JAAOS Plus Webinar
Join Dr. Moucha, Dr. Weiser, and Dr. Levin for the interactive JAAOS Plus Webinar discussing “Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty,” on Tuesday, March 22, 2016, at 8 pm Eastern Time. The moderator will be Henry D. Clarke, MD, the Journal's Deputy Editor for Hip and Knee topics. Sign up now at AAOS CME Courses & Webinars.
Total knee arthroplasty (TKA) is a notoriously painful procedure. This fact has prompted the study and application of multimodal pain modulation techniques to improve patient satisfaction and outcomes. Failure to control postoperative pain has been associated with an increase in sympathetic tone, causing vasoconstriction and end-organ damage, a decrease in intestinal motility, increased nausea and vomiting, the downregulation of immune function, a delay in discharge, increased healthcare costs, and potentiation of chronic postoperative pain, leading to chronic regional pain syndrome.1
Increasing evidence shows that the types of anesthesia and analgesia administered in the perioperative period may affect the rates of surgical site infection, urinary retention, ileus, nausea and vomiting, and the ability to safely participate in early postoperative rehabilitation.2-12 The American healthcare system is entering an era in which physician and hospital compensation may be tied to patient satisfaction and preventable complications. The surgeon should have an understanding of the current anesthetic and analgesic options for TKA as a basis for informed discussions with patients and anesthesia colleagues to better optimize patient outcomes.
Multimodal analgesia refers to the combination of several types of medications and delivery routes, including peripheral nerve block (PNB), periarticular injection, patient-controlled analgesia (PCA), and oral narcotic and nonnarcotic medication. The goal of multimodal analgesia is to provide superior postoperative pain control through the simultaneous modulation of several pain pathways while minimizing the undesired adverse effects of excessive narcotic consumption, which can result in nausea, vomiting, sedation, ileus, respiratory depression, and pruritus. Most multimodal protocols focus on oral analgesics, which may be started several days before surgery and usually are combined with oral opioids. The ultimate goal is to provide adequate pain relief without using intravenous opioids (Table 1).
Preemptive analgesia begins before surgery, with the goal of preventing peripheral and central nervous system sensitization secondary to the surgical incision and surgical tissue manipulation. The concept of preemptive analgesia is based on preventing the production of inflammatory chemicals during a painful stimulus, thus avoiding the sensitization of peripheral and central nociceptors. The sensitization of these nerve fibers lowers the pain threshold and contributes to hypersensitivity to innocuous stimuli during the postoperative period, leading to chronic neuropathic pain. The prevention of this sensitization can improve the patient’s postoperative pain and reduce the risk for the development of chronic neuropathic pain.13
Preemptive analgesics need to be relatively easy to administer, provide rapid onset, and have an adverse-effect profile that will not interfere with the planned surgical procedure. Typically, NSAIDs, such as cyclooxygenase-2 (COX-2) inhibitors, pregabalin, gabapentin, and acetaminophen, are used for this purpose and are administered in the preoperative holding area 1 to 2 hours before incision. These medications are an important part of multimodal anesthesia, and the practice guidelines for acute pain management in the perioperative setting of the American Society of Anesthesiologists Task Force on Acute Pain Management recommend that a combination of these medications be used in the perioperative period, along with neuraxial and regional anesthesia techniques, and supplemented with intravenous PCA if necessary.14
COX-2 inhibitors work peripherally to prevent the production of prostaglandins. They have a favorable adverse-effect profile, with reduced risk for gastric ulcers and minimal platelet dysfunction compared with traditional NSAIDs, which are nonspecific COX-1 and COX-2 inhibitors. Although COX-2 inhibitors have been implicated in increasing the risk for adverse cardiovascular events, doses of celecoxib of up to 400 mg a day have not been shown to increase this risk.15 In a meta-analysis of eight randomized controlled trials (RCTs), with a total of 571 patients undergoing TKA who received perioperative COX-2 inhibitors, the authors concluded that the perioperative use of COX-2 inhibitors resulted in lower pain scores as measured on the visual analog scale (VAS), greater range of motion, less opioid consumption, and a reduction in opioid-related adverse effects at 3 days postoperatively.16 A randomized double-blind placebo-controlled study by Schroer et al17 of 107 patients undergoing TKA suggested clinical benefits to the administration of 200 mg of celecoxib twice daily for 6 weeks postoperatively. They found statistically significant reductions in total postoperative narcotic pill consumption (76.3 ± 55 versus 138 ± 117; P = 0.003) and VAS pain scores at 3, 6, and 12 weeks in the treatment group. They also noted statistically significant improvements in knee flexion up to 1 year, American Knee Society Scores and Oxford Knee Score scales at 3 and 6 weeks, and Medical Outcomes Study 12-Item Short Form (SF-12) disability scores at 6 weeks postoperatively.
Pregabalin and gabapentin work centrally on gamma-aminobutyric acid (GABA) receptors to reduce central sensitization at the level of the spinal cord and brain. Pregabalin is more potent than gabapentin and requires a lower dose to achieve the desired effect. It should be noted that the perioperative and postoperative administration of these medications for acute pain prevention is an off-label use. A study by Buvanendran et al18 demonstrated that a one-time preoperative dose of 150 mg of pregabalin in 9 patients undergoing TKA rapidly achieved cerebrospinal fluid concentrations within 2 hours of administration, equivalent to an anticonvulsant level, and peaked by 6 to 8 hours at a concentration high enough to prevent allodynia in a rat model. A randomized double-blind controlled study of 240 patients undergoing TKA compared a preoperative dose of 300 mg of pregabalin followed by a 14-day taper with placebo. The study demonstrated that the treatment group had a substantial reduction in chronic neuropathic pain at 6 months postoperatively (0% versus 5.2%). In the acute postoperative period, those who received pregabalin required fewer epidural opioids and lower amounts of oral opioids, and achieved increased flexion at 30 days.19
The mechanism of action for acetaminophen is not understood fully, but it is believed to work through several centrally mediated pathways, including as a cannabinoid receptor agonist, as an inhibitor of COX-2 isoenzyme, and as an agonist of transient receptor potential cation channel, subfamily V, member 1, a central antinociceptor.20 Intravenous acetaminophen can be used for analgesia in all phases of the perioperative period, is as effective as 10 mg of intravenous morphine, and avoids opioid-related adverse effects. It is also useful in the preoperative period because it rapidly achieves peak concentration in cerebrospinal fluid within 30 minutes of administration and is not subject to the delayed absorption of oral medications.21
General and Neuraxial Anesthesia
General and/or neuraxial anesthesia is appropriate for TKA and is familiar to most surgeons and anesthesiologists. General anesthesia is associated with reduced perioperative tissue oxygen tension22 as well as postoperative nausea, vomiting, and delirium, which are avoided by using neuraxial anesthesia.3 The administration of neuraxial anesthesia requires technical procedural skill, however, and although usually very successful, is associated with a failure rate of approximately 4%, necessitating conversion to general anesthesia.23 The complication rate of spinal and epidural anesthesia has been reported to be extremely low (0.03%) but does include serious yet uncommon complications, such as spinal and epidural hematoma, abscess formation, cauda equina syndrome, and meningitis.24 More common adverse effects include postoperative hypotension and urinary retention.
A retrospective study by Memtsoudis et al2 examined 528,495 total joint arthroplasty patients in a national healthcare database from 2006 to 2010. The authors evaluated the types of anesthesia used and determined whether anesthetic choice had any impact on perioperative outcomes. Comparing general anesthesia with neuraxial anesthesia in the TKA subgroup, they found that general anesthesia was associated with higher risks of pulmonary compromise (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.43 to 2.35; P < 0.0001), pneumonia (OR, 1.27; 95% CI, 1.05 to 1.53; P = 0.0083), all infections (OR, 1.38; 95% CI, 1.26 to 1.52; P < 0.0001), acute renal failure (OR, 1.44; 95% CI, 1.24 to 1.67; P < 0.0001), and overall 30-day mortality (OR, 1.83; 95% CI, 1.08 to 3.1; P = 0.0211).
Similarly, a retrospective study by Pugely et al3 examined the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database from 2005 to 2010, comparing 30-day postoperative complications among 14,052 TKA patients, of whom 6,030 patients (42.9%) received general anesthesia and of whom 8,022 patients (57.1%) received neuraxial anesthesia. Patients who received neuraxial anesthesia had statistically significant lower rates of surgical site infection (0.68% versus 0.92%; P = 0.0003), blood transfusions (5.02% versus 6.07%; P = 0.0086), and overall complications (10.72% versus 12.34%; P = 0.0032) as well as shorter surgical times (96 versus 100 minutes; P < 0.0001) and length of stay (3.45 versus 3.77 days; P < 0.0001). The most noticeable benefits were seen in patients who had higher American Society of Anesthesiologists classifications.
The use of epidural anesthesia for postoperative pain control was examined in a meta-analysis of eight RCTs comparing epidural anesthesia with PNB in 510 patients, 464 of whom underwent TKA. The meta-analysis found equivalent pain scores and morphine consumption between both groups up to 48 hours postoperatively. The use of epidural anesthesia was associated with a higher incidence of hypotension and urinary retention, however, suggesting that PNB provides equivalent pain relief with a more favorable adverse-effect profile.4
The American Society of Regional Anesthesiologists has published consensus guidelines for the use of neuraxial anesthesia and chemothromboprophylaxis.25 They do not endorse using a twice-daily or once-daily dosing scheme of low-molecular-weight heparin (LMWH) specifically, but they do note that twice-daily dosing schemes of LMWH prophylaxis are associated with a higher risk of spinal hematoma formation. They recommend removing an epidural catheter before any LMWH has been given and waiting 2 hours after catheter removal to begin the initiation of prophylaxis. If desired, LMWH prophylaxis may be initiated 6 to 8 hours after surgery, but 10 to 12 hours must elapse after the last LMWH administration before removing the epidural catheter. In this setting, 2 hours must elapse after catheter removal before administering another dose of LMWH. In the setting of warfarin use, they recommend the removal of an epidural catheter when the international normalized ratio is <1.4. The guidelines mention no specific concerns with regard to neuraxial techniques or the timing of catheter removal in patients treated with aspirin or NSAIDs.
Peripheral Nerve Blocks
PNB often is used in TKA to provide supplemental anesthesia and analgesia during the perioperative and postoperative periods. The primary sensory innervation to the knee is supplied by the femoral nerve anteriorly and the posterior cutaneous nerve of the thigh posteriorly. The lateral femoral cutaneous nerve and the obturator nerve provide variable contributions to sensation laterally and medially, respectively. The degree and pattern of nerve blockade depends on the targeted nerve and whether or not the anesthesia is achieved via a single shot or a continuous catheter. Some of the purported benefits of regional anesthesia include a shorter length of stay; reduced opioid consumption with a concomitant reduction in opioid adverse effects, such as reduced cognition, nausea, vomiting, and pruritus;5,6 a reduced risk of hypotension and urinary retention compared with epidural anesthesia;4 and earlier participation in physical therapy.7 Although regional anesthetic techniques are useful adjuncts in pain management, they require a specialized technical skill on the part of the anesthesiologist and are associated with a reported failure rate ranging from 0% to 67%.7 The reported complication rates from regional anesthesia techniques are low (0.1%) and include cardiac arrest, death, seizure, and peripheral nerve injury.23 Common medications and dosages used in regional nerve blocks are listed in Table 2. Femoral nerve blocks (FNBs) and adductor canal blocks (ACBs) are among the most frequently used PNBs in TKA and, because of recent controversies in postoperative fall rates,10,11 are the primary focus in this article.
Three-in-One Perivascular Femoral Nerve Block
This block targets the femoral nerve in the femoral canal, relying on diffusion of the local anesthetic to provide blockade of the femoral, lateral femoral cutaneous, and obturator nerves. The term three-in-one FNB is somewhat of a misnomer because the obturator nerve rarely is anesthetized successfully using this block. Traditionally, it has been performed using nerve stimulation, but ultrasonography is now being used increasingly to reduce the rate of failed blockade and inadvertent arterial or intraneural puncture. This block is a mixed motor and sensory nerve block and results in numbness of the anterior, lateral, and medial aspects of the thigh, causing profound quadriceps weakness. When this block is performed, the patient is positioned supine, and ultrasonography is used to identify the nerve at the confluence of the iliacus and psoas muscles. The needle is inserted from a laterally based starting point and is advanced using ultrasonography for visualization. Ultrasonography is also used to visualize the injected local anesthetic layering under and about the femoral nerve. A catheter may be inserted for continued analgesia in the postoperative period.26
The FNB predictably results in quadriceps weakness, increasing the risk of fall in the postoperative period. Some of these falls may be prevented by mandating that the patient use a knee immobilizer while ambulating until able to perform a straight leg raise. Attempts have been made to vary the concentration of the anesthetic to reduce the degree of quadriceps weakness, but the degree of weakness is fairly consistent regardless of the concentration or dosing schedule of the anesthetic administered.8,9 A recent meta-analysis by Ilfeld et al10 showed that the postoperative risk of fall after receiving an FNB or lumbar plexus block was 7%. Sharma et al11 examined postoperative falls in their own institution in patients who received FNB for TKA over a 2-year period and found a fall rate of 1.6%, resulting in a reoperation rate of 0.4%. The benefits of FNB in TKA patients were examined in a recent Cochrane Review of 47 RCTs incorporating 2,710 patients. The authors found no substantial difference in pain relief between epidural anesthesia and FNB for 72 hours postoperatively (standardized mean difference [SMD], −0.05; 95% CI, −0.43 to 0.32), but FNB was noted to produce less nausea and vomiting (relative risk [RR], 0.63%; 95% CI, 0.41 to 0.97) and greater patient satisfaction (SMD, 0.6; 95% CI, 0.23 to 0.97).12
Adductor Canal Block
This block is becoming increasingly popular because it targets several mostly sensory nerves in the adductor canal while reducing the degree of quadriceps weakness. The targeted nerves include the saphenous nerve, articular branches of the obturator nerve, the medial retinacular nerve, and the nerve to the vastus medialis, which is the only motor nerve involved in the blockade. This technique results in a sensory blockade of the anteromedial knee at the level of the superior pole of the patella and the medial lower leg, with minimal loss of quadriceps strength. The block is performed by positioning the patient supine, with the ultrasonographic probe applied at the medial mid-distal thigh level, 2 to 3 cm proximal to the adductor hiatus. The femoral artery and vein are located deep to the sartorius muscle, with the saphenous nerve lateral to them at this level. Local anesthetic is injected around the saphenous nerve using ultrasonography for visualization. A catheter may be inserted to provide continued analgesia in the postoperative period.27 The ACB has not been examined in large RCTs, but it has been shown to be a promising modality in several smaller studies. Studies comparing FNBs and ACBs are summarized in Table 3. Figure 1 demonstrates the difference between the sensory coverage areas of FNBs and ACBs.
Single-Shot Versus Continuous Catheter Infusion Peripheral Nerve Blocks
Most local anesthetics used in PNBs wear off within 24 hours of administration when given as a single shot. Infusion catheters may be placed at the time of block administration to provide continued analgesia in the postoperative period. A prospective nonblinded randomized study compared postoperatively placed continuous FNBs with single-shot FNBs in 36 TKA patients, with catheter removal on postoperative day 2 for the continuous group. The authors found that patients who had the continuous catheter infusion FNB had lower VAS scores at rest and during activity than did the patients who received the single-shot FNB, beginning on postoperative day 1 and continuing until postoperative day 3. The continuous catheter infusion FNB group also consumed less total morphine during the hospital stay. No differences were seen in length of stay or knee flexion at 6 and 12 weeks postoperatively.30 These findings agree with those of the Cochrane Review of FNBs, which found moderate-quality to high-quality evidence that continuous catheter infusion FNBs improve pain scores both at rest (SMD, 0.62; 95% CI, −1.17 to −0.07) and with movement (SMD, −0.42; 95% CI, −0.67 to −0.17) and reduce morphine consumption (mean difference, −13.81 mg; 95% CI, −23.27 to −4.35) compared with single-shot blocks.12
Alternative Peripheral Nerve Blocks
Several other PNBs are available, such as the psoas compartment lumbar plexus block, the fascia iliaca block, and the sciatic nerve block (SNB), which also can provide suitable anesthesia and analgesia in TKA.26 Perhaps the most useful alternative PNB is the SNB because it provides anesthesia to the posterior aspect of the knee. When combined with an FNB, it theoretically provides more complete postoperative pain relief. The use of SNB should be restricted to patients with varus deformity of the knee because it may complicate the interpretation of a postoperative neurovascular examination in patients with valgus deformity. A systematic review by Abdallah and Brull31 included four RCTs and three observational studies comparing SNB plus FNB with SNB alone in 391 TKA patients and suggested that modest improvements in VAS pain scores and opioid consumption occur within the first 24 hours postoperatively when using a combination of SNB plus FNB. The heterogeneity of the studies made it impossible to perform a meta-analysis, however.
Local Infiltration Analgesia
Interest in local infiltration anesthesia (LIA) has been increasing since Busch et al32 performed the first high-quality prospective RCT to compare the efficacy of LIA plus PCA and PCA alone administered for postoperative pain control after TKA with regard to postoperative pain scores, morphine consumption, and patient satisfaction. They found a statistically significant reduction (P < 0.001) in morphine consumption within the first 24 hours postoperatively in the group that received LIA, along with statistically significant improvement in VAS pain scores (P = 0.007) and VAS patient satisfaction scores (P = 0.013) at 4 hours postoperatively.
LIA consists of an intraoperative injection of a compound mixture of medications, most often including a long-acting anesthetic, an NSAID, and epinephrine, which is administered to the posterior capsule, collateral ligaments, capsular incision, quadriceps tendon, and subcutaneous tissues. Wide variability exists in the strength of the medication and in the type of medications combined in LIA cocktails. Some LIA cocktails also may include corticosteroids instead of NSAIDs, antibiotics, and clonidine. Common LIA medications are listed in Table 4 and common LIA cocktails are listed in Table 5.
To understand the essential components of a LIA cocktail, Kelley et al33 evaluated the postoperative pain relief provided by four different periarticular injection admixtures in 150 patients undergoing TKA. They found that patients who had received periarticular injections containing ropivacaine, ketorolac, and epinephrine with or without clonidine, had substantially less pain in the immediate postoperative period than did those patients who received injections containing ropivacaine and epinephrine alone, suggesting that ketorolac is a key component of the injection. Parvataneni et al34 performed an RCT of 60 TKA patients assigned to receive LIA or FNB plus PCA postoperatively. Both groups also received a standardized multimodal oral analgesic protocol. The authors found that the LIA group had an improved ability to perform a straight leg raise on postoperative day 1 (63% [31 patients] versus 21% [29 patients]; P < 0.05), with similar pain scores between both groups during their postoperative hospital course, suggesting that LIA provides pain control equivalent to that of FNB while maintaining quadriceps motor strength.
Similar findings were also demonstrated by Spangehl et al35 in a nonblinded RCT of 160 patients undergoing primary TKA who were randomized to receive either a continuous femoral nerve catheter and single-shot SNB (79 patients) or an LIA cocktail of ropivacaine, ketorolac, epinephrine, and morphine (81 patients). The authors noted no difference in postoperative pain scores between the two groups during the first two postoperative days. Although the LIA group had a shorter average length of stay compared with the PNB group (2.44 and 2.84 days, respectively), on average, the LIA group consumed more morphine on the first day after surgery. Notably, the patients in the PNB group, compared with the LIA group, experienced more acute postoperative falls (3 and 0, respectively), lower quadriceps function as measured by the ability to perform a straight leg raise on postoperative day 1 (24% and 79%, respectively), and more peripheral nerve dysesthesias (12% and 1.3%, respectively) at 6 weeks postoperatively. Studies comparing the effectiveness of LIA with other pain-management modalities are summarized in Table 6.
Recently, a delayed-release liposomal formulation of bupivacaine was approved for use in the United States. This formulation is purported to provide long-acting pain relief of up to 72 hours postoperatively via a controlled release, thus minimizing the risk of bupivacaine toxicity. It is surgeon administered in the same manner as a traditional periarticular local infiltration injection using multiple passes with a 25-gauge needle to inject small aliquots. Importantly, it must be administered in isolation because admixture with nonbupivacaine- or nonliposomal-based anesthetics may cause an inadvertent immediate release of the bupivacaine. The concomitant administration of nonliposomal bupivacaine with liposomal bupivacaine is not recommended and should be done with caution because this can alter the pharmacokinetics of the liposomal bupivacaine, resulting in local anesthetic toxicity. When considering LIA strategies, it is important to note that the average wholesale price of a single 20-mL vial containing 266 mg of liposomal bupivacaine is 95 times more expensive than a 10-mL vial of traditional 0.25% bupivacaine ($285 and $3, respectively).37
In an industry-sponsored prospective RCT on postoperative pain relief using LIA in TKA patients, Bramlett et al38 examined varying doses of liposomal bupivacaine (133 to 532 mg) compared with a control of nonliposomal bupivacaine (150 mg). The liposomal bupivacaine group had substantially reduced pain scores compared with control subjects at a dose that was twice the recommended value (532 mg), and this benefit was seen only on postoperative day 1. Bagsby et al39 reported similar results in a retrospective cohort study of 150 consecutive TKA patients, comparing liposomal bupivacaine with a traditional periarticular injection of ropivacaine, morphine, and epinephrine. They did not find any difference between the two groups in the amount of pain experienced in the first 24 hours after surgery or in morphine consumption during the entire hospital stay. After the first postoperative day, the traditional LIA group actually experienced less self-reported pain during the remaining hospital stay compared with the liposomal bupivacaine group (4.4 versus 4.9 on the VAS pain scale). In a prospective single-blind RCT performed by Collis et al,40 105 consecutive patients undergoing primary TKA with a single surgeon were randomized to receive LIA with either liposomal bupivacaine (54 patients) or a standard LIA cocktail of ropivacaine, ketorolac, epinephrine, and clonidine (51 patients). The authors found no statistical differences in morphine consumption, pain scores, knee range of motion, length of stay, or walking distances at any time point out to 8 weeks postoperatively. Schroer et al41 reported similar results in a prospective single-blind RCT of 111 consecutive patients undergoing primary TKA with a single surgeon. The patients were randomized to receive either liposomal bupivacaine mixed with nonliposomal bupivacaine (58 patients) or nonliposomal bupivacaine alone (53 patients). The authors also reported no statistical differences in morphine consumption, pain scores, length of stay, or knee range of motion out to 3 weeks postoperatively. Current available evidence suggests no added benefit to using liposomal bupivacaine instead of a traditional LIA cocktail in primary TKA. Larger RCTs are needed to clarify whether any cost-benefit of liposomal bupivacaine exists compared with traditional LIA cocktails in TKA. Studies comparing the effectiveness of liposomal bupivacaine with traditional periarticular injections are summarized in Table 7.
Effect of Multimodal Anesthesia on Length of Stay
Assessing whether multimodal techniques can reduce the length of hospital stay after TKA can be challenging because a variety of factors, such as patient preconceptions, medical comorbidities, postoperative complications, and social factors, can play a role in determining the overall length of stay. A retrospective study by Peters et al42 examining the application of a multimodal anesthesia protocol to 200 total joint arthroplasty patients (100 TKAs) highlighted this difficulty. In the TKA subgroup, the average length of stay was 3.1 days in the traditional group versus 3 days in the multimodal group (P = 0.7). Of the 50 TKA patients who received multimodal anesthesia, however, 2 had postoperative complications, rendering them outliers in the statistical analysis of the effect of multimodal anesthesia on length of stay. Removal of these patients from the analysis reduced the average length of stay in the multimodal group to 2.5 days (P = 0.002). In a more recent prospective randomized controlled study by Lamplot et al,43 36 TKA patients were randomized to receive a periarticular injection and multimodal oral analgesics or PCA. The authors reported no difference in length of stay between the multimodal group and the PCA group (1.9 days and 2.3 days, respectively).
Postoperative pain control following TKA and related medication adverse effects remains a driver of patient satisfaction and postoperative complications and may present a barrier to patient discharge. Furthermore, a mounting body of evidence suggests that the choice of perioperative anesthesia in TKA may influence the risk of postoperative complications and the mortality rate. A combination of multimodal analgesia, preemptive analgesia, and neuraxial anesthesia is supplemented by either a PNB, periarticular injection, or both to effectively control postoperative pain while minimizing opioid-related adverse effects and improving patient satisfaction. The ability of multimodal analgesic protocols to reduce the length of hospital stay, although promising, is still controversial, and further investigation with large high-quality RCTs is warranted. The surgeon should collaborate with anesthesia and pain-management colleagues to develop a multimodal protocol that suits the skills of all the physicians involved in the care of the patient undergoing TKA.
Evidence-based Medicine: Levels of evidence are described in the table of contents. In this article, references 12, 14, 19, 25, 32, 33, 35, 38, 40, and 41 are level I studies. References 4, 7-10, 16, 17, 29, 30, 31, 34, 36, and 43 are level II studies. References 2, 3, 11, 37, 39, and 42 are level III studies. References 5, 18, 21, 22, and 27 are level IV studies.
References printed in bold type are those published within the past 5 years.
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