another relatively frequent injury than can occur during TKA performed with a standard midline skin incision is transection of the infrapatellar branch of the saphenous nerve or some of its terminal branches&#46; This usually results in numbness in the area around the nerve distal to the point of nerve dissection&#46; Occasionally&#44; it can cause neuropathic pain&#44; which can occur with knee flexion or when climbing stairs&#44; or even painful neuroma<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a>&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Prior surgery is&#44; in general&#44; a risk factor for postoperative pain&#44; and both arthroscopy and ligament reconstruction have been linked to earlier TKA&#46; However&#44; no studies have so far investigated the association between prior arthroscopy and chronic post-TKA pain&#46; Revision surgery after TKA is associated with a higher risk of chronic postoperative pain&#44; lower quality of life&#44; physical function&#44; and satisfaction compared with primary TKA&#46; Pain&#44; often more severe than the initial pain&#44; will persist in approximately 50&#37; of patients with osteoarthritis who undergo revision surgery for TKA-related pain<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a>&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Anaesthesia factors</span><p id="par0185" class="elsevierStylePara elsevierViewall">The decision of whether to administer general or neuraxial anaesthesia depends on several factors&#44; including anticoagulant treatment&#44; cardiopulmonary reserve&#44; patient preference&#44; and the protocols in place in each institution&#46; There is no consensus on the superiority of one technique over the other&#44; but recent evidence has shown that neuraxial anaesthesia is associated with lower morbidity and mortality and a shorter hospital stay&#46; However&#44; these benefits can vary&#44; depending on the anaesthetic technique &#40;nerve blocks and airway management&#41; and drugs &#40;halogenated&#44; total intravenous anaesthesia&#41; used&#46; For example&#44; some authors have reported that total intravenous general anaesthesia using target-controlled infusion &#40;TCI&#41; of propofol and remifentanil results in less nausea and vomiting&#44; shorter time to ambulation&#44; and shorter hospital stay<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a>&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">There is no evidence to date to show that any particular intraoperative anaesthesia technique&#44; beyond correct analgesic management&#44; prevents the development of post-TKA PPP&#46; Therefore&#44; the choice of technique should be individualised to each patient&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">Special mention should be made of intraoperative intrathecal administration of morphine&#46; Although we are aware of its potential role in postoperative analgesia&#44; and the use of low-dose morphine to reduce the risk of side effects &#40;pruritus&#44; nausea and vomiting or respiratory depression&#41;&#44; there is no evidence of its superiority to other locoregional techniques in TKA<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">50&#8211;52</span></a>&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">This&#44; coupled with the potential risk of adverse effects&#44; is why clinical guidelines on anaesthetic management in TKA do not recommend morphine as a first line strategy&#44; and further research is required to determine its potential impact on fast-track programmes in TKA and its role in the prevention of PPP<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">53</span></a>&#46;</p></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Postoperative factors</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Management of acute postoperative pain</span><p id="par0205" class="elsevierStylePara elsevierViewall">Acute pain in the first 72&#8239;h of TKA is associated with the development of PPP&#46; Buvanendran et al&#46;&#44; using the WOMAC index&#44; found acute postoperative pain to be a predictor of chronic pain 6 months after TKA&#46; According to the authors&#44; their findings show that more suitable analgesic strategies and postoperative interventions to treat anxiety and catastrophizing are needed in order to limit the role of unmodifiable factors associated with PPP&#44; such as genetics<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Enhanced recovery after surgery &#40;ERAS&#41; programmes</span><p id="par0210" class="elsevierStylePara elsevierViewall">The aim of fast-track surgery and ERAS programmes is to restore physical function and reduce postoperative pain as quickly as possible&#46; This call for a multidisciplinary approach that has so far succeeded in reducing postoperative complications and surgery-related morbidity and mortality&#46; ERAS programmes involve various perioperative actions&#58; preoperative education and preparation &#40;treatment of anaemia&#44; diabetes mellitus&#44; malnutrition and smoking&#41;&#44; minimally invasive surgery&#44; multimodal anaesthesia and analgesia&#44; and early rehabilitation<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a>&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">In ERAS programmes&#44; managing patient expectations&#44; identifying patients with psychiatric comorbidities&#44; catastrophism&#44; or chronic pain &#40;with or without associated opioid treatment&#41; are the key to improving patient satisfaction and preventing the occurrence of PPP&#46; However&#44; there is currently no evidence of the impact that ERAS programmes might have on the appearance of PPP<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a>&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Physiotherapy</span><p id="par0220" class="elsevierStylePara elsevierViewall">Physiotherapy in the first 24 postoperative hours has been shown to reduce hospital stay&#44; pain after surgery and opioid consumption&#44; and is therefore a core component of ERAS programmes<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;56</span></a>&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">There is no consensus on the duration&#44; frequency or intensity of physiotherapy after TKA&#46; Some studies have shown that protocols involving specific activities &#40;for example&#44; walking or climbing stairs&#41; improve range of motion&#44; proprioception and muscle function and therefore reduce the risk of PPP after TKA&#46; However&#44; there is a need for more research on this and also on the benefit of home rehabilitation under the guidance of physiotherapist vs hospital-based physiotherapy<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a>&#46;</p><p id="par0230" class="elsevierStylePara elsevierViewall">The physiotherapy and preoperative physical exercise regimens included in prehabilitation programmes can reduce morbidity and mortality in certain surgical populations&#44; and also improve preoperative function&#46; There is limited evidence from studies in patients scheduled for TKA&#44; and those published so far have not shown clinically relevant benefits in function&#44; quality of life&#44; or pain after surgery&#46; This is because patients with more advanced osteoarthritis and several comorbidities would benefit the most from physical exercise&#44; but experience difficulty in performing the exercises&#46; Therefore&#44; more research is required to determine the potential impact of prehabilitation on patients scheduled for TKA and on the subsequent development of PPP<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a>&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Analgesic techniques</span><p id="par0235" class="elsevierStylePara elsevierViewall">Multimodal analgesic protocols are based on the inhibition of pain signals from peripheral nociceptors to the central nervous system using oral and intravenous analgesics&#44; analgesic adjuvants&#44; regional anaesthesia techniques&#44; surgical wound infiltration&#44; and non-pharmacological techniques&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Locoregional anaesthesia&#44; which combines local periarticular infiltration &#40;local analgesia infiltration&#41; or distal peripheral nerve blocks with adductor canal blockade &#40;with or without a catheter&#41;&#44; is one of the core elements of these protocols&#46; These distal approaches include iPACK &#40;Interspace between the popliteal artery and capsule of the posterior knee block&#41;&#44; selective tibial nerve blocks&#44; and geniculate nerve blocks<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">58&#44;59</span></a>&#46; Although there is no solid evidence to show their superiority in terms of analgesia&#44; they have been shown to cause less muscle paralysis and to be as effective as femoral and sciatic nerve blocks in TKA<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a>&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Multimodal perioperative analgesia in TKA can involve the administration of various drugs&#44; such as dexmedetomidine&#44; dexamethasone&#44; paracetamol&#44; non-steroidal anti-inflammatory drugs&#44; ketamine and gabapentinoids to achieve different analgesic targets&#46; However&#44; there is scant evidence to show the usefulness of these drugs in the prevention of PPP<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">61</span></a>&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">Dexmedetomidine is an alpha-2 adrenergic agonist&#46; When used as an anaesthesia adjuvant it prolongs the duration of analgesia while reducing both opioid requirements and the incidence of postoperative delirium&#46; However&#44; although intraoperative dexmedetomidine may be effective in preventing post-surgical chronic pain due to its anti-inflammatory and antinociceptive effect&#44; there is currently no evidence of its benefit in TKA<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">62&#44;63</span></a>&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">Dexamethasone is a long-acting corticosteroid widely used perioperatively as a component of multimodal analgesia regimens &#40;at intermediate doses&#41; and as an antiemetic &#40;at low doses&#41;&#46; In TKA&#44; it has been shown to reduce postoperative pain&#44; opioid consumption&#44; and hospital stay without increasing the incidence of postoperative complications<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;64</span></a>&#46; However&#44; despite its potential role in neuroinflammation&#44; it cannot be recommended to treat post-surgical chronic pain on the basis of the evidence currently available<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">65</span></a>&#46;</p><p id="par0260" class="elsevierStylePara elsevierViewall">Paracetamol and nonsteroidal anti-inflammatory drugs&#44; which when administered in combination have a synergistic effect&#44; are essential in the postoperative multimodal treatment of TKA<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a>&#46; Selective cyclooxygenase 2 inhibitors have emerged as an alternative&#44; as they are associated with fewer gastrointestinal side effects and have a minimal effect on the coagulation cascade&#46; Studies have also shown that they do not increase osseointegration deficits or bleeding<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">67</span></a>&#46; Although they could theoretically reduce secondary hyperalgesia and central sensitization&#44; there is no evidence that their administration in the postoperative period can reduce the risk of postoperative chronic pain<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">68</span></a>&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">Ketamine&#44; at subanaesthetic doses&#44; has a powerful analgesic effect that reduces acute pain and opioid consumption in the postoperative period of TKA&#46; It could also help prevent post-surgical chronic pain&#44; although this needs to be confirmed in studies focussed on obtain clinically relevant outcomes stratified by pre-surgical pain and central sensitization&#46; In the case of chronic post-TKA pain&#44; there is limited evidence showing a decrease in neuropathic pain at 12 months after surgery in patients who received continuous perfusion of ketamine during surgery and in the first 48 postoperative months&#46; However&#44; further studies that stratify its benefit by pain and pre-surgical central sensitization are needed<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">55&#44;69</span></a>&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Buvanendran et al&#46; observed that perioperative administration of pregabalin in patients undergoing TKA can reduce the incidence of neuropathic pain at 3 and 6 months after surgery<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a>&#46; However&#44; caution should be exercised when gabapentinoids are co-administered with opioids&#44; since this has recently been observed to increase the incidence of postoperative respiratory complications after primary knee and hip arthroplasties&#46; This finding&#44; coupled with uncertainties surrounding their beneficial effect on acute postoperative pain&#44; has ruled out gabapentinoids as a first-line analgesic in the fast-track management of TKA<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">53&#44;70&#8211;72</span></a>&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Similarly&#44; duloxetine could reduce the effects of central sensitization associated with TKA-induced tissue damage&#44; but current evidence shows that&#44; despite its opioid-sparing effect&#44; it provides no analgesic benefit after surgery<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">73</span></a>&#46; However&#44; it could reduce pain and improve the quality of recovery after 2 postoperative weeks when administered in patients with criteria for central sensitization measured on the Central Sensitization Inventory scale<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a>&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Transcutaneous electrical nerve stimulation &#40;TENS&#41; has an analgesic effect in the immediate postoperative period of TKA that reduces the need for rescue opioids and could improve long-term pain control<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">75&#44;76</span></a>&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Acupuncture and cryotherapy could also be effective in controlling pain in the immediate postoperative period and reduce the need for opioids&#46; Although the use of continuous passive motion &#40;CPM&#41; devices could reduce postoperative opioid consumption&#44; they do not seem to confer benefits in terms of function&#44; pain and quality of life after TKA<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">76</span></a>&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Inflammatory factors</span><p id="par0290" class="elsevierStylePara elsevierViewall">Osteoarthritis is often associated with inflammatory joint changes&#44; such as synovitis&#44; and inflammation is considered a risk factor for the progression of osteoarthritis&#46; Peripheral injury is known to lead to local inflammation and increased levels of IL-1&#946;&#44; IL-6&#44; IL-8&#44; and TNF-&#945;&#44; which in turn increases peripheral sensitization to pain&#46; Studies have also shown that an increase in preoperative levels of TNF-&#945;&#44; matrix metalloproteinase-13 &#40;MMP-13&#41; and IL-6 in synovial fluid are associated with a higher incidence of chronic pain<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a>&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Periprosthetic joint infections&#44; though rare &#40;0&#8211;2&#37;&#46;4&#37;&#41;&#44; are associated with severe pain&#44; impaired function&#44; poor quality of life&#44; and even death in severe cases&#46; Some infections respond well to revision surgery&#44; which may involve debridement or prosthetic replacement&#46; This can achieve good functional outcomes&#44; similar to those achieved in prosthetic replacement due to aseptic failure&#46; However&#44; chronic infections that require multiple surgeries are generally associated with a higher risk of chronic postoperative pain&#44; less quality of life&#44; and greater sensitivity to pain<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">77</span></a>&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">Smoking&#44; body mass index greater than 30&#8239;kg&#47;m<span class="elsevierStyleSup">2</span>&#44; diabetes&#44; depression&#44; frailty&#44; and the use of corticosteroids are associated with a high risk of periprosthetic infection&#46; Identifying and correcting these factors at an early stage could reduce the risk of periprosthetic infection&#44; and with it&#44; chronic postoperative pain<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">78</span></a>&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusions</span><p id="par0305" class="elsevierStylePara elsevierViewall">TKA is the most common indication for hospital admission in Spain&#46; Estimates suggest that by 2030 the number of procedures will quadruple&#44; mainly due to an increase in the number of risk factors for developing knee osteoarthritis&#46; More than 20&#37; of patients undergoing TKA will experience persistent pain that will affect their quality of life&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Preoperative screening to identify patients at risk for developing painful prostheses may help clinicians evaluate whether they will really benefit from the procedure&#44; or whether conservative treatment would be more advisable&#46; Another approach would be to prevent and reverse factors associated with PPP&#46; in this regard&#44; the future might lie in the creation of multimodal perioperative programmes &#40;prehabilitation&#41; that allow clinicians to closely monitor this risk group during surgery in order to prevent the appearance of PPP&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interests</span><p id="par0315" class="elsevierStylePara elsevierViewall">None&#46;</p></span></span>"
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          "titulo" => "Introduction"
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              "titulo" => "Enhanced recovery after surgery &#40;ERAS&#41; programmes"
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            0 => "Total knee arthroplasty"
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            0 => "Artroplastia total de rodilla"
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            2 => "Dolor cr&#243;nico"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Total knee arthroplasty is one of the most frequently performed orthopaedic surgeries&#46; However&#44; up to 20&#37; of patients develop persistent postoperative pain&#46; Persistent postoperative pain may be an extension of acute postoperative pain&#44; but can also occur after more than 3 months without symptoms&#46; Risk factors associated with persistent postoperative pain after arthroplasty have now been characterised within the patient&#8217;s perioperative context &#40;preoperative&#44; intraoperative and postoperative&#41;&#44; and can be grouped under genetic&#44; demographic&#44; clinical&#44; surgical&#44; analgesic&#44; inflammatory and psychological factors&#46; Identification and prevention of persistent postoperative pain through a multimodal and biopsychosocial approach is essential in the context of perioperative medicine&#44; and has been shown to prevent or ameliorate postoperative pain&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">La artroplastia total de rodilla &#40;ATR&#41; es una de las cirug&#237;as realizadas con m&#225;s frecuencia en ortopedia&#46; No obstante&#44; hasta un 20&#37; de los pacientes mostrar&#225;n persistencia del dolor despu&#233;s del procedimiento&#46; El dolor postquir&#250;rgico persistente &#40;DPP&#41; puede ser una continuaci&#243;n del dolor agudo tras la cirug&#237;a o aparecer despu&#233;s de un per&#237;odo asintom&#225;tico durante m&#225;s de 3 meses&#46;</p><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">En la actualidad&#44; se han caracterizado los factores de riesgo que se asocian a DPP tras la ATR&#46; Forman parte del contexto perioperatorio del paciente &#40;preoperatorio&#44; intraoperatorio y postoperatorio&#41; y se pueden agrupar en diferentes dimensiones&#58; gen&#233;ticas&#44; demogr&#225;ficas&#44; cl&#237;nicas&#44; quir&#250;rgicas&#44; analg&#233;sicas&#44; inflamatorias y psicol&#243;gicas&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Su identificaci&#243;n y prevenci&#243;n&#44; mediante un abordaje multimodal y biopsicosocial&#44; es esencial en el contexto de la medicina perioperatoria y ha demostrado que puede prevenir o mejorar el dolor tras la cirug&#237;a&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Cu&#241;at T&#44; Mart&#237;nez-Pastor JC&#44; D&#252;rsteler C&#44; Hern&#225;ndez C&#44; Sala-Blanch X&#46; Papel de la medicina perioperatoria en la prevenci&#243;n de la pr&#243;tesis de rodilla dolorosa&#46; Rev Esp Anestesiol Reanim&#46; 2022&#59;69&#58;411&#8211;420&#46;</p>"
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                  \t\t\t\t"><span class="elsevierStyleItalic">Identification and stratification of patients at risk</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Demographic factors&#58; female gender&#44; young age &#40;under 65 years&#41;&#44; scant socioeconomic support&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Clinical factors&#58; presence and severity of preoperative comorbidities&#44; anxiety and depression&#44; preoperative chronic pain and impact on physical function&#44; central sensitization&#44; opioid consumption&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Psychological factors&#58; anxiety and depression&#44; catastrophizing and kinesiophobia&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hospitalisation based on ERAS programmes&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Appropriate management of acute postoperative pain&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Early physiotherapy and rehabilitation&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Use of locoregional anaesthesia techniques that promote early rehabilitation&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Perioperative use of multimodal pharmacological analgesic measures &#40;dexamethasone&#44; non-steroidal anti-inflammatory drugs&#44; dexmedetomidine&#44; ketamine&#44; gabapentin and duloxetine&#41; and non-pharmacological measures &#40;TENS&#41;&nbsp;\t\t\t\t\t\t\n
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