Treatment of Anterior Cruciate Ligament Injuries, Part 2

Transcription

1 Clinical Sports Medicine Update Treatment of Anterior Cruciate Ligament Injuries, Part 2 Bruce D. Beynnon,* PhD, Robert J. Johnson, MD, Joseph A. Abate, MD, Braden C. Fleming, PhD, and Claude E. Nichols, MD From the Department of Orthopaedics and Rehabilitation, McClure Musculoskeletal Research Center, University of Vermont, Burlington, Vermont, and the Department of Orthopaedic Research, Brown Medical School, Providence, Rhode Island Anterior cruciate ligament tears, common among athletes, are functionally disabling; they predispose the knee to subsequent injuries and the early onset of osteoarthritis. A total of 3810 studies published between January 1994 and the present were identified and reviewed to determine the current state of knowledge regarding the treatment of anterior cruciate ligament injuries. Part 1 of this article focused on studies pertaining to the biomechanical behavior of the anterior cruciate ligament, the prevalence of and risk factors for injuries related to it, the natural history of the ligament-deficient knee, injuries associated with anterior cruciate ligament disruption, indications for the treatment of anterior cruciate ligament injuries, as well as nonoperative and operative treatments. Part 2 includes technical aspects of anterior cruciate ligament surgery, bone tunnel widening, graft healing, rehabilitation after anterior cruciate ligament reconstruction, and the effects of sex, age, and activity level on the outcome of such reconstructive surgery. Keywords: anterior cruciate ligament (ACL); knee; reconstruction Anterior cruciate ligament tears are common among athletes, and although their true natural history remains unclear, these injuries are functionally disabling; they predispose the knee to subsequent injuries and the early onset of osteoarthritis. This article, the second of a 2-part series, was initiated with the use of the PubMed database ( and a comprehensive search of publications that appeared between January 1994 and the present, with anterior cruciate ligament as keywords. A total of 3810 citations were identified and reviewed to determine the current state of knowledge regarding the treatment of ACL injuries. Part 1 focused on studies that pertained to the biomechanical behavior of the ACL, the prevalence of and risk factors for ACL injuries, the natural history of the ACL-deficient knee, injuries associated with ACL disruption, indications for treatment of ACL injuries, and nonoperative and operative treatments. Part 2 includes technical aspects of ACL surgery, bone tunnel widening, graft healing, rehabilitation after ACL reconstruction, and the effects of sex, age, and activity level on the outcome of ACL surgery. Our approach was to build on *Address correspondence to Bruce D. Beynnon, PhD, University of Vermont College of Medicine, Department of Orthopaedics and Rehabilitation, Stafford Hall, Room 438A, Burlington, VT ( bruce.beynnon@uvm.edu). No potential conflict of interest declared. The American Journal of Sports Medicine, Vol. 33, No. 11 DOI: / American Orthopaedic Society for Sports Medicine prior outstanding reviews 41,59,102 and to provide an overview of the literature for each of the aforementioned areas of study by summarizing the highest level of scientific evidence available. For the areas that required a descriptive approach to research, we focused on the prospective studies that were available; for the areas that required an experimental approach, we focused on the prospective, randomized, controlled trials (RCTs) and when otherwise necessary, the highest level of evidence available on the subjects presented. As with part 1, we were pleasantly surprised to learn that considerable advances were made during the past decade with regard to the treatment of this devastating injury. TECHNICAL ASPECTS OF ACL RECONSTRUCTION Graft Position (Single-Tunnel Technique) The ACL has a complex, 3-dimensional attachment to bone. The femoral insertion of the ACL does not insert on a flat area that is aligned in an anatomical plane, as many publications have suggested; rather, it is located on a curved surface, with the wall of the femoral notch becoming the roof of the femoral notch. Our review of the literature revealed that different approaches for characterizing the location of tunnel position in relation to anatomical landmarks (eg, the location of bone tunnels, or an ACL graft fixed within bone tunnels, in relation to anatomical landmarks) were a source of confusion. These different 1751

2 1752 Beynnon et al The American Journal of Sports Medicine approaches stem in part from the fact that arthroscopic visualization of the knee occurs when it is flexed, whereas standard anatomical nomenclature is referenced to the fully extended knee. 7 Although most orthopaedic surgeons would agree that graft position is a critical variable affecting the outcome of ACL reconstruction, our review found no prospective RCTs that studied the superiority of one position as opposed to another. This finding is not surprising because it would be unethical to perform a superiority or equivalency trial involving the placement of a graft in any location other than where it is considered optimal. Consequently, the effect of graft position on clinical outcome has been, and probably will remain, based on prospective studies that are descriptive in design. Our review of the literature revealed 2 prospective studies that evaluated the relationship between ACL graft insertion site and outcome. 45,66 In the well-designed study by Good et al 45 of bone patellar tendon bone (BPTB) ACL reconstruction, the center of the femoral tunnel was measured from a lateral radiograph of the knee, was expressed as a percentage of the total condylar depth measured along a line constructed parallel to the Blumensaat line, and was then referenced to the center of the anatomical insertion of the ACL. 44 Two years after surgery, subjects with an ACL graft insertion greater than 2 mm anterior to the center of the anatomical femoral insertion had significantly greater anterior-posterior (A-P) knee laxity values than subjects with centrally or posteriorly positioned femoral tunnels. Khalfayan et al 66 built on the earlier work of Good et al 45 by measuring the tibial and femoral tunnel positions of central third BPTB grafts with the use of lateral and anteroposterior view radiographs; they also reported that graft tunnel position has a direct effect on clinical outcome. A femoral tunnel placed too far anteriorly was found to limit knee flexion or produce graft attrition. Position of the tibial tunnel is also important. Anterior placement causes graft impingement against the roof of the femoral notch when the knee is extended, with persistent flexion contracture or graft attrition and subsequent failure. It is important for us to point out that most of what is known about the effect of graft impingement on outcome has been derived from retrospective studies, and this issue is a concern because when making a diagnosis of graft impingement after failure of ACL reconstruction, one must consider that anterior subluxation of the tibia relative to the femur may give a false impression of impingement. 5 Howell and Clark 53 performed a retrospective study with a 6-month follow-up period of BPTB grafts and reported that knee stability and extension were significantly better when the center of the tibial tunnel was 2 to 3 mm posterior to the center of the normal ACL insertion on the tibia. In a subsequent retrospective study, Howell et al 54 reported that a tibial tunnel angle of 75 or more in the coronal plane was associated with greater loss of flexion and increased anterior knee laxity. A tibial tunnel angle between 65 and 70 was recommended. Our group evaluated the relationship between the elongation behavior of central third BPTB grafts produced by flexion-extension of the knee at the time of surgery (a measurement that is dependent on the location of the graft s insertion to bone) and clinical outcome. 16 Graft elongation values produced by knee flexion-extension motion, at the time of surgery, outside the 95% confidence limits of the normal ACL resulted in significant increases in anterior knee laxity at 5-year follow-up, whereas grafts with elongation values similar to the normal ACL had A-P knee laxity values similar to the normal knee. 19 This finding suggests that it is not only important to restore A-P laxity to within normal limits at the time of surgery, it is also important to consider the biomechanical behavior of the graft at the time of surgery. Arthroscopic visualization, combined with modern drill guides, allows experienced surgeons to identify where they want to locate bone tunnels relative to landmarks such as the ACL footprint, the over-the-top position, and the clock face (eg, 2 o clock) positions. Even with the use of these advanced tools, placing the tibial and femoral bone tunnels in desired locations without creating impingement of the graft against the femoral notch is a challenging task. This point is well emphasized by the work of Kohn et al, 68 who studied a series of cadaveric knees after endoscopic ACL reconstruction with a BPTB graft. Only 17% of the knees were considered to have correct tunnel placement without graft impingement. Femoral tunnel placement was considered excellent, acceptable, or unacceptable in 17%, 33%, and 50% of the knees, respectively. Similarly, tibial tunnel placement was classified as excellent, acceptable, or unacceptable in 42%, 33%, and 25% of the knees, correspondingly. The position of an ACL graft is the most critical surgical variable because it has a direct effect on knee biomechanics and, ultimately, on clinical outcome. Our review of the literature revealed that the position of an ACL graft has been measured with 2-dimensional, radiographically based approaches. When the radiographic technique is obtained in a standardized manner for example, with the posterior aspects of the femoral condyles superimposed in a lateral view and measurements are made relative to reproducible bone-fixed coordinate systems, this approach has the advantage of characterizing graft position in a manner that is clinically relevant and that can be reproduced in biomechanical studies. However, an accurate description of an ACL graft s position requires a 3-dimensional technique that is applied to make measurements relative to standardized bone-fixed coordinate systems. Although such technology has recently become available in the form of electromagnetic and video-based position tracking systems, there has been no clinical study reported that has determined the relationship between the 3-dimensional position of an ACL graft and clinical outcome. Currently, there are limited data available from prospective studies that identify the optimal intra-articular position of an ACL graft on the femur and tibia. There is, however, considerable lower-level evidence that derives from retrospective studies. Our assessment of the literature is that the center of the femoral attachment of an ACL graft should be located along a line parallel to the Blumensaat line just posterior to the center of the normal ACL s insertion to bone and at either the 2 o clock position (left knee) or the

3 Vol. 33, No. 11, 2005 Treatment of ACL Injuries, Part o clock position (right knee) when observed through the femoral notch. The tibial tunnel should be placed to avoid impingement of the graft against the roof of the femoral notch as the knee is brought into extension. Graft Tension at the Time of Fixation Most surgeons would agree that the initial tension applied to an ACL graft at the time of fixation has a direct effect on outcome; an undertensioned graft may result in abnormal knee laxity and an unstable knee, and an overtensioned graft may lead to graft failure, fixation failure, or restricted range of knee motion. Our review revealed 4 prospective RCTs that evaluated the effect of this critical surgical variable on clinical and functional outcomes. In an investigation by Yasuda et al, 114 subjects were randomized into 3 groups with initial graft tensions of 20, 40, and 80 N applied to a 4-strand hamstring graft connected in series with polyester tape and fixed extra-articularly with double staples. Follow-up measurements were made at a mean interval of 2.5 years (range, years) and included 94% of the subjects. The 6% of patients who were lost to follow-up were evenly divided between the 20-N and 40-N tension groups; all of the subjects in the 80-N initial tension group returned for follow-up. A significant correlation was found between the initial tension applied to the graft at the time of fixation and A-P knee laxity measurements after healing was complete. Subjects in the hightension group had anterior laxity values closer to normal compared with similar values in the low-tension group. There were, however, no differences between the initial tension groups with regard to knee motion and clinical outcome (Noyes scale 85 ). The same surgeon performed all reconstruction procedures, yet the method of randomization was not described, A-P knee laxity was not measured immediately after graft fixation to establish baseline laxity values for each treatment group, and there was no description of whether the examiner responsible for making the follow-up measurements was blinded to the treatment groups. 114 A prospective RCT was performed by van Kampen et al 107 to determine the effect of tensioning BPTB grafts at 20 and 40 N with the knee in 20 of flexion. The details of how the randomization was performed were not presented. Surgery was performed by 2 surgeons using the same single-incision procedure, and all subjects followed the same rehabilitation program, which included immediate full range of motion, weightbearing as tolerated, and return to sport 9 months after surgery. Follow-up measurements were made at 1 year and included all study participants; there was, however, no description of whether the patients and the researcher making the follow-up measurements were blinded to the treatment groups. Immediately after surgery (baseline) and at the 1-year follow-up interval, there was no difference in A-P laxity between the 2 treatment groups. It may be that the difference in the 2 tension levels was not of sufficient magnitude to create differences in knee laxity at baseline or that a large proportion of the tension applied to the bone block was lost at the bone block tunnel interface. From this perspective, the observation of similar knee laxity between the 2 initial graft tension groups at the 1-year follow-up may be attributed, at least in part, to the fact that the initial tension groups had similar knee laxity values at baseline. 107 Yoshiya et al 115 performed a similar prospective RCT comparing 2 groups in which initial tensions of 25 and 50 N were applied to BPTB grafts with the knee in full extension. Follow-ups were performed immediately after surgery (KT-1000 arthrometer measurement) and at 3, 6, 12, and 24 months. Among the 50 subjects enrolled in the study, 88% of those in the 25-N initial tension group and 84% of those in the 50-N initial tension group returned for all follow-up visits. Immediately after surgery and at the 2-year follow-up, there was no difference in A-P knee laxity between the 2 groups. Similarly, no differences were found between the treatment groups in terms of knee motion, isokinetic thigh muscle strength, and International Knee Documentation Committee (IKDC) rating. Two surgeons performed the procedures; however, the method used to perform the randomization was not presented, and there was no description of whether the patients and examiners were blinded to the treatment groups. As with the earlier study by van Kampen et al, 107 the observation of similar knee laxity values between the 2 initial tension groups after healing may be explained by the fact that laxity values for the 2 groups were the same at baseline. 115 Nicholas et al 82 performed a prospective, randomized, double-blind clinical trail that compared 2 groups in which initial tension loads of 45 and 90 N were applied by the same surgeon to central third BPTB grafts with the knee in full extension. Knee motion and A-P knee laxity were measured before surgery and at 1 week and 20 months after surgery. A total of 49 subjects enrolled in the study; 100% of those in the 45-N initial tension group and 82% of those in the 90-N initial tension group returned for all follow-up visits. Subjects receiving the 45-N tension load had increased anterior knee laxity, whereas patients receiving the 90-N tension load had laxity values similar to normal. At follow-up, 23% of the subjects in the 45-N initial tension group had side-to-side differences in knee laxity greater than 5 mm, whereas none of the subjects in the 90-N initial tension group showed such abnormal changes. Subjects in both groups had similar range of motion. Our review revealed that 1 RCT of ACL reconstruction with a BPTB graft compared the effect of preloading (application of a 39-N tensile load for 10 minutes before graft implantation) to no preloading before graft implantation. 32 Two years after surgery, there were no differences between the treatment groups with regard to activity level, clinical outcome (IKDC grade), and A-P knee laxity. Graft tensioning at the time of fixation involves consideration of the knee s position during the tensioning procedure (eg, the flexion angle and internal-external rotational position of the tibia relative to the femur) and, of course, the magnitude of tension applied to the graft at the time of its fixation to bone. Both variables interact and have a direct effect on knee biomechanics. It was difficult to compare the RCTs that were reviewed and to develop a con-

4 1754 Beynnon et al The American Journal of Sports Medicine sensus because different tensioning procedures and graft materials were used. If a BPTB graft is used and the tensioning procedure is performed with the knee in extension, application of high tension (90 N) appears to produce more normal A-P knee laxity values compared to application of low tension (45 N). Similarly, if a 4-strand hamstring graft is used, application of high tension (80 N) appears to produce A-P knee laxity values similar to normal, whereas low tension (40 N and less) results in increased anterior knee laxity. The effect that graft tensioning at the time of fixation has on the contact stress distribution of healing articular cartilage about the tibiofemoral joint is currently unknown and requires study. Graft Fixation Substitutes for the ACL can be prepared as either bonetendon-bone grafts or tendon grafts. Depending on the graft material that is selected for ACL reconstruction, the bony or soft tissue portions of these constructs can be fixed either within bone tunnels or externally to cortical bone. From a biomechanical perspective, fixation represents the weak link during the early stages of healing. The longterm goal is to obtain biological incorporation of the graft at the anatomical attachment site of the ACL and to restore the transition from soft tissue to fibrocartilage, to calcified fibrocartilage, and to bone. This review did not focus on the techniques and associated biomechanical characteristics of the wide array of fixation devices used in cruciate ligament surgery; this topic has been covered in outstanding review articles by Brand et al 22 and Wilson et al. 111 Instead, we focused on the 3 prospective RCTs of ACL graft fixation that have been published. Aglietti et al, 3 performing an RCT of ACL reconstruction with a central third BPTB graft, compared 2 different types of tibial fixation. Graft fixations in the tibial tunnel were performed on 2 groups of subjects, with an interference screw placed either at the level of the tibial plateau (aperture fixation) or distal to the plateau. The same fixation device was used in the femoral tunnels for both groups. The ACL reconstruction was performed by the same surgeon, randomization was performed using an alternating scheme, all subjects underwent the same rehabilitation program, and follow-up was performed by an independent examiner at a mean interval of 18 months. There were no differences between the treatments in range of motion, A-P laxity, symptoms, and subjective evaluation of outcome. Tibial tunnel enlargement was less frequent in the group that underwent graft fixation at the level of the tibial plateau (23% vs 43%); however, tibial tuberosity pain, attributed to harvesting a longer tibial bone block, was more frequent in this group. Presenting an RCT of ACL reconstruction with a central third BPTB graft, Fink and colleagues 39 compared 2 different types of femoral fixation. Subjects were randomized to undergo graft fixation in the femoral tunnel with either a titanium interference screw or a polyglyconate (a copolymer of polyglycolic acid and trimethylene carbonate) bioabsorbable interference screw. The same metal interference fit fixation was used in the tibial tunnels of both groups. Two surgeons performed the single-incision procedures, all subjects observed the same rehabilitation protocol, and follow-up evaluations were made over a 2-year period. Graft fixation with the bioabsorbable screw produced the same clinical outcome and A-P knee laxity values compared to graft fixation with the metal screw. Complete degradation of the bioabsorbable screw was apparent at 1 year, and replacement of the screw with bone occurred by 3 years. A similar investigation by the same group revealed that fixation of BPTB grafts with a polyglyconate interference screw was safe and effective compared to fixation with a titanium interference screw. 15 Our review of the literature on ACL graft fixation revealed that the fixation of BPTB grafts with interference screws is adequate for the loads produced by current rehabilitation programs. In contrast, the frequent publication of new techniques to fix free-tendon grafts, such as the 4- strand hamstring graft, suggests that an optimal technique of fixation has yet to be identified, particularly when rehabilitation includes immediate weightbearing, early use of the quadriceps muscles with the knee near extension, and early return to sport. BONE TUNNEL WIDENING Jansson et al 57 performed an RCT that studied ACL reconstruction using a 4-strand hamstring graft fixed proximally with an EndoButton and distally with a screw and a spiked washer, compared to reconstruction using a central third BPTB graft fixed with interference screws in the tibia and femur. Subjects were randomized by birth year, given the same rehabilitation protocol, and followed up over 2 years. No details were presented with regard to the number of surgeons who performed the procedures or whether the follow-up measurements were made by an independent examiner. No differences were observed between the groups in A-P knee laxity values, clinical findings, and knee scores. At the 2-year follow-up, however, the femoral and tibial tunnel diameters detected on anteroposterior view radiographs for subjects who underwent reconstruction with the 4-strand hamstring graft had increased by means of 33% and 23%, respectively. Although the increases in tunnel diameters were considerable, the 2 graft materials and corresponding fixation methods were reported to produce similar outcomes. 57 Webster et al 108 carried out an RCT, over a 2-year interval, that focused on whether tunnel enlargement in ACL reconstruction differed when performed with a central third BPTB or 4-strand hamstring graft. Subjects were randomized via a computer-based random-number generator to undergo ACL reconstruction with either a central third BPTB graft (fixed proximally to the femur with an EndoButton and in the tibial tunnels with a metal interference screw) or a 4-strand hamstring graft (fixed proximally to the femur with an EndoButton and to the tibia with suture tied to a fixation post). All subjects had the same single-incision procedure performed by the same surgeon, they all observed the same postoperative rehabilitation program, and 94% of the subjects were followed up at 4 months, 1 year, and 2 years. The clinical outcome was

5 Vol. 33, No. 11, 2005 Treatment of ACL Injuries, Part similar between the treatments; however, bone tunnel enlargement was more common and greater with the 4- strand hamstring graft. Eleven percent of the subjects who underwent ACL reconstruction with a BPTB graft had tunnel widening greater than 25%, compared to 94% of subjects who received a hamstring graft. 108 Although it is clear that bone tunnel enlargement occurs more frequently and is greater after ACL reconstruction with hamstring grafts compared to BPTB grafts, the cause and clinical relevance of tunnel widening remain unclear. One explanation for the increased tunnel widening associated with hamstring grafts secured with EndoButton fixation has been offered by Jorgensen and Thomsen, 61 who observed movement of the graft in the proximal two thirds of the tibial tunnel with cinematic MRI. Alternatively, L Insalata et al 71 reported that the tunnel expansion associated with hamstring grafts may be produced by the greater distance between fixation points, in comparison to BPTB grafts, and the corresponding larger force-moment produced during graft cycling. To date, we are unaware of any study confirming that tunnel widening has an adverse effect on the outcome of ACL reconstruction. Perhaps such an effect will be found as the number of cases identified with this condition and the length of follow-up periods increase. Significantly enlarged bone tunnels, however, make revision ACL reconstruction more difficult. GRAFT HEALING Although it has been reported that BPTB autografts used to reconstruct the ACL in the rabbit model undergo biological remodeling and incorporation after implantation (a process termed ligamentization 6 ), the fully incorporated graft never replicates the normal ACL, and it appears to function as a check rein of organized scar tissue. 28 Oaks and associates 87 have performed quantitative ultrastructural morphometric analysis of collagen fibril populations in the ACL and patellar tendon grafts using the goat model. The graft remodeling process was found to change the ultrastructural profile of the original patellar tendon at the time of harvest to one containing a larger number of small-diameter fibrils (<100 nm). A rapid decrease in the number of large-diameter collagen fibers (>100 nm) was found after 12 weeks of healing. Remodeling was found to begin from the outside of the graft and then move toward the graft center as the remodeling progressed over time. Oaks et al 87 found this remodeling behavior to be consistent with revascularization of the graft from synovium, demonstrating the importance of not only investigating the surface and central portions of the graft but also studying different regions along the length of the graft. Remodeling was found to continue for as long as 52 weeks after reconstruction. Arnoczky et al 9 evaluated the temporal revascularization behavior of the patellar tendon autograft using a canine model. They demonstrated that revascularization of the patellar tendon graft came from the bone tunnels and progressed from the proximal and distal regions to the central portion of the graft. After 5 months of healing, revascularization was complete. The choice of graft material and the method of fixation affect the healing and remodeling response at the graft bone tunnel interface, and this relationship has been studied in various animal models. Rodeo et al 94 used the canine model to study the tensile failure properties of digital extensor tendons fixed in bone tunnels. After 2, 4, and 8 weeks, graft failure occurred by pullout from the bone tunnels; after 12 and 26 weeks, the graft failed at its midsubstance. Grana et al 46 studied the healing response of a hamstring autograft used to reconstruct the ACL in rabbits. They found that hamstring grafts healed by formation of a fibrous insertion to bone, and the fixation strength of the bone-graft composite in the bone tunnel exceeded the intra-articular portion of the autograft strength early in the postoperative period. At 3 weeks, failure of the bone hamstring graft bone construct occurred at the intra-articular portion of the graft and not by pullout from the bone tunnels. 46 In a subsequent study of hamstring graft insertion-site healing in rabbits reported by the same group, the formation of the fibrous insertion was found to be complete after 26 weeks of healing. 21 Tomita and colleagues 105 compared intraosseous graft healing between a doubled flexor tendon graft and a BPTB graft used to reconstruct the ACL in canines. Tensile failure testing revealed that the weakest site of the doubled flexor tendon graft was the graft tunnel wall interface at 3 weeks and the intraosseously grafted tendon at 6 weeks. For the BPTB graft, the weakest site was the graft tunnel wall interface at 3 weeks and the proximal site in the bone plug at 6 weeks. 105 After 3 weeks, the ultimate failure strength of the doubled flexor tendon graft was 45% of the BPTB graft, and this value had increased to 85% at 6 weeks of healing. 105 It is important to point out that experimental studies using the animal knee joint as a model are limited with respect to the lack of similarity to the human knee joint and that animals have an uncontrolled postoperative rehabilitation regimen. Although animal investigations have provided insight into graft remodeling and biomechanical behavior during graft healing, direct application of these results to clinical practice must be made with caution. For example, BPTB grafts used to reconstruct the ACL may not undergo the dramatic decrease in structural properties that have been reported from animal studies. 17 This opinion is supported by a case study of a patient who underwent ACL reconstruction with a central third BPTB autograft. 17 Eight months after surgery, the linear stiffness and ultimate failure load values of the graft approached those of the contralateral, normal ACL, whereas laxity of the injured knee was greater than the normal knee. More recently, Delay et al 30 described a case study of a central third BPTB autograft after 18 months of healing. They found complete osseous union of both tibial and femoral bone blocks, although deep areas of necrosis associated with bone graft remodeling were observed. The deep and superficial regions of the proximal half of the soft tissue graft had become revascularized, whereas the deep portion of the distal half of the graft had persistent regions of necrosis that were acellular and avascular. These findings are supported by the work of Rougraff and

6 1756 Beynnon et al The American Journal of Sports Medicine Shelbourne, 96 who performed second-look arthroscopy and biopsy of patellar tendon grafts on 9 subjects after 3 to 8 weeks of healing. Although all specimens showed regions of acellularity and degeneration, the researchers observed that graft vascularity was present at 3 weeks and continued to increase over the 8-week sample interval. Petersen and Laprell 90 obtained biopsy specimens of BPTB and hamstring grafts from patients undergoing revision surgery. Both graft materials healed within the femoral and tibial tunnels, but the insertions were different. The insertion of the BPTB grafts to the bone tunnels healed by bone plug incorporation and resembled the chondral insertion of the normal ACL, whereas the hamstring grafts healed by the fibrils of the graft penetrating the bone directly and resulted in a fibrous insertion of the tendon, not the normal chondral insertion of the ACL to the tibia or femur. The temporal change in the structural and material properties of different autografts used for ACL reconstruction has been investigated using primate, canine, goat, sheep, and rabbit models. 81 Animal studies that have investigated the iliotibial tract (ITT) autograft for as long as 1 year indicate that the ultimate failure load values of this graft ranged between 23% and 40% of the control ACL, whereas the graft stiffness was 45% of the average uninjured ACL. 81 Studies in animals that have investigated the healing response of patellar tendon autografts a year or more after reconstruction have reported ultimate failure load values ranging between 30% and 45% of the control ACL, whereas the stiffness has been reported to range between 35% and 57% of the normal ACL. 81 Hunt et al 55 used the superficial digital flexor tendon as an autograft to simulate hamstring reconstruction of the ACL in sheep. After 1 year, grafts fixed anatomically with interference screws in the tibia and femur had an ultimate failure load value that was 45% of the normal ACL. It is not enough to evaluate the structural and material properties of an ACL graft; in addition to having adequate strength and stiffness, an ACL graft must also control anterior translation of the tibia relative to the femur and, to a lesser degree, internal-external and varus-valgus laxity of the knee joint. Butler 25 used the canine model to investigate the A-P displacement response of the knee joint at 4 time intervals after a combined ACL reconstruction using the fascia lata and lateral one third of the patellar tendon. At implantation, the A-P laxity of the operated knee was 154% of the control limb; after 4 weeks of healing, this ratio increased to 306%. After 12 and 26 weeks of healing, the A-P laxity had decreased to 209% and 153% of the control limb, respectively. Animal studies of ACL allografts have shown a slower rate of biological incorporation, a greater decrease in structural properties, and a prolonged inflammatory response compared to ACL autografts. 56 Human retrieval studies have shown that remodeling of ACL allografts is slow. 52,74 After 2 years of transplantation, the central portions of the allografts were found to remain acellular. Complete remodeling and cellular replacement of the entire graft were seen in grafts studied 3 years after transplantation. The healing of BPTB and hamstring grafts is different both temporally and histologically. Thus, aggressive rehabilitation within the first 6 weeks after ACL reconstruction with a hamstring graft may cause greater anterior knee laxity compared to reconstruction with a BPTB graft. Attempts to improve healing by treating ACL autografts with growth factors and gene therapy are in the development stages, and although these approaches hold great promise, 109,113 there are no proven clinical applications for these procedures at the present time. REHABILITATION AFTER ACL RECONSTRUCTION Although most clinicians would agree that the strains applied to an ACL graft by body weight, muscle activity, and joint motion affect its healing response, there is little consensus on how these factors influence the biomechanical behavior of the healing graft and, in turn, how this behavior modulates the healing response of the graft, cartilage, and knee. Our review of the literature did not identify a consensus regarding which variables should be used to characterize a rehabilitation program, nor did it reveal how this information should be used to compare different programs. Although it is clear that rehabilitation after ACL reconstruction includes characteristics such as the series of activities (or restrictions) that a subject is directed to perform, the time when the activities are recommended, the duration of the activities (eg, the number or sets and repetitions per day, week, month), the overall length of the program, and the time when a subject is advised to return to sport-specific training and subsequently to sport, it is unclear how a single term such as accelerated rehabilitation can be used to provide insight into these characteristics. As a consequence, there is little consensus in the literature about what composes an accelerated versus a more conservative rehabilitation program or an aggressive versus a nonaggressive approach to rehabilitation. Our review identified a substantial number of RCTs that have focused on rehabilitation after ACL reconstruction, but very few of these reports described the rehabilitation protocol adequately or provided details with regard to subject compliance. These concerns made it difficult to arrive at a consensus with regard to optimal rehabilitation programs after ACL reconstruction. Our review of RCTs of rehabilitation programs after ACL reconstruction was categorized according to the use of the following approaches: cold therapy, immediate versus delayed motion, immediate versus delayed weightbearing, closed versus open kinetic chain exercises, bracing, homeversus clinic-based rehabilitation, neuromuscular electrical stimulation versus voluntary muscle contraction, specific exercise programs, and intensity and duration of rehabilitation. Use of Cold Therapy Immediately After ACL Reconstruction We identified a prospective RCT by Konrath et al 69 that focused on the effectiveness of postoperative cold therapy in patients undergoing ACL reconstruction. After ACL reconstruction with a BPTB graft, patients were random-

7 Vol. 33, No. 11, 2005 Treatment of ACL Injuries, Part ized to receive 1 of 4 treatments: a cooling pad filled with water ranging between 40 F and 50 F, a cooling pad filled with water ranging between 70 F and 80 F, a bag of crushed ice, or no cold therapy. Both the cooling pad and crushed ice treatments were found to produce a significant decrease in knee temperature; however, there were no differences among the 4 treatments regarding duration of hospital stay, range of knee motion at the time of discharge, or the use of intramuscular and oral pain medication. Immediate Versus Delayed Motion Our review identified 5 RCTs comparing immediate to delayed knee motion during the initial stages of rehabilitation, and there appears to be reasonable consensus that immediate motion is beneficial for the healing ACL graft and soft tissue structures that span the knee. 47,50,86,92,95 Haggmark and Eriksson were among the first to perform a prospective RCT of rehabilitation after ACL reconstruction with a patellar tendon graft. 35,47 Patients were treated with a dorsal plaster splint during the first week after surgery and were then randomly assigned to continue rehabilitation during the following 4 weeks while wearing either a hinged cast that allowed knee motion or an ordinary cylinder cast that prevented knee motion. All of the patients were followed up during a 1-year interval; those treated with standard cast immobilization had significant atrophy of the slow-twitch muscle fibers of the vastus lateralis, whereas those treated with the hinged cast and early motion demonstrated no changes in the cross-sectional area of the slow- or fast-twitch fibers. Haggmark and Eriksson 47(p55) noted that there appeared to be no difference in the end result of the surgical procedure and that treatment with the hinged cast facilitated an early return to sports. A prospective RCT that compared immediate to delayed range of motion after ACL reconstruction was carried out by Noyes et al. 86 Subjects in the immediate motion program began continuous passive motion of the knee on the second postoperative day, whereas those in the delayed motion group had their knees placed in a brace at 10 of flexion and began continuous passive motion on the seventh postoperative day. Subjects in both rehabilitation programs reported similar rates of joint effusion, hemarthrosis, soft tissue swelling, flexion and extension limits of the knee, use of pain medications, and time of stay in the hospital. Continuous passive knee motion immediately after ACL reconstruction did not lead to an increase in anterior knee laxity during healing. Rosen et al 95 carried out a prospective RCT of rehabilitation after arthroscopically assisted ACL reconstruction with a central third BPTB autograft performed by the same surgeon. After surgery, subjects were randomized via a lottery system to 1 of 3 programs: early active motion, continuous passive motion, or a combination of both. This work extended the research of Noyes et al 86 by showing that continuous passive motion during the first month after ACL reconstruction, compared with early active motion, produced similar range of joint motion and KT arthrometer measurements of A-P knee laxity. Richmond et al 92 reported the results of a prospective RCT that compared the effects of continuous passive knee motion for 4 to 14 days after arthroscopically assisted ACL reconstruction with a BPTB autograft. They found similar values for knee range of motion and lower limb girth between treatment groups. More recently, Henriksson et al 50 described a prospective RCT of rehabilitation after ACL reconstruction with a BPTB graft performed by 1 of 4 surgeons using the same technique. After surgery, subjects were randomly assigned to rehabilitation protocols consisting of cast immobilization or early range of motion training with a brace. Subjects in both groups underwent similar supervised rehabilitation, and during the first 5 weeks, all rehabilitation exercises, with the exception of range of motion exercises, were the same for both treatments. Follow-up measurements made after 2 years included 88% and 92% of subjects in the brace and plaster cast treatment groups, respectively. The researchers found that rehabilitation with the use of a brace and early range of motion training after ACL reconstruction produced equivalent knee laxity, knee motion, subjective knee function, and activity level in comparison to rehabilitation with plaster cast immobilization for 5 weeks. There were, however, differences in terms of strength. At 2-year follow-up, subjects in the brace group had a larger strength deficit of the knee flexors (5.9% loss compared to the contralateral, normal side) in comparison to subjects in the plaster cast group (0.9% loss). As well, there was a strong trend for subjects in the brace group to have a strength deficit of the knee extensors (11.1% decrease compared to the contralateral side) in comparison to patients in the plaster cast group (3.8% decrease). Of the 5 RCTs reviewed above, only Rosen et al 95 adequately described their method of randomization, and only Haggmark and Eriksson 47 and Henriksson et al 50 had minimal loss of patients at follow-up; no author stated whether the investigators were blinded at follow-up. After ACL reconstruction, it is clear that extended immobilization of the knee, or limited motion without muscle activity, is detrimental (inferior structural and material properties) to the structures that surround the knee (ligaments, cartilage, bone, and musculature). 4,10,62-65,70,84,112 There is little doubt that early joint motion after ACL reconstruction is beneficial; it leads to a reduction in pain, lessens adverse changes in articular cartilage, and helps prevent the formation of scar and capsular contractions that have the potential to limit joint motion. 24,65 Immediate Versus Delayed Weightbearing Two prospective RCTs have compared immediate versus delayed weightbearing rehabilitation programs after ACL reconstruction, and both have reported that immediate weightbearing programs produce similar clinical, patient, and functional outcomes to delayed weightbearing programs. 60,106

8 1758 Beynnon et al The American Journal of Sports Medicine Jorgensen et al 60 performed a prospective RCT to evaluate the effect of weightbearing on the results of ACL reconstruction with the iliotibial band graft. After surgery, subjects were randomized to undergo rehabilitation with either immediate weightbearing or nonweightbearing for 5 weeks followed by a gradual return to full weightbearing during the first 9 weeks of healing. Evaluation 2 years after surgery revealed no differences between the groups with regard to A-P knee laxity and patient activity level (evaluated with the Tegner and International Knee Documentation Committee [IKDC] scores). In a subsequent prospective RCT of ACL reconstruction with a central third BPTB autograft, Tyler et al 106 compared rehabilitation with immediate weightbearing to delayed weightbearing for 2 weeks. Only 2 subjects in each treatment group were lost to follow-up. At a mean followup of 7.3 months, there were no differences between the treatments with regard to knee range of motion, vastus medialis oblique function, and A-P knee laxity (clinical examination and KT-1000 arthrometer measurement). However, patients treated with immediate weightbearing had a decreased incidence of anterior knee pain. Authors of these RCTs did not describe their method of randomization, and they did not mention if the subjects or investigators responsible for the follow-up measurements were blinded to the treatments that were studied. The findings from these investigations indicate that immediate weightbearing after ACL reconstruction does not produce excessive loads that permanently deform the graft or its fixation and suggest that immediate weightbearing may be beneficial because it lowers the incidence of anterior knee pain. After ACL injury and reconstruction, the effect of weightbearing on the healing response of injured articular cartilage or meniscus repair is currently unknown. Closed Versus Open Kinetic Chain Rehabilitation Our review revealed 3 randomized trials comparing the use of closed versus open kinetic chain exercises during ACL rehabilitation. Bynum et al 26 performed a prospective RCT comparing open versus closed kinetic chain rehabilitation after ACL reconstruction with a central third BPTB autograft. Immediately after surgery, patients knees were placed in a rehabilitation brace that was adjusted to allow 0 through 90 of motion, and continuous passive motion from 0 to 60 of flexion was started. Rehabilitation was begun on the first postoperative day and for all patients included passive and active motions of the knee without external resistance. Partial weightbearing with the use of crutches was permitted, and subjects progressed to full weightbearing as tolerated. Patients were then randomized via a computer-generated list of random numbers to either open or closed kinetic chain rehabilitation groups. Subjective and objective follow-up measurements were taken on 66% of patients 1 year after surgery; the examiner was blinded to the patients rehabilitation program. The subjects in the closed kinetic chain group had KT-1000 arthrometer measurements that were closer to normal, in addition to less anterior knee pain, earlier return to normal daily activities, and greater satisfaction compared to the subjects in the open kinetic chain group. The authors attributed the decreased anterior knee pain in patients from the closed kinetic chain group to reduced patellofemoral reaction forces associated with exercises performed with the knee near extension, in contrast to the open kinetic chain treatment exercises, which were performed with the knee in a more flexed position. 26 Mikkelsen et al 77 reported the results of an RCT that compared closed kinetic chain to combined closed and open kinetic chain rehabilitation programs initiated 6 weeks after single-incision BPTB reconstruction of the ACL performed by 1 of 3 surgeons. The randomization procedure appeared to be designed to match patients with regard to age, gender, and type and level of physical activity, although the details of how this design was accomplished were not presented, and it is unclear whether the followup measurements were made with the investigator blinded to the treatment groups. Assessment at 6 months after surgery revealed that the addition of open kinetic chain exercises produced a significant improvement in quadriceps strength (evidenced by moderate improvements in extension torque), an earlier return to sport at the preinjury level, and no effect on KT-1000 arthrometer measurements of A-P knee laxity. Hooper et al 51 reported the results of a prospective RCT comparing closed to open kinetic chain rehabilitation exercises during the early phase of healing. Reconstruction was performed by 3 surgeons: 1 surgeon reconstructed the ACL with a ligament augmentation device, and the other 2 surgeons used a central third BPTB graft. Patients were assigned to the treatment groups using a block randomization scheme; there were no details given with regard to whether the follow-up measurements were made with blinding of the examiner to the treatment groups. Two weeks after ACL surgery, the patients underwent a baseline gait analysis and were then randomly assigned to either closed or open kinetic chain rehabilitation exercises administered 3 times per week during a 4-week interval. At the 6-week follow-up, the patients underwent a second gait analysis. At this early stage of healing, no differences were found between the closed and open kinetic chain programs in the gait variables associated with level walking, ascending stairs, and descending stairs; however, subjects in both groups had functional deficits in the involved side compared to their contralateral, normal side. Subsequent investigation of the same patients revealed no differences in anterior knee pain or knee laxity between treatment groups. 79,80 In the 3 RCTs reviewed above, different open and closed kinetic chain rehabilitation programs were compared over different times, and it is therefore impossible to come to a consensus regarding the effectiveness of one approach compared to another. The report by Bynum and colleagues 26 had the longest follow-up interval. This study indicated that rehabilitation with closed kinetic chain exercises is more effective in terms of patient satisfaction,

9 Vol. 33, No. 11, 2005 Treatment of ACL Injuries, Part reduced anterior knee pain, and earlier return to daily activities compared to programs that include open kinetic chain exercises. Rehabilitation Braces Three prospective RCTs have compared rehabilitation with and without the use of a rehabilitation brace. 23,48,78 A prospective RCT of rehabilitation after ACL reconstruction with a central third BPTB graft was performed by Harilainen et al. 48 Subjects were randomized by their birth year to either the braced group (rehabilitation with a gradual increase in weightbearing and the use of a brace for 12 weeks postoperatively) or the unbraced group (rehabilitation with crutch use for 2 weeks postoperatively followed by weightbearing as tolerated but without use of a brace). The number of surgeons involved with the investigation and the specific details of the rehabilitation program were not presented. The 1- and 2-year follow-up intervals included 100% and 93% of subjects enrolled, respectively, and these follow-ups revealed no differences between the treatments in activity level, joint laxity, and isokinetic thigh muscle strength. Moller et al 78 performed a prospective RCT that focused on the use of a rehabilitation brace during the first 6 weeks after ACL reconstruction with a BPTB graft. The rehabilitation program included early weightbearing and lasted 6 months. Four surgeons were involved in the study (2 performed a single-incision procedure, 2 performed a 2- incision procedure). Subjects were randomized to undergo rehabilitation without a brace or with a brace during the initial 6 weeks of healing (the first 2 weeks during the day and night, the subsequent 4 weeks during the day). Ninety-eight percent of the subjects were evaluated at 6- month follow-up, and those who did not receive a rehabilitation brace had a better Tegner activity score. However, at the 2-year follow-up, which included 90% of subjects enrolled, there were no differences between the treatments in subjective outcome (Lysholm score and visual analog scale measurements of pain, discomfort, and instability), range of knee motion, functional performance (1- legged hop test), isokinetic strength, and A-P knee laxity. A prospective RCT focusing on the use of a rehabilitation brace was also performed by Brandsson et al. 23 After single-incision ACL reconstruction with a central third BPTB graft, patients were randomized to undergo 6 months of rehabilitation without a brace or the same 6- month program with a rehabilitation brace during the initial 3 weeks of healing. Follow-up measurements were performed by an independent investigator through a 2-year follow-up interval; the results included 92% and 80% of subjects in the braced and unbraced groups, respectively. Rehabilitation with a brace resulted in fewer problems with swelling, a lower prevalence of hemarthrosis and wound drainage, and less pain throughout the early recovery period compared to rehabilitation without a brace. At the 2-year follow-up, no differences were found between the treatments in terms of activity level (Tegner scale), IKDC rating, function (1-legged hop test and isokinetic strength), and knee laxity (KT-1000 arthrometer measurement). In the 3 randomized trials described above, only Harilainen et al 48 described their method of randomization; only Brandsson et al 23 indicated that follow-up measurements were performed by an independent investigator, and it was unclear if this examiner was blinded to the treatment groups. All studies revealed a minimal loss of patients to follow-up. There appears to be a consensus among investigators that, during the early phase of recovery, the use of a rehabilitation brace results in fewer problems with swelling, lower prevalence of hemarthrosis and wound drainage, and less pain compared to rehabilitation without a brace; however, at longer-term follow-up, rehabilitation bracing does not appear to have an effect on clinical outcome, range of knee motion, subjective outcome, A-P knee laxity, activity level, or function (thigh muscle strength and 1- legged hop test). It should be mentioned that one of the primary reasons for using rehabilitation braces is to help prevent flexion contractures by maintaining full knee extension during the early phase of healing. Functional Braces The effect of a functional brace on the knee and ACL graft is determined by the brace attachment technique, brace design parameters, the brace-limb attachment interface, and the loading environment to which the braced knee is exposed. Our review revealed 2 RCTs that studied the effect of functional bracing on healing after ACL reconstruction with a BPTB graft. McDevitt and associates 75 presented a prospective RCT comparing rehabilitation using functional bracing for 1 year to rehabilitation without bracing after ACL reconstruction with a BPTB graft. The patients were randomized by random numbers or a coin toss. Both groups of 50 patients were treated for the first 3 weeks after surgery with a rehabilitation brace locked in extension. The brace was removed 2 to 3 times per day for range of motion activities. In the functional brace group, the knee was mobilized gradually from 3 to 6 weeks with the rehabilitation brace used intermittently. Then, the patient was fitted for a functional brace at 6 weeks and was allowed full range of motion. The brace was worn full-time for the following 6 months and thereafter during all rigorous activities until 1 year after surgery. In the nonbraced group, bracing was discontinued after 3 weeks. Other details of the rehabilitation protocol were not provided. Ninety-five percent of the patients were followed up for a minimum of 2 years (mean, 29 months). At the time of final follow-up, no differences were revealed between the groups in terms of A- P knee laxity, 1-legged hop distance, IKDC and Lysholm scores, range of motion, and isokinetic strength. Two braced subjects and 3 nonbraced subjects sustained reinjuries to their ACL graft. The authors concluded that there were no significant differences between the braced and nonbraced treatment groups. In a prospective RCT, Risberg et al 93 compared rehabilitation with functional bracing to rehabilitation without bracing after ACL reconstruction with BPTB grafts in 60 patients. The number of surgeons was not provided; the

10 1760 Beynnon et al The American Journal of Sports Medicine patients were randomized into braced and nonbraced groups by an unspecified method. The braced group was protected by a rehabilitation brace for 2 weeks, and a functional brace was used nearly full-time for the following 10 weeks. Thereafter, the functional brace was used as needed for sports. The nonbraced group had no brace at any time postoperatively. Otherwise, both groups followed the same postoperative rehabilitation protocol, which was described in detail. Ninety-three percent of the patients were followed up for 2 years. The authors found no evidence that bracing had an effect on knee joint laxity, range of motion, strength, functional knee tests, patient satisfaction, or pain at final follow-up. No evidence that bracing reduced the risk of new injury was observed. The 2 studies reviewed in this section do not identify a compelling reason to use functional braces after ACL reconstruction. Home- Versus Clinic-Based Rehabilitation Three RCTs have compared home-based rehabilitation (limited supervision by a physical therapist during healing) to clinic-based rehabilitation (supervision by a physical therapist throughout the entire rehabilitation program), and there appears to be reasonable consensus that home-based programs produce similar outcomes compared to clinic-based programs. 14,40,97 Schenck et al 97 studied rehabilitation after 2-incision ACL reconstruction with a central third BPTB graft performed by the same surgeon. Subjects were randomized after surgery via a lottery drawing to rehabilitation with either a clinic-based program (mean of 14.2 visits to physical therapy) or a home-based program that was monitored by a physical therapist (mean of 2.9 visits to physical therapy). All patients were examined at a minimum of 1 year after surgery. There were no differences in functional or subjective outcomes between the clinic- and home-based rehabilitation programs. Fischer and colleagues 40 performed an RCT of rehabilitation after ACL reconstruction with a BPTB graft performed with a 2-incision technique. Patients were randomized to undergo rehabilitation with either a homebased program that included a mean of 5 physical therapy visits (range, 3-7 visits) or a clinic-based program that included 20 physical therapy visits (range, visits). Compliance with the rehabilitation programs was documented with a training log. Details were not presented regarding the specific activities and restrictions associated with both programs; instead a goal-based approach was used, with the following temporal sequence of activities: restoration of range of motion, beginning strengthening, advanced strengthening, and improvement of agility and speed. All of the subjects in the home-based program and 96% of those in the clinic-based program (1 patient was excluded because of unanticipated foot surgery) were followed up for 6 months. There were no differences between the treatments with regard to clinical examinations (range of motion, thigh atrophy, knee laxity, and pivot-shift examinations), 1-legged hop test, and the health status questionnaire. More recently, Beard and Dodd 14 reported the results of rehabilitation after ACL reconstruction with a central third BPTB graft performed by the same surgeon. During the first month after surgery, all patients participated in the same regimen. They were subsequently randomized to either home-based rehabilitation (attending physical therapy only for education, assessment, and monitoring of the treatment plan) or the same home-based program with supervision (attending physical therapy twice weekly). Randomization was performed with a computer-based random-number generator, the study subjects and investigator responsible for making the follow-up measurements were blinded to the treatment groups, and follow-up at 12 and 24 weeks was performed on 86% and 81% of subjects in the home and supervised programs, correspondingly. No differences were found between the treatments in terms of activity level, IKDC rating, function, muscle strength, and knee laxity. These findings led the authors to conclude that supervised exercises, in addition to a home program, has minimal extra benefit for patients that have undergone ACL reconstruction. 14(p134) In the 3 randomized trials reviewed above, both Schenck et al 97 and Beard and Dodd 14 described their methods of randomization; only Beard and Dodd 14 stated that the study subjects and investigators were blinded to the treatments that were studied. However, all 3 studies revealed a minimal loss of subjects at follow-up. It is important to point out that the studies we reviewed compared rehabilitation programs with different amounts of supervision and that none of the programs was completely unsupervised. These reports suggest that rehabilitation after ACL reconstruction need not be monitored by a physical therapist in a continuous manner, but attending physical therapy for the purpose of education, assessment, and monitoring of the treatment plan remains a critical aspect of a safe and effective rehabilitation program. Neuromuscular Electrical Stimulation Versus Voluntary Muscle Contraction Snyder-Mackler and colleagues 104 performed an RCT of rehabilitation after ACL reconstruction with either a semitendinosus tendon combined with a ligament augmentation device or a central third BPTB preparation. After surgery, patients were randomized to undergo rehabilitation with neuromuscular electrical stimulation and volitional exercises or with volitional exercises alone. All subjects documented compliance with the use of a training log; follow-up measurements of gait and thigh muscle strength were made at 8 weeks. Patients who underwent rehabilitation incorporating combined volitional exercises and neuromuscular electrical stimulation had more normal gait parameters and stronger quadriceps muscles compared to patients who underwent volitional exercises alone. Subsequent to this effort, Snyder-Mackler et al 103 reported the results of a multicenter RCT of rehabilitation after ACL reconstruction with a variety of graft materials and surgical techniques. All patients participated in the same rehabilitation program 3 times per week for the first 6 weeks and were then randomized to have additional

11 Vol. 33, No. 11, 2005 Treatment of ACL Injuries, Part treatments of either high-intensity neuromuscular electrical stimulation, high-level volitional exercises, low-intensity neuromuscular electrical stimulation, or combined highand low-intensity neuromuscular electrical stimulation. Rehabilitation was monitored with training logs, and the investigators making the follow-up measurements were blinded to the treatment groups. The 4-week follow-up revealed that high-intensity neuromuscular electrical stimulation combined with volitional exercises was better at restoring extensor strength compared to volitional exercises alone. The methods used to perform the randomization were not presented, and the proportion of subjects who were followed up was not described in either of the above-mentioned studies. In the more recent study, 103 the investigators making the follow-up measurements were blinded to the treatment groups that the subjects were assigned to, whereas there was no mention of whether this procedure was followed in the earlier study. 104 There appears to be consensus that rehabilitation with volitional exercises combined with neuromuscular electrical stimulation results in more normal gait parameters and better restoration of extensor strength compared to rehabilitation with volitional exercises alone. Specific Exercise Programs There have been 4 prospective RCTs focusing on the effect of specific exercises on thigh muscle strength after ACL reconstruction. 20,49,72,76 The effect of adding isokinetic strength training to rehabilitation programs after augmented repair or reconstruction of the ACL was studied by Hehl et al. 49 Significant improvements in muscle strength were found with the addition of isokinetic strength training between the seventh and ninth weeks after ACL reconstruction; at the 6- month follow-up, there was no difference in knee joint laxity. Blanpied and associates 20 carried out an RCT of rehabilitation after ACL reconstruction with a central third BPTB graft performed by the same surgeon. After surgery, subjects were randomized to a home-based rehabilitation program that included lateral slide exercises or the same home-based program without lateral slide exercises. All of the study subjects were followed up at 8- and 14-week intervals; results revealed that the group rehabilitated with the lateral slide exercises showed significant improvement in knee extension strength compared to patients rehabilitated without lateral slide exercises. Meyers and colleagues 76 performed an RCT of rehabilitation after ACL reconstruction with a central third BPTB graft performed by the same surgeon. All patients followed the same aggressive rehabilitation program for 4 weeks after surgery, at which time patients were randomized to undergo either 8 weeks of rehabilitation with stair climbing or 8 weeks of rehabilitation with cycling. Twelve weeks after surgery, there were no differences between the rehabilitation programs with regard to isokinetic thigh muscle strength. An RCT of rehabilitation after ACL reconstruction with a semitendinosus tendon was presented by Liu-Ambrose et al. 72 After surgery, patients underwent 12 weeks of rehabilitation with either isotonic strength training or proprioceptive training. Compliance with these programs was monitored through direct supervision and the use of training logs, and follow-up measurements were made over the same time interval. Follow-up included all 5 study participants in each group, a sample size that was chosen a priori based on a 10% difference in time to create peak torque between the treatments. At the end of the 12-week training period, subjects in both programs experienced similar improvements in function and subjective scores. Patients who underwent proprioceptive training experienced a greater increase in isokinetic torque compared to those who underwent strength training. In the 4 randomized studies reviewed above, no authors adequately described their method of randomization, no authors stated whether the investigators were blinded at follow-up, and only Blanpied et al 20 and Liu-Ambrose et al 72 revealed that they had minimal loss of study patients at follow-up. Intensity and Duration of Rehabilitation Shelbourne and colleagues were one of the first groups to report that rehabilitation with immediate walking and full weightbearing, combined with early return to sport, was effective and safe. 99,100,101 Shelbourne et al 100 studied the effect of rehabilitation on subjects undergoing ACL reconstruction with a BPTB graft. Follow-up at a mean interval of 4 years (range, 2-9 years) included 81% of patients treated. Patients were able to return to sport-specific activities at a mean of 6.2 weeks (range, 1-13 weeks) and to athletic competition at full capacity at a mean of 6.2 months (range, 2-18 months). This achievement was accomplished while only 2.6% of the subjects retore their ACL graft at a mean interval of 2.5 years postoperatively (range, 4-78 months). The duration and intensity of rehabilitation after ACL reconstruction have been evaluated in 3 RCTs. 18,34,42 Ekstrand 34 performed a prospective RCT of soccer athletes after ACL reconstruction and compared standard rehabilitation (a 6-month program) to extended rehabilitation (an 8-month program). At baseline and 1-year followup, there were no differences between the groups. There was, however, a trend for subjects in the extended treatment group to have more normal knee laxity compared to those in the standard group. 34 Using the criteria of 90% quadriceps strength in comparison to the contralateral side and full range of joint motion, the subjects who participated in the standard program were allowed to return to sports at 6 months, whereas those in the extended program returned at 9 months. Frosch et al 42 carried out an RCT comparing prolonged rehabilitation (2.5-hour sessions performed 3-5 times/wk) to a standard rehabilitation program (30-minute sessions performed 2-3 times/wk). Baseline data were not reported, and at the 1-year follow-up, subjects receiving the prolonged program had better joint position sense and Lysholm scores and returned to work earlier than those receiving the standard program.

12 1762 Beynnon et al The American Journal of Sports Medicine Recently, our group reported the results of a prospective RCT comparing accelerated versus delayed rehabilitation. 18 Patients who had ACL reconstruction with a BPTB graft were randomized to either accelerated rehabilitation (a 19-week program that allowed unrestricted weightbearing after 1 week, no brace use after 2 weeks, open kinetic chain exercises involving contraction of the quadriceps muscle group with the knee near extension [0-45 ] after 4 weeks, and return to preinjury activity at 24 weeks) or nonaccelerated rehabilitation (a 32-week program that included the same exercises prescribed over a delayed time interval, including unrestricted weightbearing after 3 weeks, no brace use after 4 weeks, open kinetic chain exercises involving contraction of the quadriceps muscles [0-45 ] at 12 weeks, and return to preinjury activity at 32 weeks). Compliance with the rehabilitation programs was monitored with training logs. At the time of surgery, and then 3, 6, 12, and 24 months later, measurements of A-P knee laxity (KT-1000 arthrometer), clinical assessment (IKDC evaluation), patient satisfaction (Knee Osteoarthritis Outcome Score), function (1-legged hop test), and cartilage metabolism (synovial fluid based biomarkers of synthesis and cleavage of type II collagen, and turnover of aggrecan) were completed. At 2-year follow-up, there was no difference in the increase of anterior knee laxity between the 2 groups (a 2.2-mm vs 1.8-mm increase relative to the normal knee for the nonaccelerated and accelerated programs, respectively). The treatments were also similar in terms of clinical assessment, patient satisfaction, activity level, function, and the response of the synovial fluid biomarkers of articular cartilage metabolism. There was concern that the biomarkers from subjects in both groups remained elevated over periods considerably longer than modern rehabilitation programs and substantially greater than the interval after which most people attempt to return to preinjury activities. Soon after injury and just before surgery, the levels of cleavage and synthesis of type II collagen and turnover of aggrecan were elevated compared to normal values. After 12 months of healing, cleavage of type II collagen returned to normal values, whereas synthesis of collagen and turnover of aggrecan remained elevated. Synthesis of type II collagen remained elevated at 24-month follow-up, whereas the turnover of aggrecan approached normal limits. In the 3 RCTs reviewed above, only Beynnon et al 18 adequately described their method of randomization, both Beynnon et al 18 and Frosch et al 42 stated that the investigators were blinded at follow-up, and all authors revealed a minimal loss of patients to follow-up. Our review of the ACL rehabilitation literature revealed several concerns with the quality of the studies. Although most studies claimed to be based on prospective RCT designs, many reports did not describe how the randomization was performed, it was often unclear if the assessors and study subjects were blinded to the treatment groups, in most reports the follow-up intervals were quite short, and in some studies the proportion of subjects lost to follow-up was not presented. Most of the randomized studies that were reviewed clearly described the activities (and restrictions) a subject was advised to perform and the time that the activities were recommended. Little information, however, was presented regarding the frequency and duration of the activities and how well subjects complied with the prescribed program. Many of the articles delineated when subjects were allowed to return to sports, but few reports provided data describing whether subjects actually returned to sport and if so, at what level. Furthermore, no consensus was given on what primary outcome measure should be used to determine if a rehabilitation program is both safe and effective. A common outcome for most of the investigations we reviewed was A-P knee laxity. Although most orthopaedic surgeons would agree that an increase in anterior laxity of more than 3 mm in the index knee compared to the normal knee is a concern from a biomechanical perspective, 29 it remains unclear what magnitude of an increase in A-P laxity is a concern from a biological perspective. It may be that increases of knee laxity that are within certain limits of normal do not result in altered metabolism of the articular cartilage, damage to the meniscus, or additional intra-articular injury. However, we do not know the relationship between increased anterior knee laxity and metabolism of the menisci and articular cartilage, and therefore, any increased laxity has the potential to lead to adverse changes within the joint over time. There also appears to be a place for determining the control of rotational laxity by modern reconstruction procedures. Single-bundle procedures, especially involving femoral tunnel placement high in the notch (11 o clock to 12 o clock), may well be unable to prevent abnormal rotational kinematics of the tibia relative to the femur. Our interpretation of the ACL rehabilitation literature is that there is some information available from prospective RCTs regarding how much loading and motion a knee with a healing BPTB graft can sustain without permanently stretching the graft (as evidenced by abnormal increases of anterior knee laxity), disrupting the graft, or creating failure of graft fixation. In contrast, there is very little information available about the effect of rehabilitation on other graft materials, such as the 4-strand hamstring graft. As well, there is little information available about the effect of rehabilitation on the healing response of an ACL graft with combined injuries to the articular cartilage and meniscus. EFFECTS OF SEX, AGE, AND ACTIVITY LEVEL ON THE OUTCOME OF ACL RECONSTRUCTION There are many studies on the outcome of ACL reconstruction in the literature. Unfortunately, few of these articles have addressed the potential differences between male and female patients. There are no prospective, controlled studies directly comparing the outcomes on men and women after ACL reconstruction. Barber-Westin and colleagues 12 published one of the first studies comparing the outcome of ACL reconstruction with BPTB grafts between male and female patients. Their report showed that sex alone should not be the basis for selection regarding surgical intervention. Failure rates were low, and outcomes were similar between male and female subjects.

13 Vol. 33, No. 11, 2005 Treatment of ACL Injuries, Part Ferrari et al 38 also studied the use of autogenous BPTB grafts for ACL reconstruction in men and women. Their retrospective review showed no significant difference between the sexes with regard to clinical and functional outcomes; they reported that equal functional scores and overall high subjective satisfaction levels can be expected after ACL reconstruction in both men and women. Ott and associates 88 also looked at the results of ACL reconstruction with a BPTB graft between male and female patients and concluded that ACL reconstruction was equally successful in similar populations of men and women. Wiger et al 110 compared the results of ACL reconstruction in male and female competitive athletes. All athletes had a preinjury Tegner activity level 7 and a normal contralateral knee. No differences were seen in Lysholm score, Tegner activity level, IKDC score, A-P knee laxity (KT arthrometer measurement), anterior knee pain, and subjective evaluation between the 2 groups. The main conclusion of the study was that the overall results were comparable for male and female athletes 2 to 5 years after ACL reconstruction. In an earlier study by Aglietti et al, 1 it was reported that patellofemoral problems were more frequent after BPTB ACL reconstruction in female subjects, although gender comparisons were not a specific focus of that study. When evaluating hamstring ACL reconstructions, Aglietti et al 2 and Maeda et al 73 used quadruple hamstring tendon autografts fixed outside the bone tunnels with posts or staples and found no significant differences between male and female patients with regard to the prevalence of anterior knee pain and clinical outcome. In contrast, a study by Noojin and colleagues 83 comparing the outcome of autogenous semitendinosus and gracilis tendon grafts in men and women showed increased laxity for female subjects, as measured by KT arthrometer, Lachman, and pivot-shift tests. They reported more pain and lower rates of return to preinjury levels of activity for female patients, as judged by the Tegner activity score after ACL reconstruction. Female subjects also had a significantly higher rate of graft failure after ACL reconstruction in this study. In reviewing the available literature, it appears that ACL reconstruction with a BPTB autograft is equally successful in male and female patients. Whether there is a difference when the ACL is reconstructed with an autogenous hamstring graft has not been answered in the literature to date. Three studies 27,43,83 have reported possible increased laxity and poorer outcomes when hamstring ACL grafts are used in female subjects, but those studies were not prospective, controlled investigations, and such a study needs to be conducted. The effect of age and activity level on outcomes after ACL reconstruction is more difficult to determine, as most studies we reviewed were not designed to investigate these variables. A study by Barber et al 11 investigated outcomes of ACL reconstructions in patients both younger and older than 40 years. At a mean follow-up of 21 months, there were no differences between the 2 groups in activity level (Tegner score), A-P knee laxity (KT-1000 arthrometer measurement), clinical outcome (Lachman and pivot-shift tests), and complications. Based on the current literature, age alone should not determine whether a person is a good candidate for ACL reconstruction. No study in the literature has looked directly at the issue of activity level on ACL reconstruction outcomes. Clearly, activity level before ACL injury should be considered before advising patients to undergo ACL reconstruction, but the literature does not currently show that one group of patients will have a poorer outcome based on preoperative activity levels alone. CONCLUSION The complex attachment of the normal ACL and ACL graft requires 3 dimensions to fully describe; very little is known, however, about the relationship between the 3- dimensional position of an ACL graft and clinical outcomes. Indeed, almost everything that is known has been based on 2-dimensional measurements obtained from planar radiographs. The footprint of the normal ACL attachment to bone or to the Blumensaat line has been used as a coordinate system to describe the intra-articular location of the femoral bone tunnel. Placement of the tibial tunnel is important to prevent graft impingement against the roof of the femoral notch as the knee is extended. The center of the femoral attachment of an ACL graft should be located along a line parallel to the Blumensaat line just posterior to the center of the normal ACL s insertion to bone, and at either the 2 o clock position (left knee) or the 10 o clock position (right knee) when observed through the femoral notch. Patients with a femoral insertion of the ACL graft that is greater then 2 mm anterior to the center of the normal ACL insertion along a line parallel to the Blumensaat line have greater A-P knee laxity at follow-up than patients with posterior positioned tunnels along a line parallel to the Blumensaat line. The tibial tunnel should be placed to avoid impingement of the graft against the roof of the femoral notch as the knee is brought into extension. The tension applied to an ACL graft at the time of fixation and the knee position during the tensioning procedure have a direct effect on knee biomechanics and clinical outcome. With regard to the 4-strand hamstring graft, there is a significant correlation between the tension applied to the graft at the time of fixation and A-P knee laxity measurements after healing is complete. Patients receiving 80 N of tension with the knee in full extension during graft fixation have A-P knee laxity values that are closer to normal than those receiving 20 N and 40 N of tension. Likewise, for the central third BPTB graft, patients receiving 90 N of tension with the knee in full extension during graft fixation have A-P knee laxity values that are close to normal at 2-year follow-up, whereas those receiving 45 N have increased laxity values. Fixation of BPTB grafts with interference screws is adequate for the loads produced by current rehabilitation programs; however, the frequent publication of new techniques to fix free-tendon grafts, such as the 4-strand hamstring graft, suggests that an optimal technique of fixation has yet to be identified. BPTB grafts heal in the bone tunnels through bone plug incorporation and resemble the

14 1764 Beynnon et al The American Journal of Sports Medicine chondral insertion of the normal ACL, whereas freetendon grafts heal more slowly by the fibrils of the graft penetrating the bone directly and result in a fibrous insertion of the tendon. This characteristic implies that aggressive rehabilitation, including immediate weightbearing, open chain quadriceps contraction near extension, and early return to sport, may be a concern during the first few weeks after ACL reconstruction with free-tendon grafts. Bone tunnel enlargement occurs more frequently and is greater after ACL reconstruction with hamstring grafts compared to BPTB grafts; however, tunnel widening does not appear to have an adverse effect on the outcome of ACL reconstruction, although it can certainly make revision reconstruction more difficult. The use of a rehabilitation brace results in fewer problems with swelling and wound drainage and less pain compared to rehabilitation without the use of a brace; at longer follow-up intervals, however, rehabilitation bracing has no effect on outcome. Similarly, the use of a functional knee brace after ACL reconstruction does not appear to have an effect on outcome. The literature on rehabilitation after ACL reconstruction, derived from RCTs, provides information on how much loading and motion a knee with a healing BPTB graft can sustain without permanently stretching the graft (as evidenced by abnormal increases of anterior knee laxity), disrupting the graft, or causing failure of graft fixation. In contrast, there is little information derived from RCTs on the effect of rehabilitation on other graft materials (such as the 4-strand hamstring graft) or on other structures that are commonly injured at the time of an ACL tear (such as the articular cartilage and meniscus). After ACL replacement with a BPTB graft, it is clear that immobilization of the knee, or restricted motion without muscle contraction, leads to undesired outcomes for the ligamentous, articular, and muscular structures that surround the joint. Rehabilitation that incorporates early joint motion is beneficial for reducing pain, minimizing capsular contractions, and decreasing scar formation that can limit joint motion, as well as beneficial for articular cartilage. Immediately after ACL reconstruction with a BPTB graft, weightbearing is possible without producing an unwanted increase in anterior knee laxity; weightbearing is beneficial because it lowers the incidence of anterior knee pain. Recent studies of healing BPTB grafts indicate that accelerated rehabilitation (a 19-week program allowing unrestricted weightbearing after 1 week, no brace use after 2 weeks, open kinetic chain exercises involving contraction of the quadriceps muscle group with the knee near extension after 4 weeks, and return to preinjury activity at 24 weeks) produces the same clinical, functional, and patient-oriented outcomes compared to nonaccelerated rehabilitation (a 32-week program that includes unrestricted weightbearing after 3 weeks, no brace use after 4 weeks, open kinetic chain exercises involving contraction of the dominant quadriceps muscles at 12 weeks, and return to preinjury activity at 32 weeks). Relatively few studies have been published that advocate return to sport between 4 and 6 months after an ACL reconstruction. 53,98,99 Six months after ACL reconstruction, patients walk with normal kinematics but do so with dramatic alterations in torque and power about the hip and knee joints, which has the potential to affect both the graft and articular cartilage metabolism. 31 Despite these observations, many recent articles recommend return to rigorous sports 6 months after surgery, 8,13,33,36,37,58,91,98 whereas others recommend return at 9 months or later. 26,27,67,89 From these perspectives, there is little evidence in the literature that early return to high-risk sports involving activities such as jumping, planting and pivoting, or planting and cutting is safe and effective. 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