Sodium Hyaluronatetrbchemedica.co.uk/docs/viscoseal brochure.pdf · *p
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––––––––––––––––– [ Synovial Fluid Replacement ] ––––––––– Sodium Hyaluronate Aiding Recovery After Arthroscopy
Transcript of Sodium Hyaluronatetrbchemedica.co.uk/docs/viscoseal brochure.pdf · *p
–––––––––––––––––[ Synovial Fluid Replacement ]–––––––––
Sodium Hyaluronate
Aiding Recovery After Arthroscopy
––––––––[Post-arthroscopic changes to the
ArthroscopyArthroscopic surgery is a valuable technique that hasbrought significant benefit to millions of patients. Theprocedure minimises disruption of the tissuessurrounding the joint and has fewer postoperativeproblems than open surgery. However, arthroscopymay be associated with some surgical trauma, themost important features of which are pain, swellingand reduced joint mobility.1
Synovial fluid is flushed out of the joint during arthroscopy
Hyaluronan in the synovial fluidHyaluronan is an essential component of the synovial fluid. It is a biopolymermade of repeating disaccharide units, which gives the synovial fluid itscharacteristic viscoelastic properties. It enables the fluid to act as a lubricant,a shock absorber and a filter controlling the movement of cells and largemolecules within the joint.2,3
During arthroscopy, the joint is flushed with irrigatingsolution to improve visualisation by distending thetissues, washing out debris and controlling any mildbleeding. Irrigation also leads to a loss of thesynovial fluid, which is vital for joint function.
Under gradual shear stress, hyaluronanacts as a lubricant
Under sudden loading, hyaluronan actsas a shock absorber
Hyaluronan acts as a filter, hindering themovement of potentially damaging cellsand molecules
articular environment]––––––––––––––––Hyaluronan in the cartilage and synovial membraneHyaluronan forms a coating over the surface of the articular cartilage and the synovialmembrane.4 This coating acts as a viscoelastic shield, protecting the joint structures frommechanical damage. Hyaluronan also protects from pain by masking the localnociceptors.5,6 In addition, the coating hinders the migration of free radicals and otherinflammatory cells into the joint space.7–9
Hyaluronan also forms the backbone of the proteoglycan aggregates that are essential forthe structural and functional integrity of the articular cartilage.10,11
Consequences of the irrigation procedureDuring arthroscopy, the joint is flushed with irrigating solution, which washes out thesynovial fluid and, therefore, hyaluronan from the joint. This displacement of hyaluronanleads to:
loss of viscoelastic properties, shock absorptionand lubrication, causing stiffness and pain
loss of the protective hyaluronan coating of thecartilage and synovium, leaving these structuresopen to inflammatory mediators and mechanicaldamage
loss of the masking effect on nociceptors,resulting in increased pain.
In addition, the irrigating solutions used duringarthroscopy may have a negative effect on themetabolism of articular cartilage.12–14
Aiding Recovery After Arthroscopy
Inde
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100
80
60
40
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0Control Ringer’s
solutionRinger’sglucose
Ringer’slactate
Normalsaline
Betadine
* ** *
*
*p <0.05 vs control
Post-arthroscopic symptoms may be associated with loss of hyaluronan from the joint
The irrigating solutions used during arthroscopy impaircartilage metabolism14
Pain receptor
Macrophage-likesynoviocyte
Fibroblast-likesynoviocyte
Collagen
Chondrocyte
Proteoglycanmonomer
Hyaluronanbackbone
Cartilage Synovial membrane
Hyaluronan layer
Hyaluronan layer
––––––––––[Rationale for hyaluronan as a Once the synovial fluid is flushed out of the joint, the balance of the articularenvironment is lost. Replacement of the synovial fluid with hyaluronan maypromote restoration of homeostasis inside the joint.
Restoring the articular homeostasisStudies have shown that exogenous hyaluronan:
restores cartilage metabolism following the physiological disturbance causedby irrigating solution15,16
protects the articular cartilage and synovial membrane from damage throughits functional and structural properties17–25
suppresses chondrolysis of cartilage by reducing penetration of fibronectinfragments4
restores cartilage glycosaminoglycan content following 6 weeks of jointimmobilisation; in addition, treatment with remobilisation and hyaluronanincreased glycosaminoglycan content more than remobilisation alone26
promotes repair of degraded cartilage, reverses the damage caused by exposureto fibronectin or interleukin-1, and restores proteoglycan to normal levels27
35S-
sulp
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atio
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to p
rote
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(dpm
)
100
80
60
40
20
0Control
*
*p <0.001
Saline (7 days) Saline plus 5 mg/mLhyaluronan
Men
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20
15
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**p <0.05
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Prop
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Status of ACL laceration after 12 weeksNot covered
25
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Partially covered Completely covered
HyaluronanSaline
Saline irrigation significantly inhibits cartilage metabolism, asshown by reduced 35S-sulphate incorporation into proteoglycans. It is restored to normal by the addition of hyaluronan16
Following partial meniscectomy, hyaluronan promotesmeniscal regeneration compared with saline29
Exogenous hyaluronan stimulates healing of damage to theanterior cruciate ligament (ACL)33
promotes meniscal regeneration followingmeniscectomy and appears to inhibitdegeneration of articular cartilage for up to 6 months28,29
stimulates collagen remodelling and inhibitsswelling during healing of meniscal tears in arabbit model of total medial meniscectomy30
stimulates the synthesis of endogenoushyaluronan31
promotes wound healing32 and the healingresponse following surgical laceration of theanterior cruciate ligament in rabbit models.33
synovial fluid replacement]–––––––––––––Introduction of exogenous hyaluronan into the joint space immediately afterarthroscopy decreases postoperative symptoms. Hyaluronan has been shown toaccelerate joint recovery by reducing pain and swelling, and improving joint function.
Clinical benefitHyaluronan has also been shown to achieve symptomatic relief by:
reducing pain in the joint caused by pain mediators.5,34,35
In combination with arthroscopic surgery or lavage, hyaluronan is effective in:
reducing pain and improving joint mobility in patients with chronic jointderangement36–39
protecting the joint and facilitating surgery40
relieving postoperative pain of the knee joint.39
Aiding Recovery After Arthroscopy
Post-arthroscopic recovery may be aided byadministration of exogenous hyaluronan
Inde
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60
80
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Months after start of treatment2 5
20
1 3 4 6
HyaluronanControl
*p <0.05 vs pre-treatment
*
*
Pain
less
RO
M
120
80
100
40
00
Days after arthroscopy2 5
20
1 3 4
60
HyaluronanControl
Alg
esic
sco
re
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2
0
Hyaluronan 5 mg/mlControl
1
310 kDa
*p <0.05 vs control
**
860 kDa 2300 kDa
Hyaluronan improves painless range of movement (ROM)compared with standard procedure after arthroscopy39
Exogenous hyaluronan reduces pain in patients with chronicjoint derangement38
Exogenous hyaluronan reduces joint pain induced by pain mediators5
––––––––[Viscoseal®: product characteristic
What is Viscoseal®? Viscoseal® is indicated for relief of pain and promotion of joint recoveryfollowing arthroscopy or joint lavage.
CompositionViscoseal® is an isotonic solution of hyaluronan with a physiological pH that isdesigned to be used as a synovial fluid substitute. The concentration ofhyaluronan in Viscoseal® is 0.5%, similar to that in synovial fluid.
Fermentation sourceThe hyaluronan in Viscoseal® is produced by bacterial fermentation.
Viscoseal® is a highly purified product; because it contains no animal proteincontamination, the allergenic potential of Viscoseal® is negligible.
PresentationViscoseal® is presented in a 10-mL, mono-use container equipped with a Luer tipand packaged in a sealed sterile sachet.
Sterility Viscoseal® mono-use containers are terminally sterilised by autoclaving. The deviceis sterile when packaged in order to facilitate aseptic use in a surgery theatre.
cs and administration]–––––––––––––––––How does Viscoseal® work?Following arthroscopy, Viscoseal® displaces any irrigatingsolution left in the joint space, preventing this solution fromimpairing cartilage metabolism.
Viscoseal® acts as a temporary substitute for the synovial fluid,restoring normal physiological functions. Viscoseal®:
restores the lubricating, shock-absorbing and filteringproperties of the fluid
re-establishes the protective coating over the surface of thecartilage and the synovial membrane, hindering themigration of pro-inflammatory and catabolic mediatorsand protecting from mechanical damage
reduces inflammation of the synovium
alleviates pain by masking nociceptors
enhances the production of endogenous hyaluronan.
How to administer Viscoseal®?Viscoseal® is introduced into the joint space at the end of arthroscopic surgery,immediately after completion of the irrigation procedure. Viscoseal® can beadministered by two alternative techniques:
attach the Luer tip of the container to the portal already placed in the joint.Squeeze the container to introduce Viscoseal® into the joint
aspirate the contents of the container into a syringe. Inject Viscoseal® into thejoint cavity through a portal already placed in the joint.
If a drain is placed in the operated joint, introduce Viscoseal® and manipulate thejoint for several minutes before opening the drain.
Aiding Recovery After Arthroscopy
Viscoseal® is designed to aid recovery after arthroscopy
Viscoseal® substitutes for synovial fluid anddisplaces the irrigating solution left in the joint
General pain reliefIn a clinical study of patients who underwent kneearthroscopy, those treated with Viscoseal® reported asignificant reduction in pain, measured on the 100 mm visual analogue scale (VAS), comparedwith those who underwent the standard procedurewith saline lavage only. The improvement wassignificant 1 week after surgery (p <0.01) and wasmaintained for at least 1 month.41
Pain relief andfunctional improvementViscoseal® confers advantages over anaesthetic(bupivacaine) 3–6 weeks after arthroscopy.42 In arandomised study, patients undergoing arthroscopyreceived 10 mL of bupivacaine 0.5% or Viscoseal®
following surgery. Patients who received Viscoseal®
had significantly less pain measured on the VAS,required significantly less analgesia and had asignificant improvement in function demonstrated bya larger decrease in WOMAC score (p ≤0.05) thanpatients who received bupivacaine.
WO
MA
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50
0
30
Pre-op Day 1
*p <0.05
40
20
*
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Bupivacaine
Day 7 Week 3 Week 6
10
*
Viscoseal®
Bupivacaine
Num
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5
02 h
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Pre-op Day 1
*p ≤0.02
4
2
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Day 7 Week 3 Week 6
1
*
VAS
(cm
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5
02 h
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Pre-op Day 1
*p ≤0.01
4
2
*
Viscoseal®
Bupivacaine
Day 7 Week 3 Week 6
1
*
VAS
50
40
00
Days2 5
20
1 3 4 6
*p <0.01
30
10
7 12 14 21 28
*
Viscoseal® (n = 48)
Control (n = 45)
Post-surgery, Viscoseal® reduces pain on the VAS compared tothe standard procedure41
Viscoseal® reduces pain on weight bearing according to the10 cm VAS compared with bupivacaine42
Post-arthroscopy, Viscoseal® reduces the need for analgesicscompared with bupivacaine42
Post-arthroscopy, Viscoseal® reduces the mean WOMAC scorecompared with bupivacaine42
––––––––––––[Viscoseal® accelerates post-
Reduction in joint swellingIn another study involving patients who underwent arthroscopic partialmeniscectomy and joint lavage, there was markedly less swelling in the joints ofpatients who received Viscoseal® (n = 20), compared with those who did not (n = 20). This reduction in the severity of swelling remained apparent at day 28.43
Effective in aiding recoveryIn the same study, patients treated with Viscoseal® were more satisfied with theirtreatment than patients who underwent standard arthroscopy. Patients ratedglobal efficacy over 1 month. At each time point, more patients in the Viscoseal®
arm rated efficacy as optimum/good than in the control arm.43
Aiding Recovery After Arthroscopy
Patie
nts
with
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wel
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70
50
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Days0
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60
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Viscoseal®
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Patie
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80
0Day 7
60
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Day 12 Day 28
Viscoseal®
Standardtreatment
90
70
50
30
10
Viscoseal® reduces post-arthroscopic swellingcompared with controls43
Followingarthroscopy, thepercentage ofpatients who ratedglobal efficacy asoptimum or goodwas higher amongthe Viscoseal®
group than amongthe control group43
Viscoseal® promotes pain relief, reducesswelling and improves function in patients
recovering from arthroscopy
arthroscopic recovery]––––––––––––––––
––––––––[Viscoseal®: immediate and long-
Rapid pain relief A synergistic effect is seen when Viscoseal® is administered with a local anaesthetic.
Following arthroscopic shoulder surgery, 58 patients were given either 10 mL Viscoseal®
plus 10 mL bupivacaine 0.5% or 20 mL bupivacaine alone. Patients treated withViscoseal® showed improved pain relief. Indeed, among 28 patients who receivedViscoseal® plus bupivacaine following arthroscopic shoulder surgery, 29% reported nopain 4 h after the operation compared with 0% in the bupivacaine group.44
Reduced analgesia consumptionIn the same study, at 4 h post-arthroscopy, 25% of patients who received Viscoseal® plusbupivacaine required no further analgesia, whereas all of the patients in the bupivacainearm required some form of analgesia. Moreover, only 11% of patients treated withViscoseal® plus bupivacaine required opiates compared with 33% of patients who receivedbupivacaine alone.44
Reduced time to discharge from hospitalIn addition to experiencing less pain, the 28 patients who received Viscoseal® plusbupivacaine were discharged in half the time taken to discharge those who receivedbupivacaine alone (5.2 vs 9.6 h; p =0.0001).44
Num
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Mild Moderate Severe
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No Viscoseal®
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2
NSAIDs Paracetamol&/or Codeine
NSAIDs &Coproxamol
10
6
4
Viscoseal®
No Viscoseal®
Opiates
Following arthroscopy, painrelief was greater amongpatients who receivedViscoseal® than among thosewho did not44
Following arthroscopy,patients who receivedViscoseal® required lessanalgesia than patients whoreceived bupivacaine alone44
term outcomes]––––––––––––––––––––––
Aiding Recovery After Arthroscopy
Long-lasting benefitsPatients scheduled to undergo arthroscopy for degenerative osteoarthritis of the knee wererandomised to Viscoseal® (n = 36) or standard treatment (n = 38).45 The relative benefit ofViscoseal® on pain when walking remained apparent 1 year after arthroscopy.
SafetyThe studies conducted with Viscoseal® have demonstrated the excellent safety profile oftreatment. No adverse events relating to Viscoseal® have been reported in studies.41–45
Patie
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Viscoseal® Standard treatment
2 weeks 3 months 1 year
80
20
60
40
Time after arthroscopy
Viscoseal®
Patie
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100
06 h
Standard treatment
2 weeks 3 months 1 year
80
20
60
40
Time after arthroscopy
Viscoseal® provides both short- and long-termpost-arthroscopic efficacy and has an
excellent safety profile
Viscoseal® reduced pain, whenwalking 100 m, for at least 1 year after arthroscopy45
The percentage of patientswho rated their globalimpression of treatment as‘clearly improved’ or ‘nocomplaints’ was higher withViscoseal® than with standardtreatment45
Patients in the Viscoseal® arm also gave superior ratings for clinical global impressioncompared with those in the standard treatment arm.
1. Arthroscopy. In: Metcalf RW, ed. Textbook of Rheumatology. 4th edition. Philadelphia:Saunders, 1993: Chapter 38.
2. Balasz EA, Denlinger JL. J Rheumatol 1993;29(Suppl 39):3–9.
3. Peyron JG. Osteoarthritis Cartilage 1993;1:85–7.
4. Homandberg GA et al. Osteoarthritis Cartilage 1997;5:309–19.
5. Gotoh S et al. Ann Rheum Dis 1993;52:817–22.
6. Miyazaki K et al. Pharmacometrics 1984;28:1123–35.
7. Abatangelo G et al. Eur J Cell Biol 1989;49(Suppl 28):18.
8. Goto H et al. Tohoku J Exp Med 1999;187:1–13.
9. Kvam BJ et al. Exp Cell Res 1995;218:79–86.
10. Hardingham TE, Muir E. Biochem Biophys Acta 1972;279:401–5.
11. Hascall VC J Supramol Struct 1977;7:101–20.
12. Reagan BF et al. J Bone Joint Surg Am 1983;65:629–31.
13. Straehley D et al. Trans Orthop Res Soc 1985;10:260.
14. Bulstra SK et al. J Bone Joint Surg Br 1994;76:468–70.
15. Bulstra SK et al. Presented at the Annual Meeting of the Dutch Orthopaedic Society. May 17–18, 2001.
16. Bulstra SK et al. Presented at the 45th Annual Meeting of the Orthopedic ResearchSociety. February 1–4, 1999.
17. Ghosh P et al. J Rheumatol Suppl 1995;43:155–7.
18. Kikuchi T et al. Osteoarthritis Cartilage 1996;4:99–110.
19. Sonoda M et al. Am J Sports Med 1997;24:755–62.
20. Yoshioka M et al. Osteoartritis Cartilage 1997;5:251–60.
21. Asari A et al. Arch Histol Cytol 1998;61:125–35.
22. Shimizu C et al. Osteoarthritis Cartilage 1998;6:1–9.
23. Suzuki Y et al. Arch Orthop Trauma Surg 1998;117:303–6.
24. Wenz W et al. Z Orthop Ihre Grenzgeb 1998;136:298–303.
25. Shimizu C et al. J Rheumatol 1998;25:1813–9.
26. Fu LLK et al. Clin Rheumatol 2001;20:98–103.
27. Homandberg GA et al. Osteoarthritis Cartilage 2003;11:177–86.
28. Hope N et al. Semin Arthritis Rheum 1993;22:43–51.
29. Kobayashi K et al. Osteoarthritis Cartilage 2000;8:359–65.
30. Sonoda M et al. Am J Sports Med 2000;28:90–7.
31. Smith MM, Ghosh P. Rheumatol Int 1987;7:113–22.
32. Chen WYJ, Abatangelo G. Wound Rep Reg 1999;7:79–89.
33. Wiig ME et al. J Orthop Res 1990;8:425–34.
34. Gotoh S et al. Nippon Yakurigaku Zasshi 1988;92:17–27.
35. Yamashita I et al. Nippon Sikeigakka Gakkai Zasshi 1995;69:735–43.
36. Miyamoto H et al. Austr Dent J 1998;43:301–4.
37. Hirota W et al. Br J Oral Maxillofac Surg 1998;36:35-8.
38. Sato S et al. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:241–4.
39. Dai GF et al. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2002;16:16–8.
40. McCain JP et al. J Oral Maxillofac Surg 1989;47:1161–8.
41. Villamor A et al. Presented at the 9th World Congress of the Osteoarthritis ResearchSociety International. December 2–5, 2004; poster P200.
42. Anand S et al. Presented at the 9th World Congress of the Osteoarthritis Research SocietyInternational. December 2–5, 2004; poster P342.
43. Mathies B. Presented at the 8th World Congress of the Osteoarthritis Research SocietyInternational. October 12–15, 2003; poster P134.
44. Funk L, Wykes PR. Presented at the 9th World Congress of the Osteoarthritis ResearchSociety International. December 2–5, 2004; poster P309.
45. Hempfling H. Presented at the 8th World Congress of the Osteoarthritis Research SocietyInternational. October 12–15, 2003; poster P220.
VISCOSEAL®: 0.5% Sodium Hyaluronate
Synovial fluid substitute.10 ml mono-use container in a sterile sachet.
Sterile by moist heat.
Composition: Each 1ml of solution contains: sodium hyaluronate 5.0 mg, sodiumchloride, disodium-hydrogenphosphate, monosodium-hydrogenphosphate and water forinjections. The solution is isotonic.
Indication: To relieve pain, improve mobility and promote joint recovery by flushing outirrigating solution and substituting the synovial fluid following arthroscopic procedures orjoint lavage.
Directions for use: The contents and outer surface of the VISCOSEAL® mono-use containerare sterile as long as the sachet remains unbroken. VISCOSEAL® should be used at the end ofthe arthroscopy after completion of the normal irrigating procedure. Remove the containerfrom the sachet. Twist off the cap and remove the air bubble by squeezing the container.Attach its luer tip to a portal already placed in the joint. Introduce VISCOSEAL® into the jointcavity by squeezing the container. This will help to wash out the remaining irrigating solution.
Precautions: The general precautions for arthroscopic procedures should be observed.VISCOSEAL® should be instilled accurately into the joint cavity. As VISCOSEAL® does notcontain preservatives any solution not used immediately after opening should be discarded.Do not use if the mono-use container or sterile sachet are damaged. Store at below 25ºC.Do not use after the expiry date indicated on the box. Keep out of the reach of children.
Contra-Indications: Known hypersensitivity to any of the constituents of the product.
Interactions: No information on the incompatibility of VISCOSEAL® with other solutions forintra-articular use is available to date.
Characteristics and mode of action: Arthroscopy is a common procedure to visualise,diagnose and treat problems inside a joint. The joint is normally irrigated with solutions suchas saline or Ringer lactate before and during arthroscopy in order to allow a clear view of theoperation site and to rinse out debris. There is evidence that the presence of these solutions inthe joint after irrigation may be detrimental to the cartilage. Furthermore, during theprocedure the synovial fluid, which has particular viscoelastic and protective properties due toits hyaluronic acid content, is washed from the joint. Therefore, although the intervention mayresult in a long-term improvement of joint function, in the short-term patients may sufferfrom post-arthroscopy complaints like pain, swelling and impaired mobility of the joint.
VISCOSEAL® has been developed to relieve these symptoms and promote joint recovery. Itcontains a highly purified specific fraction of hyaluronic acid produced by fermentation andis devoid of animal protein. Flushing VISCOSEAL® through the joint cavity will help removethe remaining irrigating solution and efficiently coat all surfaces of the joint. The VISCOSEAL®
left in the joint will act as a lubricant and a shock absorber and its macromolecularmeshwork will prevent the free passage of inflammatory cells and molecules through thejoint cavity. In addition, hyaluronic acid is able to promote wound healing.
Presentation: 1 x 10ml mono-use container of VISCOSEAL® in a sterile sachet.
To be used under the direction of a physician.
Med IC3Keele University Science Park,Keele, Staffordshire, ST5 5NP
Tel: 0845 330 7556Fax: 0845 330 7557www.trbchemedica.co.uk
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