Advances in perioperative pain management for total knee arthroplasty: a review of multimodal analgesic approaches

Abstract

Despite significant advancements in total knee arthroplasty (TKA), managing postoperative pain remains a substantial clinical challenge. With advances in surgical techniques and pharmacology, TKA perioperative analgesic strategies continue to evolve, necessitating ongoing reassessment of current data. Multimodal analgesia has become the standard for perioperative pain management in TKA; however, variations in its specific components and applications across studies create challenges in selecting the optimal analgesic approach. Evaluating these pain management strategies is essential for understanding their benefits, limitations, and appropriate use, allowing the development of individualized perioperative analgesic plans. This review aims to summarize current research on perioperative pain control in TKA and assess the effectiveness of different analgesic interventions.

Background

Total knee arthroplasty (TKA), one of the most common orthopedic procedures, enhances joint function and relieves pain by replacing damaged knee joints with artificial implants. It is widely regarded as the most effective treatment for end-stage knee disease [1]. Primary knee osteoarthritis is the leading indication for TKA, accounting for over 95% of cases [2]. Epidemiological studies show a steady global increase in TKA incidence, with a notable rise among younger patients [3, 4]. By 2030, the demand for primary TKA in the United States is projected to increase by 673%, reaching an estimated 3.48 million procedures [5].

Despite significant advancements in TKA, managing postoperative pain remains a substantial clinical challenge. Studies report that more than 60% of TKA patients undergoing TKA suffer moderate to severe pain following surgery [6]. The fear of severe postoperative pain may even cause some patients to delay surgery [7]. Postoperative pain in TKA patients is associated with prolonged hospital stays [8], lower patient satisfaction [9], increased opioid use [10, 11], delayed rehabilitation [12], and a higher risk of adverse events [11]. In contrast, effective pain management supports early functional recovery, improves patient satisfaction, reduces readmission rates, shortens hospital stays, and minimizes complications, such as anxiety, depression, chronic pain syndrome, atelectasis, and deep venous thrombosis of lower extremity, thus lowering healthcare costs and improving care quality [13]. Therefore, developing effective and safe perioperative analgesic strategies is crucial for optimizing patient outcomes.

With advances in surgical techniques and pharmacology, TKA postoperative analgesic strategies continue to evolve, necessitating ongoing reassessment of current data [14]. Multimodal analgesia has become the standard for perioperative pain management in TKA; however, variations in its specific components and applications across studies create challenges in selecting the optimal analgesic approach [15]. Evaluating these pain management strategies is essential for understanding their benefits, limitations, and appropriate use, allowing the development of individualized perioperative analgesic plans. This review aims to summarize current research on perioperative pain control in TKA and assess the effectiveness of different analgesic interventions.

Mechanisms of postoperative pain in TKA

Postoperative pain following TKA originates from both peripheral and central mechanisms. Peripheral sources include impacts on bone and knee joint soft tissue, involving processes such as nociceptor stimulation, release of inflammatory mediators, localized ischemic responses, and direct nerve branch damage at the incision site. In contrast, central mechanisms contain the activation of N-methyl-D-aspartate (NMDA) receptors in the spinal cord, which subsequently act at the cortical level to initiate or modulate pain pathways [16].

Pain in TKA is a complex process, with acute postoperative pain linked to mechanical, thermal, and chemical injuries. These injuries trigger the release of cellular mediators—such as bradykinin, prostaglandins, substance P, and histamine—that sensitize nociceptors and lower the pain threshold [17]. Additionally, direct nerve damage contributes to postoperative pain, as the deep surgical field in TKA requires osteotomy and soft tissue release, exposing sensory nerve fibers around the patella, which lacks adequate soft tissue protection, thereby exacerbating pain [18, 19]. The distribution of nociceptors also plays a role, as they are densely located in the subchondral bone, periosteum, joint capsule, retinaculum, ligament attachment points, and infrapatellar fat pad [20].

From a neurological standpoint, pain transmission begins with signals carried by unmyelinated C-fibers and myelinated A-fibers, which deliver the initial pain impulses to the dorsal root ganglion. In this region, these fibers establish synaptic connections in the dorsal horn, after which the signals progress upward through neurons in the spinothalamic tract. Neurons in the spinal cord transmit signals related to pain on the same side of the body (ipsilateral) and temperature sensations from the opposite side (contralateral) to the central nervous system, where they undergo processing and modulation [21]. Throughout this neural pathway, there are opportunities for surgical and pharmacological interventions to modify pain perception [22]. At the surgical site, pain can be managed with cryotherapy, local anesthetics, cyclooxygenase (COX) inhibitors, anti-inflammatory drugs, which help to reduce inflammation and block peripheral pain signals. For the spinal cord level, combining local anesthetics with opioids, alpha-receptor agonists, or NMDA receptor blockers can further inhibit pain transmission. Additionally, central analgesics, including acetaminophen, opioids, alpha-agonists, and nonsteroidal anti-inflammatory drugs (NSAIDs), act on higher centers in the nervous system to provide pain relief and reduce inflammatory responses (Fig. 1).

Fig. 1.

Modulation of the pain pathway. Lines marked with a (−) sign indicate inhibitory effects, while lines with a ( +) sign represent stimulatory effects. NMDA, N-Methyl-D-Aspartate receptor antagonists; NSAIDs, nonsteroidal anti-inflammatory drugs. This figure highlights the critical importance of targeting multiple points along the pain signaling pathway to effectively manage pain

Multimodal analgesia

The concept of multimodal analgesia, introduced by Kehlet and Dahl in 1993, involves using various drugs with distinct mechanisms of action to minimize opioid consumption, thereby enhancing analgesic efficacy and reducing side effects [22]. Although opioids are highly effective, their perioperative use is often associated with numerous adverse effects, including constipation, nausea, vomiting, drowsiness, dizziness, urinary retention, delirium, cognitive impairment, respiratory depression, etc. The most serious of which is respiratory depression [23]. Furthermore, the risks of addiction, misuse, and abuse are increasingly concerning [24]. Opioids may also induce hyperalgesia and acute tolerance, potentially exacerbating postoperative pain, which limits their perioperative use [24].

Advances in understanding the mechanisms of postoperative pain in TKA confirm the involvement of both peripheral and central pathways [16, 23]. Therefore, a single drug is unlikely to provide sufficient analgesia. Multimodal analgesia integrates preoperative, intraoperative, and postoperative pain management strategies, including preemptive analgesia, neuraxial anesthesia, peripheral nerve blocks, local infiltration analgesia, and oral or intravenous medications [6]. As is well known, multimodal analgesia involves the use of multiple agents or modalities with different mechanisms of action targeting various pain pathways. The applied regional anesthesia methods not only provide postoperative pain palliation, but also shorten the duration of hospital stay and support the rehabilitation of patients [25]. While specific protocols vary across institutions, multimodal approaches generally outperform opioid-centered regimens [26].

Lu et al. conducted a systematic review of 98 randomized controlled trials (RCTs), encompassing a total of 7452 patients who underwent TKA. The study evaluated 18 different pain management strategies, with several analgesic methods analyzed through individual meta-analyses. Their findings demonstrated that local infiltration analgesia and peripheral nerve blocks significantly reduced postoperative pain intensity and morphine use, while also improving functional outcomes [27]. Furthermore, the use of multimodal analgesia has been shown to significantly reduce opioid use, enhance pain relief, increase patient satisfaction, facilitate quicker recovery, and shorten the duration of hospital stays [7, 8, 28]. Consequently, it is widely adopted in perioperative pain management for TKA.

Preemptive analgesia

Preemptive analgesia, first introduced by Wall, involves the administration of pain-relieving treatments prior to surgery [29]. The goal of this strategy is to minimize or prevent the peripheral and central sensitization that typically results from tissue injury, ultimately reducing the risk of hyperalgesia, decreasing the intensity of postoperative pain, and lowering the likelihood of developing chronic neuropathic pain [30]. Additionally, preemptive analgesia can help increase the pain threshold, which in turn reduces the need for postoperative analgesics [31]. However, the effectiveness of this approach can vary between individuals, as some patients may still experience moderate to severe pain following surgery. It is also important to consider potential side effects of certain medications, such as gastrointestinal or renal complications. Therefore, an individualized pain management plan, tailored to the patient’s overall health and specific needs, should be chosen. A variety of oral medications can be used to target different pathways involved in inflammation and nociception, providing effective pain relief and preventing the development of postoperative sensitization. These medications include opioids, acetaminophen, NSAIDs, selective COX-2 inhibitors, and gabapentinoids [32].

Systemic medications

Opioids

Opioids, known for their potent analgesic effects, are widely used to manage moderate to severe pain following TKA. These include conventional opioids, long-acting oral opioids, and transdermal opioid formulations [24, 33]. However, literature increasingly highlights the risks concerned with perioperative opioid consumption, including respiratory depression, constipation, drowsiness, nausea, and heightened potential for addiction [23]. Studies show that although opioids are effective in reducing pain immediately following TKA, their adverse effects can hinder recovery and decrease patient satisfaction [1]. For instance, excessive perioperative opioid use has been linked to longer hospital stays, delayed rehabilitation, and increased healthcare costs [34].

To mitigate these risks, current guidelines advocate for opioids as a secondary option within a multimodal analgesia framework, rather than the primary analgesic approach [6]. Research supports the effectiveness of multimodal strategies in reducing opioid requirements while achieving comparable pain control outcomes [12, 13]. A meta-analysis further indicates that such strategies effectively reduce opioid consumption and improve functional recovery, emphasizing that opioids should be reserved for breakthrough pain rather than routine postoperative management in TKA [27].

Acetaminophen

Acetaminophen is a commonly utilized analgesic for managing perioperative pain and is a critical part of multimodal pain management strategies. It is favored for its affordability, reliable effectiveness, minimal side effects, and its general safety profile [35]. While the exact mechanisms by which acetaminophen exerts its analgesic effects are not fully understood, research indicates it may act through multiple pathways, including serotonin, opioid, prostaglandin, and nitric oxide systems, with a primary action of inhibiting COX activity within the central nervous system [36]. Although considered safe when used appropriately, exceeding a daily dose of 4 g can result in liver toxicity.

In 2010, the U.S. Food and Drug Administration approved intravenous (IV) acetaminophen, which has garnered attention for its potential role in managing perioperative pain, particularly in joint replacement surgeries. IV acetaminophen offers higher bioavailability compared to its oral counterpart; however, oral administration remains more economical [37]. A RCT involving patients undergoing joint replacements found no significant difference in analgesic outcomes between IV and oral acetaminophen [36]. Similarly, two meta-analyses evaluating postoperative pain relief following joint replacement also reported no notable difference between the two forms in terms of pain reduction or length of hospital stay [38]. However, one of these studies did observe a reduction in early postoperative morphine use in patients receiving IV acetaminophen [39], which suggests that further research into the cost-effectiveness of IV administration may be beneficial. Current clinical recommendations favor IV acetaminophen primarily for patients who are unable to tolerate oral formulations.

NSAIDs and selective COX-2 inhibitors

NSAIDs exert their analgesic effects by inhibiting the COX-1 and COX-2 enzymes, with a stronger preference for COX-1. This action decreases prostaglandin production, which is responsible for sensitizing afferent nerve fibers and contributing to pain [32]. COX-1 is widely distributed throughout the body, whereas COX-2 is predominantly found in areas of inflammation. To reduce the adverse effects associated with COX-1 inhibition, such as gastrointestinal bleeding, ulcers, and renal dysfunction, selective COX-2 inhibitors (e.g., celecoxib) were developed to target the inflammation more specifically [40].

Numerous prospective studies have assessed the effectiveness of selective COX-2 inhibitors in pain management. These studies consistently show that COX-2 inhibitors are more effective than placebo in managing postoperative pain following TKA, supporting their role in multimodal pain management regimens. Additionally, one study found that initiating COX-2 inhibitors early in the postoperative period led to better pain control and improved functional recovery [41, 42]. Another trial comparing preoperative intravenous administration of NSAIDs, including diclofenac and ketorolac, with a placebo, demonstrated that preoperative use of COX-2 inhibitors or NSAIDs significantly reduced postoperative pain intensity and opioid consumption, while also decreasing the incidence of side effects typically associated with NSAIDs use [43]. These findings emphasize the efficacy of COX-2 inhibitors in managing pain with fewer complications compared to traditional NSAIDs.

Gabapentinoids

Gabapentinoids, such as pregabalin and gabapentin, are primarily prescribed for seizures, neuropathic pain, and fibromyalgia but have been recently incorporated into multimodal analgesia protocols to reduce opioid use. the exact mechanism is not completely understood, but gabapentinoids are believed to reduce postoperative central sensitization and inflammation, potentially by binding to subunits of presynaptic calcium channels [44].

The literature on perioperative gabapentinoid efficacy is mixed. A prospective study on gabapentinoid use after TKA found no significant differences in opioid use, pain at rest or during ambulation, or hospital stay [45], raising questions about their utility in TKA. However, a meta-analysis reported that preoperative pregabalin reduced postoperative morphine requirements [46]. An RCT evaluating pregabalin for TKA found that pregabalin had no beneficial effect on pain improvement and may lead to an increase in sedation [47]. While gabapentinoids may cause drowsiness, potentially delaying recovery and decreasing patient satisfaction [44, 47], they may still benefit specific patients.

Corticosteroids

Corticosteroids are widely recognized for their potent anti-inflammatory properties, which help alleviate postoperative pain by modulating various inflammatory pathways and lowering the levels of acute-phase proteins such as interleukin-6 and C-reactive protein [40, 48]. Additionally, they contribute to reducing the incidence of postoperative nausea and vomiting through their effects on the central nervous system [49]. Numerous systematic reviews and meta-analyses have shown that the use of corticosteroids in the perioperative period for joint replacement surgeries can significantly enhance pain relief, decrease the need for opioids, and reduce the occurrence of nausea [50]. In a recent RCT, patients who received two doses of dexamethasone perioperatively reported notably higher satisfaction six weeks after surgery [51].

Despite these benefits, corticosteroid use is associated with potential risks, particularly in terms of increasing the likelihood of postoperative infections. However, studies on this topic remain mixed. For instance, a large retrospective analysis involving more than 18,000 patients undergoing primary joint replacements found no significant difference in infection rates between those who received systemic dexamethasone and those who did not [52]. This suggests that while corticosteroids may have certain risks, their use in the appropriate context may not necessarily result in an increased infection risk.

N-Methyl-d-aspartate (NMDA) receptor antagonists

NMDA receptor antagonists, such as ketamine, have gained attention in TKA for their role in modulating central sensitization and reducing postoperative pain. NMDA antagonists work by blocking glutamate-mediated excitatory pathways, which are often activated in response to surgical trauma, thus potentially minimizing the development of hyperalgesia and opioid tolerance [53].

Recent research indicates that NMDA antagonists, especially when combined with multimodal analgesia strategies, can be effective in reducing opioid use and improving pain management after TKA. A systematic review revealed that administering low-dose ketamine perioperatively resulted in lower postoperative pain scores and reduced opioid consumption, without causing significant side effects like hallucinations or sedation [54]. However, a more recent RCT found that intraoperative ketamine did not lead to a clinically meaningful improvement in pain management or opioid use following TKA [55]. As a result, further studies are still needed to determine the optimal dosing, timing, and overall effectiveness of ketamine in TKA pain management.

Local infiltration analgesia

Local infiltration analgesia (LIA) is a widely employed technique for pain management in orthopedic procedures, particularly in joint replacement surgeries. Its popularity stems from its simplicity, cost-effectiveness, and reliable pain-relieving properties with minimal side effects. LIA involves administering a mixture of local anesthetics and adjuvants—such as opioids, neuromodulators, corticosteroids, and NSAIDs—via multiple injections directly into the surgical site [35, 56]. This cocktail helps target the painful areas around the joint, particularly those with high concentrations of free nerve endings. Local anesthetics work by blocking voltage-gated sodium channels on nociceptors, which reduces the transmission of pain signals to the brain [20].

Ropivacaine, a long-acting amide-type local anesthetic, has become a preferred choice for LIA due to its ability to selectively block sensory nerves while sparing motor function. Varying concentrations of ropivacaine produce different effects: lower doses primarily block sensory nerves with minimal impact on motor function, making it particularly suitable for procedures like TKA, which require postoperative functional rehabilitation [57]. Additionally, ropivacaine is considered safer than bupivacaine because it has a lower risk of cardiovascular and central nervous system toxicity. As a result, ropivacaine is the preferred local anesthetic in LIA [58].

Several studies support the use of LIA in joint replacement surgeries, demonstrating its effectiveness in improving pain control and reducing opioid consumption in the perioperative period [59]. A meta-analysis comparing LIA to placebo or non-infiltration approaches revealed significant reductions in both pain scores and opioid use [60]. Adding agents such as codeine to the LIA cocktail has also been shown to further reduce opioid consumption and shorten hospital stays after TKA [28]. Moreover, incorporating corticosteroids, such as methylprednisolone, into the mixture has been shown to enhance pain relief and improve functional recovery on the first postoperative day [61]. Research has also highlighted the benefit of combining ropivacaine with both codeine and morphine, which significantly improves pain control and decreases opioid use compared to using ropivacaine alone [62].

In recent years, liposomal bupivacaine (LB) has been explored as a longer-acting alternative to traditional local anesthetics in joint replacement surgeries. Although some studies suggest that LB can provide extended pain relief [63], other RCTs have found no significant advantages over standard bupivacaine in terms of postoperative pain management or opioid reduction [64, 65]. Meta-analyses comparing LB to other local infiltration cocktails in TKA surgeries have also shown no clear benefit in pain control or recovery, although one study did report a reduction in opioid use among patients receiving LB [66]. While LB extends analgesia in some cases, its high cost and lack of clear benefits in clinical trials have limited its widespread adoption.

Compared to peripheral nerve blocks, LIA is simpler to perform and provides satisfactory postoperative pain relief without affecting muscle strength or causing opioid-related complications [21, 67, 68]. However, the commonly used LIA cocktail formulations often fall short in providing adequate pain relief after TKA. One limitation of LIA is its relatively short duration of action, typically lasting no more than 10 to 18 h, due to the short half-life of the local anesthetics used, which prevents sustained analgesia [67]. Recent research has sought to extend the duration of analgesia by adding two novel adjuvants, sodium bicarbonate and magnesium sulfate, to the standard cocktail. Animal studies demonstrated good safety for the modified cocktail, while clinical trials showed that it significantly prolonged pain relief, reduced opioid use, improved knee joint function recovery, shortened hospital stays, and led to no notable complications [69].

Current research continues to explore ways to enhance the duration and effectiveness of LIA. While various combinations of agents are described in the literature, there is no consensus on the optimal cocktail formulation, injection sites, or dosage. These variables often depend on the surgeon's experience, which leads to inconsistency in techniques across different institutions [69]. As such, there is a clear need for standardized guidelines to optimize the use of LIA in clinical practice.

Peripheral nerve blocks

Femoral nerve block

The femoral nerve block (FNB) is a commonly employed method for managing postoperative pain following TKA. This technique involves the injection of a local anesthetic near the femoral nerve to block its sensory branches, providing effective pain relief. However, one of the notable drawbacks of FNB is its potential to induce motor blockade, which can lead to weakness in the quadriceps muscle, delayed ambulation, and a heightened risk of falls [70]. Despite these concerns, FNB has been extensively studied, and the majority of research supports its efficacy in alleviating pain after TKA [71, 72]. For instance, a recent meta-analysis comparing single-injection FNB with patient-controlled analgesia alone found that FNB offered superior early postoperative pain relief and significantly reduced opioid consumption [73].

To prolong the analgesic effects of a single-injection FNB, the continuous femoral nerve block technique has been developed. This method involves the use of a catheter placed at the FNB site, which continuously administers local anesthetic postoperatively. Several RCTs have examined the effectiveness of continuous FNB and found that it does not provide a significant advantage over the single-injection approach [74]. While both techniques offer substantial pain relief, continuous FNB may lead to prolonged motor blockade, which can negatively affect quadriceps strength and slow down the rehabilitation process. Additionally, the use of a catheter introduces the risk of complications such as dislodgement, kinking, or infection, and managing these catheters requires additional healthcare resources [75]. As a result, it is recommended to implement preventive strategies, including identifying high-risk patients and conducting thorough fall risk assessments, to minimize complications associated with FNB.

Sciatic nerve block

The sciatic nerve block (SNB) is frequently used alongside the FNB to provide comprehensive pain relief following TKA, as the sciatic nerve covers the posterior knee region, an area that FNB alone cannot effectively anesthetize. Recent studies have explored the benefits of combining SNB with FNB for enhanced postoperative pain management. An RCT compared single-injection SNB with FNB and found that patients who received the combined approach required less opioid medication during the first 8 h after surgery. However, the study also noted that functional outcomes on the first postoperative day were poorer in these patients [74].

Another RCT assessed the effects of single-injection versus continuous SNB, revealing that both approaches were effective in reducing knee pain and minimizing early opioid consumption. Continuous SNB, in particular, offered a longer duration of pain relief [76]. Despite its benefits, SNB can also have some unintended consequences, such as impairing foot dorsiflexion and plantarflexion. This restriction in movement could potentially obscure the clinical detection of intraoperative peroneal nerve injury, which occurs in a small percentage of patients (ranging from 0.3 to 4%) [15]. Therefore, it is important to consider the potential impact of SNB on both pain management and the risk of nerve-related complications following TKA.

Adductor canal block

The adductor canal is home to several important nerves, including the saphenous nerve, the nerve to the vastus medialis, and other smaller sensory branches that serve the knee joint. While the nerve to the vastus medialis is motor in nature, the other nerves in the canal are primarily sensory, which gives the adductor canal block (ACB) a potential advantage over the FNB. Several studies have indicated that ACB can provide similar levels of pain relief as FNB, while also preserving quadriceps function for approximately 6–8 h postoperatively [70, 77]. Two recent RCTs compared ACB with periarticular multimodal injections, but their results were mixed. One study found that ACB significantly reduced morphine consumption, although there were no notable differences in pain scores compared to the periarticular injection group [78]. In contrast, another trial reported higher pain scores in the ACB group but highlighted the advantage of shorter surgical times in the ACB group compared to the periarticular approach [79].

As with FNB, research into the different methods of administering ACB, including continuous, intermittent, and single-injection techniques, has yielded inconsistent results regarding their effectiveness in pain management and opioid reduction [80, 81]. A key factor influencing the overall efficacy of ACB is that it only anesthetizes the sensory nerves on the anteromedial aspect of the knee, leaving the posterolateral sensory nerves intact. This limitation has led to ongoing debate about the comprehensive analgesic benefits of ACB in comparison to other nerve blocks [82].

IPACK block (interspace between the popliteal artery and the posterior capsule of the knee)

To overcome the limitations of the SNB, the IPACK block was introduced as a new peripheral nerve block technique. This procedure involves the injection of a local anesthetic behind the knee, specifically targeting the terminal branches of the sciatic nerve. One of the primary advantages of the IPACK block is its ability to provide effective analgesia to the posterior knee without affecting the saphenous or common peroneal nerves, which are often involved in other nerve blocks [83, 84]. Additionally, the IPACK block addresses the shortcomings of the ACB, particularly its inability to provide analgesia to the posterolateral knee. When combined with ACB, the IPACK block enhances overall pain relief and facilitates improved ambulation.

Research supports the use of the IPACK block as a viable alternative to SNB, with studies showing that it offers effective posterior knee pain management while preserving lower limb muscle strength [83–85]. A prospective study highlighted the benefits of combining the IPACK block with ACB for TKA, demonstrating significantly improved postoperative pain control and greater walking distances for patients following surgery [86].

Epidural analgesia

Epidural analgesia, once a common approach for pain control in TKA, involves administering a continuous infusion of anesthetic and opioid directly into the epidural space. Epidural analgesia provides potent and long-lasting pain relief [87]; however, its use has declined with the rise of peripheral nerve blocks and LIA due to associated risks, such as urinary retention, hypotension, and delayed mobilization [88]. In patients with contraindications to other methods, epidural analgesia remains an option.

RCTs comparing epidural analgesia with peripheral nerve blocks indicate that while both methods offer effective pain control, nerve blocks tend to have fewer adverse effects and allow for faster ambulation and recovery [89]. As a result, epidural analgesia is now reserved for specific cases where other techniques are ineffective or unsuitable.

Patient-controlled analgesia

Patient-controlled analgesia (PCA) is a system that allows patients to administer their own analgesics by pressing a button, typically delivering small, controlled doses of medication when needed. Previously, this approach has been widely used to treat post-TKA pain. Commonly, PCA systems use opioids such as oxycodone, morphine, fentanyl, and hydromorphone to provide pain relief [90, 91]. Despite its effectiveness, the use of PCA has declined due to the potential for opioid-related side effects. These include nausea, vomiting, respiratory depression, and urinary retention, which can complicate recovery and lead to increased risk during the perioperative period of TKA. As a result, there has been a shift towards alternative pain management strategies that minimize these adverse effects. In contrast, enhanced recovery protocols and multimodal analgesia approaches have become more popular. A recent RCT comparing PCA with periarticular injections found that although functional recovery was similar between the groups, PCA patients had significantly higher antiemetic requirements and pain scores two weeks postoperatively [92]. As TKA hospital stays have shortened and outpatient surgeries have become more common, the role of PCA has gradually diminished.

In addition to traditional oral or topical analgesics, various local analgesic methods are integral to postoperative pain management for TKA. Periarticular injections using multimodal drug mixtures provide both intraoperative preventive analgesia and postoperative pain relief. Different local block techniques also offer effective pain control, although they may impact local muscle and nerve function, and some techniques may need to be combined for optimal results. Traditional PCA, while effective systemically, is associated with numerous adverse effects, which limits its application (Table 1).

Table 1.

Common pain management measures for TKA

Technique	Benefit	Limitation	Recommended use
LIA [21, 35, 56, 67–69]	Immediate localized analgesia, minimal motor impairment	Limited duration of effect	Effective in early postoperative period, combined in multimodal regimens
FNB [70–75]	Effective pain relief, reduced opioid use	Risk of motor blockade, delayed ambulation	Standard for TKA, balanced with other techniques
SNB [15, 74, 76]	Complements FNB, covers posterior knee	May obscure peroneal nerve injury symptoms	Combined with FNB for comprehensive coverage
ACB [70, 77–82]	Preserves quadriceps strength, comparable to FNB in pain relief	Limited posterior knee coverage	Alternative to FNB when quadriceps preservation is needed
IPACK block [83–86]	Posterior knee analgesia without motor impact	Does not cover entire knee	Combined with ACB to cover posterolateral knee
Epidural Analgesia [87–89]	Potent and lasting analgesia	Hypotension, urinary retention, delayed recovery	Reserved for patients unable to use other techniques
PCA [90–92]	Definitive analgesic effect	Adverse effects such as nausea, respiratory depression, constipation, and urinary retention	Not routinely recommended in ERAS

TKA total knee arthroplasty, LIA local infiltration analgesia, FNB femoral nerve block, SNB sciatic nerve block, ACB adductor canal block, IPACK interspace between the popliteal artery and the posterior capsule of the knee, PCA patient-controlled analgesia, ERAS enhanced recovery after surgery

Nonpharmacological strategies

Multimodal analgesia protocols encompass a variety of approaches, combining both pharmacological and nonpharmacological strategies to optimize pain control. In addition to medications, techniques like cryotherapy, electrotherapy, acupuncture, and peripheral nerve stimulation have shown promise in improving pain management outcomes. Cryotherapy, for instance, is frequently used to reduce postoperative pain and swelling. It works by constricting blood vessels, which in turn limits the release of inflammatory mediators. Research has demonstrated that postoperative cryotherapy significantly reduces pain levels and the need for opioid medications following TKA procedures [93]. Similarly, peripheral nerve stimulation, which involves applying mild electrical impulses to nerves, has emerged as a potential tool for enhancing analgesia and promoting faster recovery. Studies indicate that this technique can improve pain relief and speed up the rehabilitation process [94].

Additionally, minimizing the duration of tourniquet use during surgery has been shown to alleviate postoperative pain and swelling. Several studies have indicated that shorter application times for the tourniquet result in better patient outcomes, including reduced pain intensity and faster recovery of joint function [95]. When incorporated into multimodal analgesia protocols, these nonpharmacological methods contribute to more effective pain management, improving both the overall recovery experience and long-term outcomes for patients undergoing TKA.

Conclusions

As the global population continues to age, the incidence of TKA is expected to increase significantly. Effective pain management is a crucial aspect of TKA, playing a key role in enhancing recovery, improving patient satisfaction, and optimizing overall healthcare outcomes. Multimodal analgesia has emerged as the standard approach for perioperative pain control in TKA, providing more effective pain relief with fewer adverse effects compared to opioid-based therapies. This method not only supports quicker recovery but also helps minimize opioid consumption.

The optimal strategy for multimodal analgesia ideally begins before surgery and continues throughout the perioperative period, extending into the post-discharge phase. A combination of oral and intravenous medications—including NSAIDs, selective COX-2 inhibitors, corticosteroids, gabapentinoids, acetaminophen, and opioids—can be utilized both before and after surgery to control pain effectively. In addition to pharmacological interventions, techniques like peripheral nerve blocks and periarticular local infiltration analgesia are valuable in managing postoperative pain and should be coordinated with the anesthesia team. Nonpharmacological methods, such as cryotherapy and physical therapy, should also be considered as part of the overall pain management plan.

Despite the growing adoption of multimodal analgesia, there is still no universally agreed-upon protocol for its implementation. Practices vary widely between healthcare institutions, underscoring the need for further studies to identify and standardize the most effective multimodal strategies for TKA patients.

Abbreviations

TKA

Total knee arthroplasty

NMDA

N-Methyl-d-aspartate

COX

Cyclooxygenase

NSAIDs

Nonsteroidal anti-inflammatory drugs

RCT

Randomized controlled trial

IV

Intravenous

LIA

Local infiltration analgesia

LB

Liposomal bupivacaine

FNB

Femoral nerve block

SNB

Sciatic nerve block

ACB

Adductor canal block

IPACK

Interspace between the popliteal artery and the posterior capsule of the knee

PCA

Patient-controlled analgesia

Author contributions

All authors contributed to planning, analysis of various papers and writing and concluding the paper.

Funding

No funding was obtained for this study.

Availability of data and materials

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.