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5th MuscleTech Network Workshop Research on Muscle and Tendon Injuries: from scientific evidence to clinical practiseAnders Boesen, MD , PhD. Student Institut of Sports Medicine Copenhagen H:S Bispebjerg Hospital Team Doctor F.C Copenhagen Barcelona 14 th and 15 th October 2013

Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

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RCT in PRPs. From theory to practice

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Page 1: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

5th MuscleTech Network Workshop ”Research on Muscle and Tendon Injuries: from scientific evidence to clinical practise” Anders Boesen, MD , PhD. Student Institut of Sports Medicine Copenhagen H:S Bispebjerg Hospital Team Doctor F.C Copenhagen

Barcelona 14th and 15th October 2013

Page 2: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection (HVI) in Achilles Tendinopathy

è

High Volume Injection

Possible treatment option for Tendinopathy???

Page 3: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Platelet-rich Plasma or High Volume injection (HVI) in Achilles Tendinopathy (RCT, double blinded).

è ç

ACP (4mls)

High Volume Injection 10 mls Marcain 0,5 % + 1/3 ml. Depomedrol 40 mg/ml + 40 mls Saline

+

12 wk Eccentric traning

Page 4: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Dr. Otto Chan, London SportsCare, London Independent Hospital

Page 5: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

December 2011 London SportsCare, London Independent Hospital

Page 6: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection:

�  10 mls Marcaine 2,5 mg/ml �  ∼ 1/3 ml Depomedrol (40mg/ml) �  40 mls Saline

What is High Volume Injection?

Page 7: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection steps:

Step 1: Ultrasound Diagnostic

Page 8: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection steps:

Step 2: Material (whats needed?)

•  Marcaine, Depomedrol and Saline •  10 mls. Syringes (5 pieces) •  Tube and needle (green) •  Gloves •  Desinfection (klorhexidin)

Page 9: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection steps:

Step 3: Injection Procedure

Page 10: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection:

Step 3: Injection Procedure

Page 11: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection:

Step 3: Injection Procedure

Page 12: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection:

Step 3: Injection Procedure

Page 13: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark
Page 14: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection:

When should you use HVI?

Page 15: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection steps: Step 4: Rehab Program (Otto Chan group)

Day 1-3: Rest from sport, jumping, running, long walk Day 4: Fitness work (3 x 40 minute sessions/week)- Swimming, cycling or rowing Day 6: Start Alfredson 12 wk eccentric training protocol- 3x15 calf drops-knee bent and 3x15 calf drops-knee straight (Twice per day) Start with bodyweight, add 5kg increments if there is no discomfort. Mild to moderate pain during is acceptable (VAS <4/10), but should settle quickly. Day 10: Commence stretch-shorten cycle/impact activity Start with 5-10 minutes of sport, at modified intensity (ie no sprinting or maximal jumps). Then increase by 5-10 minutes per week based on this pain monitoring system and gradually increase intensity.

Page 16: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection: Step 4: Rehab Program (Modified by our Group)

Day 1-5: Rest from sport, jumping, running, long walk Day 6: Start Alfredson 12 wk eccentric training protocol (Twice per day) Start with bodyweight, add 5kg increments if there is no discomfort. Mild to moderate pain during is acceptable (VAS <4/10), but should settle quickly. Day 7: Fitness work (3 x 20-30 minute sessions/week) - Swimming, light cycling or rowing. Day 28 Introducing jogging on flat surface progressing to trampoline. If no pain start running 5-10 minutes, flat surface, slow/steady pace. Increase by 5-10 minutes per week. No more than every 2nd to 3rd day. Only progress if symptoms are stable. When running 30 minutes, progressively commence sport.

è Should be monitored by a Physiotherapist

Page 17: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection:

•  Complications? -  No infections or skin complication seen

-  Relapse: Approx. 15-20 % in the Tendon Clinic out of 150 Achilles and 75 Patella Tendons. -  One case of (1/150 Achilles) partiel rupture 3 1/2 months after HVI during high intensity running on sand. -  One case of (1/150 Achilles) total rupture 3 1/2 months after HVI (startet playing football and trained full after only 2 wks)

Page 18: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

1) High volume image guided injections in chronic Achilles tendinopathy. Chan O et al, Disabil Rehabil. 2008;30(20-22):1697-708. 21 patients (no control group) Conclusion: HVI significantly reduces pain (VAS) and improves function (VISA-A) in the short (4 weeks) - and long-term (6 month). 2) High volume ultrasound guided injections at the interface between the patellar tendon and Hoffa's body are effective in chronic patellar tendinopathy. Crisp T et al, Disabil Rehabil. 2008;30(20-22):1625-34. 9 patients (no control group) Conclusion: HVI significantly reduces pain (VAS) and improves function (VISA-P) in the short (2 weeks) - and long-term (9 month). 3) The short-term effects of high volume image guided injections in resistant non-insertional Achilles tendinopathy. Humphrey J et al, Sci Med Sport. 2010 May;13(3):295-8. 11 patients (no control group) Conclusion: HVI improved symptoms (VAS) and function (VISA-A), reduce neovascularisation, and decrease maximal tendon thickness at short-term follow-up (3 weeks).

Page 19: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

1) High volume image guided injections in chronic Achilles tendinopathy. Chan O et al, Disabil Rehabil. 2008;30(20-22):1697-708. 21 patients (no control group) Conclusion: HVI significantly reduces pain (VAS) and improves function (VISA-A) in the short (4 weeks) - and long-term (6 month). 3) High volume ultrasound guided injections at the interface between the patellar tendon and Hoffa's body are effective in chronic patellar tendinopathy. Crisp T et al, Disabil Rehabil. 2008;30(20-22):1625-34. 9 patients (no control group) Conclusion: HVI significantly reduces pain (VAS) and improves function (VISA-P) in the short (2 weeks) - and long-term (9 month). 4) The short-term effects of high volume image guided injections in resistant non-insertional Achilles tendinopathy. Humphrey J et al, Sci Med Sport. 2010 May;13(3):295-8. 11 patients (no control group) Conclusion: HVI improved symptoms (VAS) and function (VISA-A), reduce neovascularisation, and decrease maximal tendon thickness at short-term follow-up (3 weeks).

Page 20: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Platelet-rich Plasma or High Volume injection (HVI) in Achilles Tendinopathy (RCT, double blinded).

è ç

ACP (4mls)

High Volume Injection 10 mls Marcain 0,5 % + 1/3 ml. Depomedrol 40 mg/ml + 40 mls Saline

+

12 wk Eccentric traning

Page 21: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Platelet-Rich Plasma or High Volume injections in Achilles tendinopathy (RCT, double blinded)

Design: •  Subjects: 60 randomized healthy male patients age 25-60 years with unilateral Achilles tendinopathy > 3 months. (no steroid inj.<6 month)

•  12 weeks eccentric training (all patients).

•  Randomized: ACP (N=20), HVI (N=20) or Placebo (N=20) – all included.

•  Follow-up after 6 weeks, 3 month and 6 months (12 month). – lost to follow-up (one in each group)

Page 22: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark
Page 23: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Review of litt

Page 24: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

PRP is simple

Page 25: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

These cytokines play important roles in cell proliferation, chemotaxis, cell differentiation, and angiogenesis

Page 26: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Review of litt

Page 27: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark
Page 28: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

The symphony of GF of tendon healing

Page 29: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Challenges in use of PRP

•  Timing of the various growth factors •  Readiness of the tissue •  Local injection – right spot •  Other stimuli – loading ?

Page 30: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

First 6 month study design (n= 3 X 19 patients):

                 2  wks

Diagnosed Achilles tendinopathy clinically and with ultrasound

Blodsample (10ml) X X X X

ACP (n=19) (4ml) X X X X

HVI (n=19) X (after first HVI injection the groups revieve only placebo)

Placebo (n=19) X

Ultrasound X X X X X X

VISA-A score X X X X X

VAS score X X X X X X

Heel-rise test X X X X

Start eccentric train. X

End eccentric train. X (performed 3 times/wk from week 12)

                 2  wks                  2  wks                  6  wks                  12  wks

Page 31: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

High Volume Injection:

Page 32: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

ACP (Artrex system) procedure:

1)  Whole Blood is taken out (10-12 mls). 2) Blood centrifugation (spinning) 3) Separation of the ACP (4 mls)

Page 33: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Alfredson 12 wk Eccentric Program: 15 rep. X 3 bended knee 15 rep. X 3 straigth knee è Twice a day 12 – 24 wk: 3 times a week

All participants performed eccentric training

Page 34: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

• VISA-A (function) and VAS score (pain symptoms) • Range of motion and heel-rise test (MuscleLab). • Ultrasound (gray-scale and Doppler) • Analyse ACP: Platelets concentration and growth factors (PDGF, TGF-ß, IGF-1, PDEGF, PDAF, PF-4, EGF and VEGF)

Measurements (6 wk, 3 month and 6 month):

Measure the exact heel hight and number of reps (total workload)

- Use it during rehab after achilles rupture

Page 35: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Results VISA-A 6 wk., 3 month and 6 month

Significant increase in all groups after 6,12 and 24 weeks from baseline Significant difference between HVI vs ACP and Placebo (6wk and 3 month) Significant difference ACP/HVI vs Plc (24 wk.)

*

| | | —— | | |

—— | |

*

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—— | | | |

| | |

—* * *

Page 36: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Results VAS 6 wk., 3 month and 12 month

Significant increase in all groups after 6 and 12 weeks from baseline Significant increase between HVI vs ACP and Placebo (6wk) Significant increase between HVI/ACP vs Placebo (12 wk and 24 wk)

*

* —— | | |

*

* —— | | —— | | * ——

——

—— —— | —— | | | | |

| —* *

—*

Page 37: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Results Ultrasound 6 wk., 3 month and 6 month

§

Significant increase in HVI and ACP group in all follow-ups vs baseline Significant increase between HVI vs ACP and Placebo (6wk and 12 wk) Significant increase between ACP and Placebo (12 wk) Significant increase between ACP/HVI vs Placebo (24 wk)

* * *

—— * —— | |

—— | | | * —— | |

* |

—— | | *

——

—— | ——

| | | |

| |

|

*

*

* *

—— | |

Page 38: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Results Heel-rise 6 wk., 3 month and 6 month

§

- Significant increase in HVI, ACP and Placebo group in all follow-ups compared to baseline. - No differences between groups

*

Total  work  load  (heel-­‐rise  test)

0

200

400

600

800

1000

1200

1400

1600

1800

2000

After  6  weeks After  3  month After  6  month

Chances  in  total  w

ork  load  from

 baseline  (Jo

ule)

HVIACPPlacebo

* *

*

* *

*

* *

*

Page 39: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

• VISA-A score (functional score): All groups improved at 6 wk, 12 wk and 24 wk follow-up! 6 wk and 3 month- Significant differences (P<0.01) between HVI vs. ACP and Placebo!! 6 month- Significant differences (P<0.01) between HVI and ACP vs. Placebo!! • VAS score (pain score): All groups improved at 6 wk, 12 wk and 24 wk follow-up! 6 wk and 3 month- Significant differences (P<0.01) between HVI vs. ACP and Placebo!! 6 month- Significant differences (P<0.05) between HVI and ACP vs. Placebo!! • Ultrasound (gray-scale): All groups improved at 6 wk, 12 wk and 24 wk follow-up! 6 wk and 3 month- Significant differences (P<0.01) between HVI vs. ACP and Placebo!! 6 month- Significant differences (P<0.05) between HVI and ACP vs. Placebo!!

Summarize results ( 6 month follow-up)

Page 40: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Conclusion •  HVI or ACP in combination with eccentric training seems more effective than eccentric training, per se! - Reducing pain symptoms, - Improving activity level and - Reducing tendon thickness ⇒ HVI appears more effective than ACP in the short-term (3 month).

Started up a new pilot project (6 wk, 3 month and 6 month follow-up): 12 patients HVI (+Depomedrol) vs. 12 patients HVI (÷ Depomedrol)

è See how how much effect corticosteroid has compared to volume effect ???

Page 41: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Case 1 •  A young talented player

with symptoms in the patella tendon (on and off pain during warm up or after training, better during activity) during the preseason training

•  what to do? •  continue training? adjust

training? add treatment?

Page 42: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Case 2 •  A very important

player during season experience increasing symptoms (pain and stiffness in the morning) in the Patellar Tendon weeks before an important match

•  What to do ??

Page 43: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Case 3

•  One of you players experiences sudden unset of pain in the Insertional Achilles tendon during training but only during high loading.

•  What to do ?

Page 44: Henning Langberg. Professor at the Institute of Health University of Copenhagen, Copenhagen, Denmark

Thanks to: Morten Boesen Rudi Hansen Otto Chan Peter Malliaras Michael Kjaer Henning Langberg (PhD. Supervisor)