Pain control strategies after total knee arthroplasty (TKA) have significantly evolved over the last three decades. The 1980s heralded the conception of intramuscular narcotic injection, followed by patient-controlled analgesic pumps in the 1990s [1]. In the mid-2000s, driven in part by early rehabilitation protocols and faster discharge from the hospital, there was a shift toward multimodal analgesia protocols and avoidance of narcotic medications. Currently, most regiments include a combination of multimodal oral medications and Periarticular Injection (PAI) with a selective motor-sparing nerve block, such as adductor canal nerve blocks (ACB) [1].

Peripheral nerve blocks (PNB) are commonly used in TKA as a means of adjunctive analgesia. Sensory innervation of the knee originates anteriorly from the femoral nerve, and posteriorly from the posterior cutaneous nerve of the thigh emanating from the sciatic nerve. Additionally, variable contributions from the saphenous nerve and the lateral femoral cutaneous nerve provide sensory innervation to the medial and lateral aspects of the knee, respectively [1, 2]. These nerves and their respective tributaries are common targets for peripheral nerve blockade. PNBs have the purported benefit of reducing hospital Length Of Stay (LOS), allowing for earlier participation in post-operative physical therapy, as well as reducing opioid consumption and the side-effects associated with such medications [3-5]. Furthermore, compared to epidural anesthesia, a reduction in the risk of post-operative hypotension and urinary retention has been observed [6].

Historically, Femoral Nerve Blocks (FNB) have been the mainstay of PNBs performed for TKA [2]. The resultant effect consists of both a motor and sensory blockade through the diffusion of a local anesthetic to the femoral, lateral femoral cutaneous, and obturator nerves. The term “three-in-one block” has been coined to describe the FNB. The resultant anesthetic effect is localized to the anterior, lateral, and medial aspects of the knee. Overall, FNBs have demonstrated to provide excellent analgesia, especially when combined with a Sciatic Nerve Block (SNB) [7, 8]. In a recent Cochrane review, FNBs were found to provide similar analgesic effect and greater patient satisfaction, while reducing post-operative nausea and vomiting when compared to epidural anesthesia [9]. The resultant motor blockade associated with FNBs, however, leads to profound quadriceps weakness [10, 11]. This inhibition has been associated with a slower post-operative rehabilitation process and a risk of falls estimated at 7% [11]. Furthermore, in a study by Sharma et al, the risk of reoperation secondary to falls in the post-operative period was noted to be 0.4% [12]. Lastly, when an SNB is utilized in conjunction with an FNB, the resultant analgesic effect to the heel can place patients at risk of developing pressure ulcers if precautionary measures are not ensured during the post-operative period [13, 14].

ACBs are performed under ultrasound guidance and affect the peripheral nerves within the adductor canal: the saphenous nerve, articular branches of the obturator nerve, medial retinacular nerve, and nerve to vastus medialis [2]. The use of ACB has gained popularity, especially with the push towards outpatient TKA, as it provides a good analgesic effect on the anteromedial aspect of the knee with minimal motor blockade [10]. In a randomized, double-blind, placebo-controlled study by Jaeger et al., FNBs and ACBs using ropivacaine were compared for quadriceps weakness. The authors noted that in healthy volunteers, the adductor canal block reduced quadriceps strength by only 8% compared with 49% who received a femoral nerve block [10]. Furthermore, a reduction in the early post-operative visual analogue scale scores and opioid consumption was noted, whereas early mobility at one- and six-hours post-blockade was improved for patients having undergone an ACB compared to an FNB. However, ACBs, similar to FNBs, do not provide analgesia to the posterior capsule of the knee. Therefore, a combination of ACB and PAI is often employed to supplement deficiencies in analgesic coverage. Results of such a combination, although intuitively logical, have demonstrated mixed results [15]. Significant variation in PAI technique and location is likely to play a role in the varied results [16]. Recent interest in infiltration between the popliteal artery and capsule of the knee (IPACK) to provide additional, targeted analgesia to the posterior aspect of the knee has demonstrated promising early results [17-19].

Nerve sensation to the knee is in part provided by the femoral, saphenous, obturator, common peroneal, and tibial nerves. The current literature would suggest that 45-80% of nerve fibers in the knee are nociceptors [20]. Furthermore, numerous studies have looked at the nociceptor anatomic distribution in the knee. Biedert et al., performed a histologic survey of 8 human cadaveric knees in order to identify nociceptor density within the various structures of the knee and found the highest concentrations were located in the medial and lateral retinacula, patellar tendon, pes anserinus, and meniscofemoral ligaments [21]. Other studies have identified the capsule and periosteum as a pain generator when interrogated during arthroscopy in awake participants [22].

The pharmacology of PAI cocktails has been studied extensively. Injections are usually a mixture of a long-acting anesthetic, NSAIDs, and epinephrine as a base. The addition of corticosteroids has been more variable. Chia et al., randomized patients to receive either a conventional cocktail without corticosteroids or cocktails containing various dosages of corticosteroids [23]. No difference was noted among groups. Kulkarni et al., however, demonstrated a reduction in visual analogue scale (VAS) scores at 24hrs and 72hrs after surgery with the addition of methylprednisolone to PAI in TKA [24]. Furthermore, they noted an increase in post-operative flexion, as well as an increase in inflammatory signs in those patients receiving corticosteroid infiltration [24]. The addition of morphine to PAIs has also been studied. Iwakiri et al., randomized patients to receive periarticular cocktails with and without morphine and demonstrated similar VAS scores between groups, with an increase in the number of vomiting episodes, and the total dose of antiemetic drugs in patients receiving morphine [25].

The evolution of pain control strategies has shifted toward local and regional pain control. ACBs have become more popular due to equivalent pain control and decreased motor blockade as compared to FNBs [1]. Grosso et al., performed a study randomizing patients to receive ACB alone, PAI alone, or ACB plus PAI [26]. Patients that received ACB alone had higher pain scores and increased opioid consumption versus patients who received PAI alone or PAI plus ACB. The latter two were found to have equivalent pain scores. Similar outcomes have been noted in the anesthesia literature. Sawhney et al., performed an RCT with three groups of patients identical to that of Grosso et al., and found similar results with patients undergoing ACB alone having increased pain scores [27].

The introduction of liposomal bupivacaine (LB), was initially approved for use in surgical wounds to provide postoperative analgesia. The efficacy of LB over traditional bupivacaine is yet unproven due to differences in study design, methodology, infiltration techniques, etc. The PILLAR study attempted to reconcile confounding variables that may have contributed to inconsistent results and randomized two sets of patients undergoing TKA to receive standard bupivacaine versus LB [28]. Using robust statistics, the authors were able to show a significant difference in improved pain control in patients receiving the liposomal bupivacaine cocktail. However, a large systematic review and meta-analysis failed to provide a true clinical benefit for the use of liposomal bupivacaine in either PAIs or PNBs [29].

There has been a strong impetus in the orthopedic community and elsewhere to provide opioid-sparing analgesia in surgical patients. As a result, there has been an emphasis on administering care in the context of multimodal pain control with periarticular injections and nerve blocks being important elements in many protocols. PNBs and PAI play an important role in the mitigation of post-operative pain, with the ideal therapy providing robust analgesia, minimal risk of adverse events, and allowing for early engagement in post-operative rehabilitation. Current evidence appears to suggest that a combination of an ACB supplemented by posterior capsular analgesic coverage through PAI or IPACK may provide optimal results.