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Pain management in total knee replacement
Apollo Medicine 2012 December Volume 9, Number 4; pp. 323e335
Review Article
Pain management in total knee replacement Raju Vaishyaa,*, Ajaz Majeedb
ABSTRACT Total knee replacement (TKR) is one of the most commonly done surgical procedures, with over 150,000 total knee replacements and THR performed annually in England and Wales in the National Health Service (NHS). In India although clear-cut data is not available but the incidence is increasing. In the US, 431,000 TKRs are performed yearly and the utilization of TKR has increased over the last two decades, especially among younger patients .TKR may be associated with severe post-operative pain. The International Association for the Study of Pain (IASP) has defined pain as “an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has made adequate pain management a priority and has deemed monitoring pain as the “fifth” vital sign. Copyright © 2012, Indraprastha Medical Corporation Ltd. All rights reserved. Keywords: International association for the study of pain, Deep vein thrombosis, Nosocomial infection
Total knee replacement (TKR) is one of the most commonly done surgical procedures, with over 150,000 total knee replacements and THR performed annually in England and Wales in the National Health Service (NHS).1 In India although clear-cut data is not available but the incidence is increasing. In the US, 431,000 TKRs are performed yearly2 and the utilization of TKR has increased over the last two decades, especially among younger patients.3 TKR may be associated with severe post-operative pain. The International Association for the Study of Pain (IASP) has defined pain as “an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.4 The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has made adequate pain management a priority and has deemed monitoring pain as the “fifth” vital sign.5
BACKGROUND TKR may result in severe post-operative pain usually requiring hospitalization from 5 to 10 days to provide effective analgesia. This prolonged hospital stay and relative immobilization a
of the patient in bed may invite nosocomial infection and deep vein thrombosis (DVT). In addition to causing unnecessary distress and discomfort during the post-operative period, poorly managed post-operative pain can have negative consequences for long-term surgical outcomes. Adequate post-operative pain relief following TKR is very important to optimal post-operative recovery (Table 1). The faster that mobilization and rehabilitation can progress, the better the ultimate outcome will be. Adequate pain control post-operatively should allow earlier patient mobilization with the aim of increasing strength and proprioception and decreasing the incidence of the development of thromboembolism. In complicated cases, prolonged immobility due to pain can cause the development of muscular contractures or atrophy that eventually cause the development of long-term functional impairments (Table 2). Adequate management of post-operative pain still poses a significant challenge to healthcare, as demonstrated by a review of the literature which concluded that approximately 60% of patients experienced severe pain and approximately 30% patients experienced moderate pain after surgery.6 In a recent study at the Avon Orthopedic Center, 58% of TKR patients reported moderate or severe pain on the first post-operative day.7
Professor, Senior Consultant, bDNB student, Department of Orthopaedics & Joint Replacement Surgery, Indraprastha Apollo Hospitals, Mathura Road, New Delhi 110076, India. * Corresponding author. Tel.: þ91 9810123331, email: [email protected] Received: 9.8.2012; Accepted: 27.8.2012; Available online 5.9.2012 Copyright Ó 2012, Indraprastha Medical Corporation Ltd. All rights reserved. http://dx.doi.org/10.1016/j.apme.2012.08.012
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Table 1 Advantages of adequate analgesia in TKR.
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risk of heart attack while overdoses can lead to liver damage. Navigating these side effects amongst the co-morbidities and potential drug interactions with concurrent medications in the elderly population is typically problematic.
PAIN PERCEPTION
Current pharmaceutical pain relief options for TKR pain have limitations due to associated side effects, often requiring additional treatment for them. Unfortunately, there are very few pain management options available that can provide a treatment that is both non-invasive and without side effects. Side effects of the opiate pain medication include lethargy, sedation, respiratory depression, nausea, vomiting, numbness, weakness, urinary retention, hypotension and digestive discomfort, including gastro paresis and constipation. Opioids may also alter mood negatively and/or induce euphoria. The side effects of non-steroidal anti-inflammatory agents (NSAIDS) include gastric upset, sometimes predisposing symptoms leading to peptic ulcers. COX-2 inhibitors have been found to increase Table 2 Effect of inadequate analgesia in TKR.
Pain is generated because of local inflammation and nerve damage due to trauma or temperature change, during TKR. Tissue insult causes local release of inflammatory mediators such as bradykinin, prostaglandins, substance P, and histamine. Receptors detect changes in pain and temperature and initiate afferent signals in the peripheral nervous system through unmyelinated C fibers or myelinated A fibers. Signals reach the dorsal root ganglion and synapse in the dorsal horn of the spinal cord. At this juncture, spinal modulation of the afferent signals occurs through opioids, a2 agonists, and Nmethyl-D-aspartate (NMDA) receptor antagonists. Neurotransmission is further modulated by other substances such as gamma-aminobutyric acid (GABA). From here, spinothalamic tracts carry ascending signals, where further central modulation can occur in supraspinal modulatory centers.4 The various agents used as part of a multimodal strategy affect nociceptors and different regions of common pain pathways to achieve an overall reduction in perceived pain (Fig. 1).
Assessment of pain In the assessment of pain intensity, various rating scale techniques are used. The most commonly used forms are:
The category rating scales (Fig. 2) (e.g. none, mild, moderate, severe, unbearable or 1e5). The visual analog scales (VAS) (Fig. 3) The VAS has been shown to be more sensitive to change and is therefore more widely used. These scales may also be incorporated into pain diaries. McGill pain questionnaire (MPQ) (Melzack, 1975) (78 pain adjectives arranged into 20 groups further arranged into sets of words describing sensory aspects of the quality of pain).
POST-OPERATIVE PAIN CONTROL AFTER TOTAL KNEE REPLACEMENT Traditionally, acute post-operative pain following TKR has been managed with:
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Fig. 1 Pain pathways and multimodal analgesic therapy.
1. Peripheral nerve blocks 2. Epidural analgesia 3. Parental (IV) analgesia (e.g., analgesia) 4. Multimodal analgesia 5. Local infiltration analgesia (LIA)
patient-controlled
Peripheral nerve blocks Innervation of the knee joint Knowledge about the innervation of the knee joint is important in performing a peripheral nerve block. Innervation of the knee joint (Fig. 4) is derived from (i) femoral nerve via the branch to vastus medialis (anterior aspect of the joint
Fig. 2 Category rating scale.
capsule); (ii) sciatic nerve via genicular branches of both tibial and common peroneal components (posterior aspect of the joint capsule and all of the intra-articular structures); and (iii) obturator nerve by a branch from its posterior division that accompanies the femoral artery through adductor Magnus into the popliteal fossa. Cutaneous innervation of the anterior aspect of the knee is supplied by the femoral nerve. The obturator nerve supplies the skin on the medial aspect of the knee in less than 40% of people.
Peripheral nerve blocks Peripheral nerve blocks with a local anesthetic have been used commonly in total joint replacements (Table 3). Patients undergoing TKR may have a femoral nerve block
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Fig. 3 VAS scale.
and/or a sciatic nerve block. Peripheral nerve blocks may be continuous or administered as a one-time dose. Continuous peripheral nerve blocks provide the most effective and long-lasting analgesia with fewer side effects when compared with PCA morphine or continuous epidural analgesia. Potential side effects include nerve damage and a lack of muscle control in the immediate rehabilitation period. Local infection due to an indwelling catheter has been reported in between 0% and 3% of cases.8 Comparisons have shown that one-time blocks fail to provide the prolonged relief of continuous blocks, with no difference after the first four to 6 h following a total joint arthroplasty.9 Kardash et al administered one-time doses of bupivacaine and epinephrine in the form of a femoral nerve block or
Fig. 4 Innervation of lower limb.
obturator nerve block, or gave a placebo, to patients treated with total knee arthroplasty.10 All patients were concurrently receiving multimodal pain agents. Results showed that an obturator block was no different from the placebo, and the femoral nerve block lowered only pain scores, not morphine consumption. In another study, Ozen et al compared the so-called three-in-one femoral nerve block (femoral nerve, lateral femoral cutaneous nerve, and obturator nerve blocks) with the use of no block in patients undergoing total knee arthroplasty.11 Less consumption of patient-controlled opioid analgesia and lower visual analog scale (VAS) pain scores were recorded for the three-in-one femoral nerve block cohort. In another investigation, patients receiving the nerve block were able to undergo faster rehabilitation than the cohort patients receiving patient-controlled analgesia with morphine.12 A peripheral nerve block with continuous infusion provides analgesia superior to that resulting from a one-time injection.13 Most studies in the literature support the use of a continuous peripheral nerve block in multimodal pain management. A meta-analysis by Richman et al demonstrated significantly improved pain control (p < 0.05) in patients receiving a peripheral nerve block compared with that associated with opioid analgesia alone.14 According to Fowler et al, peripheral nerve blocks have a side-effect profile that is more desirable than that of epidural analgesia while maintaining a similar level of pain relief.15 Peripheral nerve blocks created less urinary retention and hypotension in that study. Patients treated with a unilateral nerve block had less restriction of movement than those who received epidural analgesia. The primary concern about the use of peripheral nerve blocks is the development of late neurological sequelae, including permanent nerve damage. A recent investigation of over 6000 patients was performed to examine these complications.16 While 0.5% of patients developed nerve symptoms post-operatively, the incidence of symptoms related to the peripheral nerve block was only 0.04%. A meta-analysis of peripheral nerve block studies done between 1995 and 2005 revealed a 0.34% incidence of symptomatic post-operative neuropathy with femoral nerve blocks64. The best combination of peripheral nerve blocks and choice of local anesthetic solution for continuous infusion following total knee arthroplasty is currently unknown.
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Table 3 Features of peripheral nerve blocks. Nerve block Femoral nerve block
Advantages d d d d
Sciatic nerve block
d
Disadvantages
Easy to perform Good efficacy Less side effects Faster rehabilitation Combined with femoral nerve block provide adequate analgesia with less side effects
d d
d
d d
Obturator nerve block
d
Lumbosacral block
d
d
Adding obturator block to sciatic and femoral nerve blocks improve analgesia Better than femoral nerve block because it blocks the femoral, obturator, and lateral femoral cutaneous nerves more reliably Facilitate earlier mobilization
Femoral nerve block The knee is innervated by the femoral nerve, which is the largest branch of the lumbosacral plexus. The femoral nerve supplies about 80% of the sensation in the knee. The femoral nerve supplies the motor contraction of the iliacus, pectineus, and anterior thigh muscles. The femoral nerve also supplies the cutaneous and articular branches to the front and inner thigh, leg and foot, and hip and knee. Femoral nerve block has a high success rate and carries a low risk of complications. However, proximal spread of local anesthetic to the other branches of the lumbar plexus is unreliable. Single-shot femoral nerve block using a longacting amide local anesthetic will provide analgesia to the anterior aspect of the knee for up to 24 h, although the incidence of profound motor block of the quadriceps muscles will be unacceptably high if large volumes of concentrated local anesthetic agents are used. The benefit of using a continuous femoral nerve block to control pain after total knee replacement surgery has been tested and proven to be effective. By using this method for pain control, fewer narcotic medications will be needed to control the pain. By using fewer narcotics there will be fewer side effects. Advantages Continuous femoral nerve block is technically simple to perform with a low incidence of side effects. The infusion is continued for 48e72 h before catheter removal and patients are allowed to mobilize during this time provided they have adequate motor power and proprioception. Several recent studies have confirmed that the analgesic efficacy of this technique is equivalent to both continuous epidural analgesia and continuous lumbar plexus block following total knee arthroplasty; however, continuous
d d d
Neurovascular injury Localization
Time consuming procedure to give two simultaneous blocks Sciatic nerve injury Isolated block not adequate Localization difficult Inadequate analgesia, if performed alone Difficult to perform
femoral nerve block was associated with fewer side effects than the other techniques.17 Ozen et al (2006) found that the use of a FNB led to a reduction in post-operative opioid administration and its associated side effects. Sciatic nerve block Pain behind the knee is a problem for a significant proportion of patients who only receive femoral nerve block because all of the intra-articular structures are innervated by the tibial nerve. The benefit of adding a sciatic nerve block to a femoral nerve block has become the subject of debate in regional anesthesia circles. Advantages Single-shot sciatic nerve block combined with femoral nerve block will provide analgesia for up to 24 h. When performing the block using a nerve stimulator, success rates are highest if inversion (tibial and peroneal nerve) or plantar flexion (tibial nerve) of the foot is elicited. The combination of continuous femoral and sciatic nerve blocks has been shown to provide superior analgesia with less PONV when compared to other analgesic techniques. Disadvantages The potential disadvantages of adding a continuous sciatic block to continuous femoral nerve block are increased time required to perform two continuous blocks and the potential problems mobilizing patients post-operatively because of more extensive motor block. The practical alternative is to use continuous femoral nerve block combined with single-shot sciatic nerve block. Lumbar plexus block It has been suggested that lumbar plexus (Fig. 5) block may be better than femoral nerve block because it blocks the
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Fig. 5 Anatomy of lumbar plexus.
femoral, obturator, and lateral femoral cutaneous nerves more reliably. However, there is little evidence from clinical trials to support this hypothesis. Continuous lumbar plexus block is a logical and effective technique that has been shown to improve analgesia and facilitate earlier mobilization following total knee arthroplasty compared with single-shot lumbar plexus block.18 Again, the combination of a sciatic nerve block should be considered. Obturator nerve block The addition of a separate obturator block to a femoral or lumbar plexus block is contentious. Femoral nerve block has been shown to spare the obturator nerve in as many as 50% of patients, contrasting with lumbar plexus block when the obturator nerve is missed in <10%. It is interesting to note that a comparative study of continuous lumbar plexus and continuous femoral nerve block found no difference in analgesia. On the other hand, there is some evidence that adding a single-shot obturator block to single-shot sciatic and femoral nerve blocks may improve analgesia.19
Epidural analgesia Administration of epidural analgesia/anesthesia is one of the most popular techniques used in TKR surgery as it is associated with improved pain control compared with that provided by patient-controlled analgesia.20 In a direct comparison with patient-controlled analgesia with
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morphine, epidural analgesia was found to decrease the duration of post-operative inpatient rehabilitation.21 Analgesic agents delivered to the epidural space can be administered continuously or as a single dose. Typically, an opioid combined with epinephrine is administered during administration of epidural anesthesia. Epinephrine, through local vasoconstriction, reduces opioid absorption and leads to a relatively higher local concentration of the opioid agent and greater analgesia from the local anesthetic. Ketamine can also be added as a synergistic agent. Side effects of epidural injection include hypotension and decreased motor function. Newer extended-release one-time dosage formulations consisting of a single epidural injection of morphine may relieve problems associated with catheter malfunction. Casati et al followed patients who received epidural 0.125% levobupivacaine through a catheter for 72 h following total knee arthroplasty.22 All patients also received patient-controlled analgesia with morphine. As compared with a group that received only patient-controlled morphine post-operatively, those who received the levobupivacaine had better pain scores and decreased morphine consumption over the 3 days for which the epidural was maintained. Most importantly, no decrease in motor function was noted, which minimized loss of physical therapy. Förster and Rosenberg studied the effect of adding clonidine to a fentanyl epidural infusion and reported a decrease in morphine consumption compared with that by patients who had not received the clonidine additive.23 The only problem was an average drop in blood pressure of 5 mmHg and an average drop in the pulse rate of 3 beats per minute in the clonidine group. Another relatively recent advancement includes the availability of microsomal delivery technology that allows epidural delivery of extended-release opioids as a one-time injection. One such product is extended-release epidural morphine, commercially available as DepoDur, which provides 48 h of extended morphine release. In a study of patients treated with total knee arthroplasty who received extended-release epidural morphine through a single injection and post-operative patient-controlled analgesia opioids, Hartrick et al noted decreased pain and opioid consumption, compared with the values for patients who received a sham epidural, although four patients over 64 years of age experienced serious respiratory depression.24 Currently, it is recommended that extended-release epidural morphine be used cautiously in older patients and patients with sleep apnea. Meta-analyses of studies of epidural analgesia have demonstrated improved pain control, especially during early post-operative periods.25 Significant side effects include pruritus (odds ratio ¼ 4.74), urinary retention (odds ratio ¼ 3.50), and hypotension (odds ratio ¼ 2.78). The odds ratios for respiratory depression and nausea were not significant (the confidence interval included 1).
Pain management in TKR
Patient-controlled analgesia (PCA) This method provides an intravenous pump attached to the intravenous site-allowing patient to administer his own pain medication after surgery. The machine has been used for over 20 years and has a safe record of use. The machine has a control button that can be pushed 8e10 times per hour when pain is experienced. The PCA has several advantages as well as disadvantages due to the nature of the medication being administered. Since the medicine is administered directly into the intravenous line, the medication works very quickly. If patient is in pain, patient does not need to call the nurse to be given pain medication. The main disadvantage of PCA is that the medication used can be quite sedating for some patients, making it difficult to participate in post-operative physical therapy. Other disadvantages are the side effects associated with narcotics including nausea, vomiting, itching and urinary retention (inability to urinate). The PCA cannot be used if patient has an allergy or sensitivity to these medications. Contrary to popular belief, patient cannot become addicted to morphine by using a PCA in a controlled environment and for a limited period of time. The use of PCA is limited to 72 h or less to prevent or decrease side effects. The effectiveness of analgesia attributed to the PCA pump is about 75% so breakthrough pain medications are readily available for all patients on PCA.
Multimodal analgesia As the name implies, multimodal pain management involves the use of multiple agents that act at different regions of the pain pathway. The rationale for this strategy is that it reduces the use of opioid agents and their adverse side effects. A combination approach allows better overall pain control. One aspect of multimodal pain management involves pre-emptive administration of analgesics and/or anti-inflammatory agents. These agents are given prior to the initiation of operative treatment and the release of local inflammatory pain mediators. Pre-emptive analgesia was first described by Wall in 1985. Since then, there has been extensive research related to administration of agents before surgery in an effort to alleviate post-operative pain. Kehlet and Dahl introduced multimodal pain management in 1993 with encouragement and equivocation.26 Much of the pain pathway had been investigated, but strong clinical evidence supporting multimodal pain management was lacking. Since that report, evidence has mounted to support much of this pain management process. Currently, the American Society of Anesthesiologists Task Force on Acute Pain Management recommends a multimodal pain
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regimen, specifically with the incorporation of non-steroidal anti-inflammatory drugs (NSAIDs) when medically appropriate.27 Over the past 10 years, multimodal pain management protocol after TKA has undergone several changes using various agents to reduce post-operative pain, including the adoption of pre-emptive analgesia, the use of local periarticular injections, and the introduction of a comprehensive post-operative pain protocol.28,29
Local infiltration analgesia In order to avoid the problems of regional analgesia or opioid, and to minimize the complications, recently, a local infiltration analgesia (LIA) technique was developed by Kerr and Kohan in Sydney, Australia (Röstlund and Kehlet 2007, Kerr and Kohan 2008).30 The technique involves the infiltration of a large volume dilute solution of a long-acting local anesthetic agent, often with adjuvants (e.g. epinephrine, ketorolac, an opioid), throughout the wound at the time of surgery (Figs. 6 and 7). The technique, known as local infiltration analgesia (LIA), was developed specifically to avoid sedation and facilitate rapid physiological recovery after lower limb arthroplasty in order to enable early mobilization and discharge. The idea of administering analgesia directly to the operative site with minimal systemic side effects is an attractive option. Surgical trauma during total knee replacement modifies the responsiveness of the nervous system in two ways. It causes peripheral sensitization by reducing the threshold for afferent nociceptive neurons, and it causes central sensitization by increasing the excitability of spinal
Fig. 6 Intra-operative photograph showing the locations for deep intra-operative injection: posterior capsule (1); posteromedial structures (2); periarticular synovium (3).
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knee arthroplasty to be treated with cryotherapy or normal compressive dressings and found that the cryotherapy group required less morphine.34 Current evidence supports the use of cryotherapy, as this modality has little or no side effects.
Pharmaceutical agents
Fig. 7 Intra-operative photograph showing the locations for superficial intra-operative injection.
neurons. Together these changes contribute to post-operative pain hypersensitivity, which increases the response to noxious stimuli and decreases the pain threshold at the site of the injured tissue as well as the surrounding uninjured tissue. The pre-emptive use of analgesia has been shown to prevent central sensitization and improve postoperative pain control. It may be that the window of opportunity for pre-empting central pain activation is limited. The existing literature provides evidence that the use of local anesthetic wound infiltration as part of a multimodal anesthetic regimen reduces short-term post-operative pain and length of hospital stay and improves joint function after knee joint replacement.31,32
NON-INVASIVE MANAGEMENT OF PAIN IN TKR Cryotherapy There is emerging evidence that application of ice to the site of an arthroplasty results in improved pain control. Ice is believed to work by reducing inflammation, metabolism, and nerve conduction velocity. It is possible that combining ice application with compression for edema prevention could result in further vasoconstriction and inflammation reduction. Kullenberg et al prospectively randomized patients treated with total knee arthroplasty to receive cryotherapy or epidural analgesia.33 Opioid consumption and VAS data were equivalent in the two groups, and the patients treated with cryotherapy had an earlier discharge from the hospital. Levy and Marmar randomized eighty patients undergoing unilateral total
Acetaminophen Acetaminophen in moderate dosages has become ubiquitous as an antipyretic and analgesic agent. It lacks the side effects of NSAIDs and acts as a central analgesic agent. Acetaminophen is available in oral form, and recently it has become available, outside the United States, as an intravenous agent. While hepatotoxicity is the primary side effect, dosages associated with this complication thus far have ranged on the order of 1e4 g/day. Available in Europe, intravenous acetaminophen has proven efficacious for post-operative pain control following major orthopedic surgery. Compared with patients treated with a placebo, those who received intravenous acetaminophen reported decreased pain for the first 6 h following surgery and consumed less morphine during the first 24 h post-operatively. In a similar study, Zhou et al administered 2 g of intravenous paracetamol to patients with moderate or severe pain.35 In the first 5 h after administration, the intravenous paracetamol resulted in decreased pain compared with that provided by a placebo and its efficacy was similar to that of ketorolac over the same time period. The addition of acetaminophen to a multimodal pain regimen seems to have utility, but a complete understanding requires additional evidence. NSAIDs and COX-2 inhibitors In comparison with acetaminophen, NSAIDs and their related cyclooxygenase type-2 (COX-2) inhibitors have a larger evidence base. The traditional NSAIDs inhibit the activity of both COX-1 and COX-2 enzymes. COX-2 enzyme is seen more specifically in acute or chronic inflammatory tissue. Use of selective COX-2 inhibitors dampens adverse effects on gastric mucosa and decreases inhibition of prostaglandin production in the gastrointestinal tract. COX-2 drugs are 100e1000 times more selective for COX-2 than for COX-1. Celecoxib was the first COX-2 drug to be approved for marketing by the FDA, over a decade ago. Despite inconsistent evidence of increases in cardiac morbidity with COX-2 usage, pain relief with improved gastric tolerance remains the foundation of the benefit of selective COX-2 inhibition. Inan et al reported on the use of lornoxicam (a COX-1 agent) for pain control in patients treated with total knee
Pain management in TKR
arthroplasty.36 These subjects received pre-operative and post-operative lornoxicam as well as patient-controlled analgesia with morphine post-operatively. Patients in the control group received patient-controlled analgesia with morphine only. During the first 48 h after the arthroplasty, opioid consumption was significantly lower in the patients receiving lornoxicam (p < 0.05). The patients in the control group also exhibited a trend toward a higher rate of opioid-related side effects. Another study demonstrated the efficacy of COX-2 in reducing both pain and opioid consumption.37 Celecoxib was administered 1 h before total knee arthroplasty and every 12 h thereafter. Patientcontrolled analgesia with opioid medication was also provided. The control cohort received patient-controlled analgesia only. The patients receiving celecoxib reported significantly decreased pain on a VAS at forty-eight (p ¼ 0.03) and seventy-two (p ¼ 0.02) hours following the total knee arthroplasty. Opioid consumption was reduced by 40% in the celecoxib group. The active knee range of motion was significantly greater (10e15 ) during the first three post-operative days in the celecoxib group (p ¼ 0.03). Similar evidence presented by Buvanendran et al supports COX-2 usage. Compared with a placebo, rofecoxib administered pre-operatively and for 8 days following the index total knee arthroplasty resulted in significantly decreased opioid consumption (p < 0.05), decreased VAS pain scores (p < 0.001), decreased side effects (p ¼ 0.047), and an increased knee range of motion over 1 month (p ¼ 0.01). Extrapolation of these results also demonstrated improved patient satisfaction and a shorter period of physical therapy to achieve an adequate range of motion. Analysis of side effects in these studies shows no statistically significant difference in bleeding or the need for transfusion post-operatively. There is overwhelming evidence supporting the use of NSAIDs and COX-2 inhibitors as an integral part of multimodal pain management in orthopedic patients. Concerns have been raised regarding the effect of COX-2 inhibitors and NSAIDs on osseointegration and fracture healing. At this point, little Level-I or II evidence is available to support or refute this concern. There is also a concern regarding bleeding and inhibition of platelet aggregation, which also is not supported by Level-I or Level-II evidence. However, the latter concern may be mitigated by pre-emptively discontinuing use of all NSAIDs 7e10 days prior to surgery. In addition, COX-2 inhibitors with anti-inflammatory properties alone do not seem to be associated with these potential side effects. While previous research has indicted COX-2 inhibitors for increasing thromboembolic events in patients undergoing coronary artery bypass graft surgery, no increase in association with other surgical procedures has been established.
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Gabapentin/pregabalin Marketed as an anticonvulsant and used for neuropathic pain, gabapentin acts on the a2d subunit of the presynaptic voltage gated calcium channels. These channels are accessed along the dorsal horn synapse in spinal neurons. The end result is a decrease in excitatory signal release along the afferent pathway. Peri-operative use of gabapentin and pregabalin has been investigated in prospective trials. In one study, patients were randomized to receive or not receive pregabalin before and for 14 days after total knee arthroplasty.38 The patients who had received the drug had less neuropathic pain at 3 and 6 months, reduced opioid consumption while they were hospitalized, and improved knee flexion over the first 30 days after the operation. A higher risk of side effects (increased confusion and sedation during post-operative day 0 and 1) was reported in the pregabalin group. Using a peri-operative model, Clarke et al found similar results for patients undergoing total knee arthroplasty.39 However, they evaluated all permutations of pre-operative and post-operative gabapentin administration. Post-operative doses of gabapentin decreased opioid consumption during the first 2 days after the operation and significantly improved knee flexion on days 2 and3. The sample size was limited to thirty-six patients, and the study did not demonstrate improved efficacy with the pre-operative use of gabapentin. In a related study examining patients undergoing total hip arthroplasty, Clarke et al found no difference between groups treated with and without gabapentin.40 However, this study also had limited power, and only one dose of gabapentin was administered pre-operatively and post-operatively. The gabapentinoids studied outside the setting of total joint arthroplasty have demonstrated efficacy when used in combination with other agents or alone. More research is needed to identify the true efficacy with respect to the duration and timing of administration to patients undergoing orthopedic procedures. Common side effects of these agents are dizziness and somnolence.
Tramadol Tramadol is a synthetic centrally acting opioid agonist and monoamine uptake inhibitor (acting on noradrenaline and serotonin). These two synergistic pathways create a potential for a unique adjuvant for pain control. However, efficacy has been found to be limited in prospective trials. Stubhaug et al provided 50 and 100-mg doses of tramadol in a placebo-controlled study of patients undergoing total joint arthroplasty.41 There was no difference in any pain control outcome variable between the placebo and tramadol
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groups. Stiller et al evaluated tramadol use in a multimodal role as an adjuvant to patient-controlled analgesia with morphine in patients treated with total knee arthroplasty.42 While pain relief was not significantly different between those receiving tramadol with patient-controlled analgesia and those using patient-controlled analgesia alone, morphine consumption was significantly decreased in the tramadol group (p < 0.05). Differences in the designs of these prospective studies make it difficult to ascertain the role of tramadol in multimodal pain management.
N-Methyl-D-aspartate non-competitive antagonists N-methyl-D-aspartate (NMDA) receptor antagonists potentiate the effect of opioids and prevent hyperalgesic complications from uncontrolled pain. Agents used to modulate the pain pathway in the central nervous system include ketamine, magnesium, and dextromethorphan. In a study of forty patients randomized to receive magnesium sulfate or saline solution parenterally during spinal anesthesia, with both groups receiving patient-controlled analgesia with morphine and ketorolac post-operatively, the magnesium group had lower pain scores and utilized less opioid without any difference in side effects.43 In another study, evaluating the role of magnesium added to epidural fentanyl, patients receiving magnesium required significantly (p < 0.05) less fentanyl without any increase in side effects.44 Ketamine is another NMDA antagonist advocated for nociceptive relief. Remérand et al studied 154 patients treated with total joint arthroplasty; seventy-nine received intravenous ketamine pre-operatively and for 24 h post-operatively and the placebo group received saline solution infusion.45 All patients were managed with a multimodal pain management regimen concurrently. The results showed significantly decreased morphine consumption (p ¼ 0.004) and significantly decreased pain in the patients receiving ketamine (p ¼ 0.036). There appears to be a promising role for ketamine as a multimodal analgesic, although potential side effects include hallucinations, nausea, emesis, and vision changes. Transdermal patches While transdermal fentanyl patches add to the total narcotic dosage, they also provide an alternative route for administration of pain control agents. Comparisons with patientcontrolled morphine analgesia have demonstrated comparable efficacy and safety. Given the varying delivery and time course of narcotic administration, the synergistic effects of fentanyl patches with other routes of pain control may be beneficial. Minville et al reported on a small group of patients who had had a 50-mg/h matrix fentanyl patch
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applied 10 h prior to a total hip arthroplasty.46 No difference in respiratory depression was noted between that group and patients who had not received the patch. The application of the patch decreased post-operative use of patient-controlled analgesia with morphine; however, transdermal patches may not curtail overall opioid consumption due to the administration of fentanyl in this study. Because of a concern regarding unpredictable delivery and potential adverse effects, most centers do not consider transdermal patches as a suitable modality for management of acute post-operative pain.
DISCUSSION Total knee replacement (TKR) is one of the most successful surgical procedures. Management of pain following TKR is an important aspect of this procedure. Satisfactory pain management after TKR has several important implications. Adequate pain control allows faster rehabilitation1 and reduces the risk of post-operative complications. Pain control is also the most important component of patient satisfaction. Patients with well-controlled post-operative pain have an improved health-related quality of life and less time lost from work, and they are more satisfied with their treatment. Appropriate and adequate post-operative pain management is associated with shorter hospital stays, reduced rates of unanticipated hospital admissions and readmissions due to pain, and an overall reduced cost of care. Opioids are very effective analgesics and constitute the foundation of the management of moderate-to-severe acute post-operative pain despite their association with increased respiratory, cardiac, urinary, gastrointestinal, and neurological complications. In addition, opiate-induced respiratory depression and the associated post-operative hypoxia is linked with myocardial ischemia, tachycardia, acute cognitive disturbances, delayed wound-healing, and an increased incidence of wound infection. Because of concerns about side effects, physicians often prescribe doses of opioids that are lower than what would have the optimal effect. A newer concept in pain management in TKR is multimodal pain management. This concept was introduced in an attempt to control pain with less reliance on opioids. Multimodal analgesia is a multidisciplinary approach to pain management with a goal to maximize the analgesic effect and minimize the side effects of the medications. It takes advantage of the additive or synergistic effects of various analgesics, permitting the use of smaller doses with a concomitant reduction in side effects. Because many of the negative effects of analgesic therapy are related to parenteral opioid limiting its use is a major principle of
Pain management in TKR
Table 4 Pain management in TKR.
multimodal analgesia. Over the past decade, a greater understanding of pain mechanisms has led to the concept of pre-emptive analgesia. Pre-emptive analgesia involves the administration of analgesics prior to painful stimuli to prevent the establishment of central sensitization and thus the amplification of post-operative pain. It starts before surgery and covers both the period of surgery and the initial post-operative period. In order to understand multimodal pain management, a fundamental knowledge of how pain is generated is required. Available evidence indicates that multimodal pain management has a useful role for patients undergoing total joint arthroplasty. The rationale for multimodal pain management is to provide pain relief for the patient with less reliance on opioids. There is ample evidence to suggest that traditional NSAIDs and the associated COX-2 inhibitors are the most effective agents for decreasing opioid consumption. Fewer investigators have analyzed pain levels and the impact on post-operative mobilization. Overall, NSAIDs, spinal analgesia, peripheral nerve blocks, and intra-articular injections have resulted in improved VAS pain scores, with variable strengths of evidence. The most information has been reported for NSAID use. There is still a lack of research on many adjunctive agents and potential outcomes. However, most agents have shown trends toward improved activity in physical therapy and patient satisfaction. Thus, the primary goal of modern pain management is to reduce pain at both the central and the peripheral levels, in combination with pre-emptive analgesia using a multimodal protocol (Table 4). This strategy should enhance restoration of function by allowing patients to participate in the rehabilitation programs more easily, thereby improving the overall post-operative outcome.
CONFLICTS OF INTEREST All authors have none to declare.
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REFERENCES 1. National Joint Registry. 7th Annual Report; 2010. 2. Agency for Healthcare Research and Quality. HCUP: A Tool for Identifying, Tracking, and Analyzing National Hospital Statistics. http://www.hcup-us.ahrq.gov/reports/statbriefs/ sb34.jsp. 3. Jain NB, Higgins LD, Ozumba D, et al. Trends in epidemiology of knee arthroplasty in the United States, 1990e2000. Arthritis Rheum. 2005;52:3928e3933. 4. Task Force on Taxonomy Part III. Pain Terms. A Current List with Definitions and Notes on Usage. International Association for the Study of Pain Web site, http://www.iasp-pain.org/Content/ NavigationMenu/GeneralResource-Links/PainDefinitions/ default.htm; Published 1994. Accessed 12.01.11. 5. Phillips DM. JCAHO pain management standards are unveiled. Joint Commission on Accreditation of Healthcare Organizations. JAMA. 2000;284(4):428e429. http://dx.doi. org/10.1001/jama.284.4.428 [CrossRef]. 6. Bonica JJ. Postoperative pain. In: Bonica JJ, ed. The Management of Pain. 2nd ed. Philadelphia: Lea and Febiger; 1990: 461e480. 7. Wylde V, Rooker J, Halliday L, Blom A. Acute post-operative pain at rest after hip and knee arthroplasty: severity, sensory qualities and impact on sleep. Orthop Traumatol Surg Res. in press. 8. Capdevila X, Bringuier S, Borgeat A. Infectious risk of continuous peripheral nerve blocks. Anesthesiology. 2009;110: 182e188. 9. Biboulet P, Morau D, Aubas P, Bringuier-Branchereau S, Capdevila X. Postoperative analgesia after total-hip arthroplasty: comparison of intravenous patientcontrolled analgesia with morphine and single injection of femoral nerve or psoas compartment block. A prospective, randomized, double-blind study. Reg Anesth Pain Med. 2004;29:102e109. 10. Kardash K, Hickey D, Tessler MJ, Payne S, Zukor D, Velly AM. Obturator versus femoral nerve block for analgesia after total knee arthroplasty. Anesth Analg. 2007;105: 853e858. 11. Ozen M, Inan N, Tümer F, Uyar A, Baltaci B. The effect of 3in-1 femoral nerve block with ropivacaine 0.375% on postoperative morphine consumption in elderly patients after total knee replacement surgery. Agri. 2006;18:44e50. 12. Singelyn FJ, Deyaert M, Jorist D, Pendeville E, Gouverneur JM. Effects of intravenous patient-controlled analgesia with morphine, continuous epidural analgesia, and continuous three-in-one block on postoperative pain and knee rehabilitation after unilateral total knee arthroplasty. Anesth Analg. 1998;87:88e92. 13. Ilfeld BM, Ball ST, Gearen PF, et al. Ambulatory continuous posterior lumbar plexus nerve blocks after hip arthroplasty:
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a dual-center, randomized, triple-masked, placebo-controlled trial. Anesthesiology. 2008;109:491e501. Richman JM, Liu SS, Courpas G, et al. Does continuous peripheral nerve block provide superior pain control to opioids? A meta-analysis. Anesth Analg. 2006;102: 248e257. Fowler SJ, Symons J, Sabato S, Myles PS. Epidural analgesia compared with peripheral nerve blockade after major knee surgery: a systematic review and metaanalysis of randomized trials. Br J Anaesth. 2008;100:154e164. Barrington MJ, Watts SA, Gledhill SR, et al. Preliminary results of the Australasian Regional Anaesthesia Collaboration: a prospective audit of more than 7000 peripheral nerve and plexus blocks for neurologic and other complications. Reg Anesth Pain Med. 2009;34:534e541. Postoperative analgesia and functional recovery after totalknee replacement: comparison of a continuous posterior lumbar plexus (psoas compartment) block, a continuous femoral nerve block, and the combination of a continuous femoral and sciatic nerve block. Reg Anesth Pain Med. 2005;30:434e445. CrossRefMedlineWeb of Science. Continuous versus single injection lumbar plexus blocks: comparison of the effects on morphine use and early recovery after total knee arthroplasty. Reg Anesth Pain Med. 2005;30: 541e547. CrossRefMedlineWeb of Science. Postoperative analgesia following total knee replacement: an evaluation of the addition of an obturator nerve block to combined femoral and sciatic nerve block. Acta Anaesthesiol Scand. 2002;46:95. CrossRefMedlineWeb of Science. Block BM, Liu SS, Rowlingson AJ, Cowan AR, Cowan JA Jr, Wu CL. Efficacy of postoperative epidural analgesia: a meta-analysis. JAMA. 2003;290:2455e2463. Capdevila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d’Athis F. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology. 1999;91:8e15. Casati A, Ostroff R, Casimiro C, et al. Chiropolis Study Group. 72-hour epidural infusion of 0.125% levobupivacaine following total knee replacement: a prospective, randomized, controlled, multicenter evaluation. Acta Biomed. 2008;79: 28e35. Förster JG, Rosenberg PH. Small dose of clonidine mixed with low-dose ropivacaine and fentanyl for epidural analgesia after total knee arthroplasty. Br J Anaesth. 2004;93:670e677. Hartrick CT, Martin G, Kantor G, Koncelik J, Manvelian G. Evaluation of a singledose, extended-release epidural morphine formulation for pain after knee arthroplasty. J Bone Jt Surg Am. 2006;88:273e281. Choi PT, Bhandari M, Scott J, Douketis J. Epidural analgesia for pain relief following hip or knee replacement. Cochrane Database Syst Rev. 2003;3:CD003071.
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26. Kehlet H, Dahl JB. The value of “multimodal” or “balanced analgesia” in postoperative pain treatment. Anesth Analg. 1993;77:1048e1056. 27. American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2004;100:1573e1581. 28. Ranawat CS, Ranawat AS, Mehta A. Total knee arthroplasty rehabilitation protocol: what makes the difference? J Arthroplasty. 2003;18(3 suppl 1):27e30. http://dx.doi.org/ 10.1054/arth.2003.50080 [CrossRef]. 29. Ranawat AS, Ranawat CS. Pain management and accelerated rehabilitation for total hip and total knee arthroplasty. J Arthroplasty. 2007;22(7 suppl. 3):12e15. http://dx.doi.org/ 10.1016/j.arth.2007.05.040 [CrossRef]. 30. Kerr DR, Kohan L. Local infiltration analgesia: a technique for the control of acute postoperative pain following knee and hip surgery: a case study of 325 patients. Acta Orthop. 2008;79:174e183. 31. Adam F, Chauvin M, Du Manoir B, Langlois M, Sessler DI, Fletcher D. Small-dose ketamine infusion improves postoperative analgesia and rehabilitation after total knee arthroplasty. Anesth Analg. 2005;100(2):475e480. http://dx.doi.org/10. 1213/01.ANE.0000142117.82241.DC [PMC free article] [PubMed] [Cross Ref]. 32. Liu SS, Richman JM, Thirlby RC, Wu CL. Efficacy of continuous wound catheters delivering local anesthetic for postoperative analgesia: a quantitative and qualitative systematic review of randomized controlled trials. J Am Coll Surg. 2006;203(6):914e932. http://dx.doi.org/10.1016/j.jamcollsurg.2006.08.007 [PubMed] [Cross Ref]. 33. Kullenberg B, Ylipää S, Söderlund K, Resch S. Postoperative cryotherapy after total knee arthroplasty: a prospective study of 86 patients. J Arthroplasty. 2006;21:1175e1179. 34. Levy AS, Marmar E. The role of cold compression dressings in the postoperative treatment of total knee arthroplasty. Clin Orthop Relat Res. 1993;297:174e178. 35. Zhou TJ, Tang J, White PF. Propacetamol versus ketorolac for treatment of acute postoperative pain after total hip or knee replacement. Anesth Analg. 2001;92:1569e1575. 36. Inan N, Ozcan N, Takmaz SA, Ozcan A, Erdo gan I, Baltaci B. Efficacy of lornoxicam in postoperative analgesia after total knee replacement surgery. Agri. 2007;19:38e45. 37. Huang YM, Wang CM, Wang CT, Lin WP, Horng LC, Jiang CC. Perioperative celecoxib administration for pain management after total knee arthroplasty e a randomized, controlled study. BMC Musculoskelet Disord. 2008;9:77. 38. Buvanendran A, Kroin JS, Della Valle CJ, Kari M, Moric M, Tuman KJ. Perioperative oral pregabalin reduces chronic pain
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after total knee arthroplasty: a prospective, randomized, controlled trial. Anesth Analg. 2010;110:199e207. Clarke H, Pereira S, Kennedy D, et al. Gabapentin decreases morphine consumption and improves functional recovery following total knee arthroplasty. Pain Res Manag. 2009;14: 217e222. Clarke H, Pereira S, Kennedy D, et al. Adding gabapentin to a multimodal regimen does not reduce acute pain, opioid consumption or chronic pain after total hip arthroplasty. Acta Anaesthesiol Scand. 2009;53:1073e1083. Stubhaug A, Grimstad J, Breivik H. Lack of analgesic effect of 50 and 100 mg oral tramadol after orthopaedic surgery: a randomized, double-blind, placebo and standard active drug comparison. Pain. 1995;62:111e118. Stiller CO, Lundblad H, Weidenhielm L, et al. The addition of tramadol to morphine via patient-controlled analgesia does not lead to better post-operative pain relief
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after total knee arthroplasty. Acta Anaesthesiol Scand. 2007;51:322e330. Hwang JY, Na HS, Jeon YT, Ro YJ, Kim CS, Do SH. I.V. infusion of magnesium sulphate during spinal anaesthesia improves postoperative analgesia. Br J Anaesth. 2010;104: 89e93. Bilir A, Gulec S, Erkan A, Ozcelik A. Epidural magnesium reduces postoperative analgesic requirement. Br J Anaesth. 2007;98:519e523. Remérand F, Le Tendre C, Baud A, et al. The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study. Anesth Analg. 2009;109:1963e1971. Minville V, Lubrano V, Bounes V, et al. Postoperative analgesia after total hip arthroplasty: patient-controlled analgesia versus transdermal fentanyl patch. J Clin Anesth. 2008;20: 280e283.
Review Article
Pain management in total knee replacement Raju Vaishyaa,*, Ajaz Majeedb
ABSTRACT Total knee replacement (TKR) is one of the most commonly done surgical procedures, with over 150,000 total knee replacements and THR performed annually in England and Wales in the National Health Service (NHS). In India although clear-cut data is not available but the incidence is increasing. In the US, 431,000 TKRs are performed yearly and the utilization of TKR has increased over the last two decades, especially among younger patients .TKR may be associated with severe post-operative pain. The International Association for the Study of Pain (IASP) has defined pain as “an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has made adequate pain management a priority and has deemed monitoring pain as the “fifth” vital sign. Copyright © 2012, Indraprastha Medical Corporation Ltd. All rights reserved. Keywords: International association for the study of pain, Deep vein thrombosis, Nosocomial infection
Total knee replacement (TKR) is one of the most commonly done surgical procedures, with over 150,000 total knee replacements and THR performed annually in England and Wales in the National Health Service (NHS).1 In India although clear-cut data is not available but the incidence is increasing. In the US, 431,000 TKRs are performed yearly2 and the utilization of TKR has increased over the last two decades, especially among younger patients.3 TKR may be associated with severe post-operative pain. The International Association for the Study of Pain (IASP) has defined pain as “an unpleasant sensory or emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.4 The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) has made adequate pain management a priority and has deemed monitoring pain as the “fifth” vital sign.5
BACKGROUND TKR may result in severe post-operative pain usually requiring hospitalization from 5 to 10 days to provide effective analgesia. This prolonged hospital stay and relative immobilization a
of the patient in bed may invite nosocomial infection and deep vein thrombosis (DVT). In addition to causing unnecessary distress and discomfort during the post-operative period, poorly managed post-operative pain can have negative consequences for long-term surgical outcomes. Adequate post-operative pain relief following TKR is very important to optimal post-operative recovery (Table 1). The faster that mobilization and rehabilitation can progress, the better the ultimate outcome will be. Adequate pain control post-operatively should allow earlier patient mobilization with the aim of increasing strength and proprioception and decreasing the incidence of the development of thromboembolism. In complicated cases, prolonged immobility due to pain can cause the development of muscular contractures or atrophy that eventually cause the development of long-term functional impairments (Table 2). Adequate management of post-operative pain still poses a significant challenge to healthcare, as demonstrated by a review of the literature which concluded that approximately 60% of patients experienced severe pain and approximately 30% patients experienced moderate pain after surgery.6 In a recent study at the Avon Orthopedic Center, 58% of TKR patients reported moderate or severe pain on the first post-operative day.7
Professor, Senior Consultant, bDNB student, Department of Orthopaedics & Joint Replacement Surgery, Indraprastha Apollo Hospitals, Mathura Road, New Delhi 110076, India. * Corresponding author. Tel.: þ91 9810123331, email: [email protected] Received: 9.8.2012; Accepted: 27.8.2012; Available online 5.9.2012 Copyright Ó 2012, Indraprastha Medical Corporation Ltd. All rights reserved. http://dx.doi.org/10.1016/j.apme.2012.08.012
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Table 1 Advantages of adequate analgesia in TKR.
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risk of heart attack while overdoses can lead to liver damage. Navigating these side effects amongst the co-morbidities and potential drug interactions with concurrent medications in the elderly population is typically problematic.
PAIN PERCEPTION
Current pharmaceutical pain relief options for TKR pain have limitations due to associated side effects, often requiring additional treatment for them. Unfortunately, there are very few pain management options available that can provide a treatment that is both non-invasive and without side effects. Side effects of the opiate pain medication include lethargy, sedation, respiratory depression, nausea, vomiting, numbness, weakness, urinary retention, hypotension and digestive discomfort, including gastro paresis and constipation. Opioids may also alter mood negatively and/or induce euphoria. The side effects of non-steroidal anti-inflammatory agents (NSAIDS) include gastric upset, sometimes predisposing symptoms leading to peptic ulcers. COX-2 inhibitors have been found to increase Table 2 Effect of inadequate analgesia in TKR.
Pain is generated because of local inflammation and nerve damage due to trauma or temperature change, during TKR. Tissue insult causes local release of inflammatory mediators such as bradykinin, prostaglandins, substance P, and histamine. Receptors detect changes in pain and temperature and initiate afferent signals in the peripheral nervous system through unmyelinated C fibers or myelinated A fibers. Signals reach the dorsal root ganglion and synapse in the dorsal horn of the spinal cord. At this juncture, spinal modulation of the afferent signals occurs through opioids, a2 agonists, and Nmethyl-D-aspartate (NMDA) receptor antagonists. Neurotransmission is further modulated by other substances such as gamma-aminobutyric acid (GABA). From here, spinothalamic tracts carry ascending signals, where further central modulation can occur in supraspinal modulatory centers.4 The various agents used as part of a multimodal strategy affect nociceptors and different regions of common pain pathways to achieve an overall reduction in perceived pain (Fig. 1).
Assessment of pain In the assessment of pain intensity, various rating scale techniques are used. The most commonly used forms are:
The category rating scales (Fig. 2) (e.g. none, mild, moderate, severe, unbearable or 1e5). The visual analog scales (VAS) (Fig. 3) The VAS has been shown to be more sensitive to change and is therefore more widely used. These scales may also be incorporated into pain diaries. McGill pain questionnaire (MPQ) (Melzack, 1975) (78 pain adjectives arranged into 20 groups further arranged into sets of words describing sensory aspects of the quality of pain).
POST-OPERATIVE PAIN CONTROL AFTER TOTAL KNEE REPLACEMENT Traditionally, acute post-operative pain following TKR has been managed with:
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Fig. 1 Pain pathways and multimodal analgesic therapy.
1. Peripheral nerve blocks 2. Epidural analgesia 3. Parental (IV) analgesia (e.g., analgesia) 4. Multimodal analgesia 5. Local infiltration analgesia (LIA)
patient-controlled
Peripheral nerve blocks Innervation of the knee joint Knowledge about the innervation of the knee joint is important in performing a peripheral nerve block. Innervation of the knee joint (Fig. 4) is derived from (i) femoral nerve via the branch to vastus medialis (anterior aspect of the joint
Fig. 2 Category rating scale.
capsule); (ii) sciatic nerve via genicular branches of both tibial and common peroneal components (posterior aspect of the joint capsule and all of the intra-articular structures); and (iii) obturator nerve by a branch from its posterior division that accompanies the femoral artery through adductor Magnus into the popliteal fossa. Cutaneous innervation of the anterior aspect of the knee is supplied by the femoral nerve. The obturator nerve supplies the skin on the medial aspect of the knee in less than 40% of people.
Peripheral nerve blocks Peripheral nerve blocks with a local anesthetic have been used commonly in total joint replacements (Table 3). Patients undergoing TKR may have a femoral nerve block
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Fig. 3 VAS scale.
and/or a sciatic nerve block. Peripheral nerve blocks may be continuous or administered as a one-time dose. Continuous peripheral nerve blocks provide the most effective and long-lasting analgesia with fewer side effects when compared with PCA morphine or continuous epidural analgesia. Potential side effects include nerve damage and a lack of muscle control in the immediate rehabilitation period. Local infection due to an indwelling catheter has been reported in between 0% and 3% of cases.8 Comparisons have shown that one-time blocks fail to provide the prolonged relief of continuous blocks, with no difference after the first four to 6 h following a total joint arthroplasty.9 Kardash et al administered one-time doses of bupivacaine and epinephrine in the form of a femoral nerve block or
Fig. 4 Innervation of lower limb.
obturator nerve block, or gave a placebo, to patients treated with total knee arthroplasty.10 All patients were concurrently receiving multimodal pain agents. Results showed that an obturator block was no different from the placebo, and the femoral nerve block lowered only pain scores, not morphine consumption. In another study, Ozen et al compared the so-called three-in-one femoral nerve block (femoral nerve, lateral femoral cutaneous nerve, and obturator nerve blocks) with the use of no block in patients undergoing total knee arthroplasty.11 Less consumption of patient-controlled opioid analgesia and lower visual analog scale (VAS) pain scores were recorded for the three-in-one femoral nerve block cohort. In another investigation, patients receiving the nerve block were able to undergo faster rehabilitation than the cohort patients receiving patient-controlled analgesia with morphine.12 A peripheral nerve block with continuous infusion provides analgesia superior to that resulting from a one-time injection.13 Most studies in the literature support the use of a continuous peripheral nerve block in multimodal pain management. A meta-analysis by Richman et al demonstrated significantly improved pain control (p < 0.05) in patients receiving a peripheral nerve block compared with that associated with opioid analgesia alone.14 According to Fowler et al, peripheral nerve blocks have a side-effect profile that is more desirable than that of epidural analgesia while maintaining a similar level of pain relief.15 Peripheral nerve blocks created less urinary retention and hypotension in that study. Patients treated with a unilateral nerve block had less restriction of movement than those who received epidural analgesia. The primary concern about the use of peripheral nerve blocks is the development of late neurological sequelae, including permanent nerve damage. A recent investigation of over 6000 patients was performed to examine these complications.16 While 0.5% of patients developed nerve symptoms post-operatively, the incidence of symptoms related to the peripheral nerve block was only 0.04%. A meta-analysis of peripheral nerve block studies done between 1995 and 2005 revealed a 0.34% incidence of symptomatic post-operative neuropathy with femoral nerve blocks64. The best combination of peripheral nerve blocks and choice of local anesthetic solution for continuous infusion following total knee arthroplasty is currently unknown.
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Table 3 Features of peripheral nerve blocks. Nerve block Femoral nerve block
Advantages d d d d
Sciatic nerve block
d
Disadvantages
Easy to perform Good efficacy Less side effects Faster rehabilitation Combined with femoral nerve block provide adequate analgesia with less side effects
d d
d
d d
Obturator nerve block
d
Lumbosacral block
d
d
Adding obturator block to sciatic and femoral nerve blocks improve analgesia Better than femoral nerve block because it blocks the femoral, obturator, and lateral femoral cutaneous nerves more reliably Facilitate earlier mobilization
Femoral nerve block The knee is innervated by the femoral nerve, which is the largest branch of the lumbosacral plexus. The femoral nerve supplies about 80% of the sensation in the knee. The femoral nerve supplies the motor contraction of the iliacus, pectineus, and anterior thigh muscles. The femoral nerve also supplies the cutaneous and articular branches to the front and inner thigh, leg and foot, and hip and knee. Femoral nerve block has a high success rate and carries a low risk of complications. However, proximal spread of local anesthetic to the other branches of the lumbar plexus is unreliable. Single-shot femoral nerve block using a longacting amide local anesthetic will provide analgesia to the anterior aspect of the knee for up to 24 h, although the incidence of profound motor block of the quadriceps muscles will be unacceptably high if large volumes of concentrated local anesthetic agents are used. The benefit of using a continuous femoral nerve block to control pain after total knee replacement surgery has been tested and proven to be effective. By using this method for pain control, fewer narcotic medications will be needed to control the pain. By using fewer narcotics there will be fewer side effects. Advantages Continuous femoral nerve block is technically simple to perform with a low incidence of side effects. The infusion is continued for 48e72 h before catheter removal and patients are allowed to mobilize during this time provided they have adequate motor power and proprioception. Several recent studies have confirmed that the analgesic efficacy of this technique is equivalent to both continuous epidural analgesia and continuous lumbar plexus block following total knee arthroplasty; however, continuous
d d d
Neurovascular injury Localization
Time consuming procedure to give two simultaneous blocks Sciatic nerve injury Isolated block not adequate Localization difficult Inadequate analgesia, if performed alone Difficult to perform
femoral nerve block was associated with fewer side effects than the other techniques.17 Ozen et al (2006) found that the use of a FNB led to a reduction in post-operative opioid administration and its associated side effects. Sciatic nerve block Pain behind the knee is a problem for a significant proportion of patients who only receive femoral nerve block because all of the intra-articular structures are innervated by the tibial nerve. The benefit of adding a sciatic nerve block to a femoral nerve block has become the subject of debate in regional anesthesia circles. Advantages Single-shot sciatic nerve block combined with femoral nerve block will provide analgesia for up to 24 h. When performing the block using a nerve stimulator, success rates are highest if inversion (tibial and peroneal nerve) or plantar flexion (tibial nerve) of the foot is elicited. The combination of continuous femoral and sciatic nerve blocks has been shown to provide superior analgesia with less PONV when compared to other analgesic techniques. Disadvantages The potential disadvantages of adding a continuous sciatic block to continuous femoral nerve block are increased time required to perform two continuous blocks and the potential problems mobilizing patients post-operatively because of more extensive motor block. The practical alternative is to use continuous femoral nerve block combined with single-shot sciatic nerve block. Lumbar plexus block It has been suggested that lumbar plexus (Fig. 5) block may be better than femoral nerve block because it blocks the
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Fig. 5 Anatomy of lumbar plexus.
femoral, obturator, and lateral femoral cutaneous nerves more reliably. However, there is little evidence from clinical trials to support this hypothesis. Continuous lumbar plexus block is a logical and effective technique that has been shown to improve analgesia and facilitate earlier mobilization following total knee arthroplasty compared with single-shot lumbar plexus block.18 Again, the combination of a sciatic nerve block should be considered. Obturator nerve block The addition of a separate obturator block to a femoral or lumbar plexus block is contentious. Femoral nerve block has been shown to spare the obturator nerve in as many as 50% of patients, contrasting with lumbar plexus block when the obturator nerve is missed in <10%. It is interesting to note that a comparative study of continuous lumbar plexus and continuous femoral nerve block found no difference in analgesia. On the other hand, there is some evidence that adding a single-shot obturator block to single-shot sciatic and femoral nerve blocks may improve analgesia.19
Epidural analgesia Administration of epidural analgesia/anesthesia is one of the most popular techniques used in TKR surgery as it is associated with improved pain control compared with that provided by patient-controlled analgesia.20 In a direct comparison with patient-controlled analgesia with
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morphine, epidural analgesia was found to decrease the duration of post-operative inpatient rehabilitation.21 Analgesic agents delivered to the epidural space can be administered continuously or as a single dose. Typically, an opioid combined with epinephrine is administered during administration of epidural anesthesia. Epinephrine, through local vasoconstriction, reduces opioid absorption and leads to a relatively higher local concentration of the opioid agent and greater analgesia from the local anesthetic. Ketamine can also be added as a synergistic agent. Side effects of epidural injection include hypotension and decreased motor function. Newer extended-release one-time dosage formulations consisting of a single epidural injection of morphine may relieve problems associated with catheter malfunction. Casati et al followed patients who received epidural 0.125% levobupivacaine through a catheter for 72 h following total knee arthroplasty.22 All patients also received patient-controlled analgesia with morphine. As compared with a group that received only patient-controlled morphine post-operatively, those who received the levobupivacaine had better pain scores and decreased morphine consumption over the 3 days for which the epidural was maintained. Most importantly, no decrease in motor function was noted, which minimized loss of physical therapy. Förster and Rosenberg studied the effect of adding clonidine to a fentanyl epidural infusion and reported a decrease in morphine consumption compared with that by patients who had not received the clonidine additive.23 The only problem was an average drop in blood pressure of 5 mmHg and an average drop in the pulse rate of 3 beats per minute in the clonidine group. Another relatively recent advancement includes the availability of microsomal delivery technology that allows epidural delivery of extended-release opioids as a one-time injection. One such product is extended-release epidural morphine, commercially available as DepoDur, which provides 48 h of extended morphine release. In a study of patients treated with total knee arthroplasty who received extended-release epidural morphine through a single injection and post-operative patient-controlled analgesia opioids, Hartrick et al noted decreased pain and opioid consumption, compared with the values for patients who received a sham epidural, although four patients over 64 years of age experienced serious respiratory depression.24 Currently, it is recommended that extended-release epidural morphine be used cautiously in older patients and patients with sleep apnea. Meta-analyses of studies of epidural analgesia have demonstrated improved pain control, especially during early post-operative periods.25 Significant side effects include pruritus (odds ratio ¼ 4.74), urinary retention (odds ratio ¼ 3.50), and hypotension (odds ratio ¼ 2.78). The odds ratios for respiratory depression and nausea were not significant (the confidence interval included 1).
Pain management in TKR
Patient-controlled analgesia (PCA) This method provides an intravenous pump attached to the intravenous site-allowing patient to administer his own pain medication after surgery. The machine has been used for over 20 years and has a safe record of use. The machine has a control button that can be pushed 8e10 times per hour when pain is experienced. The PCA has several advantages as well as disadvantages due to the nature of the medication being administered. Since the medicine is administered directly into the intravenous line, the medication works very quickly. If patient is in pain, patient does not need to call the nurse to be given pain medication. The main disadvantage of PCA is that the medication used can be quite sedating for some patients, making it difficult to participate in post-operative physical therapy. Other disadvantages are the side effects associated with narcotics including nausea, vomiting, itching and urinary retention (inability to urinate). The PCA cannot be used if patient has an allergy or sensitivity to these medications. Contrary to popular belief, patient cannot become addicted to morphine by using a PCA in a controlled environment and for a limited period of time. The use of PCA is limited to 72 h or less to prevent or decrease side effects. The effectiveness of analgesia attributed to the PCA pump is about 75% so breakthrough pain medications are readily available for all patients on PCA.
Multimodal analgesia As the name implies, multimodal pain management involves the use of multiple agents that act at different regions of the pain pathway. The rationale for this strategy is that it reduces the use of opioid agents and their adverse side effects. A combination approach allows better overall pain control. One aspect of multimodal pain management involves pre-emptive administration of analgesics and/or anti-inflammatory agents. These agents are given prior to the initiation of operative treatment and the release of local inflammatory pain mediators. Pre-emptive analgesia was first described by Wall in 1985. Since then, there has been extensive research related to administration of agents before surgery in an effort to alleviate post-operative pain. Kehlet and Dahl introduced multimodal pain management in 1993 with encouragement and equivocation.26 Much of the pain pathway had been investigated, but strong clinical evidence supporting multimodal pain management was lacking. Since that report, evidence has mounted to support much of this pain management process. Currently, the American Society of Anesthesiologists Task Force on Acute Pain Management recommends a multimodal pain
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regimen, specifically with the incorporation of non-steroidal anti-inflammatory drugs (NSAIDs) when medically appropriate.27 Over the past 10 years, multimodal pain management protocol after TKA has undergone several changes using various agents to reduce post-operative pain, including the adoption of pre-emptive analgesia, the use of local periarticular injections, and the introduction of a comprehensive post-operative pain protocol.28,29
Local infiltration analgesia In order to avoid the problems of regional analgesia or opioid, and to minimize the complications, recently, a local infiltration analgesia (LIA) technique was developed by Kerr and Kohan in Sydney, Australia (Röstlund and Kehlet 2007, Kerr and Kohan 2008).30 The technique involves the infiltration of a large volume dilute solution of a long-acting local anesthetic agent, often with adjuvants (e.g. epinephrine, ketorolac, an opioid), throughout the wound at the time of surgery (Figs. 6 and 7). The technique, known as local infiltration analgesia (LIA), was developed specifically to avoid sedation and facilitate rapid physiological recovery after lower limb arthroplasty in order to enable early mobilization and discharge. The idea of administering analgesia directly to the operative site with minimal systemic side effects is an attractive option. Surgical trauma during total knee replacement modifies the responsiveness of the nervous system in two ways. It causes peripheral sensitization by reducing the threshold for afferent nociceptive neurons, and it causes central sensitization by increasing the excitability of spinal
Fig. 6 Intra-operative photograph showing the locations for deep intra-operative injection: posterior capsule (1); posteromedial structures (2); periarticular synovium (3).
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knee arthroplasty to be treated with cryotherapy or normal compressive dressings and found that the cryotherapy group required less morphine.34 Current evidence supports the use of cryotherapy, as this modality has little or no side effects.
Pharmaceutical agents
Fig. 7 Intra-operative photograph showing the locations for superficial intra-operative injection.
neurons. Together these changes contribute to post-operative pain hypersensitivity, which increases the response to noxious stimuli and decreases the pain threshold at the site of the injured tissue as well as the surrounding uninjured tissue. The pre-emptive use of analgesia has been shown to prevent central sensitization and improve postoperative pain control. It may be that the window of opportunity for pre-empting central pain activation is limited. The existing literature provides evidence that the use of local anesthetic wound infiltration as part of a multimodal anesthetic regimen reduces short-term post-operative pain and length of hospital stay and improves joint function after knee joint replacement.31,32
NON-INVASIVE MANAGEMENT OF PAIN IN TKR Cryotherapy There is emerging evidence that application of ice to the site of an arthroplasty results in improved pain control. Ice is believed to work by reducing inflammation, metabolism, and nerve conduction velocity. It is possible that combining ice application with compression for edema prevention could result in further vasoconstriction and inflammation reduction. Kullenberg et al prospectively randomized patients treated with total knee arthroplasty to receive cryotherapy or epidural analgesia.33 Opioid consumption and VAS data were equivalent in the two groups, and the patients treated with cryotherapy had an earlier discharge from the hospital. Levy and Marmar randomized eighty patients undergoing unilateral total
Acetaminophen Acetaminophen in moderate dosages has become ubiquitous as an antipyretic and analgesic agent. It lacks the side effects of NSAIDs and acts as a central analgesic agent. Acetaminophen is available in oral form, and recently it has become available, outside the United States, as an intravenous agent. While hepatotoxicity is the primary side effect, dosages associated with this complication thus far have ranged on the order of 1e4 g/day. Available in Europe, intravenous acetaminophen has proven efficacious for post-operative pain control following major orthopedic surgery. Compared with patients treated with a placebo, those who received intravenous acetaminophen reported decreased pain for the first 6 h following surgery and consumed less morphine during the first 24 h post-operatively. In a similar study, Zhou et al administered 2 g of intravenous paracetamol to patients with moderate or severe pain.35 In the first 5 h after administration, the intravenous paracetamol resulted in decreased pain compared with that provided by a placebo and its efficacy was similar to that of ketorolac over the same time period. The addition of acetaminophen to a multimodal pain regimen seems to have utility, but a complete understanding requires additional evidence. NSAIDs and COX-2 inhibitors In comparison with acetaminophen, NSAIDs and their related cyclooxygenase type-2 (COX-2) inhibitors have a larger evidence base. The traditional NSAIDs inhibit the activity of both COX-1 and COX-2 enzymes. COX-2 enzyme is seen more specifically in acute or chronic inflammatory tissue. Use of selective COX-2 inhibitors dampens adverse effects on gastric mucosa and decreases inhibition of prostaglandin production in the gastrointestinal tract. COX-2 drugs are 100e1000 times more selective for COX-2 than for COX-1. Celecoxib was the first COX-2 drug to be approved for marketing by the FDA, over a decade ago. Despite inconsistent evidence of increases in cardiac morbidity with COX-2 usage, pain relief with improved gastric tolerance remains the foundation of the benefit of selective COX-2 inhibition. Inan et al reported on the use of lornoxicam (a COX-1 agent) for pain control in patients treated with total knee
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arthroplasty.36 These subjects received pre-operative and post-operative lornoxicam as well as patient-controlled analgesia with morphine post-operatively. Patients in the control group received patient-controlled analgesia with morphine only. During the first 48 h after the arthroplasty, opioid consumption was significantly lower in the patients receiving lornoxicam (p < 0.05). The patients in the control group also exhibited a trend toward a higher rate of opioid-related side effects. Another study demonstrated the efficacy of COX-2 in reducing both pain and opioid consumption.37 Celecoxib was administered 1 h before total knee arthroplasty and every 12 h thereafter. Patientcontrolled analgesia with opioid medication was also provided. The control cohort received patient-controlled analgesia only. The patients receiving celecoxib reported significantly decreased pain on a VAS at forty-eight (p ¼ 0.03) and seventy-two (p ¼ 0.02) hours following the total knee arthroplasty. Opioid consumption was reduced by 40% in the celecoxib group. The active knee range of motion was significantly greater (10e15 ) during the first three post-operative days in the celecoxib group (p ¼ 0.03). Similar evidence presented by Buvanendran et al supports COX-2 usage. Compared with a placebo, rofecoxib administered pre-operatively and for 8 days following the index total knee arthroplasty resulted in significantly decreased opioid consumption (p < 0.05), decreased VAS pain scores (p < 0.001), decreased side effects (p ¼ 0.047), and an increased knee range of motion over 1 month (p ¼ 0.01). Extrapolation of these results also demonstrated improved patient satisfaction and a shorter period of physical therapy to achieve an adequate range of motion. Analysis of side effects in these studies shows no statistically significant difference in bleeding or the need for transfusion post-operatively. There is overwhelming evidence supporting the use of NSAIDs and COX-2 inhibitors as an integral part of multimodal pain management in orthopedic patients. Concerns have been raised regarding the effect of COX-2 inhibitors and NSAIDs on osseointegration and fracture healing. At this point, little Level-I or II evidence is available to support or refute this concern. There is also a concern regarding bleeding and inhibition of platelet aggregation, which also is not supported by Level-I or Level-II evidence. However, the latter concern may be mitigated by pre-emptively discontinuing use of all NSAIDs 7e10 days prior to surgery. In addition, COX-2 inhibitors with anti-inflammatory properties alone do not seem to be associated with these potential side effects. While previous research has indicted COX-2 inhibitors for increasing thromboembolic events in patients undergoing coronary artery bypass graft surgery, no increase in association with other surgical procedures has been established.
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Gabapentin/pregabalin Marketed as an anticonvulsant and used for neuropathic pain, gabapentin acts on the a2d subunit of the presynaptic voltage gated calcium channels. These channels are accessed along the dorsal horn synapse in spinal neurons. The end result is a decrease in excitatory signal release along the afferent pathway. Peri-operative use of gabapentin and pregabalin has been investigated in prospective trials. In one study, patients were randomized to receive or not receive pregabalin before and for 14 days after total knee arthroplasty.38 The patients who had received the drug had less neuropathic pain at 3 and 6 months, reduced opioid consumption while they were hospitalized, and improved knee flexion over the first 30 days after the operation. A higher risk of side effects (increased confusion and sedation during post-operative day 0 and 1) was reported in the pregabalin group. Using a peri-operative model, Clarke et al found similar results for patients undergoing total knee arthroplasty.39 However, they evaluated all permutations of pre-operative and post-operative gabapentin administration. Post-operative doses of gabapentin decreased opioid consumption during the first 2 days after the operation and significantly improved knee flexion on days 2 and3. The sample size was limited to thirty-six patients, and the study did not demonstrate improved efficacy with the pre-operative use of gabapentin. In a related study examining patients undergoing total hip arthroplasty, Clarke et al found no difference between groups treated with and without gabapentin.40 However, this study also had limited power, and only one dose of gabapentin was administered pre-operatively and post-operatively. The gabapentinoids studied outside the setting of total joint arthroplasty have demonstrated efficacy when used in combination with other agents or alone. More research is needed to identify the true efficacy with respect to the duration and timing of administration to patients undergoing orthopedic procedures. Common side effects of these agents are dizziness and somnolence.
Tramadol Tramadol is a synthetic centrally acting opioid agonist and monoamine uptake inhibitor (acting on noradrenaline and serotonin). These two synergistic pathways create a potential for a unique adjuvant for pain control. However, efficacy has been found to be limited in prospective trials. Stubhaug et al provided 50 and 100-mg doses of tramadol in a placebo-controlled study of patients undergoing total joint arthroplasty.41 There was no difference in any pain control outcome variable between the placebo and tramadol
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groups. Stiller et al evaluated tramadol use in a multimodal role as an adjuvant to patient-controlled analgesia with morphine in patients treated with total knee arthroplasty.42 While pain relief was not significantly different between those receiving tramadol with patient-controlled analgesia and those using patient-controlled analgesia alone, morphine consumption was significantly decreased in the tramadol group (p < 0.05). Differences in the designs of these prospective studies make it difficult to ascertain the role of tramadol in multimodal pain management.
N-Methyl-D-aspartate non-competitive antagonists N-methyl-D-aspartate (NMDA) receptor antagonists potentiate the effect of opioids and prevent hyperalgesic complications from uncontrolled pain. Agents used to modulate the pain pathway in the central nervous system include ketamine, magnesium, and dextromethorphan. In a study of forty patients randomized to receive magnesium sulfate or saline solution parenterally during spinal anesthesia, with both groups receiving patient-controlled analgesia with morphine and ketorolac post-operatively, the magnesium group had lower pain scores and utilized less opioid without any difference in side effects.43 In another study, evaluating the role of magnesium added to epidural fentanyl, patients receiving magnesium required significantly (p < 0.05) less fentanyl without any increase in side effects.44 Ketamine is another NMDA antagonist advocated for nociceptive relief. Remérand et al studied 154 patients treated with total joint arthroplasty; seventy-nine received intravenous ketamine pre-operatively and for 24 h post-operatively and the placebo group received saline solution infusion.45 All patients were managed with a multimodal pain management regimen concurrently. The results showed significantly decreased morphine consumption (p ¼ 0.004) and significantly decreased pain in the patients receiving ketamine (p ¼ 0.036). There appears to be a promising role for ketamine as a multimodal analgesic, although potential side effects include hallucinations, nausea, emesis, and vision changes. Transdermal patches While transdermal fentanyl patches add to the total narcotic dosage, they also provide an alternative route for administration of pain control agents. Comparisons with patientcontrolled morphine analgesia have demonstrated comparable efficacy and safety. Given the varying delivery and time course of narcotic administration, the synergistic effects of fentanyl patches with other routes of pain control may be beneficial. Minville et al reported on a small group of patients who had had a 50-mg/h matrix fentanyl patch
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applied 10 h prior to a total hip arthroplasty.46 No difference in respiratory depression was noted between that group and patients who had not received the patch. The application of the patch decreased post-operative use of patient-controlled analgesia with morphine; however, transdermal patches may not curtail overall opioid consumption due to the administration of fentanyl in this study. Because of a concern regarding unpredictable delivery and potential adverse effects, most centers do not consider transdermal patches as a suitable modality for management of acute post-operative pain.
DISCUSSION Total knee replacement (TKR) is one of the most successful surgical procedures. Management of pain following TKR is an important aspect of this procedure. Satisfactory pain management after TKR has several important implications. Adequate pain control allows faster rehabilitation1 and reduces the risk of post-operative complications. Pain control is also the most important component of patient satisfaction. Patients with well-controlled post-operative pain have an improved health-related quality of life and less time lost from work, and they are more satisfied with their treatment. Appropriate and adequate post-operative pain management is associated with shorter hospital stays, reduced rates of unanticipated hospital admissions and readmissions due to pain, and an overall reduced cost of care. Opioids are very effective analgesics and constitute the foundation of the management of moderate-to-severe acute post-operative pain despite their association with increased respiratory, cardiac, urinary, gastrointestinal, and neurological complications. In addition, opiate-induced respiratory depression and the associated post-operative hypoxia is linked with myocardial ischemia, tachycardia, acute cognitive disturbances, delayed wound-healing, and an increased incidence of wound infection. Because of concerns about side effects, physicians often prescribe doses of opioids that are lower than what would have the optimal effect. A newer concept in pain management in TKR is multimodal pain management. This concept was introduced in an attempt to control pain with less reliance on opioids. Multimodal analgesia is a multidisciplinary approach to pain management with a goal to maximize the analgesic effect and minimize the side effects of the medications. It takes advantage of the additive or synergistic effects of various analgesics, permitting the use of smaller doses with a concomitant reduction in side effects. Because many of the negative effects of analgesic therapy are related to parenteral opioid limiting its use is a major principle of
Pain management in TKR
Table 4 Pain management in TKR.
multimodal analgesia. Over the past decade, a greater understanding of pain mechanisms has led to the concept of pre-emptive analgesia. Pre-emptive analgesia involves the administration of analgesics prior to painful stimuli to prevent the establishment of central sensitization and thus the amplification of post-operative pain. It starts before surgery and covers both the period of surgery and the initial post-operative period. In order to understand multimodal pain management, a fundamental knowledge of how pain is generated is required. Available evidence indicates that multimodal pain management has a useful role for patients undergoing total joint arthroplasty. The rationale for multimodal pain management is to provide pain relief for the patient with less reliance on opioids. There is ample evidence to suggest that traditional NSAIDs and the associated COX-2 inhibitors are the most effective agents for decreasing opioid consumption. Fewer investigators have analyzed pain levels and the impact on post-operative mobilization. Overall, NSAIDs, spinal analgesia, peripheral nerve blocks, and intra-articular injections have resulted in improved VAS pain scores, with variable strengths of evidence. The most information has been reported for NSAID use. There is still a lack of research on many adjunctive agents and potential outcomes. However, most agents have shown trends toward improved activity in physical therapy and patient satisfaction. Thus, the primary goal of modern pain management is to reduce pain at both the central and the peripheral levels, in combination with pre-emptive analgesia using a multimodal protocol (Table 4). This strategy should enhance restoration of function by allowing patients to participate in the rehabilitation programs more easily, thereby improving the overall post-operative outcome.
CONFLICTS OF INTEREST All authors have none to declare.
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