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© 2019 THE AUTHORS. ORTHOPAEDIC SURGERY PUBLISHED BY CHINESE ORTHOPAEDIC ASSOCIATION AND JOHN WILEY & SONS AUSTRALIA, LTD.

REVIEW ARTICLE

Postoperative Pain Management in Total Knee

Arthroplasty
Jing-wen Li, MSc1,2, Ye-shuo Ma, PhD3, Liang-kun Xiao, MSc1,2
1
Department of Orthopaedic Surgery, Yueyang Second People’s Hospital and 2Department of Orthopaedic Surgery, Yueyang Hospital Affiliated
to Hunan Normal University, Yueyang and 3Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, China

Total knee arthroplasty (TKA) is one of the most common surgeries performed to relieve joint pain in patients with end-
stage osteoarthritis or rheumatic arthritis of the knee. However, TKA is followed by moderate to severe postoperative
pain that affects postoperative rehabilitation, patient satisfaction, and overall outcomes. Historically, opioids have
been widely used for perioperative pain management of TKA. However, opioids are associated with undesirable
adverse effects, such as nausea, respiratory depression, and retention of urine, which limit their application in daily
clinical practice. The aim of this review was to discuss the current postoperative pain management regimens for TKA.
Our review of the literature demonstrated that multimodal analgesia is considered the optimal regimen for periopera-
tive pain management of TKA and improves clinical outcomes and patient satisfaction, through a combination of sev-
eral types of medications and delivery routes, including preemptive analgesia, neuraxial anesthesia, peripheral nerve
blockade, patient-controlled analgesia and local infiltration analgesia, and oral opioid/nonopioid medications. Multi-
modal analgesia provides superior pain relief, promotes recovery of the knee, and reduces opioid consumption and
related adverse effects in patients undergoing TKA.
Key words: Knee joint pain; Multimodal analgesia; Postoperative pain; Total knee arthroplasty

Introduction nerve blockade, local infiltration analgesia, patient-controlled

T otal knee arthroplasty (TKA) is commonly performed in

patients with end-stage osteoarthritis or rheumatic
arthritis of the knee to relieve joint pain, increase mobility,
analgesia, and multimodal analgesia. Adequate postoperative
analgesia could not only reduce pain, opioid consumption,
and, consequently, opioid-related adverse events, but also
and improve quality of life. However, TKA is followed by reduce length of hospital stay and costs, and improve rehabil-
moderate to severe postoperative pain1. In patients received itation and patient satisfaction4. Therefore, it is necessary for
TKA, 60% experience severe postoperative knee pain and surgeons to fully understand current anesthetic and analgesic
30% experience moderate pain2. Some patients even put off regimens for TKA to improve patient outcomes (Fig. 1).
this operation because of the fear of this acute postoperative
pain3. Furthermore, postoperative pain in TKA inhibits early Materials and Methods
ambulation and range of motion, risking thromboembolism,
and affects rehabilitation, patient satisfaction, and overall
outcomes.
A review of the available literature was performed on
8 January 2019 through searching PubMed, Cochrane
Library and EMBASE databases. The keyword terms “pain
In 1996, the American Pain Society declared that pain management,” “pain control,” and “total knee arthroplasty”
was “the fifth vital sign”3. In an attempt to relieve severe post- were used for searching the literature. The titles, abstracts,
operative pain, several routine approaches have been pro- and full texts of published studies were screened. As a result,
posed, such as use of preemptive analgesia, opioids, 67 studies were included in this review. This entire process is
cyclooxygenase-2 inhibitors, epidural anesthesia, peripheral depicted in Fig. 2.

Address for correspondence Liang-kun Xiao, MSc, Department of Orthopaedic Surgery, Yueyang Second People’s Hospital, 263 Baling East Road,
Yueyang, China 414000; Tel: 0730-8333555; Fax: 0730-8333555; Email: [email protected]
Disclosure: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. All authors
declare that they have no conflict of interest.
Received 2 June 2019; accepted 19 August 2019

Orthopaedic Surgery 2019;11:755–761 • DOI: 10.1111/os.12535

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
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ORTHOPAEDIC SURGERY POSTOPERATIVE PAIN MANAGEMENT IN TKA
VOLUME 11 • NUMBER 5 • OCTOBER, 2019

Fig. 1 Commonly used postoperative pain

management regimes for total knee arthroplasty
(TKA). COX-2, cyclooxygenase-2.

Fig. 2 Flow chart of the search for published reports

showing the process of inclusion and exclusion. TKA,
total knee arthroplasty.

Multimodal Analgesia peripheral and central mechanisms are involved. Therefore,

W ith exploration of the mechanisms underlying postop-

erative pain in TKA, it has been verified that both
monotherapy alone is not enough to provide satisfactory
postoperative pain relief after TKA. At present, multimodal
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analgesia is considered as the optimal method for periopera- Enrolled patients were given celecoxib 400 mg and
tive pain management of TKA through targeting numerous pregabalin 150 mg 1 h before the operation, or celecoxib
pain pathways. Multimodal analgesia was first introduced by 200 mg and pregabalin 75 mg twice daily starting from
Wall in 1988, referring to a combination of several types of 3 days before the operation, or a placebo. The results showed
medications and delivery routes, including preemptive anal- that preemptive analgesia with celecoxib and pregabalin was
gesia, neuraxial anesthesia, peripheral nerve blockade (PNB), effective in reducing postoperative usage of morphine inde-
patient-controlled analgesia (PCA), local infiltration analge- pendent of the dosage. Another investigation by Xu et al.11
sia (LIA), and oral opioid and nonopioid medication5. evaluated the efficacy of combination of celecoxib (200 mg,
Multimodal analgesia includes preoperative, intraoper- BID) and tramadol/acetaminophen (37.5 mg/325 mg, TID)
ative, and postoperative analgesic regimens, aiming to maxi- 3 days preoperatively in treating postoperative pain of
mize the analgesic efficacy through the combination of several patients undergoing unilateral TKA. It verified that this regi-
analgesic regimens, while minimizing undesired adverse men of preemptive analgesia significantly decreased resting
effects. Adequate preemptive analgesia could prevent pain pain at 3 weeks and 6 weeks, and movement pain at
nociceptors from entering a state of hyperalgesia, and make 1/3/6 weeks and 3 months postoperatively11. Therefore, pre-
acute postoperative pain easier to control, ultimately reducing emptive analgesia is an important component in multimodal
opioid consumption. Intraoperatively, LIA is performed by a analgesia to reduce postoperative analgesia usage.
surgeon near the conclusion of a procedure that directly pre-
vents the generation and conduction of pain signals from inci- Opioids
sion. Several medicines are available for LIA during the Opioids have long been used for the treatment of knee
surgery, which will be discussed in detail later. Postoperatively, arthritis and perioperative pain management of patients
multimodal analgesia includes pharmacologic agents, undergoing primary TKA and revision knee arthroplasty. As
neuraxial anesthesia, PNB, and PCA, each of which will be analgesics, opioids inhibit the conduction of pain signals
described below. Compared with a monotherapy, multimodal through activation of opioid receptors through several deliv-
analgesia provides superior postoperative pain relief to pro- ery methods, such as oral, intravenous, intramuscular, subcu-
mote recovery of the knee, and reduce opioid consumption taneous, and transdermal. Although opioids are effective in
and related side effects1,4. Consequently, multimodal analgesia pain management after TKA, there are some adverse effects
is used widely for perioperative pain control in patients associated with them, such as itchiness, nausea, somnolence,
undergoing TKA. respiratory depression, retention of urine, and constipation.
In addition, long-term use of opioid medications may lead to
Preoperative Analgesic Regimens tolerance and dependence that require increasing doses to
achieve the same effects. Therefore, it is practical to apply
Preemptive Analgesia other analgesic regimens to reduce the amount of opioid
Preemptive analgesia is defined as an antinociceptive inter- consumption.
vention that starts before a surgical procedure. It is more Bedard et al. (2017) suggested that approximately one-
effective than the same intervention when started after sur- third of TKA patients used opioids within 3 months prior to
gery6. Preemptive analgesia is intended to prevent peripheral surgery12. Compared with total hip arthroplasty patients, TKA
and central hypersensitivity, decrease the incidence of patients were twice as likely to require refill opioid prescrip-
hyperalgesia, and reduce the intensity of postoperative tions and were prescribed a greater total morphine equivalent
pain6,7. Preemptive analgesia also increases the pain thresh- dose for a longer period of time postoperatively13. Increasing
old, contributing to lower postoperative application of anal- evidence reveals that preoperative chronic use of opioids
gesic medication. reduces the effect of pain relief postoperation, and increases
Cyclooxygenase-2 (COX-2) inhibitors, such as postoperative opioid consumption in TKA patients12,14–16. In
parecoxib sodium and celecoxib, administered 30–60 min addition, preoperative opioid use is associated with early revi-
before surgery significantly decrease postoperative pain and sion, postoperative complications, worse clinical outcomes
morphine consumption without increasing the incidence of due to developed tolerance, and hyperalgesia, which can com-
other postoperative complications8,9. Parecoxib sodium plicate recovery and rehabilitation17–19. These results suggest
40 mg administered 30 min before surgery significantly that limiting preoperative opioid use can optimize the benefits
decreased postoperative pain in a post-anesthesia care unit of TKA. Furthermore, Nguyen et al.20 evaluated whether
without increasing the incidence of other postoperative com- weaning of opioid use (50% reduction in morphine-equivalent
plications8. Patients administered with celecoxib 400 mg dose) in the preoperative period improved total joint
within 1 h before surgery had less pain at rest and walking arthroplasty outcomes. Their results showed that the patients
during the first week postoperatively, and received less mor- successfully weaned before surgery had substantially improved
phine at 48 h after the procedure9. Lubis et al. (2018)10 dem- clinical outcomes, including for The Western Ontario and
onstrated that a combination of pregabalin (an antiallodynic McMaster Universities Arthritis Index, SF12v2, and the Uni-
and antihyperalgesic) and celecoxib could be used as pre- versity of California at Los Angeles activity score, which were
emptive analgesia in TKA through their synergic effects. comparable to patients who did not use opioids at all. This
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VOLUME 11 • NUMBER 5 • OCTOBER, 2019

study highlights the importance of reduction of preoperative

TABLE 1 Common local infiltration analgesia cocktails
opioid use to improve postoperative recovery in TKA
patients. Year Authors Components

2017 Wall et al.29 150 mg 0.25% levobupivacaine

Cyclooxygenase-2 Inhibitors hydrochloride, 10 mg morphine
Traditional nonsteroidal anti-inflammatory drugs (NSAID) sulphate, 30 mg ketorolac trometamol,
and COX-2 inhibitors provide perioperative analgesia and 0.25 mg adrenaline diluted with
saline to a total volume of 150 mL
through inhibition of COX-2 and prostaglandins. NSAID
2018 Tong QJ et al.65 150 mg ropivacaine, 30 mg ketorolac,
also inhibit the activity of COX-1 that is associated with gas- 10 mg morphine, and 200 mcg
trointestinal effects. In addition, NSAID increase the risk of adrenaline in a total volume of 75 mL
perioperative blood loss. Fortunately, COX-2 inhibitors have 2018 Mont MA et al.35 266 mg/20 mL liposomal bupivacaine
admixed with bupivacaine HCl 0.5%,
a favorable adverse effect profile with reduced gastrointesti- 20 mL diluted with saline to a total
nal effects and risk of blood loss21. COX-2 inhibitors exert volume of 120 mL
the effect of analgesia through reducing the synthesis of 2019 McCarthy D et al.66 2 mg/ kg levobupivacaine and 0.5 mg
peripheral prostaglandin to relieve inflammation and inhibit adrenaline diluted with saline to a total
volume of 100 mL
peripheral and central COX-2 expression, ultimately 2019 Koniuch KL et al.67 30 mg ketorolac, 80 μg clonidine, 0.5 mg
preventing the sensitization of central nerve system. epinephrine and weight-based dosing of
A meta-analysis conducted by Lin et al.22 with ropivacaine (270 mg for patients
weighing 80 kg or more)
571 patients showed that perioperative administration of
selective COX-2 inhibitors could reduce pain and opioid
consumption in patients undergoing TKA, without increas-
ing the risk of blood loss. Furthermore, a randomized con-
trolled trial (RCT) by Munteanu et al.23 of 165 patients after pain scores and comparable satisfaction levels, with reduced
TKA suggested that preoperative administration of etoricoxib total narcotic consumption in the early postoperative period
120 mg orally was superior to postoperative administration compared to those with placebo infiltration26,27. FNB is
of the same dose in terms of its morphine-sparing effect dur- widely considered as an effective postoperative pain manage-
ing the first postoperative 48 h, without difference in the ment protocol. A meta-analysis conducted by Zhang LK
incidence of side effects. Apart from analgesia, celecoxib and et al.28, including 10 studies with 950 patients, showed that
parecoxib could also decrease early postoperative cognitive LIA was as effective as FNB in terms of visual analog scale
dysfunction incidence after TKA in elderly patients24,25. At score for pain control at 24/48/72 h, total morphine con-
present, COX-2 inhibitors are usually added to multimodal sumption, range of motion, knee society score, complica-
analgesia to reduce the consumption of opioids, without seri- tions, and length of hospital stay. Wall et al.29 performed an
ous complications8. RCT and demonstrated that the patients with LIA used less
morphine in the first postoperative day after TKA compared
Intraoperative Analgesic Regimens with the patients with FNB. Another meta-analysis con-
ducted by Hu et al.30 with 1206 patients showed that LIA
Local Infiltration Analgesia provided superior postoperative pain relief at rest and pre-
Local infiltration analgesia (LIA) has received increasing served quadriceps function in the early postoperative period
interest in recent years because of the associated low risk, compared with epidural analgesia/peripheral nerve block.
simple performance, low complication rates, and reduced These results suggest that LIA is a viable and safe alternative
local anesthetic systemic toxicity. LIA is performed by a sur- to FNB for postoperative pain management after TKA with-
geon intraoperatively without specialist equipment, com- out impairment of quadriceps muscle function. Furthermore,
monly near the conclusion of a procedure. Local anesthetic a meta-analysis conducted by Sardana V et al.31 showed that
combined with opioids, antibiotics, NSAID or epinephrine LIA could significantly improve postoperative pain and opi-
(cocktail) are injected into periarticular regions, including oid consumption when compared with adductor canal
the posterior capsule, collateral ligaments, capsular incision, block (ACB).
the quadriceps tendon, and subcutaneous tissues, which Liposomal bupivacaine (LB) is used as a component of
directly prevents the generation and conduction of pain sig- the LIA cocktail to prolong the effect of LIA, for LB can last
nals from incision. Recently, LIA has become an alternative up to 72 hours. Several studies have assessed the efficacy of
analgesic regimen to femoral nerve block (FNB) without LIA with LB in patients undergoing TKA, but the results are
resulting in impairment of quadriceps muscle strength. Nev- controversial32–34. Mont et al. (2018)35 performed an RCT to
ertheless, there is still no consensus on the optimal composi- compare the effects of LIA, with or without LB, on postsurgi-
tion and infiltration technique of LIA. Common LIA cal pain control by minimizing the limitations that may have
cocktails are listed in Table 1. affected previous study results. Their results showed that LIA
Among the patients undergoing TKA, those patients with LB improved postsurgical pain, opioid consumption
who received intraoperative LIA achieved improvement in (18.7 mg vs 84.9 mg, P = 0.0048), and time to first opioid
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VOLUME 11 • NUMBER 5 • OCTOBER, 2019

rescue without side effects35. Although another study showed Postoperative Analgesic Regimens
that patients in an FNB group had significantly lower pain
scores (mean 3.24 vs 3.87, P = 0.02) and higher range of Epidural Analgesia
motion (84.54 vs 78 , P < 0.001) in the first 24 h, the Formerly, epidural analgesia was used as a regular postopera-
patients receiving LIA with LB were significantly more likely tive analgesic regimen for patients after TKA, consisting of a
to perform a straight leg raise 12 h postoperatively (73% vs local anesthetic agent and an opioid. Compared with paren-
50%; P = 0.0003) and scored better in the physical function teral opioids, epidural analgesia provides better postoperative
component of the Short Form-12 (−23 vs −27, P = 0.01) analgesia with less nausea, vomiting, and pruritus43. How-
3 months postoperatively36. This suggested that LIA with LB ever, some studies show that epidural anesthesia is associated
provided excellent pain relief that was not inferior to FNB in with many adverse effects, such as urinary retention, hypo-
patients undergoing TKA. tension, pruritus, and motor block44–46. Among these, the
Different results of efficacy of LIA compared with main drawback of epidural anesthesia is inadvertent motor
other analgesia protocols are obtained from different studies, nerve block, which delays physical therapy and rehabilita-
which reach no consensus in optimal composition and infil- tion44. In addition, epidural anesthesia limits the options for
tration techniques of LIA. A previous study suggested that it postoperative prophylaxis against deep venous thrombosis. A
was intraoperative periarticular instead of intraarticular infil- meta-analysis by Li et al. (2018) of seven RCT, with
tration that was effective in pain control in the early postop- 251 patients undergoing TKA, concluded that LIA was as
erative period after TKA37. Therefore, future research should effective as epidural anesthesia for pain control47. LIA
focus on the optimal composition and infiltration technique showed an increase in the range of motion, and a reduction
of LIA to further verify the efficacy. of the occurrence of nausea and length of hospital stay47.
Another meta-analysis compared analgesic efficacy and side
effect profile of FNB and epidural anesthesia through analyz-
Spinal Anesthesia ing eight RCT with 510 patients48. The results suggested that
Anesthesia choice is an issue for better perioperative out- FNB provided a comparable postoperative analgesia but had
comes after TKA. In addition, pain management after TKA a favorable adverse effect profile with less neuraxial compli-
is affected by the type of anesthesia used for the surgery. cations. Hypotension and urinary retention occurred more
Both general and spinal anesthesia are appropriate for TKA. frequently among patients receiving epidural anesthesia, with
Because general anesthesia is associated with reduced peri- worse patient satisfaction48. These studies suggest that FNB
operative tissue oxygen tension as well as postoperative nau- and LIA may be preferable to epidural analgesia for postop-
sea, vomiting, and delirium, it is initially considered the erative pain relief after TKA.
gold standard for hip and knee arthroplasty38,39. However,
spinal anesthesia is becoming popular in TKA. Compared Peripheral Nerve Blockade
with general anesthesia, spinal anesthesia is reported to be Peripheral nerve blockade is usually used to relieve postoper-
associated with a lower rate of superficial wound infections ative pain of TKA. PNB could significantly reduce consump-
(0.68% vs 0.92%, P = 0.0003), blood transfusions (5.02% vs tion of opioid and opioid-related adverse effects. It also
6.07%, P = 0.0086), length of surgery (96 vs 100 min, promotes early mobilization and reduces the length of hospi-
P < 0.0001), and length of hospital stay (3.45 vs 3.77 days, tal stay. The knee joint is innervated by several nerves,
P < 0.0001)40. Furthermore, patients administered general including the femoral nerve, the sciatic nerve, the obturator
anesthesia have a small but significant increase in the risk of nerve, the saphenous nerve, and the lateral femoral cutane-
complications40. Another investigation conducted by Park ous nerve. Among these, the femoral nerve is an important
et al.41 showed similar results. They found that patients that one with respect to analgesic effects after TKA. Conse-
received TKA under general anesthesia had longer preopera- quently, FNB is one of the most commonly used PNB, and
tive room time (+9.4 minutes, P < 0.001), postoperative has been widely accepted as the gold standard for pain relief
room time (+12.7 min, P < 0.001), and postoperative hospi- after TKA. FNB not only provides excellent pain manage-
tal stay (+2.5 days, P = 0.001), and had more surgical site ment after TKA but also reduces opioid consumption, hospi-
infections (5 [1%] vs 0 [0%], P = 0.005) and blood transfu- tal stay, and incidence of nausea and vomiting49,50. Besides,
sions (205 [41.8%] vs 262 [35.1%], P = 0.01) compared to FNB contributes to long-term functional recovery in patients
those with spinal anesthesia. However, there were no differ- undergoing TKA49. Although FNB could provide effective
ences in operative duration and other adverse events. In postoperative analgesia, it is also associated with some seri-
addition, Mahan et al.42 (2018) reported that patients who ous complications. It may damage adjacent major blood ves-
underwent TKA with mepivacaine for spinal anesthesia had sels and nerves itself50, and reduces quadriceps muscle
a shorter length of stay (28.1  11.2 vs 33.6  14.4 h, strength, which limits extension of the knee and increases
P = 0.002), fewer episodes of straight catheterization (3.8% risk of falls postoperatively51,52. Consequently, ACB is an
vs 16.5%, P = 0.021) compared to bupivacaine, and alternative analgesic regimen to FNB52.
exhibited no differences in postoperative pain or morphine The adductor canal is located in the middle one-third
consumption. of the thigh and runs from the apex of the femoral triangle
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VOLUME 11 • NUMBER 5 • OCTOBER, 2019

proximally to the adductor hiatus distally2. ACB could block oxycodone, morphine, fentanyl, and hydromorphone56–59.
the saphenous nerve, which is the largest sensory branch of Therefore, PCA is associated with some adverse effects cau-
the femoral nerve to the knee, while spare the major motor sed by opioids, including nausea, vomiting, respiratory
branches of the femoral nerve. Therefore, ACB could provide depression, and urinary retention60. However, these adverse
postoperative pain relief as effectively as FNB without effects are less severe than those caused by conventional opi-
impairment of quadriceps muscle strength, and it is becom- oid treatment.61 PCA is safe and effective for treating moder-
ing increasingly popular2,52. Except for better quadriceps ate to severe pain and has become increasingly popular for
muscle power, patients with ACB have better early rehabili- use in patients undergoing TKA61,62. Currently, opioid drugs
tation, longer ambulation distance, and shorter length of are commonly administered by PCA, adding to multimodal
hospital stay compared with FNB53,54. Previous study also analgesia1,63,64.
suggested that continuous ACB was superior to a single shot
block in terms of pain control but was similar for early func- Summary
tional recovery55. Nevertheless, ACB is still a newly devel-
oped method of regional anesthesia after TKA, and large
RCT are needed to further evaluate its application in surgery
W ith the aging of the population, there will be an
increasing number of elderly patients receiving TKA.
Perioperative pain management in patients undergoing TKA
of the knee. is very important to improve rehabilitation, patient satisfac-
tion, and overall outcomes. Furthermore, when surgeons
Patient-controlled Analgesia make a plan for perioperative pain management after TKA,
Patient-controlled analgesia is widely used for pain manage- they must consider each patient individually. At present,
ment in patients after TKA to provide simple, fast, and ade- multimodal analgesia is the optimal analgesic regimen for
quate pain relief without a specialized anesthesiologist TKA. Multimodal analgesia could improve perioperative
postoperatively. The device is programmed according to the pain control and patient satisfaction through the combina-
analgesic used, the physical characteristics, and the baseline tion of several analgesic regimens, while reducing opioid
pain of the patients. A small amount of analgesic could be consumption and opioid-related adverse effects. However,
delivered by the patients pressing the button when they most the optimal protocol of multimodal analgesia needs to be
need it. Usually, opioids are used in PCA, such as further investigated in the future.

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