ORTHOPEDICS October 2010;33(10):724.

Intra-articular Injection of Hyaluronic Acid Following Arthroscopic Partial Meniscectomy of the Knee

by Rafael Thein, MD; Barak Haviv, MD; Amos Kidron, MD; Shlomo Bronak, MD

Abstract

The short-term recovery period post-arthroscopic meniscectomy is characterized by pain and impaired function most likely related to the irrigation of synovial fluid from the knee intraoperatively. Consequently, along with removal of harmful debris, the irrigation fluid dilutes the hyaluronic acid layer covering the joint tissues. Hyaluronic acid contributes to the homeostasis of the joint environment and is an important component of synovial fluid and cartilage matrix. Hence, the instillation of hyaluronic acid after the procedure may relieve symptoms.

This prospective, single-blind, randomized, controlled study evaluated clinical outcome after hyaluronic acid injection to patients who underwent arthroscopic meniscectomy of the knee. Patients with ligamentous injuries or severe chondral damage were excluded. Fifty-six patients with a mean age of 34 years (range, 17-44 years) were injected with Viscoseal (TRB Chemedica International S.A., Geneva, Switzerland) or normal saline immediately post-arthroscopy and divided into the Viscoseal group or control group, respectively. Patients were evaluated for pain, swelling, and function at 1, 4, and 12 weeks postoperatively. Patients in the control group reported more pain at week 1, with a mean visual analog score (VAS) of 43, than did patients in the Viscoseal group, with a mean VAS of 28 (P=.006). At 4 weeks postoperatively, none of the Viscoseal patients had consumed analgesics, where 9 (of 28) in the control group reported acetaminophen intake (P=.039). No significant difference in knee function was found between groups. Intra-articular injection of Viscoseal after arthroscopic meniscectomy reduced pain in the short-term recovery period.

Patients undergoing knee arthroscopy frequently encounter pain, swelling, and impaired function in the short-term postoperative period. Several analgesic schemes have been used to treat pain induced by arthroscopic knee surgery with partial effect.^1,2 Current practice involves lavage of the normal hyperviscous synovial fluid as an integral part of the procedure, with an irrigation fluid (normal saline) to be replaced later by the new, naturally formed synovial fluid. Consequently, along with removal of harmful debris, the irrigation fluid dilutes the hyaluronic acid layer covering the joint tissues, including the cartilage. In addition, experimental studies have shown that irrigation fluids used in arthroscopy can have a negative effect on the metabolism and structure of the joint cartilage.^3,4

The synovial fluid contains hyaluronic acid, a complex glycosaminoglycan whose viscoelastic properties serve to lubricate and allow smooth and pain-free joint motion. Hyaluronic acid contributes to the homeostasis of the joint environment and is an important component of synovial fluid and cartilage matrix. Due to its structure, it serves as a semipermeable barrier to protect the cartilage from the free movement of lytic enzymes, inflammation mediators, and inflammatory cells in the synovial fluid.^5,6

The efficacy of hyaluronic acid in osteoarthritis has been described in several studies. In a rabbit osteoarthritis model, high-molecular-weight hyaluronic acid relieved joint pain and prevented the progression of cartilage degeneration.⁷ Exogenous hyaluronic acid injected into the arthritic joint space has been shown to improve the qualitative and quantitative properties of endogenous hyaluronic acid and therefore improve joint lubrication (concept of viscosupplementation).⁸ More recent studies of human synoviocytes from osteoarthritic joints have revealed that exogenous hyaluronic acid stimulates de novo synthesis of hyaluronic acid, inhibits release of arachidonic acid, and inhibits interleukin-1α-induced prostaglandin E2 synthesis by human synoviocytes, which reduces the anti-inflammatory response.⁹ Thus, the replacement of the lost synovial fluid with a hyaluronic acid-containing synovial fluid substitute immediately after arthroscopy may be beneficial.

The purpose of this study was to assess whether the use of a hyaluronic acid-containing synovial fluid substitute (Viscoseal; TRB Chemedica International S.A., Geneva, Switzerland) after arthroscopic partial meniscectomy would relieve acute pain and result in an earlier return of joint function compared to patients undergoing standard arthroscopic partial meniscectomy.

Materials and Methods

This was a prospective, single-blind, randomized, controlled study. The inclusion criteria for this study included symptomatic patients with meniscal tear and minimal chondral damage of the knee (ie, no more than Outerbridge¹⁰ grade 2). Additional exclusion criteria were the presence of associated ligament injuries, previous surgery on the same knee, infection, or inflammatory joint disease.

During the study period (2004-2006), 452 knee arthroscopies were performed at our institution. A total of 88 patients with presurgery diagnosis of meniscal pathology requiring arthroscopic intervention were recruited. Three patients cancelled their arthroscopy for unknown reasons, while 5 patients were lost to follow-up at 3 months. Twenty-four patients presented exclusion criteria during arthroscopy (eg, anterior cruciate ligament tear, advanced chondral damage, or intact menisci) and were not randomized. Overall, 56 patients participated in this study (32 men and 24 women). Mean patient age was 34 years (range, 17-44 years). Patients were divided randomly into 2 groups. The Viscoseal group (N=28) was treated with 10 mL intra-articular of Viscoseal while the control group (N=28) was treated with normal saline. Patients were blind to this treatment.

The indication for surgery was knee pain accompanied by mechanical symptoms. All patients had meniscal injury signs on physical examination. Imaging studies included anteroposterior and lateral radiographic views of the painful knee and preoperative magnetic resonance imaging to confirm the diagnosis.

All patients received general anesthesia using pneumatic tourniquet and were randomized to the treatment groups during arthroscopy once the inclusion and exclusion criteria were confirmed. Joint irrigation was performed with the assistance of an arthroscopic pump system using 0.9% NaCl solution at room temperature. At the end of the surgery, all the remaining fluids were drained from the knee and 10 mL of Viscoseal preparation or 10 mL of saline were injected. The knee was dressed while the tourniquet was still inflated.

All surgeries were performed in a day-surgery facility. Postoperatively, full weight bearing was allowed. Crutches were recommended for the first 48 hours. Anti-inflammatory medications were avoided. However, consumption of escape medication (eg, acetaminophen) was recorded. All patients followed a rehabilitation protocol for meniscectomy and were asked to return for assessment at weeks 1, 4, and 12. At each visit they were questioned on any adverse events they may have experienced since their last visit. Their escape medication intake since the previous visit was also recorded.

Preoperative assessments were undertaken 2 days prior to and on the day of the index surgery. Postoperative assessments were then performed at 1, 4, and 12 weeks. Permission was obtained from all patients prior to surgery to use their data.

The following parameters were assessed at each time period:

• Pain (the mean at rest and squatting), using a 100-point visual analog score (VAS) (0=no pain, 100=extreme pain).
• The Knee Injury and Osteoarthritis Outcome Score, a questionnaire designed to assess short- and long-term patient-relevant outcomes following knee injury.¹¹ The questionnaire is self-administered and assesses 5 outcomes: pain, symptoms, activities of daily living, sport and recreation function, and knee-related quality of life.
• Joint swelling, evaluated as measuring and comparing the circumference of both knees at the patellar level (the broadest point).
• Analgesic consumption.

Viscoseal is a viscosified synovial fluid substitute specifically developed for use after arthroscopy. It is approved as a medical device in the European Union and other countries. It is a 0.5% isotonic solution of 1.2 million-dalton-molecular-weight hyaluronan. This concentration of sodium hyaluronate is similar to the concentration of hyaluronic acid present in normal synovial fluid.⁸ The hyaluronic acid in Viscoseal is a specific, highly purified fraction obtained by bacterial fermentation (Streptococcus zooepidemicus) and is devoid of animal proteins. The solution is sufficiently viscous (intrinsic viscosity 15 dL/g) to act as a synovial fluid substitute after arthroscopy.

Results were expressed with descriptive methods (mean, range). Nonparametric analysis was performed with the Mann-Whitney U test for comparison between corresponding parameters in each group for all available time points. P<.05 was considered statistically significant.

Results

All 56 patients completed the study. The 2 groups were homogeneous for age and sex. At arthroscopy the 2 groups had similar chondral findings. Specifically, we found no chondral damage in 13 patients in the Viscoseal group and 10 in the control group. Grade 1 chondral lesions were found in 8 patients in the Viscoseal group and 9 in the control group, while grade 2 lesions were found in 11 and 12 patients, respectively. Chondral lesions were unicompartmental in 12 patients, bicompartmental in 2, and tricompartmental in 1 in the Viscoseal group, and unicompartmental in 11, bicompartmental in 4, and tricompartmental in 3 in the control group.

Overall, the reduction in pain at 12 weeks was similar for both groups (Figure 1). However, patients in the control group reported more pain at week 1, with a mean VAS of 43, than did patients in the Viscoseal group, with a mean VAS of 28. This difference was statistically significant (P=.006). At 4 weeks postoperatively, the mean VAS was almost equal.

Figure 1: Pain in both groups at baseline and follow-up. Abbreviation: VAS, visual analog score.

Figure 2: Knee Injury and Osteoarthritis Outcome Score (KOOS) in both groups at baseline and follow-up.

The improvement in the Knee Injury and Osteoarthritis Outcome Score was also nearly equivalent in both groups at all follow-up time points (Figure 2). However, at baseline, Knee Injury and Osteoarthritis Outcome Scores were significantly lower in the Viscoseal group, with a mean of 41.8 (range, 3-79.2), compared to the control group, with a mean of 52.3 (range, 20.2-83.3) (P=.005). This was attributed mainly to the differences in joint swelling between groups. More patients in the Viscoseal group (19 of 28) had joint effusion compared to the control group (8 of 28) at baseline. However, assessments at 4 and 12 weeks showed a mild superiority in joint effusion (fewer patients with measured swelling) in the Viscoseal group.

Analgesic intake was lower throughout the follow-up period in the Viscoseal group compared to the control group, but it was significant at the second follow-up assessment. At 4 weeks postoperatively, none of the Viscoseal patients had consumed analgesics, where 9 (of 28) in the control group reported acetaminophen intake (P=.039).

No serious or unexpected adverse events were reported in either group. Viscoseal was well tolerated by all patients.

Discussion

Our results suggest that immediate postoperative hyaluronic acid injection can relieve pain in the first 4 weeks after arthroscopic meniscectomy.

Hyaluronic acid is widely used in the treatment of osteoarthritis by intra-articular injection into affected joints. Several clinical trials have shown that hyaluronic acid therapy is effective and safe for osteoarthritis patients who have ongoing pain or are unable to tolerate other conservative treatments.^12-14 To test the value of incorporating hyaluronic acid immediately after arthroscopic meniscectomy, we used a hyaluronic acid-based synovial fluid substitute (Viscoseal) after final irrigation. Viscoseal contains 0.5% hyaluronic acid, which is close to the concentration of hyaluronic acid present in normal synovial fluid (0.2%-0.4%).⁸ Pain, effusion, and function were compared between patients who received intra-articular hyaluronic acid and patients who underwent standard therapy. Follow-up time was 12 weeks based on previous studies that demonstrated rapid elimination of intra-articular hyaluronic acid injection from the synovial fluid.^15-17

Statistically significant pain reduction was found 1 week postoperatively in the Viscoseal group. Although pain had leveled in the control group at 4 weeks, patients in the control group consumed more analgesics during that period. In a similar previous study, Mathies¹⁸ found a lower increase in pain in the Viscoseal group compared to the control group, with the trend remaining in favor of Viscoseal for the first 3 days postoperatively. In his study, the Viscoseal group also had a proven superiority in diclofenac intake on days 3, 4, and 7, indicating a nonsteroidal anti-inflammatory drug-sparing effect. No significant between-group differences were observed in joint function both in Mathies’ study¹⁸ (tested by the Lysholm score) and in our study (tested by the Knee Injury and Osteoarthritis Outcome Score), although at baseline Knee Injury and Osteoarthritis Outcome Score values were significantly lower in the Viscoseal group. This was attributed mainly to the differences in joint swelling between groups. More patients in the Viscoseal group had joint effusion compared to the control group at baseline.

Our study demonstrated that patients in the Viscoseal group had a more rapid recovery from arthroscopic partial meniscectomy with less pain, less effusion, and a lower intake of analgesics compared to the control group. Other short- and long-term benefits can be found in the literature but were mainly performed on osteoarthritis patients. A prospective, randomized, controlled, double-blind study of 66 patients with various degrees of chondral damage at 2 years after treatment showed that the postarthroscopic instillation of a hyaluronic acid-based synovial fluid substitute into the joint is a suitable way of achieving long-term stabilization of the treatment outcome.¹⁹ Another multicenter, prospective, open study showed that hylan G-F 20 in knee osteoarthritis patients provides effective pain relief and improves stiffness and physical function at 4 to 12 weeks after arthroscopic meniscectomy.²⁰ Symptomatic efficacy was maximized at 12 weeks and maintained at 26 and 52 weeks.

The distinctive strength of our study is in its methodology as a prospective, randomized, controlled, single-blind study. In contrast to most other publications, the target population included patients with meniscal tear without significant chondral changes. Pain and function in both study groups were almost identical by the end of our follow-up (at 12 weeks); however, the Viscoseal group proved to be less painful within the first 4 weeks. We believe that this instant improvement with intra-articular hyaluronic acid should be considered cost effective after arthroscopic meniscectomy as it can shorten the recovery time and allow more rapid return to work or other occupations.

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