3/7/2013
AUDIT
EXOGEN 4000 significance for the treatment of non-union
The delayed union of fracture treatment by Low Intensity Pulse Ultrasound LIPUS is already approved type of treatment but still new entity in our hospital. The National Institute for Health and Clinical Excellence already released NHS guidelines:
‘Low-intensity pulsed ultrasound to promote fracture healing’. Issue date is December 2010.
‘EXOGEN Ultrasound bone healing system for long bone fractures with non-union or delayed healing’. Issue date January is 2013.
Method and patients
We found a list of patients who was treated by LIPUS. 47 cases were treated in YG using Ultrasound bone healing system EXOGEN 4000, Smith and Nephew GmbH from 19/2/2010 to 10/9/2012. The ultrasound was administered for 20 minutes daily through a transducer by patient himself during fife month.
We went through all x-rays in Synapse System and collected information from the notes in to Excel table. We grouped all details and compared with existing NICE guidelines as standard. We found in the guidelines that LIPUS can reduce healing time of non-union compared with surgery. We found articles about surgical treatment of non-union and collected common healing timing in PubMed System. Finally we asked consultants personal opinion about each case and counted cases with obvious EXOGEN effect and bone healing acceleration, cases where no benefit from EXOGEN and cases were was impossible to make any decision.
We collected the following data:
1. Name, middle name and Surname of the patient
2. D number and DOB, Gender, age of patient when Non-union happened;
3. Consumption of alcohol, smoking, BMI
4. PMH, Medication and detailed injury and treatment story, exact mechanism of trauma
5. Diagnosis
6. Bone which was broken or was operated on
7. Location of non-union in the bone;
8. Left or Right Limb was broken, comminuted, segmental, displaced, open or closed
9. Date of injury
10. Which consultant was responsible for treatment
11. Time in weeks from fracture till non-union
12. Date when non-union was confirmed by x-rays
13. Date when non-union was confirmed in a notes;
14. Operation date if operation was before treatment by US
15. Type of operation, was the graft used or not and what type of graft
16. Was metal work removed or not
17. Time from fracture till start of Ultrasound
18. Time from date of diagnosis of non-union till Ultrasound machine was given to patient
19. Indication for treatment is it for treatment of long standing condition as non-union or it was just like prophylaxis for possible delayed union
20. Ultrasound fitting date
21. Finish date of Ultrasound
22. Ultrasound treatment time
23. Date of Consolidation confirmation by notes
24. Date of Confirmation in the Notes by doctor
25. Time from Ultrasound fitting to Consolidation
26. Type of non-union on x-ray
27. Last x-ray pictures in a system
28. Last review dictation in a notes
29. Phone of patient
30. Effect by Ultrasound decided by Person who done the Audit
31. Effect of Ultrasound decided by Consultant who treated the patient
32. Number of Clinic reviews
33. Number of X-rays were done for the patient (related with non-union)
34. Number of MRI or CT was done
35. Evidence of bone healing on Radiograph.
36. Callus formation velocity
37. Possible side effects and complications of EXOGEN and device, related adverse events.
38. Power of EXOGEN related scientific articles mentioned in guidelines
It was impossible to collect and to group some details which were in a prospect of the Audit:
1. Date of the start of Full Weight Bearing FWB
2. Date of Painless Weight Bearing PWB
3. Date of Normal Daily Living NDL
4. Date of Return To Work RTW
5. Total fracture healing time TFHT
6. Price of EXOGEN treatment per person
Evaluation of existing standards
Low-intensity pulsed ultrasound to promote fracture healing’. The Guideline issue date is December 2010.
Interventional procedure guidance No 374 is two page short document. Efficacy of type of treatment is confirmed by 7 articles which cannot be found in data bases and evaluated because there are no the articles and authors names. It is mentioned that LIPUS ‘can reduce fracture healing time and there are no major safety concerns’. Indications for that treatment are described vaguely with mentioning of fractures closed and open. There is no mentioning the use of LIPUS in treatment of replacement revision complications. It is difficult to understand when we should start the treatment by Ultrasound. We can find opinion that fractures ‘usually heal within a few weeks’.
EXOGEN Ultrasound bone healing system for long bone fractures with non-union or delayed healing. Guideline issue date January is 2013.
1.1 EXOGEN Indication is for treatment and not for prophylaxis. Indication is non-union. Non-union is described as failure to heal after 9 month which is not usual in usual in current literature. The timing for different bone non-union is not specified. The EXOGEN is recommended for treatment of long bone non-union but not for Clavicle or Ankle fractures or for Great trochanter non-union after THR revision or THR resurfacing related hip pain.
1.2 It was mentioned possible patient’s treatment cost saving through avoiding surgery but there are other expenses as transportation cost, EXOGEN machine price or rent cost, inability to work – thick note price which are related more with patient’s personal expenses but not hospital itself.
1.3 We can find recommendation to evaluate EXOGEN treatment result using Radiological type of testing. X-rays are common but there are no standardised method how to quantify bone healing and it is quite subjective and person specific. CT and MRI are sensitive but too expensive to make for everyone with delayed healing. Delayed healing is described as absence of radiological evidence of healing of long bone after approximately 3 month. The timing for different bone delayed healing is not specified which is not precise under the current literature.
2.1 The EXOGEN action mechanism was described but there were no references mentioned. It is mentioned that indication for treatment by EXOGEN is only stable and well aligned fractures but there are no description which types of fractures are stable. It could be that comminuted fracture with delayed healing which is quite common situation in clinic has no indication for EXOGEN. LIPUS is contraindicated for children and adolescents but it is difficult to understand does it depend on age of person or should we evaluate Riser Index.
3.4 References related with non-union treatment by surgery timing have no definite name of article. It is difficult to find the article. Some of them are quite old. No one article was induced in UK. All studies are small.
Reference / Patients / Abstract / Full article / CountryLivani et al. (2010) / 15 / Accessible / Accessible / Brazil
Ring et al. (1997) / 42 / Accessible / Accessible / USA
Birjandinejad et al. 2009 / 13/tib/fem / Accessible / ? / Iran
Khalil et al. 2010 / 21/ulna / Accessible / Accessible / India
Lin et al. 2010/ prosp / 65/humer / Accessible / Accessible / Taiwan
Only two articles were accessible as full article to evaluate LIPUS treatment efficacy.
Reference / Patients / Abstract / Full article / CountryMayr et al. (2000) / 256 / Accessible / ? / ?
Mayr et al. (2000) / 696 / ? / ? / ?
Gebauer et al. (2005) / 51 / Accessible / ? / ?
Jingushi et al. (2007) / 72 / Accessible / ? / ?
Nolte et al. (2001) / 22 / Accessible / Accessible / Netherlands
Romano et al. (1999) / 13 / ? / ? / ?
Schofer et al. (2010) / 101 / Accessible / Accessible / USA
Lerner et al. (2004) / 16 / Accessible / ? / Israel
5.1 The Guidelines identified economic studies.
Reference / Patients / Abstract / Full article / CountryTaylor et al. (2009) / ? / Accessible / ? / UK
Kanakaris et al. (2007) / Review / Accessible / Accessible / UK
Patil et al. (2006) / 41 / Accessible / Accessible / UK
Appendix A. The Medical Technologies Advisory Committee was formed by different specialities as medical and economical science. No one orthopaedics and statistician had taken part in the Committee. Leading Orthopaedics gave their expert personal view on EXOGEN but had not taken part in discussion and making of conclusions. Expert comments of Orthopaedics specialist were not found in the Guidelines.
The overall union rate was
Article / Location / Union rateRomano 1999 / 62%
Mayr 2000 / Humerus / 76 %
Fibula / 96%
Jingushi et al. (2007) / 83 %
SUM* / 80% (62-96)
*(62+76+96+83)/4=317/4=79.25~ 80%
Cost evidence of non-union. Best case scenario
Article / Location / Type / Union rateKanakaris et al (2007) / Humerus / Plate + graft / 15,566 £
Femur / Plate + graft / 17,200 £
Tibia / Plate + graft / 16,330 £
Taylor et al. (2009) / Tibia / IM / 6,718 £
Tibia / LIPUS / 3,926 £
Patil et al. (2006) / Tibia / Ex-Fix / 30.000 £
Femur / Ex-Fix / 30,000 £
Terminology
Non-union is defined as persistent fracture line with or without pain at the site for more than 6 months post-fracture or no progression of healing on radiographs taken 3 months apart;
Delayed union was generally defined as delayed healing in less than 6 months post-fracture.
Extracorporeal shockwave therapy: A systematic review of its use in fracture management.BA Petrisor. Indian J Orthop. 2009 Apr-Jun; 43(2): 161–167.
There are important differences in fracture healing at the diaphyseal bone compared to the mechanisms of bone healing in the metaphysis. Diaphyseal bone usually heals indirectly with visible periosteal callus formation or—in absolutely stable conditions—directly with lamellar bone formation. Metaphyseal bone usually heals directly with endosteal bone bridging by micro-callus and without significant periosteal callus formation. In addition, osteoporotic changes seen in diaphyseal bone are considerably less and differ compared to those occurring in metaphyseal, trabecular bone.
Estrogen and raloxifene improve metaphyseal fracture healing in the early phase of osteoporosis. A new fracture-healing model at the tibia in rat. E. K. Stuermer. Langenbecks Arch Surg (2010) 395:163–172
Full patient cohort description
We have found all 47 cases which were treated by using Ultrasound bone healing system EXOGEN 4000, Smith and Nephew GmbH in Ysbyty Gwynedd. Exclusion criteria of patients were: impossibility to find notes or x-rays, no signs of delayed union or non-union in the notes or x-rays, patients younger than 16 years old. We got 41 patients group were treated from 19/2/2010 to 10/9/2012. The mean age of our cohort was 54. Inter-quartile range was 40-60 year. Youngest patient was 22 years old and oldest was 91 year old. 61 % of patients were females. Delayed union problems were more related with ladies in 22-60 year and in man 46-69 year old.
38 % of patients were smokers. One patient was diagnosed alcohol abuse in a youth. Two patients were used to take more than 16 units per week. It was found in the notes that 38 % patients were total abstinent and only 10 % consumed alcohol just occasionally.
We collected past medical history details of the patients and roughly grouped all information in to 9 groups:
Groups of disorders and PMH / DiagnosesMicrocirculation and cardiovascular disorders / 30 / Hypertension (12), the fracture is part of polytrauma, diabetes insulin dependent, diabetes in family, maculopathy of eye, age-related macular degeneration, Raynaud disease, Vit B deficiency, anaemia in a past, multiple blood transfusions in a past, non traumatic SUFE in youth, TIA, DVT in a past, cholesterolemija, varicose veins, pace maker, systolic murmur, aortic roof dilatation, aortic valve transplant
Disorders with possible influence to Ca turnover / 23 / Osteoporosis in the past (6), multiple fractures in a past (3), hypo (3) or hyperthyroid (1), thyroid lump excision, gallstone pancreatitis, cholecystectomy, breath feeding at present, stomach or duodenal ulcers, vagotomy or postvagotomy syndrome, Patella bipartitae bilateral, NOF aneurismal cist in a bone with cortical infraction
Disorders with possible female hormone disturbance / 12 / Dysmenorea (2), sterilisation in female, salpingectomy, early menopause, breast carcinoma, axillary node wide excision due to breast carcinoma, lumpectomy of the breast, leiomyomata uteri, hysterectomy, intermenstrual bleeding, postmenopausal bleeding
Inflammatory and infection related disorders which can increase anti inflammatory medication and antibiotics use / 12 / Arthritis (2), gout, arthroscopy in a past, neck spondylosis, eczema, psoriasis, tonsillectomy, adenoidectomy, lymphedema, previous infection complications, Staphylococcus aureus positive
Central nerve system disorders / 8 / Depression (3), cognitive behavioural problems, psychosis, claustrophobia, alcohol abuse in youth, steriotactic radiation due to acustic neuroma
Disorders which can be related with male hormone lack / 7 / Gynecomastia (2), vasectomy (2), epididymal cyst excision, hydrocelle in a testis, atrophic testicle
Spine problems which can increase anti inflammatory medication use and can influence innervation of legs / 7 / Back pain (3), intervertebral disc prolaps (2), spinal stenosis, laminectomy,
Urinary - kidney system disturbance which can influence Ca turnover / 6 / Renal failure in a past (2), enuresis, glomerulonephritis, IgA nephropathy, Goodpasture’s syndrome (antiglomerular antibodies)
Pulmonary system disturbance with hypoxia possibility / 4 / Asthma (2), COPD, pneumothorax is part of trauma
Others / 3 / Carpal tunnel syndrome, multiple lipomatosis, appendectomy
60% of patients had no PMH or just diagnoses from one of groups. 40% patients had significant co-morbidity related with 2 or even 5 groups of this table. The mean age of this group of patients is 54 year for this reason there is no surprise that there were usual diagnoses as hypertension, osteoporosis, multiple fractures and depression.
17 % patients were overweight or obese, BMI 24.9-40. Others 83 % weight was normal or we
couldn’t find the details in notes.
Medication
It possible that delayed union can be caused by medication which is taken by the patient. Literature search about possible influence medicament in to bone healing, up to September 9, 2013, was undertaken on the BubMed based medical literature database. Searches employed a combination of keywords (Medication name bone healing, drug class, action mechanism, side effects and adverse effects. The search was not limited to human subjects and articles published in the English language. We interested which stage of bone formation is influenced by definite medication. We divided available articles in three groups and separate them from articles about medication which can increase fracture risk: