Pain Management in TKA: Periarticular Injections and Peripheral Nerve Blocks
Most multimodal pain control regimens for total knee arthroplasty patients include a combination of oral medications, periarticular injection of anesthetics and/or analgesics, and selective motor-sparing nerve blocks. What is the evidence for this approach?
Alexander Gaukhman, MD; Simon Garceau, MD; Ran Schwarzkopf, MD, MSc; and James Slover, MD, MS
Strategies for pain control following total knee arthroplasty (TKA) have significantly evolved over the last 3 decades: 
- The 1980s saw a rise in the use of intramuscular injections of narcotics.
- In the 1990s, the patient-controlled analgesia pump was often the modality of choice for managing postoperative pain.
- By the 2000s, surgeons had shifted toward protocols that minimized the use of opioids, driven in part by early rehabilitation protocols and faster discharge from the hospital.
Today, most multimodal pain control regimens include a combination of oral medications, periarticular injection (PAI) of anesthetics and/or analgesics, and selective motor-sparing nerve blocks. 
Pros and Cons of Peripheral Nerve Blocks
Peripheral nerve blocks (PNB) are commonly used in TKA for 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. In addition, 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.
The use of PNBs has the purported benefit of: [3-5]
- Reduced hospital length of stay (LOS)
- Earlier participation in postoperative physical therapy
- Decreased opioid consumption, as well as fewer side effects associated with these drugs
Compared with epidural anesthesia, the use of PNBs has been observed to reduce the risk of postoperative hypotension and urinary retention. 
Femoral nerve blocks (FNB) have historically been the mainstay of PNBs performed for TKAs,  providing motor and sensory blockade through diffusion of local anesthetic to the femoral, lateral femoral cutaneous, and obturator nerves. The term “3-in-1 block” has been coined to describe FNBs. The resultant anesthetic effect is localized to the anterior, lateral, and medial aspects of the knee.
Overall, FNBs offer excellent analgesia, especially when combined with a sciatic nerve block (SNB). [7,8] Compared with epidural anesthesia, FNBs have been found to provide a similar analgesic effect, greater patient satisfaction, and reduced postoperative nausea and vomiting. 
The motor blockade associated with FNBs, however, leads to profound quadriceps weakness, [10,11] which has been associated with a slower postoperative rehabilitation process and an estimated 7% risk of falls.  Sharma et al  reported a 0.4% risk of reoperation secondary to falls in the postoperative period in patients who had received an FNB. When an SNB is utilized in conjunction with an FNB, the anesthetic effect to the heel can put patients at risk for pressure ulcers if precautionary measures are not ensured during the postoperative period. [13-14]
Adductor canal blocks (ACB) 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.  The use of ACBs has gained popularity, especially with the push toward outpatient TKA, as they provide good analgesic effect to the anteromedial aspect of the knee with minimal motor blockade. 
In a randomized, double-blind, placebo-controlled study, Jaeger et al  compared quadriceps weakness in healthy volunteers who received either an ACB or an FNB using ropivacaine. They noted an 8% versus 49% reduction in quadriceps strength, respectively, up to 6 hours after surgery, as well as a reduction in early postoperative visual analog scale (VAS) scores and opioid consumption in the ACB group.  Early mobility at 1 and 6 hours post-blockade was improved in the ACB group compared with the FNB group. 
However, similar to FNBs, ACBs do not provide analgesia to the posterior capsule of the knee. Therefore, a combination of an ACB and PAI is often employed to supplement deficiencies in analgesic coverage. Although this combination is intuitively logical, study results have been mixed,  likely related to significant variation in PAI technique and location.  Infiltration between the popliteal artery and the capsule of the knee (IPACK) has demonstrated promising early results in providing additional targeted analgesia to the posterior aspect of the knee. [17-19]
Periarticular Injections: Where and What to Inject
Nerve sensation to the knee is, in part, provided by the femoral, saphenous, obturator, common peroneal, and tibial nerves. The current literature suggests that 45% to 80% of nerve fibers in the knee are nociceptors.  Numerous studies have investigated nociceptor anatomic distribution in the knee. In a histologic survey of 8 human cadaveric knees, Biedert et al  sought to identify nociceptor density within the various structures of the knee. They found the highest concentrations in the medial and lateral retinacula, patellar tendon, pes anserinus, and meniscofemoral ligaments.  Other studies have identified the capsule and periosteum as a pain generator. 
The pharmacology of PAI cocktails has been studied extensively. Injections are usually a mixture of a long-acting anesthetic, non-steroidal anti-inflammatory drugs, and epinephrine as a base. The addition of corticosteroids has had variable results. Chia et al  randomized patients to receive either a conventional cocktail without corticosteroids or cocktails containing various dosages of corticosteroids. They noted no difference among groups.
Kulkarni et al,  however, demonstrated a reduction in VAS scores at 24 and 72 hours after surgery with the addition of methylprednisolone to PAI in patients undergoing TKA. They also noted an increase in postoperative flexion and an increase in inflammatory signs in patients who received corticosteroid infiltration. 
The addition of morphine to PAIs has also been studied. Iwakiri et al  randomized patients to receive periarticular cocktails with or without morphine. They found similar VAS scores between groups, but an increase in the number of vomiting episodes and the total dose of antiemetic drugs in patients who had received morphine. 
Liposomal bupivacaine was initially approved for use in surgical wounds to provide postoperative analgesia. The efficacy of liposomal bupivacaine over traditional bupivacaine in periarticular injection has yet to be proven due to differences in study design, methodology, and infiltration techniques, among others.
The PILLAR study has attempted to reconcile confounding variables that may have contributed to inconsistent results, randomizing 2 sets of patients undergoing TKA to receive standard bupivacaine versus liposomal bupivacaine.  Using robust statistics, the study authors were able to show a significant improvement in pain control among patient receiving the liposomal bupivacaine cocktail.
However, a large systematic review and meta-analysis failed to show a true clinical benefit for the use of liposomal bupivacaine in either PAIs or PNBs. 
Peripheral Nerve Blocks versus Periarticular Injection
As mentioned above, ACBs have become more popular due to equivalent pain control and decreased motor blockade when compared with FNBs.  Periarticular injections are also being used more frequently as part of a multimodal pain control strategy.  Is one more effective than the other in managing postoperative pain following TKA?
In a study by Grosso et al,  patients were randomized to receive ACB alone, PAI alone, or ACB plus PAI. Patients who received ACB alone had higher pain scores and increased opioid consumption compared with patients who received PAI alone or PAI plus ACB. The latter 2 groups had equivalent pain scores. 
Similar outcomes have been noted in the anesthesia literature. Sawhney et al  randomized patients to the same interventions as Grosso et al,  with similar results: Patients receiving an ACB alone had greater pain scores than patients in the other 2 intervention groups.
With the ongoing opioid crisis in the US, the orthopaedic community has a strong impetus to provide opioid-sparing analgesia to surgical patients. The result has been an emphasis on administering care in the context of multimodal pain control, with PAIs and PNBs being key elements in many protocols. These modalities play an important role in the mitigation of postoperative pain in TKA patients, with the ideal therapy providing robust analgesia with minimal risk of adverse events and allowing for early engagement in postoperative rehabilitation. Current evidence suggests that an ACB supplemented by a PAI or IPACK for posterior capsular analgesic coverage may provide optimal results.
Alexander Gaukhman, MD; Simon Garceau, MD; Ran Schwarzkopf, MD, MSc; and James Slover, MD, MS, are from the Division of Orthopedics, Adult Joint Reconstruction, at NYU Langone Health, New York, New York.
Disclosures: Dr. Gaukhman, Dr. Garceau, and Dr. Schwarzkopf have no disclosures relevant to this article. Dr. Slover has disclosed that he is a paid consultant for Horizon Pharma.
- Chung AS, Spangehl MJ. Peripheral Nerve Blocks vs Periarticular Injections in Total Knee Arthroplasty. J Arthroplasty. 2018;33(11):3383-8.
- Moucha CS, Weiser MC, Levin EJ. Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty. J Am Acad Orthop Surg. 2016;24(2):60-73.
- Lund J, Jenstrup MT, Jaeger P, Sørensen AM, Dahl JB. Continuous adductor-canal-blockade for adjuvant post-operative analgesia after major knee surgery: preliminary results. Acta Anaesthesiol Scand. 2011;55(1):14-9.
- Jenstrup MT, Jæger P, Lund J, Fomsgaard JS, Bache S, Mathiesen O, et al. Effects of adductor-canal-blockade on pain and ambulation after total knee arthroplasty: a randomized study. Acta Anaesthesiol Scand. 2012;56(3):357-64.
- Macfarlane AJ, Prasad GA, Chan VW, Brull R. Does regional anesthesia improve outcome after total knee arthroplasty? Clin Orthop Relat Res. 2009;467(9):2379-402.
- Fowler SJ, Symons J, Sabato S, Myles PS. Epidural analgesia compared with peripheral nerve blockade after major knee surgery: a systematic review and meta-analysis of randomized trials. Br J Anaesth. 2008;100(2):154-64.
- Abdallah FW, Brull R. Is sciatic nerve block advantageous when combined with femoral nerve block for postoperative analgesia following total knee arthroplasty? A systematic review. Reg Anesth Pain Med. 2011;36(5):493-8.
- Abdallah FW, Madjdpour C, Brull R. Is sciatic nerve block advantageous when combined with femoral nerve block for postoperative analgesia following total knee arthroplasty? a meta-analysis. Can J Anaesth. 2016;63(5):552-68.
- Chan EY, Fransen M, Parker DA, Assam PN, Chua N. Femoral nerve blocks for acute postoperative pain after knee replacement surgery. Cochrane Database Syst Rev. 2014(5):CD009941.
- Jaeger P, Nielsen ZJ, Henningsen MH, Hilsted KL, Mathiesen O, Dahl JB. Adductor canal block versus femoral nerve block and quadriceps strength: a randomized, double-blind, placebo-controlled, crossover study in healthy volunteers. Anesthesiology. 2013;118(2):409-15.
- Ilfeld BM, Shuster JJ, Theriaque DW, Mariano ER, Girard PJ, Loland VJ, et al. Long-term pain, stiffness, and functional disability after total knee arthroplasty with and without an extended ambulatory continuous femoral nerve block: a prospective, 1-year follow-up of a multicenter, randomized, triple-masked, placebo-controlled trial. Reg Anesth Pain Med. 2011;36(2):116-20.
- Sharma S, Iorio R, Specht LM, Davies-Lepie S, Healy WL. Complications of femoral nerve block for total knee arthroplasty. Clin Orthop Relat Res. 2010;468(1):135-40.
- Todkar M. Sciatic nerve block causing heel ulcer after total knee replacement in 36 patients. Acta Orthop Belg. 2005;71(6):724-5.
- Apsingi S, Dussa CU. Can peripheral nerve blocks contribute to heel ulcers following total knee replacement? Acta Orthop Belg. 2004;70(5):502-4.
- Hinarejos P, Capurro B, Santiveri X, Ortiz P, Leal J, Pelfort X, et al. Local infiltration analgesia adds no clinical benefit in pain control to peripheral nerve blocks after total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2016;24(10):3299-305.
- Sardana V, Burzynski JM, Scuderi GR. Adductor Canal Block or Local Infiltrate Analgesia for Pain Control After Total Knee Arthroplasty? A Systematic Review and Meta-Analysis of Randomized Controlled Trials. J Arthroplasty. 2019;34(1):183-9.
- Kim DH, Beathe JC, Lin Y, YaDeau JT, Maalouf DB, Goytizolo E, et al. Addition of Infiltration Between the Popliteal Artery and the Capsule of the Posterior Knee and Adductor Canal Block to Periarticular Injection Enhances Postoperative Pain Control in Total Knee Arthroplasty: A Randomized Controlled Trial. Anesth Analg. 2019;129(2):526-35.
- Jinadu S, Pai P, Lai Y. Ambulatory knee replacements with IPACK block. J Clin Anesth. 2019;60:55-6.
- Sankineani SR, Reddy ARC, Eachempati KK, Jangale A, Gurava Reddy AV. Comparison of adductor canal block and IPACK block (interspace between the popliteal artery and the capsule of the posterior knee) with adductor canal block alone after total knee arthroplasty: a prospective control trial on pain and knee function in immediate postoperative period. Eur J Orthop Surg Traumatol. 2018;28(7):1391-5.
- Ross JA, Greenwood AC, Sasser P, Jiranek WA. Periarticular Injections in Knee and Hip Arthroplasty: Where and What to Inject. J Arthroplasty. 2017;32(9S):S77-S80.
- Biedert RM, Stauffer E, Friederich NF. Occurrence of free nerve endings in the soft tissue of the knee joint. A histologic investigation. Am J Sports Med. 1992;20(4):430-3.
- Kellgren JH, Samuel EP. The sensitivity and innervation of the articular capsule. J Bone Joint Surg Br. 1950;32-B(1): 84-92.
- Chia SK, Wernecke GC, Harris IA, Bohm MT, Chen DB, Macdessi SJ. Peri-articular steroid injection in total knee arthroplasty: a prospective, double blinded, randomized controlled trial. J Arthroplasty. 2013;28(4):620-3.
- Kulkarni M, Mallesh M, Wakankar H, Prajapati R, Pandit H. Effect of Methylprednisolone in Periarticular Infiltration for Primary Total Knee Arthroplasty on Pain and Rehabilitation. J Arthroplasty. 2019;34(8):1646-9.
- Iwakiri K, Ohta Y, Kobayashi A, Minoda Y, Nakamura H. Local Efficacy of Periarticular Morphine Injection in Simultaneous Bilateral Total Knee Arthroplasty: A Prospective, Randomized, Double-Blind Trial. J Arthroplasty. 2017;32(12):3637-42.
- 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 Controlled Trial. J Arthroplasty. 2018;33(1):90-6.
- Yayac M, Li WT, Ong AC, Courtney PM, Saxena A. The Efficacy of Liposomal Bupivacaine Over Traditional Local Anesthetics in Periarticular Infiltration and Regional Anesthesia During Total Knee Arthroplasty: A Systematic Review and Meta-Analysis. J Arthroplasty. 2019;34(9):2166-83
- Grosso MJ, Murtaugh T, Lakra A, Brown AR, Maniker RB, Cooper HJ, et al. Adductor Canal Block Compared with Periarticular Bupivacaine Injection for Total Knee Arthroplasty: A Prospective Randomized Trial. J Bone Joint Surg Am. 2018;100(13):1141-6.
- Sawhney M, Mehdian H, Kashin B, Ip G, Bent M, Choy J, et al. Pain After Unilateral Total Knee Arthroplasty: A Prospective Randomized Controlled Trial Examining the Analgesic Effectiveness of a Combined Adductor Canal Peripheral Nerve Block with Periarticular Infiltration Versus Adductor Canal Nerve Block Alone Versus Periarticular Infiltration Alone. Anesth Analg. 2016;122(6):2040-6.