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13 Articles in Volume 12, Issue #11
“Doc” Holliday: A Story of Tuberculosis, Pain, and Self-medication in the Wild West
"Doc's" Woman: Doc Holliday's Wife
Activation of Latent Lyme Disease Following Epidural Steroid Injection: Case Challenge
An Overview of Complex Regional Pain Syndrome and its Management
Extracorporeal Shock Wave Therapy: Applications in Tendon-related Injuries
Mission Impossible—Developing a Program to Help Chronic Pain Patients
New Ideas for Helping Difficult Pain Patients
Postoperative Pain Relief After Knee and Hip Replacement: A Review
Using Dynamic MRI to Diagnose Neck Pain: The Importance of Positional Cervical Cord Compression (PC3)
December 2012 Pain Research Updates
Best Practices For High-dose Opioid Prescribing
Does Sulindac Affect Renal Function Less Than Other NSAIDs?
The Bewildering Terminology of Genetic Testing

Postoperative Pain Relief After Knee and Hip Replacement: A Review

In 2010, an estimated 50 million American adults were diagnosed with some form of arthritis, with osteoarthritis (OA) being the most common.1 Concurrent with the increasing diagnosis of OA, the demand for total joint arthroplasty (TJA) has also risen steadily over the past decade. In 2004, there were a reported 454,652 total knee arthroplasties (TKAs) and 232,857 total hip arthroplasties (THAs) performed primarily for the treatment of arthritis.1 In the past, many patients have elected not to undergo lower extremity arthroplasty procedures due to the fear of severe postoperative pain and prolonged periods of rehabilitation. Fortunately, in recent years, our understanding of how to properly manage postoperative pain has grown immensely.2-7

There exist numerous protocols for the management of postoperative pain in patients undergoing elective lower extremity arthroplasty (ELEA). In this article, we review a number of pain management methods to determine which method is most efficacious in reducing postoperative pain, length of hospital stay (LOS), and effectiveness of rehabilitation.

Noninvasive Pharmaceutical Management
The most commonly used pharmaceuticals for postoperative pain management are some combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid analgesics. A number of other pharmaceutical agents have been used as adjuncts to NSAIDs and opioids, including propacetamol, acetaminophen, gabapentin, duloxetine (Cymbalta), and the cyclooxygenase (COX)-2 inhibitor celecoxib (Celebrex). We reviewed 6 studies illustrating the efficacy of these agents in managing postoperative pain following ELEA. The results of the studies are summarized in Table 1.

Table 1. Noninvasive Pharmaceutical Management Studies

Propacetamol is the more soluble pro-drug of paracetamol (acetaminophen), which is given intravenously. When compared to intravenous (IV) ketorolac, IV propacetamol resulted in a similarly shorter time to onset of analgesia versus control.8 More recently, IV propacetamol and IV acetaminophen were compared to placebo. Both acetaminophen and propacetamol resulted in both higher pain relief scores (P<0.05) and lower morphine consumption (P<0.01) than placebo over a 6-hour period and continuing over the 24-hour study interval. Patients’ global evaluations of satisfaction with treatment after the initial dose and at 24 hours were higher for both acetaminophen and propacetamol (P<0.01). Patients receiving acetaminophen and placebo, however, experienced fewer adverse effects compared with propacetamol (P<0.05).9

Gabapentin, a drug traditionally used for the relief of neuropathic pain, was compared in variable doses to placebo in relieving postoperative pain. Gabapentin resulted in less total patient-controlled analgesia (PCA) morphine use over 48 hours postoperatively (P<0.05), better active knee flexion on postoperative days (PODs) 2 and 3 (P<0.05 for both), and less pruritus (P<0.05) than placebo.10

Duloxetine, a serotonin-norepinephrine reuptake inhibitor, has also been administered to manage postoperative pain. Duloxetine combined with traditional opioid analgesia was compared to placebo in managing postoperative pain. Duloxetine treatment resulted in lower morphine consumption in the first 24 hours postoperatively than placebo (P=0.017).11

Selective COX-2 inhibitors such as celecoxib have classically been used in postoperative pain management. Celecoxib, when compared with IV PCA alone, resulted in improved visual assessment scale (VAS) scores over a 72-hour period (P=0.02), and higher active range of motion (ROM) over 72 hours (P=0.004). Also, opioid requirements were lower in the celecoxib-treated group by 40% (P=0.03).12

Periarticular and Intra-Articular Injections
Another multimodal approach to managing postoperative pain following ELEA involves the use of local anesthetic injection mixtures containing a variety of agents including corticosteroids, opioids, epinephrine, and clonidine. When periarticular injections of a local anesthetic mixture (ropivacaine with epinephrine and ketorolac) combined with PCA morphine were compared with morphine alone, the local anesthetic mixture significantly reduced opioid consumption over 48 hours postoperatively (P=0.003). The local anesthetic group also reported lower mean VAS pain scores at rest (P=0.01) and during exercise on POD 1 (P=0.008) and on POD 2 (P=0.02), as well as less postoperative nausea (P=0.011) compared to the control group.13

Intra-articular injection of ropivacaine with morphine and ropivacaine alone, however, did not significantly affect pain scores or narcotic consumption. Similarly, ropivacaine injection—when compared with placebo injection—had no significant effects on pain scores or narcotic consumption.14,15

These local anesthetic injection mixtures can also be administered periarticularly. Periarticular injection of a steroid-containing local anesthetic mixture (bupivacaine, morphine, epinephrine, and methylprednisolone) resulted in lower pain scores and higher patient satisfaction (P=0.05 for both), in addition to lower opioid consumption when compared to patients receiving PCA with or without femoral nerve block (FNB). Also, patients receiving the injections achieved active straight leg raise sooner and had a shorter mean LOS.16

Periarticular injection of bupivacaine and epinephrine with triamcinolone acetonide was compared with bupivacaine and epinephrine alone. Pain scores were lower with the steroid-containing injection (P=0.02) along with decreased cumulative morphine consumption (P=0.03). The steroid-containing injection also resulted in a shorter LOS (P=0.02) and achieved greater ROM on POD 2 up to 6 months postoperatively (P=0.01).17

Peripheral Femoral Nerve Block
A less localized method of multimodal analgesia is the placement of a peripheral nerve block, with the most common site being the femoral nerve. A continuous ropivacaine FNB with a fentanyl PCA was compared with PCA alone. The control had a higher total opioid consumption (P<0.001) and required more PCA dose increases compared to the FNB group. Those with an FNB, however, experienced lower ROM in both flexion and extension (P<0.006 and P<0.04, respectively).18

Similarly, when levobupivacaine FNB with patient-controlled epidural analgesia (PCEA) was compared with PCEA alone, the FNB group had lower VAS scores from 0 to 24 hours (P<0.001), and 24 to 48 hours (P=0.025). Patients receiving FNB also experienced significantly less nausea (P<0.001), vomiting (P=0.033), and demand for rescue antiemetics (P=0.037) in the 0- to 6-hour period, as well as required significantly less meperidine in the 0- to 6-hour period (P=0.005).19

In contrast to an FNB with PCA versus PCA alone, a ropivacaine solution used with a stimulating femoral nerve catheter (FNC) compared to a non-stimulating FNC did not yield any significant results in terms of pain control or ROM.20

Regional Spinal Analgesia
Epidural analgesia is another method of pain management used for patients undergoing a TJA. Varying doses of extended-release epidural morphine (EREM) were compared with normal morphine sulfate PCA. Pain scores were lower overall with EREM (P=0.004); however, EREM resulted in higher pain scores on POD 3 (P=0.003) and caused greater nausea and vomiting on POD 0 and POD 1 (P<0.001 and P=0.005, respectively). In addition, EREM caused greater pruritus on POD 0 through POD 2 (P<0.001, P<0.0001, and P=0.01, respectively).21

The duration of epidural catheter placement has also been shown to affect postoperative pain management. When the epidural catheter, which administered a mixture of lidocaine, bupivacaine, and often hydromorphone, was removed on POD 1 compared to POD 2, patients experienced a shorter LOS (P<0.001) and achieved greater distance walked (P<0.002).22

A distantly related pain management method, spinal cord stimulation, was evaluated in a case study that followed a single patient’s chronic knee pain after a TKA. Following numerous trials of medications, physical therapy, and other interventional modalities such as nerve blocks, spinal cord stimulation was offered. While the patient in this study did not achieve satisfactory Oxford Knee Scores, it was reported that she was able to walk with less discomfort and had less pain with certain activities such as dancing. In addition, the Oxford Knee Score at the 4 months and 1-year follow up declined from 28% to 26%.23

Discussion
Although many analgesia protocols for ELEA have been evaluated, each method has its own benefits and drawbacks. The most commonly practiced method for analgesia is a combination of NSAIDs and opioids, and while this has proven effective, the inclusion of opioids does predispose the patient to numerous side effects including nausea, vomiting, pruritus, sedation, constipation, and urinary retention. In a retrospective study, investigators found that constipation (P<0.0001), emesis (P<0.001), and confusion (P<0.01) are associated with an increased LOS in patients receiving opioids following orthopedic surgery. Nausea and vomiting occurred in 36.1% of patients, constipation in 6.5%, and emesis in 3.7% of patients, with more than half of patients experiencing at least one adverse effect.24 In light of these adverse effects, many of the authors in this review have sought reduction in opioid consumption as a primary outcome measure by which to gauge the efficacy of their respective pain management protocols. Despite the effectiveness of this traditional analgesia combination, the addition of other non-opioid pharmaceutical agents has been proven to be more effective than NSAIDs and opioids alone.

Both propacetamol and ketorolac were shown to be superior to morphine PCA alone in the management of postoperative pain following ELEA, yielding an earlier onset of analgesia. When compared to each other, both propacetamol and ketorolac were similarly efficacious in lowering pain relief scores.8 However, maximum pain relief scores were shown to be significantly greater in patients receiving either acetaminophen or propacetomol.9 Other drugs such as duloxetine were successful in reducing morphine consumption up to 48 hours after surgery.11 The same holds true for the addition of gabapentin, with patients in this study requiring significantly less PCA versus placebo.10 The COX-2 inhibitor celecoxib also showed improvements in pain management over traditional methods. Celecoxib was found to improve VAS pain scores and active ROM compared to the placebo, in addition to lowering opioid requirements.12 Patients receiving rofecoxib, which was banned from the market in 2004, had similarly lower total epidural consumption, lower VAS scores, and less opioid consumption.25 However, while COX-2 inhibitors have been shown superior to other pharmaceutical agents in providing analgesia, recent studies have demonstrated certain cardiovascular risks associated with these drugs. The risk of adverse cardiovascular effects is related to a reduction in prostacyclin synthesis secondary to COX-2 inhibition without a concomitant decrease in thromboxane synthesis, resulting in unopposed thromboxane-mediated platelet aggregation and vasoconstriction. Similarly, this also increases the risk of thrombosis, hypertension, and worsening of atherosclerosis.26 One study demonstrated that rofecoxib was associated with an increased risk of renal dysfunction and myocardial infarction at both low and high doses. Although not as significant, rofecoxib was also associated with an increased risk of arrhythmia (including ventricular fibrillation), cardiac arrest, and sudden cardiac death.27 Given the predominantly elderly patient base undergoing ELEA and the ever-increasing prevalence of cardiovascular disease in this patient population, like all therapies, the risks and benefits associated with COX-2 inhibitors should be taken into consideration when administered as a postoperative analgesic.

Local anesthetics administered via periarticular or intra-articular injections have been shown to decrease pain scores and opioid consumption. The most common agents used in either route of administration were the local anesthetics ropivacaine and bupivacaine. A combination of intraoperative and postoperative intra-articular ropivacaine-ketorolac injections resulted in lower pain scores, and less opioid consumption and opioid-associated side effects.13 While effective in reducing postoperative pain, this method was not shown to decrease LOS.14 The combination ropivacaine/NSAID injection was shown to be effective; however, a mixture containing a local anesthetic and corticosteroid was proven to be just as effective if not more so. The corticosteroid component reduces the inflammatory response at the surgical site while reducing blood loss by inhibiting prostaglandin synthesis. The addition of the epinephrine, via its vasoconstrictive mechanism, keeps the analgesic drugs localized to the surgical site longer, maximizing its efficacy and reducing its systemic side effects. Patients receiving a combination of bupivacaine, triamcinolone, and epinephrine injection before closure had significantly lower pain scores, demanded less parenteral morphine, achieved greater ROM, and had a shorter LOS compared to those who received a similar mixture without the corticosteroid component.17 When the intra-articular injections are compared, the ropivacaine-ketorolac combination administered before prosthesis implantation, before wound closure, and on POD 1 is more efficacious than a single injection of ropivacaine alone following wound closure. When the periarticular injections are compared, the bupivacaine-triamcinolone combination administered postimplantation is more efficacious than ropivacaine alone as well as a ropivacaine-morphine combination administered before closure. Given these findings, it appears that administration of a local anesthetic either intra-articular or periarticular in combination with a steroid or an NSAID before wound closure is more efficacious than the administration of a local anesthetic alone or in combination with an opioid after closure. This could be explained by a reduction in pain secondary to a decreased inflammatory response, which is seen with steroids and NSAIDs but not with opioid or local anesthetics by themselves. Further studies are needed to assess the effects of time of injection relative to wound closure using the local anesthetic-NSAID and local anesthetic-steroid combination, as well as differences in route of administration (intra- versus periarticular), and administration of the NSAID or steroid alone.

Local anesthetic could also be administered through an FNC; however, the benefits may not outweigh the risks when other analgesia protocols are available. Studies have shown there is no difference in the duration of PCA use when fentanyl/morphine PCA is used in combination with a continuous infusion of ropivacaine administered via FNC compared to the control group.20 FNB resulted in significantly lower fentanyl consumption, but lower ROM in both flexion and extension.18 However, when an FNB consisting of a single injection of levobupivacaine is administered with PCEA, patients reported significantly lower pain scores and less postoperative nausea and vomiting.19 It is clear that FNBs can provide adequate analgesia to patients who have undergone THA or TKA. However, the benefits associated with this method do not outweigh the risks. For example, this technique is more invasive than previous methods discussed. Not only may more attempts be needed for proper placement of the catheter, operator-dependent errors can also be made that can damage nearby vascular structures. In addition, the decreased ROM associated with this particular protocol can lead to a longer LOS and a longer rehabilitation period. Both of these factors alone will increase the healthcare cost of managing a patient who has undergone ELEA and are detrimental to the overall recovery of the patient.

Among the highest risk pain management modalities is administration of epidural analgesia. Traditional epidural analgesia involving the administration of opioids into the epidural space, although effective, may no longer play a role amidst the multiple more modern and safer techniques available. However, modifications to this traditional method of pain management attempt to reinforce the efficacy of epidural analgesia in the management of postoperative pain. Overall, patients receiving EREM have significantly lower pain scores and less opioid consumption than those receiving spinal anesthesia alone. Interestingly, while patients receiving EREM used less additional narcotics, the action of the long-acting morphine caused these patients to experience significantly more episodes of postoperative nausea and vomiting as well as pruritis.21 Given these results, future studies comparing the efficacy of EREM and traditional morphine or other opioid administration would be beneficial. Additionally, modifying traditional epidural analgesia by shortening the duration of administration has also been beneficial in postoperative pain management. Patients receiving epidural analgesia for only one POD versus two achieved a greater distance walked and had a significantly shorter LOS.22

It appears that the duration of epidural administration plays a bigger role in its efficacy in postoperative pain management than does the specific opioid being administered. It is important to note that although a shorter duration may allow for more rapid rehabilitation and shorter LOS, the generally invasive nature of placing an epidural may not make this the optimum method of achieving adequate postoperative analgesia, especially in light of the efficacy of other, less invasive modalities.

While distantly related to epidural analgesia, spinal cord stimulation is gradually finding its place amongst other postoperative analgesia protocols. The process involved in placing a permanent spinal cord stimulator can be time consuming, as the precise location and current passed through the device is vital to effectively provide pain control. In addition, this particular protocol is entertained only when a patient’s pain has been refractory to traditional methods such as medications, physical therapy, and nerve blocks.23 This method certainly provides greater patient satisfaction and ability to perform daily activities, but the true efficacy of this method is difficult to ascertain due to the small sample size of the individual case study reviewed, as well as the inherent difficulty in performing a placebo procedure to serve as an adequate control. Further studies involving spinal cord stimulation are recommended, as it may be a viable option for patients with chronic hip and/or knee pain following ELEA who have failed traditional therapy.

Summary
After having evaluated the efficacy of the various multimodal pain management protocols, the recommended method of pain management following ELEA is a periarticular injection of a mixture containing a corticosteroid, local anesthetic, and epinephrine administered before wound closure. Relative to the other modalities reviewed, this particular method is the least invasive, yet most effective multimodal analgesia protocol. Although not reviewed in terms of periarticular injections, a possible alternative is the replacement of the corticosteroid component with an NSAID, which was shown to be efficacious when given intra-articularly. While results of the periarticular injection of steroid and local anesthetic are similar to an intra-articular cocktail of an NSAID and local anesthetic, the significantly shorter LOS makes the former method preferred over the latter. Decreased length of hospital stay is associated with increased patient satisfaction, decreased risk to the patient, and decreased healthcare-associated costs. In conclusion, while the optimum pain management protocol will most certainly vary from case to case, the recommended protocol should provide adequate pain relief to the majority of patients who will be undergoing lower extremity arthroplasty in the near future.

Last updated on: April 4, 2014
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