Strategies for the management of postoperative pain in total knee arthroplasty: integrative review

Márcia Carla Morete-Pinto Arthur Fogel Sousa-Correa About the authors

ABSTRACT

BACKGROUND AND OBJECTIVES:

Total knee arthroplasty is one of the most common surgeries performed on patients with osteoarthritis or rheumatic arthritis of the knee. However, total knee arthroplasty is associated with moderate to severe pain after the operation. In orthopedics, the prevalence of chronic pain after total knee arthroplasty is much higher than after total hip arthroplasty. The aim of this study was to analyze the current knowledge about postoperative pain in knee arthroplasty.

CONTENTS:

An integrative review of clinical trials published in English and Portuguese was carried out in the Scielo, Pubmed and LILACS databases. The inclusion criteria consisted of articles published in the last five years, available in full, that addressed the proposed theme. Editorials, letters to the editor, dissertations, repeated articles that did not correspond to the theme were excluded. The search and selection process of the studies followed the PRISMA recommendations. Of the 155 articles found, 58 articles were selected for the present study following the above-mentioned recommendations.

CONCLUSION:

Several classes of local and systemic drugs, including non-steroidal anti-inflammatory drugs, opioids, and local anesthetics have been used to fight the nociceptive component of postoperative pain. Furthermore, early rehabilitation contributes to better quality of life, self-esteem and reduce the time of hospitalization and hospital expenses.

Keywords:
Arthroplasty; Knee; Pain; Postoperative pain

RESUMO

JUSTIFICATIVA E OBJETIVOS:

A artroplastia total do joelho é uma das cirurgias mais comuns realizadas em pacientes com osteoartrite ou artrite reumatoide do joelho. No entanto, a artroplastia total do joelho está associada a dor moderada a intensa no pós-operatório. Na ortopedia, a prevalência de dor crônica após a artroplastia total do joelho é muito maior do que após a artroplastia total do quadril. O objetivo deste estudo foi analisar as evidências científicas sobre o manejo da dor no pós-operatório de artroplastia de joelho.

CONTEÚDO:

Foi realizada uma revisão integrativa nas bases de dados Scielo, Pubmed e LILACS de ensaios clínicos nos idiomas inglês e português. Os critérios de inclusão consistiram em artigos publicados nos últimos cinco anos, disponíveis na íntegra, que abordassem a temática proposta. Excluíram-se editoriais, cartas ao editor, dissertações, artigos repetidos e que não correspondessem à temática. O processo de busca e seleção dos estudos seguiu as recomendações PRISMA. Dos 155 artigos encontrados, 58 artigos foram selecionados para o presente estudo seguindo as recomendações citadas.

CONCLUSÃO:

Várias classes de fármacos locais e sistêmicos, incluindo anti-inflamatórios não esteroides, opioides e anestésicos locais, têm sido utilizadas para combater o componente nociceptivo da dor pós-operatória. Além disso, a reabilitação precoce contribui para a melhora na qualidade de vida, autoestima e reduz o tempo de internação e os custos hospitalares.

Descritores:
Artroplastia; Dor; Dor pós-operatória; Joelho

INTRODUCTION

Total knee arthroplasty (TKA) has been identified as one of the most effective surgeries for knee arthritis11 Xing LZ, LI L, Zhang LJ. Can intravenous steroid administration reduce postoperative pain scores following total knee arthroplasty? A Meta-analysis. Medicine. 2017;96(24):e7134.,22 Dong CC, Dong SL, He FC. Comparison of the adductor canal block and femoral nerve block for postoperative pain in total knee arthroplasty: a systematic review and meta-analysis. Medicine (Baltimore) 2016;95(12):e2983.. TKA is one of the most common elective surgical procedures done in elderly patients to treat pain and functional limitation due to refractory knee arthritis33 Ethgen O, Bruyère O, Richy F, Dardennes C, Reginster JY. Health-related quality of life in total hip and knee arthroplasty: a qualitative and systematic review of the literature. J Bone Joint Surg Am. 2004;86(5):963-74. and is associated with optimal arthritis pain relief in the majority of these patients. However, many patients experience moderate to severe pain during the immediate postoperative period because the surgery involves extensive bone resection22 Dong CC, Dong SL, He FC. Comparison of the adductor canal block and femoral nerve block for postoperative pain in total knee arthroplasty: a systematic review and meta-analysis. Medicine (Baltimore) 2016;95(12):e2983.,44 Sun XL, Zhao ZH, Ma JX, Li FB, Li YJ, Meng XM, et al. Continuous local infiltration analgesia for pain control after total knee arthroplasty: a meta-analysis of randomized clinical trials. Medicine (Baltimore). 2015;94(45):e2005.,55 Zhai L, Song Z, Liu K. The effect of gabapentin on acute postoperative pain in patients undergoing total knee arthroplasty: a meta-analysis. Medicine (Baltimore). 2016;95(20):e3673.. In the United States, 8 to 15% of patients submitted to TKA have moderate to severe residual joint pain persisting for 2 to 5 years after the procedure66 Singh JA, Gabriel S, Lewallen D. The impact of gender, age and preoperative pain severity on pain after TKA. Clin Orthop Relat Res. 2008;466(11):2717-23.,77 Wylde V, Hewlett S, Learmonth ID, Dieppe P. Persistent pain after joint replacement: prevalence, sensory qualities and postoperative determinants. Pain. 2011;152(3):566-72.. Postoperative pain (POP) is most often underestimated and undertreated22 Dong CC, Dong SL, He FC. Comparison of the adductor canal block and femoral nerve block for postoperative pain in total knee arthroplasty: a systematic review and meta-analysis. Medicine (Baltimore) 2016;95(12):e2983.

3 Ethgen O, Bruyère O, Richy F, Dardennes C, Reginster JY. Health-related quality of life in total hip and knee arthroplasty: a qualitative and systematic review of the literature. J Bone Joint Surg Am. 2004;86(5):963-74.
-44 Sun XL, Zhao ZH, Ma JX, Li FB, Li YJ, Meng XM, et al. Continuous local infiltration analgesia for pain control after total knee arthroplasty: a meta-analysis of randomized clinical trials. Medicine (Baltimore). 2015;94(45):e2005., resulting in distress and low patient satisfaction, also associated with longer hospital stays, resistance to rehabilitation exercises, poorer health-related quality of life, and increased morbidity related to complications88 Rosenberg J, Kehlet H. Does effective postoperative pain treatment influence surgical morbidity? Eur Surg Res. 1999;31(2):133-7.,99 Wu CL, Naqibuddin M, Rowlingson AJ, Lietman SA, Jermyn RM, Fleisher LA. The effect of pain on health-related quality of life in the immediate postoperative period. Anesth Analg. 2003;97(4):1078-85..

At the present time, no gold-standard1010 Li JW, Ma YS, Xiao LK. Postoperative pain management in total knee arthroplasty. Orthop Surg. 2019;11(5):755-61. protocol for the reduction of pain intensity without increasing nausea and vomit was identified. Previous studies have reported that postoperative serum levels of interleukin-6 (IL-6) cytokine and C-reactive protein (CRP) may be high1111 Hall GM, Peerbhoy D, Shenkin A, Parker CJ, Salmon P. Relationship of functional recovery after hip arthroplasty with neuroendocrine and inflammatory responses. Br J Anaesth. 2001;87(4):537-42.,1212 Smith C, Erasmus PJ, Myburgh KH. Endocrine and immune effects of dexamethasone in unilateral total knee replacement. J Int Med Res. 2006;34(6):603-11.. Steroids may be associated with reduced levels of IL-6 and CRP and thus relieve pain associated with various procedures11 Xing LZ, LI L, Zhang LJ. Can intravenous steroid administration reduce postoperative pain scores following total knee arthroplasty? A Meta-analysis. Medicine. 2017;96(24):e7134..

Several studies have compared the efficacy of adjuvant steroids as a component of multimodal anesthesia after TKA. However, previous results must be interpreted with caution due to the lack of robustness and homogeneity among these studies11 Xing LZ, LI L, Zhang LJ. Can intravenous steroid administration reduce postoperative pain scores following total knee arthroplasty? A Meta-analysis. Medicine. 2017;96(24):e7134.. Long-term unfavorable pain outcomes have been observed in 10 to 34% of patients after TKA1313 Shyu YI, Chen ML, Chen MC, Wu CC, Su JY. Postoperative pain and its impact on the quality of life of elderly people with hip fractures more than 12 months after hospital discharge. J Clin Nurs. 2009;18(5):755-64..

Studies that have assessed pain and its postoperative consequences in the medium and long term are scarce. Studies to date have not comprehensively examined the post-TKA pain experience or evaluated the presence of discrete subgroups of individuals with different pain patterns at 6 to 12 months after TKA. This factor is an important knowledge gap, given (1) the co-occurrence of POP during post-TKA physical rehabilitation1414 Singelyn FJ, Deyaert M, Joris D, Pendeville E, Gouverneur JM. Effects of patient-controlled intravenous analgesia with morphine, continuous epidural analgesia and three-in-one block on postoperative pain and knee rehabilitation after unilateral total knee arthroplasty. Anesth Analg. 1998;87(1):88-92.,1515 Munin MC, Rudy TE, Glynn NW, Crossett LS, Rubash HE. Early hospital rehabilitation after elective hip and knee arthroplasty. JAMA. 1998; 279(11):847-52.; (2) the treatment of early POP with opioids1616 Goesling J, Moser SE, Zaidi B, Hassett AL, Hilliard P, Hallstrom B, et al. Trends and predictors of opioid use after total knee and total hip arthroplasty. Pain. 2016;157(6):1259-65.,1717 Singh JA, Lewallen DG. Predictors of analgesic use for persistent knee pain after primary total knee arthroplasty: a cohort study using an institutional joint record. Arthritis Res Ther. 2012;14(6):R248. and the indiscriminate use of opioids1818 Manchikanti L, Helm S 2nd, Fellows B, Janata JW, Pampati V, Grider JS, et al. Opioid epidemic in the United States. Pain Physician. 2012;15(3 Suppl):ES9-38.,1919 Manchikanti L, Abdi S, Atluri S, Balog CC, Benyamin RM, Boswell MV, et al. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible prescription of opioids in chronic noncancerous pain, Part I--evidence assessment. Pain Physician. 2012;15(3 Suppl):S1-65.; and (3) the significant prevalence of persistent pain after TKA66 Singh JA, Gabriel S, Lewallen D. The impact of gender, age and preoperative pain severity on pain after TKA. Clin Orthop Relat Res. 2008;466(11):2717-23.

7 Wylde V, Hewlett S, Learmonth ID, Dieppe P. Persistent pain after joint replacement: prevalence, sensory qualities and postoperative determinants. Pain. 2011;152(3):566-72.

8 Rosenberg J, Kehlet H. Does effective postoperative pain treatment influence surgical morbidity? Eur Surg Res. 1999;31(2):133-7.

9 Wu CL, Naqibuddin M, Rowlingson AJ, Lietman SA, Jermyn RM, Fleisher LA. The effect of pain on health-related quality of life in the immediate postoperative period. Anesth Analg. 2003;97(4):1078-85.

10 Li JW, Ma YS, Xiao LK. Postoperative pain management in total knee arthroplasty. Orthop Surg. 2019;11(5):755-61.

11 Hall GM, Peerbhoy D, Shenkin A, Parker CJ, Salmon P. Relationship of functional recovery after hip arthroplasty with neuroendocrine and inflammatory responses. Br J Anaesth. 2001;87(4):537-42.

12 Smith C, Erasmus PJ, Myburgh KH. Endocrine and immune effects of dexamethasone in unilateral total knee replacement. J Int Med Res. 2006;34(6):603-11.
-1313 Shyu YI, Chen ML, Chen MC, Wu CC, Su JY. Postoperative pain and its impact on the quality of life of elderly people with hip fractures more than 12 months after hospital discharge. J Clin Nurs. 2009;18(5):755-64..

If early patterns of pain can be used to identify patients likely to have prolonged pain, clinical treatment options can be developed and adapted to change this outcome. Emerging tools for trajectory analysis that have been shown to be associated with different patterns of care and health care costs2020 Downey L, Engelberg RA. Trajectories of quality of life at the end of life: assessments over time by patients with and without cancer. J Am Geriatr Soc. 2010;58(3):472-9. offer new insights into patients pain experience and outcomes after TKA.

Authors2121 Attal N, Brasseur L, Parker F, Chauvin M, Bouhassira D. Effects of gabapentin on the different components of peripheral and central neuropathic pain syndromes: a pilot study. Eur Neurol. 1998;40(4):191-200. have reported that pain occurring after TKA is more painful than in any other orthopedic surgery, including total hip arthroplasty. The mechanism of POP involves sensitization of peripheral nociceptive nerve terminals and central neurons2222 Bannister JP, Adebiyi A, Zhao G, Narayanan D, Thomas CM, Feng JY, et al. Smooth muscle cell alph2delta-1 subunits are essential for vasoregulation by CaV1.2 channels. Circ Res. 2009;105(10):948-55.. Recently, sensitization of central neurons has been shown to be more important than peripheral nerve sensitization2323 Patel R, Dickenson AH. Mechanisms of gabapentinoids and α2δ-1 calcium channel subunit in neuropathic pain. Pharmacol Res Perspect. 2016;4(2):e00205.,2424 Kaczocha M, Azim S, Nicholson J, Rebecchi MJ, Lu Y, Feng T, Romeiser JL, Reinsel R, Rizwan S, Shodhan S, Volkow ND, Benveniste H. Intrathecal morphine administration reduces postoperative pain and peripheral endocannabinoid levels in total knee arthroplasty patients: a randomized clinical trial. BMC Anesthesiol. 2018;18(1):27..

Moderate or severe pain after TKA delays recovery and rehabilitation. POP is a mixed pain model, with nociceptive and neuropathic components. This pain leads to local inflammatory response, nociceptor stimulation and nociceptive pain. Surgical stimulation also leads to sensitization of the neurons, which is associated with increased pain2424 Kaczocha M, Azim S, Nicholson J, Rebecchi MJ, Lu Y, Feng T, Romeiser JL, Reinsel R, Rizwan S, Shodhan S, Volkow ND, Benveniste H. Intrathecal morphine administration reduces postoperative pain and peripheral endocannabinoid levels in total knee arthroplasty patients: a randomized clinical trial. BMC Anesthesiol. 2018;18(1):27.,2525 Turan A, Kaya G, Karamanlioglu B, Pamukçu Z, Apfel CC. Effect of oral gabapentin on postoperative epidural analgesia. Br J Anaesth. 2006;96(2):242-6.. This is called central sensitization (CS).

CS may be temporary or permanent, depending on the neuronal phenotypic alterations, and is an important phenomenon because it helps in the understanding of chronic or amplified pain. CS occurs after intense or repetitive stimulation of the nociceptor present in the periphery, inducing a reversible increase in excitability and synaptic efficacy of the neurons of the central nociceptive pathway2626 Ashmawi HA, Freire GM. Peripheral and central sensitization. Rev Dor. 2016;17(Suppl 1):S31-4.. The sensitivity induced in the nociceptor of the somatosensory system is adaptive, making the system hyperalert in conditions where there is a greater risk of new injury, such as immediately after exposure to intense or noxious stimuli. Several classes of drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, and local anesthetics have been used to fight the nociceptive component of POP2727 Jain P, Jolly A, Bholla V, Adatia S, Sood J. Evaluation of the effectiveness of oral pregabalin in reducing postoperative pain in patients undergoing total knee arthroplasty. Indian J Orthop. 2012;46(6):646-52.,2828 Bannister K, Sikandar S, Bauer CS, Dolphin AC, Porreca F, Dickenson AH. Pregabalin suppresses neuronal hyperexcitability and visceral hypersensitivity in the absence of peripheral pathophysiology. Anesthesiology. 2011;115(1):144-52..

The objective of the updated POP therapy is to increase pain relief and decrease opioid consumption by combining drugs and analgesic techniques to reduce opioid-related complications. Several modalities are employed to reduce POP after TKA. One study, for instance, investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that interrupts descending serotoninergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid-induced hyperalgesia. The researchers observed that the inhibitory action of pregabalin in animals with opioid-induced hyperalgesia is neither dependent on neuropathy nor dependent on the positive regulation of the voltage-dependent calcium channel subunit, proposed mechanisms essential for the efficacy of pregabalin in neuropathy, concluding that pregabalin reduces spinal neuronal hyperexcitability in morphine-treated animals2828 Bannister K, Sikandar S, Bauer CS, Dolphin AC, Porreca F, Dickenson AH. Pregabalin suppresses neuronal hyperexcitability and visceral hypersensitivity in the absence of peripheral pathophysiology. Anesthesiology. 2011;115(1):144-52..

Another study illustrated the central impact of neuropathy, leading to an imbalance in descending excitations and inhibitions, where underlying noradrenergic mechanisms explain the relationship between conditioned pain modulation and tapentadol and duloxetine use in patients, suggesting that pharmacological strategies through the manipulation of the monoamine system can be used to increase diffuse noxious inhibitory control (DNIC) in patients by blocking descending facilities with ondansetron or increasing norepinephrine inhibitions, possibly reducing chronic pain2929 Bannister K, Patel R, Gonçalves L, Townson L, Dickenson AH. Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending monoamine inhibitions and facilitations. Pain. 2015;156(9):1803-11.. The use of opioids is restricted due to adverse effects such as nausea, vomiting, and pruritus3030 Bauer CS, Nieto-Rostro M, Rahman W, Tran-Van-Minh A, Ferron L, Douglas L, et al. The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin. J Neurosci. 2009;29(13):4076-88..

The objective of the present study was to perform an analysis on the current knowledge about POP in TKA.

CONTENTS

Literature integrative review that methodically, orderly and comprehensively summarizes the results obtained in research on a specific topic. Thus, the reviewer/researcher can elaborate an integrative review with distinct goals, directing it to the definition of concepts, theory review or methodological analysis of research included within a determined subject3131 Mendes KDS, Silveira RCCP, Galvão CM. Integrative review: research method for incorporating evidence in health and nursing. Text Contexto Enferm. 2008;17(4);758-64..

Based on the above, the present work opted for the integrative review based on the Whittemore and Knafl3232 Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs. 2005;52(5):546-53. referential, revised by Hopia, Latvala e Liimatainen3333 Hopia H, Latvala E, Liimatainen L. Reviewing the methodology of an integrative review. Scand J Caring Sci. 2016;30(4):662-9., in order to answer the following guiding question: ‘’what is the current knowledge of studies about POP in TKA’’?

The search was conducted in Pubmed, LILACS and Scielo databases in the months of January and February 2020. The search strategy started with the selection of Health Science Descriptors (DeCS) pertinent to the guiding question. The search in Pubmed used the Medical Subject Headings (MeSH) and the Boolean operator AND to cross-reference the descriptors “pain”, “postoperative pain” and “knee arthroplasty”, in English and Portuguese, as follows: “X AND Y”.

The inclusion criteria consisted of articles published in the last five years, available in full, in English and Portuguese, and that addressed the proposed subject. Editorials, letters to the editor, dissertations, duplicate articles, and those which did not correspond to the theme were excluded.

The search and selection process followed the PRISMA3434 Moher D, Liberati A, Tetzlaff J, Altman DG. The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyzes: the PRISMA statement. PLoS Med. 2009;6(7):e1000097. recommendations as shown in figure 1.

Figure 1
PRISMA flowchart of data on knee arthroplasty postoperative pain. São Paulo, 2020

Included studies should have been clinical trials on humans published in the last five years in Portuguese and English. For data collection, an instrument was constructed containing the following variables: authors; study objective(s); methodological approach; type of study; sample (size, recruitment, characteristics, inclusion and/or exclusion criteria); statistical analysis (statistical treatment); results; conclusions; implications for clinical practice; assessment of methodological rigor; and identification of limitations or biases.

Of the 155 preselected articles, 97 were excluded (for not corresponding to the proposed topic).

Of the 58 that compose the sample, all are in the English language. The studies were represented by 22 countries of origin, being: Taiwan (n=1/0.6%), Iceland (n=1/0.6%), Spain (n=1/0.6%), Bosnia (n=1/0.6%), Switzerland (n=1/0.6 %), Denmark (n=1/0.6%), Poland (n=1/0.6%), Argentina (n=1/0.6%), India (n=1/0.6%), Brazil (n=2/1.2%), Australia (n=2/ 1.2%), Sweden (n=2/ 1.2%), Netherlands (n=2/1.2%), Italy (n=2/1.2%), Thailand (n=3/1.8%), Japan (n=3/1.8%), Korea (n=4/1.8%), UK (n=4/2.4%), Turkey (n=5/3%), USA (n=11/6.8%), China (n=10/6%).

As for language, the studies are in English (94%) and Portuguese (6%). Regarding the type of study, all are clinical trials.

As for the year of publication, 8 are from 2015, 9 from 2016, 9 from 2017, 19 from 2018 and 13 from 2019, showing that they are relatively current research and, like any study, they have limitations, biases, and disagreements with each other.

The objectives of the researches related to pain after knee arthroplasty are presented in table 2.

Table 1
Synthesis of assessed studies, in chronological order, their methodological differences and conclusions. São Paulo, Brazil, 2020.
Table 2
Presentation of the research objectives related to pain after knee arthroplasty according to the studies' results. São Paulo, 2020.

DISCUSSION

This study presented several therapeutic alternatives with the purpose of solving or minimizing POP from TKA. The various results are effective and promising, but did not reach a consensus or gold standard1010 Li JW, Ma YS, Xiao LK. Postoperative pain management in total knee arthroplasty. Orthop Surg. 2019;11(5):755-61. for pain treatment due to the researches presenting different methodologies and samples.

As for the analysis of the results, the present study found a large number of publications (clinical trials) on the subject, demonstrating the great interest of the medical community in solving POP. Another strength of this study is that these clinical trials are recent. The sample consisted of 14.705 patients of both genders, aged between 45 and 83 years. As for the countries of origin, it was possible to observe that the scientific interest on POP of TKA is present in the American, European, and Asian continent.

The treatment of pain after TKA is challenging and the recommendation is to assess combined treatments and individualized targeted treatments according to the patient particularities. In order to ensure therapeutic success it’s necessary to evaluate the clinical and cost effectiveness of multidisciplinary and individualized interventions3535 Liu J, Wang F. Preoperative celecoxib analgesia is more efficient and equally tolerated compared to postoperative celecoxib analgesia in knee osteoarthritis patients undergoing total knee arthroplasty: A randomized, controlled study. Medicine (Baltimore). 2018;97(51):e13663.,3636 Koo K, Park DK, Youm YS, Sung DC, Hwang CH. Enhanced reality showing long-lasting analgesia after total knee arthroplasty: prospective, randomized clinical trial. Sci Rep. 2018;8:2343..

Techniques employed for pain minimization and early patient rehabilitation have been evaluated as effective, such as FNB and sciatic nerve block applied in TKA, which can obviously inhibit tourniquet reaction, maintain hemodynamic stability, reduce anesthetic dose and relieve POP3737 Li J, Dong BH, Wu XC, Xu P. Effect of femoral and sciatic nerve block on the tourniquet reaction and postoperative pain during total knee arthroplasty. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2015;37(6):641-4, with lower pain scores after 24h and lower incidence of adverse effects and bleeding compared to subarachnoid morphine3838 Álvarez NER, Ledesma RJG, Hamaji A, Hamaji MWM, Vieira JE. Continuous femoral nerve blockade and single-shot sciatic nerve block promotes better analgesia and lower bleeding for total knee arthroplasty compared to intrathecal morphine: a randomized trial. BMC Anesthesiol. 2017;17(1):64., providing more potent analgesia in the first six hours after the operation.

The quality of postoperative recovery was higher when3939 Kanadli H, Dogru S, Karaman T, Karaman S, Tapar H, Sahin A, et al. Comparison of the efficacy of femoral nerve block and fascia iliaca compartment block in patients with total knee replacement. Minerva Anestesiol. 2018;84(10):1134-41. associated with less intense pain perception due to the ACB, thus promoting early mobility rehabilitation4040 Borys M, Domagala M, Wenclaw K, Jarczynska-Domagala J, Czuczwar M. Continuous femoral nerve block is more effective than continuous adductor channel block for treating pain after total knee arthroplasty: A randomized, double-blind, controlled trial. Medicine (Baltimore). 2019;98(39):e17358.,4141 Ali A, Sundberg M, Hansson U, Malmvik J, Flivik G. Doubtful effect of continuous intraarticular analgesia after total knee arthroplasty: a randomized double-blind study of 200 patients. Acta Orthop. 2015;86(3):373-7.. Periarticular infiltration is a viable and safe alternative to FNB for immediate postoperative pain relief after TKA4242 Wall PDH, Parsons NR, Parsons H, Achten J, Balasubramanian S, Thompson P, et al. PAKA Study Group. A pragmatic randomised controlled trial comparing the efficacy of a femoral nerve block and periarticular infiltration for early pain relief following total knee arthroplasty. Bone Joint J. 2017;99-B(7):904-11.,4343 Laoruengthana A, Jarusriwanna A, Rattanaprichavej P, Rasamimongkol S, Varakornpipat P, Pongpirul K. Timing of periarticular injection has no effect on postoperative pain and functional recovery in simultaneous bilateral total knee arthroplasty: a prospective randomized, double-blinded trial. BMC Musculoskelet Disord. 2019;20(1):162.. Perineural dexamethasone improves postoperative analgesia4444 Ortiz-Gómez JR, Perepérez-Candel M, Vázquez-Torres JM, Rodriguez-Del Río JM, Torrón-Abad B, Fornet-Ruiz I, et al. Postoperative analgesia for elective total knee arthroplasty under subarachnoid anesthesia with opioids: comparison between epidural, femoral block and adductor canal block techniques (with and without perineural adjuvants). A prospective, randomized, clinical trial. Minerva Anestesiol. 2017;83(1):50-8..

ACB accompanied by intraoperative periarticular local anesthetic infiltration accompanied by analgesia the day after TKA is improved with a catheter inserted at the level of the midpoint between the anterior superior iliac spine and the superior border of the patella compared to a more distal insertion closer to the adductor hiatus4545 Sztain JF, Khatibi B, Monahan AM, Said ET, Abramson WB, Gabriel RA, et al. Proximal versus distal continuous adductor canal blocks: does varying perineural catheter location influence analgesia? a randomized, subject-masked, controlled clinical trial. Anesth Analg. 2018;127(1):240-6.. Pain control after TKA was found to be better in patients treated with CACB compared to those treated with single-dose ACB. Patients treated with CACB also had better ambulation and functional recovery after TKA4646 Canbek U, Akgun U, Aydogan NH, Kilinc CY, Uysal AI. Continuous adductor channel block following total knee arthroplasty provides a better analgesia compared to single shot: a prospective randomized controlled trial. Acta Orthop Traumatol Turc. 2019;53(5):334-9.

47 Sargant SC, Lennon MJ, Khan RJ, Fick D, Robertson H, Haebich S. Extended duration regional analgesia for total knee arthroplasty: a randomised controlled trial comparing five days to three days of continuous adductor canal ropivacaine infusion. Anaesth Intensive Care. 2018;46(3):326-31.
-4848 Jaeger P, Baggesgaard J, Sørensen JK, Ilfeld BM, Gottschau B, et al. Adductor canal block with continuous infusion versus intermittent boluses and morphine consumption: a randomized, blinded, controlled clinical trial. Anesth Analg. 2018;126(6):2069-77..

The addition of percutaneous periarticular injection of multiple drugs the day after TKA may provide better relief of POP, but more studies are needed to confirm the safety of percutaneous injection4949 Iseki T, Tsukada S, Wakui M, Kurosaka K, Yoshiya S. Percutaneous periarticular multi-drug injection at one day after total knee arthroplasty as a component of multimodal pain management: a randomized control trial. BMC Musculoskelet Disord. 2019;20(1):61.,5050 Blikman T, Rienstra W, van Raaij TM, ten Hagen AJ, Dijkstra B, Zijlstra WP, et al. Duloxetine in OsteoArthritis (DOA) study: study protocol of a pragmatic open-label randomised controlled trial assessing the effect of preoperative pain treatment on postoperative outcome after total hip or knee arthroplasty. BMJ Open. 2016;6(3):e010343..

ACB-L was superior to PAI-L in the treatment of pain after TKA; however, PAI-L was superior to ACB-L with respect to postoperative ROM and walking capacity5151 Cicekci F, Yildirim A, Önal Ö, Celik JB, Kara I. Ultrasound-guided adductor canal block using levobupivacaine versus periarticular infiltration of levobupivacaine after total knee arthroplasty: a randomized clinical trial. Sao Paulo Med J. 2019;137(1):45-53..

As for surgical approach techniques, the configuration of the catheter orifice did not influence the efficacy of CFNB in this setting: the quality of analgesia was similar, with no reduction in local anesthetic or morphine consumption and equivalent postoperative quadriceps weakness5252 Novello-Siegenthaler A, Hamdani M, Iselin-Chaves I, Fournier R. Ultrasound-guided continuous femoral nerve block: a randomized trial on the influence of femoral nerve catheter orifice configuration (six-hole versus end-hole) on postoperative analgesia after total knee arthroplasty. BMC Anesthesiol. 2018;18(1):191.. Feasibility suggests that for TKA, percutaneous ultrasound-guided SNP is feasible in the immediate perioperative period and may provide analgesia without the undesirable systemic effects of opioids or quadriceps weakness induced by local anesthetic-based peripheral nerve blocks5353 Ilfeld BM, Ball ST, Gabriel RA, Sztain JF, Monahan AM, Abramson WB, et al. A feasibility study of percutaneous peripheral nerve stimulation for the treatment of postoperative pain following total knee arthroplasty. Neuromodulation. 2019;22(5):653-60..

Some studies discuss the technique of the intraoperative tourniquet for pain control. According to study5454 Alexandersson M, Wang EY, Eriksson S. A small difference in recovery between total knee arthroplasty with and without tourniquet use the first 3 months after surgery: a randomized controlled study. Knee Surg Sports Traumatol Arthrosc. 2019;27(4):1035-42., the hypothesis that rehabilitation-related outcomes would be improved without a tourniquet is not supported by their results. When comparing the results of the surgeries performed with and without a tourniquet, no clear benefit was observed for either, as the greater amount of pain exhibited by the non-tourniquet group was only evident for a short period, and the improved mobility in the latter was not observed at a clinically relevant level. The lateral via provided better postoperative lateral patellar tilt in valgus knee arthroplasties5555 Tonelli Filho JR, Passarelli MC, Brito JAS, Campos GC, Zorzi AR, Miranda JB. Keblish's lateral surgical approach enhances patellar tilt in valgus knee arthroplasty. Rev Bras Ortop. 2016;51(6):680-6..

The ERAS Program is safer and more effective in elderly patients with TKA compared to the traditional route. It relieves perioperative pain, improves joint function, reduces blood transfusion, length of hospital stay, and overall complications without increasing short-term mortality5656 Jiang HH, Jian XF, Shangguan YF, Qing J, Chen LB. Effects of enhanced recovery after surgery in total knee arthroplasty for patients older than 65 years. Orthop Surg. 2019;11(2):229-35..

As for drugs, intravenous administration of dexmedetomidine in the perioperative period decreases serum IL-6 levels postoperatively in patients submitted to bilateral TKA and has a postoperative analgesic effect5757 Yun SH, Park JC, Kim SR, Choi YS. Effects of dexmedetomidine on interleukin-6 serum, hemodynamic stability and postoperative pain relief in elderly patients under spinal anesthesia. Acta Med Okayama. 2016;70(1):37-43..

Preemptive analgesia added to a multimodal analgesic regimen improved analgesia, reduced inflammatory reaction and accelerated functional recovery in the first postoperative week, but did not improve long-term function5858 Jianda X, Yuxing Q, Yi G, Hong Z, Libo P, Jianning Z. Impact of preemptive analgesia on inflammatory responses and rehabilitation after primary total knee arthroplasty: a controlled clinical study. Sci Rep. 2016;6:30354.. An alternative is preoperative home exercises that provided better preoperative KS and FS and improved knee scores up to six months postoperatively. However, at 12 months after operation there was no significant difference between the intervention and control group for the KS and FS5959 Jahic D, Omerovic D, Tanovic AT, Dzankovic F, Campara MT. The effect of prehabilitation on postoperative outcome in patients following primary total knee arthroplasty. Med Arch. 2018;72(6):439-43..

The fast-track protocol for primary TKA showed significantly lower knee pain scores and improved functional outcome in the first 7 days after TKA compared to a regular protocol6060 Fransen BL, Hoozemans MJM, Argelo KDS, Keijser LCM, Burger BJ. Fast-track total knee arthroplasty improved clinical and functional outcome in the first 7 days after surgery: a randomized controlled pilot study with 5-year follow-up. Arch Orthop Trauma Surg. 2018;138 (9):1305-16..

The continuous analgesia infusion pump, compared to the formal intermittent intravenous regimen, presented better pain control and perception, improving tolerance to physical therapy, and reducing, on average, 15h of hospitalization, consequently decreasing surgical cost6161 Iglesias SL, Rodríguez-Urmenyi C, Mangupli MM, Pioli I, Gómez J, Allende BL. Continuous intravenous analgesia vs. intermittent for total primary knee replacement: analysis of the quality of pain control, hospital stay and costs. Acta Ortop Mex. 2018:32(3):134-9..

Advancing the timing of periarticular injection can provide clinically significant improvement in pain after TKA under general anesthesia6262 Bugada D, Allegri M, Gemma M, Ambrosoli AL, Gazzerro G, Chiumiento F, et al. Effects of anaesthesia and analgesia on long-term outcome after total knee replacement: a prospective, observational, multicentre study. Eur J Anaesthesiol. 2017;34(10):665-72.. Continuous local anesthesia provides analgesic benefit for up to one month after surgery, but did not influence PPSP at six months. Better pain control in the first month was associated with a reduction in PPSP. Patients with higher expectations of surgery, higher baseline inflammation and a pessimistic outlook are more likely to develop PPSP6363 Tsukada S, Kurosaka K, Maeda T, Iida A, Nishino M, Hirasawa N. Early-stage periarticular injection during total knee arthroplasty may provide a better postoperative pain relief than late-stage periarticular injection: a randomized-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2019;27(4):1124-31.. The addition of corticosteroid to periarticular injection significantly decreased early POP. More studies are needed to confirm the safety of corticosteroid in periarticular injection6464 YaDeau JT, Lin Y, Mayman DJ, Goytizolo EA, Alexiades MM, Padgett DE, et al. Pregabalin and pain after total knee arthroplasty: a double-blind, randomized, placebo-controlled, multidose trial. Br J Anaesth. 2015;115(2):285-93..

Pregabalin showed no beneficial effects, but increased sedation and decreased patient satisfaction. Study6565 Olive DJ, Barrington MJ, Simone SA, Kluger R. A randomized controlled study comparing three schemes of analgesia after total knee joint replacement: continuous femoral nerve block, intrathecal morphine or both. Anaest Intensive Care. 2015;43(4):454-60. does not support routine perioperative pregabalin for patients with TKA.

Study5555 Tonelli Filho JR, Passarelli MC, Brito JAS, Campos GC, Zorzi AR, Miranda JB. Keblish's lateral surgical approach enhances patellar tilt in valgus knee arthroplasty. Rev Bras Ortop. 2016;51(6):680-6. demonstrated that CFNB resulted in reduced pain and was associated with lower morphine consumption and better mobilization within 24h compared to SMI. This study showed no statistically significant differences between CFNB alone and CFNB + SMI.

The use of parecoxib + continuous femoral block provided superior analgesic efficacy and opioid-sparing effects in patients undergoing TKA6666 Sarridou DG, Chalmouki G, Braoudaki M, Koutsoupaki A, Mela A, Vadalouka A. Intravenous parecoxib and continuous femoral block for postoperative analgesia after total knee arthroplasty. A randomized, double-blind, prospective trial. Pain Physician. 2015;18(3):267-76.. In this context, intra-articular bupivacaine in combination with intravenous parecoxib may improve pain relief and reduce the demand for rescue analgesics in patients undergoing TKA6767 Shen SJ, Peng PY, Chen HP, Lin JR, Lee MS, Yu HP. Analgesic effects of intra-articular bupivacaine/ intravenous parecoxib combination therapy versus intravenous parecoxib monotherapy in patients receiving total knee arthroplasty: a randomized, double-blind trial. Biomed Res Int. 2015;2015:450805.. Compared to postoperative CFNB analgesia alone, CFNB + PALI could relieve pain at rest and pain during passive movement after TKA to achieve 90° knee flexion6868 Deng Y, Jiang TL, Yang XX, Li M, Wang J, Guo XY. Effect of continuous femoral nerve block combined with periarticular local infiltration analgesia on early operative functional recovery after total knee arthroplasty: a randomized, double-blind, controlled study. Beijing Da Xue Xue Bao Yi Xue Ban. 2017;49(1):137-41..

Thus, some patients could improve the postoperative rehabilitation training6969 Bian YY, Wang LC, Qian WW, Lin J, Jin J, Peng HM, et al. Role of parecoxib sodium in the multimodal analgesia after total knee arthroplasty: a randomized double-blinded controlled trial. Orthop Surg. 2018;10(4):321-7.. In preemptive multimodal analgesia strategies, parecoxib sodium can significantly decrease the VAS score in the short term, relieve pain right after surgery, and does not increase the incidence of complications. Parecoxib sodium is a safe and effective drug in the perioperative analgesic treatment of TKA1010 Li JW, Ma YS, Xiao LK. Postoperative pain management in total knee arthroplasty. Orthop Surg. 2019;11(5):755-61.,7070 Shi ZB, Dang XQ. Efficacy of the multimodal perioperative analgesia protocol with periarticular injection of medications and use of non-steroidal anti-inflammatory drugs in total knee arthroplasty. Niger J Clin Pract. 2018;21(9):1221-7..

Intraoperative anesthetic and periarticular infiltration with multimodal drugs significantly relieved pain after surgery and reduced requirements for NSAIDs, improved patient satisfaction and joint ROM without apparent risks after TKA7171 Mont MA, Beaver WB, Dysart SH, Barrington JW, Del Gaizo DJ. Local infiltration analgesia with liposomal bupivacaine improves pain scores and reduces opioid use after total knee arthroplasty: results of a randomized clinical trial. J Arthroplasty. 2018;33(1):90-6.. LIA with LB 266 mg plus bupivacaine significantly reduced opioid requirements and intensity of pain and significantly improved readiness and discharge satisfaction from zero to 24h after TKA compared to bupivacaine alone. These findings support the use of LIA with LB for TKA when early discharge is the goal7272 Wylde V, Lenguerrand E, Gooberman-Hill R, Beswick AD, Marques E, Noble S, et al. Effect of local anesthetic infiltration on chronic postsurgical pain after total hip and knee replacement: APEX randomized clinical trials. Pain. 2015;156(6):1161-70.. In conclusion, these studies provide evidence that local anesthetic infiltration reduces chronic pain for up to 1 year after operation, suggesting that routine use of infiltration could improve long-term pain relief7373 Mei SY, Jin S, Chen Z, Ding X, Zhao X, Li Q. Analgesia para artroplastia total do joelho: uma metanálise comparando infiltração local e bloqueio do nervo femoral. Clínicas. 2015;70(9):648-53..

Authors7474 Wu Y, Lu X, Ma Y. Low dose multiple dexamethasone in the perioperative period improves postoperative clinical results after total knee arthroplasty. Musculoskeletal Dis BMC. 2018;19(1):428. performed a meta-analysis of randomized clinical trials and concluded that local infiltration provides analgesia comparable to a FNB for patients undergoing TKA based on pain during rest and opioid consumption, but a FNB reduces pain on movement.

The use of 10mg dexamethasone 1h before surgery and repeated at 6h postoperatively can significantly reduce the postoperative CRP and IL-6 levels and the incidence of PONV, relieve pain, achieve an additional analgesic effect, and improve early ROM compared to the other two groups in TKA7575 Tan Z, Kang P, Pei F, Shen B, Zhou Z, Yang J. A comparison of adductor canal block and femoral nerve block after total-knee arthroplasty regarding analgesic effect, effectiveness of early rehabilitation, and lateral knee pain relief in the early stage. Medicine (Baltimore). 2018;97(48):e13391.. ACB does not relieve lateral knee pain in the early stage but provides similar analgesic effect and better early rehabilitation efficacy compared to FNB in patients undergoing TKA7575 Tan Z, Kang P, Pei F, Shen B, Zhou Z, Yang J. A comparison of adductor canal block and femoral nerve block after total-knee arthroplasty regarding analgesic effect, effectiveness of early rehabilitation, and lateral knee pain relief in the early stage. Medicine (Baltimore). 2018;97(48):e13391.,7676 Gudmundsdottir S, Franklin JL. Continuous adductor canal block added to local infiltration analgesia (LIA) after total knee arthroplasty has no additional benefits on pain and ambulation on postoperative day 1 and 2 compared with LIA alone. Acta Orthop. 2017;88(5):537-42..

As for fentanyl, additional use showed no prominent increase in analgesic effect in the field of CFNB after TKA7777 Heo BH, Lee HJ, Lee HG, Kim MY, Park KS, Choi JI, et al. Femoral nerve block for patient undergoing total knee arthroplasty: prospective, randomized, double-blinded study evaluating analgesic effect of perineural fentanyl additive to local anesthetics. Medicine (Baltimore). 2016;95(36):e4771.. The use of combined ibuprofen and acetaminophen showed additional benefits in terms of improved pain scores only on postoperative day 3, fewer potential adverse events related to opioid use, and less opioid use when compared to ibuprofen alone7878 Gupta A, Abubaker H, Demas E, Ahrendtsen L. A randomized study comparing the safety and efficacy of intravenous ibuprofen versus ibuprofen and acetaminophen in knee or hip arthroplasty. Pain Physician. 2016;19(6):349-56.. Intravenous or oral acetaminophen do not provide additional analgesia in the immediate postoperative period when given as adjunct multimodal analgesia in patients undergoing TKA in the context of spinal anesthesia7979 O'Neal JB, Freiberg AA, Yelle MD, Jiang Y, Zhang C, Gu Y, et al. Intravenous vs oral acetaminophen as an adjunct to multimodal analgesia after total knee arthroplasty: a prospective, randomized, double-blind clinical trial. J Arthroplasty. 2017;32(10):3029-33..

Studies indicate that subarachnoid morphine reduces POP in patients with TKA. Furthermore, activation of central opioid receptors negatively modulates endocannabinoid tone, suggesting that potent analgesics may reduce the stimulus for peripheral endocannabinoid production. This study is the first to document the existence of fast communication between the central opioid and peripheral endocannabinoid systems in humans8080 Sundarathiti P, Thammasakulsiri J, Supboon S, Sakdanuwatwong S, Piangjai M. Comparison of continuous femoral nerve block (BNFC/SA) and continuous femoral nerve block with mini-dose spinal morphine (BNFC/SAMO) for postoperative analgesia after total knee arthroplasty (TKA): a randomized controlled study. BMC Anesthesiol. 2016;16(1):38.. Although in some patients CFNB is inadequate, a lower dose of subarachnoid morphine (0.035mg) in addition to CFNB has been shown to be effective, with minimal adverse effects8181 Tan Z, Kang P, Pei F, Shen B, Zhou Z, Yang J. A comparison of adductor canal block and femoral nerve block after total-knee arthroplasty regarding analgesic effect, effectiveness of early rehabilitation, and lateral knee pain relief in the early stage. Medicine (Baltimore). 2018;97(48):e13391..

The technique of SPC blockade with bupivacaine HCL has guaranteed greater hemodynamic efficiency in the perioperative period in high-risk elderly patients8282 Barrington JW, Emerson RH, Lovald ST, Lombardi AV, Berend KR. No difference in early analgesia between liposomal bupivacaine injection and intrathecal morphine after TKA. Clin Orthop Relat Res. 2017;475(1):94-105.,8383 Canakci E, Unal D, Guzel Y. The Effect of unilateral spinal anesthesia and psoas compartment with sciatic block on the postoperative pain management in total knee artroplastic surgery. Pain Res Manag. 2017;2017:4127424.. The use of LB and plain bupivacaine showed superiority over pain control strategies, but they were relatively equivalent to each other in direct comparison8484 Zlotnicki JP, Hamlin BR, Plakseychuk AY, Levison TJ, Rothenberger SD, Urish KL. Liposomal bupivacaine vs plain bupivacaine in periarticular injection for control of pain and early motion in total knee arthroplasty: a randomized, prospective study. J Arthroplasty. 2018;33(8):2460-4..

The use of sufentanil 30µg was effective and well tolerated in the treatment of moderate to severe acute POP8585 Hutchins JL, Leiman D, Minkowitz HS, Jove M, DiDonato KP, Palmer PP. An open study of sufentanil sublingual tablet 30 mcg in patients with postoperative pain. Pain Med. 2018;19(10):2058-68., while the preemptive administration of oral gabapentin did not reduce POP, but attenuated IL-6 production on the first postoperative day8686 Erkiliç E, Kesimci E, Sahin D, Bektaser B, Yalçin N, Ellik S, Aylin Sepici-Dinçel A. Does preemptive gabapentin modulate the cytokine response in total knee arthroplasty? A placebo-controlled study. Adv Clin Exp Med. 2018;27(4):487-91..

The effect of adjunct gabapentin on multimodal postoperative analgesia is controversial1313 Shyu YI, Chen ML, Chen MC, Wu CC, Su JY. Postoperative pain and its impact on the quality of life of elderly people with hip fractures more than 12 months after hospital discharge. J Clin Nurs. 2009;18(5):755-64.,6363 Tsukada S, Kurosaka K, Maeda T, Iida A, Nishino M, Hirasawa N. Early-stage periarticular injection during total knee arthroplasty may provide a better postoperative pain relief than late-stage periarticular injection: a randomized-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2019;27(4):1124-31.,7272 Wylde V, Lenguerrand E, Gooberman-Hill R, Beswick AD, Marques E, Noble S, et al. Effect of local anesthetic infiltration on chronic postsurgical pain after total hip and knee replacement: APEX randomized clinical trials. Pain. 2015;156(6):1161-70.. The main mechanism of action of gabapentin is achieved in combination with the 21 subunits of voltage-dependent presynaptic calcium channels. The expression of these channels is up-regulated in the case of nerve injury. Furthermore, gabapentin can decrease the hyperexcitability of secondary nociceptive neurons in the dorsal horn2323 Patel R, Dickenson AH. Mechanisms of gabapentinoids and α2δ-1 calcium channel subunit in neuropathic pain. Pharmacol Res Perspect. 2016;4(2):e00205..

The combined administration of tranexamic acid + dexamethasone significantly reduced the postoperative levels of CRP and IL-6, relieved POP, improved the incidence of PONV, provided additional analgesic and antiemetic effects, reduced postoperative fatigue, without increasing the risk of complications in primary TKA8787 Yu Y, Lin H, Wu Z, Xu P, Lei Z. Perioperative combined administration of tranexamic acid and dexamethasone in total knee arthroplasty-benefit versus harm? Medicine (Baltimore). 2019;98(34):e15852..

The presence of a suction drain significantly reduced opioid consumption during the first 6h after TKA. The use of a drain made no difference to functional outcome at one year postoperatively. With the use of tranexamic acid in TKA, total blood loss and the need for blood transfusion were not affected by the presence or absence of closed suction drainage or by the drain orifice used. Clinical parameters such as swelling, ROM, infection, and deep vein thrombosis also remained the same8888 Maniar RN, Pradhan P, Bhatnagar N, Maniar A, Bidwai R, Bindal P. Role of the suction drain after knee arthroplasty in the tranexamic acid era: a randomized controlled study. Clin Orthop Surg. 2019;11(1):73-81..

As for the use of Mg, there are controversies8989 Frassanito L, Messina A, Vergari A, Colombo D, Chierichini A, Della Corte F, et al. Intravenous infusion of magnesium sulfate and postoperative analgesia in total knee arthroplasty. Minerva Anestesiol. 2015;81(11):1184-91.,9090 Shin HJ, Kim EY, Na HS, Kim TK, Kim MH, Do SH. Magnesium sulfate attenuates acute postoperative pain and increased pain intensity after surgical injury in bilateral total knee arthroplasty in staging: a randomized, double-blind, placebo-controlled study. Br J Anaesth. 2016;117(4):497-503.. For authors9090 Shin HJ, Kim EY, Na HS, Kim TK, Kim MH, Do SH. Magnesium sulfate attenuates acute postoperative pain and increased pain intensity after surgical injury in bilateral total knee arthroplasty in staging: a randomized, double-blind, placebo-controlled study. Br J Anaesth. 2016;117(4):497-503., perioperative intravenous administration of Mg did not influence POP control and analgesic consumption after TKA. Further studies should be conducted with different intraoperative and postoperative pain protocols to increase the antinociceptive effect potential of Mg8989 Frassanito L, Messina A, Vergari A, Colombo D, Chierichini A, Della Corte F, et al. Intravenous infusion of magnesium sulfate and postoperative analgesia in total knee arthroplasty. Minerva Anestesiol. 2015;81(11):1184-91.. However, RCT studies6666 Sarridou DG, Chalmouki G, Braoudaki M, Koutsoupaki A, Mela A, Vadalouka A. Intravenous parecoxib and continuous femoral block for postoperative analgesia after total knee arthroplasty. A randomized, double-blind, prospective trial. Pain Physician. 2015;18(3):267-76.,6767 Shen SJ, Peng PY, Chen HP, Lin JR, Lee MS, Yu HP. Analgesic effects of intra-articular bupivacaine/ intravenous parecoxib combination therapy versus intravenous parecoxib monotherapy in patients receiving total knee arthroplasty: a randomized, double-blind trial. Biomed Res Int. 2015;2015:450805. with 44 patients reported that magnesium sulfate administration significantly reduced POP and minimized the difference in pain intensity between the first and second surgery.

Another unsuccessful approach is the application of a compression dressing after TKA. The use of this technique didn’t result in any clinical improvement in limb circumference, ROM, or pain. Based on this study, the belief is that the application of a compressive dressing after TKA neither benefits nor harms the patient. Therefore, the authors9090 Shin HJ, Kim EY, Na HS, Kim TK, Kim MH, Do SH. Magnesium sulfate attenuates acute postoperative pain and increased pain intensity after surgical injury in bilateral total knee arthroplasty in staging: a randomized, double-blind, placebo-controlled study. Br J Anaesth. 2016;117(4):497-503.,9191 Matthews CN, Chen AF, Daryoush T, Rothman RH, Maltenfort MG, Hozack WJ. Does an elastic compression bandage provide any benefit after primary TKA? Clin Orthop Relat Res. 2019;477(1):134-44. suggested not using compression dressings for routine primary TKA.

The RCT9292 Manassero A, Fanelli A, Ugues S, Bailo C, Dalmasso S. Oxycodone/naloxone prolonged oral release offers analgesia equivalent to analgesia controlled by a patient with intravenous morphine after total knee replacement. A randomized controlled study. Minerva Anestesiol. 2018;84(9):1016-23. with 20 patients showed that in the immediate postoperative period of TKA, patients receiving oral extended-release oxycodone/naloxone had better pain control than those receiving IVPCA morphine, with a similar degree of PONV.

The limitations of the present study are related to the quality of the sample, which is heterogeneous, and the methodology of the studies being different, in approach, duration and dose of drugs and duration of follow-up.

The “implications for clinical practice” variables reinforce the understanding that there are benefits to anesthetic infiltration and multimodal drugs in modulating POP in TKA.

The causes of chronic pain after TKA are still not fully understood, although research interest is growing and it’s clear that this pain has a multifactorial etiology, with a wide range of possible biological, surgical, and psychosocial factors that may influence outcomes.

CONCLUSION

Several classes of local and systemic drugs, including NSAIDs, opioids, and local anesthetics have been used to fight the nociceptive component of POP, aid early rehabilitation, improve quality of life, self-esteem, and reduce hospitalization and hospital expenses.

  • Sponsoring sources: none.

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Publication Dates

  • Publication in this collection
    08 Oct 2021
  • Date of issue
    Jul-Sep 2021

History

  • Received
    10 Sept 2020
  • Accepted
    24 July 2021
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