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1 1770 ORIGINAL ARTICLE Loss of Knee-Extension Strength Is Related to Knee Swelling After Total Knee Arthroplasty Bente Holm, MSc, Morten T. Kristensen, PhD, Jesper Bencke, PhD, Henrik Husted, MD, Henrik Kehlet, PhD, Thomas Bandholm, PhD ABSTRACT. Holm B, Kristensen MT, Bencke J, Husted H, Kehlet H, Bandholm T. Loss of knee-extension strength is related to knee swelling after total knee arthroplasty. Arch Phys Med Rehabil 2010;91: Objective: To examine whether changes in knee-extension strength and functional performance are related to knee swelling after total knee arthroplasty (TKA). Design: Prospective, descriptive, hypothesis-generating study. Setting: A fast-track orthopedic arthroplasty unit at a university hospital. Participants: Patients (N 24; mean age, 66y; 13 women) scheduled for primary unilateral TKA were investigated 1 week before surgery and on the day of hospital discharge 2.4 days postsurgery. Interventions: Not applicable. Main Outcome Measures: We assessed all patients for knee-joint circumference, knee-extension strength, and functional performance using the Timed Up & Go, 30-second Chair Stand, and 10-m fast speed walking tests, together with knee pain during all active test procedures. Results: All investigated variables changed significantly from pre- to postsurgery independent of knee pain. Importantly, knee circumference increased (knee swelling) and correlated significantly with the decrease in knee-extension strength (r.51; P.01). Reduced fast-speed walking correlated significantly with decreased knee-extension strength (r.59; P.003) and decreased knee flexion (r.52; P.011). Multiple linear regression showed that knee swelling (P.023), adjusted for age and sex, could explain 27% of the decrease in kneeextension strength. Another model showed that changes in knee-extension strength (P.009) and knee flexion (P.018) were associated independently with decreased performance in fast-speed walking, explaining 57% of the variation in fastspeed walking. Conclusions: Our results indicate that the well-known finding of decreased knee-extension strength, which decreases functional performance shortly after TKA, is caused in part by From The Lundbeck Center for Fast-Track Hip- and Knee Arthroplasty (Holm, Husted, Kehlet); Departments of Physical Therapy (Holm, Kristensen, Bandholm) and Orthopedic Surgery (Kristensen, Husted, Bandholm), Gait Analysis Laboratory (Bencke), and Clinical Research Center (Bandholm), Gait Analysis Laboratory (Bencke), Clinical Research Center (Bandholm), Copenhagen University Hospital at Hvidovre, Hvidovre; and Section for Surgical Pathophysiology (Kehlet), Rigshospitalet, Copenhagen University, Copenhagen, Denmark. Supported by the Lundbeck Foundation for Fast-Track Hip and Knee Arthroplasty, Denmark. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated. Reprint requests to Bente Holm, MSc, Physiotherapist for Research and Development, Dept of Physical Therapy 236, Copenhagen University Hospital at Hvidovre, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark, bente.holm@hvh.regionh.dk /10/ $36.00/0 doi: /j.apmr postoperative knee swelling. Future studies may look at specific interventions aimed at decreasing knee swelling postsurgery to preserve knee-extension strength and facilitate physical rehabilitation after TKA. Key Words: Arthroplasty, replacement, knee; Muscle strength; Pain, postoperative; Rehabilitation by the American Congress of Rehabilitation Medicine PATIENTS UNDERGOING TOTAL knee arthroplasty are characterized pre- and postsurgery by pain and a decrease in knee-extension strength, knee motion, and functional performance. 1-4 Decreased functional performance in the early phase after TKA seems to be related to quadriceps weakness. 3 Many patients are not able to fully activate the quadriceps muscle of the operated leg initially, 5 probably related to the surgical technique, but also to arthrogenic reflex inhibition of the muscle caused by knee pain or swelling Twitch-interpolation techniques applied during maximal voluntary knee extensions before and after TKA have indicated increased central activation failure of the quadriceps muscle after TKA. 4,11 Thus, central activation failure of the quadriceps muscle seems to contribute considerably more to the acute decrease in knee-extension strength after TKA than the amount of quadriceps muscle atrophy 2 and postoperative knee pain. 4 It suggests that other factors, such as knee swelling, may be more closely related to the initial decrease in knee-extension strength after TKA. Preserving knee-extension strength after TKA is important because knee-extension strength is related to functional performance after TKA. 3 Hence, the mechanisms underlying this acute decrease in knee-extension strength need to be identified to improve postoperative recovery and rehabilitation protocols after TKA. With respect to knee swelling, experimental knee-effusion models have provided evidence that the quadriceps muscle is substantially inhibited, in the absence of knee pain, after intraarticular injections with isotonic saline The effect seemed to be reflex mediated because decreased excitability of the quadriceps motor neurones is seen during experimental knee effusion in healthy subjects, 10 and decreased efferent (electromyography) drive is seen with experimental knee effusion in subjects with knee arthritis. 12 Moreover, in chronically effused knees, aspiration from the knee joint increased knee-extension strength immediately by an average of 13%. 6 Similar relationships between knee swelling, knee-extension strength, and functional performance may exist in elective TKA. ICC ROM TKA TUG VAS List of Abbreviations intraclass correlation coefficient range of motion total knee arthroplasty Timed Up & Go visual analog scale

2 KNEE-EXTENSION STRENGTH AND KNEE SWELLING, Holm 1771 The objective of this study therefore was to examine whether changes in knee-extension strength and functional performance are related to knee swelling shortly after TKA. METHODS Design The study was designed as a prospective, descriptive, hypothesis-generating study in which patients scheduled for primary unilateral TKA because of severe osteoarthritis were investigated 1 week before surgery and again postsurgery on the day of discharge from a specialized fast-track orthopedic unit. 13 Participants Patients (N 25) from the Department of Orthopedic Surgery at the Copenhagen University Hospital at Hvidovre were consecutively included between December 2008 and June The inclusion criterion was planned primary unilateral TKA. Exclusion criteria were inability to speak and understand Danish and inability to perform functional measurements because of other diseases. One patient was excluded after inclusion because of the inability to complete the postsurgery test session due to fatigue, leaving 24 patients (13 women) in this study. Participants had a mean SD age, height, body mass, and body mass index of 66 7 years, cm, kg, and kg/m 2, respectively. All patients were given written information about the procedures of the study, and informed consent was obtained in accordance with the Declaration of Helsinki. The Ethical Committee in Copenhagen approved the study (H-D-2008-FSP). Procedures Perioperative care. All patients followed a fast-track program for TKA. 13 It included preoperative multidisciplinary education, a specialized ward for patients receiving arthroplasty only, well-defined optimized multimodal pain treatment, postoperative rehabilitation that included early ambulation, and early oral nutrition. Two experienced surgeons performed all operations. All patients underwent surgery using the medial parapatellar approach (midline skin incision) with a cemented tricompartmental prosthesis with fixed bearing (including resurfacing of the patella). Surgery was performed using spinal anesthesia supplemented with local infiltration analgesia used peri- and postoperatively for 24 hours, 14,15 together with a daily dose of gabapentin (900mg/d), paracetamol (4g/d), and celecoxib (400mg/d) initiated preoperatively on the morning of surgery and the following 6 postoperative days. Oxycodone, 5mg, was used as rescue analgesic for moderate or severe pain. All patients were advised to elevate the operated leg when resting. Postoperative rehabilitation included mobilization with a high walker on wheels on the day of surgery, with further daily standardized physical therapy according to an established clinical pathway. 16 All patients were discharged to their homes according to well-defined discharge criteria. 13 Study measurements. All postsurgery measurements were performed no earlier than 1 hour after the daily physical therapy session. Knee Circumference With the patient relaxed in the supine position, the circumference of the extended knee was measured 1 cm proximal to the base of the patella using the same tape measure in all patients. 17 Intratester and intraday reliability of this measurement recently was reported to be excellent, with an ICC 2.1 of Fig 1. Set-up for the knee-extension strength measurement with use of a fixed hand-held dynamometer..98 and smallest detectable difference of 1cm. 18 We quantified changes in knee joint circumference as absolute (centimeters) and relative (%) changes from presurgery values. Knee-Extension Strength After warm-up and familiarization with the procedure, maximal knee-extension force was measured using a hand-held dynamometer. a Patients sat at the end of the examination couch with hip angle of 90, knee angle of 60 (0 full extension), and the feet supported by a small bench to ensure the correct knee joint angle (60 ). A large Velcro strap was attached to the examination couch and the patient s ankle (perpendicular to the lower leg) 5cm proximal to the lateral malleolus. The transducer then was placed at the front of the ankle under the Velcro strap to measure knee extension force (fig 1). Patients were instructed to contract as forcefully as possible with a gradual increase in force, and strong verbal encouragement was provided during the contractions. They performed 5 contractions separated by 60-second pauses, and the highest value was used as the result. Knee-extension strength subsequently was expressed at the maximal voluntary torque per kilo of body mass using the external lever-arm length and body mass of each patient. High intratester, interday reliability (ICC ) of a similar knee-extensor strength measurement has been reported. 19 We quantified changes in knee-extension strength as absolute (Newton meter per kilogram of body mass) and relative (%) changes from presurgery values. Functional Performance For all measures of functional performance, no walking aid was used at presurgery testing, and elbow crutches were used at postsurgery testing. The TUG test was used to measure the time (in seconds) it took patients (as quickly and safely as possible) to rise from a chair (chair seat height,.45m), walk 3m to a line drawn on the floor, and return to the chair. Time was measured from the seated position (back against the backrest) with a stopwatch started on the command ready-go and stopped when the seated position was regained. No personal assistance was allowed, but verbal cueing was provided, if necessary. Patients were given 1 practice trial followed by 1 timed trial. The TUG test has shown excellent reliability and validity. 20

3 1772 KNEE-EXTENSION STRENGTH AND KNEE SWELLING, Holm The 30-second Chair Stand test was used to measure how many times patients were able to rise from a chair and sit down again in 30 seconds. Patients were seated at the middle of a chair with both feet parallel on the floor and arms crossed on the chest. On the command ready-go, the patient rose to a fully upright position and sat down again. No personal assistance was allowed, but verbal cueing was provided, if necessary. Patients were given 1 practice trial followed by 1 timed trial. The 30-second Chair Stand test is both reliable and valid. 21 The 10-m fast-speed walking test was used to measure how long it took patients to walk 10m as quickly as possible. It was measured from a standing position. A stopwatch was started on the command go and stopped when the patient s first foot crossed a 10-m line. Maximal gait speed then was expressed as meters a second. 22 We quantified changes in all functional performance measures as absolute and relative (%) changes from presurgery values. Postural Control Postural control was measured using a biomechanical forceplate. b Patients stood with their feet 5cm apart, eyes open, and hands folded across the chest. After a practice trial, they were instructed to fixate their vision at a mark 3m away and stand as still as possible for 20 seconds during 3 valid trials, separated by 1-minute pauses. 23 Postural control was expressed as the total length of the center of foot-pressure displacement (sway length) during each trial (millimeters) and subsequently calculated as the mean of 3 trials. We quantified changes in postural control as absolute (millimeters) and relative (%) changes from presurgery values. Knee-Joint ROM Active ROM of knee extension and flexion was measured using a standardized manual, 18 tested for validity and reliability. 18,24 Patients lay supine during measurements. The center of a 360 plastic goniometer with 30-cm movable arms, scale in 1 increments, c was placed over the lateral femur epicondyle, the proximal arm was aligned with the lateral midline of the femur using the greater trochanter as a reference, and the distal arm was aligned with the lateral midline of the fibula using the lateral malleolus as reference. For flexion measurements, patients were asked to draw the heel toward the buttock, allowing lift of the heel. The highest value of 2 measurements was used. For extension measurements, the heel was placed on a small cylinder firm back roll, and patients were asked to extend the knee as much as possible. Extension deficits were registered as positive degrees, and extension beyond 0 (hyperextension), as minus degrees. The lowest value of 2 measurements was used. We quantified changes in ROM as absolute (degrees, in 1 increments) and relative (%) changes from presurgery values. Knee Pain The VAS was used to quantify knee pain during each active assessment. Patients rated pain in and around the knee immediately after all measurements by using a VAS ruler d with a scale from 0 to 100mm, with 0 representing no pain and 100 representing the worst pain imaginable. 25 We quantified changes in pain as absolute (millimeters) and relative (%) changes from presurgery values. Blinding The same experienced physiotherapist performed and recorded all measurements. After presurgery measurements were recorded, presurgery results were not accessible until after postsurgery measurements had been recorded, in an attempt to avoid recall bias. Statistical Methods We initially performed a power analysis to determine the number of patients required to establish a significant (P.05) and clinically meaningful correlation of 0.5 with 80% power between knee-extension strength and knee-joint circumference. It showed that at least 23 patients needed to be included. Variability around mean values was expressed as 1SD because data were normally distributed (Kolmogorov-Smirnoff). Differences between pre- and postsurgery data were examined by using paired-samples t tests. Between-variable correlations were quantified by using Pearson correlation coefficients. Univariate analysis was performed to determine whether significant relationships existed between changes in measurements of knee-extension strength, knee swelling, and measures of functional performance. Multiple linear regression models (enter model) with age and sex as known factors influencing muscle strength and functional performance, 26 in addition to factors with significant associations in univariate testing, were performed for knee-extension strength and 10m fast-speed walking as dependent variables. All data analyses were performed using SPSS. e The level of significance was P less than.05. RESULTS Changes Due to Surgery Results from the pre- and postsurgery assessments are listed in table 1. At discharge, nights postsurgery, patients showed increased knee-joint circumference (knee swelling; mean increase, 12%), decreased knee-extension strength (83%), poorer performance in all measurements of functional performance (133%, TUG test; 48%, 30-second Chair Stand test; 50%, 10-m fast-speed walking), decreased postural control (ie, increased sway length [33%]), and decreased knee-joint ROM (74%, extension; 40%, flexion) (P.007). Knee pain during the different measurements showed increases of 0% to 75%, but only knee pain during the knee-extension strength measurement tended to increase significantly (P.05). At the postsurgery assessment, 1 patient declined to perform the 10-m fast-speed walking test because of fatigue, and postural sway data from 3 patients had to be discarded because of technical problems. Between-Variable Correlations Between-variable correlations are listed in table 2, and correlations between knee swelling, knee-extension strength, fast-speed walking, and knee-flexion ROM are shown as scatterplots in fig 2. Knee swelling (increased knee-joint circumference) correlated significantly with knee-extension strength loss (r.51; P.01) (fig 2A). Knee swelling did not correlate significantly with changes in functional performance, although a trend was observed for the 10-m fast-speed walking (r.35; P.10) (fig 2B). However, knee-extension strength loss correlated with decreased functional performance evaluated by using the 10-m fast-speed walking test (r.59; P.003) (fig 2C), and the decrease in 10-m fast-speed walking also correlated with the decrease in knee-flexion ROM (r.52; P.01) (fig 2D), but not with the TUG or 30-second Chair Stand test results (P.288). Knee pain did not correlate with any of the applied measurements pre- or postsurgery, and the change in knee pain did not correlate with changes in any of the applied measurements (P.05).

4 KNEE-EXTENSION STRENGTH AND KNEE SWELLING, Holm 1773 Variables Table 1: Results of Measurements for All Patients Presurgery Postsurgery/At Discharge P Change in Mean % From Presurgery Knee circumference (cm)* Knee-extension strength (Nm/kg body weight)* Pain during knee-extension strength test, VAS (mm)* TUG test (s) Pain during TUG test, VAS (mm) s Chair Stand test (no. of sit-to-stand) Pain during 30-s Chair Stand, VAS (mm) m fast-speed walking (m/s) Pain during 10-m fast-speed walking, VAS (mm) Postural control (length of sway, mm) Knee-extension ROM deficit ( )* Pain during knee-extension ROM, VAS (mm)* Knee-flexion ROM ( )* Pain during knee-flexion ROM, VAS (mm)* NOTE. Pre- and postsurgery results presented as mean SD, and P values refer to analyses between pre- and postsurgery results using paired-samples t test. Abbreviation: Nm, Newton meter. *Operated knee. n 23. n 21. Multiple Regressions A multiple linear regression model showed that knee swelling (P.023), adjusted for age and sex, explained 27% of the variation in change in knee-extension strength (table 3). Of concern, very high residuals ( 24) were seen in 2 patients in this model, and a new regression model without these 2 extreme outliers was able to explain 50% (R 2 ) of the variation in change in knee-extension strength. However, knee swelling was the only variable significantly (P.04) influencing this change. The multiple linear regression model using 10-m fastspeed walking as the dependent variable showed that changes in knee-extension strength (P.009) and knee-flexion ROM (P.018) were significant predictor variables in a model that also included changes in knee swelling, age, and sex (table 4). This model was statistically stable and able to explain 57% (R 2 ) of the variation in change in 10-m fast-speed walking. No multicollinearity was seen in any of the multiple regression models. DISCUSSION To our knowledge, this is the first study to examine the extent to which postoperative knee swelling is related to changes in knee-extension strength and functional performance shortly after TKA. We found that the greater the postoperative knee swelling, the greater the decrease in knee-extension strength. That is, an increase of 1.9% in knee circumference was associated with a decrease of 1.0% in knee-extension strength (see table 3), which was independent of changes in knee pain. Changes in functional performance (10-m fast-speed walking) were related to decreased knee-extension strength and Table 2: Correlations and Significance Between Changes (%) From Pre- to Postsurgery for Knee Swelling, Knee-Extension Strength, Functional Performance, Postural Control, and Knee-Joint ROM Variables r and P Knee Swelling* Knee Extension Strength* TUG 30-s Chair Stand 10-m Fast-Speed Walking (n 23) Postural Control (n 21) Knee-Extension ROM* Knee-extension strength* r.51 NA NA NA NA NA NA P.010 NA NA NA NA NA NA TUG test r NA NA NA NA NA P NA NA NA NA NA 30-s Chair Stand test r NA NA NA NA P NA NA NA NA 10-m fast-speed walking r NA NA NA P NA NA NA Postural control r NA NA P NA NA Knee-extension ROM* r NA P NA Knee-flexion ROM* r P Abbreviation: r, Pearson coefficient of correlation; NA, not applicable. *Operated knee. n 23. n 21.

5 1774 KNEE-EXTENSION STRENGTH AND KNEE SWELLING, Holm Fig 2. Scatterplots of correlations between changes in (A) knee circumference (swelling) and knee-extension strength, (B) knee swelling and 10-m fast-speed walking (n 23), (C) 10-m fast-speed walking and knee-extension strength (n 23), and (D) 10-m fast-speed walking and knee-flexion ROM (n 23) for patients who underwent TKA. knee-flexion ROM. Again, this relationship was independent of changes in knee pain. Our findings correspond to data obtained using experimental knee-effusion models in healthy subjects. Knee-extension strength decreased immediately after effusions of the healthy knee joint with isotonic saline, 7,9,27 which can be abolished by means of aspiration or injection of a local anesthetic into the joint. 6 Table 3: Multivariate Linear Regression Analysis Indicating Factors Independently Influencing Changes (%) From Pre- to Postsurgery for Knee-Extension Strength Predictor Variables Adjusted B 95% CI for B Lower Upper Age (y) Sex (men) Knee swelling* Constant NOTE. Knee-extension strength measured in Newton meters per kilogram. n 24. B stands for regression coefficient; Adjusted B indicates the adjusted regression coefficient. Abbreviation: CI, confidence interval. *Values are % change. Operated knee. P This effect likely is mediated through strain-sensitive mechanoreceptors located within the knee joint capsule, 28 which change afferent input to the central nervous system by their activation during knee effusion or swelling, resulting in diminished ipsilateral 29 efferent drive to the quadriceps muscle. 27,30 Table 4: Multivariate Linear Regression Analysis Indicating Factors Independently Influencing Changes (%) From Pre- to Postsurgery for 10-m Fast-Speed Walking Predictor Variables Adjusted B 95% CI for B Lower Upper Age (y) Sex (men) Knee swelling* Knee-extension strength* Knee-flexion ROM* Constant NOTE. Fast-speed walking measured in meters per second. n 23. B stands for regression coefficient; Adjusted B indicates the adjusted regression coefficient. Abbreviation: CI, confidence interval. *Values are % change. Operated knee. P

6 KNEE-EXTENSION STRENGTH AND KNEE SWELLING, Holm 1775 The involved spinal mechanisms seem to include postsynaptic inhibition and disfascilitation of the quadriceps motor neuron pool. 31 Hence, the well-known clinical observation that quadriceps inhibition is common after TKA likely is caused by reflex inhibition of the alfa motor neurons supplying the quadriceps muscle. In the present study, it is uncertain whether the observed knee swelling was caused by intra- and/or extra-articular fluid accumulation because knee swelling was quantified by changes in knee-joint circumference. Future studies using magnetic resonance imaging or ultrasonography might verify locations of the swelling for the purpose of decreasing it. With respect to circumference measurements, it may seem a crude measurement. Nevertheless, in an earlier study, the measurement was shown to be highly reliable in patients after TKA as long as it was performed by the same examiner at the different times. 18 In addition, the measurement is easily applicable in daily practice and may help monitor knee-joint swelling in TKA rehabilitation. Quantification of knee-extension strength at discharge after fast-track TKA was not reported before. Our study showed a dramatic decrease in knee-extension strength (83%), which corresponds to previous reports of knee-extension strength decreases of 60% to 64% at 1 month after TKA 2,4,11 and with residual deficits that may persist for years. 32 Any large kneeextension strength decrease poses a problem with respect to functional performance after TKA, especially because kneeextension strength before surgery has been reported to be on average 25% lower than that of healthy older adults. 2 Consequently, studies have focused on the effect of resistance exercises postsurgery and found improvements in both muscle strength and functional performance. 32,33 For any quadriceps strength training to have an effect in the very early period after TKA, quadriceps inhibition should be decreased. That is, quadriceps strength training likely should be preceded by interventions that temporarily or more permanently decrease quadriceps inhibition. It may be changes in surgical procedures 34 or interventions postsurgery, such as cryotherapy, electrical stimulation, or exercise. 9,33,35,36 The latter 3 interventions have shown promising results with respect to decreasing quadriceps inhibition in experimental knee-effusion models. 9,36 Of the functional performance measures, only the 10-m fast-speed walking change was related to the decrease in kneeextension strength. Knee-extension strength and knee-flexion ROM change were found to be independent predictors of 10-m fast-speed walking change, explaining 57% of the variation in the decrease in 10-m fast-speed walking. Thus, a decrease in knee-extension strength of 0.5% and/or 0.4% in knee flexion was associated with a 1% decrease in 10-m fast-speed walking (see table 4). We had expected that changes in more functional performance measures would relate to the knee-extension strength loss, as indicated in previous studies performed at a later time after surgery. 3,37 It indicates that at discharge, kneeextension strength loss was so severe in most patients that for the TUG and 30-second Chair Stand tests, psychological (eg, fear of movement) and submaximal motor-control factors (eg, decreased intermuscular coordination) may be more closely related to the decreased performance in these 2 tests at this time. Hence, it seems that at discharge, the 10-m fast-speed test is an important measure of functional performance after TKA surgery. Because of technical problems, we had to exclude postural control data for 3 patients. Hence, the postural control analyses may have been underpowered. CONCLUSIONS The well-known finding of decreased knee-extension strength after TKA, which decreases functional performance, seems to be caused in part by postoperative knee swelling in the very early postoperative phase. This is new and important information. Moreover, decreased functional performance after TKA seems to be related to both decreased knee-extension strength and decreased knee-flexion ROM. Knee pain does not appear to influence knee-extension strength or functional performance at this early point after TKA. Future studies may seek to identify additional mechanisms causing knee-extension strength loss after TKA because knee swelling could not explain the entire decrease. Future studies also may seek to identify the location of the postoperative swelling to design specific interventions aimed at decreasing the degree of knee swelling after TKA, which may help preserve knee-extension strength and facilitate physical rehabilitation. Acknowledgments: We thank the physiotherapists and nurses from the Department of Orthopedic Surgery at Copenhagen University Hospital at Hvidovre for assistance related to performing this investigation and Thomas Linding Jakobson, PT, for valuable discussions about the validity and reliability of measurements. References 1. Mizner RL, Petterson SC, Snyder-Mackler L. Quadriceps strength and the time course of functional recovery after total knee arthroplasty. J Orthop Sports Phys Ther 2005;35: Mizner RL, Petterson SC, Stevens JE, Vandenborne K, Snyder- Mackler L. Early quadriceps strength loss after total knee arthroplasty. The contributions of muscle atrophy and failure of voluntary muscle activation. J Bone Joint Surg Am 2005;87: Mizner RL, Snyder-Mackler L. Altered loading during walking and sit-to-stand is affected by quadriceps weakness after total knee arthroplasty. J Orthop Res 2005;23: Stevens JE, Mizner RL, Snyder-Mackler L. Quadriceps strength and volitional activation before and after total knee arthroplasty for osteoarthritis. J Orthop Res 2003;21: Kullenberg B, Ylipaa S, Soderlund K, Resch S. Postoperative cryotherapy after total knee arthroplasty: a prospective study of 86 patients. J Arthroplasty 2006;21: Fahrer H, Rentsch HU, Gerber NJ, Beyeler C, Hess CW, Grunig B. Knee effusion and reflex inhibition of the quadriceps. A bar to effective retraining. J Bone Joint Surg Br 1988;70: Hopkins JT, Ingersoll CD, Krause BA, Edwards JE, Cordova ML. Effect of knee joint effusion on quadriceps and soleus motoneuron pool excitability. Med Sci Sports Exerc 2001;33: Hopkins JT. Knee joint effusion and cryotherapy alter lower chain kinetics and muscle activity. J Athl Train 2006;41: McNair PJ, Marshall RN, Maguire K. Swelling of the knee joint: effects of exercise on quadriceps muscle strength. Arch Phys Med Rehabil 1996;77: Spencer JD, Hayes KC, Alexander IJ. Knee joint effusion and quadriceps reflex inhibition in man. Arch Phys Med Rehabil 1984;65: Mizner RL, Stevens JE, Snyder-Mackler L. Voluntary activation and decreased force production of the quadriceps femoris muscle after total knee arthroplasty. Phys Ther 2003;83: Geborek P, Moritz U, Wollheim FA. Joint capsular stiffness in knee arthritis. Relationship to intraarticular volume, hydrostatic pressures, and extensor muscle function. J Rheumatol 1989;16: Husted H, Holm G, Jacobsen S. Predictors of length of stay and patient satisfaction after hip and knee replacement surgery: fasttrack experience in 712 patients. Acta Orthop 2008;79: Andersen LO, Husted H, Otte KS, Kristensen BB, Kehlet H. High-volume infiltration analgesia in total knee arthroplasty: a

7 1776 KNEE-EXTENSION STRENGTH AND KNEE SWELLING, Holm randomized, double-blind, placebo-controlled trial. Acta Anaesthesiol Scand 2008;52: 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: Holm B, Kristensen MT, Myhrmann L, et al. The role of pain for early rehabilitation in fast track total knee arthroplasty. Disabil Rehabil 2010;32: Gumpel JM, Matthews SA, Altman DG, Spencer JD, Wilkins EA. An objective assessment of synovitis of the knee: measurement of the size of the suprapatellar pouch on xeroradiography. Ann Rheum Dis 1980;39: Jakobsen TL, Christensen M, Christensen SS, Olsen M, Bandholm T. Reliability of knee joint range of motion and circumference measurements after total knee arthroplasty: does tester experience matter? Physiother Res Int 2010;15: Roy MA, Doherty TJ. Reliability of hand-held dynamometry in assessment of knee extensor strength after hip fracture. Am J Phys Med Rehabil 2004;83: Yeung TS, Wessel J, Stratford PW, MacDermid JC. The Timed Up and Go Test for use on an inpatient orthopaedic rehabilitation ward. J Orthop Sports Phys Ther 2008;38: Rikli RE. Reliability, validity, and methodological issues in assessing physical activity in older adults. Res Q Exerc Sport 2000;71(2 Suppl):S Watson MJ. Refining the ten-metre walking test for use with neurologically impaired people. Physiotherapy 2002;88: Jancova J. Measuring the balance control system review. Acta Med (Hradec Kralove) 2008;51: Gogia PP, Braatz JH, Rose SJ, Norton BJ. Reliability and validity of goniometric measurements at the knee. Phys Ther 1987;67: Coll AM, Ameen JR, Mead D. Postoperative pain assessment tools in day surgery: literature review. J Adv Nurs 2004;46: Rikli RE, Jones CJ. Functional fitness normative scores for community-residing older adults, ages J Aging Phys Act 1999;7: Wood L, Ferrell WR, Baxendale RH. Pressures in normal and acutely distended human knee joints and effects on quadriceps maximal voluntary contractions. Q J Exp Physiol 1988;73: Wood L, Ferrell WR. Response of slowly adapting articular mechanoreceptors in the cat knee joint to alterations in intra-articular volume. Ann Rheum Dis 1984;43: Palmieri RM, Ingersoll CD, Edwards JE, et al. Arthrogenic muscle inhibition is not present in the limb contralateral to a simulated knee joint effusion. Am J Phys Med Rehabil 2003;82: Rice D, McNair PJ, Dalbeth N. Effects of cryotherapy on arthrogenic muscle inhibition using an experimental model of knee swelling. Arthritis Rheum 2009;61: Rice DA, McNair PJ. Quadriceps arthrogenic muscle inhibition: neural mechanisms and treatment perspectives. Semin Arthritis Rheum Available at: Accessed November 30, Lastayo PC, Meier W, Marcus RL, Mizner R, Dibble L, Peters C. Reversing muscle and mobility deficits 1 to 4 years after TKA: a pilot study. Clin Orthop Relat Res 2009;467: Petterson SC, Mizner RL, Stevens JE, et al. Improved function from progressive strengthening interventions after total knee arthroplasty: a randomized clinical trial with an imbedded prospective cohort. Arthritis Rheum 2009;61: Levy O, Martinowitz U, Oran A, Tauber C, Horoszowski H. The use of fibrin tissue adhesive to reduce blood loss and the need for blood transfusion after total knee arthroplasty. A prospective, randomized, multicenter study. J Bone Joint Surg Am 1999;81: Avramidis K, Strike PW, Taylor PN, Swain ID. Effectiveness of electric stimulation of the vastus medialis muscle in the rehabilitation of patients after total knee arthroplasty. Arch Phys Med Rehabil 2003;84: Hopkins JT, Ingersoll CD, Edwards J, Klootwyk E. Cryotherapy and transcutaneous electric neuromuscular stimulation decrease arthrogenic muscle inhibitation of the vastus medialis after knee joint effusion. J Athl Train 2001;37: Yoshida Y, Mizner RL, Ramsey DK, Snyder-Mackler L. Examining outcomes from total knee arthroplasty and the relationship between quadriceps strength and knee function over time. Clin Biomech (Bristol, Avon) 2008;23: Suppliers a. Chiroform ApS, Tingsvej 7, DK-8800 Viborg, Denmark. b. Vicon, 14 Minns Business Park, West Way, Oxford 0X2 OJB, United Kingdom. c. Chattanooga Group, 2733 Kanasita Dr, Hixson, TN d. Norpharma A/S, Slotsmarken 15, DK-2970, Horsholm, Denmark Hørsholm, Denmark. e. SPSS version 12.0; SPSS Inc, 233 S Wacker Dr, 11th Fl, Chicago, IL

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