JORT Journal

Keywords: Anterior cruciate ligament; Blood flow restriction; Muscle atrophy; Rehabilitation; Resistance training

Introduction

Anterior Cruciate Ligament (ACL) injury is one of the most frequent musculoskeletal conditions worldwide. In the USA, more than 250,000 cases per year are reported [1]. Muscle weakness and atrophy of the quadriceps and hamstrings is a common feature in patients following operations such as ACL reconstruction [2]. Τhe reduced weight bearing and unloading context of ACL rehabilitation during the early postoperative stages predispose to muscle atrophy [3]. In recent decades, postoperative rehabilitation methods have been significantly differentiated from an approach of minimal muscle activity and full immobilization [4-6]towards one of increased muscle activation and range of movement (ROM) in the early stages following surgery [4,5]. The American College of Sports Medicine recommends a minimum resistance training load of 60% to 70% of 1 repetition maximum (1 RM) in order to gain strength and 70% to 85% of 1 RM to achieve muscle hypertrophy. Nevertheless, training with these high loads may not be feasible or safe in painful early-operated knees [2].

Studies have shown that exercise with Blood Flow Restriction (BFR) is an efficient technique to attenuate muscle atrophy and ameliorate muscle strength and hypertrophy in patients following ACLR surgery [3,7-9]. BFR is an innovative training method that aims to partially restrict arterial inflow and fully restrict venous outflow by placing a pressurized cuff to the proximal thigh during exercise [1]. During low-resistance exercises, reduced oxygen is delivered to muscle cells. The induced anaerobic environment has been reported to promote muscle hypertrophy by initiating cell signaling and hormonal changes that trigger protein synthesis, proliferation of myogenic satellite cells, and preferential activation and mobilization of type II muscle fibers [10,11]. By using BFR as a rehabilitation tool after ACL reconstruction, it has been shown that exercises performed at lower loads (20%-50% of 1RM) can enhance muscle hypertrophy similar to traditional strengthening protocols without causing pain or straining the knee joint [3,10,1214]. At the early post-operative stage of an ACLR surgery (0-2 weeks), the application of passive BFR can mitigate muscle atrophy [15]. Additionally, low intensity NMES (neuromuscular electrical stimulation) combined with BFR have interestingly increased thigh size and strength, without placing any strain on the graft or exacerbating any cartilage, meniscal and bruising injuries, in the acute phase of ACLR [15]. During the progressive limb loading phase of ACL rehabilitation, low-load BFR training could be integrated to accelerate muscle hypertrophy and improve strength [3]. Nevertheless, there are only few studies that have investigated BFR-RT in the post-operative ACL rehabilitation [7,9,16]. The main objective of this trial was to evaluate if the addition of BFR interventions to a postoperative ACL rehabilitation program (12^th-18^th week post ACLR) can reduce muscle atrophy, improve strength, and muscle hypertrophy, and restore imbalance between the two limbs compared to conventional physical therapy.

Materials and Methods

Study Design

This study was a parallel group, two-arm, between-groups, randomized clinical trial and conducted at the physiotherapy department of our Orthopaedic Center. Informed consent was sought and acquired. This trial has been designed in agreement with the CONSORT guidelines for reporting randomized controlled trials.

Participants

We enrolled 16 patients who had undergone an ACLR with a hamstring autograft prior to 12^th postoperatively week (Table 1). Inclusion and exclusion criteria are described in detail in Figure 1. Moreover, both groups were evaluated to find out that they met the criteria required to join the intervention program. The swelling in the operated limb, the range of motion of the knee (0-90o), as well as the ability to lift their body weight without the appearance of pain (sit to stand test) were examined. Once all these criteria were qualified, participants attended a familiarization session and underwent some measurements.

BFR-blood flow restriction, ACLR anterior cruciate ligament reconstruction

Table 1: Demographics.

Figure 1: CONSORT statement flow diagram.

Randomization and Blinding

Patients who consent and met the eligibility criteria were randomly divided into two groups: Group A: the BFR group that performed Blood Flow Restriction (BFR) protocol in addition to the standard physical therapy and Group B: the control group that performed exercise protocol without restriction, following standard physical therapy (3 times per week, including passive and active ROM exercises, open/closed kinetic chain resistance exercises, balance & proprioceptive training) supervised by an appointed physiotherapist at the designated outpatient rehabilitation unit. Randomization was performed using a random number generator. An independent member of the research team then chose a random unmarked envelop in order to assign each number to one of the groups: blood flow restriction training or standard physical therapy.

Experimental Procedure

The only difference between the two groups was the application or not of BFR protocol. The study was performed during the 12^th-18^th week postoperatively. A 6-week intervention program (week 12^th -18^th) begun at 12 weeks following ACLR surgery and completed at 18 weeks for the Group A.

Blood Flow Restriction Pressure Calculation

In this study, an automatic personalized tourniquet system (MAD-UP system, Angers, France) was used only in the injured limb to achieve partial vascular occlusion of the lower limb (LOP), defined as the minimum pressured required for full arterial occlusion (AOP). MAD-UP patented technology allows you to adjust the pressure applied to the limb via the cuffs. During the session, pressure is regulated in real time and is synchronized with movement and muscular contraction. Additionally, the physiological evolution of the participant is continuously analyzed and taken into account so as to attain safety and comfort. Prior to intervention program the cuff was placed on the proximal thigh and LOP was calculated in the supine position. BFR pressure was set at 80% LOP to increase fast twitch fibre recruitment and induce hypertrophic adaptations.

Interventions

The Group A performed an intervention program twice a week, totaling 12 sessions each separated by a minimum of 48 h. All BFR interventions were conducted under the direct supervision of a trained member of the research team. Three strengthening exercises were selected: a) knee isometric extensions, b) seated knee extensions and c) half-seats performed slowly (2s concentric, 2s eccentric phase, paced by a metronome). One set of 30-1515-15 repetitions with 30 seconds rest between each set for each exercise were performed and the rest between exercises lasted 3 minutes. The Group A performed each exercise with partial vascular occlusion (60-80%) of the LOP in addition to standard physical therapy. For the first two weeks occlusion was at 60% of the LOP. From the 3rd to the 6th week occlusion increased to 80% of LOP and a small load corresponding to 10-20% of 1RM was added (10-20% of 1RM was calculated approximately according to the feedback we received from the participants and was adapted to the dynamics of each one individually). The BFR-cuff remained inflated throughout the session. In case participants were incapable of completing the repetitions without pain or discomfort, the external load was reduced. Regarding the Group B, all participants completed the intervention program without the addition of BFR.

Outcome Measurements

Outcome evaluation included muscle bulk, muscle strength and symptoms evaluation as measured by patient-reported scores. Measurements were performed at the beginning and after the completion of the intervention program of both groups.

Muscle Morphology

Thigh girth measurements were taken at 10-cm and 20-cm measured proximal to the superior patellar pole using a standard tape measure in order to identify the muscle thickness of both limbs (operated & healthy). All measurements were taken with participants lying supine.

Muscle Strength

Μuscle deficits of knee extensor and flexor muscles were measured with the isokinetic evaluation on a Cybex Isokinetic Dynamometer by an experienced physical therapist. Isokinetic strength testing was performed after a 5-minute bicycling warm-up. Each patient was positioned on the dynamometer as per manufacturer’s instructions in an upright, seated position. Following five submaximal warm-up repetitions and 3 min of rest, participants performed five maximal effort repetitions of knee extension and flexion through full ROM at 60^°/s.

Patient-Reported Outcome Measures

Patient-Reported function was assessed using IKDC, KOOS and VAS score. The International Knee Documentation Committee (IKDC) Questionnaire is a knee-specific patientreported outcome measure, which assesses symptoms, sports activity, and knee function in daily living. It is scored on a 0-100 scale with 100 representing higher knee function. The Knee Injury and Osteoarthritis Outcome Score (KOOS) is a questionnaire that assesses both the long-term and short-term consequences of knee injury and osteoarthritis. It consists of 5 domains: pain, symptoms, activities of daily living, quality of life, and sport functions. It is scored on a 0-100 scale with 0 representing extreme symptoms and 100 representing no symptoms. Pain was also measured using the visual analog scale (VAS). As 0 rates no pain and 100 rates extreme pain.

Statistical Analysis

For the statistical processing of the data collected from the above measurements, the statistical program SPSS 20.0 (Statistical Package for Social Sciences) software for Windows was used. Levels of importance of the statistically significant differences was set at p <0.5. Normal distribution of data was assessed using the Shapiro-Wilk of Normality test (p>0.05) and Ιndependent t-test. For nonparametric data, Wilcoxon signed-rank test & MannWhitney U Test were used.

Results

Demographics

Twenty-six patients were enrolled, randomized and assessed for eligibility in order to complete the study protocol. Six participants were excluded from the study because they did not meet the participation criteria and prerequisites of the survey and four participants declined to participate. There were no significant differences between groups for any baseline anthropometric variable (Table 1). Both groups joined during the same postoperative stage (92 ± 2 days vs 94± 2 days) and completed the same measurements before the implementation of the BFR protocol (12^th week postoperatively) and after the completion of 12 sessions (18^th week postoperatively) in order to identify and evaluate differences between the two groups.

Muscle Morphology

Table 2 shows the results of thigh circumference at 10cm and 20cm for both groups. There was statistically significant improvement for group A at 10cm (p<0.004) and 20cm (p<0.001) (1.4 ± 0.9% and 2.25 ± 1.6%) compared to the Group B (0.6 ± 0.9% and 1.1 ± 1.2%).

Table 2: Thigh Girth (cm) Proximal to Superior Patellar Pole.

Scaled Isokinetic Strength

Table 3 shows the muscle strength deficits for the injured limb as measured with the use of the isokinetic evaluation at 60 N/s from pre-BFR protocol to post-BFR protocol. There was statistically significant improvement for the muscle deficit of flexor muscles between the two groups (p<0.024), while no significant changes were observed in extensor muscles (p>0.226).

Table 3: Muscle strength deficit at 60/s (Nm/kg) through the isokinetic evaluation CYBEX.

Patient-Reported Outcome Measures

Patient-reported outcomes (KOOS, IKDC, VAS) improved statistically significant for the Group A before and after the BFR interventions (Table 4). For the Group B no such difference was observed (Table 5). In-between groups analysis however, showed no statistically significant differences, probably due to small sample size (Table 6). No patients BFR group reported any adverse effect during this trial.

Table 4: Patient-Reported and Physical Outcome Measures.

Table 5: Patient-Reported and Physical Outcome Measures.

Table 6: Between groups statistics of Patient-Reported and Physical Outcome Measures.